1000 discrete sites scattered throughout the genome. Here we show that replication of all yeast chromosomes was markedly delayed in rrm3 cells. Delayed replication was seen even in a region that lacks any predicted Rrm3p-dependent sites. Based on the pattern of replication intermediates in two-dimensional gels, the rate of fork movement in rrm3 cells appeared similar to wild-type except at known Rrm3p-dependent sites. These data suggest that although Rrm3p has a global role in DNA replication, its activity is needed only or primarily at specific, difficult-to-replicate sites. By the criterion of chromatin immunoprecipitation, Rrm3p was associated with both Rrm3p-dependent and -independent sites, and moved with the replication fork through both. In addition, Rrm3p interacted with Pol2p, the catalytic subunit of DNA polymerase epsilon, in vivo. Thus, rather than being recruited to its sites of action when replication forks stall at these sites, Rrm3p is likely a component of the replication fork apparatus.","title":"The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes."},{"docid":"6106004","text":"Publisher Summary The budding yeast Saccharomyces cerevisiae ( S. cerevisiae ) divides asymmetrically. In vegetative growth, yeast cells reproduce by budding, and the position where the bud forms ultimately determines the plane of cell division. This chapter describes the detailed procedures for the separation and isolation of mothers and daughters. These protocols have been used by investigators studying aging, bud site selection, and other aspects of asymmetric cell division. The chapter describes the procedures for performing life span analysis by micromanipulation and the steps for the large-scale collection of old cells. At the beginning and the end of a life span, it can be difficult to distinguish mothers from daughters. At most points in the life span, daughter cells are smaller than the mothers that produced them. In addition, mother cells will generally bud a second time before their daughter cells form their first bud. One method for effective isolation of virgin daughter cells from mother cells, but not for recovery of old mothers, is called a “baby machine. ” Mother cells are attached to a membrane and allowed to divide. Daughter cells from these attached cells are eluted continuously by washing the membrane.","title":"Separation of mother and daughter cells."}],"string":"[\n {\n \"docid\": \"7643848\",\n \"text\": \"We have characterized the membrane topology of a 60-kDa inner membrane protein from Escherichia coli that is homologous to the recently identified Oxa1p protein in Saccharomyces cerevisiae mitochondria implicated in the assembly of mitochondrial inner membrane proteins. Hydrophobicity and alkaline phosphatase fusion analyses suggest a membrane topology with six transmembrane segments, including an N-terminal signal-anchor sequence not present in mitochondrial Oxa1p. In contrast to partial N-terminal fusion protein constructs, the full-length protein folds into a protease-resistant conformation, suggesting that important folding determinants are present in the C-terminal part of the molecule.\",\n \"title\": \"Membrane topology of the 60-kDa Oxa1p homologue from Escherichia coli.\"\n },\n {\n \"docid\": \"2817000\",\n \"text\": \"In S. cerevisiae, histone variant H2A.Z is deposited in euchromatin at the flanks of silent heterochromatin to prevent its ectopic spread. We show that H2A.Z nucleosomes are found at promoter regions of nearly all genes in euchromatin. They generally occur as two positioned nucleosomes that flank a nucleosome-free region (NFR) that contains the transcription start site. Astonishingly, enrichment at 5' ends is observed not only at actively transcribed genes but also at inactive loci. Mutagenesis of a typical promoter revealed a 22 bp segment of DNA sufficient to program formation of a NFR flanked by two H2A.Z nucleosomes. This segment contains a binding site of the Myb-related protein Reb1 and an adjacent dT:dA tract. Efficient deposition of H2A.Z is further promoted by a specific pattern of histone H3 and H4 tail acetylation and the bromodomain protein Bdf1, a component of the Swr1 remodeling complex that deposits H2A.Z.\",\n \"title\": \"Histone Variant H2A.Z Marks the 5′ Ends of Both Active and Inactive Genes in Euchromatin\"\n },\n {\n \"docid\": \"86231298\",\n \"text\": \"Protein modification by the ubiquitin-like SUMO protein contributes to many cellular regulatory mechanisms. In Saccharomyces cerevisiae, both sumoylating and desumoylating activities are essential for viability. Of its two known desumoylating enzymes, Ubl-specific protease (Ulp)1 and Ulp2/Smt4, Ulp1 is specifically required for cell cycle progression. A ∼200-residue segment, the Ulp domain (UD), is conserved among Ulps and includes a core cysteine protease domain that is even more widespread. Here we demonstrate that the Ulp1 UD by itself can support wild-type growth rates and in vitro can cleave SUMO from substrates. However, in cells expressing only the UD of Ulp1, many SUMO conjugates accumulate to high levels, indicating that the nonessential Ulp1 NH2-terminal domain is important for activity against a substantial fraction of sumoylated targets. The NH2-terminal domain also includes sequences necessary and sufficient to concentrate Ulp1 at nuclear envelope sites. Remarkably, NH2-terminally deleted Ulp1 variants are able, unlike full-length Ulp1, to suppress defects of cells lacking the divergent Ulp2 isopeptidase. Thus, the NH2-terminal regulatory domain of Ulp1 restricts Ulp1 activity toward certain sumoylated proteins while enabling the cleavage of others. These data define key functional elements of Ulp1 and strongly suggest that subcellular localization is a physiologically significant constraint on SUMO isopeptidase specificity.\",\n \"title\": \"The Ulp1 SUMO isopeptidase distinct domains required for viability, nuclear envelope localization, and substrate specificity\"\n },\n {\n \"docid\": \"32638085\",\n \"text\": \"Histone acetylation and deacetylation in the yeast Saccharomyces cerevisiae occur by targeting acetyltransferase and deacetylase enzymes to gene promoters and, in an untargeted and global manner, by affecting most nucleosomes. Recently, new roles for histone acetylation have been uncovered, not only in transcription but also in DNA replication, repair and heterochromatin formation. Interestingly, specific acetylatable lysines can function as binding sites for regulatory factors. Moreover, histone deacetylation is not only repressive but can be required for gene activity.\",\n \"title\": \"Histone acetylation and deacetylation in yeast\"\n },\n {\n \"docid\": \"39462488\",\n \"text\": \"Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Saccharomyces cerevisiae proteins Tof1 and Mrc1 facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint.\",\n \"title\": \"Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility\"\n },\n {\n \"docid\": \"145335387\",\n \"text\": \"As in other countries, suburbanization in China occurred after the cities had experienced a period of sustained industrial and population growth. This study examines suburbanization in Beijing, Shanghai, Shenyang, and Dalian. As a result of economic restructuring, the urban core registered net population loss from 1982 to 1990 because of decentralization while the inner suburbs gained population. Among the forces driving suburbanization were marketization of urban land, the shift of industrial land to tertiary use, transportation improvement, the availability of foreign and domestic capital, housing rehabilitation in the city, and new housing construction in the suburbs. There were certain similarities but major differences between American and Chinese suburbanization. Unlike the current metropolitan landscape in the United States where suburban growth has given rise to a polycentric spatial structure, suburbanization in China is still at the incipient stage of development with suburbs dominated by centra...\",\n \"title\": \"ECONOMIC RESTRUCTURING AND SUBURBANIZATION IN CHINA\"\n },\n {\n \"docid\": \"13613916\",\n \"text\": \"Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief of glucose repression.\",\n \"title\": \"Glucose repression in Saccharomyces cerevisiae\"\n },\n {\n \"docid\": \"9704467\",\n \"text\": \"We developed the Yeast Gene Order Browser (YGOB; http://wolfe.gen.tcd.ie/ygob) to facilitate visual comparisons and computational analysis of synteny relationships in yeasts. The data presented in YGOB, currently covering seven species, are based on sets of homologous genes that have been intensively manually curated based on both sequence similarity and genomic context (synteny). We reconciled different laboratories' lists of paralogous Saccharomyces cerevisiae gene pairs formed by genome duplication (ohnologs), and present near-exhaustive lists of the ohnolog pairs retained in S. cerevisiae (551, including 22 previously unidentified), Saccharomyces castellii (599), and Candida glabrata (404).\",\n \"title\": \"in polyploid species\"\n },\n {\n \"docid\": \"4414481\",\n \"text\": \"Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals. We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide). In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals.\",\n \"title\": \"Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration\"\n },\n {\n \"docid\": \"34074902\",\n \"text\": \"Abstract Feline leukemia virus (FeLV), Gammaretrovirus, and feline immunodeficiency virus, a Lentivirus, are members of the family Retroviridae, and may establish persistent infections in the domestic cat (Felis catus). Cytoproliferative and cytosuppressive disorders may result from infection with these viruses. Morbidity and mortality rates are high in domestic cats worldwide. Infection of endangered neotropic small felids with these viruses could be devastating. To investigate the prevalence of FeLV and feline lentiviruses in neotropic small felids kept in captivity in São Paulo state, Brazil, serum samples from 104 animals belonging to the species Leopardus pardalis, Leopardus tigrinus, Leopardus wiedii, Herpailurus yaguarondi, and Oncifelis geoffroyi were tested for FeLV and feline lentiviruses by commercially available immunoassays. All results were negative, suggesting that retrovirus infection is not an important clinical problem in these populations. Because domestic cats in São Paulo city are naturally infected with these pathogens, and feral cats are commonly found in zoologic facilities in Brazil, preventive measures should be taken to avoid transmission of retroviruses to naive populations of wild and captive neotropic felids in Brazil.\",\n \"title\": \"SEROSURVEY FOR FELINE LEUKEMIA VIRUS AND LENTIVIRUSES IN CAPTIVE SMALL NEOTROPIC FELIDS IN SÃO PAULO STATE, BRAZIL\"\n },\n {\n \"docid\": \"14145440\",\n \"text\": \"BACKGROUND DNA replication and mitosis are triggered by activation of kinase complexes, each made up of a cyclin and a cyclin-dependent kinase (Cdk). It had seemed possible that the association of Cdks with different classes of cyclins specifies whether S phase (replication) or M phase (mitosis) will occur. The recent finding that individual B-type cyclins (encoded by the genes CLB1-CLB6) can have functions in both processes in the budding yeast Saccharomyces cerevisiae casts doubt on this notion. RESULTS S. cerevisiae strains lacking C1b1-C1b4 undergo DNA replication once but fail to enter mitosis. We have isolated mutations in two genes, SIM1 and SIM2 (SIM2 is identical to SEC72), which allow such cells to undergo an extra round of DNA replication without mitosis. The Clb5 kinase, which promotes S phase, remains active during the G2-phase arrest of cells of the parental strain, but its activity declines rapidly in sim mutants. Increased expression of the CLB5 gene prevents re-replication. Thus, a cyclin B-kinase that promotes DNA replication in G1-phase cells can prevent re-replication in G2-phase cells. Inactivation of C1b kinases by expression of the specific C1b-Cdk1 inhibitor p40SIC1 is sufficient to induce a prereplicative state at origins of replication in cells blocked in G2/M phase by nocodazole. Re-activation of C1b-Cdk1 kinases induces a second round of DNA replication. CONCLUSIONS We propose that S-phase-promoting cyclin B--Cdk complexes prevent re-replication during S, G2 and M phases by inhibiting the transition of replication origins to a pre-replicative state. This model can explain both why origins 'fire' only once per S phase and why S phase is dependent on completion of the preceding M phase.\",\n \"title\": \"S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state\"\n },\n {\n \"docid\": \"365896\",\n \"text\": \"We describe methods for obtaining a quantitative description of RNA processing at high resolution in budding yeast. As a model gene expression system, we constructed tetON (for induction studies) and tetOFF (for repression, derepression, and RNA degradation studies) yeast strains with a series of reporter genes integrated in the genome under the control of a tetO7 promoter. Reverse transcription and quantitative real-time-PCR (RT-qPCR) methods were adapted to allow the determination of mRNA abundance as the average number of copies per cell in a population. Fluorescence in situ hybridization (FISH) measurements of transcript numbers in individual cells validated the RT-qPCR approach for the average copy-number determination despite the broad distribution of transcript levels within a population of cells. In addition, RT-qPCR was used to distinguish the products of the different steps in splicing of the reporter transcripts, and methods were developed to map and quantify 3'-end cleavage and polyadenylation. This system permits pre-mRNA production, splicing, 3'-end maturation and degradation to be quantitatively monitored with unprecedented kinetic detail, suitable for mathematical modeling. Using this approach, we demonstrate that reporter transcripts are spliced prior to their 3'-end cleavage and polyadenylation, that is, cotranscriptionally.\",\n \"title\": \"RiboSys, a high-resolution, quantitative approach to measure the in vivo kinetics of pre-mRNA splicing and 3'-end processing in Saccharomyces cerevisiae.\"\n },\n {\n \"docid\": \"25462689\",\n \"text\": \"We have investigated HO endonuclease-induced double-strand break (DSB) recombination and repair in a LACZ duplication plasmid in yeast. A 117-bp MATa fragment, embedded in one copy of LACZ, served as a site for initiation of a DSB when HO endonuclease was expressed. The DSB could be repaired using wild-type sequences located on a second, promoterless, copy of LACZ on the same plasmid. In contrast to normal mating-type switching, crossing-over associated with gene conversion occurred at least 50% of the time. The proportion of conversion events accompanied by exchange was greater when the two copies of LACZ were in direct orientation (80%), than when inverted (50%). In addition, the fraction of plasmids lost was significantly greater in the inverted orientation. The kinetics of appearance of intermediates and final products were also monitored. The repair of the DSB is slow, requiring at least an hour from the detection of the HO-cut fragments to completion of repair. Surprisingly, the appearance of the two reciprocal products of crossing over did not occur with the same kinetics. For example, when the two LACZ sequences were in the direct orientation, the HO-induced formation of a large circular deletion product was not accompanied by the appearance of a small circular reciprocal product. We suggest that these differences may reflect two kinetically separable processes, one involving only one cut end and the other resulting from the concerted participation of both ends of the DSB.\",\n \"title\": \"Genetic and physical analysis of double-strand break repair and recombination in Saccharomyces cerevisiae.\"\n },\n {\n \"docid\": \"984825\",\n \"text\": \"Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs, enhances the function of transfer RNA and ribosomal RNA by stabilizing the RNA structure. Messenger RNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function--it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding centre. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological relevance was unclear. Here we present a comprehensive analysis of pseudouridylation in Saccharomyces cerevisiae and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as many novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1-4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease.\",\n \"title\": \"Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells\"\n },\n {\n \"docid\": \"23604601\",\n \"text\": \"The IME1 gene of Saccharomyces cerevisiae is required for initiation of meiosis. Transcription of IME1 is detected under conditions which are known to induce initiation of meiosis, namely starvation for nitrogen and glucose, and the presence of MATa1 and MAT alpha 2 gene products. In this paper we show that IME1 is also subject to translational regulation. Translation of IME1 mRNA is achieved either upon nitrogen starvation, or upon G1 arrest. In the presence of nutrients, constitutively elevated transcription of IME1 is also sufficient for the translation of IME1 RNA. Four different conditions were found to cause expression of Ime1 protein in vegetative cultures: elevated transcription levels due to the presence of IME1 on a multicopy plasmid; elevated transcription provided by a Gal-IME1 construct; G1 arrest due to alpha-factor treatment; G1 arrest following mild heat-shock treatment of cdc28 diploids. Using these conditions, we obtained evidence that starvation is required not only for transcription and efficient translation of IME1, but also for either the activation of Ime1 protein or for the induction/activation of another factor that, either alone or in combination with Ime1, induces meiosis.\",\n \"title\": \"Post-transcriptional regulation of IME1 determines initiation of meiosis in Saccharomyces cerevisiae.\"\n },\n {\n \"docid\": \"9548440\",\n \"text\": \"Trisomic and monosomic (aneuploid) embryos account for at least 10% of human pregnancies and, for women nearing the end of their reproductive lifespan, the incidence may exceed 50%. The errors that lead to aneuploidy almost always occur in the oocyte but, despite intensive investigation, the underlying molecular basis has remained elusive. Recent studies of humans and model organisms have shed new light on the complexity of meiotic defects, providing evidence that the age-related increase in errors in the human female is not attributable to a single factor but to an interplay between unique features of oogenesis and a host of endogenous and exogenous factors.\",\n \"title\": \"Human aneuploidy: mechanisms and new insights into an age-old problem\"\n },\n {\n \"docid\": \"14446279\",\n \"text\": \"In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.\",\n \"title\": \"Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region\"\n },\n {\n \"docid\": \"43752562\",\n \"text\": \"Subcellular membranes of Saccharomyces cerevisiae, including mitochondria, microsomes, plasma membranes, secretory vesicles, vacuoles, nuclear membranes, peroxisomes, and lipid particles, were isolated by improved procedures and analyzed for their lipid composition and their capacity to synthesize phospholipids and to catalyze sterol delta 24-methylation. The microsomal fraction is heterogeneous in terms of density and classical microsomal marker proteins and also with respect to the distribution of phospholipid-synthesizing enzymes. The specific activity of phosphatidylserine synthase was highest in a microsomal subfraction which was distinct from heavier microsomes harboring phosphatidylinositol synthase and the phospholipid N-methyltransferases. The exclusive location of phosphatidylserine decarboxylase in mitochondria was confirmed. CDO-diacylglycerol synthase activity was found both in mitochondria and in microsomal membranes. Highest specific activities of glycerol-3-phosphate acyltransferase and sterol delta 24-methyltransferase were observed in the lipid particle fraction. Nuclear and plasma membranes, vacuoles, and peroxisomes contain only marginal activities of the lipid-synthesizing enzymes analyzed. The plasma membrane and secretory vesicles are enriched in ergosterol and in phosphatidylserine. Lipid particles are characterized by their high content of ergosteryl esters. The rigidity of the plasma membrane and of secretory vesicles, determined by measuring fluorescence anisotropy by using trimethylammonium diphenylhexatriene as a probe, can be attributed to the high content of ergosterol.\",\n \"title\": \"Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae.\"\n },\n {\n \"docid\": \"9451052\",\n \"text\": \"Histone variant H2A.Z-containing nucleosomes are incorporated at most eukaryotic promoters. This incorporation is mediated by the conserved SWR1 complex, which replaces histone H2A in canonical nucleosomes with H2A.Z in an ATP-dependent manner. Here, we show that promoter-proximal nucleosomes are highly heterogeneous for H2A.Z in Saccharomyces cerevisiae, with substantial representation of nucleosomes containing one, two, or zero H2A.Z molecules. SWR1-catalyzed H2A.Z replacement in vitro occurs in a stepwise and unidirectional fashion, one H2A.Z-H2B dimer at a time, producing heterotypic nucleosomes as intermediates and homotypic H2A.Z nucleosomes as end products. The ATPase activity of SWR1 is specifically stimulated by H2A-containing nucleosomes without ensuing histone H2A eviction. Remarkably, further addition of free H2A.Z-H2B dimer leads to hyperstimulation of ATPase activity, eviction of nucleosomal H2A-H2B, and deposition of H2A.Z-H2B. These results suggest that the combination of H2A-containing nucleosome and free H2A.Z-H2B dimer acting as both effector and substrate for SWR1 governs the specificity and outcome of the replacement reaction.\",\n \"title\": \"Stepwise Histone Replacement by SWR1 Requires Dual Activation with Histone H2A.Z and Canonical Nucleosome\"\n },\n {\n \"docid\": \"16686383\",\n \"text\": \"The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We identify posttranslational modifications of Saccharomyces cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants shows growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody, we show that the association of phosphorylated Cse4 with centromeres increases in response to defective microtubule attachment or reduced cohesion. We determine that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 are reduced at centromeres in ipl1 strains in vivo, and in vitro assays show phosphorylation of Cse4 by Ipl1. Consistent with these results, we observe that a phosphomimetic cse4-4SD mutant suppresses the temperature-sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80, which are defective for chromosome biorientation. Furthermore, cell biology approaches using a green fluorescent protein-labeled chromosome show that cse4-4SD suppresses chromosome segregation defects in dam1 spc34 strains. On the basis of these results, we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our results provide a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation.\",\n \"title\": \"Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in Saccharomyces cerevisiae\"\n },\n {\n \"docid\": \"23664875\",\n \"text\": \"Termination of replication forks at the natural termini of the rDNA of Saccharomyces cerevisiae is controlled in a sequence-specific and polar mode by the interaction of the Fob1p replication terminator protein with the tandem Ter sites located in the nontranscribed spacers. Here we show, by both 2D gel analyses and chromatin immunoprecipitations (ChIP), that there exists a second level of global control mediated by the intra-S-phase checkpoint protein complex of Tof1p and Csm3p that protect stalled forks at Ter sites against the activity of the Rrm3p helicase (\\\"sweepase\\\"). The sweepase tends to release arrested forks presumably by the transient displacement of the Ter-bound Fob1p. Consistent with this mechanism, very few replication forks were arrested at the natural replication termini in the absence of the two checkpoint proteins. In the absence of the Rrm3p helicase, there was a slight enhancement of fork arrest at the Ter sites. Simultaneous deletions of the TOF1 (or CSM3), and the RRM3 genes restored fork arrest by removing both the fork-releasing and fork-protection activities. Other genes such as MRC1, WSS1, and PSY2 that are also involved in the MRC1 checkpoint pathway were not involved in this global control. This observation suggests that Tof1p-Csm3p function differently from MRC1 and the other above-mentioned genes. This mechanism is not restricted to the natural Ter sites but was also observed at fork arrest caused by the meeting of a replication fork with transcription approaching from the opposite direction.\",\n \"title\": \"The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae.\"\n },\n {\n \"docid\": \"42267740\",\n \"text\": \"Various proteins have been found to play roles in both the repair of UV damaged DNA and heterochromatin-mediated silencing in the yeast Saccharomyces cerevisiae. In particular, factors that are involved in the methylation of lysine-79 of histone H3 by Dot1p have been implicated in both processes, suggesting a bipartite function for this modification. We find that a dot1 null mutation and a histone H3 point mutation at lysine-79 cause increased sensitivity to UV radiation, suggesting that lysine-79 methylation is important for efficient repair of UV damage. Epistasis analysis between dot1 and various UV repair genes indicates that lysine-79 methylation plays overlapping roles within the nucleotide excision, post-replication and recombination repair pathways, as well as RAD9-mediated checkpoint function. In contrast, epistasis analysis with the H3 lysine-79 point mutation indicates that the lysine-to-glutamic acid substitution exerts specific effects within the nucleotide excision repair and post-replication repair pathways, suggesting that this allele only disrupts a subset of the functions of lysine-79 methylation. The overall results indicate the existence of distinct and separable roles of histone H3 lysine-79 methylation in the response to UV damage, potentially serving to coordinate the various repair processes.\",\n \"title\": \"Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.\"\n },\n {\n \"docid\": \"4319844\",\n \"text\": \"Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that occurs in a subset of cancers. By analyzing telomerase-positive cells and their human TERC knockout-derived ALT human cell lines, we show that ALT cells harbor more fragile telomeres representing telomere replication problems. ALT-associated replication defects trigger mitotic DNA synthesis (MiDAS) at telomeres in a RAD52-dependent, but RAD51-independent, manner. Telomeric MiDAS is a conservative DNA synthesis process, potentially mediated by break-induced replication, similar to type II ALT survivors in Saccharomyces cerevisiae Replication stresses induced by ectopic oncogenic expression of cyclin E, G-quadruplexes, or R-loop formation facilitate the ALT pathway and lead to telomere clustering, a hallmark of ALT cancers. The TIMELESS/TIPIN complex suppresses telomere clustering and telomeric MiDAS, whereas the SMC5/6 complex promotes them. In summary, ALT cells exhibit more telomere replication defects that result in persistent DNA damage responses at telomeres, leading to the engagement of telomeric MiDAS (spontaneous mitotic telomere synthesis) that is triggered by DNA replication stress, a potential driver of genomic duplications in cancer.\",\n \"title\": \"Alternative Lengthening of Telomeres Mediated by Mitotic DNA Synthesis Engages Break-Induced Replication Processes.\"\n },\n {\n \"docid\": \"1256116\",\n \"text\": \"The YEAst Search for Transcriptional Regulators And Consensus Tracking (YEASTRACT) information system (http://www.yeastract.com) was developed to support the analysis of transcription regulatory associations in Saccharomyces cerevisiae. Last updated in June 2010, this database contains over 48,200 regulatory associations between transcription factors (TFs) and target genes, including 298 specific DNA-binding sites for 110 characterized TFs. All regulatory associations stored in the database were revisited and detailed information on the experimental evidences that sustain those associations was added and classified as direct or indirect evidences. The inclusion of this new data, gathered in response to the requests of YEASTRACT users, allows the user to restrict its queries to subsets of the data based on the existence or not of experimental evidences for the direct action of the TFs in the promoter region of their target genes. Another new feature of this release is the availability of all data through a machine readable web-service interface. Users are no longer restricted to the set of available queries made available through the existing web interface, and can use the web service interface to query, retrieve and exploit the YEASTRACT data using their own implementation of additional functionalities. The YEASTRACT information system is further complemented with several computational tools that facilitate the use of the curated data when answering a number of important biological questions. Since its first release in 2006, YEASTRACT has been extensively used by hundreds of researchers from all over the world. We expect that by making the new data and services available, the system will continue to be instrumental for yeast biologists and systems biology researchers.\",\n \"title\": \"YEASTRACT: providing a programmatic access to curated transcriptional regulatory associations in Saccharomyces cerevisiae through a web services interface\"\n },\n {\n \"docid\": \"10874408\",\n \"text\": \"DNA double-strand breaks (DSBs), which are formed by the Spo11 protein, initiate meiotic recombination. Previous DSB-mapping studies have used rad50S or sae2Δ mutants, which are defective in break processing, to accumulate Spo11-linked DSBs, and report large (≥ 50 kb) “DSB-hot” regions that are separated by “DSB-cold” domains of similar size. Substantial recombination occurs in some DSB-cold regions, suggesting that DSB patterns are not normal in rad50S or sae2Δ mutants. We therefore developed a novel method to map genome-wide, single-strand DNA (ssDNA)–associated DSBs that accumulate in processing-capable, repair-defective dmc1Δ and dmc1Δ rad51Δ mutants. DSBs were observed at known hot spots, but also in most previously identified “DSB-cold” regions, including near centromeres and telomeres. Although approximately 40% of the genome is DSB-cold in rad50S mutants, analysis of meiotic ssDNA from dmc1Δ shows that most of these regions have substantial DSB activity. Southern blot assays of DSBs in selected regions in dmc1Δ, rad50S, and wild-type cells confirm these findings. Thus, DSBs are distributed much more uniformly than was previously believed. Comparisons of DSB signals in dmc1, dmc1 rad51, and dmc1 spo11 mutant strains identify Dmc1 as a critical strand-exchange activity genome-wide, and confirm previous conclusions that Spo11-induced lesions initiate all meiotic recombination.\",\n \"title\": \"Mapping Meiotic Single-Strand DNA Reveals a New Landscape of DNA Double-Strand Breaks in Saccharomyces cerevisiae\"\n },\n {\n \"docid\": \"36904081\",\n \"text\": \"The yeast ribosomal protein gene RPL32 of Saccharomyces cerevisiae is of particular interest for two reasons: 1) it is adjacent to another ribosomal protein gene, RP29, whose divergent transcription may be driven from the same control sequences, and 2) it appears that the splicing of its transcript is regulated by the product of the gene, ribosomal protein in L32. RPL32 has been analyzed in detail. It is essential for cell growth. Its sequence predicts L32 to be a protein of 105 amino acids, somewhat basic near the NH2 terminus, rather acidic near the COOH terminus, and homologous to ribosomal protein L30 of mammals. The reading frame has been confirmed by partial NH2-terminal analysis of L32. The nucleotide sequence also predicts an intron of 230 nucleotides, which begins with the unusual sequence GTCAGT and ends 40 nucleotides downstream of the consensus sequence TAC-TAAC. The intron has been confirmed by determination of the sequence of a cDNA clone. Transcription initiates 58 nucleotides upstream of the AUG initiation codon, and the polyadenylation site occurs 100 nucleotides downstream of the termination codon. Regulation of the transcription of ribosomal protein genes has been linked to two related consensus sequences. Analysis of the intergenic region between RP29 and RPL32 reveals three copies of these sequences. A deletion removing all three sequences reduces synthesis of a L32-LacZ fusion protein by more than 90%. Some residual activity, however, remains.\",\n \"title\": \"The yeast ribosomal protein L32 and its gene.\"\n },\n {\n \"docid\": \"516867\",\n \"text\": \"The unicellular eukaryotic organisms represent the popular model systems to understand aging in eukaryotes. Candida albicans, a polymorphic fungus, appears to be another distinctive unicellular aging model in addition to the budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe. The two types of Candida cells, yeast (blastospore) form and hyphal (filamentous) form, have similar replicative lifespan. Taking the advantage of morphologic changes, we are able to obtain cells of different ages. Old Candida cells tend to accumulate glycogen and oxidatively damaged proteins. Deletion of the SIR2 gene causes a decrease of lifespan, while insertion of an extra copy of SIR2 extends lifespan, indicating that like in S. cerevisiae, Sir2 regulates cellular aging in C. albicans. Interestingly, Sir2 deletion does not result in the accumulation of extra-chromosomal rDNA molecules, but influences the retention of oxidized proteins in mother cells, suggesting that the extra-chromosomal rDNA molecules may not be associated with cellular aging in C. albicans. This novel aging model, which allows efficient large-scale isolation of old cells, may facilitate biochemical characterizations and genomics/proteomics studies of cellular aging, and help to verify the aging pathways observed in other organisms including S. cerevisiae.\",\n \"title\": \"Candida albicans, a distinctive fungal model for cellular aging study\"\n },\n {\n \"docid\": \"21425864\",\n \"text\": \"Glycosyl phosphatidylinositols (GPIs) anchor many proteins to the surface of eukaryotic cells and may also serve as sorting signals on proteins and participate in signal transduction. We have isolated a Saccharomyces cerevisiae GPI anchoring mutant, gpi1, using a colony screen for cells blocked in [3H]inositol incorporation into protein. The gpi1 mutant is defective in vitro in the synthesis of N-acetylglucosaminyl phosphatidylinositol, the first intermediate in GPI synthesis, and is also temperature-sensitive for growth. Completion of the first step in GPI assembly is therefore required for growth of the unicellular eukaryote S. cerevisiae. GPI synthesis could therefore be exploited as a target for antifungal or antiparasitic agents.\",\n \"title\": \"A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis.\"\n },\n {\n \"docid\": \"26083387\",\n \"text\": \"The Saccharomyces cerevisiae DNA helicase Rrm3p is needed for normal fork progression through >1000 discrete sites scattered throughout the genome. Here we show that replication of all yeast chromosomes was markedly delayed in rrm3 cells. Delayed replication was seen even in a region that lacks any predicted Rrm3p-dependent sites. Based on the pattern of replication intermediates in two-dimensional gels, the rate of fork movement in rrm3 cells appeared similar to wild-type except at known Rrm3p-dependent sites. These data suggest that although Rrm3p has a global role in DNA replication, its activity is needed only or primarily at specific, difficult-to-replicate sites. By the criterion of chromatin immunoprecipitation, Rrm3p was associated with both Rrm3p-dependent and -independent sites, and moved with the replication fork through both. In addition, Rrm3p interacted with Pol2p, the catalytic subunit of DNA polymerase epsilon, in vivo. Thus, rather than being recruited to its sites of action when replication forks stall at these sites, Rrm3p is likely a component of the replication fork apparatus.\",\n \"title\": \"The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes.\"\n },\n {\n \"docid\": \"6106004\",\n \"text\": \"Publisher Summary The budding yeast Saccharomyces cerevisiae ( S. cerevisiae ) divides asymmetrically. In vegetative growth, yeast cells reproduce by budding, and the position where the bud forms ultimately determines the plane of cell division. This chapter describes the detailed procedures for the separation and isolation of mothers and daughters. These protocols have been used by investigators studying aging, bud site selection, and other aspects of asymmetric cell division. The chapter describes the procedures for performing life span analysis by micromanipulation and the steps for the large-scale collection of old cells. At the beginning and the end of a life span, it can be difficult to distinguish mothers from daughters. At most points in the life span, daughter cells are smaller than the mothers that produced them. In addition, mother cells will generally bud a second time before their daughter cells form their first bud. One method for effective isolation of virgin daughter cells from mother cells, but not for recovery of old mothers, is called a “baby machine. ” Mother cells are attached to a membrane and allowed to divide. Daughter cells from these attached cells are eluted continuously by washing the membrane.\",\n \"title\": \"Separation of mother and daughter cells.\"\n }\n]"}}},{"rowIdx":2695,"cells":{"query_id":{"kind":"string","value":"917"},"query":{"kind":"string","value":"If I helped my friend to file taxes; can I represent her on a phone call with FTB?"},"positive_passages":{"kind":"list like","value":[{"docid":"379233","text":"In order for you to be able to talk to the FTB on someone's behalf, that someone has to submit form 3520. Note that since you're not a professional, this form must be paper-filed (CRTP, EA, CPA or attorneys can have this filed on-line). Once the form is accepted by the FTB, you can contact the FTB on behalf of your friend. Pay attention: you're going to represent the partnership, not the individual.","title":""}],"string":"[\n {\n \"docid\": \"379233\",\n \"text\": \"In order for you to be able to talk to the FTB on someone's behalf, that someone has to submit form 3520. Note that since you're not a professional, this form must be paper-filed (CRTP, EA, CPA or attorneys can have this filed on-line). Once the form is accepted by the FTB, you can contact the FTB on behalf of your friend. Pay attention: you're going to represent the partnership, not the individual.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"366761","text":"I called the IRS (click here for IRS contact info) and they said I do not need to get a new EIN. I could have just filed the appropriate employer federal tax return (940/941) and then the filing requirements would have been updated. But while I was on the phone, they just updated the filing requirements for my LLC so I am all good now (I still need to file the correct form and make the correct payments, etc. but I can use this same EIN going forward). Disclaimer: Don't trust me (or this answer) for tax advice (your situation may be different). The IRS person on the phone was very helpful so I recommend calling them if you are in a similar situation. FYI, I have found calling the IRS to always be very helpful.","title":""},{"docid":"222726","text":"\"What is the right way to handle this? Did you check the forms? Did the form state $0 tax due on the FTB LLC/Corp form (I'm guessing you operate as LLC/Corp, since you're dealing with the Franchise Tax)? The responsibility is ultimately yours. You should cross check all the numbers and verify that they're correct. That said, if the CPA filled the forms incorrectly based on your correct data - then she made a mistake and can be held liable. CPA filing forms from a jurisdiction on the other end of the country without proper research and knowledge may be held negligent if she made a grave mistake. You can file a law suit against the CPA (which will probably trigger her E&O insurance carrier who'll try to settle if there's a good chance for your lawsuit to not be thrown away outright), or complain to the State regulatory agency overseeing CPAs in the State of her license. Or both. Am I wrong for expecting the CPA should have properly filled out and filed my taxes? No, but it doesn't shift the responsibility from you. How can I find out if the CPA has missed anything else? Same as with doctors and lawyers - get a second opinion. Preferably from a CPA licensed in California. You and only you are responsible for your taxes. You may try to pin the penalties and interest on the CPA if she really made a mistake. California is notorious for very high LLC/Corp franchise tax (cost of registering to do business in the State). It's $800 a year. You should have read the forms and the instructions carefully, it is very prominent. It is also very well discussed all over the Internet, any search engine would pop it up for you with a simple \"\"California Franchise Tax for LLC/Corp\"\" search. CA FTB is also very aggressive in assessing and collecting the fee, and the rules of establishing nexus in CA are very broad. From your description it sounds like you were liable for the Franchise tax in CA, since you had a storage facility in CA. You may also be liable for sales taxes for that period.\"","title":""},{"docid":"105158","text":"\"Does location of EA or CPA matter? Not in particular. The FTB has field offices all over the State, so if a meeting needs to be arranged - it will be in the nearest office. When you interview the potential candidates, you can ask them how they would deal the case if there's a need of an in-person visit to the FTB, and if it is even an option you should be worrying about. Likely not, since as you mentioned before you're in a mail audit process. Are there websites that rate EAs or CPAs, for example, on how many audits they have won? Or should I simply rely on yelp.com ratings. There's no \"\"winning\"\" in audits. Ideally, given the same data, any EA or CPA would reach the same result in the discussion re audits with the FTB. Obviously, some are more experienced and some are less, and some are specializing on specific types of audits/entities, etc. Yelp is a place to start, but take the reviews there with a grain of salt since most reviewers are probably there to rant. If you see a repetitive pattern in the reviews - take that into consideration. For example, you probably don't want to hire someone who's been repeatedly unresponsive to their clients, not returning calls, not answering questions, being late, etc. Are all EAs and CPAs equal No. Some are generalists, some specialize in a specific area. Some build practice elusively on representation (IRS or FTB, or both), some provide a wide range of services from bookkeeping to Tax Court representation. I suggest looking for those who prominently advertise themselves as specializing in your area (whatever your type of business is), and representation in front of the FTB. Specialists, especially experienced, cost much more. Keep in mind - you'll be getting what you paid for. Also, when you hire a \"\"big shot\"\" EA/CPA - check who's actually going to do the work, and how much oversight the \"\"big shot\"\" is going to provide. Anything else that I potentially missed? Any specific questions that I should ask EA or CPA on initial interview? For example, if my EA/CPA could also talk with auditor in case FTB would want to talk directly with taxpayer, if possible? Well, that's the point of representation - to represent. They should be talking to the FTB in your name. You should verify credentials (IRS for EAs, CA CBA for CPAs), make sure their license is current. You can ask them about their continued education and how much of it is dedicated to the CA State law and FTB regulations. Ask them about their experience with similar cases. Overall, a decently qualified tax professional should be able to handle a mail audit without an issue, in-person representation may be harder since it does not only require being competent in the tax law, but also have some people skills.\"","title":""},{"docid":"467390","text":"For Federal Return, Schedule H and its Instructions are a great start. You are the nanny's employer, and are responsible for FICA (social security and medicare) withholding, and also paying the employer portion. You will offer her a W4 so she can tell you how much federal and state tax to withhold. You'll use Circular E the employer's tax guide to calculate withholding. In January, you'll give her a W-2, and file the information with your own tax return. For State, some of the above applies, but as I recall, in my state, I had to submit withholding quarterly separate from my return. As compared to Federal, where I adjusted my own withholding so at year end the tax paid was correct. Unemployment insurance also needs to be paid, I believe this is state. This issue is non-political - I told my friends at the IRS that (a) the disparity between state and federal to handle the nanny tax was confusing for those of us trying to comply, and (b) even though we are treated as an employer, a 'guide to the nanny tax' would be helpful, a single IRS doc that doesn't mix non-nanny type issues into the mix. In the end, if a service is cost effective, go for it, your time is valuable, and thi is something that only lasts a few years.","title":""},{"docid":"237331","text":"If you're under audit - you should get a proper representation. I.e.: EA or CPA licensed in California and experienced with the FTB audit representation. There's a penalty on failure to file form 1099, but it is with the IRS, not the FTB. If I remember correctly, it's something like $50 or $100 per instance. Technically they can disqualify deductions claiming you paid under the table and no taxes were paid on the other side, however I doubt they'd do it in a case of simple omission of filing 1099 forms. Check with your licensed tax adviser. Keep in mind that for the IRS 2011 is now closed, since the 3-year statute of limitations has passed. For California the statute is 4 years, and you're almost at the end of it. However since you're already under audit they may ask you to agree to extend it.","title":""},{"docid":"204703","text":"The request for your parent's income comes from Form 8615, Tax for Certain Children Who Have Unearned Income. I typically see this form appear as I'm doing my daughter's taxes and start to enter data from stock transactions. In other words, your earned income is your's. But if you are a dependent, or 'can be,' the flow avoids the potentially lucrative results from gifting children appreciated stock, and have them take the gain at their lower, potentially zero cap gain rate. I suggest you grab a coffee and thumb through Pub 929 Tax Rules for Children and Dependents to understand this better. From page 14 of the linked doc - Parent's return information not available. If a child can’t get the required information about his or her parent's tax return, the child (or the child's legal representative) can request the necessary information from the Internal Revenue Service (IRS). How to request. After the end of the tax year, send a signed, written request for the information to the Internal Revenue Service Center where the parent's return will be filed. (The IRS can’t process a request received before the end of the tax year.) It also suggests that you file for an extension for the due date of your return. Include payment for the tax you expect to pay, say by plugging in $200K for parent income as an estimate. My parents' accountant tells them I do not need it. Well, a piece of software told you that you do, and 3 people on line who collectively qualify as experts documented why. (Note, I am not full of myself. This board operates via the wisdom of crowds. Members DStanley, and Ben Miller, commented and edited to help me form a well documented response that would be tough to argue against.)","title":""},{"docid":"357481","text":"\"Sue the debt collectors in small claims court. There are several example stories around the internet, but this is a well written one from the consumerist. If your phone is a cell phone: \"\"it is against the law for a company to leave a pre-recorded message on your cell phone.\"\" In fact, the call frequency increased once they realized they had reached a live person. I called each of these companies multiple times, and though I was given assurances each time that my number would be taken off of their lists, the calls continued, morning, noon and night. At my wits end, I decided the only way to have the harassing calls stop was to file suits against the collection companies. It's very important to understand that it is against the law for a company to leave a pre-recorded message on your cell phone. Armed with this knowledge, I filed suit against several of the collection companies. I filed in small claims court so I did not need to hire an attorney, and the process was as simple as completing a paragraph on a complaint form. For evidence, I had over a hundred Google Voicemail transcripts showing the times the companies called and the text of the pre-recorded messages. Mysteriously, the calls all stopped immediately on the same date the collection companies received the certified letters stating they were being sued. Then a new flurry of calls began pouring in. This time it was their attorneys. The attorneys representing these out of state collection companies were all desperate to settle out of court. hey did not want to incur the expense of traveling for court or hiring a local law firm who wasn't on retainer. They also understood they had no justifiable defense for the calls. To make a long story short, so far I have successfully sued 3 of these collection companies and settled for more than $5,000 out of court. All it cost me was $35 and 20 minutes per suit. Making these companies pay is the only incentive for them to stop their illegal and harassing practices. If more consumers knew their rights and actually took a few minutes to stand up for them, it would become less profitable for these companies to conduct business the way they do now. -Source And whether you have a cell phone or land line, It is illegal for the debt collectors to tell you they are calling to collect a debt for someone else under the Fair Debt Collection Practices Act (wikipedia, ftc docs). What Remedies Are Available If The Debt Collector Violates The Law Under the Fair Debt Collection Practices Act, you have the right to sue a debt collector in state or federal court within one year from the date of the violation. If you win, you may recover damages in the amount of any losses you suffered as a result of the violation, plus an additional amount of up to $1,000.00. You may also be able to recover court costs and attorney fees. If the same debt collector has engaged in unlawful conduct with a number of consumers, it may be possible to find a lawyer who will file a class action lawsuit. -Source With regard to whether you can sue under FDCPA if you are not the debtor, one FDCPA lawyer (take with grain of salt) says yes: Did you know that it doesn't matter if you owe the account the debt collector is calling you about or not? If a debt collector violates the FDCPA (the federal Fair Debt Collection Practices Act, 15 USC 1692 et. seq.) that debt collector could be liable to pay you statutory damages, actual damages, attorney's fees, and court costs. -Source\"","title":""},{"docid":"382712","text":"\"The seriousness of your situation depends on whether your girlfriend was owed a refund for each tax return she failed to file, or whether she owed additional money. If she owed money on one or more of the tax returns she failed to file, stop! It is time to consult a lawyer. At the very least, you need to contact an accountant who specialises in this sort of thing. She will owe interest and penalties, and may be liable for criminal prosecution. There are options available and lawyers who specialise in this sort of thing (e.g. this one, from a simple google search). If she is in this position, you need professional help and you need it soon, so you can make a voluntary disclosure and head off criminal prosecution. Assuming the taxes are fairly simple, you are likely looking at a few thousand dollars, but probably less than $7,500, for professional help. There will be substantial penalties assessed as well, for any taxes owing. If you wait until the CRA starts proceedings, you are most likely looking at $10,000 to $50,000, assuming the matter is not too complicated, and would be facing the possibility of a jail term not exceeding five years. If she was due a refund on every single one of the tax returns she failed to file, or at least if she did not owe additional money, you are probably in a situation you can deal with yourself. She will want to file all of the tax returns as soon as possible, but will not be assessed a penalty. I have personally filed taxes several months late a number of times, when I was owed a refund. You may still want to consider professional help, but it is probably not necessary. Under no circumstances should she allow her father near her finances again, ever. You should also be careful to trust any responses to this question, including my response, because we are unlikely to be professional accountants (I certainly am not). You are well outside the abilities of an H&R Block \"\"accountant\"\" in this matter and need a real certified accountant and/or a lawyer who specialises in Failure To File cases.\"","title":""},{"docid":"37327","text":"I was in a similar (but not quite as bad situation) a couple years ago, and I had a stroke of luck that helped me, but your friend might be able to force a similar situation. My parents refused to take out the huge parent loan (understandably so), but my dad made enough money that I wasn't eligible for much aid. My stroke of luck came when they got divorced; I could refile my FAFSA with only one parent (using my mom with very little income), my aid shot through the roof and nearly covered my undergrad (this happened in California, I don't know if this works in other states). My advice for your friend would be to take the 6 units/part time job option, but do what she can to earn enough to pay her own rent/food/other bills. I think the requirement for filing as an independent is that you supply >50% of your own income. It won't kick in right away, but for next school year this would end up getting her a lot more money from the state/federal governments. For me it was enough to cover my school, food, rent, gas, car payment, and still have a little left over. (I don't know if this is still possible, and I know it doesn't work for graduate school, or if it applies to every state. It might be an option worth pursuing though)","title":""},{"docid":"166522","text":"\"I had about $16k in student loans. I defaulted on the loans, and they got > passed to a collection type agency (OSCEOLA). These guys are as legitimate as a collection agency can be. One thing that I feel is very sketchy is when they were verifying my identity they said \"\"Does your Social Security Number end in ####. Is your Birthday Month/Day/Year.\"\" That is not sketchy. It would be sketchy for a caller to ask you to give that information; that's a common scheme for identity theft. OSCEOLA are following the rules on this one. My mom suggested I should consider applying for bankruptcy Won't help. Student loans can't be discharged in bankruptcy. You have the bankruptcy \"\"reform\"\" act passed during the Bush 43 regime for that. The loan itself is from school. What school? Contact them and ask for help. They may have washed their hands of your case when they turned over your file to OSCEOLA. Then again, they may not. It's worth finding out. Also, name and shame the school. Future applicants should be warned that they will do this. What can I do to aid in my negotiations with this company? Don't negotiate on the phone. You've discovered that they won't honor such negotiations. Ask for written communications sent by postal mail. Keep copies of everything, including both sides of the canceled checks you use to make payments (during the six months and in the future). Keep making the payments you agreed to in the conversation six months ago. Do not, EVER, ignore a letter from them. Do not, EVER, skip going to court if they send you a summons to appear. They count on people doing this. They can get a default judgement if you don't show up. Then you're well and truly screwed. What do you want? You want the $4K fee removed. If you want something else, figure out what it is. Here's what to do: Write them a polite letter explaining what you said here. Recount the conversation you had with their telephone agent where they said they would remove the $4K fee if you made payments. Recount the later conversation. If possible give the dates of both conversations and the names of the both agents. Explain the situation completely. Don't assume the recipient of your letter knows anything about your case. Include evidence that you made payments as agreed during the six months. If you were late or something, don't withhold that. Ask them to remove the extra $4K from your account, and ask for whatever else you want. Send the letter to them with a return receipt requested, or even registered mail. That will prevent them from claiming they didn't get it. And it will show them you're serious. Write a cover letter admitting your default, saying you relied on their negotiation to set things straight, and saying you're dismayed they aren't sticking to their word. The cover letter should ask for help sorting this out. Send copies of the letter with the cover letter to: Be sure to mark your letter to OSCEOLA \"\"cc\"\" all these folks, so they know you are asking for help. It can't hurt to call your congressional representative's office and ask to whom you should send the letter, and then address it by name. This is called Constituent Service, and they take pride in it. If you send this letter with copies you're letting them know you intend to fight. The collection agency may decide it's not worth the fight to get the $4K and decide to let it go. Again, if they call to pressure you, say you'd rather communicate in writing, and that they are not to call you by telephone. Then hang up. Should I hire a lawyer? Yes, but only if you get a court summons or if you don't get anywhere with this. You can give the lawyer all this paperwork I've suggested here, and it will help her come up to speed on your case. This is the kind of stuff the lawyer would do for you at well over $100 per hour. Is bankruptcy really an option Certainly not, unfortunately. Never forget that student lenders and their collection agencies are dangerous and clever predators. You are their lawful prey. They look at you, lick their chops, and think, \"\"food.\"\" Watch John Oliver's takedown of that industry. https://www.youtube.com/watch?v=hxUAntt1z2c Good luck and stay safe.\"","title":""},{"docid":"15319","text":"\"3) NOT to claim her as my dependent. No additional tax return (since she is NOT my dependent), but also no penalty. My end of year balance would be $0 No. Not claiming her as a dependent does not save you from being responsible for her penalty. You are responsible for her penalty if she is your dependent (i.e. she meets the conditions for being your dependent), regardless of whether you claim her on your tax return or not. If you have the option of claiming her or not, then she is your dependent, and you are responsible for her penalty. 26 CFR 1.5000A-1(c)(2)(i): For a month when a nonexempt individual does not have minimum essential coverage, if the nonexempt individual is a dependent (as defined in section 152) of another individual for the other individual's taxable year including that month, the other individual is liable for the shared responsibility payment attributable to the dependent's lack of coverage. An individual is a dependent of a taxpayer for a taxable year if the individual satisfies the definition of dependent under section 152, regardless of whether the taxpayer claims the individual as a dependent on a Federal income tax return for the taxable year. [...] Form 1040 instructions, Line 61: [...] If you had qualifying health care coverage (called minimum essential coverage) for every month of 2015 for yourself, your spouse (if filing jointly), and anyone you can or do claim as a dependent, check the box on this line and leave the entry space blank. Otherwise, do not check the box on this line. If you, your spouse (if filing jointly), or someone you can or do claim as a dependent didn’t have coverage for each month of 2015 you must either claim a coverage exemption on Form 8965 or report a shared responsibility payment on line 61. [...] So you cannot check the box and must report exemptions for your sister, or report a shared responsibility payment. Form 8965 instructions, Definitions, \"\"Tax household\"\": For purposes of Form 8965, your tax household generally includes you, your spouse (if filing a joint return), and any individual you claim as a dependent on your tax return. It also generally includes each individual you can, but don't, claim as a dependent on your tax return. [...] Your sister is part of your tax household regardless of whether you claim her, and you must compute her shared responsibility payment for any months she did not have insurance and did not qualify for an exemption.\"","title":""},{"docid":"162405","text":"I hate apples business practice down to the core, but whenever a not-so-tech-savvy friend or older gentleman/lady asks me what I think about Apple,...I cite their customer service. A lot of the other companies out there either require a million dollar service package, or you are on the phone with a call center in India. I don't mind this myself as I love the freedom it gives me over Apple (Hell, none of my software/hardware (except my laptop) is an OEM package)...but for an older lady who just cant seem to figure out how to get her email open...an apple care center (or whatever they call them, genius bars?) down the road is a fantastic option.","title":""},{"docid":"446628","text":"Does this technically mean that she has to pay AMT on $400,000? Yes. Well, not exactly 400,000. She paid $1 per share, so 390,000. And if so, is %28 the AMT for this sum? (0.28 * $400,000 = $112,000)? Or does she have to include her salary on top of that before calculating AMT? (Suppose in the fake example that her salary is $100,000 after 401k). All her income is included in calculating the AMT, minus the AMT exemption amount. The difference between the regular calculated tax and the calculated AMT is then added to the regular tax. Note that some deductions allowed for the regular calculation are not allowed for the AMT calculation. How does California state tax come into play for this? California has its own AMT rules, and in California any stock option exercise is subject to AMT, unless you sell the stock in the same year. Here's a nice and easy to understand write up on the issue from the FTB. When would she have to pay the taxes for this huge AMT? Tax is due when income is received (i.e.: when you exercise the options). However, most people don't actually pay the tax then, but rather discover the huge tax liability when they prepare to submit their tax return on April 15th. To avoid that, I'd suggest trying to estimate the tax and adjust your withholding using form W4 so that by the end of the year you have enough withheld. Suppose in the worst case, the company goes completely under. Does she get her massive amounts of tax back? Or if it's tax credit, where can I find more info on this? That would be capital loss, and only up to $3K a year of capital loss can be deducted from the general income. So it will continue offsetting other capital gains or being deducted $3K a year until it all clears out. Is there any way to avoid this tax? (Can she file an 83b election?) You asked and answered. Yes, filing 83(b) election is the way to go to avoid this situation. This should be done within 30 days of the grant, and submitted to the IRS, and a copy attached to the tax return of the grant year. However, if you're considering exercise - that ship has likely sailed a long time ago. Any advice for Little Susie on how she can even afford to pay that much tax on something she can't even sell anytime soon? Don't exercise the options? Should she take out a loan? (e.g. I've heard that in the extreme case, you can find angel investors who are willing to pay all your taxes/strike price, but want 50% of your equity? I've also heard that you can sell your illiquid shares on SecondMarket?) Is she likely to get audited by IRS for pulling something like this? You can take a loan secured by shares you own, there's nothing illegal in it. If you transfer your shares - the IRS only cares about the taxes being paid, however that may be illegal depending on the terms and the conditions of the grant. You'll need to talk to a lawyer about your situation. I suggest talking to a licensed tax adviser (EA/CPA licensed in your State) about the specifics concerning your situation.","title":""},{"docid":"324417","text":"\"**Reposted so you don't have to look at silly GIFs for 50% of the article.** Sophie is a physical penetration tester and information security consultant. She specializes in social engineering security assessments including physical, voice (vishing) and text (phishing). She consults in remediation and prevention of security incidents through creation of policy and procedures, as well as customized training for your individual office culture. Prior to working in infosec, Sophie was a journalist, photographer, and a mom. Hello! My name is Sophie and I break into buildings. I get paid to think like a criminal. Organizations hire me to evaluate their security, which I do by seeing if I can bypass it. During tests I get to do some lockpicking, climb over walls or hop barbed wire fences. I get to go dumpster diving and play with all sorts of cool gadgets that Q would be proud of. But usually, I use what is called social engineering to convince the employees to let me in. Sometimes I use email or phone calls to pretend to be someone I am not. Most often I get to approach people in-person and give them the confidence to let me in. My frequently asked questions include: What break-in are you most proud of? What have you done for a test that you were the most ashamed of? What follows is the answer to both of these questions. A few months ago, a client had hired me to test two of their facilities. A manufacturing plant, plus data center and office building nearby. First step: open source intelligence, or OSINT. I look at maps, satellite images, study what I can of their delivery and supply schedules, and so on. The manufacturing facility looked like a prison. No windows, heavy iron gates, no landscaping. Generally a monstrosity of architecture. This facility had armed guards, badge readers, biometric security controls and turnstiles at every entrance. I remember thinking, \"\"It's got to be hell to work in there. I wonder if I can use that…\"\" One thing was for sure… The chances of tailgating (following behind an employee with valid credentials) into this building were next to non-existent. I was going to have to get down and dirty with my social engineering. First stop: LinkedIn. Your LinkedIn is my best friend. The more information you have on your LinkedIn, the more options I have. I have several fake LinkedIn profiles that you are probably connected to. I scour profiles of employees who work at these facilities, and cross-reference them to other social media sites. And I find a lovely young woman who I'm going to call Mary. Mary was a brand-new hire working as an assistant at the manufacturing facility. Mary had a public Facebook account too. On Mary's public Facebook account, she documented all of her family's adventures. Side note: Now I know where Mary went to high school, her mother's maiden name, the names of her pets, etc. Answers to those \"\"security questions\"\" you use to reset your passwords are very easy to find if you aren't careful with that information. Not to mention that now I know where Mary works, where her kids go to school, where they vacation…I could go on. Scary stuff. This is not an advanced investigation. I'm not a private investigator and I don't have the resources of the NSA. But I can do a lot of damage with simple methods. Most notably to me, there were photos Mary posted of her time volunteering with a certain maternity support center. Her passion for children and caring new moms was very plain. So of course, I took advantage of it. For this assessment I played two roles. For the first, I spoofed my phone number to make it look like it was coming from the company's headquarters. I called the front desk of the manufacturing facility and was transferred to Mary. \"\"Hi Mary!\"\" I said, \"\"My name is Barbara.\"\" \"\"I am a project coordinator with facilities management. We are renovating a few of our facilities. We are sending an interior designer out to you tomorrow so she can put together proposals to update your space!\"\" Mary replied, \"\"Well that's great! But why the short notice?\"\" I could feel her getting suspicious, so I pulled out my trump card… *Sigh* \"\"Well Mary… You really should have heard from me sooner. I've just been so overloaded at work…I feel like I can't catch up, and to top it off the baby is due in 6 weeks. If my boss finds out I messed this up he's going to flip.\"\" I was really getting into this, voice shaking. (Yes, I know, I'm a terrible human being.) She cut me off, \"\"Oh hunny, hunny it's ok. We will work this out! Tell me about the baby! Is it your first? Boy or girl?!\"\" Our Mary was committed at this point. Not because she is stupid, but because she is a good person. She wanted to help me. We talked babies and birth plans for a while (never pick a pretext you can't speak about at length.) Mary took down the name of the \"\"designer\"\" who was coming by the next day and we said our goodbyes. Mary could have saved her company a lot of heartache by simply verifying that I was who I claimed to be. (Just to be clear here, I would never give out Mary's real identity. I'm not totally heartless. This could have happened to anyone. She has not been fired.) I showed up the next day as \"\"Claire\"\" with a fictional architecture firm that I had made business cards and a website for. My alter-ego Barb had done most of the leg work for me. When I arrived, Mary and her boss were waiting for me with smiles. I shook hands all around and handed them the business card I printed out the night before. I was given a visitor badge and the red carpet was rolled out. I gained rapport with the staff there by asking them to tell me what they wanted in an office space. They were so excited. I might have claimed to be on the team that put together the Google offices…(Yes, I am HORRIBLE. This is my inner demon child.) \"\"You want a standing desk? New chairs over here?! Ergonomic keyboards for everyone! Let's look at swatches!\"\" We became best buds. I was given complete and unaccompanied access to the facility where I stayed for several hours. I gained network access and stole several thousands of dollars in physical primitives by picking my way through cheap locks (credit to Deviant Ollam for the rad lockpicking animations.) This client had been pretty confident that I wouldn't get into either facility, much less be able to hit both in a short time span. So the timeline was left to my discretion, but it was assumed that I would need to fly to the area twice. I didn't see the need in burdening them with two round-trip expenses. I went back to Mary's office and said, \"\"Well I think I have what I need from here. How do I get to the office center?\"\" She looked at her watch and said, \"\"It's almost lunch time. I'll take you there!\"\" A whole group of us piled into the parking lot, and they took me to a nearby taco shop. That's right. My Marks took me to get tacos… I love my job. After lunch they drove me to the offices and a few of them came in with me to show me around. I took FOREVER looking around this office space, and eventually they said their goodbyes because they had to go back to work. They had a strict policy of escorting visitors. But I had been seen walking around with trusted insiders so no one questioned me. I was free to take my time. I made myself at home. My main objective at this site was to weasel my way into private corner offices. When I accomplished my goals, I tracked down my point of contact's office. This is the man who hired me in the first place. This is the best part of every job. Steve was there, hard at work when I disturbed his groove by knocking on the door. He glanced up, \"\"Hi there, can I help you?\"\" I smiled. \"\"Hi Steve! I'm Sophie from Sincerely Security. It's nice to meet you in-person!\"\" I will never forget the look on his face… Pure gold. \"\"Who?.... Wait, what? How? How did you get in here?!\"\" We stayed in his office and talked for a long time. I went over exactly the steps that could have prevented my success. First of all, the desire to help others is human and natural. We don't want to discourage that. Second, I'm sure they did have some sort of policy that required visitors to check in showing government issued identification, but they weren't following it. We also need to post by every computer, phone and door: \"\"TRUST, BUT VERIFY.\"\" An employee who does their homework can ruin my day. Third, if it seems too good to be true, it probably is. Is your company going to hire the team who designed Google's offices? Magic 8 ball says no. Lastly, the team who took me to the second location should have found someone else to escort me through the building. I've been doing this job for a couple years now, and almost every job is a variant of this story. Very rarely do I go through an entire assessment without some sort of social engineering. There are ways to protect yourself and your company from attacks like this. I think it starts by sharing stories like these, and educating and empowering each other to be vigilant.\"","title":""},{"docid":"34338","text":"\"If you live outside the US, then you probably need to deal with foreign tax credits, foreign income exclusions, FBAR forms (you probably have bank account balances enough for the 10K threshold) , various monsters the Congress enacted against you like form 8939 (if you have enough banking and investment accounts), form 3520 (if you have a IRA-like local pension), form 5471 (if you have a stake in a foreign business), form 8833 (if you have treaty claims) etc ect - that's just what I had the pleasure of coming across, there's more. TurboTax/H&R Block At Home/etc/etc are not for you. These programs are developed for a \"\"mainstream\"\" American citizen and resident who has nothing, or practically nothing, abroad. They may support the FBAR/FATCA forms (IIRC H&R Block has a problem with Fatca, didn't check if they fixed it for 2013. Heard reports that TurboTax support is not perfect as well), but nothing more than that. If you know the stuff well enough to fill the forms manually - go for it (I'm not sure they even provide all these forms in the software though). Now, specifically to your questions: Turbo tax doesn't seem to like the fact that my wife is a foreigner and doesn't have a social security number. It keeps bugging me to input a valid Ssn for her. I input all zeros for now. Not sure what to do. No, you cannot do that. You need to think whether you even want to include your wife in the return. Does she have income? Do you want to pay US taxes on her income? If she's not a US citizen/green card holder, why would you want that? Consider it again. If you decide to include here after all - you have to get an ITIN for her (instead of SSN). If you hire a professional to do your taxes, that professional will also guide you through the ITIN process. Turbo tax forces me to fill out a 29something form that establishes bonafide residency. Is this really necessary? Again in here it bugs me about wife's Ssn Form 2555 probably. Yes, it is, and yes, you have to have a ITIN for your wife if she's included. My previous state is California, and for my present state I input Foreign. When I get to the state tax portion turbo doesn't seem to realize that I have input foreign and it wants me to choose a valid state. However I think my first question is do i have to file a California tax now that I am not it's resident anymore? I do not have any assets in California. No house, no phone bill etc If you're not a resident in California, then why would you file? But you might be a partial resident, if you lived in CA part of the year. If so, you need to file 540NR for the part of the year you were a resident. If you have a better way to file tax based on this situation could you please share with me? As I said - hire a professional, preferably one that practices in your country of residence and knows the provisions of that country's tax treaty with the US. You can also hire a professional in the US, but get a good one, that specializes on expats.\"","title":""},{"docid":"520395","text":"\"I've received letters notifying me of data breaches in the past. In the end, I've never signed up for the offered protection service, figuring if \"\"they\"\" can hack Target or ADP or the IRS, they can hack anybody, like... Equifax. And now Equifax has been hacked. My family's Social Security Numbers were stolen from a hospital database. I think that information, plus public information was used to gain further data from the IRS FAFSA tool. (we got a letter from the IRS). Ultimately, fraudsters used whatever data they had to file a tax return with the IRS and with the Cali FTB (we don't and never have lived in California). We got letters from both, and managed to stop the fraud before it really impacted us...other than having to file a paper tax form this past tax season. Anyway... in a world where Equifax gets hacked: the only solution is: I don't bother with the crazy password schemes you talk about... I have a few different passwords I use, but most my investment accounts use the same username and password. It's all about risk. Bruce Schneier says the same thing. The amount to spend on security should depend on what you're trying to protect. I don't care much if somebody gets into my google account, because I have a google account just because I have to. I barely use it at all. Similarly my yahoo account. My yahoo account uses my \"\"insecure password\"\", and my investment accounts use my \"\"secure password\"\". Credit Card info? Meh. Unless they get into the credit card company database, which undoubtedly has my Social Security Number, it's not that big of a deal. Yeah, they can make fraudulent charges, but there are legal protections, so in theory I can't be out any money. So think this way: what's the risk, and what's the appropriate level of effort to take to mitigate that risk.\"","title":""},{"docid":"342400","text":"Look I'm up for a dialogue, but I'd appreciate civility. If you look back at my responses on this post I've said multiple times that I'm willing to help people who help themselves. I'm also pointing out that 1.) this article 'slavery' aspect is off and 2.) I'm not 100% convinced she is doing all she can to further better herself (maybe she is but the article didn't convince me). I've said before I give her props for getting her ass off, good on her. And I'm all for helping out people (for a limited time) who actually deserve it and have actually worked hard for it. In the lead featured in the article sounds like she would be a very very good candidate. I am a generous person, I want to help people and I'm willing to do so. They just need to want help. My generosity ends when it becomes mandatory to support anyone who has made any number of bad decisions and is not deserving of my help (we can talk about who deserves help in more detail anytime). Should I support a family of people in which the parents keep pumping out kids, and the mom is a stat at home mom and the dad works at a slightly above minimum wage? No! Should I support single mom who chooses not to work, and mooches off friends and family? No Both of these cases may seem cherry picked, and while they are to an extent they are both real cases that I've/a personal friend have witnessed.","title":""},{"docid":"133235","text":"\"Do I understand correctly, that we still can file as \"\"Married filing jointly\"\", just add Schedule C and Schedule SE for her? Yes. Business registration information letter she got once registered mentions that her due date for filing tax return is January 31, 2016. Does this prevent us from filing jointly (as far as I understand, I can't file my income before that date)? IRS sends no such letters. IRS also doesn't require any registration. Be careful, you might be a victim to a phishing attack here. In any case, sole proprietor files a regular individual tax return with the regular April 15th deadline. Do I understand correctly that we do not qualify as \"\"Family partnership\"\" (I do not participate in her business in any way other than giving her money for initial tools/materials purchase)? Yes. Do I understand correctly that she did not have to do regular estimated tax payments as business was not expected to generate income this year? You're asking or saying? How would we know what she expected? In any case, you can use your withholding (adjust the W4) to compensate.\"","title":""},{"docid":"169723","text":"I agree with mhoran_psprep's answer, but would like to add a few additional points to consider. TurboTax and the professional it will send to represent you in case of a tax audit have no more information about your tax return than what you entered into the program. Now, there are three (or four) different kinds of audits. The correspondence audit is the most common kind where IRS sends a letter requesting copies of documents supporting a deduction or tax credit that you have claimed. Representation is hardly necessary in this case. The office audit is more serious where you have to make an appointment and go to the local IRS office with paperwork that the examining agent needs to see physically, and to answer questions, etc. It would be better to be accompanied by a representative at these meetings. But, office audits are not as common as correspondence audits, and, because they are expensive for the IRS, usually occur when the IRS is fairly sure of recovering a substantial sum of money. If you have been cutting corners and pushing the envelope in taking large enough deductions to make it worthwhile for the IRS to go after you, you probably should not have been using TurboTax to file your income tax return but should have been using an accountant or tax preparer, who would be representing you in case of an audit. If the reason that you used TurboTax is that no accountant was willing to prepare a tax return with the deductions that you wished to claim, I doubt that having TurboTax's representative with you when you go to the IRS office will help you all that much. An example of a field audit is when the IRS agent comes to your home to see if you actually have a space set aside to use exclusively as your home office as you claimed you did etc. A Taxpayer Compliance Measurement Program (TCMP) audit is where the IRS randomly chooses returns for statistical checks that taxpayers are complying with the regulations. The taxpayer has to prove every line of the return. You claim to be filing as Married Filing Jointly? Bring in your marriage certificate. Submit birth certificates and Social Security cards of your dependent children. And so on. Yes, having TurboTax represent you for only $49.95 will help, but not if you are not married and cannot provide the IRS with a marriage certificate etc. So, pay the fee for peace of mind if you like, and as insurance as littleadv suggests. But be sure you understand what you might be getting for the money. Most tax returns selected for audit are selected for what the IRS believes are good reasons, not at random. If what you said If my tax return is randomly selected for audit they will represent me. is interpreted literally, TurboTax will represent you only if your return is selected for examination under the TCMP program, not if it is selected for audit because the IRS believes that something is fishy about your return. And as always, you get what you pay for.","title":""},{"docid":"350972","text":"\"I'm working from 6am-2pm today (from home, since it's Saturday) and I'm on call from 2pm-4am tomorrow. If the phone rings at our company help desk at any time from 2pm-4am, I am expected to answer it or return the call promptly. I'm not paid for the entire time of 2pm-4am, but only for the time I'm \"\"on a call\"\" essentially. It was a shock when I found out that was the terms of the job (3 months in, there were dramatic changes in my schedule) and most of my friends seem to agree with me. Am I off base?\"","title":""},{"docid":"131926","text":"\"I agree about not wanting to get into your friend's personal business, and it's a scummy bill collector that repeatedly calls friends or family to track down a debtor. On the other hand, at least he's made it obvious he's calling about a debt as opposed to pretending to be tracking down your friend with some other pretext. Nevertheless, you want the calls to stop. Here are two suggestions: Perhaps, a small fib: \"\"The creep owes me money too! Grrr! Let me know when you find him!\"\" The bill collector probably won't call you again :-) Or, if you're like me and uncomfortable fibbing – even to a scummy bill collector! – then here's a more truthful yet direct approach: \"\"I told you already it's not my debt, it's none of my business, and that I want you to stop calling me. You have no right to harass me and if you call again I will involve the police. There will be no other warning.\"\" Then have the phone company block the bill collector's phone number from calling you.\"","title":""},{"docid":"521061","text":"\"This is exactly what I feel. Having doing tech support for offices, friends and family, it dawned on me that they had no one else to call. If Grandma calls \"\"Sony\"\" because she can't find her email, well then they tell her to call Microsoft. Then she calls Microsoft and it seems it's a hardware issue, they send her back to Sony. In the end, the customer doesn't fully understand why they are being sent back and forth, they just want it fixed, or a reason. Apple is almost completely vertically integrated, they can solve most of the problems or at least provide the illusion that the customer is being helped.\"","title":""},{"docid":"218986","text":"\"You don't have to hire a tax consultant, there is a number of companies who sell software (installable or web-based) that helps you do it by asking for all relevant data interview-style. These typically cost between 15 and 25 EUR. I'm not sure whether any of them are available in English, but if you can read German well, you should be OK. taxback.com is in English, but to be honest it looks a bit dodgy to me. Now for your questions: are there some tricky fields (lines) that after filling in my taxes will be counted higher? This is rare, at least for employees you nearly always get something back. are there some tricky fields (lines) that after filling in my taxes could be counted lower? Not in general. Marriage is mentioned below, and otherwise it's all about individual deductibles. Ah, one important factor: if you have investment income and have not filed a Freistellungsauftrag with your bank, you can get some of the taxes by filling out the \"\"Anlage KAP\"\" form with data you got in the Jahressteuerbescheinigung from your bank. are there some flat-rates (Pauschals) that I could get advantage from? Absolutely. As an employee, the biggest factor is the Werbungskostenpauschale of (I think currently) 1000 EUR for general work-related expenses, which will be accepted without proof. If your expenses are higher than that and you file individual expenses, there are flat rates for work-related moving and for commuting distance. is it better to give a tax return together with my wife (who was only a girlfriend in 2013 living with me in one household) or to give it separately? It's not possible to do a joint tax filing for the time before your marriage. What you should consider is to apply for a different tax class from now on, if one of you earns significantly more than the other. when separately, do I have to fill her information in my tax return or can I just pretend there is nobody else in my apartment? As far as taxes are concerned, unmarried roommates are treated completely separately with one exception: only one of you can deduct service charges included in your rent. You have to get a Nebenkostenabrechnung from your landlord, and service charges, i.e. janitor, gardener, etc. should be marked separately. But this may not be worth bothering with, usually it results in a tax return of maybe 15 EUR. is there any guide in English that could be of help with filling in the tax return form? I couldn't find anything that looked really useful in a short search.\"","title":""},{"docid":"23675","text":"I asked my realtor, but she recommends to go with just one banker (her friend), and not to do any rate shopping. You need a new realtor. Anyone who would offer such advice is explicitly stating they are not advocating on your behalf. I'd do the rate shopping first. When you make an offer, once it's accepted, time becomes critical. The seller expects you to go to closing in so many days after signing the P&S. The realtor is specifically prohibited from pushing a particular lender on you. She should know better. In response to comment - Rate Shopping can be as simple as making a phone call, and having a detailed conversation. Jasper's list can be conveyed verbally. Prequalification is the next step, where a bank actually writes a letter indicating they have a high confidence you will qualify for the loan.","title":""},{"docid":"544663","text":"\"This is more of a long comment but may answer user's situation too. I have dealt with joint mortgages before in 3 states in the US. Basically in all three states if one party wants to sell, the home goes up for sale. This can be voluntary or it can go up via auction (not a great choice). In 2 of the 3 states the first person to respond to the court about the property, the other party pays all legal fees. Yes you read this right. In one case I had an ex who was on my mortgage, she had no money invested in the house ($0 down and still in college with no job). [If she wasn't on the mortgage I wouldn't have gotten loan - old days of dumb rules] When we split her lawyer was using the house as a way to extort other money from me. Knowing the state's laws I already filed a petition for the property but put it on hold with the clerk. Meaning that no one else could file but if someone tried mine would no longer be on hold. My ex literally spent thousands of dollars on this attorney and they wanted to sell the house and get half the money from the house. So sale price minus loan amount divided between us. This is the law in almost every state if there is no formal contract. I was laughing because she wanted what would be maybe 50-75K for paying no rent, no money down, and me paying for her college. Finally I broke her attorney down (I didn't lawyer up but had many friends who were lawyers advising). After I told her lawyer she wasn't getting anything - might have said it in not a nice way - her lawyer gave me her break down. To paraphrase she said, \"\"We are going to file now. My assistant is in the court clerk's office. You can tell the court whatever you want. Maybe they will give you a greater percentage since you put the money down and paid for everything but you are taking that chance. But you will pay for your lawyer and you will need one. And you will pay for me the entire time. And this will be a lengthy process. You would be better served to pay my client half now.\"\" Her office was about 2 blocks from court. I laughed at her and simply told her to have her assistant do whatever she wanted. I then left to go to clerk's office to take the hold off. She had beat me to the office (I moved my car out of her garage). By the time I got there she was outside yelling at her assistant, throwing a hissy fit, and papers were flying everywhere. We \"\"settled\"\" the next day. She got nothing other than the things she had already stolen from me. If I wouldn't have known about this loophole my ex would have gotten or cost me through attorney's fees around 40-50K for basically hiring a lawyer. My ex didn't really have any money so I am pretty sure lawyer was getting a percent. Moral of the story: In any contract like this you always want to be the one bringing in the least amount of money. There are no laws that I know of in any country where the person with the least amount on a contract will come out worse (%-wise). Like I said in the US the best case scenario that I know of for joint property is that the court pays out the stakeholder all of their contributions then it splits things 50/50. This is given no formal contract that the court upholds. Don't even get me started with hiring attorneys because I have seen the courts throw out so many property contracts it isn't even funny. One piece of advice on a contract if you do one. Make it open and about percentages. Party A contributes 50K, Party B 10K, Party A will pay this % of mortgage and maintenance and will get this % when home is sold. I have found the more specific things are the more loopholes for getting out of them. There are goofy ass laws everywhere that make no sense. Why would the person first filing get their lawyers paid for??? The court systems in almost all countries can have their comical corners. You will never be able to write a contract that covers everything. If the shower handle breaks, who pays for it? There is just too many one-off things with a house. You are in essence getting in a relationship with this person. I hear others say it is a business transaction. NO. You are living with this person. There is no way to make it purely business. For you to be happy with this outcome both of you must remain somewhat friends and at the very least civil with each other. To add on to the previous point, the biggest risk is this other person's character and state of mind. They are putting in the most money so you don't exactly have a huge money risk. You do have a time and a time-cost risk. Your time or the money you do have in this may be tied up in trying to get your money out or house sold. A jerk could basically say that you get nothing, and make you traverse the court system for a couple years to get a few thousand back. And that isn't the worst case scenario. Always know your worst case scenario. Yours is this dude is in love with you. When he figures out 2-3 years later after making you feel uncomfortable the entire time that you are not in love with him, he starts going nuts. So he systematically destroys your house. Your house worth plummets, you want out, you can't sell the house for price of loan, lenders foreclose or look to sue you, you pay \"\"double rent\"\" because you can't live with the guy, and you have to push a scooter to get to work. That is just the worst case scenario. Would I do this if I were 25 and had no family? Yea, why not if I trusted the other person and was friends with them? If it were just a co-worker? That is really iffy with me. Edit: Author said he will not be living with the person. So wording can be changed to say \"\"potentially\"\" in front of living with him in my examples.\"","title":""},{"docid":"115172","text":"I have been in a similar position for quite a while now and the only thing that seems to help is screening phone calls. I have a long list of collector numbers set to not ring on my phone. They can still leave a voice mail but they never do. As far as I know there aren't any laws that protect you from nuisance phone calls. FDCPA letters only apply to the debtor and the collector it is sent to it doesn't protect an unrelated third party from getting annoying phone calls. I have a feeling that sending FDCPA letters is just confirming that you probably are the debtor and prolong the collection calls.","title":""},{"docid":"324445","text":"\"Having worked in insurance, I can give you a few pointers. Firstly, state that you \"\"may have to complain\"\". Insurers hate complaints because they really complicate matters, are loads of work and must be tracked. I would advise not actually escalating it to a complaint until later as this may cause a delay as the actual process is quite convoluted. Mentioning the possibility of complaint sometimes makes people a bit more active. Try and resolve the issue, and if you aren't getting anywhere then make a complaint. Maintain a friendly, assertive, polite demeanor. If you get angry and aggressive you'll not likely get far. Remember that the people on the end of the phone are both human and more knowledgeable about insurance than you. You want them on your side, not against you. Make copious notes. If you can, record calls. If you are recording calls you will likely legally need to give them the option of not being recorded, so make sure you mention that you're recording each individual call as soon as you start speaking to the handler. Refer to your notes and make sure you carry out actions you say you will. If you spend a few days sending something you said you'd email over that day, and you then chase them a few days after that they may not have had the document through their workflow yet. It also engenders urgency if you're acting promptly, and suggests that you don't really care if you're taking your time. Get Names. This is an important step, as this gives the handler someone to talk to who may be familiar with your case. You may end up speaking to the same people more than once, so try and build a rapport if you do. \"\"I like this guy\"\" may lead to a bit more effort being put in, and a potentially better outcome. In my experience, GoSkippy can be a bit slow to respond to things, so you'll likely have to chase them up. If you chase them up and say \"\"I called on X date, discussing Y with Z and Z said they would do A, B and C. Has this been done yet?\"\" it looks better than saying \"\"I called about a week ago and spoke to one of your colleagues who said he'd do something for me. He's not done it, what's going on?\"\", As to a plan of action, I would split this into two points: Mis-sold policy and definition of commuting. Mis-sold policy - If they truly gave your wife two options, then they messed up. The standard 3 offered by goskippy are Social Domestic and Pleasure (SDP), SDP+Commuting, and SDP+C and Business use. Other companies sometimes roll commuting into SDP as standard. On the comparison sites however, there are usually the three separate options, and if you used one to set the policy up and clicked \"\"SDP Only\"\" then you may be in trouble. Social domestic and pleasure only DOES NOT include commuting. Whilst it is your responsibility to thoroughly check any documentation that comes through, it could be argued that if given two options between Business Use and SDP, then a reasonable person could be considered to assume that Goskippies definition of SDP did include commuting. Therefore, they need to prove to you that there were three options offered and that your wife specifically excluded commuting. IF they can't, then you should be able to argue that only two were offered and that commuting could have reasonably been assumed to be included. Use that term \"\"reasonable person\"\" btw, it's used in a lot of internal literature - at least at the insurer, I worked at. not commuting - Firstly, clarify their definition of \"\"commuting\"\". If your wife was on her way to work afterwards, then they may well consider she was commuting. For instance, at present, I drive from my house to my son's childminders, then to my wife's work and finally to mine. My commute could be argued to be 1 minute (my workplace is probably a minutes drive from my wife's, but I can't park in her car-park), but if I were to have an accident between my house and my son's childminder (~15 mins drive) the insurers would probably consider that commuting. If she was not on her way to work afterwards, and assuming your wife arranged her visit via text (or whatsapp, fb messenger or similar) you should easily be able to show that your wife had driven from a friends house to the childminder. If she was on a holiday day or was not working on that day, then that's also something you should be able to prove either with proof of her working pattern or proof of her holiday. If she doesn't have a job at all, then again, that's something that's provable. Proof reigns king in claims, so if you can prove certain key facts then you should be on to a winner.\"","title":""},{"docid":"221502","text":"I was in that same situation years ago with my parents. One way she could apply for a loan in her name without her parents is if she is not currently living with them she shouldn't need them to cosign if she doesn't have bad credit. But if she isn't living with them and they aren't financing her room and board they can't claim her as a dependent so if she really wants to stick it to them she can go and try to politely explain how the loans work and tell them if they don't cosign for her then she will apply on her own (which she can only do while not living with them I believe but not sure) and they will HAVE to STOP claiming her as a dependent on their taxes. If they don't agree she can put her foot down and force them to stop claiming her and tell them she will file her own application anyway and if they continue claiming her and get in trouble for it it's their own fault cause she warned them to stop first. They may agree to cosign rather than lose her as a dependent if it makes that big of a difference on their taxes, if they don't then she can forcefully punish them financially and their taxes will go up. Those were my choices when my parents refused to cosign for me to live at school but that was back in 1999-2000 and things may have changed since then, things also change state by state and I live in PA.","title":""},{"docid":"396792","text":"\"Paypal linked with my bank account. 1.Can I use my Saving bank account to receive payments from my clients? Or is it necessary to open a current account? Yes you can get funds into your savings account. However it is advisable to keep a seperate account as it would help with your IT Returns. 2.I will be paying a certain % as commission on every sales to a couple of sales guys (who are not my employees but only working on commission). Can I show this as an expense in my IT returns? As you are earning as freelancer, you are eligible for certain deductions like Phone calls, Laptop, other hardware, payments to partners. It is important that you maintain a book of records. An accountant for a small fee of Rs 5 K should be able to help you. In the Returns you have to show Net income after all these deductions, there is no place to enter expenses. 3.Since I will be receiving all the payments in Euros so am I falling under a category of \"\"Exporter of services\"\"? The work you are doing can be Free Lancing. 4.Do I need an Import Export Code (IEC) for smoothly running this small business? You can run this without one as Free lancing. IEC would be when you grow big and are looking for various benefits under tax and pay different taxes and are incorporated as a company.\"","title":""},{"docid":"520026","text":"You could do a voluntary repossession. While a repossession never looks good on your credit a voluntary repossession is slightly better. A good friend of mine had a situation like this about 11 years ago. She was in an accident didn't have replacement coverage insurance and was left with a large chunk of debt on a wrecked vehicle that she then rolled into a new car. In the end it came down to the simple fact that she could not afford a car loan on a vehicle that never was worth as much as she owed. Since the car was worth less than the loan she really couldn't sell it to fix the problem. She called and arranged a voluntary repossession. She stopped making payments, and parked the car till they came and picked it up. (Took about 4 months and 20 phone calls from her for them to come get it.) In the mean time, I purchased her a much older used but decent car for a couple thousand and she paid me back over the next year. The total she paid me back was less than the money she would have paid in the 4 months it took them to come get the car. In fact by the time they picked up the car she had paid back over half on the car I bought her. Yes the repossession did stay on her credit for seven years but during that time she was approved for a mortgage, cellphone plans, and credit cards etc. Therefore I don't know that it did that much damage to her credit. When her car was sold at auction by the repo company it sold for much less than the loan amount. Technically she was on the hook for the remaining amount. The outstanding balance on the loan was then sold several times to several different collection agencies. Over the years since then she has gotten letters every now and then demanding she pay the amount off, she ignores these. Most of these letters even included very favorable terms (full forgiveness for 20% of the amount) At this point the statute time has run out on the debt so there is no recourse for anyone to collect from her. The statute time limit varies from state to state. Some states it is as long as 10 years in others it is as short as 3 years. What this means is that counting from the date of the repossession, incurrance of debt, last payment, or agreement to pay whichever is later if the statute period has elapsed and the lender/collector has not filed a suit against you by the end of the period then they have effectively abandoned the debt and cannot collect. Find out what that period of time is in your state. If you can avoid the collection agencies till that period runs out you are scott free. You just have to make sure that you do not ever send them any money, or agree to pay them anything as this resets the calendar. If you do not want to wait for the calendar to run out if you wait long enough you will probably be offered favorable terms to pay only a fraction of the remaining amount, you just have to wait it out. Note, I normally would not endorse anyone not paying off their debts. However sometimes it is necessary and it is for this type of situation that we have things like this and bankruptcy.","title":""}],"string":"[\n {\n \"docid\": \"366761\",\n \"text\": \"I called the IRS (click here for IRS contact info) and they said I do not need to get a new EIN. I could have just filed the appropriate employer federal tax return (940/941) and then the filing requirements would have been updated. But while I was on the phone, they just updated the filing requirements for my LLC so I am all good now (I still need to file the correct form and make the correct payments, etc. but I can use this same EIN going forward). Disclaimer: Don't trust me (or this answer) for tax advice (your situation may be different). The IRS person on the phone was very helpful so I recommend calling them if you are in a similar situation. FYI, I have found calling the IRS to always be very helpful.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"222726\",\n \"text\": \"\\\"What is the right way to handle this? Did you check the forms? Did the form state $0 tax due on the FTB LLC/Corp form (I'm guessing you operate as LLC/Corp, since you're dealing with the Franchise Tax)? The responsibility is ultimately yours. You should cross check all the numbers and verify that they're correct. That said, if the CPA filled the forms incorrectly based on your correct data - then she made a mistake and can be held liable. CPA filing forms from a jurisdiction on the other end of the country without proper research and knowledge may be held negligent if she made a grave mistake. You can file a law suit against the CPA (which will probably trigger her E&O insurance carrier who'll try to settle if there's a good chance for your lawsuit to not be thrown away outright), or complain to the State regulatory agency overseeing CPAs in the State of her license. Or both. Am I wrong for expecting the CPA should have properly filled out and filed my taxes? No, but it doesn't shift the responsibility from you. How can I find out if the CPA has missed anything else? Same as with doctors and lawyers - get a second opinion. Preferably from a CPA licensed in California. You and only you are responsible for your taxes. You may try to pin the penalties and interest on the CPA if she really made a mistake. California is notorious for very high LLC/Corp franchise tax (cost of registering to do business in the State). It's $800 a year. You should have read the forms and the instructions carefully, it is very prominent. It is also very well discussed all over the Internet, any search engine would pop it up for you with a simple \\\"\\\"California Franchise Tax for LLC/Corp\\\"\\\" search. CA FTB is also very aggressive in assessing and collecting the fee, and the rules of establishing nexus in CA are very broad. From your description it sounds like you were liable for the Franchise tax in CA, since you had a storage facility in CA. You may also be liable for sales taxes for that period.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"105158\",\n \"text\": \"\\\"Does location of EA or CPA matter? Not in particular. The FTB has field offices all over the State, so if a meeting needs to be arranged - it will be in the nearest office. When you interview the potential candidates, you can ask them how they would deal the case if there's a need of an in-person visit to the FTB, and if it is even an option you should be worrying about. Likely not, since as you mentioned before you're in a mail audit process. Are there websites that rate EAs or CPAs, for example, on how many audits they have won? Or should I simply rely on yelp.com ratings. There's no \\\"\\\"winning\\\"\\\" in audits. Ideally, given the same data, any EA or CPA would reach the same result in the discussion re audits with the FTB. Obviously, some are more experienced and some are less, and some are specializing on specific types of audits/entities, etc. Yelp is a place to start, but take the reviews there with a grain of salt since most reviewers are probably there to rant. If you see a repetitive pattern in the reviews - take that into consideration. For example, you probably don't want to hire someone who's been repeatedly unresponsive to their clients, not returning calls, not answering questions, being late, etc. Are all EAs and CPAs equal No. Some are generalists, some specialize in a specific area. Some build practice elusively on representation (IRS or FTB, or both), some provide a wide range of services from bookkeeping to Tax Court representation. I suggest looking for those who prominently advertise themselves as specializing in your area (whatever your type of business is), and representation in front of the FTB. Specialists, especially experienced, cost much more. Keep in mind - you'll be getting what you paid for. Also, when you hire a \\\"\\\"big shot\\\"\\\" EA/CPA - check who's actually going to do the work, and how much oversight the \\\"\\\"big shot\\\"\\\" is going to provide. Anything else that I potentially missed? Any specific questions that I should ask EA or CPA on initial interview? For example, if my EA/CPA could also talk with auditor in case FTB would want to talk directly with taxpayer, if possible? Well, that's the point of representation - to represent. They should be talking to the FTB in your name. You should verify credentials (IRS for EAs, CA CBA for CPAs), make sure their license is current. You can ask them about their continued education and how much of it is dedicated to the CA State law and FTB regulations. Ask them about their experience with similar cases. Overall, a decently qualified tax professional should be able to handle a mail audit without an issue, in-person representation may be harder since it does not only require being competent in the tax law, but also have some people skills.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"467390\",\n \"text\": \"For Federal Return, Schedule H and its Instructions are a great start. You are the nanny's employer, and are responsible for FICA (social security and medicare) withholding, and also paying the employer portion. You will offer her a W4 so she can tell you how much federal and state tax to withhold. You'll use Circular E the employer's tax guide to calculate withholding. In January, you'll give her a W-2, and file the information with your own tax return. For State, some of the above applies, but as I recall, in my state, I had to submit withholding quarterly separate from my return. As compared to Federal, where I adjusted my own withholding so at year end the tax paid was correct. Unemployment insurance also needs to be paid, I believe this is state. This issue is non-political - I told my friends at the IRS that (a) the disparity between state and federal to handle the nanny tax was confusing for those of us trying to comply, and (b) even though we are treated as an employer, a 'guide to the nanny tax' would be helpful, a single IRS doc that doesn't mix non-nanny type issues into the mix. In the end, if a service is cost effective, go for it, your time is valuable, and thi is something that only lasts a few years.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"237331\",\n \"text\": \"If you're under audit - you should get a proper representation. I.e.: EA or CPA licensed in California and experienced with the FTB audit representation. There's a penalty on failure to file form 1099, but it is with the IRS, not the FTB. If I remember correctly, it's something like $50 or $100 per instance. Technically they can disqualify deductions claiming you paid under the table and no taxes were paid on the other side, however I doubt they'd do it in a case of simple omission of filing 1099 forms. Check with your licensed tax adviser. Keep in mind that for the IRS 2011 is now closed, since the 3-year statute of limitations has passed. For California the statute is 4 years, and you're almost at the end of it. However since you're already under audit they may ask you to agree to extend it.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"204703\",\n \"text\": \"The request for your parent's income comes from Form 8615, Tax for Certain Children Who Have Unearned Income. I typically see this form appear as I'm doing my daughter's taxes and start to enter data from stock transactions. In other words, your earned income is your's. But if you are a dependent, or 'can be,' the flow avoids the potentially lucrative results from gifting children appreciated stock, and have them take the gain at their lower, potentially zero cap gain rate. I suggest you grab a coffee and thumb through Pub 929 Tax Rules for Children and Dependents to understand this better. From page 14 of the linked doc - Parent's return information not available. If a child can’t get the required information about his or her parent's tax return, the child (or the child's legal representative) can request the necessary information from the Internal Revenue Service (IRS). How to request. After the end of the tax year, send a signed, written request for the information to the Internal Revenue Service Center where the parent's return will be filed. (The IRS can’t process a request received before the end of the tax year.) It also suggests that you file for an extension for the due date of your return. Include payment for the tax you expect to pay, say by plugging in $200K for parent income as an estimate. My parents' accountant tells them I do not need it. Well, a piece of software told you that you do, and 3 people on line who collectively qualify as experts documented why. (Note, I am not full of myself. This board operates via the wisdom of crowds. Members DStanley, and Ben Miller, commented and edited to help me form a well documented response that would be tough to argue against.)\",\n \"title\": \"\"\n },\n {\n \"docid\": \"357481\",\n \"text\": \"\\\"Sue the debt collectors in small claims court. There are several example stories around the internet, but this is a well written one from the consumerist. If your phone is a cell phone: \\\"\\\"it is against the law for a company to leave a pre-recorded message on your cell phone.\\\"\\\" In fact, the call frequency increased once they realized they had reached a live person. I called each of these companies multiple times, and though I was given assurances each time that my number would be taken off of their lists, the calls continued, morning, noon and night. At my wits end, I decided the only way to have the harassing calls stop was to file suits against the collection companies. It's very important to understand that it is against the law for a company to leave a pre-recorded message on your cell phone. Armed with this knowledge, I filed suit against several of the collection companies. I filed in small claims court so I did not need to hire an attorney, and the process was as simple as completing a paragraph on a complaint form. For evidence, I had over a hundred Google Voicemail transcripts showing the times the companies called and the text of the pre-recorded messages. Mysteriously, the calls all stopped immediately on the same date the collection companies received the certified letters stating they were being sued. Then a new flurry of calls began pouring in. This time it was their attorneys. The attorneys representing these out of state collection companies were all desperate to settle out of court. hey did not want to incur the expense of traveling for court or hiring a local law firm who wasn't on retainer. They also understood they had no justifiable defense for the calls. To make a long story short, so far I have successfully sued 3 of these collection companies and settled for more than $5,000 out of court. All it cost me was $35 and 20 minutes per suit. Making these companies pay is the only incentive for them to stop their illegal and harassing practices. If more consumers knew their rights and actually took a few minutes to stand up for them, it would become less profitable for these companies to conduct business the way they do now. -Source And whether you have a cell phone or land line, It is illegal for the debt collectors to tell you they are calling to collect a debt for someone else under the Fair Debt Collection Practices Act (wikipedia, ftc docs). What Remedies Are Available If The Debt Collector Violates The Law Under the Fair Debt Collection Practices Act, you have the right to sue a debt collector in state or federal court within one year from the date of the violation. If you win, you may recover damages in the amount of any losses you suffered as a result of the violation, plus an additional amount of up to $1,000.00. You may also be able to recover court costs and attorney fees. If the same debt collector has engaged in unlawful conduct with a number of consumers, it may be possible to find a lawyer who will file a class action lawsuit. -Source With regard to whether you can sue under FDCPA if you are not the debtor, one FDCPA lawyer (take with grain of salt) says yes: Did you know that it doesn't matter if you owe the account the debt collector is calling you about or not? If a debt collector violates the FDCPA (the federal Fair Debt Collection Practices Act, 15 USC 1692 et. seq.) that debt collector could be liable to pay you statutory damages, actual damages, attorney's fees, and court costs. -Source\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"382712\",\n \"text\": \"\\\"The seriousness of your situation depends on whether your girlfriend was owed a refund for each tax return she failed to file, or whether she owed additional money. If she owed money on one or more of the tax returns she failed to file, stop! It is time to consult a lawyer. At the very least, you need to contact an accountant who specialises in this sort of thing. She will owe interest and penalties, and may be liable for criminal prosecution. There are options available and lawyers who specialise in this sort of thing (e.g. this one, from a simple google search). If she is in this position, you need professional help and you need it soon, so you can make a voluntary disclosure and head off criminal prosecution. Assuming the taxes are fairly simple, you are likely looking at a few thousand dollars, but probably less than $7,500, for professional help. There will be substantial penalties assessed as well, for any taxes owing. If you wait until the CRA starts proceedings, you are most likely looking at $10,000 to $50,000, assuming the matter is not too complicated, and would be facing the possibility of a jail term not exceeding five years. If she was due a refund on every single one of the tax returns she failed to file, or at least if she did not owe additional money, you are probably in a situation you can deal with yourself. She will want to file all of the tax returns as soon as possible, but will not be assessed a penalty. I have personally filed taxes several months late a number of times, when I was owed a refund. You may still want to consider professional help, but it is probably not necessary. Under no circumstances should she allow her father near her finances again, ever. You should also be careful to trust any responses to this question, including my response, because we are unlikely to be professional accountants (I certainly am not). You are well outside the abilities of an H&R Block \\\"\\\"accountant\\\"\\\" in this matter and need a real certified accountant and/or a lawyer who specialises in Failure To File cases.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"37327\",\n \"text\": \"I was in a similar (but not quite as bad situation) a couple years ago, and I had a stroke of luck that helped me, but your friend might be able to force a similar situation. My parents refused to take out the huge parent loan (understandably so), but my dad made enough money that I wasn't eligible for much aid. My stroke of luck came when they got divorced; I could refile my FAFSA with only one parent (using my mom with very little income), my aid shot through the roof and nearly covered my undergrad (this happened in California, I don't know if this works in other states). My advice for your friend would be to take the 6 units/part time job option, but do what she can to earn enough to pay her own rent/food/other bills. I think the requirement for filing as an independent is that you supply >50% of your own income. It won't kick in right away, but for next school year this would end up getting her a lot more money from the state/federal governments. For me it was enough to cover my school, food, rent, gas, car payment, and still have a little left over. (I don't know if this is still possible, and I know it doesn't work for graduate school, or if it applies to every state. It might be an option worth pursuing though)\",\n \"title\": \"\"\n },\n {\n \"docid\": \"166522\",\n \"text\": \"\\\"I had about $16k in student loans. I defaulted on the loans, and they got > passed to a collection type agency (OSCEOLA). These guys are as legitimate as a collection agency can be. One thing that I feel is very sketchy is when they were verifying my identity they said \\\"\\\"Does your Social Security Number end in ####. Is your Birthday Month/Day/Year.\\\"\\\" That is not sketchy. It would be sketchy for a caller to ask you to give that information; that's a common scheme for identity theft. OSCEOLA are following the rules on this one. My mom suggested I should consider applying for bankruptcy Won't help. Student loans can't be discharged in bankruptcy. You have the bankruptcy \\\"\\\"reform\\\"\\\" act passed during the Bush 43 regime for that. The loan itself is from school. What school? Contact them and ask for help. They may have washed their hands of your case when they turned over your file to OSCEOLA. Then again, they may not. It's worth finding out. Also, name and shame the school. Future applicants should be warned that they will do this. What can I do to aid in my negotiations with this company? Don't negotiate on the phone. You've discovered that they won't honor such negotiations. Ask for written communications sent by postal mail. Keep copies of everything, including both sides of the canceled checks you use to make payments (during the six months and in the future). Keep making the payments you agreed to in the conversation six months ago. Do not, EVER, ignore a letter from them. Do not, EVER, skip going to court if they send you a summons to appear. They count on people doing this. They can get a default judgement if you don't show up. Then you're well and truly screwed. What do you want? You want the $4K fee removed. If you want something else, figure out what it is. Here's what to do: Write them a polite letter explaining what you said here. Recount the conversation you had with their telephone agent where they said they would remove the $4K fee if you made payments. Recount the later conversation. If possible give the dates of both conversations and the names of the both agents. Explain the situation completely. Don't assume the recipient of your letter knows anything about your case. Include evidence that you made payments as agreed during the six months. If you were late or something, don't withhold that. Ask them to remove the extra $4K from your account, and ask for whatever else you want. Send the letter to them with a return receipt requested, or even registered mail. That will prevent them from claiming they didn't get it. And it will show them you're serious. Write a cover letter admitting your default, saying you relied on their negotiation to set things straight, and saying you're dismayed they aren't sticking to their word. The cover letter should ask for help sorting this out. Send copies of the letter with the cover letter to: Be sure to mark your letter to OSCEOLA \\\"\\\"cc\\\"\\\" all these folks, so they know you are asking for help. It can't hurt to call your congressional representative's office and ask to whom you should send the letter, and then address it by name. This is called Constituent Service, and they take pride in it. If you send this letter with copies you're letting them know you intend to fight. The collection agency may decide it's not worth the fight to get the $4K and decide to let it go. Again, if they call to pressure you, say you'd rather communicate in writing, and that they are not to call you by telephone. Then hang up. Should I hire a lawyer? Yes, but only if you get a court summons or if you don't get anywhere with this. You can give the lawyer all this paperwork I've suggested here, and it will help her come up to speed on your case. This is the kind of stuff the lawyer would do for you at well over $100 per hour. Is bankruptcy really an option Certainly not, unfortunately. Never forget that student lenders and their collection agencies are dangerous and clever predators. You are their lawful prey. They look at you, lick their chops, and think, \\\"\\\"food.\\\"\\\" Watch John Oliver's takedown of that industry. https://www.youtube.com/watch?v=hxUAntt1z2c Good luck and stay safe.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"15319\",\n \"text\": \"\\\"3) NOT to claim her as my dependent. No additional tax return (since she is NOT my dependent), but also no penalty. My end of year balance would be $0 No. Not claiming her as a dependent does not save you from being responsible for her penalty. You are responsible for her penalty if she is your dependent (i.e. she meets the conditions for being your dependent), regardless of whether you claim her on your tax return or not. If you have the option of claiming her or not, then she is your dependent, and you are responsible for her penalty. 26 CFR 1.5000A-1(c)(2)(i): For a month when a nonexempt individual does not have minimum essential coverage, if the nonexempt individual is a dependent (as defined in section 152) of another individual for the other individual's taxable year including that month, the other individual is liable for the shared responsibility payment attributable to the dependent's lack of coverage. An individual is a dependent of a taxpayer for a taxable year if the individual satisfies the definition of dependent under section 152, regardless of whether the taxpayer claims the individual as a dependent on a Federal income tax return for the taxable year. [...] Form 1040 instructions, Line 61: [...] If you had qualifying health care coverage (called minimum essential coverage) for every month of 2015 for yourself, your spouse (if filing jointly), and anyone you can or do claim as a dependent, check the box on this line and leave the entry space blank. Otherwise, do not check the box on this line. If you, your spouse (if filing jointly), or someone you can or do claim as a dependent didn’t have coverage for each month of 2015 you must either claim a coverage exemption on Form 8965 or report a shared responsibility payment on line 61. [...] So you cannot check the box and must report exemptions for your sister, or report a shared responsibility payment. Form 8965 instructions, Definitions, \\\"\\\"Tax household\\\"\\\": For purposes of Form 8965, your tax household generally includes you, your spouse (if filing a joint return), and any individual you claim as a dependent on your tax return. It also generally includes each individual you can, but don't, claim as a dependent on your tax return. [...] Your sister is part of your tax household regardless of whether you claim her, and you must compute her shared responsibility payment for any months she did not have insurance and did not qualify for an exemption.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"162405\",\n \"text\": \"I hate apples business practice down to the core, but whenever a not-so-tech-savvy friend or older gentleman/lady asks me what I think about Apple,...I cite their customer service. A lot of the other companies out there either require a million dollar service package, or you are on the phone with a call center in India. I don't mind this myself as I love the freedom it gives me over Apple (Hell, none of my software/hardware (except my laptop) is an OEM package)...but for an older lady who just cant seem to figure out how to get her email open...an apple care center (or whatever they call them, genius bars?) down the road is a fantastic option.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"446628\",\n \"text\": \"Does this technically mean that she has to pay AMT on $400,000? Yes. Well, not exactly 400,000. She paid $1 per share, so 390,000. And if so, is %28 the AMT for this sum? (0.28 * $400,000 = $112,000)? Or does she have to include her salary on top of that before calculating AMT? (Suppose in the fake example that her salary is $100,000 after 401k). All her income is included in calculating the AMT, minus the AMT exemption amount. The difference between the regular calculated tax and the calculated AMT is then added to the regular tax. Note that some deductions allowed for the regular calculation are not allowed for the AMT calculation. How does California state tax come into play for this? California has its own AMT rules, and in California any stock option exercise is subject to AMT, unless you sell the stock in the same year. Here's a nice and easy to understand write up on the issue from the FTB. When would she have to pay the taxes for this huge AMT? Tax is due when income is received (i.e.: when you exercise the options). However, most people don't actually pay the tax then, but rather discover the huge tax liability when they prepare to submit their tax return on April 15th. To avoid that, I'd suggest trying to estimate the tax and adjust your withholding using form W4 so that by the end of the year you have enough withheld. Suppose in the worst case, the company goes completely under. Does she get her massive amounts of tax back? Or if it's tax credit, where can I find more info on this? That would be capital loss, and only up to $3K a year of capital loss can be deducted from the general income. So it will continue offsetting other capital gains or being deducted $3K a year until it all clears out. Is there any way to avoid this tax? (Can she file an 83b election?) You asked and answered. Yes, filing 83(b) election is the way to go to avoid this situation. This should be done within 30 days of the grant, and submitted to the IRS, and a copy attached to the tax return of the grant year. However, if you're considering exercise - that ship has likely sailed a long time ago. Any advice for Little Susie on how she can even afford to pay that much tax on something she can't even sell anytime soon? Don't exercise the options? Should she take out a loan? (e.g. I've heard that in the extreme case, you can find angel investors who are willing to pay all your taxes/strike price, but want 50% of your equity? I've also heard that you can sell your illiquid shares on SecondMarket?) Is she likely to get audited by IRS for pulling something like this? You can take a loan secured by shares you own, there's nothing illegal in it. If you transfer your shares - the IRS only cares about the taxes being paid, however that may be illegal depending on the terms and the conditions of the grant. You'll need to talk to a lawyer about your situation. I suggest talking to a licensed tax adviser (EA/CPA licensed in your State) about the specifics concerning your situation.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"324417\",\n \"text\": \"\\\"**Reposted so you don't have to look at silly GIFs for 50% of the article.** Sophie is a physical penetration tester and information security consultant. She specializes in social engineering security assessments including physical, voice (vishing) and text (phishing). She consults in remediation and prevention of security incidents through creation of policy and procedures, as well as customized training for your individual office culture. Prior to working in infosec, Sophie was a journalist, photographer, and a mom. Hello! My name is Sophie and I break into buildings. I get paid to think like a criminal. Organizations hire me to evaluate their security, which I do by seeing if I can bypass it. During tests I get to do some lockpicking, climb over walls or hop barbed wire fences. I get to go dumpster diving and play with all sorts of cool gadgets that Q would be proud of. But usually, I use what is called social engineering to convince the employees to let me in. Sometimes I use email or phone calls to pretend to be someone I am not. Most often I get to approach people in-person and give them the confidence to let me in. My frequently asked questions include: What break-in are you most proud of? What have you done for a test that you were the most ashamed of? What follows is the answer to both of these questions. A few months ago, a client had hired me to test two of their facilities. A manufacturing plant, plus data center and office building nearby. First step: open source intelligence, or OSINT. I look at maps, satellite images, study what I can of their delivery and supply schedules, and so on. The manufacturing facility looked like a prison. No windows, heavy iron gates, no landscaping. Generally a monstrosity of architecture. This facility had armed guards, badge readers, biometric security controls and turnstiles at every entrance. I remember thinking, \\\"\\\"It's got to be hell to work in there. I wonder if I can use that…\\\"\\\" One thing was for sure… The chances of tailgating (following behind an employee with valid credentials) into this building were next to non-existent. I was going to have to get down and dirty with my social engineering. First stop: LinkedIn. Your LinkedIn is my best friend. The more information you have on your LinkedIn, the more options I have. I have several fake LinkedIn profiles that you are probably connected to. I scour profiles of employees who work at these facilities, and cross-reference them to other social media sites. And I find a lovely young woman who I'm going to call Mary. Mary was a brand-new hire working as an assistant at the manufacturing facility. Mary had a public Facebook account too. On Mary's public Facebook account, she documented all of her family's adventures. Side note: Now I know where Mary went to high school, her mother's maiden name, the names of her pets, etc. Answers to those \\\"\\\"security questions\\\"\\\" you use to reset your passwords are very easy to find if you aren't careful with that information. Not to mention that now I know where Mary works, where her kids go to school, where they vacation…I could go on. Scary stuff. This is not an advanced investigation. I'm not a private investigator and I don't have the resources of the NSA. But I can do a lot of damage with simple methods. Most notably to me, there were photos Mary posted of her time volunteering with a certain maternity support center. Her passion for children and caring new moms was very plain. So of course, I took advantage of it. For this assessment I played two roles. For the first, I spoofed my phone number to make it look like it was coming from the company's headquarters. I called the front desk of the manufacturing facility and was transferred to Mary. \\\"\\\"Hi Mary!\\\"\\\" I said, \\\"\\\"My name is Barbara.\\\"\\\" \\\"\\\"I am a project coordinator with facilities management. We are renovating a few of our facilities. We are sending an interior designer out to you tomorrow so she can put together proposals to update your space!\\\"\\\" Mary replied, \\\"\\\"Well that's great! But why the short notice?\\\"\\\" I could feel her getting suspicious, so I pulled out my trump card… *Sigh* \\\"\\\"Well Mary… You really should have heard from me sooner. I've just been so overloaded at work…I feel like I can't catch up, and to top it off the baby is due in 6 weeks. If my boss finds out I messed this up he's going to flip.\\\"\\\" I was really getting into this, voice shaking. (Yes, I know, I'm a terrible human being.) She cut me off, \\\"\\\"Oh hunny, hunny it's ok. We will work this out! Tell me about the baby! Is it your first? Boy or girl?!\\\"\\\" Our Mary was committed at this point. Not because she is stupid, but because she is a good person. She wanted to help me. We talked babies and birth plans for a while (never pick a pretext you can't speak about at length.) Mary took down the name of the \\\"\\\"designer\\\"\\\" who was coming by the next day and we said our goodbyes. Mary could have saved her company a lot of heartache by simply verifying that I was who I claimed to be. (Just to be clear here, I would never give out Mary's real identity. I'm not totally heartless. This could have happened to anyone. She has not been fired.) I showed up the next day as \\\"\\\"Claire\\\"\\\" with a fictional architecture firm that I had made business cards and a website for. My alter-ego Barb had done most of the leg work for me. When I arrived, Mary and her boss were waiting for me with smiles. I shook hands all around and handed them the business card I printed out the night before. I was given a visitor badge and the red carpet was rolled out. I gained rapport with the staff there by asking them to tell me what they wanted in an office space. They were so excited. I might have claimed to be on the team that put together the Google offices…(Yes, I am HORRIBLE. This is my inner demon child.) \\\"\\\"You want a standing desk? New chairs over here?! Ergonomic keyboards for everyone! Let's look at swatches!\\\"\\\" We became best buds. I was given complete and unaccompanied access to the facility where I stayed for several hours. I gained network access and stole several thousands of dollars in physical primitives by picking my way through cheap locks (credit to Deviant Ollam for the rad lockpicking animations.) This client had been pretty confident that I wouldn't get into either facility, much less be able to hit both in a short time span. So the timeline was left to my discretion, but it was assumed that I would need to fly to the area twice. I didn't see the need in burdening them with two round-trip expenses. I went back to Mary's office and said, \\\"\\\"Well I think I have what I need from here. How do I get to the office center?\\\"\\\" She looked at her watch and said, \\\"\\\"It's almost lunch time. I'll take you there!\\\"\\\" A whole group of us piled into the parking lot, and they took me to a nearby taco shop. That's right. My Marks took me to get tacos… I love my job. After lunch they drove me to the offices and a few of them came in with me to show me around. I took FOREVER looking around this office space, and eventually they said their goodbyes because they had to go back to work. They had a strict policy of escorting visitors. But I had been seen walking around with trusted insiders so no one questioned me. I was free to take my time. I made myself at home. My main objective at this site was to weasel my way into private corner offices. When I accomplished my goals, I tracked down my point of contact's office. This is the man who hired me in the first place. This is the best part of every job. Steve was there, hard at work when I disturbed his groove by knocking on the door. He glanced up, \\\"\\\"Hi there, can I help you?\\\"\\\" I smiled. \\\"\\\"Hi Steve! I'm Sophie from Sincerely Security. It's nice to meet you in-person!\\\"\\\" I will never forget the look on his face… Pure gold. \\\"\\\"Who?.... Wait, what? How? How did you get in here?!\\\"\\\" We stayed in his office and talked for a long time. I went over exactly the steps that could have prevented my success. First of all, the desire to help others is human and natural. We don't want to discourage that. Second, I'm sure they did have some sort of policy that required visitors to check in showing government issued identification, but they weren't following it. We also need to post by every computer, phone and door: \\\"\\\"TRUST, BUT VERIFY.\\\"\\\" An employee who does their homework can ruin my day. Third, if it seems too good to be true, it probably is. Is your company going to hire the team who designed Google's offices? Magic 8 ball says no. Lastly, the team who took me to the second location should have found someone else to escort me through the building. I've been doing this job for a couple years now, and almost every job is a variant of this story. Very rarely do I go through an entire assessment without some sort of social engineering. There are ways to protect yourself and your company from attacks like this. I think it starts by sharing stories like these, and educating and empowering each other to be vigilant.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"34338\",\n \"text\": \"\\\"If you live outside the US, then you probably need to deal with foreign tax credits, foreign income exclusions, FBAR forms (you probably have bank account balances enough for the 10K threshold) , various monsters the Congress enacted against you like form 8939 (if you have enough banking and investment accounts), form 3520 (if you have a IRA-like local pension), form 5471 (if you have a stake in a foreign business), form 8833 (if you have treaty claims) etc ect - that's just what I had the pleasure of coming across, there's more. TurboTax/H&R Block At Home/etc/etc are not for you. These programs are developed for a \\\"\\\"mainstream\\\"\\\" American citizen and resident who has nothing, or practically nothing, abroad. They may support the FBAR/FATCA forms (IIRC H&R Block has a problem with Fatca, didn't check if they fixed it for 2013. Heard reports that TurboTax support is not perfect as well), but nothing more than that. If you know the stuff well enough to fill the forms manually - go for it (I'm not sure they even provide all these forms in the software though). Now, specifically to your questions: Turbo tax doesn't seem to like the fact that my wife is a foreigner and doesn't have a social security number. It keeps bugging me to input a valid Ssn for her. I input all zeros for now. Not sure what to do. No, you cannot do that. You need to think whether you even want to include your wife in the return. Does she have income? Do you want to pay US taxes on her income? If she's not a US citizen/green card holder, why would you want that? Consider it again. If you decide to include here after all - you have to get an ITIN for her (instead of SSN). If you hire a professional to do your taxes, that professional will also guide you through the ITIN process. Turbo tax forces me to fill out a 29something form that establishes bonafide residency. Is this really necessary? Again in here it bugs me about wife's Ssn Form 2555 probably. Yes, it is, and yes, you have to have a ITIN for your wife if she's included. My previous state is California, and for my present state I input Foreign. When I get to the state tax portion turbo doesn't seem to realize that I have input foreign and it wants me to choose a valid state. However I think my first question is do i have to file a California tax now that I am not it's resident anymore? I do not have any assets in California. No house, no phone bill etc If you're not a resident in California, then why would you file? But you might be a partial resident, if you lived in CA part of the year. If so, you need to file 540NR for the part of the year you were a resident. If you have a better way to file tax based on this situation could you please share with me? As I said - hire a professional, preferably one that practices in your country of residence and knows the provisions of that country's tax treaty with the US. You can also hire a professional in the US, but get a good one, that specializes on expats.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"520395\",\n \"text\": \"\\\"I've received letters notifying me of data breaches in the past. In the end, I've never signed up for the offered protection service, figuring if \\\"\\\"they\\\"\\\" can hack Target or ADP or the IRS, they can hack anybody, like... Equifax. And now Equifax has been hacked. My family's Social Security Numbers were stolen from a hospital database. I think that information, plus public information was used to gain further data from the IRS FAFSA tool. (we got a letter from the IRS). Ultimately, fraudsters used whatever data they had to file a tax return with the IRS and with the Cali FTB (we don't and never have lived in California). We got letters from both, and managed to stop the fraud before it really impacted us...other than having to file a paper tax form this past tax season. Anyway... in a world where Equifax gets hacked: the only solution is: I don't bother with the crazy password schemes you talk about... I have a few different passwords I use, but most my investment accounts use the same username and password. It's all about risk. Bruce Schneier says the same thing. The amount to spend on security should depend on what you're trying to protect. I don't care much if somebody gets into my google account, because I have a google account just because I have to. I barely use it at all. Similarly my yahoo account. My yahoo account uses my \\\"\\\"insecure password\\\"\\\", and my investment accounts use my \\\"\\\"secure password\\\"\\\". Credit Card info? Meh. Unless they get into the credit card company database, which undoubtedly has my Social Security Number, it's not that big of a deal. Yeah, they can make fraudulent charges, but there are legal protections, so in theory I can't be out any money. So think this way: what's the risk, and what's the appropriate level of effort to take to mitigate that risk.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"342400\",\n \"text\": \"Look I'm up for a dialogue, but I'd appreciate civility. If you look back at my responses on this post I've said multiple times that I'm willing to help people who help themselves. I'm also pointing out that 1.) this article 'slavery' aspect is off and 2.) I'm not 100% convinced she is doing all she can to further better herself (maybe she is but the article didn't convince me). I've said before I give her props for getting her ass off, good on her. And I'm all for helping out people (for a limited time) who actually deserve it and have actually worked hard for it. In the lead featured in the article sounds like she would be a very very good candidate. I am a generous person, I want to help people and I'm willing to do so. They just need to want help. My generosity ends when it becomes mandatory to support anyone who has made any number of bad decisions and is not deserving of my help (we can talk about who deserves help in more detail anytime). Should I support a family of people in which the parents keep pumping out kids, and the mom is a stat at home mom and the dad works at a slightly above minimum wage? No! Should I support single mom who chooses not to work, and mooches off friends and family? No Both of these cases may seem cherry picked, and while they are to an extent they are both real cases that I've/a personal friend have witnessed.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"133235\",\n \"text\": \"\\\"Do I understand correctly, that we still can file as \\\"\\\"Married filing jointly\\\"\\\", just add Schedule C and Schedule SE for her? Yes. Business registration information letter she got once registered mentions that her due date for filing tax return is January 31, 2016. Does this prevent us from filing jointly (as far as I understand, I can't file my income before that date)? IRS sends no such letters. IRS also doesn't require any registration. Be careful, you might be a victim to a phishing attack here. In any case, sole proprietor files a regular individual tax return with the regular April 15th deadline. Do I understand correctly that we do not qualify as \\\"\\\"Family partnership\\\"\\\" (I do not participate in her business in any way other than giving her money for initial tools/materials purchase)? Yes. Do I understand correctly that she did not have to do regular estimated tax payments as business was not expected to generate income this year? You're asking or saying? How would we know what she expected? In any case, you can use your withholding (adjust the W4) to compensate.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"169723\",\n \"text\": \"I agree with mhoran_psprep's answer, but would like to add a few additional points to consider. TurboTax and the professional it will send to represent you in case of a tax audit have no more information about your tax return than what you entered into the program. Now, there are three (or four) different kinds of audits. The correspondence audit is the most common kind where IRS sends a letter requesting copies of documents supporting a deduction or tax credit that you have claimed. Representation is hardly necessary in this case. The office audit is more serious where you have to make an appointment and go to the local IRS office with paperwork that the examining agent needs to see physically, and to answer questions, etc. It would be better to be accompanied by a representative at these meetings. But, office audits are not as common as correspondence audits, and, because they are expensive for the IRS, usually occur when the IRS is fairly sure of recovering a substantial sum of money. If you have been cutting corners and pushing the envelope in taking large enough deductions to make it worthwhile for the IRS to go after you, you probably should not have been using TurboTax to file your income tax return but should have been using an accountant or tax preparer, who would be representing you in case of an audit. If the reason that you used TurboTax is that no accountant was willing to prepare a tax return with the deductions that you wished to claim, I doubt that having TurboTax's representative with you when you go to the IRS office will help you all that much. An example of a field audit is when the IRS agent comes to your home to see if you actually have a space set aside to use exclusively as your home office as you claimed you did etc. A Taxpayer Compliance Measurement Program (TCMP) audit is where the IRS randomly chooses returns for statistical checks that taxpayers are complying with the regulations. The taxpayer has to prove every line of the return. You claim to be filing as Married Filing Jointly? Bring in your marriage certificate. Submit birth certificates and Social Security cards of your dependent children. And so on. Yes, having TurboTax represent you for only $49.95 will help, but not if you are not married and cannot provide the IRS with a marriage certificate etc. So, pay the fee for peace of mind if you like, and as insurance as littleadv suggests. But be sure you understand what you might be getting for the money. Most tax returns selected for audit are selected for what the IRS believes are good reasons, not at random. If what you said If my tax return is randomly selected for audit they will represent me. is interpreted literally, TurboTax will represent you only if your return is selected for examination under the TCMP program, not if it is selected for audit because the IRS believes that something is fishy about your return. And as always, you get what you pay for.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"350972\",\n \"text\": \"\\\"I'm working from 6am-2pm today (from home, since it's Saturday) and I'm on call from 2pm-4am tomorrow. If the phone rings at our company help desk at any time from 2pm-4am, I am expected to answer it or return the call promptly. I'm not paid for the entire time of 2pm-4am, but only for the time I'm \\\"\\\"on a call\\\"\\\" essentially. It was a shock when I found out that was the terms of the job (3 months in, there were dramatic changes in my schedule) and most of my friends seem to agree with me. Am I off base?\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"131926\",\n \"text\": \"\\\"I agree about not wanting to get into your friend's personal business, and it's a scummy bill collector that repeatedly calls friends or family to track down a debtor. On the other hand, at least he's made it obvious he's calling about a debt as opposed to pretending to be tracking down your friend with some other pretext. Nevertheless, you want the calls to stop. Here are two suggestions: Perhaps, a small fib: \\\"\\\"The creep owes me money too! Grrr! Let me know when you find him!\\\"\\\" The bill collector probably won't call you again :-) Or, if you're like me and uncomfortable fibbing – even to a scummy bill collector! – then here's a more truthful yet direct approach: \\\"\\\"I told you already it's not my debt, it's none of my business, and that I want you to stop calling me. You have no right to harass me and if you call again I will involve the police. There will be no other warning.\\\"\\\" Then have the phone company block the bill collector's phone number from calling you.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"521061\",\n \"text\": \"\\\"This is exactly what I feel. Having doing tech support for offices, friends and family, it dawned on me that they had no one else to call. If Grandma calls \\\"\\\"Sony\\\"\\\" because she can't find her email, well then they tell her to call Microsoft. Then she calls Microsoft and it seems it's a hardware issue, they send her back to Sony. In the end, the customer doesn't fully understand why they are being sent back and forth, they just want it fixed, or a reason. Apple is almost completely vertically integrated, they can solve most of the problems or at least provide the illusion that the customer is being helped.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"218986\",\n \"text\": \"\\\"You don't have to hire a tax consultant, there is a number of companies who sell software (installable or web-based) that helps you do it by asking for all relevant data interview-style. These typically cost between 15 and 25 EUR. I'm not sure whether any of them are available in English, but if you can read German well, you should be OK. taxback.com is in English, but to be honest it looks a bit dodgy to me. Now for your questions: are there some tricky fields (lines) that after filling in my taxes will be counted higher? This is rare, at least for employees you nearly always get something back. are there some tricky fields (lines) that after filling in my taxes could be counted lower? Not in general. Marriage is mentioned below, and otherwise it's all about individual deductibles. Ah, one important factor: if you have investment income and have not filed a Freistellungsauftrag with your bank, you can get some of the taxes by filling out the \\\"\\\"Anlage KAP\\\"\\\" form with data you got in the Jahressteuerbescheinigung from your bank. are there some flat-rates (Pauschals) that I could get advantage from? Absolutely. As an employee, the biggest factor is the Werbungskostenpauschale of (I think currently) 1000 EUR for general work-related expenses, which will be accepted without proof. If your expenses are higher than that and you file individual expenses, there are flat rates for work-related moving and for commuting distance. is it better to give a tax return together with my wife (who was only a girlfriend in 2013 living with me in one household) or to give it separately? It's not possible to do a joint tax filing for the time before your marriage. What you should consider is to apply for a different tax class from now on, if one of you earns significantly more than the other. when separately, do I have to fill her information in my tax return or can I just pretend there is nobody else in my apartment? As far as taxes are concerned, unmarried roommates are treated completely separately with one exception: only one of you can deduct service charges included in your rent. You have to get a Nebenkostenabrechnung from your landlord, and service charges, i.e. janitor, gardener, etc. should be marked separately. But this may not be worth bothering with, usually it results in a tax return of maybe 15 EUR. is there any guide in English that could be of help with filling in the tax return form? I couldn't find anything that looked really useful in a short search.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"23675\",\n \"text\": \"I asked my realtor, but she recommends to go with just one banker (her friend), and not to do any rate shopping. You need a new realtor. Anyone who would offer such advice is explicitly stating they are not advocating on your behalf. I'd do the rate shopping first. When you make an offer, once it's accepted, time becomes critical. The seller expects you to go to closing in so many days after signing the P&S. The realtor is specifically prohibited from pushing a particular lender on you. She should know better. In response to comment - Rate Shopping can be as simple as making a phone call, and having a detailed conversation. Jasper's list can be conveyed verbally. Prequalification is the next step, where a bank actually writes a letter indicating they have a high confidence you will qualify for the loan.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"544663\",\n \"text\": \"\\\"This is more of a long comment but may answer user's situation too. I have dealt with joint mortgages before in 3 states in the US. Basically in all three states if one party wants to sell, the home goes up for sale. This can be voluntary or it can go up via auction (not a great choice). In 2 of the 3 states the first person to respond to the court about the property, the other party pays all legal fees. Yes you read this right. In one case I had an ex who was on my mortgage, she had no money invested in the house ($0 down and still in college with no job). [If she wasn't on the mortgage I wouldn't have gotten loan - old days of dumb rules] When we split her lawyer was using the house as a way to extort other money from me. Knowing the state's laws I already filed a petition for the property but put it on hold with the clerk. Meaning that no one else could file but if someone tried mine would no longer be on hold. My ex literally spent thousands of dollars on this attorney and they wanted to sell the house and get half the money from the house. So sale price minus loan amount divided between us. This is the law in almost every state if there is no formal contract. I was laughing because she wanted what would be maybe 50-75K for paying no rent, no money down, and me paying for her college. Finally I broke her attorney down (I didn't lawyer up but had many friends who were lawyers advising). After I told her lawyer she wasn't getting anything - might have said it in not a nice way - her lawyer gave me her break down. To paraphrase she said, \\\"\\\"We are going to file now. My assistant is in the court clerk's office. You can tell the court whatever you want. Maybe they will give you a greater percentage since you put the money down and paid for everything but you are taking that chance. But you will pay for your lawyer and you will need one. And you will pay for me the entire time. And this will be a lengthy process. You would be better served to pay my client half now.\\\"\\\" Her office was about 2 blocks from court. I laughed at her and simply told her to have her assistant do whatever she wanted. I then left to go to clerk's office to take the hold off. She had beat me to the office (I moved my car out of her garage). By the time I got there she was outside yelling at her assistant, throwing a hissy fit, and papers were flying everywhere. We \\\"\\\"settled\\\"\\\" the next day. She got nothing other than the things she had already stolen from me. If I wouldn't have known about this loophole my ex would have gotten or cost me through attorney's fees around 40-50K for basically hiring a lawyer. My ex didn't really have any money so I am pretty sure lawyer was getting a percent. Moral of the story: In any contract like this you always want to be the one bringing in the least amount of money. There are no laws that I know of in any country where the person with the least amount on a contract will come out worse (%-wise). Like I said in the US the best case scenario that I know of for joint property is that the court pays out the stakeholder all of their contributions then it splits things 50/50. This is given no formal contract that the court upholds. Don't even get me started with hiring attorneys because I have seen the courts throw out so many property contracts it isn't even funny. One piece of advice on a contract if you do one. Make it open and about percentages. Party A contributes 50K, Party B 10K, Party A will pay this % of mortgage and maintenance and will get this % when home is sold. I have found the more specific things are the more loopholes for getting out of them. There are goofy ass laws everywhere that make no sense. Why would the person first filing get their lawyers paid for??? The court systems in almost all countries can have their comical corners. You will never be able to write a contract that covers everything. If the shower handle breaks, who pays for it? There is just too many one-off things with a house. You are in essence getting in a relationship with this person. I hear others say it is a business transaction. NO. You are living with this person. There is no way to make it purely business. For you to be happy with this outcome both of you must remain somewhat friends and at the very least civil with each other. To add on to the previous point, the biggest risk is this other person's character and state of mind. They are putting in the most money so you don't exactly have a huge money risk. You do have a time and a time-cost risk. Your time or the money you do have in this may be tied up in trying to get your money out or house sold. A jerk could basically say that you get nothing, and make you traverse the court system for a couple years to get a few thousand back. And that isn't the worst case scenario. Always know your worst case scenario. Yours is this dude is in love with you. When he figures out 2-3 years later after making you feel uncomfortable the entire time that you are not in love with him, he starts going nuts. So he systematically destroys your house. Your house worth plummets, you want out, you can't sell the house for price of loan, lenders foreclose or look to sue you, you pay \\\"\\\"double rent\\\"\\\" because you can't live with the guy, and you have to push a scooter to get to work. That is just the worst case scenario. Would I do this if I were 25 and had no family? Yea, why not if I trusted the other person and was friends with them? If it were just a co-worker? That is really iffy with me. Edit: Author said he will not be living with the person. So wording can be changed to say \\\"\\\"potentially\\\"\\\" in front of living with him in my examples.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"115172\",\n \"text\": \"I have been in a similar position for quite a while now and the only thing that seems to help is screening phone calls. I have a long list of collector numbers set to not ring on my phone. They can still leave a voice mail but they never do. As far as I know there aren't any laws that protect you from nuisance phone calls. FDCPA letters only apply to the debtor and the collector it is sent to it doesn't protect an unrelated third party from getting annoying phone calls. I have a feeling that sending FDCPA letters is just confirming that you probably are the debtor and prolong the collection calls.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"324445\",\n \"text\": \"\\\"Having worked in insurance, I can give you a few pointers. Firstly, state that you \\\"\\\"may have to complain\\\"\\\". Insurers hate complaints because they really complicate matters, are loads of work and must be tracked. I would advise not actually escalating it to a complaint until later as this may cause a delay as the actual process is quite convoluted. Mentioning the possibility of complaint sometimes makes people a bit more active. Try and resolve the issue, and if you aren't getting anywhere then make a complaint. Maintain a friendly, assertive, polite demeanor. If you get angry and aggressive you'll not likely get far. Remember that the people on the end of the phone are both human and more knowledgeable about insurance than you. You want them on your side, not against you. Make copious notes. If you can, record calls. If you are recording calls you will likely legally need to give them the option of not being recorded, so make sure you mention that you're recording each individual call as soon as you start speaking to the handler. Refer to your notes and make sure you carry out actions you say you will. If you spend a few days sending something you said you'd email over that day, and you then chase them a few days after that they may not have had the document through their workflow yet. It also engenders urgency if you're acting promptly, and suggests that you don't really care if you're taking your time. Get Names. This is an important step, as this gives the handler someone to talk to who may be familiar with your case. You may end up speaking to the same people more than once, so try and build a rapport if you do. \\\"\\\"I like this guy\\\"\\\" may lead to a bit more effort being put in, and a potentially better outcome. In my experience, GoSkippy can be a bit slow to respond to things, so you'll likely have to chase them up. If you chase them up and say \\\"\\\"I called on X date, discussing Y with Z and Z said they would do A, B and C. Has this been done yet?\\\"\\\" it looks better than saying \\\"\\\"I called about a week ago and spoke to one of your colleagues who said he'd do something for me. He's not done it, what's going on?\\\"\\\", As to a plan of action, I would split this into two points: Mis-sold policy and definition of commuting. Mis-sold policy - If they truly gave your wife two options, then they messed up. The standard 3 offered by goskippy are Social Domestic and Pleasure (SDP), SDP+Commuting, and SDP+C and Business use. Other companies sometimes roll commuting into SDP as standard. On the comparison sites however, there are usually the three separate options, and if you used one to set the policy up and clicked \\\"\\\"SDP Only\\\"\\\" then you may be in trouble. Social domestic and pleasure only DOES NOT include commuting. Whilst it is your responsibility to thoroughly check any documentation that comes through, it could be argued that if given two options between Business Use and SDP, then a reasonable person could be considered to assume that Goskippies definition of SDP did include commuting. Therefore, they need to prove to you that there were three options offered and that your wife specifically excluded commuting. IF they can't, then you should be able to argue that only two were offered and that commuting could have reasonably been assumed to be included. Use that term \\\"\\\"reasonable person\\\"\\\" btw, it's used in a lot of internal literature - at least at the insurer, I worked at. not commuting - Firstly, clarify their definition of \\\"\\\"commuting\\\"\\\". If your wife was on her way to work afterwards, then they may well consider she was commuting. For instance, at present, I drive from my house to my son's childminders, then to my wife's work and finally to mine. My commute could be argued to be 1 minute (my workplace is probably a minutes drive from my wife's, but I can't park in her car-park), but if I were to have an accident between my house and my son's childminder (~15 mins drive) the insurers would probably consider that commuting. If she was not on her way to work afterwards, and assuming your wife arranged her visit via text (or whatsapp, fb messenger or similar) you should easily be able to show that your wife had driven from a friends house to the childminder. If she was on a holiday day or was not working on that day, then that's also something you should be able to prove either with proof of her working pattern or proof of her holiday. If she doesn't have a job at all, then again, that's something that's provable. Proof reigns king in claims, so if you can prove certain key facts then you should be on to a winner.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"221502\",\n \"text\": \"I was in that same situation years ago with my parents. One way she could apply for a loan in her name without her parents is if she is not currently living with them she shouldn't need them to cosign if she doesn't have bad credit. But if she isn't living with them and they aren't financing her room and board they can't claim her as a dependent so if she really wants to stick it to them she can go and try to politely explain how the loans work and tell them if they don't cosign for her then she will apply on her own (which she can only do while not living with them I believe but not sure) and they will HAVE to STOP claiming her as a dependent on their taxes. If they don't agree she can put her foot down and force them to stop claiming her and tell them she will file her own application anyway and if they continue claiming her and get in trouble for it it's their own fault cause she warned them to stop first. They may agree to cosign rather than lose her as a dependent if it makes that big of a difference on their taxes, if they don't then she can forcefully punish them financially and their taxes will go up. Those were my choices when my parents refused to cosign for me to live at school but that was back in 1999-2000 and things may have changed since then, things also change state by state and I live in PA.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"396792\",\n \"text\": \"\\\"Paypal linked with my bank account. 1.Can I use my Saving bank account to receive payments from my clients? Or is it necessary to open a current account? Yes you can get funds into your savings account. However it is advisable to keep a seperate account as it would help with your IT Returns. 2.I will be paying a certain % as commission on every sales to a couple of sales guys (who are not my employees but only working on commission). Can I show this as an expense in my IT returns? As you are earning as freelancer, you are eligible for certain deductions like Phone calls, Laptop, other hardware, payments to partners. It is important that you maintain a book of records. An accountant for a small fee of Rs 5 K should be able to help you. In the Returns you have to show Net income after all these deductions, there is no place to enter expenses. 3.Since I will be receiving all the payments in Euros so am I falling under a category of \\\"\\\"Exporter of services\\\"\\\"? The work you are doing can be Free Lancing. 4.Do I need an Import Export Code (IEC) for smoothly running this small business? You can run this without one as Free lancing. IEC would be when you grow big and are looking for various benefits under tax and pay different taxes and are incorporated as a company.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"520026\",\n \"text\": \"You could do a voluntary repossession. While a repossession never looks good on your credit a voluntary repossession is slightly better. A good friend of mine had a situation like this about 11 years ago. She was in an accident didn't have replacement coverage insurance and was left with a large chunk of debt on a wrecked vehicle that she then rolled into a new car. In the end it came down to the simple fact that she could not afford a car loan on a vehicle that never was worth as much as she owed. Since the car was worth less than the loan she really couldn't sell it to fix the problem. She called and arranged a voluntary repossession. She stopped making payments, and parked the car till they came and picked it up. (Took about 4 months and 20 phone calls from her for them to come get it.) In the mean time, I purchased her a much older used but decent car for a couple thousand and she paid me back over the next year. The total she paid me back was less than the money she would have paid in the 4 months it took them to come get the car. In fact by the time they picked up the car she had paid back over half on the car I bought her. Yes the repossession did stay on her credit for seven years but during that time she was approved for a mortgage, cellphone plans, and credit cards etc. Therefore I don't know that it did that much damage to her credit. When her car was sold at auction by the repo company it sold for much less than the loan amount. Technically she was on the hook for the remaining amount. The outstanding balance on the loan was then sold several times to several different collection agencies. Over the years since then she has gotten letters every now and then demanding she pay the amount off, she ignores these. Most of these letters even included very favorable terms (full forgiveness for 20% of the amount) At this point the statute time has run out on the debt so there is no recourse for anyone to collect from her. The statute time limit varies from state to state. Some states it is as long as 10 years in others it is as short as 3 years. What this means is that counting from the date of the repossession, incurrance of debt, last payment, or agreement to pay whichever is later if the statute period has elapsed and the lender/collector has not filed a suit against you by the end of the period then they have effectively abandoned the debt and cannot collect. Find out what that period of time is in your state. If you can avoid the collection agencies till that period runs out you are scott free. You just have to make sure that you do not ever send them any money, or agree to pay them anything as this resets the calendar. If you do not want to wait for the calendar to run out if you wait long enough you will probably be offered favorable terms to pay only a fraction of the remaining amount, you just have to wait it out. Note, I normally would not endorse anyone not paying off their debts. However sometimes it is necessary and it is for this type of situation that we have things like this and bankruptcy.\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":2696,"cells":{"query_id":{"kind":"string","value":"815"},"query":{"kind":"string","value":"Mutations in RIM1 decrease levels of IME1 RNA."},"positive_passages":{"kind":"list like","value":[{"docid":"8148304","text":"In the yeast Saccharomyces cerevisiae, genetic studies suggest that the RIM1 gene encodes a positive regulator of meiosis. rim1 mutations cause reduced expression of IME1, which is required for expression of many meiotic genes, and thus lead to a partial defect in meiosis and spore formation. We report the sequence of RIM1 and functional analysis of its coding region. The RIM1 gene product (RIM1) contains three regions similar to C2H2 zinc fingers. Serine substitutions for cysteine in each of the putative zinc fingers abolish RIM1 function. The carboxyl-terminus of RIM1 is enriched in acidic amino acids and is required for full RIM1 activity. RIM1 also contains two putative cAMP-dependent protein kinase (cAPK) phosphorylation sites. At one site, substitution of alanine for serine does not affect RIM1 activity; at the other site, this substitution impairs activity. This analysis of RIM1 suggests that the protein may function as a transcriptional activator. We have used the cloned RIM1 gene to create a complete rim1 deletion. This null allele, like previously isolated rim1 mutations, causes a partial meiotic defect. In addition to RIM1, maximum IME1 expression requires the MCK1 and IME4 gene products. Defects associated with rim1, mck1, and ime4 mutations in expression of a meiotic reporter gene (ime2-lacZ) and in sporulation are additive. These findings suggest that RIM1 acts independently of MCK1 and IME4 to stimulate IME1 expression.","title":"Molecular characterization of the yeast meiotic regulatory gene RIM1."}],"string":"[\n {\n \"docid\": \"8148304\",\n \"text\": \"In the yeast Saccharomyces cerevisiae, genetic studies suggest that the RIM1 gene encodes a positive regulator of meiosis. rim1 mutations cause reduced expression of IME1, which is required for expression of many meiotic genes, and thus lead to a partial defect in meiosis and spore formation. We report the sequence of RIM1 and functional analysis of its coding region. The RIM1 gene product (RIM1) contains three regions similar to C2H2 zinc fingers. Serine substitutions for cysteine in each of the putative zinc fingers abolish RIM1 function. The carboxyl-terminus of RIM1 is enriched in acidic amino acids and is required for full RIM1 activity. RIM1 also contains two putative cAMP-dependent protein kinase (cAPK) phosphorylation sites. At one site, substitution of alanine for serine does not affect RIM1 activity; at the other site, this substitution impairs activity. This analysis of RIM1 suggests that the protein may function as a transcriptional activator. We have used the cloned RIM1 gene to create a complete rim1 deletion. This null allele, like previously isolated rim1 mutations, causes a partial meiotic defect. In addition to RIM1, maximum IME1 expression requires the MCK1 and IME4 gene products. Defects associated with rim1, mck1, and ime4 mutations in expression of a meiotic reporter gene (ime2-lacZ) and in sporulation are additive. These findings suggest that RIM1 acts independently of MCK1 and IME4 to stimulate IME1 expression.\",\n \"title\": \"Molecular characterization of the yeast meiotic regulatory gene RIM1.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"23604601","text":"The IME1 gene of Saccharomyces cerevisiae is required for initiation of meiosis. Transcription of IME1 is detected under conditions which are known to induce initiation of meiosis, namely starvation for nitrogen and glucose, and the presence of MATa1 and MAT alpha 2 gene products. In this paper we show that IME1 is also subject to translational regulation. Translation of IME1 mRNA is achieved either upon nitrogen starvation, or upon G1 arrest. In the presence of nutrients, constitutively elevated transcription of IME1 is also sufficient for the translation of IME1 RNA. Four different conditions were found to cause expression of Ime1 protein in vegetative cultures: elevated transcription levels due to the presence of IME1 on a multicopy plasmid; elevated transcription provided by a Gal-IME1 construct; G1 arrest due to alpha-factor treatment; G1 arrest following mild heat-shock treatment of cdc28 diploids. Using these conditions, we obtained evidence that starvation is required not only for transcription and efficient translation of IME1, but also for either the activation of Ime1 protein or for the induction/activation of another factor that, either alone or in combination with Ime1, induces meiosis.","title":"Post-transcriptional regulation of IME1 determines initiation of meiosis in Saccharomyces cerevisiae."},{"docid":"19255949","text":"Mutations in the PARN gene (encoding poly(A)-specific ribonuclease) cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita, but how PARN deficiency impairs telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem cells (iPSCs) from patients with dyskeratosis congenita with PARN mutations, we show that PARN is required for the 3′-end maturation of the telomerase RNA component (TERC). Patient-derived cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3′ termini shows that PARN is required for removal of post-transcriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased proportion of oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results demonstrate a new role for PARN in the biogenesis of TERC and provide a mechanism linking PARN mutations to telomere diseases.","title":"Poly(A)-specific ribonuclease (PARN) mediates 3′-end maturation of the telomerase RNA component"},{"docid":"33370","text":"Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioblastoma stem cells (GSCs). GSCs are regulated by molecular pathways distinct from the bulk tumor that may be useful therapeutic targets. We determined that A20 (TNFAIP3), a regulator of cell survival and the NF-kappaB pathway, is overexpressed in GSCs relative to non-stem glioblastoma cells at both the mRNA and protein levels. To determine the functional significance of A20 in GSCs, we targeted A20 expression with lentiviral-mediated delivery of short hairpin RNA (shRNA). Inhibiting A20 expression decreased GSC growth and survival through mechanisms associated with decreased cell-cycle progression and decreased phosphorylation of p65/RelA. Elevated levels of A20 in GSCs contributed to apoptotic resistance: GSCs were less susceptible to TNFalpha-induced cell death than matched non-stem glioma cells, but A20 knockdown sensitized GSCs to TNFalpha-mediated apoptosis. The decreased survival of GSCs upon A20 knockdown contributed to the reduced ability of these cells to self-renew in primary and secondary neurosphere formation assays. The tumorigenic potential of GSCs was decreased with A20 targeting, resulting in increased survival of mice bearing human glioma xenografts. In silico analysis of a glioma patient genomic database indicates that A20 overexpression and amplification is inversely correlated with survival. Together these data indicate that A20 contributes to glioma maintenance through effects on the glioma stem cell subpopulation. Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival. A20 anticancer therapies should therefore be viewed with caution as effects will likely differ depending on the tumor type.","title":"Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth"},{"docid":"26495128","text":"B23 (NPM/nucleophosmin) is a multifunctional nucleolar protein and a member of the nucleoplasmin superfamily of acidic histone chaperones. B23 is essential for normal embryonic development and plays an important role in genomic stability, ribosome biogenesis, and anti-apoptotic signaling. Altered protein expression or genomic mutation of B23 is encountered in many different forms of cancer. Although described as multifunctional, a genuine molecular function of B23 is not fully understood. Here we show that B23 is associated with a protein complex consisting of ribosomal proteins and ribosome-associated RNA helicases. A novel, RNA-independent interaction between ribosomal protein S9 (RPS9) and B23 was further investigated. We found that S9 binding requires an intact B23 oligomerization domain. Depletion of S9 by small interfering RNA resulted in decreased protein synthesis and G(1) cell cycle arrest, in association with induction of p53 target genes. We determined that S9 is a short-lived protein in the absence of ribosome biogenesis, and proteasomal inhibition significantly increased S9 protein level. Overexpression of B23 facilitated nucleolar storage of S9, whereas knockdown of B23 led to diminished levels of nucleolar S9. Our results suggest that B23 selectively stores, and protects ribosomal protein S9 in nucleoli and therefore could facilitate ribosome biogenesis.","title":"Ribosomal protein S9 is a novel B23/NPM-binding protein required for normal cell proliferation."},{"docid":"24705390","text":"BACKGROUND & AIMS Helicobacter pylori is an important etiologic factor in the development of gastric cancer. The aim of this study was to analyze the role of H. pylori infections in the induction of mutagenic events in gastric epithelial cells. The effect of a high-salt diet as a genotoxic risk factor was also investigated. METHODS Big Blue transgenic male mice (C57Bl/6) were inoculated with H. pylori (strain SS1) or Helicobacter felis (strain CS1) for 6 and 12 months. The frequency and spectrum of mutations at the stomach level were assessed. Inflammatory host response and inducible nitric oxide synthase (iNOS) expression by reverse-transcription polymerase chain reaction and immunohistochemistry analysis were also performed. RESULTS After 6 months, the gastric mutant frequency was 4-fold and 1.7-fold higher in mice infected with H. pylori and H. felis, respectively, than in uninfected mice. It was associated with a high frequency of transversions (AT --> CG and GC --> TA) known to result from oxidative damages. The Helicobacter-infected mice exhibited severe gastritis and a high level of iNOS messenger RNA expression. Hyperplasia developed 12 months after inoculation, and both the mutagenic effects and iNOS expression decreased in H. pylori- and H. felis-infected mice. No synergistic effects of a high-salt diet and Helicobacter infection were observed regarding the frequency of gastric mutation. CONCLUSIONS A direct gastric mutagenic effect due to H. pylori infection in the Big Blue transgenic mouse model has been shown 6 months after inoculation. This genotoxicity can be attributable to oxidative DNA damage involving the inflammatory host response.","title":"Chronic Helicobacter pylori infections induce gastric mutations in mice."},{"docid":"7317051","text":"Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.","title":"Mutant KRAS is a druggable target for pancreatic cancer."},{"docid":"15248287","text":"Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.","title":"Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival"},{"docid":"25014337","text":"We previously identified a rare mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), I132M, which confers high-level resistance to the nonnucleoside RT inhibitors (NNRTIs) nevirapine and delavirdine. In this study, we have further characterized the role of this mutation in viral replication capacity and in resistance to other RT inhibitors. Surprisingly, our data show that I132M confers marked hypersusceptibility to the nucleoside analogs lamivudine (3TC) and tenofovir at both the virus and enzyme levels. Subunit-selective mutagenesis studies revealed that the mutation in the p51 subunit of RT was responsible for the increased sensitivity to the drugs, and transient kinetic analyses showed that this hypersusceptibility was due to I132M decreasing the enzyme's affinity for the natural dCTP substrate but increasing its affinity for 3TC-triphosphate. Furthermore, the replication capacity of HIV-1 containing I132M is severely impaired. This decrease in viral replication capacity could be partially or completely compensated for by the A62V or L214I mutation, respectively. Taken together, these results help to explain the infrequent selection of I132M in patients for whom NNRTI regimens are failing and furthermore demonstrate that a single mutation outside of the polymerase active site and inside of the p51 subunit of RT can significantly influence nucleotide selectivity.","title":"The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs."},{"docid":"4409524","text":"In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal–fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.","title":"Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy"},{"docid":"16172576","text":"BACKGROUND High genetic diversity at both inter- and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. METHODS AND PRINCIPAL FINDINGS We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. CONCLUSIONS AND SIGNIFICANCE Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.","title":"Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak"},{"docid":"19828689","text":"Key features of diabetic nephropathy (DN) include the accumulation of extracellular matrix proteins such as collagen 1-alpha 1 and -2 (Col1a1 and -2). Transforming growth factor beta1 (TGF-beta), a key regulator of these extracellular matrix genes, is increased in mesangial cells (MC) in DN. By microarray profiling, we noted that TGF-beta increased Col1a2 mRNA in mouse MC (MMC) but also decreased mRNA levels of an E-box repressor, deltaEF1. TGF-beta treatment or short hairpin RNAs targeting deltaEF1 increased enhancer activity of upstream E-box elements in the Col1a2 gene. TGF-beta also decreased the expression of Smad-interacting protein 1 (SIP1), another E-box repressor similar to deltaEF1. Interestingly, we noted that SIP1 is a target of microRNA-192 (miR-192), a key miR highly expressed in the kidney. miR-192 levels also were increased by TGF-beta in MMC. TGF-beta treatment or transfection with miR-192 decreased endogenous SIP1 expression as well as reporter activity of a SIP1 3' UTR-containing luciferase construct in MMC. Conversely, a miR-192 inhibitor enhanced the luciferase activity, confirming SIP1 to be a miR-192 target. Furthermore, miR-192 synergized with deltaEF1 short hairpin RNAs to increase Col1a2 E-box-luc activity. Importantly, the in vivo relevance was noted by the observation that miR-192 levels were enhanced significantly in glomeruli isolated from streptozotocin-injected diabetic mice as well as diabetic db/db mice relative to corresponding nondiabetic controls, in parallel with increased TGF-beta and Col1a2 levels. These results uncover a role for miRs in the kidney and DN in controlling TGF-beta-induced Col1a2 expression by down-regulating E-box repressors.","title":"MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors."},{"docid":"6315132","text":"We describe a case of severe neonatal anemia with kernicterus caused by compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1-null human. The phenotype of severe nonspherocytic hemolytic anemia, jaundice, hepatosplenomegaly, and marked erythroblastosis is more severe than that present in congenital dyserythropoietic anemia type IV as a result of dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found that human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell-cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control, and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis.","title":"KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome."},{"docid":"711256","text":"Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation detection. To test whether EGFR analysis from RNA is less prone to interference from nontumour cells that have no or lower EGFR expression, we compared three methods (sequencing from cell-derived RNA versus sequencing and mass-spectrometric analysis from genomic DNA), in parallel, for EGFR mutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus 44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance, EGFR sequencing from RNA provided satisfactory detection of T790M (54.2%). These results demonstrated that EGFR sequencing using RNA as template greatly improves sensitivity for EGFR mutation detection from samples of MPE, highlighting RNA as the favourable source for analysing EGFR mutations from heterogeneous MPE specimens in NSCLC.","title":"RNA is favourable for analysing EGFR mutations in malignant pleural effusion of lung cancer."},{"docid":"13108582","text":"Osteopontin (OPN), a key component of the extracellular matrix, is associated with the fibrotic process during tissue remodeling. OPN and the cytokine interleukin (IL)-18 have been shown to be overexpressed in an array of human cardiac pathologies. In the present study, we determined the role of IL-18 in the regulation of cardiac OPN expression and the subsequent interstitial fibrosis and diastolic dysfunction. We demonstrated parallel increases in IL-18, OPN expression, and interstitial fibrosis in murine models of left ventricular pressure and volume overload. Exogenous recombinant (r)IL-18 administered for 2 wk increased cardiac OPN expression, interstitial fibrosis, and diastolic dysfunction. Stimulation of the T helper (Th)1 lymphocyte phenotype with a selective toll-like receptor (TLR)9 agonist induced cardiac IL-18 and OPN expression, which was associated with increased cardiac fibrillar collagen concentrations and interstitial fibrosis resulting in diastolic dysfunction. rIL-18 induced OPN expression and protein levels in primary of cardiac fibroblast cultures. Conditioned media from TLR9-stimulated T lymphocyte cultures induced IL-18 and OPN expression in cardiac fibroblasts, while blockade of the IL-18 receptor with a neutralizing antibody abolished the increase in OPN expression. Furthermore, a mutation in the transcriptional factor interferon regulatory factor (IRF)1 or IRF1 small interfering RNA (siRNA) resulted in the decreased expression of IL-18 and OPN in cardiac fibroblasts. With pressure overload, IRF1-mutant mice showed downregulation of IL-18 and OPN expression in cardiac tissue, reduced cardiac fibrotic development, and increased left ventricular function compared with wild type. These results provide direct evidence that the induction of IL-18 regulates OPN-mediated cardiac fibrosis and diastolic dysfunction.","title":"IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice."},{"docid":"12652963","text":"MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.","title":"miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA."},{"docid":"17648235","text":"De-regulation of the wingless and integration site growth factor (WNT) signaling pathway via mutations in APC and Axin, proteins that target β-catenin for destruction, have been linked to various types of human cancer. These genetic alterations rarely, if ever, are observed in breast tumors. However, various lines of evidence suggest that WNT signaling may also be de-regulated in breast cancer. Most breast tumors show hypermethylation of the promoter region of secreted Frizzled-related protein 1 (sFRP1), a negative WNT pathway regulator, leading to downregulation of its expression. As a consequence, WNT signaling is enhanced and may contribute to proliferation of human breast tumor cells. We previously demonstrated that, in addition to the canonical WNT/β-catenin pathway, WNT signaling activates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in mouse mammary epithelial cells via epidermal growth factor receptor (EGFR) transactivation. Using the WNT modulator sFRP1 and short interfering RNA-mediated Dishevelled (DVL) knockdown, we interfered with autocrine WNT signaling at the ligand-receptor level. The impact on proliferation was measured by cell counting, YOPRO, and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay; β-catenin, EGFR, ERK1/2 activation, and PARP (poly [ADP-ribose]polymerase) cleavages were assessed by Western blotting after treatment of human breast cancer cell lines with conditioned media, purified proteins, small-molecule inhibitors, or blocking antibodies. Phospho-DVL and stabilized β-catenin are present in many breast tumor cell lines, indicating autocrine WNT signaling activity. Interfering with this loop decreases active β-catenin levels, lowers ERK1/2 activity, blocks proliferation, and induces apoptosis in MDA-MB-231, BT474, SkBr3, JIMT-1, and MCF-7 cells. The effects of WNT signaling are mediated partly by EGFR transactivation in human breast cancer cells in a metalloprotease- and Src-dependent manner. Furthermore, Wnt1 rescues estrogen receptor-positive (ER+) breast cancer cells from the anti-proliferative effects of 4-hydroxytamoxifen (4-HT) and this activity can be blocked by an EGFR tyrosine kinase inhibitor. Our data show that interference with autocrine WNT signaling in human breast cancer reduces proliferation and survival of human breast cancer cells and rescues ER+ tumor cells from 4-HT by activation of the canonical WNT pathway and EGFR transactivation. These findings suggest that interference with WNT signaling at the ligand-receptor level in combination with other targeted therapies may improve the efficiency of breast cancer treatments.","title":"Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation"},{"docid":"12582729","text":"BACKGROUND Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2. METHODS AND RESULTS Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA. In silico analysis predicted that miR-92a could bind to the 3' untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow. CONCLUSIONS Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.","title":"Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a."},{"docid":"42065070","text":"Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four mandrills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected mandrill. Two noninfected control animals were monitored in parallel. Blood and lymph nodes were collected at three time points before infection, twice a week during the first month, and at days 60, 180, and 360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 x 10(6) to 2 x 10(8) RNA equivalents/ml). Viremia then decreased 10- to 1,000-fold, reaching the viral set point between days 30 to 60 p.i. The levels during the chronic phase of infection were similar to that in the naturally infected donor mandrill (2 x 10(5) RNA equivalents/ml). The CD4(+) cell numbers and percentages in blood and lymph nodes decreased slightly (<10%) during primary infection, and CD8(+) cell numbers increased transiently. All values returned to preinfection infection levels by day 30 p.i. CD8(+) cell numbers or percentages, in peripheral blood and lymph nodes, did not increase during the 1 year of follow-up. In conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in mandrills. Despite high levels of viremia, CD4(+) and CD8(+) cell numbers remained stable in the post-acute phase of infection, raising questions regarding the susceptibility of mandrill T cells to activation and/or cell death in response to SIVmnd-1 infection in vivo.","title":"High levels of viral replication contrast with only transient changes in CD4(+) and CD8(+) cell numbers during the early phase of experimental infection with simian immunodeficiency virus SIVmnd-1 in Mandrillus sphinx."},{"docid":"15692098","text":"Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.","title":"Hutchinson-Gilford progeria syndrome: review of the phenotype"},{"docid":"24725136","text":"BACKGROUND The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive. METHODS We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).","title":"Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination."},{"docid":"19368793","text":"BACKGROUND Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the serum and tissue expression of miR 21 and miR 199-a to be applied as early detectors for HCC. METHODS A total of 40 serum and tissue samples (17 samples from chronic hepatitis and 23 samples from HCC patients) were collected. The levels of the two mature miRNAs (miR-21 and miR-199-a) were detected by real time quantitative reverse-transcriptase PCR (RT-qPCR) in sera and tissues of chronic hepatitis and HCC patients. Besides, miR-21 and miR-199-a levels in relation to clinical and pathological factors were explored. RESULTS We found that the expression of serum miR-21 was distinctly increased in HCC compared with chronic hepatitis (P<0.001). miR 199-a was distinctly decreased in HCC compared with chronic hepatitis (P<0.001). In addition, median of miR 21 was increased in malignant when compared to adjacent non-malignant tissues without significant differences (P=0.191) while miR 199-a was significantly decreased in malignant when compared to adjacent nonmalignant tissues (P<0.001). ROC analysis showed that miR-21 and miR-199-a might be potential biomarkers for HCC. CONCLUSIONS In conclusion, the expression of miR-21 was significantly up-regulated and miR-199-a was significantly down regulated in serum of patients with HCC. Due to their reasonable sensitivity and specificity for disease progression, miR-21 and miR-199-a could be used as potential circulating biomarkers for HCC.","title":"The potential role of miRNAs 21 and 199-a in early diagnosis of hepatocellular carcinoma."},{"docid":"19822046","text":"BACKGROUND Deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA. Little is known about the biological significance of germline mutations in PARN. METHODS We identified mutations in PARN in patients with haematological and neurological manifestations. Genomic, biochemical and knockdown experiments in human marrow cells and in zebrafish have been performed to clarify the role of PARN in the human disease. RESULTS We identified large monoallelic deletions in PARN in four patients with developmental delay or mental illness. One patient in particular had a severe neurological phenotype, central hypomyelination and bone marrow failure. This patient had an additional missense mutation on the non-deleted allele and severely reduced PARN protein and deadenylation activity. Cells from this patient had impaired oligoadenylation of specific H/ACA box small nucleolar RNAs. Importantly, PARN-deficient patient cells manifested short telomeres and an aberrant ribosome profile similar to those described in some variants of dyskeratosis congenita. Knocking down PARN in human marrow cells and zebrafish impaired haematopoiesis, providing further evidence for a causal link with the human disease. CONCLUSIONS Large monoallelic mutations of PARN can cause developmental/mental illness. Biallelic PARN mutations cause severe bone marrow failure and central hypomyelination.","title":"Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN)."},{"docid":"42441846","text":"INTRODUCTION Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD. MATERIALS AND METHODS We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype. RESULTS The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively). CONCLUSION We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.","title":"Gene--nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population."},{"docid":"9539248","text":"Mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. Maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. Although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosquito vector. An antiviral RNAi response has been shown to limit the replication of RNA viruses in flies. However, the importance of the RNAi pathway as an antiviral defense in mammals is unclear. Differences in the immune responses of mammals and mosquitoes may explain why these viruses are not generally associated with pathology in the invertebrate host. We identified virus-derived small interfering RNAs (viRNAs), 21 nt in length, in Aedes aegypti infected with the mosquito-borne virus, Sindbis (SINV). viRNAs had an asymmetric distribution that spanned the length of the SINV genome. To determine the role of viRNAs in controlling pathogenic potential, mosquitoes were infected with recombinant alphaviruses expressing suppressors of RNA silencing. Decreased survival was observed in mosquitoes in which the accumulation of viRNAs was suppressed. These results suggest that an exogenous siRNA pathway is essential to the survival of mosquitoes infected with alphaviruses and, thus, the maintenance of these viruses in nature.","title":"Alphavirus-derived small RNAs modulate pathogenesis in disease vector mosquitoes."},{"docid":"8496132","text":"Overexpression of the proto-oncogene bcl-2 promotes abnormal cell survival by inhibiting apoptosis. Expression of bcl-2 is determined, in part, by regulatory mechanisms that control the stability of bcl-2 mRNA. Elements in the 3'-untranslated region of bcl-2 mRNA have been shown to play a role in regulating the stability of the message. Previously, it was found that the RNA binding proteins nucleolin and Ebp1 have a role in stabilizing bcl-2 mRNA in HL60 cells. Here, we have identified HuR as a component of bcl-2 messenger ribonucleoprotein (mRNP) complexes. RNA coimmunoprecipitation assays showed that HuR binds to bcl-2 mRNA in vivo. We also observed an RNA-dependent coprecipitation of HuR and nucleolin, suggesting that the two proteins are present in common mRNP complexes. Moreover, nucleolin and HuR bind concurrently to bcl-2 AU-rich element (ARE) RNA in vitro, suggesting separate binding sites for these proteins on bcl-2 mRNA. Knockdown of HuR in A431 cells leads to down-regulation of bcl-2 mRNA and protein levels. Observation of a decreased ratio of bcl-2 mRNA to heterogeneous nuclear RNA in HuR knockdown cells confirmed a positive role for HuR in regulating bcl-2 stability. Recombinant HuR retards exosome-mediated decay of bcl-2 ARE RNA in extracts of HL60 cells. This supports a role for HuR in the regulation of bcl-2 mRNA stability in HL60 cells, as well as in A431 cells. Addition of nucleolin and HuR to HL60 cell extracts produced a synergistic protective effect on decay of bcl-2 ARE RNA. HuR knockdown also leads to redistribution of bcl-2 mRNA from polysomes to monosomes. Thus, HuR seems to play a positive role in both regulation of bcl-2 mRNA translation and mRNA stability.","title":"Regulation of Bcl-2 expression by HuR in HL60 leukemia cells and A431 carcinoma cells."},{"docid":"7029990","text":"One type of RNA editing involves the conversion of adenosine residues into inosine in double-stranded RNA through the action of adenosine deaminases acting on RNA (ADAR). A-to-I RNA editing of the coding sequence could result in synthesis of proteins not directly encoded in the genome. ADAR edits also non-coding sequences of target RNAs, such as introns and 3'-untranslated regions, which may affect splicing, translation, and mRNA stability. Three mammalian ADAR gene family members (ADAR1-3) have been identified. Here we investigated phenotypes of mice homozygous for ADAR1 null mutation. Although live ADAR1-/- embryos with normal gross appearance could be recovered up to E11.5, widespread apoptosis was detected in many tissues. Fibroblasts derived from ADAR1-/- embryos were also prone to apoptosis induced by serum deprivation. Our results demonstrate an essential requirement for ADAR1 in embryogenesis and suggest that it functions to promote survival of numerous tissues by editing one or more double-stranded RNAs required for protection against stress-induced apoptosis.","title":"Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene."},{"docid":"34733465","text":"BACKGROUND Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.","title":"Association of cystic fibrosis with abnormalities in fatty acid metabolism."},{"docid":"11016410","text":"Within hosts, RNA viruses form populations that are genetically and phenotypically complex. Heterogeneity in RNA virus genomes arises due to error-prone replication and is reduced by stochastic and selective mechanisms that are incompletely understood. Defining how natural selection shapes RNA virus populations is critical because it can inform treatment paradigms and enhance control efforts. We allowed West Nile virus (WNV) to replicate in wild-caught American crows, house sparrows and American robins to assess how natural selection shapes RNA virus populations in ecologically relevant hosts that differ in susceptibility to virus-induced mortality. After five sequential passages in each bird species, we examined the phenotype and population diversity of WNV through fitness competition assays and next generation sequencing. We demonstrate that fitness gains occur in a species-specific manner, with the greatest replicative fitness gains in robin-passaged WNV and the least in WNV passaged in crows. Sequencing data revealed that intrahost WNV populations were strongly influenced by purifying selection and the overall complexity of the viral populations was similar among passaged hosts. However, the selective pressures that control WNV populations seem to be bird species-dependent. Specifically, crow-passaged WNV populations contained the most unique mutations (~1.7× more than sparrows, ~3.4× more than robins) and defective genomes (~1.4× greater than sparrows, ~2.7× greater than robins), but the lowest average mutation frequency (about equal to sparrows, ~2.6× lower than robins). Therefore, our data suggest that WNV replication in the most disease-susceptible bird species is positively associated with virus mutational tolerance, likely via complementation, and negatively associated with the strength of selection. These differences in genetic composition most likely have distinct phenotypic consequences for the virus populations. Taken together, these results reveal important insights into how different hosts may contribute to the emergence of RNA viruses.","title":"Experimental Evolution of an RNA Virus in Wild Birds: Evidence for Host-Dependent Impacts on Population Structure and Competitive Fitness"},{"docid":"4459491","text":"Alzheimer’s disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer’s disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer’s disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer’s disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer’s disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer’s disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.","title":"A three-dimensional human neural cell culture model of Alzheimer’s disease"},{"docid":"4993011","text":"ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers.","title":"Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers"}],"string":"[\n {\n \"docid\": \"23604601\",\n \"text\": \"The IME1 gene of Saccharomyces cerevisiae is required for initiation of meiosis. Transcription of IME1 is detected under conditions which are known to induce initiation of meiosis, namely starvation for nitrogen and glucose, and the presence of MATa1 and MAT alpha 2 gene products. In this paper we show that IME1 is also subject to translational regulation. Translation of IME1 mRNA is achieved either upon nitrogen starvation, or upon G1 arrest. In the presence of nutrients, constitutively elevated transcription of IME1 is also sufficient for the translation of IME1 RNA. Four different conditions were found to cause expression of Ime1 protein in vegetative cultures: elevated transcription levels due to the presence of IME1 on a multicopy plasmid; elevated transcription provided by a Gal-IME1 construct; G1 arrest due to alpha-factor treatment; G1 arrest following mild heat-shock treatment of cdc28 diploids. Using these conditions, we obtained evidence that starvation is required not only for transcription and efficient translation of IME1, but also for either the activation of Ime1 protein or for the induction/activation of another factor that, either alone or in combination with Ime1, induces meiosis.\",\n \"title\": \"Post-transcriptional regulation of IME1 determines initiation of meiosis in Saccharomyces cerevisiae.\"\n },\n {\n \"docid\": \"19255949\",\n \"text\": \"Mutations in the PARN gene (encoding poly(A)-specific ribonuclease) cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita, but how PARN deficiency impairs telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem cells (iPSCs) from patients with dyskeratosis congenita with PARN mutations, we show that PARN is required for the 3′-end maturation of the telomerase RNA component (TERC). Patient-derived cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3′ termini shows that PARN is required for removal of post-transcriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased proportion of oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results demonstrate a new role for PARN in the biogenesis of TERC and provide a mechanism linking PARN mutations to telomere diseases.\",\n \"title\": \"Poly(A)-specific ribonuclease (PARN) mediates 3′-end maturation of the telomerase RNA component\"\n },\n {\n \"docid\": \"33370\",\n \"text\": \"Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioblastoma stem cells (GSCs). GSCs are regulated by molecular pathways distinct from the bulk tumor that may be useful therapeutic targets. We determined that A20 (TNFAIP3), a regulator of cell survival and the NF-kappaB pathway, is overexpressed in GSCs relative to non-stem glioblastoma cells at both the mRNA and protein levels. To determine the functional significance of A20 in GSCs, we targeted A20 expression with lentiviral-mediated delivery of short hairpin RNA (shRNA). Inhibiting A20 expression decreased GSC growth and survival through mechanisms associated with decreased cell-cycle progression and decreased phosphorylation of p65/RelA. Elevated levels of A20 in GSCs contributed to apoptotic resistance: GSCs were less susceptible to TNFalpha-induced cell death than matched non-stem glioma cells, but A20 knockdown sensitized GSCs to TNFalpha-mediated apoptosis. The decreased survival of GSCs upon A20 knockdown contributed to the reduced ability of these cells to self-renew in primary and secondary neurosphere formation assays. The tumorigenic potential of GSCs was decreased with A20 targeting, resulting in increased survival of mice bearing human glioma xenografts. In silico analysis of a glioma patient genomic database indicates that A20 overexpression and amplification is inversely correlated with survival. Together these data indicate that A20 contributes to glioma maintenance through effects on the glioma stem cell subpopulation. Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival. A20 anticancer therapies should therefore be viewed with caution as effects will likely differ depending on the tumor type.\",\n \"title\": \"Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth\"\n },\n {\n \"docid\": \"26495128\",\n \"text\": \"B23 (NPM/nucleophosmin) is a multifunctional nucleolar protein and a member of the nucleoplasmin superfamily of acidic histone chaperones. B23 is essential for normal embryonic development and plays an important role in genomic stability, ribosome biogenesis, and anti-apoptotic signaling. Altered protein expression or genomic mutation of B23 is encountered in many different forms of cancer. Although described as multifunctional, a genuine molecular function of B23 is not fully understood. Here we show that B23 is associated with a protein complex consisting of ribosomal proteins and ribosome-associated RNA helicases. A novel, RNA-independent interaction between ribosomal protein S9 (RPS9) and B23 was further investigated. We found that S9 binding requires an intact B23 oligomerization domain. Depletion of S9 by small interfering RNA resulted in decreased protein synthesis and G(1) cell cycle arrest, in association with induction of p53 target genes. We determined that S9 is a short-lived protein in the absence of ribosome biogenesis, and proteasomal inhibition significantly increased S9 protein level. Overexpression of B23 facilitated nucleolar storage of S9, whereas knockdown of B23 led to diminished levels of nucleolar S9. Our results suggest that B23 selectively stores, and protects ribosomal protein S9 in nucleoli and therefore could facilitate ribosome biogenesis.\",\n \"title\": \"Ribosomal protein S9 is a novel B23/NPM-binding protein required for normal cell proliferation.\"\n },\n {\n \"docid\": \"24705390\",\n \"text\": \"BACKGROUND & AIMS Helicobacter pylori is an important etiologic factor in the development of gastric cancer. The aim of this study was to analyze the role of H. pylori infections in the induction of mutagenic events in gastric epithelial cells. The effect of a high-salt diet as a genotoxic risk factor was also investigated. METHODS Big Blue transgenic male mice (C57Bl/6) were inoculated with H. pylori (strain SS1) or Helicobacter felis (strain CS1) for 6 and 12 months. The frequency and spectrum of mutations at the stomach level were assessed. Inflammatory host response and inducible nitric oxide synthase (iNOS) expression by reverse-transcription polymerase chain reaction and immunohistochemistry analysis were also performed. RESULTS After 6 months, the gastric mutant frequency was 4-fold and 1.7-fold higher in mice infected with H. pylori and H. felis, respectively, than in uninfected mice. It was associated with a high frequency of transversions (AT --> CG and GC --> TA) known to result from oxidative damages. The Helicobacter-infected mice exhibited severe gastritis and a high level of iNOS messenger RNA expression. Hyperplasia developed 12 months after inoculation, and both the mutagenic effects and iNOS expression decreased in H. pylori- and H. felis-infected mice. No synergistic effects of a high-salt diet and Helicobacter infection were observed regarding the frequency of gastric mutation. CONCLUSIONS A direct gastric mutagenic effect due to H. pylori infection in the Big Blue transgenic mouse model has been shown 6 months after inoculation. This genotoxicity can be attributable to oxidative DNA damage involving the inflammatory host response.\",\n \"title\": \"Chronic Helicobacter pylori infections induce gastric mutations in mice.\"\n },\n {\n \"docid\": \"7317051\",\n \"text\": \"Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.\",\n \"title\": \"Mutant KRAS is a druggable target for pancreatic cancer.\"\n },\n {\n \"docid\": \"15248287\",\n \"text\": \"Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.\",\n \"title\": \"Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival\"\n },\n {\n \"docid\": \"25014337\",\n \"text\": \"We previously identified a rare mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), I132M, which confers high-level resistance to the nonnucleoside RT inhibitors (NNRTIs) nevirapine and delavirdine. In this study, we have further characterized the role of this mutation in viral replication capacity and in resistance to other RT inhibitors. Surprisingly, our data show that I132M confers marked hypersusceptibility to the nucleoside analogs lamivudine (3TC) and tenofovir at both the virus and enzyme levels. Subunit-selective mutagenesis studies revealed that the mutation in the p51 subunit of RT was responsible for the increased sensitivity to the drugs, and transient kinetic analyses showed that this hypersusceptibility was due to I132M decreasing the enzyme's affinity for the natural dCTP substrate but increasing its affinity for 3TC-triphosphate. Furthermore, the replication capacity of HIV-1 containing I132M is severely impaired. This decrease in viral replication capacity could be partially or completely compensated for by the A62V or L214I mutation, respectively. Taken together, these results help to explain the infrequent selection of I132M in patients for whom NNRTI regimens are failing and furthermore demonstrate that a single mutation outside of the polymerase active site and inside of the p51 subunit of RT can significantly influence nucleotide selectivity.\",\n \"title\": \"The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs.\"\n },\n {\n \"docid\": \"4409524\",\n \"text\": \"In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal–fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.\",\n \"title\": \"Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy\"\n },\n {\n \"docid\": \"16172576\",\n \"text\": \"BACKGROUND High genetic diversity at both inter- and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. METHODS AND PRINCIPAL FINDINGS We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. CONCLUSIONS AND SIGNIFICANCE Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.\",\n \"title\": \"Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak\"\n },\n {\n \"docid\": \"19828689\",\n \"text\": \"Key features of diabetic nephropathy (DN) include the accumulation of extracellular matrix proteins such as collagen 1-alpha 1 and -2 (Col1a1 and -2). Transforming growth factor beta1 (TGF-beta), a key regulator of these extracellular matrix genes, is increased in mesangial cells (MC) in DN. By microarray profiling, we noted that TGF-beta increased Col1a2 mRNA in mouse MC (MMC) but also decreased mRNA levels of an E-box repressor, deltaEF1. TGF-beta treatment or short hairpin RNAs targeting deltaEF1 increased enhancer activity of upstream E-box elements in the Col1a2 gene. TGF-beta also decreased the expression of Smad-interacting protein 1 (SIP1), another E-box repressor similar to deltaEF1. Interestingly, we noted that SIP1 is a target of microRNA-192 (miR-192), a key miR highly expressed in the kidney. miR-192 levels also were increased by TGF-beta in MMC. TGF-beta treatment or transfection with miR-192 decreased endogenous SIP1 expression as well as reporter activity of a SIP1 3' UTR-containing luciferase construct in MMC. Conversely, a miR-192 inhibitor enhanced the luciferase activity, confirming SIP1 to be a miR-192 target. Furthermore, miR-192 synergized with deltaEF1 short hairpin RNAs to increase Col1a2 E-box-luc activity. Importantly, the in vivo relevance was noted by the observation that miR-192 levels were enhanced significantly in glomeruli isolated from streptozotocin-injected diabetic mice as well as diabetic db/db mice relative to corresponding nondiabetic controls, in parallel with increased TGF-beta and Col1a2 levels. These results uncover a role for miRs in the kidney and DN in controlling TGF-beta-induced Col1a2 expression by down-regulating E-box repressors.\",\n \"title\": \"MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors.\"\n },\n {\n \"docid\": \"6315132\",\n \"text\": \"We describe a case of severe neonatal anemia with kernicterus caused by compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1-null human. The phenotype of severe nonspherocytic hemolytic anemia, jaundice, hepatosplenomegaly, and marked erythroblastosis is more severe than that present in congenital dyserythropoietic anemia type IV as a result of dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found that human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell-cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control, and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis.\",\n \"title\": \"KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.\"\n },\n {\n \"docid\": \"711256\",\n \"text\": \"Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation detection. To test whether EGFR analysis from RNA is less prone to interference from nontumour cells that have no or lower EGFR expression, we compared three methods (sequencing from cell-derived RNA versus sequencing and mass-spectrometric analysis from genomic DNA), in parallel, for EGFR mutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus 44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance, EGFR sequencing from RNA provided satisfactory detection of T790M (54.2%). These results demonstrated that EGFR sequencing using RNA as template greatly improves sensitivity for EGFR mutation detection from samples of MPE, highlighting RNA as the favourable source for analysing EGFR mutations from heterogeneous MPE specimens in NSCLC.\",\n \"title\": \"RNA is favourable for analysing EGFR mutations in malignant pleural effusion of lung cancer.\"\n },\n {\n \"docid\": \"13108582\",\n \"text\": \"Osteopontin (OPN), a key component of the extracellular matrix, is associated with the fibrotic process during tissue remodeling. OPN and the cytokine interleukin (IL)-18 have been shown to be overexpressed in an array of human cardiac pathologies. In the present study, we determined the role of IL-18 in the regulation of cardiac OPN expression and the subsequent interstitial fibrosis and diastolic dysfunction. We demonstrated parallel increases in IL-18, OPN expression, and interstitial fibrosis in murine models of left ventricular pressure and volume overload. Exogenous recombinant (r)IL-18 administered for 2 wk increased cardiac OPN expression, interstitial fibrosis, and diastolic dysfunction. Stimulation of the T helper (Th)1 lymphocyte phenotype with a selective toll-like receptor (TLR)9 agonist induced cardiac IL-18 and OPN expression, which was associated with increased cardiac fibrillar collagen concentrations and interstitial fibrosis resulting in diastolic dysfunction. rIL-18 induced OPN expression and protein levels in primary of cardiac fibroblast cultures. Conditioned media from TLR9-stimulated T lymphocyte cultures induced IL-18 and OPN expression in cardiac fibroblasts, while blockade of the IL-18 receptor with a neutralizing antibody abolished the increase in OPN expression. Furthermore, a mutation in the transcriptional factor interferon regulatory factor (IRF)1 or IRF1 small interfering RNA (siRNA) resulted in the decreased expression of IL-18 and OPN in cardiac fibroblasts. With pressure overload, IRF1-mutant mice showed downregulation of IL-18 and OPN expression in cardiac tissue, reduced cardiac fibrotic development, and increased left ventricular function compared with wild type. These results provide direct evidence that the induction of IL-18 regulates OPN-mediated cardiac fibrosis and diastolic dysfunction.\",\n \"title\": \"IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice.\"\n },\n {\n \"docid\": \"12652963\",\n \"text\": \"MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.\",\n \"title\": \"miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA.\"\n },\n {\n \"docid\": \"17648235\",\n \"text\": \"De-regulation of the wingless and integration site growth factor (WNT) signaling pathway via mutations in APC and Axin, proteins that target β-catenin for destruction, have been linked to various types of human cancer. These genetic alterations rarely, if ever, are observed in breast tumors. However, various lines of evidence suggest that WNT signaling may also be de-regulated in breast cancer. Most breast tumors show hypermethylation of the promoter region of secreted Frizzled-related protein 1 (sFRP1), a negative WNT pathway regulator, leading to downregulation of its expression. As a consequence, WNT signaling is enhanced and may contribute to proliferation of human breast tumor cells. We previously demonstrated that, in addition to the canonical WNT/β-catenin pathway, WNT signaling activates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in mouse mammary epithelial cells via epidermal growth factor receptor (EGFR) transactivation. Using the WNT modulator sFRP1 and short interfering RNA-mediated Dishevelled (DVL) knockdown, we interfered with autocrine WNT signaling at the ligand-receptor level. The impact on proliferation was measured by cell counting, YOPRO, and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay; β-catenin, EGFR, ERK1/2 activation, and PARP (poly [ADP-ribose]polymerase) cleavages were assessed by Western blotting after treatment of human breast cancer cell lines with conditioned media, purified proteins, small-molecule inhibitors, or blocking antibodies. Phospho-DVL and stabilized β-catenin are present in many breast tumor cell lines, indicating autocrine WNT signaling activity. Interfering with this loop decreases active β-catenin levels, lowers ERK1/2 activity, blocks proliferation, and induces apoptosis in MDA-MB-231, BT474, SkBr3, JIMT-1, and MCF-7 cells. The effects of WNT signaling are mediated partly by EGFR transactivation in human breast cancer cells in a metalloprotease- and Src-dependent manner. Furthermore, Wnt1 rescues estrogen receptor-positive (ER+) breast cancer cells from the anti-proliferative effects of 4-hydroxytamoxifen (4-HT) and this activity can be blocked by an EGFR tyrosine kinase inhibitor. Our data show that interference with autocrine WNT signaling in human breast cancer reduces proliferation and survival of human breast cancer cells and rescues ER+ tumor cells from 4-HT by activation of the canonical WNT pathway and EGFR transactivation. These findings suggest that interference with WNT signaling at the ligand-receptor level in combination with other targeted therapies may improve the efficiency of breast cancer treatments.\",\n \"title\": \"Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation\"\n },\n {\n \"docid\": \"12582729\",\n \"text\": \"BACKGROUND Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2. METHODS AND RESULTS Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA. In silico analysis predicted that miR-92a could bind to the 3' untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow. CONCLUSIONS Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.\",\n \"title\": \"Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a.\"\n },\n {\n \"docid\": \"42065070\",\n \"text\": \"Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four mandrills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected mandrill. Two noninfected control animals were monitored in parallel. Blood and lymph nodes were collected at three time points before infection, twice a week during the first month, and at days 60, 180, and 360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 x 10(6) to 2 x 10(8) RNA equivalents/ml). Viremia then decreased 10- to 1,000-fold, reaching the viral set point between days 30 to 60 p.i. The levels during the chronic phase of infection were similar to that in the naturally infected donor mandrill (2 x 10(5) RNA equivalents/ml). The CD4(+) cell numbers and percentages in blood and lymph nodes decreased slightly (<10%) during primary infection, and CD8(+) cell numbers increased transiently. All values returned to preinfection infection levels by day 30 p.i. CD8(+) cell numbers or percentages, in peripheral blood and lymph nodes, did not increase during the 1 year of follow-up. In conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in mandrills. Despite high levels of viremia, CD4(+) and CD8(+) cell numbers remained stable in the post-acute phase of infection, raising questions regarding the susceptibility of mandrill T cells to activation and/or cell death in response to SIVmnd-1 infection in vivo.\",\n \"title\": \"High levels of viral replication contrast with only transient changes in CD4(+) and CD8(+) cell numbers during the early phase of experimental infection with simian immunodeficiency virus SIVmnd-1 in Mandrillus sphinx.\"\n },\n {\n \"docid\": \"15692098\",\n \"text\": \"Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.\",\n \"title\": \"Hutchinson-Gilford progeria syndrome: review of the phenotype\"\n },\n {\n \"docid\": \"24725136\",\n \"text\": \"BACKGROUND The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive. METHODS We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).\",\n \"title\": \"Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination.\"\n },\n {\n \"docid\": \"19368793\",\n \"text\": \"BACKGROUND Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the serum and tissue expression of miR 21 and miR 199-a to be applied as early detectors for HCC. METHODS A total of 40 serum and tissue samples (17 samples from chronic hepatitis and 23 samples from HCC patients) were collected. The levels of the two mature miRNAs (miR-21 and miR-199-a) were detected by real time quantitative reverse-transcriptase PCR (RT-qPCR) in sera and tissues of chronic hepatitis and HCC patients. Besides, miR-21 and miR-199-a levels in relation to clinical and pathological factors were explored. RESULTS We found that the expression of serum miR-21 was distinctly increased in HCC compared with chronic hepatitis (P<0.001). miR 199-a was distinctly decreased in HCC compared with chronic hepatitis (P<0.001). In addition, median of miR 21 was increased in malignant when compared to adjacent non-malignant tissues without significant differences (P=0.191) while miR 199-a was significantly decreased in malignant when compared to adjacent nonmalignant tissues (P<0.001). ROC analysis showed that miR-21 and miR-199-a might be potential biomarkers for HCC. CONCLUSIONS In conclusion, the expression of miR-21 was significantly up-regulated and miR-199-a was significantly down regulated in serum of patients with HCC. Due to their reasonable sensitivity and specificity for disease progression, miR-21 and miR-199-a could be used as potential circulating biomarkers for HCC.\",\n \"title\": \"The potential role of miRNAs 21 and 199-a in early diagnosis of hepatocellular carcinoma.\"\n },\n {\n \"docid\": \"19822046\",\n \"text\": \"BACKGROUND Deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA. Little is known about the biological significance of germline mutations in PARN. METHODS We identified mutations in PARN in patients with haematological and neurological manifestations. Genomic, biochemical and knockdown experiments in human marrow cells and in zebrafish have been performed to clarify the role of PARN in the human disease. RESULTS We identified large monoallelic deletions in PARN in four patients with developmental delay or mental illness. One patient in particular had a severe neurological phenotype, central hypomyelination and bone marrow failure. This patient had an additional missense mutation on the non-deleted allele and severely reduced PARN protein and deadenylation activity. Cells from this patient had impaired oligoadenylation of specific H/ACA box small nucleolar RNAs. Importantly, PARN-deficient patient cells manifested short telomeres and an aberrant ribosome profile similar to those described in some variants of dyskeratosis congenita. Knocking down PARN in human marrow cells and zebrafish impaired haematopoiesis, providing further evidence for a causal link with the human disease. CONCLUSIONS Large monoallelic mutations of PARN can cause developmental/mental illness. Biallelic PARN mutations cause severe bone marrow failure and central hypomyelination.\",\n \"title\": \"Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN).\"\n },\n {\n \"docid\": \"42441846\",\n \"text\": \"INTRODUCTION Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD. MATERIALS AND METHODS We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype. RESULTS The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively). CONCLUSION We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.\",\n \"title\": \"Gene--nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population.\"\n },\n {\n \"docid\": \"9539248\",\n \"text\": \"Mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. Maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. Although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosquito vector. An antiviral RNAi response has been shown to limit the replication of RNA viruses in flies. However, the importance of the RNAi pathway as an antiviral defense in mammals is unclear. Differences in the immune responses of mammals and mosquitoes may explain why these viruses are not generally associated with pathology in the invertebrate host. We identified virus-derived small interfering RNAs (viRNAs), 21 nt in length, in Aedes aegypti infected with the mosquito-borne virus, Sindbis (SINV). viRNAs had an asymmetric distribution that spanned the length of the SINV genome. To determine the role of viRNAs in controlling pathogenic potential, mosquitoes were infected with recombinant alphaviruses expressing suppressors of RNA silencing. Decreased survival was observed in mosquitoes in which the accumulation of viRNAs was suppressed. These results suggest that an exogenous siRNA pathway is essential to the survival of mosquitoes infected with alphaviruses and, thus, the maintenance of these viruses in nature.\",\n \"title\": \"Alphavirus-derived small RNAs modulate pathogenesis in disease vector mosquitoes.\"\n },\n {\n \"docid\": \"8496132\",\n \"text\": \"Overexpression of the proto-oncogene bcl-2 promotes abnormal cell survival by inhibiting apoptosis. Expression of bcl-2 is determined, in part, by regulatory mechanisms that control the stability of bcl-2 mRNA. Elements in the 3'-untranslated region of bcl-2 mRNA have been shown to play a role in regulating the stability of the message. Previously, it was found that the RNA binding proteins nucleolin and Ebp1 have a role in stabilizing bcl-2 mRNA in HL60 cells. Here, we have identified HuR as a component of bcl-2 messenger ribonucleoprotein (mRNP) complexes. RNA coimmunoprecipitation assays showed that HuR binds to bcl-2 mRNA in vivo. We also observed an RNA-dependent coprecipitation of HuR and nucleolin, suggesting that the two proteins are present in common mRNP complexes. Moreover, nucleolin and HuR bind concurrently to bcl-2 AU-rich element (ARE) RNA in vitro, suggesting separate binding sites for these proteins on bcl-2 mRNA. Knockdown of HuR in A431 cells leads to down-regulation of bcl-2 mRNA and protein levels. Observation of a decreased ratio of bcl-2 mRNA to heterogeneous nuclear RNA in HuR knockdown cells confirmed a positive role for HuR in regulating bcl-2 stability. Recombinant HuR retards exosome-mediated decay of bcl-2 ARE RNA in extracts of HL60 cells. This supports a role for HuR in the regulation of bcl-2 mRNA stability in HL60 cells, as well as in A431 cells. Addition of nucleolin and HuR to HL60 cell extracts produced a synergistic protective effect on decay of bcl-2 ARE RNA. HuR knockdown also leads to redistribution of bcl-2 mRNA from polysomes to monosomes. Thus, HuR seems to play a positive role in both regulation of bcl-2 mRNA translation and mRNA stability.\",\n \"title\": \"Regulation of Bcl-2 expression by HuR in HL60 leukemia cells and A431 carcinoma cells.\"\n },\n {\n \"docid\": \"7029990\",\n \"text\": \"One type of RNA editing involves the conversion of adenosine residues into inosine in double-stranded RNA through the action of adenosine deaminases acting on RNA (ADAR). A-to-I RNA editing of the coding sequence could result in synthesis of proteins not directly encoded in the genome. ADAR edits also non-coding sequences of target RNAs, such as introns and 3'-untranslated regions, which may affect splicing, translation, and mRNA stability. Three mammalian ADAR gene family members (ADAR1-3) have been identified. Here we investigated phenotypes of mice homozygous for ADAR1 null mutation. Although live ADAR1-/- embryos with normal gross appearance could be recovered up to E11.5, widespread apoptosis was detected in many tissues. Fibroblasts derived from ADAR1-/- embryos were also prone to apoptosis induced by serum deprivation. Our results demonstrate an essential requirement for ADAR1 in embryogenesis and suggest that it functions to promote survival of numerous tissues by editing one or more double-stranded RNAs required for protection against stress-induced apoptosis.\",\n \"title\": \"Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene.\"\n },\n {\n \"docid\": \"34733465\",\n \"text\": \"BACKGROUND Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.\",\n \"title\": \"Association of cystic fibrosis with abnormalities in fatty acid metabolism.\"\n },\n {\n \"docid\": \"11016410\",\n \"text\": \"Within hosts, RNA viruses form populations that are genetically and phenotypically complex. Heterogeneity in RNA virus genomes arises due to error-prone replication and is reduced by stochastic and selective mechanisms that are incompletely understood. Defining how natural selection shapes RNA virus populations is critical because it can inform treatment paradigms and enhance control efforts. We allowed West Nile virus (WNV) to replicate in wild-caught American crows, house sparrows and American robins to assess how natural selection shapes RNA virus populations in ecologically relevant hosts that differ in susceptibility to virus-induced mortality. After five sequential passages in each bird species, we examined the phenotype and population diversity of WNV through fitness competition assays and next generation sequencing. We demonstrate that fitness gains occur in a species-specific manner, with the greatest replicative fitness gains in robin-passaged WNV and the least in WNV passaged in crows. Sequencing data revealed that intrahost WNV populations were strongly influenced by purifying selection and the overall complexity of the viral populations was similar among passaged hosts. However, the selective pressures that control WNV populations seem to be bird species-dependent. Specifically, crow-passaged WNV populations contained the most unique mutations (~1.7× more than sparrows, ~3.4× more than robins) and defective genomes (~1.4× greater than sparrows, ~2.7× greater than robins), but the lowest average mutation frequency (about equal to sparrows, ~2.6× lower than robins). Therefore, our data suggest that WNV replication in the most disease-susceptible bird species is positively associated with virus mutational tolerance, likely via complementation, and negatively associated with the strength of selection. These differences in genetic composition most likely have distinct phenotypic consequences for the virus populations. Taken together, these results reveal important insights into how different hosts may contribute to the emergence of RNA viruses.\",\n \"title\": \"Experimental Evolution of an RNA Virus in Wild Birds: Evidence for Host-Dependent Impacts on Population Structure and Competitive Fitness\"\n },\n {\n \"docid\": \"4459491\",\n \"text\": \"Alzheimer’s disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer’s disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer’s disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer’s disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer’s disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer’s disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.\",\n \"title\": \"A three-dimensional human neural cell culture model of Alzheimer’s disease\"\n },\n {\n \"docid\": \"4993011\",\n \"text\": \"ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers.\",\n \"title\": \"Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers\"\n }\n]"}}},{"rowIdx":2697,"cells":{"query_id":{"kind":"string","value":"2184"},"query":{"kind":"string","value":"Ideal investments for a recent college grad with very high risk tolerance?"},"positive_passages":{"kind":"list like","value":[{"docid":"17823","text":"\"I'd suggest you start by looking at the mutual fund and/or ETF options available via your bank, and see if they have any low-cost funds that invest in high-risk sectors. You can increase your risk (and potential returns) by allocating your assets to riskier sectors rather than by picking individual stocks, and you'll be less likely to make an avoidable mistake. It is possible to do as you suggest and pick individual stocks, but by doing so you may be taking on more risk than you suspect, even unnecessary risk. For instance, if you decide to buy stock in Company A, you know you're taking a risk by investing in just one company. However, without a lot of work and financial expertise, you may not be able to assess how much risk you're taking by investing in Company A specifically, as opposed to Company B. Even if you know that investing in individual stocks is risky, it can be very hard to know how risky those particular individual stocks are, compared to other alternatives. This is doubly true if the investment involves actions more exotic than simply buying and holding an asset like a stock. For instance, you could definitely get plenty of risk by investing in commercial real estate development or complicated options contracts; but a certain amount of work and expertise is required to even understand how to do that, and there is a greater likelihood that you will slip up and make a costly mistake that negates any extra gain, even if the investment itself might have been sound for someone with experience in that area. In other words, you want your risk to really be the risk of the investment, not the \"\"personal\"\" risk that you'll make a mistake in a complicated scheme and lose money because you didn't know what you were doing. (If you do have some expertise in more exotic investments, then maybe you could go this route, but I think most people -- including me -- don't.) On the other hand, you can find mutual funds or ETFs that invest in large economic sectors that are high-risk, but because the investment is diversified within that sector, you need only compare the risk of the sectors. For instance, emerging markets are usually considered one of the highest-risk sectors. But if you restrict your choice to low-cost emerging-market index funds, they are unlikely to differ drastically in risk (at any rate, far less than individual companies). This eliminates the problem mentioned above: when you choose to invest in Emerging Markets Index Fund A, you don't need to worry as much about whether Emerging Markets Index Fund B might have been less risky; most of the risk is in the choice to invest in the emerging markets sector in the first place, and differences between comparable funds in that sector are small by comparison. You could do the same with other targeted sectors that can produce high returns; for instance, there are mutual funds and ETFs that invest specifically in technology stocks. So you could begin by exploring the mutual funds and ETFs available via your existing investment bank, or poke around on Morningstar. Fees will still matter no matter what sector you're in, so pay attention to those. But you can probably find a way to take an aggressive risk position without getting bogged down in the details of individual companies. Also, this will be less work than trying something more exotic, so you're less likely to make a costly mistake due to not understanding the complexities of what you're investing in.\"","title":""},{"docid":"96110","text":"If you're sure you want to go the high risk route: You could consider hot stocks or even bonds for companies/countries with lower credit ratings and higher risk. I think an underrated cost of investing is the tax penalties that you pay when you win if you aren't using a tax advantaged account. For your speculating account, you might want to open a self-directed IRA so that you can get access to more of the high risk options that you crave without the tax liability if any of those have a big payout. You want your high-growth money to be in a Roth, because it would be a shame to strike it rich while you're young and then have to pay taxes on it when you're older. If you choose not to make these investments in a tax-advantaged account, try to hold your stocks for a year so you only get taxed at capital gains rates instead of as ordinary income. If you choose to work for a startup, buy your stock options as they vest so that if the company goes public or sells privately, you will have owned those stocks long enough to qualify for capital gains. If you want my actual advice about what I think you should do: I would increase your 401k percentage to at least 10% with or without a match, and keep that in low cost index funds while you're young, but moving some of those investments over to bonds as you get closer to retirement and your risk tolerance declines. Assuming you're not in the 25% tax bracket, all of your money should be in a Roth 401k or IRA because you can withdraw it without being taxed when you retire. The more money you put into those accounts now while you are young, the more time it all has to grow. The real risk of chasing the high-risk returns is that when you bet wrong it will set you back far enough that you will lose the advantage that comes from investing the money while you're young. You're going to have up and down years with your self-selected investments, why not just keep plugging money into the S&P which has its ups and downs, but has always trended up over time?","title":""},{"docid":"560395","text":"Congratulations on being in this position. Your problem - which I think that you identified - is that you don't know much about investing. My recommendation is that you start with three goals: The Motley Fool (www.fool.com) has a lot of good information on their site. Their approach may or may not align with what you want to do; I've subscribed to their newsletters for quite a while and have found them useful. I'm what is known as a value investor; I like to make investments and hold them for a long time. Others have different philosophies. For the second goal, it's very important to follow the money and ask how people get paid in the investment business. The real money in Wall Street is made not by investment, but by charging money to those who are in the investment business. There are numerous people in line for some of your money in return for service or advice; fees for buying/selling stocks, fees for telling you which stocks to buy/sell, fees for managing your money, etc. You can invest without spending too much on fees if you understand how the system works. For the third goal, I recommend choosing a few stocks, and creating a virtual portfolio. You can then then get used to watching and tracking your investments. If you want a place to put your money while you do this, I'd start with an S&P 500 index fund with a low expense ratio, and I'd buy it through a discount broker (I use Scottrade but there are a number of choices). Hope that helps.","title":""},{"docid":"150475","text":"\"You have a high risk tolerance? Then learn about exchange traded options, and futures. Or the variety of markets that governments have decided that people without high income are too stupid to invest in, not even kidding. It appears that a lot of this discussion about your risk profile and investing has centered around \"\"stocks\"\" and \"\"bonds\"\". The similarities being that they are assets issued by collections of humans (corporations), with risk profiles based on the collective decisions of those humans. That doesn't even scratch the surface of the different kinds of asset classes to invest in. Bonds? boring. Bond futures? craziness happening over there :) Also, there are potentially very favorable tax treatments for other asset classes. For instance, you mentioned your desire to hold an investment for over a year for tax reasons... well EVERY FUTURES TRADE gets that kind of tax treatment (partially), whether you hold it for one day or more, see the 60/40 rule. A rebuttal being that some of these asset classes should be left to professionals. Stocks are no different in that regards. Either educate yourself or stick with the managed 401k funds.\"","title":""},{"docid":"313127","text":"Cryptocurrencies like Bitcoin or Ethereum. Then check their prices daily. With daily price swings of over 10% (both up and down) being a common occurrence, you'll quickly learn how high your risk tolerance really is. :) A lot of IT people believe that cryptocurrencies will stay. Whether Bitcoin or Ethereum will be among them is anyone's guess. Compare to the Dotcom boom, which will be Amazon.com and which will be Pets.com?","title":""},{"docid":"303561","text":"An ideal investment for a highly risk tolerant college grad with a background in software and programming, is a software company. That's because it's the kind of investment that you will be able to judge better than most other people, including yours truly. Hopefully, one day the software company for a highly risk tolerant investor will be your own.(Ask Bill Gates or even Michael Dell, although the latter was more involved in hardware.)","title":""},{"docid":"369342","text":"Sorry to be boring but you have the luxury of time and do not need high-risk investments. Just put the surplus cash into a diversified blue-chip fund, sit back, and enjoy it supporting you in 50 years time. Your post makes me think you're implicitly assuming that since you have a very high risk tolerance you ought to be able to earn spectacular returns. Unfortunately the risks involved are extremely difficult to quantify and there's no guarantee they're fairly discounted. Most people would intuitively realise betting on 100-1 horses is a losing proposition but not realise just how bad it is. In reality far fewer than one in a thousand 100-1 shots actually win.","title":""},{"docid":"314300","text":"If you have been putting savings away for the longer term and have some extra funds which you would like to take some extra risk on - then I say work yourself out a strategy/plan, get yourself educated and go for it. If it is individual shares you are interested then work out if you prefer to use fundamental analysis, technical analysis or some of both. You can use fundamental analysis to help determine which shares to buy, and then use technical analysis to help determine when to get into and out of a position. You say you are prepared to lose $10,000 in order to try to get higher returns. I don't know what percentage this $10,000 is of the capital you intend to use in this kind of investments/trading, but lets assume it is 10% - so your total starting capital would be $100,000. The idea now would be to learn about money management, position sizing and risk management. There are plenty of good books on these subjects. If you set a maximum loss for each position you open of 1% of your capital - i.e $1,000, then you would have to get 10 straight losses in a row to get to your 10% total loss. You do this by setting stop losses on your positions. I'll use an example to explain: Say you are looking at a stock priced at $20 and you get a signal to buy it at that price. You now need to determine a stop price which if the stock goes down to, you can say well I may have been wrong on this occasion, the stock price has gone against me so I need to get out now (I put automatic stop loss conditional orders with my broker). You may determine the stop price based on previous support levels, using a percentage of your buy price or another indicator or method. I tend to use the percentage of buy price - lets say you use 10% - so your stop price would be at $18 (10% below your buy price of $20). So now you can work out your position size (the number of shares to buy). Your maximum loss on the position is $2 per share or 10% of your position in this stock, but it should also be only 1% of your total capital - being 1% of $100,000 = $1,000. You simply divide $1,000 by $2 to get 500 shares to buy. You then do this with the rest of your positions - with a $100,000 starting capital using a 1% maximum loss per position and a stop loss of 10% you will end up with a maximum of 10 positions. If you use a larger maximum loss per position your position sizes would increase and you would have less positions to open (I would not go higher than 2% maximum loss per position). If you use a larger stop loss percentage then your position sizes would decrease and you would have more positions to open. The larger the stop loss the longer you will potentially be in a position and the smaller the stop loss generally the less time you will be in a position. Also as your total capital increases so will your 1% of total capital, just as it would decrease if your total capital decreases. Using this method you can aim for higher risk/ higher return investments and reduce and manage your risk to a desired level. One other thing to consider, don't let tax determine when you sell an investment. If you are keeping a stock just so you will pay less tax if kept for over 12 months - then you are in real danger of increasing your risk considerably. I would rather pay 50% tax on a 30% return than 25% tax on a 15% return.","title":""},{"docid":"102501","text":"Theoretically there is limited demand for risky investments, so higher-risk asset classes should outperform lower-risk asset classes over sufficiently long time periods. In practice, I believe this is true, but it could be several decades before a risky portfolio starts to outperform a more conservative one. Stocks are considered more risky than most assets. Small-cap stocks and emerging market stocks are particularly high-risk. I would consider low-fee ETFs in these areas, like VB or VWO. If you want to seek out the absolute riskiest investments, you could pick individual stocks of companies in dire financial situations, as Bank of America was a couple years ago. Most importantly, if you don't expect to need the money soon, I would maximize your contribution to tax-advantaged accounts since they will grow exponentially faster than taxable accounts. Over 50 years, a 401(k) or IRA will generally grow at least 50% more than a taxable account, maybe more depending on the tax-efficiency of your investments. Try to contribute the maximum ($17,500 for most people in 2014) if you can. If you can save more than that, I'd suggest contributing a Roth 401k rather than a traditional 401(k) - since Roth contributions are post-tax, the effective contribution limit is higher. Also contribute to a Roth IRA (up to $5,500 in 2014), using a backdoor Roth if necessary.","title":""},{"docid":"285918","text":"I am in a very similar situation as you (software engineer, high disposable income). Maximize your contributions to all tax-advantaged accounts first. From those accounts you can choose to invest in high risk funds. At your age and date-target funds will invest in riskier investments on your behalf; and they'll do it while avoiding the 30%+/- haircut that you'll be paying in taxes anyhow. If, after that, you're looking for bigger risk plays then look into a brokerage account that will let you buy and sell options. These are big risk swingers and they are sophisticated, complicated products which are used by many people who likely understand finance far better than you. You can make money with them but you should consider it akin to gambling. It might be more to your liking to maintain a long position in a stock and then trade options against your long position. Start with trading covered calls, then you could consider buying options (defined limited downside risk).","title":""}],"string":"[\n {\n \"docid\": \"17823\",\n \"text\": \"\\\"I'd suggest you start by looking at the mutual fund and/or ETF options available via your bank, and see if they have any low-cost funds that invest in high-risk sectors. You can increase your risk (and potential returns) by allocating your assets to riskier sectors rather than by picking individual stocks, and you'll be less likely to make an avoidable mistake. It is possible to do as you suggest and pick individual stocks, but by doing so you may be taking on more risk than you suspect, even unnecessary risk. For instance, if you decide to buy stock in Company A, you know you're taking a risk by investing in just one company. However, without a lot of work and financial expertise, you may not be able to assess how much risk you're taking by investing in Company A specifically, as opposed to Company B. Even if you know that investing in individual stocks is risky, it can be very hard to know how risky those particular individual stocks are, compared to other alternatives. This is doubly true if the investment involves actions more exotic than simply buying and holding an asset like a stock. For instance, you could definitely get plenty of risk by investing in commercial real estate development or complicated options contracts; but a certain amount of work and expertise is required to even understand how to do that, and there is a greater likelihood that you will slip up and make a costly mistake that negates any extra gain, even if the investment itself might have been sound for someone with experience in that area. In other words, you want your risk to really be the risk of the investment, not the \\\"\\\"personal\\\"\\\" risk that you'll make a mistake in a complicated scheme and lose money because you didn't know what you were doing. (If you do have some expertise in more exotic investments, then maybe you could go this route, but I think most people -- including me -- don't.) On the other hand, you can find mutual funds or ETFs that invest in large economic sectors that are high-risk, but because the investment is diversified within that sector, you need only compare the risk of the sectors. For instance, emerging markets are usually considered one of the highest-risk sectors. But if you restrict your choice to low-cost emerging-market index funds, they are unlikely to differ drastically in risk (at any rate, far less than individual companies). This eliminates the problem mentioned above: when you choose to invest in Emerging Markets Index Fund A, you don't need to worry as much about whether Emerging Markets Index Fund B might have been less risky; most of the risk is in the choice to invest in the emerging markets sector in the first place, and differences between comparable funds in that sector are small by comparison. You could do the same with other targeted sectors that can produce high returns; for instance, there are mutual funds and ETFs that invest specifically in technology stocks. So you could begin by exploring the mutual funds and ETFs available via your existing investment bank, or poke around on Morningstar. Fees will still matter no matter what sector you're in, so pay attention to those. But you can probably find a way to take an aggressive risk position without getting bogged down in the details of individual companies. Also, this will be less work than trying something more exotic, so you're less likely to make a costly mistake due to not understanding the complexities of what you're investing in.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"96110\",\n \"text\": \"If you're sure you want to go the high risk route: You could consider hot stocks or even bonds for companies/countries with lower credit ratings and higher risk. I think an underrated cost of investing is the tax penalties that you pay when you win if you aren't using a tax advantaged account. For your speculating account, you might want to open a self-directed IRA so that you can get access to more of the high risk options that you crave without the tax liability if any of those have a big payout. You want your high-growth money to be in a Roth, because it would be a shame to strike it rich while you're young and then have to pay taxes on it when you're older. If you choose not to make these investments in a tax-advantaged account, try to hold your stocks for a year so you only get taxed at capital gains rates instead of as ordinary income. If you choose to work for a startup, buy your stock options as they vest so that if the company goes public or sells privately, you will have owned those stocks long enough to qualify for capital gains. If you want my actual advice about what I think you should do: I would increase your 401k percentage to at least 10% with or without a match, and keep that in low cost index funds while you're young, but moving some of those investments over to bonds as you get closer to retirement and your risk tolerance declines. Assuming you're not in the 25% tax bracket, all of your money should be in a Roth 401k or IRA because you can withdraw it without being taxed when you retire. The more money you put into those accounts now while you are young, the more time it all has to grow. The real risk of chasing the high-risk returns is that when you bet wrong it will set you back far enough that you will lose the advantage that comes from investing the money while you're young. You're going to have up and down years with your self-selected investments, why not just keep plugging money into the S&P which has its ups and downs, but has always trended up over time?\",\n \"title\": \"\"\n },\n {\n \"docid\": \"560395\",\n \"text\": \"Congratulations on being in this position. Your problem - which I think that you identified - is that you don't know much about investing. My recommendation is that you start with three goals: The Motley Fool (www.fool.com) has a lot of good information on their site. Their approach may or may not align with what you want to do; I've subscribed to their newsletters for quite a while and have found them useful. I'm what is known as a value investor; I like to make investments and hold them for a long time. Others have different philosophies. For the second goal, it's very important to follow the money and ask how people get paid in the investment business. The real money in Wall Street is made not by investment, but by charging money to those who are in the investment business. There are numerous people in line for some of your money in return for service or advice; fees for buying/selling stocks, fees for telling you which stocks to buy/sell, fees for managing your money, etc. You can invest without spending too much on fees if you understand how the system works. For the third goal, I recommend choosing a few stocks, and creating a virtual portfolio. You can then then get used to watching and tracking your investments. If you want a place to put your money while you do this, I'd start with an S&P 500 index fund with a low expense ratio, and I'd buy it through a discount broker (I use Scottrade but there are a number of choices). Hope that helps.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"150475\",\n \"text\": \"\\\"You have a high risk tolerance? Then learn about exchange traded options, and futures. Or the variety of markets that governments have decided that people without high income are too stupid to invest in, not even kidding. It appears that a lot of this discussion about your risk profile and investing has centered around \\\"\\\"stocks\\\"\\\" and \\\"\\\"bonds\\\"\\\". The similarities being that they are assets issued by collections of humans (corporations), with risk profiles based on the collective decisions of those humans. That doesn't even scratch the surface of the different kinds of asset classes to invest in. Bonds? boring. Bond futures? craziness happening over there :) Also, there are potentially very favorable tax treatments for other asset classes. For instance, you mentioned your desire to hold an investment for over a year for tax reasons... well EVERY FUTURES TRADE gets that kind of tax treatment (partially), whether you hold it for one day or more, see the 60/40 rule. A rebuttal being that some of these asset classes should be left to professionals. Stocks are no different in that regards. Either educate yourself or stick with the managed 401k funds.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"313127\",\n \"text\": \"Cryptocurrencies like Bitcoin or Ethereum. Then check their prices daily. With daily price swings of over 10% (both up and down) being a common occurrence, you'll quickly learn how high your risk tolerance really is. :) A lot of IT people believe that cryptocurrencies will stay. Whether Bitcoin or Ethereum will be among them is anyone's guess. Compare to the Dotcom boom, which will be Amazon.com and which will be Pets.com?\",\n \"title\": \"\"\n },\n {\n \"docid\": \"303561\",\n \"text\": \"An ideal investment for a highly risk tolerant college grad with a background in software and programming, is a software company. That's because it's the kind of investment that you will be able to judge better than most other people, including yours truly. Hopefully, one day the software company for a highly risk tolerant investor will be your own.(Ask Bill Gates or even Michael Dell, although the latter was more involved in hardware.)\",\n \"title\": \"\"\n },\n {\n \"docid\": \"369342\",\n \"text\": \"Sorry to be boring but you have the luxury of time and do not need high-risk investments. Just put the surplus cash into a diversified blue-chip fund, sit back, and enjoy it supporting you in 50 years time. Your post makes me think you're implicitly assuming that since you have a very high risk tolerance you ought to be able to earn spectacular returns. Unfortunately the risks involved are extremely difficult to quantify and there's no guarantee they're fairly discounted. Most people would intuitively realise betting on 100-1 horses is a losing proposition but not realise just how bad it is. In reality far fewer than one in a thousand 100-1 shots actually win.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"314300\",\n \"text\": \"If you have been putting savings away for the longer term and have some extra funds which you would like to take some extra risk on - then I say work yourself out a strategy/plan, get yourself educated and go for it. If it is individual shares you are interested then work out if you prefer to use fundamental analysis, technical analysis or some of both. You can use fundamental analysis to help determine which shares to buy, and then use technical analysis to help determine when to get into and out of a position. You say you are prepared to lose $10,000 in order to try to get higher returns. I don't know what percentage this $10,000 is of the capital you intend to use in this kind of investments/trading, but lets assume it is 10% - so your total starting capital would be $100,000. The idea now would be to learn about money management, position sizing and risk management. There are plenty of good books on these subjects. If you set a maximum loss for each position you open of 1% of your capital - i.e $1,000, then you would have to get 10 straight losses in a row to get to your 10% total loss. You do this by setting stop losses on your positions. I'll use an example to explain: Say you are looking at a stock priced at $20 and you get a signal to buy it at that price. You now need to determine a stop price which if the stock goes down to, you can say well I may have been wrong on this occasion, the stock price has gone against me so I need to get out now (I put automatic stop loss conditional orders with my broker). You may determine the stop price based on previous support levels, using a percentage of your buy price or another indicator or method. I tend to use the percentage of buy price - lets say you use 10% - so your stop price would be at $18 (10% below your buy price of $20). So now you can work out your position size (the number of shares to buy). Your maximum loss on the position is $2 per share or 10% of your position in this stock, but it should also be only 1% of your total capital - being 1% of $100,000 = $1,000. You simply divide $1,000 by $2 to get 500 shares to buy. You then do this with the rest of your positions - with a $100,000 starting capital using a 1% maximum loss per position and a stop loss of 10% you will end up with a maximum of 10 positions. If you use a larger maximum loss per position your position sizes would increase and you would have less positions to open (I would not go higher than 2% maximum loss per position). If you use a larger stop loss percentage then your position sizes would decrease and you would have more positions to open. The larger the stop loss the longer you will potentially be in a position and the smaller the stop loss generally the less time you will be in a position. Also as your total capital increases so will your 1% of total capital, just as it would decrease if your total capital decreases. Using this method you can aim for higher risk/ higher return investments and reduce and manage your risk to a desired level. One other thing to consider, don't let tax determine when you sell an investment. If you are keeping a stock just so you will pay less tax if kept for over 12 months - then you are in real danger of increasing your risk considerably. I would rather pay 50% tax on a 30% return than 25% tax on a 15% return.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"102501\",\n \"text\": \"Theoretically there is limited demand for risky investments, so higher-risk asset classes should outperform lower-risk asset classes over sufficiently long time periods. In practice, I believe this is true, but it could be several decades before a risky portfolio starts to outperform a more conservative one. Stocks are considered more risky than most assets. Small-cap stocks and emerging market stocks are particularly high-risk. I would consider low-fee ETFs in these areas, like VB or VWO. If you want to seek out the absolute riskiest investments, you could pick individual stocks of companies in dire financial situations, as Bank of America was a couple years ago. Most importantly, if you don't expect to need the money soon, I would maximize your contribution to tax-advantaged accounts since they will grow exponentially faster than taxable accounts. Over 50 years, a 401(k) or IRA will generally grow at least 50% more than a taxable account, maybe more depending on the tax-efficiency of your investments. Try to contribute the maximum ($17,500 for most people in 2014) if you can. If you can save more than that, I'd suggest contributing a Roth 401k rather than a traditional 401(k) - since Roth contributions are post-tax, the effective contribution limit is higher. Also contribute to a Roth IRA (up to $5,500 in 2014), using a backdoor Roth if necessary.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"285918\",\n \"text\": \"I am in a very similar situation as you (software engineer, high disposable income). Maximize your contributions to all tax-advantaged accounts first. From those accounts you can choose to invest in high risk funds. At your age and date-target funds will invest in riskier investments on your behalf; and they'll do it while avoiding the 30%+/- haircut that you'll be paying in taxes anyhow. If, after that, you're looking for bigger risk plays then look into a brokerage account that will let you buy and sell options. These are big risk swingers and they are sophisticated, complicated products which are used by many people who likely understand finance far better than you. You can make money with them but you should consider it akin to gambling. It might be more to your liking to maintain a long position in a stock and then trade options against your long position. Start with trading covered calls, then you could consider buying options (defined limited downside risk).\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"515060","text":"I completely agree that there are experts that recognize it as a very serious problem, and I agree that it is a serious problem that could cause a large recession or crash (my large chunk of remaining loans definitely agrees). My point is that this article isn't looking at economic data. It's looking at a survey of recent college grads and asking them to rank the risk of student loan debt vs the risk of North Korea. I wouldn't consider that a very useful indicator.","title":""},{"docid":"204227","text":"Stay away from college debt. You can't default on it. Your wages will be garnished if you're unable to pay it back. Even when your and old man, they will garnish your social security money. In effect college debt makes you an indentured servant. Maybe even worse than the 7 years of servitude people served in early America. Lots of grads are working in restaurants and retail stores.... even some computer science grads. There is great risk in the college investment compared to 40 years ago when it was a sure thing. Do not take debt for college. If that means you can't go to college then so be it. You're future self will than you.","title":""},{"docid":"599436","text":"\"1. Interest rates What you should know is that the longer the \"\"term\"\" of a bond fund, the more it will be affected by interest rates. So a short-term bond fund will not be subject to large gains or losses due to rate changes, an intermediate-term bond fund will be subject to moderate gains or losses, and a long-term bond fund will be subject to the largest gains or losses. When a book or financial planner says to buy \"\"bonds\"\" with no other qualification, they almost always mean investment-grade intermediate-term bond funds (or for individual bonds, the equivalent would be a bond ladder averaging an intermediate term). If you want technical details, look at the \"\"average duration\"\" or \"\"average maturity\"\" of the bond fund; as a rough guide, if the duration is 10, then a 1% change in interest rates would be a 10% gain or loss on the fund. Another thing you can do is look at long-term (10 years or ideally longer) performance history on some short, intermediate, and long term bond index funds, and you can see how the long term funds bounced around more. Non-investment-grade bonds (aka junk bonds or high yield bonds) are more affected by factors other than interest rates, including some of the same factors (economic booms or recessions) that affect stocks. As a result, they aren't as good for diversifying a portfolio that otherwise consists of stocks. (Having stocks, investment grade bonds, and also a little bit in high-yield bonds can add diversification, though. Just don't replace your bond allocation with high-yield bonds.) A variety of \"\"complicated\"\" bonds exist (convertible bonds are an example) and these are tough to analyze. There are also \"\"floating rate\"\" bonds (bank loan funds), these have minimal interest rate sensitivity because the rate goes up to offset rate rises. These funds still have credit risks, in the credit crisis some of them lost a lot of money. 2. Diversification The purpose of diversification is risk control. Your non-bond funds will outperform in many years, but in other years (say the -37% S&P 500 drop in 2008) they may not. You will not know in advance which year you'll get. You get risk control in at least a few ways. There's also an academic Modern Portfolio Theory explanation for why you should diversify among risky assets (aka stocks), something like: for a given desired risk/return ratio, it's better to leverage up a diverse portfolio than to use a non-diverse portfolio, because risk that can be eliminated through diversification is not compensated by increased returns. The theory also goes that you should choose your diversification between risk assets and the risk-free asset according to your risk tolerance (i.e. select the highest return with tolerable risk). See http://en.wikipedia.org/wiki/Modern_portfolio_theory for excruciating detail. The translation of the MPT stuff to practical steps is typically, put as much in stock index funds as you can tolerate over your time horizon, and put the rest in (intermediate-term investment-grade) bond index funds. That's probably what your planner is asking you to do. My personal view, which is not the standard view, is that you should take as much risk as you need to take, not as much as you think you can tolerate: http://blog.ometer.com/2010/11/10/take-risks-in-life-for-savings-choose-a-balanced-fund/ But almost everyone else will say to do the 80/20 if you have decades to retirement and feel you can tolerate the risk, so my view that 60/40 is the max desirable allocation to stocks is not mainstream. Your planner's 80/20 advice is the standard advice. Before doing 100% stocks I'd give you at least a couple cautions: See also:\"","title":""},{"docid":"424717","text":"\"Specifically, what does my broker mean when they say an asset or investment strategy is high risk? In this context, it is a statement based on past events and probability. It is based on how confident s/he is that the investment will perform to certain benchmarks. This is a math question, primarily (with some opinion mixed in, granted). This is where the Sharpe ratio and others fit well. How am I supposed to answer a question like \"\"rate your risk tolerance from low to high\"\"? This is the hard question, as you have seen. In this context, risk tolerance is derived from your current position and future plans (goals). This is a planning, goal setting, and strategy question, primarily (with some math mixed in, granted). How vulnerable is your current position and future plans to an under-performing investment? If you answer \"\"very\"\", then you choose investments that have a lower probability of under-performing. The Sharpe ratio has little to do with answering this question. It is a tool to find investments that better match your answer to this question.\"","title":""},{"docid":"433003","text":"Using a simple investment calculator to get a sense of scale here, to have 70k total, including the 500 a month invested, after ten years you just need returns of 2%. To earn 70k on top of the money invested you would need returns over 20%. To do that in five years you would need over 50% annual return. That is quite a big difference. Annualized returns of 20% would require high risk and a very large amount of time invested, skill and luck. 2% returns can be nearly guaranteed without much effort. I would encourage you to think about your money more holistically. If you get very unlucky with investments and don't make any money will you not go on the vacations even if your income allows? That doesn't make a lot of sense. As always, spend all your money with the current and future in mind. Investment return Euros are no different from any other Euros. At that point, the advice is the same for all investors try to get as much return as possible for the risk you are comfortable with. You seem to have a high tolerance for risk. Generally, for investors with a high risk tolerance a broadly diversified portfolio of stocks (with maybe a small amount of bonds, other investments) will give the most return over the long term for the risk taken. After that generally the next most useful way to boost your returns is to try to avoid taxes which is why we talk about 401(k)s so much around here. Each European country has different tax law, but please ask questions here about your own country as well as you mention money.se could use more ex-US questions.","title":""},{"docid":"53244","text":"The one thing we know for certain is that holding large amounts of cash isn't ideal - inflation will eat away at your wealth. It's understandable that you're hesitant to put all your wealth in common stock. The S&P 500's price/earnings is 18.7 right now - a little high by historical standards. But consider that the S&P 500 has given a CAGR of approximately 10% (not inflation-adjusted) since 1970. If you don't time the market correctly, you could miss out on considerable gains. So it's probably best to invest at least a portion of your wealth in common stocks, and just accept the risk of short-term losses. You'll likely come out ahead in the long run, compared to an investor who tries to time the market and ends up holding cash positions for too long. If you really think US stocks are overpriced, you could look at other markets, but you'll find similar P/Es in Europe and Japan. You could try an emerging market fund like VEMAX if you have the risk tolerance. Let's say you're not convinced, and don't want to invest heavily in stocks right now. In the current market, safe cash alternatives like Treasury bills offer very low yields - not enough to offset inflation tax. So I would invest in a diversified portfolio of long-term bonds, real estate, maybe precious metals, and whatever amount of stock you're comfortable with.","title":""},{"docid":"212004","text":"There are a couple of reasons that a person might choose to use insurance even if they could handle the financial loss if something went wrong. They know their risk better than the insurance company. While it might seem odd at first glance that an individual can be better at assessing risk than a large company with thousands of actuaries. There are limits to the amount of knowledge that an insurance company can have or use to price their insurance products. For instance if you were a very aggressive driver but didn't have any recent tickets or accidents because you were in college and didn't have a car on a regular basis, but now you have a job and drive 30 miles to work every day. You know your risk is relatively high but the insurance company sees you as relatively low risk and aren't able to price that extra risk into your premium. Just because a person can survive financial after losing something like a car or a house doesn't mean it isn't desirable to pay a small price to mitigate that risk. If you are using your savings to pay for an emergency then that money needs to be semi liquid in case you need it limiting your investment options. Where as if you purchase insurance you pay a small amount of money to be able to invest the rest of your money. Liquidity is a big deal particularly if you are a small business and investing into your business where your money can make your more money but you may or may not be able to access that money very easily.","title":""},{"docid":"189678","text":"\"Remember that risk should correlate with returns, in an investment. This means that the more risk you take on, the more return you should be receiving, in an efficient marketplace. That's why putting your money in a savings account might earn you <1% interest right now, but putting money in the stock market averages ~7% returns over time. You should be very careful not to use the word 'interest' when you mean 'returns'. In your post, you are calling capital gains (the increase in value of owned property) 'interest'. This may be understating in your head the level of risk associated with property ownership. In the case of the bank, they are not in the business of home construction. Rather than take that risk themselves, they would rather finance many projects being done by construction companies that know the business. The bank has a high degree of certainty of getting its money back, because its mortgages are protected by the value of the property. Part of the benefit of an efficient marketplace is that risk gets 'bought' by individuals who want it. This means that people with a low-risk tolerance (such as banks, people on fixed incomes, seniors, etc.) can avoid risk, and people with a high risk tolerance (stock investors, young people with high income, etc.) can take on that risk for higher average returns. The bank's reasoning should remind you of the risk associated with property ownership: increases in value are not a sure thing. If you do not understand the risk of your investment, you cannot be certain that you are being well compensated for that risk. Note also that most countries place regulations on their banks that limit the amount of their funds that can be placed in 'higher risk' asset classes. Typically, this something along the lines of \"\"If someone places a deposit with your bank, you can only invest that deposit in a low-risk debt-based asset [ie: you can take money deposited by customer A and use it to finance a mortgage for customer B]\"\". This is done in an attempt to prevent collapse of the financial sector, if risky investments start failing.\"","title":""},{"docid":"134542","text":"\"When you invest in a single index/security, you are completely exposed to the risk of that security. Diversification means spreading the investments so the losses on one side can be compensated by the gains on the other side. What you are talking about is one thing called \"\"risk apettite\"\", more formally known as Risk Tolerance: Risk tolerance is the degree of variability in investment returns that an investor is willing to withstand. (emphasis added) This means that you are willing to accept some losses in order to get a potential bigger return. Fidelity has this graph: As you can see in the table above, the higher the risk tolerance, the bigger the difference between the best and worst values. That is the variability. The right-most pie can be one example of an agressive diversified portfolio. But this does not mean you should go and buy exactly that security compostion. High-risk means playing with fire. Unless you are a professional stuntman, playing with fire usually leaves people burnt. In a financial context this usually means the money is gone. Recommended Reading: Investopedia; Risk and Diversification: The Risk-Reward Tradeoff Investopedia; How to construct a High Risk portfolio Fidelity: Guide to Diversification KPMG: Understanding and articulating Risk Appetite (pdf)\"","title":""},{"docid":"136515","text":"\"Bonds still definitely have a place in many passive portfolios. While it is true that interest rates have been unusually low, yields on reasonable passive bond exposures are still around 2-4%. This is significantly better than both recent past inflation and expected inflation both of which are near zero. This is reasonable if not great return, but Bonds continue to have other nice properties like relatively low risk and diversification of stock portfolios (the \"\"offset[ing] losses\"\" you mention in the OP). So to say that bonds are \"\"no longer a good idea\"\" is certainly not correct. One could say bonds may no longer be a good idea for some people that have a particularly high risk tolerance and very high return requirements. However, to some extent, that has always been true. It is worth remembering also that there is some compelling evidence that global growth is starting to broadly slow down and many people believe that future stock returns and, in general, returns on all investments will be lower. This is much much harder to estimate than bond returns though. Depending on who you believe, bond returns may actually look relatively better than the have in the past. Edit in response to comment: Corporate bond correlation with stocks is positive but generally not very strong (except for high-yield junk bonds) so while they don't offset stock volatility (negative correlation) they do help diversify a stock portfolio. Government bonds have essentially zero correlation so they don't really offset volatility as much as just not add any. Negative correlation assets are generally called insurance and you tend to have to pay for them. So there is no free lunch here. Assets that reduce risk cost money, assets that add little risk give less return and assets that are more risky tend to give more return in the long run but you can feel the pain. The mix that is right for you depends on a lot of things, but for many people that mix involves some corporate and government bonds.\"","title":""},{"docid":"439459","text":"Paying off the debt is low-risk, low-reward. You're effectively guaranteed a 4% return. If you buy a mutual fund, you're going to have to take some risk to have a decent chance of getting better than 4% and change return in the long run, which probably means a fund that invests primarily in stocks. Buying a stock mutual fund is high-risk, high reward, especially when you're in significant debt. On the other hand, 4% and change is very low-interest. If you wanted to buy stocks on margin, financing stock investments directly with debt, you'd pay a heck of a lot more. Bottom line: It comes down to your personal risk tolerance.","title":""},{"docid":"160105","text":"\"I was going to ask, \"\"Do you feel lucky, punk?\"\" but then it occurred to me that the film this quote came from, Dirty Harry, starring Clint Eastwood, is 43 years old. And yet, the question remains. The stock market, as measured by the S&P has returned 9.67% compounded over the last 100 years. But with a standard deviation just under 20%, there are years when you'll do better and years you'll lose. And I'd not ignore the last decade which was pretty bad, a loss for the decade. There are clearly two schools of thought. One says that no one ever lost sleep over not having a mortgage payment. The other school states that at the very beginning, you have a long investing horizon, and the chances are very good that the 30 years to come will bring a return north of 6%. The two decades prior to the last were so good that these past 30 years were still pretty good, 11.39% compounded. There is no right or wrong here. My gut says fund your retirement accounts to the maximum. Build your emergency fund. You see, if you pay down your mortgage, but lose your job, you'll still need to make those payments. Once you build your security, think of the mortgage as the cash side of your investing, i.e. focus less on the relatively low rate of return (4.3%) and more on the eventual result, once paid, your cash flow goes up nicely. Edit - in light of the extra information you provided, your profile reads that you have a high risk tolerance. Low overhead, no dependents, and secure employment combine to lead me to this conclusion. At 23, I'd not be investing at 4.3%. I'd learn how to invest in a way I was comfortable with, and take it from there. Disclosure (Updated) - I am older, and am semi-retired. I still have some time left on the mortgage, but it doesn't bother me, not at 3.5%. I also have a 16 year old to put through college but her college account i fully funded.\"","title":""},{"docid":"438294","text":"Not all debt is bad. If it carries a reasonable interest rate, you don't need to clear it immediately. As for investing in an index fund, they're an affordable, easy way to spread your money over various assets. However, asset allocation is just one of many investment strategies. Ideally, you want to invest according to your goals, tax situation, and risk tolerance. You want a portfolio that dynamically allocates to various investment strategies, both beta and alpha, according to changing market conditions. Most importantly, you want systematic risk management for every aspect of your investments.","title":""},{"docid":"402950","text":"\"Math says invest in the Market (But paying off your mortgage early is a valid option if you are very risk averse.) You are going to get a better return by investing in the stock market. In the US in 2015/2016, mortgages are 3%-4%, and give you a tax break. The rate of return on the stock market is ~10%, (closer to 6% after you subtract out inflation, taxes, fees, etc.) Since 10 > 3, (or 6% > 4%, to use the pessimistic numbers) investing in the market is the better deal. But... The market has risk, and your mortgage does not. If you are very risk averse paying off the mortgage may make sense. As an example: Family A has a single \"\"breadwinner\"\", who works a low skilled job. Family B has 2 working spouses, both in high skill white collar positions. These two families are going to have wildly different risk tolerances. It may make sense for family A to \"\"invest\"\" its extra money in paying off the mortgage, after they have tackled high interest debt, built an emergency fund, maxed the 401k, etc. Personally I would not: in the US you cannot recoup pre-payments if you lose your job. If I was very risk averse, I would keep my extra money as cash, so I could pay my mortgage after I lost my job. It is never going to make sense for family B to pay the mortgage early. At that point, any decision to pre-pay is going to be based on emotion and not logic.\"","title":""},{"docid":"118800","text":"I think we resolved this via comments above. Many finance authors are not fans of target date funds, as they have higher fees than you'd pay constructing the mix yourself, and they can't take into account your own risk tolerance. Not every 24 year old should have the same mix. That said - I suggest you give thought to the pre-tax / post tax (i.e. traditional vs Roth) mix. I recently wrote The 15% solution, which attempts to show how to minimize your lifetime taxes by using the split that's ideal for your situation.","title":""},{"docid":"481683","text":"\"Here are my reasons as to why bonds are considered to be a reasonable investment. While it is true that, on average over a sufficiently long period of time, stocks do have a high expected return, it is important to realize that bonds are a different type of financial instrument that stocks, and have features that are attractive to certain types of investors. The purpose of buying bonds is to convert a lump sum of currency into a series of future cash flows. This is in and of itself valuable to the issuer because they would prefer to have the lump sum today, rather than at some point in the future. So we generally don't say that we've \"\"lost\"\" the money, we say that we are purchasing a series of future payments, and we would only do this if it were more valuable to us than having the money in hand. Unlike stocks, where you are compensated with dividends and equity to take on the risks and rewards of ownership, and unlike a savings account (which is much different that a bond), where you are only being paid interest for the time value of your money while the bank lends it out at their risk, when you buy a bond you are putting your money at risk in order to provide financing to the issuer. It is also important to realize that there is a much higher risk that stocks will lose value, and you have to compare the risk-adjusted return, and not the nominal return, for stocks to the risk-adjusted return for bonds, since with investment-grade bonds there is generally a very low risk of default. While the returns being offered may not seem attractive to you individually, it is not reasonable to say that the returns offered by the issuer are insufficient in general, because both when the bonds are issued and then subsequently traded on a secondary market (which is done fairly easily), they function as a market. That is to say that sellers always want a higher price (resulting in a lower return), and buyers always want to receive a higher return (requiring a lower price). So while some sellers and buyers will be able to agree on a mutually acceptable price (such that a transaction occurs), there will almost always be some buyers and sellers who also do not enter into transactions because they are demanding a lower/higher price. The fact that a market exists indicates that enough investors are willing to accept the returns that are being offered by sellers. Bonds can be helpful in that as a class of assets, they are less risky than stocks. Additionally, bonds are paid back to investors ahead of equity, so in the case of a failing company or public entity, bondholders may be paid even if stockholders lose all their money. As a result, bonds can be a preferred way to make money on a company or government entity that is able to pay its bills, but has trouble generating any profits. Some investors have specific reasons why they may prefer a lower risk over time to maximizing their returns. For example, a government or pension fund or a university may be aware of financial payments that they will be required to make in a particular year in the future, and may purchase bonds that mature in that year. They may not be willing to take the risk that in that year, the stock market will fall, which could force them to reduce their principal to make the payments. Other individual investors may be close to a significant life event that can be predicted, such as college or retirement, and may not want to take on the risk of stocks. In the case of very large investors such as national governments, they are often looking for capital preservation to hedge against inflation and forex risk, rather than to \"\"make money\"\". Additionally, it is important to remember that until relatively recently in the developed world, and still to this day in many developing countries, people have been willing to pay banks and financial institutions to hold their money, and in the context of the global bond market, there are many people around the world who are willing to buy bonds and receive a very low rate of return on T-Bills, for example, because they are considered a very safe investment due to the creditworthiness of the USA, as well as the stability of the dollar, especially if inflation is very high in the investor's home country. For example, I once lived in an African country where inflation was 60-80% per year. This means if I had $100 today, I could buy $100 worth of goods, but by next year, I might need $160 to buy the same goods I could buy for $100 today. So you can see why simply being able to preserve the value of my money in a bond denominated in USA currency would be valuable in that case, because the alternative is so bad. So not all bondholders want to be owners or make as much money as possible, some just want a safe place to put their money. Also, it is true for both stocks and bonds that you are trading a lump sum of money today for payments over time, although for stocks this is a different kind of payment (dividends), and you only get paid if the company makes money. This is not specific to bonds. In most other cases when a stock price appreciates, this is to reflect new information not previously known, or earnings retained by the company rather than paid out as dividends. Most of the financial instruments where you can \"\"make\"\" money immediately are speculative, where two people are betting against each other, and one has to lose money for the other to make money. Again, it's not reasonable to say that any type of financial instrument is the \"\"worst\"\". They function differently, serve different purposes, and have different features that may or may not fit your needs and preferences. You seem to be saying that you simply don't find bond returns high enough to be attractive to you. That may be true, since different people have different investment objectives, risk tolerance, and preference for having money now versus more money later. However, some of your statements don't seem to be supported by facts. For example, retail banks are not highly profitable as an industry, so they are not making thousands of times what they are paying you. They also need to pay all of their operating expenses, as well as account for default risk and inflation, out of the different between what they lend and what they pay to savings account holders. Also, it's not reasonable to say that bonds are worthless, as I've explained. The world disagrees with you. If they agreed with you, they would stop buying bonds, and the people who need financing would have to lower bond prices until people became interested again. That is part of how markets work. In fact, much of the reason that bond yields are so low right now is that there has been such high global demand for safe investments like bonds, especially from other nations, such that bond issues (especially the US government) have not needed to pay high yields in order to raise money.\"","title":""},{"docid":"373645","text":"I used to like Applebee's when I was in Undergrad and Grad school... it was open late, it was relatively cheap (late night specials), and the food was better than your average college fair. I recently went back with my SO for some nostalgia at like 8:30 p.m. and I realized very quickly that: * Late night specials start at 10:00 p.m. - who the fuck stays out that late to eat on a weeknight? * Food was awful, definitely went downhill from what I remember * And it was super overpriced - like 9.99 for wings as an appetizer GTFO here Applebee's","title":""},{"docid":"1377","text":"\"I don't have a crystal ball but chances are your tenant is definitely lying. Rent was late and now the money intended to cover the rent; miraculously is lost in the mailbox. Anyhow, you were already nice to tolerate the late \"\"payment\"\". Keshlam's option 1.5 in the comments above is the ideal way to settle in which both parties have learned a lesson and are at a loss. Demand the rent payment but settle for half as a one time courtesy. If this continues or this tenant has shown shady predicaments such as this, you should look for legal means to evict this tenant. College students are very creative and who's to say this won't happen again? \"\"The neighbors dog took my wallet.\"\"\"","title":""},{"docid":"124230","text":"A general rule of thumb is to avoid having more than 5% of your investments in any single stock, to avoid excessive risk; it's usually even more risky if you're talking company stock because an adverse event could result in an inferior stock price and you getting laid off. Under other circumstances, the ideal amount of company stock is probably 0%. But there are tax benefits to waiting, as you've noted, and if you're reasonably confident that the stock isn't likely to jerk around too much, and you have a high risk tolerance (i.e. lots of extra savings besides this), and you're comfortable shouldering the risk of losing some money, it might make sense to hold onto the stock for a year - but never any longer. The real risk to holding a lot of company stock doesn't depend on how often you buy it and sell it per se, but having period purchases every month should make it easier for you to ladder the funds, and regularly sell your old shares as you purchase new shares. You might also consider a stop-loss order on the stock at or near the price you purchased it at. If the stock is at $100, then you buy at $85, and then the stock drops to $85, there are no more outstanding tax benefits and it makes no sense to have it as part of your portfolio instead of any other speculative instrument - you probably get better diversification benefits with any other speculative instrument, so your risk-adjusted returns would be higher.","title":""},{"docid":"175226","text":"\"As JoeTaxpayer notes in his comment, \"\"answers\"\" to this are really just opinions, so here's mine, for what it's worth. If your risk tolerance is 5 out of 5, you shouldn't have anything in Treasuries. Those are basically the most conservative of all investments. This would probably mean no TIPS as well. If you're more like 4.5 out of 5, you could have some, but just a little; a 30% allocation to government securities is quite conservative. If you want to diversify across different asset classes, you could consider a bond fund like (for instance VBMFX, the Vanguard total bond market index fund). Your portfolio doesn't currently contain any (non-government) bonds, which is something to consider. 20% seems like quite a large allocation to REITs. Most sample portfolios I've seen allocate no more than 10% to REITs, often no more than 5%. There are some that have more like the 20% you're envisioning, but you might want to ponder that a bit more especially in light of your concerns about REITs being at an all-time high. As for your question about all-time highs, it's reasonable to think about, but I think waiting for 30-50% off all-time highs is unrealistic. Looking at a chart of VFINX (essentially the S&P 500), I see that at the nadir of the recent downturn, in early 2009, the market was at about 50% of its pre-crash all-time high. At the nadir of the dot-com bust, the market was about 45% off its pre-crash high. If you're waiting for it to be 50% off it's all-time high, you're not just waiting for \"\"a good time to invest\"\", you're waiting for a major crash. It could certainly make sense not to immediately put everything into US stocks, but that doesn't mean you should put nothing in. As Trevor Wilson commented, you could put some of the money in and then gradually add the rest over time, reducing the risk of unluckily buying at the peak. (This can also reduce the psychological angst of worrying about whether you're doing the right thing, which is worth taking into account.) Also note that if you get rid of the treasuries, you eliminate a good chunk of the stuff that you thought was too close to the peak anyway. Your two basic points (asset allocation and low-cost funds) have a strong Boglehead flavor. You may already have looked at the Bogleheads wiki; if not you should take a look. If you are comfortable with that philosophy (and I think it's a sound one), you should remember that part of that philosophy is not worrying about \"\"timing the market\"\". You pursue a buy-and-hold strategy if you believe the market will go up in the long term and don't care much about what it does in the short term. That said, as mentioned above, you might want to ease in your investment over time, rather than buying all at once, if only to avoid tearing your hair out if the market goes down in the short term. Incidentally, your proposed portfolio is similar to this one that they mention, although as I said above I think this is too conservative if you are 30 years old and consider yourself a \"\"5 out of 5\"\" in terms of risk tolerance. I'm not sure if you already saw that in your research, but since that portfolio apparently has a name and is known, you might be able to find information about its risks and benefits by searching for discussion of it by name.\"","title":""},{"docid":"372417","text":"\"Here are some things to consider if you want to employ a covered call strategy for consistent returns. The discussion also applies to written puts, as they're functionally equivalent. Write covered calls only on fairly valued stock. If the stock is distinctly undervalued, just buy it. By writing the call, you cap the gains that it will achieve as the stock price gravitates to intrinsic value. If the stock is overvalued, sell it, or just stay away. As the owner of a covered call position, you have full exposure to the downside of the stock. The premium received is normally way too small to protect against much of a drop in price. The ideal candidate doesn't change in price much over the life of the position. Yes, this is low volatility, which brings low option premiums. As a seller you want high premiums. But this can't be judged in a vacuum. No matter how high the volatility in absolute terms, as a seller you're betting the market has overpriced volatility. If volatility is high, so premiums are fat, but the market is correct, then the very real risk of the stock dropping over the life of the position offsets the premium received. One thing to look at is current implied volatility for the at-the-money (ATM), near-month call. Compare it to the two-year historical volatility (Morningstar has this conveniently displayed). Moving away from pure volatility, consider writing calls about three months out, just slightly out of the money. The premium is all time value, and the time value decay accelerates in the final few months. (In theory, a series of one-month options would be higher time value, but there are frictional costs, and no guarantee that today's \"\"good deal\"\" will be repeatable twelve time per year.) When comparing various strikes and expirations, compare time value per day. To compare the same statistic across multiple companies, use time value per day as a percent of capital at risk. CaR is the price of the stock less the premium received. If you already own the stock, track it as if you just bought it for this strategy, so use the price on the day you wrote the call. Along with time value per day, compare the simple annualized percent return, again, on capital at risk, measuring the return if a) the stock is called away, and b) the stock remains unchanged. I usually concentrate more on the second scenario, as we get the capital gain on the stock regardless, without the option strategy. Ideally, you can also calculate the probability (based on implied volatility) of the stock achieving these price points by expiration. Measuring returns at many possible stock prices, you can develop an overall expected return. I won't go into further detail, as it seems outside the scope here. Finally, I usually target a minimum of 25% annualized if the stock remains unchanged. You can, of course, adjust this up or down depending on your risk tolerance. I consider this to be conservative.\"","title":""},{"docid":"197241","text":"Do developing country equities have a higher return and/or lower risk than emerging market equities? Generally in finance you get payed more for taking risk. Riskier stocks over the long run return more than less risky bonds, for instance. Developing market equity is expected to give less return over the long run as it is generally less risky than emerging market equity. One way to see that is the amount you pay for one rupee/lira/dollar/euro worth of company earnings is fewer rupees/lira and more dollars/euros. when measured in the emerging market's currency? This makes this question interesting. Risky emerging currencies like the rupee tend to devalue over time against less risky currencies euro/dollars/yen like where most international investment ends up, but the results are rather wild. Think how badly Brazil has done recently and how relatively well the rupee has been doing. This adds to the returns (roughly based on interest rates) of foreign stocks from the point of view of a emerging market investor on average but has really wild variations. Do you have data for this over a long timeframe (decades), ideally for multiple countries? Not really, unfortunately. Good data for emerging markets is a fairly new phenomenon and even where it does exist decades ago it would have been very hard to invest like we can now so it likely is not comparable. Does foreign equity pay more or less when measured in rupees (or other emerging market currency)? Probably less on average (theoretically and empirically) all things included though the evidence is not strong, but there is a massive amount of risk in a portfolio that is 85% in a single emerging market currency. Think about if you were a Brazilian and needed to retire now and 85% of your portfolio was in the Real. International goods like gas would be really expensive and your local currency portfolio would seem paltry right now. If you want to bet on emerging markets in the long run I would suggest that you at least spread the risk over many emerging markets and add a good chunk developed to the mix. As for investing goals, it's just to maximize my return in INR, or maximize my risk-adjusted return. That is up to you, but the goal I generally recommend is making sure you are comfortable in retirement. This usually involves looking for returns are high in the long run, but not having a ton of risk in a single currency or a single market. There are reasons to believe a little bias toward your homeland is good as fees tend to be lower on local investments and local investments tend to track closer to your retirement costs, but too much can be very dangerous even for countries with stronger currencies, say Greece.","title":""},{"docid":"373360","text":"Currently, in the US, you won't be able to get 4% return on a risk free investment (savings account, CDs, treasury bonds). If the banking system in India guarantees your money and the cost of transferring them to India is not prohibitive, that's the safest option. Buying a house usually is only worth it if you plan to live in it for a while, 5 years or more being the commonly cited figure. Every case is different, if you rent is very high, it might be worth to buy. I suggest posting another question specifically about that with more details about your situation. If you can tolerate a bit more risk, you might want to talk to a financial adviser and invest in the stock market.","title":""},{"docid":"343965","text":"Very unlikely to get 200k out of college, but not out of reach of as you gain experience and if you live in a high CoL area. 200k and higher is about right for all-in comp (base + bonus) as you reach IT management / specialty / sales roles. This is why talent is a concern across finance right now. Grads are going to tech instead of banks because the pay is about a wash but work environment is better. They're not wrong.","title":""},{"docid":"566069","text":"The simplest way is to invest in a few ETFs, depending on your tolerance for risk; assuming you're very short-term risk tolerant you can invest almost all in a stock ETF like VOO or VTI. Stock market ETFs return close to 10% (unadjusted) over long periods of time, which will out-earn almost any other option and are very easy for a non-finance person to invest in (You don't trade actively - you leave the money there for years). If you want to hedge some of your risk, you can also invest in Bond funds, which tend to move up in stock market downturns - but if you're looking for the long term, you don't need to put much there. Otherwise, try to make sure you take advantage of tax breaks when you can - IRAs, 401Ks, etc.; most of those will have ETFs (whether Vanguard or similar) available to invest in. Look for funds that have low expense ratios and are fairly diversified (ie, don't just invest in one small sector of the economy); as long as the economy continues to grow, the ETFs will grow.","title":""},{"docid":"178303","text":"\"Some thoughts: 1) Do you have a significant emergency fund (3-6 months of after-tax living expenses)? If not, you stand to take a significant loss if you have an unexpected need for cash that is tied up in investments. What if you lose/hate your job or your car breaks down? What if a you want to spend some time with a relative or significant other who learns they only have a few months to live? Having a dedicated emergency fund is an important way to avoid downside risk. 2) Lagerbaer has a good suggestion. Given that if you'd reinvested your dividends, the S&P 500 has returned about 3.5% over the last 5 years, you may be able to get a very nice risk-free return. 3) Do you have access to employer matching funds, such as in a 401(k) at work? If you get a dollar-for-dollar match, that is a risk-free pre-tax 100% return and should be a high priority. 4) What do you mean by \"\"medium\"\" volatility? Given that you are considering a 2/3 equity allocation, it would not be at all out of the realm of possibility that your balance could fall by 15% or more in any given year and take several years to recover. If that would spook you, you may want to consider lowering your equity weights. A high quality bond fund may be a good fit. 5) Personally, I would avoid putting money into stocks that I didn't need back for 10 years. If you only want to tie your money up for 2-5 years, you are taking a significant risk that if prices fall, you won't have time to recover before you need your money back. The portfolio you described would be appropriate for someone with a long-term investment horizon and significant risk tolerance, which is usually the case for young people saving for retirement. However, if your goals are to invest for 2-5 years only, your situation would be significantly different. 6) You can often borrow from an investment account to purchase a primary residence, but you must pay that amount back in order to avoid significant taxes and fees, unless you plan to liquidate assets. If you plan to buy a house, saving enough to avoid PMI is a good risk-free return on your money. 7) In general, and ETF or index fund is a good idea, the key being to minimize the compound effect of expenses over the long term. There are many good choices a la Vanguard here to choose from. 8) Don't worry about \"\"Buy low, sell high\"\". Don't be a speculator, be an investor (that's my version of Anthony Bourdain's, \"\"don't be a tourist, be a traveler\"\"). A speculator wants to sell shares at a higher price than they were purchased at. An investor wants to share in the profits of a company as a part-owner. If you can consistently beat the market by trying to time your transactions, good for you - you can move to Wall Street and make millions. However, almost no one can do this consistently, and it doesn't seem worth it to me to try. I don't mean to discourage you from investing, just make sure you have your bases covered so that you don't have to cash out at a bad time. Best of luck! Edit Response to additional questions below. 1) Emergency fund. I would recommend not investing in anything other than cash equivalents (money market, short-term CDs, etc.) until you've built up an emergency fund. It makes sense to want to make the \"\"best\"\" use of your money, but you also have to account for risk. My concern is that if you were to experience one or more adverse life events, that you could lose a lot of money, or need to pay a lot in interest on credit card debt, and it would be prudent to self-insure against some of those risks. I would also recommend against using an investment account as an emergency fund account. Taking money out of investment accounts is inefficient because the commissions/taxes/fees can easily eat up a significant portion of your returns. Ideally, you would want to put money in and not touch it for a long time in order to take advantage of compounding returns. There are also high penalties for early disbursements from retirement funds. Just like you need enough money in your checking account to buy food and pay the rent every month, you need enough money in an emergency fund to pay for things that are a real possibility, even if they are less common. Using a credit card or an investment account is a relatively expensive way to do this. 2) Invest at all? I would recommend starting an emergency fund, and then beginning to invest for retirement. Once your retirement savings are on track, you can begin saving for whatever other goals you may have\"","title":""},{"docid":"193012","text":"The 'standard' in such moving average crossover systems is 50/200. The numbers are essentially arbitrary as long as the long term average is greater than the short term and there is some different between the averages in terms of the smoothing they provide (i.e. comparing a 74 day MA to a 75 day MA isn't what the system is intended for) There are plenty of software programs that will let you run through many possible values for the system over historical data. I concur with the other answers in that this system/indicator alone isn't very good. However, I disagree with their blanket brushing off of technical analysis. There are many successful traders out there. The moving average cross over system is perhaps the second most primitive example of technical strategies categorized as trend following systems (buying new recent highs and selling new recent lows being the most simple). This particular system isn't very powerful because of its poor use of simple moving averages. A simple moving average is intended to smooth out data, but smoothing comes at the cost of lagging from the present. A simple moving average essentially gives you an idealized smoothing of price action for the day at that is one half of their period ago. So your 200 day simple moving average shows you an idealized smoothing of price action 100 days ago. A lot can happen in 100 days and that is why this system is far from ideal.","title":""},{"docid":"424511","text":"Your asset mix should reflect your own risk tolerance. Whatever the ideal answer to your question, it requires you to have good timing, not once, but twice. Let me offer a personal example. In 2007, the S&P hit its short term peak at 1550 or so. As it tanked in the crisis, a coworker shared with me that he went to cash, on the way down, selling out at about 1100. At the bottom, 670 or so, I congratulated his brilliance (sarcasm here) and as it passed 1300 just 2 years later, again mentions how he must be thrilled he doubled his money. He admitted he was still in cash. Done with stocks. So he was worse off than had he held on to his pre-crash assets. For sake of disclosure, my own mix at the time was 100% stock. That's not a recommendation, just a reflection of how my wife and I were invested. We retired early, and after the 2013 excellent year, moved to a mix closer to 75/25. At any time, a crisis hits, and we have 5-6 years spending money to let the market recover. If a Japanesque long term decline occurs, Social Security kicks in for us in 8 years. If my intent wasn't 100% clear, I'm suggesting your long term investing should always reflect your own risk tolerance, not some short term gut feel that disaster is around the corner.","title":""},{"docid":"368338","text":"Short time horizon, small pot of money, and low appetite for risk? That smells like low return situation to me. I guess it depends on how low your appetite for risk is, though. You could open a brokerage account (free) and purchase $10K worth of a fully diversified ETF like VTI, optionally putting maybe 20% of it in a diversified bond ETF. I consider that a reasonably conservative investment, but if you are of the mindset that you cannot tolerate a drop in your wealth, it's not going to work. Plus if you don't have any other investments, this will be the thing that requires you to report capital gains to the IRS, and that paperwork is never fun. As an alternative, you have CD's, which will make you very little. Or a high-ish interest rate electronic savings account like Capital one 360 or Emigrant Direct (there are probably newer ones now that outcompete even these). Still, with anything in this paragraph you will be lucky to beat inflation. The real interest rate was negative last time I checked, so every risk-free investment will lose money in purchasing power terms. To beat inflation you will need to take on nonnegligible risk.","title":""},{"docid":"53820","text":"Hello all, Ive recently accepted a job at one of the big banks as a marketer. Ideally this role leads to becoming a financial advisor. I was wondering if there is anyone here has experience with that career path-starting as a marketer and becoming an FA- and if it was worth doing it over going to grad school or whatever other career interests you had. Also, what were your hours like when you first started? Ive heard horror stories about people coming in before 7 and staying after 7...","title":""}],"string":"[\n {\n \"docid\": \"515060\",\n \"text\": \"I completely agree that there are experts that recognize it as a very serious problem, and I agree that it is a serious problem that could cause a large recession or crash (my large chunk of remaining loans definitely agrees). My point is that this article isn't looking at economic data. It's looking at a survey of recent college grads and asking them to rank the risk of student loan debt vs the risk of North Korea. I wouldn't consider that a very useful indicator.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"204227\",\n \"text\": \"Stay away from college debt. You can't default on it. Your wages will be garnished if you're unable to pay it back. Even when your and old man, they will garnish your social security money. In effect college debt makes you an indentured servant. Maybe even worse than the 7 years of servitude people served in early America. Lots of grads are working in restaurants and retail stores.... even some computer science grads. There is great risk in the college investment compared to 40 years ago when it was a sure thing. Do not take debt for college. If that means you can't go to college then so be it. You're future self will than you.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"599436\",\n \"text\": \"\\\"1. Interest rates What you should know is that the longer the \\\"\\\"term\\\"\\\" of a bond fund, the more it will be affected by interest rates. So a short-term bond fund will not be subject to large gains or losses due to rate changes, an intermediate-term bond fund will be subject to moderate gains or losses, and a long-term bond fund will be subject to the largest gains or losses. When a book or financial planner says to buy \\\"\\\"bonds\\\"\\\" with no other qualification, they almost always mean investment-grade intermediate-term bond funds (or for individual bonds, the equivalent would be a bond ladder averaging an intermediate term). If you want technical details, look at the \\\"\\\"average duration\\\"\\\" or \\\"\\\"average maturity\\\"\\\" of the bond fund; as a rough guide, if the duration is 10, then a 1% change in interest rates would be a 10% gain or loss on the fund. Another thing you can do is look at long-term (10 years or ideally longer) performance history on some short, intermediate, and long term bond index funds, and you can see how the long term funds bounced around more. Non-investment-grade bonds (aka junk bonds or high yield bonds) are more affected by factors other than interest rates, including some of the same factors (economic booms or recessions) that affect stocks. As a result, they aren't as good for diversifying a portfolio that otherwise consists of stocks. (Having stocks, investment grade bonds, and also a little bit in high-yield bonds can add diversification, though. Just don't replace your bond allocation with high-yield bonds.) A variety of \\\"\\\"complicated\\\"\\\" bonds exist (convertible bonds are an example) and these are tough to analyze. There are also \\\"\\\"floating rate\\\"\\\" bonds (bank loan funds), these have minimal interest rate sensitivity because the rate goes up to offset rate rises. These funds still have credit risks, in the credit crisis some of them lost a lot of money. 2. Diversification The purpose of diversification is risk control. Your non-bond funds will outperform in many years, but in other years (say the -37% S&P 500 drop in 2008) they may not. You will not know in advance which year you'll get. You get risk control in at least a few ways. There's also an academic Modern Portfolio Theory explanation for why you should diversify among risky assets (aka stocks), something like: for a given desired risk/return ratio, it's better to leverage up a diverse portfolio than to use a non-diverse portfolio, because risk that can be eliminated through diversification is not compensated by increased returns. The theory also goes that you should choose your diversification between risk assets and the risk-free asset according to your risk tolerance (i.e. select the highest return with tolerable risk). See http://en.wikipedia.org/wiki/Modern_portfolio_theory for excruciating detail. The translation of the MPT stuff to practical steps is typically, put as much in stock index funds as you can tolerate over your time horizon, and put the rest in (intermediate-term investment-grade) bond index funds. That's probably what your planner is asking you to do. My personal view, which is not the standard view, is that you should take as much risk as you need to take, not as much as you think you can tolerate: http://blog.ometer.com/2010/11/10/take-risks-in-life-for-savings-choose-a-balanced-fund/ But almost everyone else will say to do the 80/20 if you have decades to retirement and feel you can tolerate the risk, so my view that 60/40 is the max desirable allocation to stocks is not mainstream. Your planner's 80/20 advice is the standard advice. Before doing 100% stocks I'd give you at least a couple cautions: See also:\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"424717\",\n \"text\": \"\\\"Specifically, what does my broker mean when they say an asset or investment strategy is high risk? In this context, it is a statement based on past events and probability. It is based on how confident s/he is that the investment will perform to certain benchmarks. This is a math question, primarily (with some opinion mixed in, granted). This is where the Sharpe ratio and others fit well. How am I supposed to answer a question like \\\"\\\"rate your risk tolerance from low to high\\\"\\\"? This is the hard question, as you have seen. In this context, risk tolerance is derived from your current position and future plans (goals). This is a planning, goal setting, and strategy question, primarily (with some math mixed in, granted). How vulnerable is your current position and future plans to an under-performing investment? If you answer \\\"\\\"very\\\"\\\", then you choose investments that have a lower probability of under-performing. The Sharpe ratio has little to do with answering this question. It is a tool to find investments that better match your answer to this question.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"433003\",\n \"text\": \"Using a simple investment calculator to get a sense of scale here, to have 70k total, including the 500 a month invested, after ten years you just need returns of 2%. To earn 70k on top of the money invested you would need returns over 20%. To do that in five years you would need over 50% annual return. That is quite a big difference. Annualized returns of 20% would require high risk and a very large amount of time invested, skill and luck. 2% returns can be nearly guaranteed without much effort. I would encourage you to think about your money more holistically. If you get very unlucky with investments and don't make any money will you not go on the vacations even if your income allows? That doesn't make a lot of sense. As always, spend all your money with the current and future in mind. Investment return Euros are no different from any other Euros. At that point, the advice is the same for all investors try to get as much return as possible for the risk you are comfortable with. You seem to have a high tolerance for risk. Generally, for investors with a high risk tolerance a broadly diversified portfolio of stocks (with maybe a small amount of bonds, other investments) will give the most return over the long term for the risk taken. After that generally the next most useful way to boost your returns is to try to avoid taxes which is why we talk about 401(k)s so much around here. Each European country has different tax law, but please ask questions here about your own country as well as you mention money.se could use more ex-US questions.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"53244\",\n \"text\": \"The one thing we know for certain is that holding large amounts of cash isn't ideal - inflation will eat away at your wealth. It's understandable that you're hesitant to put all your wealth in common stock. The S&P 500's price/earnings is 18.7 right now - a little high by historical standards. But consider that the S&P 500 has given a CAGR of approximately 10% (not inflation-adjusted) since 1970. If you don't time the market correctly, you could miss out on considerable gains. So it's probably best to invest at least a portion of your wealth in common stocks, and just accept the risk of short-term losses. You'll likely come out ahead in the long run, compared to an investor who tries to time the market and ends up holding cash positions for too long. If you really think US stocks are overpriced, you could look at other markets, but you'll find similar P/Es in Europe and Japan. You could try an emerging market fund like VEMAX if you have the risk tolerance. Let's say you're not convinced, and don't want to invest heavily in stocks right now. In the current market, safe cash alternatives like Treasury bills offer very low yields - not enough to offset inflation tax. So I would invest in a diversified portfolio of long-term bonds, real estate, maybe precious metals, and whatever amount of stock you're comfortable with.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"212004\",\n \"text\": \"There are a couple of reasons that a person might choose to use insurance even if they could handle the financial loss if something went wrong. They know their risk better than the insurance company. While it might seem odd at first glance that an individual can be better at assessing risk than a large company with thousands of actuaries. There are limits to the amount of knowledge that an insurance company can have or use to price their insurance products. For instance if you were a very aggressive driver but didn't have any recent tickets or accidents because you were in college and didn't have a car on a regular basis, but now you have a job and drive 30 miles to work every day. You know your risk is relatively high but the insurance company sees you as relatively low risk and aren't able to price that extra risk into your premium. Just because a person can survive financial after losing something like a car or a house doesn't mean it isn't desirable to pay a small price to mitigate that risk. If you are using your savings to pay for an emergency then that money needs to be semi liquid in case you need it limiting your investment options. Where as if you purchase insurance you pay a small amount of money to be able to invest the rest of your money. Liquidity is a big deal particularly if you are a small business and investing into your business where your money can make your more money but you may or may not be able to access that money very easily.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"189678\",\n \"text\": \"\\\"Remember that risk should correlate with returns, in an investment. This means that the more risk you take on, the more return you should be receiving, in an efficient marketplace. That's why putting your money in a savings account might earn you <1% interest right now, but putting money in the stock market averages ~7% returns over time. You should be very careful not to use the word 'interest' when you mean 'returns'. In your post, you are calling capital gains (the increase in value of owned property) 'interest'. This may be understating in your head the level of risk associated with property ownership. In the case of the bank, they are not in the business of home construction. Rather than take that risk themselves, they would rather finance many projects being done by construction companies that know the business. The bank has a high degree of certainty of getting its money back, because its mortgages are protected by the value of the property. Part of the benefit of an efficient marketplace is that risk gets 'bought' by individuals who want it. This means that people with a low-risk tolerance (such as banks, people on fixed incomes, seniors, etc.) can avoid risk, and people with a high risk tolerance (stock investors, young people with high income, etc.) can take on that risk for higher average returns. The bank's reasoning should remind you of the risk associated with property ownership: increases in value are not a sure thing. If you do not understand the risk of your investment, you cannot be certain that you are being well compensated for that risk. Note also that most countries place regulations on their banks that limit the amount of their funds that can be placed in 'higher risk' asset classes. Typically, this something along the lines of \\\"\\\"If someone places a deposit with your bank, you can only invest that deposit in a low-risk debt-based asset [ie: you can take money deposited by customer A and use it to finance a mortgage for customer B]\\\"\\\". This is done in an attempt to prevent collapse of the financial sector, if risky investments start failing.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"134542\",\n \"text\": \"\\\"When you invest in a single index/security, you are completely exposed to the risk of that security. Diversification means spreading the investments so the losses on one side can be compensated by the gains on the other side. What you are talking about is one thing called \\\"\\\"risk apettite\\\"\\\", more formally known as Risk Tolerance: Risk tolerance is the degree of variability in investment returns that an investor is willing to withstand. (emphasis added) This means that you are willing to accept some losses in order to get a potential bigger return. Fidelity has this graph: As you can see in the table above, the higher the risk tolerance, the bigger the difference between the best and worst values. That is the variability. The right-most pie can be one example of an agressive diversified portfolio. But this does not mean you should go and buy exactly that security compostion. High-risk means playing with fire. Unless you are a professional stuntman, playing with fire usually leaves people burnt. In a financial context this usually means the money is gone. Recommended Reading: Investopedia; Risk and Diversification: The Risk-Reward Tradeoff Investopedia; How to construct a High Risk portfolio Fidelity: Guide to Diversification KPMG: Understanding and articulating Risk Appetite (pdf)\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"136515\",\n \"text\": \"\\\"Bonds still definitely have a place in many passive portfolios. While it is true that interest rates have been unusually low, yields on reasonable passive bond exposures are still around 2-4%. This is significantly better than both recent past inflation and expected inflation both of which are near zero. This is reasonable if not great return, but Bonds continue to have other nice properties like relatively low risk and diversification of stock portfolios (the \\\"\\\"offset[ing] losses\\\"\\\" you mention in the OP). So to say that bonds are \\\"\\\"no longer a good idea\\\"\\\" is certainly not correct. One could say bonds may no longer be a good idea for some people that have a particularly high risk tolerance and very high return requirements. However, to some extent, that has always been true. It is worth remembering also that there is some compelling evidence that global growth is starting to broadly slow down and many people believe that future stock returns and, in general, returns on all investments will be lower. This is much much harder to estimate than bond returns though. Depending on who you believe, bond returns may actually look relatively better than the have in the past. Edit in response to comment: Corporate bond correlation with stocks is positive but generally not very strong (except for high-yield junk bonds) so while they don't offset stock volatility (negative correlation) they do help diversify a stock portfolio. Government bonds have essentially zero correlation so they don't really offset volatility as much as just not add any. Negative correlation assets are generally called insurance and you tend to have to pay for them. So there is no free lunch here. Assets that reduce risk cost money, assets that add little risk give less return and assets that are more risky tend to give more return in the long run but you can feel the pain. The mix that is right for you depends on a lot of things, but for many people that mix involves some corporate and government bonds.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"439459\",\n \"text\": \"Paying off the debt is low-risk, low-reward. You're effectively guaranteed a 4% return. If you buy a mutual fund, you're going to have to take some risk to have a decent chance of getting better than 4% and change return in the long run, which probably means a fund that invests primarily in stocks. Buying a stock mutual fund is high-risk, high reward, especially when you're in significant debt. On the other hand, 4% and change is very low-interest. If you wanted to buy stocks on margin, financing stock investments directly with debt, you'd pay a heck of a lot more. Bottom line: It comes down to your personal risk tolerance.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"160105\",\n \"text\": \"\\\"I was going to ask, \\\"\\\"Do you feel lucky, punk?\\\"\\\" but then it occurred to me that the film this quote came from, Dirty Harry, starring Clint Eastwood, is 43 years old. And yet, the question remains. The stock market, as measured by the S&P has returned 9.67% compounded over the last 100 years. But with a standard deviation just under 20%, there are years when you'll do better and years you'll lose. And I'd not ignore the last decade which was pretty bad, a loss for the decade. There are clearly two schools of thought. One says that no one ever lost sleep over not having a mortgage payment. The other school states that at the very beginning, you have a long investing horizon, and the chances are very good that the 30 years to come will bring a return north of 6%. The two decades prior to the last were so good that these past 30 years were still pretty good, 11.39% compounded. There is no right or wrong here. My gut says fund your retirement accounts to the maximum. Build your emergency fund. You see, if you pay down your mortgage, but lose your job, you'll still need to make those payments. Once you build your security, think of the mortgage as the cash side of your investing, i.e. focus less on the relatively low rate of return (4.3%) and more on the eventual result, once paid, your cash flow goes up nicely. Edit - in light of the extra information you provided, your profile reads that you have a high risk tolerance. Low overhead, no dependents, and secure employment combine to lead me to this conclusion. At 23, I'd not be investing at 4.3%. I'd learn how to invest in a way I was comfortable with, and take it from there. Disclosure (Updated) - I am older, and am semi-retired. I still have some time left on the mortgage, but it doesn't bother me, not at 3.5%. I also have a 16 year old to put through college but her college account i fully funded.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"438294\",\n \"text\": \"Not all debt is bad. If it carries a reasonable interest rate, you don't need to clear it immediately. As for investing in an index fund, they're an affordable, easy way to spread your money over various assets. However, asset allocation is just one of many investment strategies. Ideally, you want to invest according to your goals, tax situation, and risk tolerance. You want a portfolio that dynamically allocates to various investment strategies, both beta and alpha, according to changing market conditions. Most importantly, you want systematic risk management for every aspect of your investments.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"402950\",\n \"text\": \"\\\"Math says invest in the Market (But paying off your mortgage early is a valid option if you are very risk averse.) You are going to get a better return by investing in the stock market. In the US in 2015/2016, mortgages are 3%-4%, and give you a tax break. The rate of return on the stock market is ~10%, (closer to 6% after you subtract out inflation, taxes, fees, etc.) Since 10 > 3, (or 6% > 4%, to use the pessimistic numbers) investing in the market is the better deal. But... The market has risk, and your mortgage does not. If you are very risk averse paying off the mortgage may make sense. As an example: Family A has a single \\\"\\\"breadwinner\\\"\\\", who works a low skilled job. Family B has 2 working spouses, both in high skill white collar positions. These two families are going to have wildly different risk tolerances. It may make sense for family A to \\\"\\\"invest\\\"\\\" its extra money in paying off the mortgage, after they have tackled high interest debt, built an emergency fund, maxed the 401k, etc. Personally I would not: in the US you cannot recoup pre-payments if you lose your job. If I was very risk averse, I would keep my extra money as cash, so I could pay my mortgage after I lost my job. It is never going to make sense for family B to pay the mortgage early. At that point, any decision to pre-pay is going to be based on emotion and not logic.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"118800\",\n \"text\": \"I think we resolved this via comments above. Many finance authors are not fans of target date funds, as they have higher fees than you'd pay constructing the mix yourself, and they can't take into account your own risk tolerance. Not every 24 year old should have the same mix. That said - I suggest you give thought to the pre-tax / post tax (i.e. traditional vs Roth) mix. I recently wrote The 15% solution, which attempts to show how to minimize your lifetime taxes by using the split that's ideal for your situation.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"481683\",\n \"text\": \"\\\"Here are my reasons as to why bonds are considered to be a reasonable investment. While it is true that, on average over a sufficiently long period of time, stocks do have a high expected return, it is important to realize that bonds are a different type of financial instrument that stocks, and have features that are attractive to certain types of investors. The purpose of buying bonds is to convert a lump sum of currency into a series of future cash flows. This is in and of itself valuable to the issuer because they would prefer to have the lump sum today, rather than at some point in the future. So we generally don't say that we've \\\"\\\"lost\\\"\\\" the money, we say that we are purchasing a series of future payments, and we would only do this if it were more valuable to us than having the money in hand. Unlike stocks, where you are compensated with dividends and equity to take on the risks and rewards of ownership, and unlike a savings account (which is much different that a bond), where you are only being paid interest for the time value of your money while the bank lends it out at their risk, when you buy a bond you are putting your money at risk in order to provide financing to the issuer. It is also important to realize that there is a much higher risk that stocks will lose value, and you have to compare the risk-adjusted return, and not the nominal return, for stocks to the risk-adjusted return for bonds, since with investment-grade bonds there is generally a very low risk of default. While the returns being offered may not seem attractive to you individually, it is not reasonable to say that the returns offered by the issuer are insufficient in general, because both when the bonds are issued and then subsequently traded on a secondary market (which is done fairly easily), they function as a market. That is to say that sellers always want a higher price (resulting in a lower return), and buyers always want to receive a higher return (requiring a lower price). So while some sellers and buyers will be able to agree on a mutually acceptable price (such that a transaction occurs), there will almost always be some buyers and sellers who also do not enter into transactions because they are demanding a lower/higher price. The fact that a market exists indicates that enough investors are willing to accept the returns that are being offered by sellers. Bonds can be helpful in that as a class of assets, they are less risky than stocks. Additionally, bonds are paid back to investors ahead of equity, so in the case of a failing company or public entity, bondholders may be paid even if stockholders lose all their money. As a result, bonds can be a preferred way to make money on a company or government entity that is able to pay its bills, but has trouble generating any profits. Some investors have specific reasons why they may prefer a lower risk over time to maximizing their returns. For example, a government or pension fund or a university may be aware of financial payments that they will be required to make in a particular year in the future, and may purchase bonds that mature in that year. They may not be willing to take the risk that in that year, the stock market will fall, which could force them to reduce their principal to make the payments. Other individual investors may be close to a significant life event that can be predicted, such as college or retirement, and may not want to take on the risk of stocks. In the case of very large investors such as national governments, they are often looking for capital preservation to hedge against inflation and forex risk, rather than to \\\"\\\"make money\\\"\\\". Additionally, it is important to remember that until relatively recently in the developed world, and still to this day in many developing countries, people have been willing to pay banks and financial institutions to hold their money, and in the context of the global bond market, there are many people around the world who are willing to buy bonds and receive a very low rate of return on T-Bills, for example, because they are considered a very safe investment due to the creditworthiness of the USA, as well as the stability of the dollar, especially if inflation is very high in the investor's home country. For example, I once lived in an African country where inflation was 60-80% per year. This means if I had $100 today, I could buy $100 worth of goods, but by next year, I might need $160 to buy the same goods I could buy for $100 today. So you can see why simply being able to preserve the value of my money in a bond denominated in USA currency would be valuable in that case, because the alternative is so bad. So not all bondholders want to be owners or make as much money as possible, some just want a safe place to put their money. Also, it is true for both stocks and bonds that you are trading a lump sum of money today for payments over time, although for stocks this is a different kind of payment (dividends), and you only get paid if the company makes money. This is not specific to bonds. In most other cases when a stock price appreciates, this is to reflect new information not previously known, or earnings retained by the company rather than paid out as dividends. Most of the financial instruments where you can \\\"\\\"make\\\"\\\" money immediately are speculative, where two people are betting against each other, and one has to lose money for the other to make money. Again, it's not reasonable to say that any type of financial instrument is the \\\"\\\"worst\\\"\\\". They function differently, serve different purposes, and have different features that may or may not fit your needs and preferences. You seem to be saying that you simply don't find bond returns high enough to be attractive to you. That may be true, since different people have different investment objectives, risk tolerance, and preference for having money now versus more money later. However, some of your statements don't seem to be supported by facts. For example, retail banks are not highly profitable as an industry, so they are not making thousands of times what they are paying you. They also need to pay all of their operating expenses, as well as account for default risk and inflation, out of the different between what they lend and what they pay to savings account holders. Also, it's not reasonable to say that bonds are worthless, as I've explained. The world disagrees with you. If they agreed with you, they would stop buying bonds, and the people who need financing would have to lower bond prices until people became interested again. That is part of how markets work. In fact, much of the reason that bond yields are so low right now is that there has been such high global demand for safe investments like bonds, especially from other nations, such that bond issues (especially the US government) have not needed to pay high yields in order to raise money.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"373645\",\n \"text\": \"I used to like Applebee's when I was in Undergrad and Grad school... it was open late, it was relatively cheap (late night specials), and the food was better than your average college fair. I recently went back with my SO for some nostalgia at like 8:30 p.m. and I realized very quickly that: * Late night specials start at 10:00 p.m. - who the fuck stays out that late to eat on a weeknight? * Food was awful, definitely went downhill from what I remember * And it was super overpriced - like 9.99 for wings as an appetizer GTFO here Applebee's\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1377\",\n \"text\": \"\\\"I don't have a crystal ball but chances are your tenant is definitely lying. Rent was late and now the money intended to cover the rent; miraculously is lost in the mailbox. Anyhow, you were already nice to tolerate the late \\\"\\\"payment\\\"\\\". Keshlam's option 1.5 in the comments above is the ideal way to settle in which both parties have learned a lesson and are at a loss. Demand the rent payment but settle for half as a one time courtesy. If this continues or this tenant has shown shady predicaments such as this, you should look for legal means to evict this tenant. College students are very creative and who's to say this won't happen again? \\\"\\\"The neighbors dog took my wallet.\\\"\\\"\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"124230\",\n \"text\": \"A general rule of thumb is to avoid having more than 5% of your investments in any single stock, to avoid excessive risk; it's usually even more risky if you're talking company stock because an adverse event could result in an inferior stock price and you getting laid off. Under other circumstances, the ideal amount of company stock is probably 0%. But there are tax benefits to waiting, as you've noted, and if you're reasonably confident that the stock isn't likely to jerk around too much, and you have a high risk tolerance (i.e. lots of extra savings besides this), and you're comfortable shouldering the risk of losing some money, it might make sense to hold onto the stock for a year - but never any longer. The real risk to holding a lot of company stock doesn't depend on how often you buy it and sell it per se, but having period purchases every month should make it easier for you to ladder the funds, and regularly sell your old shares as you purchase new shares. You might also consider a stop-loss order on the stock at or near the price you purchased it at. If the stock is at $100, then you buy at $85, and then the stock drops to $85, there are no more outstanding tax benefits and it makes no sense to have it as part of your portfolio instead of any other speculative instrument - you probably get better diversification benefits with any other speculative instrument, so your risk-adjusted returns would be higher.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"175226\",\n \"text\": \"\\\"As JoeTaxpayer notes in his comment, \\\"\\\"answers\\\"\\\" to this are really just opinions, so here's mine, for what it's worth. If your risk tolerance is 5 out of 5, you shouldn't have anything in Treasuries. Those are basically the most conservative of all investments. This would probably mean no TIPS as well. If you're more like 4.5 out of 5, you could have some, but just a little; a 30% allocation to government securities is quite conservative. If you want to diversify across different asset classes, you could consider a bond fund like (for instance VBMFX, the Vanguard total bond market index fund). Your portfolio doesn't currently contain any (non-government) bonds, which is something to consider. 20% seems like quite a large allocation to REITs. Most sample portfolios I've seen allocate no more than 10% to REITs, often no more than 5%. There are some that have more like the 20% you're envisioning, but you might want to ponder that a bit more especially in light of your concerns about REITs being at an all-time high. As for your question about all-time highs, it's reasonable to think about, but I think waiting for 30-50% off all-time highs is unrealistic. Looking at a chart of VFINX (essentially the S&P 500), I see that at the nadir of the recent downturn, in early 2009, the market was at about 50% of its pre-crash all-time high. At the nadir of the dot-com bust, the market was about 45% off its pre-crash high. If you're waiting for it to be 50% off it's all-time high, you're not just waiting for \\\"\\\"a good time to invest\\\"\\\", you're waiting for a major crash. It could certainly make sense not to immediately put everything into US stocks, but that doesn't mean you should put nothing in. As Trevor Wilson commented, you could put some of the money in and then gradually add the rest over time, reducing the risk of unluckily buying at the peak. (This can also reduce the psychological angst of worrying about whether you're doing the right thing, which is worth taking into account.) Also note that if you get rid of the treasuries, you eliminate a good chunk of the stuff that you thought was too close to the peak anyway. Your two basic points (asset allocation and low-cost funds) have a strong Boglehead flavor. You may already have looked at the Bogleheads wiki; if not you should take a look. If you are comfortable with that philosophy (and I think it's a sound one), you should remember that part of that philosophy is not worrying about \\\"\\\"timing the market\\\"\\\". You pursue a buy-and-hold strategy if you believe the market will go up in the long term and don't care much about what it does in the short term. That said, as mentioned above, you might want to ease in your investment over time, rather than buying all at once, if only to avoid tearing your hair out if the market goes down in the short term. Incidentally, your proposed portfolio is similar to this one that they mention, although as I said above I think this is too conservative if you are 30 years old and consider yourself a \\\"\\\"5 out of 5\\\"\\\" in terms of risk tolerance. I'm not sure if you already saw that in your research, but since that portfolio apparently has a name and is known, you might be able to find information about its risks and benefits by searching for discussion of it by name.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"372417\",\n \"text\": \"\\\"Here are some things to consider if you want to employ a covered call strategy for consistent returns. The discussion also applies to written puts, as they're functionally equivalent. Write covered calls only on fairly valued stock. If the stock is distinctly undervalued, just buy it. By writing the call, you cap the gains that it will achieve as the stock price gravitates to intrinsic value. If the stock is overvalued, sell it, or just stay away. As the owner of a covered call position, you have full exposure to the downside of the stock. The premium received is normally way too small to protect against much of a drop in price. The ideal candidate doesn't change in price much over the life of the position. Yes, this is low volatility, which brings low option premiums. As a seller you want high premiums. But this can't be judged in a vacuum. No matter how high the volatility in absolute terms, as a seller you're betting the market has overpriced volatility. If volatility is high, so premiums are fat, but the market is correct, then the very real risk of the stock dropping over the life of the position offsets the premium received. One thing to look at is current implied volatility for the at-the-money (ATM), near-month call. Compare it to the two-year historical volatility (Morningstar has this conveniently displayed). Moving away from pure volatility, consider writing calls about three months out, just slightly out of the money. The premium is all time value, and the time value decay accelerates in the final few months. (In theory, a series of one-month options would be higher time value, but there are frictional costs, and no guarantee that today's \\\"\\\"good deal\\\"\\\" will be repeatable twelve time per year.) When comparing various strikes and expirations, compare time value per day. To compare the same statistic across multiple companies, use time value per day as a percent of capital at risk. CaR is the price of the stock less the premium received. If you already own the stock, track it as if you just bought it for this strategy, so use the price on the day you wrote the call. Along with time value per day, compare the simple annualized percent return, again, on capital at risk, measuring the return if a) the stock is called away, and b) the stock remains unchanged. I usually concentrate more on the second scenario, as we get the capital gain on the stock regardless, without the option strategy. Ideally, you can also calculate the probability (based on implied volatility) of the stock achieving these price points by expiration. Measuring returns at many possible stock prices, you can develop an overall expected return. I won't go into further detail, as it seems outside the scope here. Finally, I usually target a minimum of 25% annualized if the stock remains unchanged. You can, of course, adjust this up or down depending on your risk tolerance. I consider this to be conservative.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"197241\",\n \"text\": \"Do developing country equities have a higher return and/or lower risk than emerging market equities? Generally in finance you get payed more for taking risk. Riskier stocks over the long run return more than less risky bonds, for instance. Developing market equity is expected to give less return over the long run as it is generally less risky than emerging market equity. One way to see that is the amount you pay for one rupee/lira/dollar/euro worth of company earnings is fewer rupees/lira and more dollars/euros. when measured in the emerging market's currency? This makes this question interesting. Risky emerging currencies like the rupee tend to devalue over time against less risky currencies euro/dollars/yen like where most international investment ends up, but the results are rather wild. Think how badly Brazil has done recently and how relatively well the rupee has been doing. This adds to the returns (roughly based on interest rates) of foreign stocks from the point of view of a emerging market investor on average but has really wild variations. Do you have data for this over a long timeframe (decades), ideally for multiple countries? Not really, unfortunately. Good data for emerging markets is a fairly new phenomenon and even where it does exist decades ago it would have been very hard to invest like we can now so it likely is not comparable. Does foreign equity pay more or less when measured in rupees (or other emerging market currency)? Probably less on average (theoretically and empirically) all things included though the evidence is not strong, but there is a massive amount of risk in a portfolio that is 85% in a single emerging market currency. Think about if you were a Brazilian and needed to retire now and 85% of your portfolio was in the Real. International goods like gas would be really expensive and your local currency portfolio would seem paltry right now. If you want to bet on emerging markets in the long run I would suggest that you at least spread the risk over many emerging markets and add a good chunk developed to the mix. As for investing goals, it's just to maximize my return in INR, or maximize my risk-adjusted return. That is up to you, but the goal I generally recommend is making sure you are comfortable in retirement. This usually involves looking for returns are high in the long run, but not having a ton of risk in a single currency or a single market. There are reasons to believe a little bias toward your homeland is good as fees tend to be lower on local investments and local investments tend to track closer to your retirement costs, but too much can be very dangerous even for countries with stronger currencies, say Greece.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"373360\",\n \"text\": \"Currently, in the US, you won't be able to get 4% return on a risk free investment (savings account, CDs, treasury bonds). If the banking system in India guarantees your money and the cost of transferring them to India is not prohibitive, that's the safest option. Buying a house usually is only worth it if you plan to live in it for a while, 5 years or more being the commonly cited figure. Every case is different, if you rent is very high, it might be worth to buy. I suggest posting another question specifically about that with more details about your situation. If you can tolerate a bit more risk, you might want to talk to a financial adviser and invest in the stock market.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"343965\",\n \"text\": \"Very unlikely to get 200k out of college, but not out of reach of as you gain experience and if you live in a high CoL area. 200k and higher is about right for all-in comp (base + bonus) as you reach IT management / specialty / sales roles. This is why talent is a concern across finance right now. Grads are going to tech instead of banks because the pay is about a wash but work environment is better. They're not wrong.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"566069\",\n \"text\": \"The simplest way is to invest in a few ETFs, depending on your tolerance for risk; assuming you're very short-term risk tolerant you can invest almost all in a stock ETF like VOO or VTI. Stock market ETFs return close to 10% (unadjusted) over long periods of time, which will out-earn almost any other option and are very easy for a non-finance person to invest in (You don't trade actively - you leave the money there for years). If you want to hedge some of your risk, you can also invest in Bond funds, which tend to move up in stock market downturns - but if you're looking for the long term, you don't need to put much there. Otherwise, try to make sure you take advantage of tax breaks when you can - IRAs, 401Ks, etc.; most of those will have ETFs (whether Vanguard or similar) available to invest in. Look for funds that have low expense ratios and are fairly diversified (ie, don't just invest in one small sector of the economy); as long as the economy continues to grow, the ETFs will grow.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"178303\",\n \"text\": \"\\\"Some thoughts: 1) Do you have a significant emergency fund (3-6 months of after-tax living expenses)? If not, you stand to take a significant loss if you have an unexpected need for cash that is tied up in investments. What if you lose/hate your job or your car breaks down? What if a you want to spend some time with a relative or significant other who learns they only have a few months to live? Having a dedicated emergency fund is an important way to avoid downside risk. 2) Lagerbaer has a good suggestion. Given that if you'd reinvested your dividends, the S&P 500 has returned about 3.5% over the last 5 years, you may be able to get a very nice risk-free return. 3) Do you have access to employer matching funds, such as in a 401(k) at work? If you get a dollar-for-dollar match, that is a risk-free pre-tax 100% return and should be a high priority. 4) What do you mean by \\\"\\\"medium\\\"\\\" volatility? Given that you are considering a 2/3 equity allocation, it would not be at all out of the realm of possibility that your balance could fall by 15% or more in any given year and take several years to recover. If that would spook you, you may want to consider lowering your equity weights. A high quality bond fund may be a good fit. 5) Personally, I would avoid putting money into stocks that I didn't need back for 10 years. If you only want to tie your money up for 2-5 years, you are taking a significant risk that if prices fall, you won't have time to recover before you need your money back. The portfolio you described would be appropriate for someone with a long-term investment horizon and significant risk tolerance, which is usually the case for young people saving for retirement. However, if your goals are to invest for 2-5 years only, your situation would be significantly different. 6) You can often borrow from an investment account to purchase a primary residence, but you must pay that amount back in order to avoid significant taxes and fees, unless you plan to liquidate assets. If you plan to buy a house, saving enough to avoid PMI is a good risk-free return on your money. 7) In general, and ETF or index fund is a good idea, the key being to minimize the compound effect of expenses over the long term. There are many good choices a la Vanguard here to choose from. 8) Don't worry about \\\"\\\"Buy low, sell high\\\"\\\". Don't be a speculator, be an investor (that's my version of Anthony Bourdain's, \\\"\\\"don't be a tourist, be a traveler\\\"\\\"). A speculator wants to sell shares at a higher price than they were purchased at. An investor wants to share in the profits of a company as a part-owner. If you can consistently beat the market by trying to time your transactions, good for you - you can move to Wall Street and make millions. However, almost no one can do this consistently, and it doesn't seem worth it to me to try. I don't mean to discourage you from investing, just make sure you have your bases covered so that you don't have to cash out at a bad time. Best of luck! Edit Response to additional questions below. 1) Emergency fund. I would recommend not investing in anything other than cash equivalents (money market, short-term CDs, etc.) until you've built up an emergency fund. It makes sense to want to make the \\\"\\\"best\\\"\\\" use of your money, but you also have to account for risk. My concern is that if you were to experience one or more adverse life events, that you could lose a lot of money, or need to pay a lot in interest on credit card debt, and it would be prudent to self-insure against some of those risks. I would also recommend against using an investment account as an emergency fund account. Taking money out of investment accounts is inefficient because the commissions/taxes/fees can easily eat up a significant portion of your returns. Ideally, you would want to put money in and not touch it for a long time in order to take advantage of compounding returns. There are also high penalties for early disbursements from retirement funds. Just like you need enough money in your checking account to buy food and pay the rent every month, you need enough money in an emergency fund to pay for things that are a real possibility, even if they are less common. Using a credit card or an investment account is a relatively expensive way to do this. 2) Invest at all? I would recommend starting an emergency fund, and then beginning to invest for retirement. Once your retirement savings are on track, you can begin saving for whatever other goals you may have\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"193012\",\n \"text\": \"The 'standard' in such moving average crossover systems is 50/200. The numbers are essentially arbitrary as long as the long term average is greater than the short term and there is some different between the averages in terms of the smoothing they provide (i.e. comparing a 74 day MA to a 75 day MA isn't what the system is intended for) There are plenty of software programs that will let you run through many possible values for the system over historical data. I concur with the other answers in that this system/indicator alone isn't very good. However, I disagree with their blanket brushing off of technical analysis. There are many successful traders out there. The moving average cross over system is perhaps the second most primitive example of technical strategies categorized as trend following systems (buying new recent highs and selling new recent lows being the most simple). This particular system isn't very powerful because of its poor use of simple moving averages. A simple moving average is intended to smooth out data, but smoothing comes at the cost of lagging from the present. A simple moving average essentially gives you an idealized smoothing of price action for the day at that is one half of their period ago. So your 200 day simple moving average shows you an idealized smoothing of price action 100 days ago. A lot can happen in 100 days and that is why this system is far from ideal.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"424511\",\n \"text\": \"Your asset mix should reflect your own risk tolerance. Whatever the ideal answer to your question, it requires you to have good timing, not once, but twice. Let me offer a personal example. In 2007, the S&P hit its short term peak at 1550 or so. As it tanked in the crisis, a coworker shared with me that he went to cash, on the way down, selling out at about 1100. At the bottom, 670 or so, I congratulated his brilliance (sarcasm here) and as it passed 1300 just 2 years later, again mentions how he must be thrilled he doubled his money. He admitted he was still in cash. Done with stocks. So he was worse off than had he held on to his pre-crash assets. For sake of disclosure, my own mix at the time was 100% stock. That's not a recommendation, just a reflection of how my wife and I were invested. We retired early, and after the 2013 excellent year, moved to a mix closer to 75/25. At any time, a crisis hits, and we have 5-6 years spending money to let the market recover. If a Japanesque long term decline occurs, Social Security kicks in for us in 8 years. If my intent wasn't 100% clear, I'm suggesting your long term investing should always reflect your own risk tolerance, not some short term gut feel that disaster is around the corner.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"368338\",\n \"text\": \"Short time horizon, small pot of money, and low appetite for risk? That smells like low return situation to me. I guess it depends on how low your appetite for risk is, though. You could open a brokerage account (free) and purchase $10K worth of a fully diversified ETF like VTI, optionally putting maybe 20% of it in a diversified bond ETF. I consider that a reasonably conservative investment, but if you are of the mindset that you cannot tolerate a drop in your wealth, it's not going to work. Plus if you don't have any other investments, this will be the thing that requires you to report capital gains to the IRS, and that paperwork is never fun. As an alternative, you have CD's, which will make you very little. Or a high-ish interest rate electronic savings account like Capital one 360 or Emigrant Direct (there are probably newer ones now that outcompete even these). Still, with anything in this paragraph you will be lucky to beat inflation. The real interest rate was negative last time I checked, so every risk-free investment will lose money in purchasing power terms. To beat inflation you will need to take on nonnegligible risk.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"53820\",\n \"text\": \"Hello all, Ive recently accepted a job at one of the big banks as a marketer. Ideally this role leads to becoming a financial advisor. I was wondering if there is anyone here has experience with that career path-starting as a marketer and becoming an FA- and if it was worth doing it over going to grad school or whatever other career interests you had. Also, what were your hours like when you first started? Ive heard horror stories about people coming in before 7 and staying after 7...\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":2698,"cells":{"query_id":{"kind":"string","value":"7542"},"query":{"kind":"string","value":"How can OTC scams affect you?"},"positive_passages":{"kind":"list like","value":[{"docid":"68187","text":"\"Am I being absurd? No. Should I be worrying? Yes. If I sell in the morning, I've only lost a couple hundred dollars, and learned a valuable lesson. Is there any reason to believe it won't be that simple? If you're lucky, you'll be able to dump your stocks to someone like you who'll be punching himself in the face tomorrow night. If not - you're stuck. You may end up selling them to your broker as worthless. You might have become a victim of a \"\"pump and dump\"\" fraud. Those are hard to identify in real-time, but after been burned like that myself (for much lesser amounts than you though), I avoid any \"\"penny\"\" stocks that go up for no apparent (and verifiable) reason. In fact, I avoid them altogether.\"","title":""}],"string":"[\n {\n \"docid\": \"68187\",\n \"text\": \"\\\"Am I being absurd? No. Should I be worrying? Yes. If I sell in the morning, I've only lost a couple hundred dollars, and learned a valuable lesson. Is there any reason to believe it won't be that simple? If you're lucky, you'll be able to dump your stocks to someone like you who'll be punching himself in the face tomorrow night. If not - you're stuck. You may end up selling them to your broker as worthless. You might have become a victim of a \\\"\\\"pump and dump\\\"\\\" fraud. Those are hard to identify in real-time, but after been burned like that myself (for much lesser amounts than you though), I avoid any \\\"\\\"penny\\\"\\\" stocks that go up for no apparent (and verifiable) reason. In fact, I avoid them altogether.\\\"\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"416941","text":"Merrill charges $500 flat fee to (I assume purchase) my untraded or worthless security. In my case, it's an OTC stock whose management used for a microcap scam, which resulted in a class action lawsuit, etc. but the company is still listed on OTC and I'm stuck with 1000s of shares. (No idea about the court decision)","title":""},{"docid":"271116","text":"Absolute scam. Any time anyone asks you to open a bank account so they can send you money and then you have to send some portion of it back to them, it's a guarantee that it's a scam. What happens is that your dad will deposit the check and transfer it to this woman, then the check will bounce (or turn out to be fake altogether) and your dad will be on the hook for the money to the bank. These schemes are dependent on the fact that people want hope and believe in quick, easy money, and it works as long as the con artists are able to get the 'mark' (the person who deposits the check and sends them the money) to send the money before the check (always drawn on some obscure foreign bank) has a chance to clear. This is another variation of a long-running type of bank scam, and if you get involved, you'll regret it. I hope you can keep your dad from getting involved, because it will create a financial mess and affect his credit as well. The basic premise of this scam is this: In the interests of providing good customer service, most banks will make some or all of a deposit available right away, even though the check hasn't cleared. The scammer has you withdraw the money (either a cashier's check, have you send a wire transfer, etc) immediately and send it to them. Eventually the check is returned because it is The bank charges the check back against your account, often imposing pretty substantial penalties and fees, so you as the account holder are left without the money you sent the scammer and all of the fees. This is the easy version of events. You could end up in legal trouble, depending on the nature of the scam and what they determine your involvement to be. It will certainly badly affect your banking history (ChexSystems tracks how we all treat bank accounts, much like the credit agencies do with our credit), so you may have trouble opening bank accounts. So there are many consequences to this to think about, and it's why you JUST SAY NO!! Don't walk away from this -- RUN!!!","title":""},{"docid":"390779","text":"\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \"\"Get Rich on Penny Stock\"\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\"","title":""},{"docid":"421688","text":"It's not enough just to check if your order doesn't exceed 10% of the 20 day average volume. I'll quote from my last answer about NSCC illiquid charges: You may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. The NSCC issues a charge to the clearing firm if in aggregate, their orders exceed the limits, and the clearing firm usually passes these charges on to the broker(s) that placed the orders. Your broker may or may not pass the charges through to you; they may simply charge you significantly higher commissions for trading OTC securities and use those to cover the charges. Since checking how the volume of your orders compares to the average past volume, ask your broker about their policies on trading OTC stocks. They may tell you that you won't face illiquid charges because the higher cost of commissions covers these, or they may give you specifics on how to verify that your orders won't incur such charges. Only your broker can answer this with certainty.","title":""},{"docid":"346407","text":"\"This is colloquially referred to as a \"\"pump and dump\"\" scheme. You basically buy up some stock, and then try to pump up the demand through false and misleading positive statements and market activity. You then close your position once market interest is sufficiently high. If your firm has access to high frequency trading mechanisms, you may even be able to front run other market participants attracted by your buying activities. >I am wondering what is the best route to go down. Definitely micro-cap stocks. Things listed on the OTC markets, especially penny stocks, have this tendency to attract retail buyers just begging to be scammed. Emerging biotech firms also have a lot of potential due to investors' hopes of successful clinical trials. I should warn you though, this is very illegal and falls under market manipulation [according to the SEC](https://www.sec.gov/fast-answers/answerspumpdumphtm.html) and can lead to up to 25 years in prison. So make sure you stay small enough to avoid the regulatory radar. (But seriously, this belongs in r/personalfinance or elsewhere, r/finance isn't the sub you want).\"","title":""},{"docid":"528576","text":"I am in complete agreement with you. The place i have found with the sort of charts you are looking for is stockcharts.com. To compare the percentage increase of several stocks over a period of 2 market-open days or more, which is quite useful to follow the changes in various stocks… etc., an example: Here the tickers are AA to EEEEE (OTC) and $GOLD / $SILVER for the spot gold / silver price (that isn't really a ticker). It is set to show the last 6 market days (one week+)...the '6' in '6&O'. You can change it in the URL above or change it on the site for the stocks you want... up to 25 in one chart but it gets really hard to tell them apart! By moving the slider just left of the ‘6’ at the bottom right corner of the chart, you can look at 2 days or more. For a specific time period in days, highlight the ‘6’ and type any number of market-open days you want (21 days = about one month, etc.). By setting a time period in days, and moving the entire slider, you can see how your stocks did in the last bull/bear run, as an example. The site has a full how-to, for this and the other types of charts they offer. The only problem is that many OTC stocks are not charted. Save the comparison charts you use regularly in a folder in your browser bookmarks. Blessings. I see the entire needed link isn't in blue... but you need it all.","title":""},{"docid":"63848","text":"The only way for a mutual fund to default is if it inflated the NAV. I.e.: it reports that its investments worth more than they really are. Then, in case of a run on the fund, it may end up defaulting since it won't have the money to redeem shares at the NAV it published. When does it happen? When the fund is mismanaged or is a scam. This happened, for example, to the fund Madoff was managing. This is generally a sign of a Ponzi scheme or embezzlement. How can you ensure the funds you invest in are not affected by this? You'll have to read the fund reports, check the independent auditors' reports and check for clues. Generally, this is the job of the SEC - that's what they do as regulators. But for smaller funds, and private (i.e.: not public) investment companies, SEC may not be posing too much regulations.","title":""},{"docid":"545752","text":"If your concern is scams, we should be talking about counterparties, not bitcoin itself. Unless you think the protocol itself is a scam, which imo it most certainly is not. You're conflating the trustworthiness of counterparties with the trustworthiness of the underlying protocol, which imo is not a very good model to operate by. You'll understand the situation better of you look at them independently. Bitcoin isn't trying to be a credit agency or the better business bureau, it's just trying to be digital money. Don't expect it to protect you from scams any more than cash will. That's not its job, and does not affect its trustworthiness as money.","title":""},{"docid":"545789","text":"\"How can I say this more clearly? SCAM, SCAM, SCAM! This is another one of the oldest scams out there, where you've won a prize or an inheritance has come in, and all you have to do is pay the taxes on it to claim it. Don't be a sucker! Ask yourself why the government couldn't (and wouldn't) just take the taxes due out of the funds they have and give the rest to the person they belong to? Wouldn't that be the smartest and easiest thing to do? As an example, let's say that you have $1,000 that belongs to me, and I owe you $100. Would you tell me to pay you the $100 and then you'll give me the $1,000 or would you take the $100 I owe you out of the $1,000 and give me the remaining $900? The fact this is someone you know from the internet and they want your \"\"help\"\" to claim their money should tell you how much of a scam this is. Stop talking to this person, and don't tell them anything personal about you. They are scam artists, and whatever you tell them could be used to steal your identity or take your money. Be careful, my friend!\"","title":""},{"docid":"42347","text":"Something to consider is that in the case of the company you chose, on the OTC market, that stock is thinly traded and with such low volume, it can be easy for it to fluctuate greatly to have trades occur. This is why volume can matter for some people when it comes to buying shares. Some OTC stocks may have really low volume and thus may have bigger swings than other stocks that have higher volume.","title":""},{"docid":"339268","text":"\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \"\"T\"\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \"\"ANET\"\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \"\"P\"\" to the end for \"\"preferreds\"\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\"","title":""},{"docid":"597519","text":"it looks like using an ADR is the way to go here. michelin has an ADR listed OTC as MGDDY. since it is an ADR it is technically a US company that just happens to be a shell company holding only shares of michelin. as such, there should not be any odd tax or currency implications. while it is an OTC stock, it should settle in the US just like any other US OTC. obviously, you are exposing yourself to exchange rate fluctuations, but since michelin derives much of it's income from the US, it should perform similarly to other multinational companies. notes on brokers: most US brokers should be able to sell you OTC stocks using their regular rates (e.g. etrade, tradeking). however, it looks like robinhood.com does not offer this option (yet). in particular, i confirmed directly from tradeking that the 75$ foreign settlement fee does not apply to MGDDY because it is an ADR, and not a (non-ADR) foreign security.","title":""},{"docid":"225030","text":"\"It's a scam. The cashier's check will be forged. Craigslist has a warning about it here (item #3). What kind of payment do you think is not fakable? Or at least not likely to be used in scams? When on craigslist - deal only locally and in person. You can ask to see the person's ID if you're being paid by check When being paid by check, how can seeing his/her ID help? In case the check isn't cashable, I can find that person by keeping record of his/her ID? If you're paid by check, the payers details should be printed on the check. By checking the ID you can verify that the details match (name/address), so you can find the payer later. Of course the ID can be faked too, but there's so much you can do to protect yourself. You'll get better protection (including verified escrow service) by selling on eBay. Is being paid by cash the safest way currently, although cash can be faked too, but it is the least common thing that is faked currently? Do you recommend to first deposit the cash into a bank (so that let the bank verify if the cash is faked), before delivering the good? For Craigslist, use cash and meet locally. That rules out most scams as a seller. What payment methods do you think are relatively safe currently? Then getting checks must be the least favorite way of being paid. Do you think cash is better than money order or cashier order? You should only accept cash. If it is a large transaction, you can meet them at your bank, have them get cash, and you receive the cash from the bank. Back to the quoted scam, how will they later manipulate me? Are they interested in my stuffs on moving sale, or in my money? They will probably \"\"accidentally\"\" overpay you and ask for a refund of some portion of the overpayment. In that case you will be out the entire amount that you send back to them and possibly some fees from your bank for cashing a bad check.\"","title":""},{"docid":"346669","text":"The OTC market is a marketplace, the location it definitely relied on the purchaser marketplace. The OTC market is mostly used to exchange bonds among the two occasions and all this technique are executed by way of manner of the third celebration. They are able to also be used to alternate equity, such because of the OTC QX and purple marketplaces within the USA. The minamargroup is the Florida, USA situated agency, who elements their purchase investor relation with to present organization into to make new ones. OTC way it's far a protection traded in some context other, changing between parties or groups inclusive of New York Stock trade.","title":""},{"docid":"343518","text":"\"This is clearly a scam, and you should stay away from it. Anyone reading this knew that from the title alone - and it seems that you know it too. Don't \"\"test\"\" whether something is a scam by putting your own money in it. That is exactly how these scammers make money, and how you lose it. How their scam works is irrelevant. The simple fact is that there is no way you can safely earn 20% return over the course of a year, let alone in 1 day*. You know this is true. Don't bother trying to figure out what makes it true in this case. There is no free lunch. Best case scenario, this is a hyper-risky investment strategy [on the level of putting your money down at a roulette wheel]. Worst case scenario, they simply steal your money. Either way, you won't come out ahead. Although I agree with others that this is likely a Ponzi scheme, that doesn't really matter. What matters is, there is no way they can guarantee those returns. Just go to a casino and throw your money away yourself, if you want that level of risk. *For reference, if you invested $100 for a year, earning 20% returns every day, you would have 6 million trillion trillion dollars by the end of the year. that's $6,637,026,647,624,450,000,000,000,000,000. that number doesn't even make sense. It's more money than exists on earth. So why would they need your $100?\"","title":""},{"docid":"263659","text":"There are several red flags here. can they get my bank account info in any way from me transferring money to them? Probably yes. Almost all bank transactions are auditable, and intentionally cause a money track. This track can be followed from both sides. If they can use your bank account as if they were you, that is a bit deeper than what you are asking, but yes they (and the polish cops) can find you through that transfer. I did look up the company and didn't find any scam or complaints concerning them. Not finding scams or complains is good, but what did you find? Did you find good reviews, the company website, its register, etc, etc? How far back does the website goes (try the wayback machine) Making a cardboard front company is very easy, and if they are into identity theft the company is under some guy in guam that never heard of poland or paypal. As @Andrew said above, it is probably a scam. I'd add that this scam leverages on the how easier is to get a PayPal refund compared to a regular bank transfer. It is almost impossible to get the money back on an international transaction. Usually reverting a bank transfer requires the agreement in writing of the receiver and of both banks. As for paypal, just a dispute from the other user: You are responsible for all Reversals, Chargebacks, fees, fines, penalties and other liability incurred by PayPal, a PayPal User, or a third party caused by your use of the Services and/or arising from your breach of this Agreement. You agree to reimburse PayPal, a User, or a third party for any and all such liability. (source) Also, you might be violating the TOS: Allow your use of the Service to present to PayPal a risk of non-compliance with PayPal’s anti-money laundering, counter terrorist financing and similar regulatory obligations (including, without limitation, where we cannot verify your identity or you fail to complete the steps to lift your sending, receiving or withdrawal limit in accordance with sections 3.3, 4.1 and 6.3 or where you expose PayPal to the risk of any regulatory fines by European, US or other authorities for processing your transactions); (emphasis mine, source) So even if the PayPal transfer is not disputed, how can you be sure you are not laundering money? Are you being paid well enough to assume that risk?","title":""},{"docid":"282196","text":"\"In general I don’t think you can blame the news stories. You can blame everyone’s preconceived notion that any sort of LBO or leveraged restructuring is the devil’s work. Every American is of course well-versed in the subject. From the Sealy example, you clearly have a journalist who has no idea what they are talking about. All you have is a cherry-picked summary of what took place. As such, the “finance scholars” jump in and explain how it’s all a giant scam. Bain LBO’d Sealy in 1997. As a part of that, it was saddled with ~$700m in debt. That of course is fodder for the \"\"finance scholars\"\" because they don't understand the benefits of debt and more generally how LBOs work, none of which are noted in the article. The article then notes that Sealy has recently encountered trouble. To the \"\"geniuses\"\" this is of course because of Romney's work and the ~$700m in debt. No one notices the fact that Bain unloaded this in 2004 for double what it paid for it. For those that did, the unloading was a textbook Bain scam. Bain unloaded this to KKR, perhaps the sharpest and most successful PE firm in history. Would KKR put $1.5b into this if it were a scam? According to the \"\"geniuses\"\", of course they would. How could Mitt Romney actually improve a business? No one looks at the fact that revenues were up considerably, margins had expanded tremendously, growth prospects were higher, and FCF yields were fantastic. This is why KKR bought the company, and this is what an LBO is supposed to be. I haven't done a ton of work on this case, it was before my time, but I would be very surprised if the growth wasn't accompanied by employee expansion as well. You also get the “I wish I had a way to just walk away from my debt” comment. I don’t even know where to begin explaining how asinine that is. Equity is subordinated to debt. That’s the definition of equity. The article also notes the one-sided-mattress idea, which is construed as Romney's giant scam to screw the average American while flipping this company and making his millions. The article of course didn't note that this one-sided mattress idea was a mere fraction of revenue. This was designed as an economy mattress, with an advertised shorter shelf life. Plus how can this be a scam? Would you go into the mattress store and pay the same amount for a mattress with only one side? If you would you deserve to get half of a mattress. So the crux of it is, this is in actuality an example of what an LBO should be. At least for Bain’s part. Bain took a business that was ripe for an LBO (reasonable steady FCF, low leverage), did the LBO, improved the business, and came out on top. What KKR did with it afterwords I have no idea. I would imagine it has more to do with deteriorating business conditions than the debt on its balance sheet. I work with restructurings over 100 hours a week. I of course don’t come up with the plans (I’m a lowly analyst building models and associated bitchwork) but I see just how brilliant these ideas are. In a lot of cases restructurings prevent the tripping of covenants and associated bankruptcy and allow for strategy to play out and for companies to grow. I can of course give a more detailed rant on the article, but I figured no one will read this anyway.\"","title":""},{"docid":"593644","text":"NSCC illiquid charges are charges that apply to the trading of low-priced over-the counter (OTC) securities with low volumes. Open net buy quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net buy quantity must be less than 5,000,000 shares per stock for your entire firm Basically, you can't hold a long position of more than 5 million shares in an illiquid OTC stock without facing a fee. You'll still be assessed this fee if you accumulate a long position of this size by breaking your purchase up into multiple transactions. Open net sell quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net sell quantity must be less than 10% percent of the 20-day average volume If you attempt to sell a number of shares greater than 10% of the stock's average volume over the last 20 days, you'll also be assessed a fee. The first link I included above is just an example, but it makes the important point: you may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. Technically, these fees are assessed to the clearing firm, not the individual investor, but usually the clearing firm will pass the fees along to the broker (and possibly add other charges as well), and the broker will charge a fee to the individual account(s) that triggered the restriction. Also, remember that when buying OTC/pink sheet stocks, your ability to buy or sell is also contingent on finding someone else to buy from/sell to. If you purchase 10,000 shares one day and attempt to sell them sometime in the future, but there aren't enough buyers to buy all 10,000 from you, you might not be able to complete your order at the desired price, or even at all.","title":""},{"docid":"467352","text":"Depends on how you measure liquidity. There's papers out there that approach this very question. Measured in order book spreads for a consolidated $100m trade, I'd say the second biggest market is FX swaps, followed or par'd by the money market (government bonds). If you disallow OTC venues, it's most definitely exchange listed government bonds. If, however, you happen to think in terms of sheer volume per time, the most liquid market phase could be considered the NYSE closing auction, as you can move billions in a matter of minutes, or expressed in speed terms: several m$/s (million dollars per second). You should pick a definition and we can provide you with a more accurate list of candidates and actual data.","title":""},{"docid":"123511","text":"\"What can I do to help him out, but at the same time protect myself from any potential scams? Find out why he can't do this himself. Whether your relative is being sincere or not, if he owns both accounts then he should be able to transfer money between them by himself. If you can find a way to solve that issue without involving your bank account, so much the better. Don't settle for \"\"something about authorized payees and expired cards.\"\" Get details, write them down. If possible, get documents. Then go to a bank or financial adviser you can trust and run those details by them to see what they have to say. Even if there's no scam, if what he's trying to do is illegal (even if he doesn't realize it himself) then you want to know before you get involved. You say you're willing to deal with \"\"other issues\"\" separately, but keep in mind that, even if there's no external scam here, those \"\"other issues\"\" could include hefty fees, censures on your own account, or jail time. Ask yourself: Does it make sense that this relative has an account overseas? I don't have any overseas accounts, because I don't do business in other countries. Is your relative a dual-citizen? Does he travel a lot? What country is the overseas account in? How long has he had this account? What bank is it with? Where the money is going is just as important as how it gets there (ie: through your account.) Arguably more so. Keep in mind that many scammers tell their marks not to share what's going on with anyone else. (Because doing so increases the odds of someone telling them to snap out of it.) It's entirely possible he's being scammed himself and just not telling you the whole story because the 419er is telling him to keep it quiet. (Check out that link for more details on common scams that your relative may be unwittingly part of, btw.) Get as many details as possible about what he's doing and why. If he's communicating with anyone else regarding this transfer, find out who. If there are emails, ask his permission to read them and watch for anything suspicious (ie: people who can't spell their own name consistently, constant pressure to act quickly, etc.)\"","title":""},{"docid":"432727","text":"\"Shares sold to private investors are sold using private contracts and do not adhere to the same level of strict regulations as publicly traded shares. You may have different classes of shares in the company with different strings attached to them, depending on the deals made with the investors at the time. Since public cannot negotiate, the IPO prospectus is in fact the investment contract between the company and the public, and the requirements to what the company can put there are much stricter than private sales. Bob may not be able to sell his \"\"special\"\" stocks on the public exchange, as the IPO specifies which class of stock is being listed for trading, and Bob's is not the same class. He can sell it on the OTC market, which is less regulated, and then the buyer has to do his due diligence. Yes, OTC-sold stocks may have strings attached to them (for example a buy back option at a preset time and price).\"","title":""},{"docid":"249643","text":"In a perfect the world, the most ideal solution would be to find a way to pay back all of your debt so that your credit will not be affected any further. Unfortunately, it does not work this way most of the time. Debt settlement is where you work with a creditor to settle your a credit card debt for less than the full amount owed. This could be a very viable solution for you instead of filing for bankruptcy. However, there are many scams out there when it applies to debt settlement so you must tread carefully. Debt settlement can only occur when you're behind on your payments. If you are currently paying off your payments successfully, the creditor has no obligation to settle when they think you should be able to pay it fully back.","title":""},{"docid":"517573","text":"\"Affinity fraud. You see, Madoff really didn't have to sell himself, people recommended him to their friends. In a similar way, it's easy once a scammer reels in one sucker to keep him on the hook long enough to get 10 friends to invest as well. I've written about Mortgage Acceleration scams, and the common thread is that they are first sold to friends, relatives, neighbors. People tell their fellow church goer about it and pretty soon people's belief just takes over as they want it to work. Edit - the scam I referenced above was the \"\"Money Merge Account\"\" and its reincarnated \"\"Wealth Unlimited.\"\" It claimed to use sophisticated software to enable one to pay their mortgage in less than half the time while not changing their budget. The sellers of the product weren't able to explain how it was supposed to work, since it was nonsense anyway. You were supposed to be able to borrow against a HELOC at a rate higher than your mortgage, yet come out ahead, enough to cut the time in half or less. The link I posted above leads to a spreadsheet I wrote in a weekend, which was better at the math than their software and free. It also linked to 66 pages of accumulated writing I did over a number of months starting in 2008. In the end, I never saw any prosecution over this scam, I suppose people were too embarrassed once they realized they wasted $3500. How can I get scammed buying S&P ETFs through Schwab? Easy, I can't.\"","title":""},{"docid":"319599","text":"Well I'm not going to advise whether it's a good idea to invest in this company (though often OTC is pretty scary), but it DOES have a product (vivio, an ad blocker), it did post financials and it's trading on the OTC-QB (which is better than the pink sheets), so you need to look these over and study up on the product to decide if it is overpriced or not. What might have occurred (viz the Patriot Berry Farm becoming Cyberfort) is that the latter bought up the stock of the former (this is, I believe, called using a shell, which is not necessarily a bad thing) and is using this as a way to be registered, i.e. sell to non-accredited investors via the OTC market. So I'm really just answering your third question: yes, you have to do a lot of due diligence to see if buying this stock is a good deal or not. It might be the next big thing. Or it might not. It certainly is the case that low trading volume allows a relatively small trade to really change the stock price, so the penny stocks do tend to be easier to 'inflate'. Side comment: the bid/ask spreads are pretty big, with a best bid of 0.35 and best ask of 0.44.","title":""},{"docid":"29571","text":"how are the ways he could scam me? There are hundreds of different ways the scam can progress ... broadly;","title":""},{"docid":"214518","text":"\"It is likely a scam. In fact the whole mystery shopping \"\"job\"\" may be a scam. There is a Snopes page about cashier's check scams, as well as a US government page which specifically mentions mystery shopping as a scam angle. As for how the scam works, from the occ.gov site I just linked: However, cashier’s checks lately have become an attractive vehicle for fraud when used for payments to consumers. Although, the amount of a cashier’s check quickly becomes \"\"available\"\" for withdrawal by the consumer after the consumer deposits the check, these funds do not belong to the consumer if the check proves to be fraudulent. It may take weeks to discover that a cashier’s check is fraudulent. In the meantime, the consumer may have irrevocably wired the funds to a scam artist or otherwise used the funds—only to find out later, when the fraud is detected—that the consumer owes the bank the full amount of the cashier’s check that had been deposited. It is somewhat unusual in that, from what you say, there has been no attempt thus far to get money back. However, your sister-in-law may have received that info separately, or received it as part of her mystery shopping job but didn't mention it to you with regard to this check. Typically the scam involves telling the recipient to transfer money to a third party (e.g., by buying goods as a mystery shopper, or via wire transfer to \"\"reimburse\"\" someone associated with a sham operation). By the time the cashier's check is revealed as fraudulent, the victim has already transferred away his/her own real money. It's probably worth taking the check to your or her bank and asking them about it. They may have more info. Also, banks usually want to know about scams like this because, in the long run, they accumulate data on them and share that with law enforcement and can eventually catch some of the scammers. Edit: Just to help anyone who may be reading this later. The letter you added confirms it is absolutely a scam. My boss was once contacted via a scam operation very similar to this. The huge red flag (in addition to others already mentioned) is that you are being \"\"given\"\" a check for over $2000, of which only $25 is purportedly for actual mystery shopping and $285 is payment for you, the mystery shopper. The whole rest of the $2000+ amount is for you to wire to \"\"another Mystery/Secret Shopper in order for them to complete their assignment\"\". They are giving you $2000 to give to someone else who is supposedly another one of their own employees/contractors. Ask yourself what sane business would conduct their operations in this way. If you work at a law office, or a hamburger stand, or a school, or anything you like, does your boss ever say \"\"Here is your paycheck for $5000. I know you only earned $1000, but I'm just going to give you the whole $5000, and you're supposed to use $4000 of it to pay your coworker Joe his wages.\"\" No. There is no reason to do that except that the \"\"other mystery shopper\"\" is actually the scammer.\"","title":""},{"docid":"526073","text":"Publicly traded companies perform dilution via an FPO (Follow-up Public Offer). It is a process similar to IPO, with announcements, prospectus, etc. You will know ahead of time when that happen. Stocks traded OTC are not required to file a lot of regulatory documents that publicly traded stocks are required to file, and may not disclose dilutions or additional issues. By buying OTC you agree to these terms. You will probably get a notice and a chance to vote on that in your proxy statement, but that happens when you already own the stock.","title":""},{"docid":"208507","text":"$15 being how much it costs to drive a car about 10 miles, and does not account for a driver's time. Hilarious shit, from the biggest payday loan scam the planet has ever seen. Because Uber is nothing but a scam where you work your ass off, to steal money from your future self, and give 25% of it to Uber! But if you think 6 cents a mile is a decent wage for a cab driver (which is what you can make, if you are lucky), then by all means, please sign up!","title":""},{"docid":"510163","text":"\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \"\"IPO Date\"\" is wrong on this one. However, there are several companies that appear to do an \"\"IPO\"\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \"\"IPO\"\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \"\"IPO\"\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \"\"IPO\"\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \"\"Initial\"\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\"","title":""},{"docid":"496370","text":"\"Yeah, I'll take the challenge...:) How trustworthy these are and what are their sources of income? These are in fact two separate questions, but the answers are related. How trustworthy? As trustworthy as they're clear about their own sources of income. If you cannot find any clue as to why, what for and how they're paying you - you probably should walk away. What's too good to be true usually is indeed too good to be true. For those of the sites that I know of their sources of income, it is usually advertisements and surveys. To get paid, you have to watch advertisements and/or answer surveys. I know of some sites who are legit, and pay people (not money, but gift cards, airline miles, etc) for participating in surveys. My own HMO (Kaiser in California) in fact pays (small amounts) to members who participate in enough surveys, so its legit. Are these sites worthwhile to consider for extra income? Not something you could live off, but definitely can get you enough gift cards for your weekly trip to Starbucks. What do I need to consider tax wise? Usually the amounts are very low, and are not paid in cash. While it is income, I doubt the IRS will chase you if you don't report the $20 Amazon gift card you got from there. It should, strictly speaking, be reported (probably as hobby income) on your tax return. Most people don't bother dealing with such small amounts though. In some cases (like the HMO I mentioned), its basically a rebate of the money paid (you pay your copays, deductibles etc. Since the surveys are only for members, you basically get your money back, not additional income). This is in fact similar to credit card rebates. Is there a best practice for handling the income? If we're talking about significant amounts (more than $20-30 a year), then you need to keep track of the income and related expenses, and report it as any other business income on your taxes, Schedule C. Is there a good test to determine what is and isn't a scam? As I said - if it looks too good to be true - it most likely is. If you're required to provide your personal/financial information without any explanation as to why, what it will be used for, and why and what for you're going to be paid - I'd walk away. Otherwise, you can also check Internet reviews, BBB ratings, FTC information and the relevant state agencies and consumer watchdogs (for example: http://www.scamadviser.com) whether they've heard of that particular site, and what is the information they have on it. A very good sign for a scam is contact information. Do they have a phone number to call to? Is it in your own country? If its not in your own country - definitely go away (for example the original link that was in the question pointed to a service whose phone number is in the UK, but listed address is in Los Angeles, CA. A clear sign of a scam). If they do have a phone number - try it, talk to them, call several times and see how many different people you're going to talk to. If its always the same person - run and hide. Do they have an address? If not - walk away. If they do - look it up. Is it a PMB/POB? A \"\"virtual\"\" office? Or do they have a proper office set up, which you can see on the map and in the listings as their office? And of course your guts. If your guts tell you its a scam - it very likely is.\"","title":""}],"string":"[\n {\n \"docid\": \"416941\",\n \"text\": \"Merrill charges $500 flat fee to (I assume purchase) my untraded or worthless security. In my case, it's an OTC stock whose management used for a microcap scam, which resulted in a class action lawsuit, etc. but the company is still listed on OTC and I'm stuck with 1000s of shares. (No idea about the court decision)\",\n \"title\": \"\"\n },\n {\n \"docid\": \"271116\",\n \"text\": \"Absolute scam. Any time anyone asks you to open a bank account so they can send you money and then you have to send some portion of it back to them, it's a guarantee that it's a scam. What happens is that your dad will deposit the check and transfer it to this woman, then the check will bounce (or turn out to be fake altogether) and your dad will be on the hook for the money to the bank. These schemes are dependent on the fact that people want hope and believe in quick, easy money, and it works as long as the con artists are able to get the 'mark' (the person who deposits the check and sends them the money) to send the money before the check (always drawn on some obscure foreign bank) has a chance to clear. This is another variation of a long-running type of bank scam, and if you get involved, you'll regret it. I hope you can keep your dad from getting involved, because it will create a financial mess and affect his credit as well. The basic premise of this scam is this: In the interests of providing good customer service, most banks will make some or all of a deposit available right away, even though the check hasn't cleared. The scammer has you withdraw the money (either a cashier's check, have you send a wire transfer, etc) immediately and send it to them. Eventually the check is returned because it is The bank charges the check back against your account, often imposing pretty substantial penalties and fees, so you as the account holder are left without the money you sent the scammer and all of the fees. This is the easy version of events. You could end up in legal trouble, depending on the nature of the scam and what they determine your involvement to be. It will certainly badly affect your banking history (ChexSystems tracks how we all treat bank accounts, much like the credit agencies do with our credit), so you may have trouble opening bank accounts. So there are many consequences to this to think about, and it's why you JUST SAY NO!! Don't walk away from this -- RUN!!!\",\n \"title\": \"\"\n },\n {\n \"docid\": \"390779\",\n \"text\": \"\\\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \\\"\\\"Get Rich on Penny Stock\\\"\\\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"421688\",\n \"text\": \"It's not enough just to check if your order doesn't exceed 10% of the 20 day average volume. I'll quote from my last answer about NSCC illiquid charges: You may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. The NSCC issues a charge to the clearing firm if in aggregate, their orders exceed the limits, and the clearing firm usually passes these charges on to the broker(s) that placed the orders. Your broker may or may not pass the charges through to you; they may simply charge you significantly higher commissions for trading OTC securities and use those to cover the charges. Since checking how the volume of your orders compares to the average past volume, ask your broker about their policies on trading OTC stocks. They may tell you that you won't face illiquid charges because the higher cost of commissions covers these, or they may give you specifics on how to verify that your orders won't incur such charges. Only your broker can answer this with certainty.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"346407\",\n \"text\": \"\\\"This is colloquially referred to as a \\\"\\\"pump and dump\\\"\\\" scheme. You basically buy up some stock, and then try to pump up the demand through false and misleading positive statements and market activity. You then close your position once market interest is sufficiently high. If your firm has access to high frequency trading mechanisms, you may even be able to front run other market participants attracted by your buying activities. >I am wondering what is the best route to go down. Definitely micro-cap stocks. Things listed on the OTC markets, especially penny stocks, have this tendency to attract retail buyers just begging to be scammed. Emerging biotech firms also have a lot of potential due to investors' hopes of successful clinical trials. I should warn you though, this is very illegal and falls under market manipulation [according to the SEC](https://www.sec.gov/fast-answers/answerspumpdumphtm.html) and can lead to up to 25 years in prison. So make sure you stay small enough to avoid the regulatory radar. (But seriously, this belongs in r/personalfinance or elsewhere, r/finance isn't the sub you want).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"528576\",\n \"text\": \"I am in complete agreement with you. The place i have found with the sort of charts you are looking for is stockcharts.com. To compare the percentage increase of several stocks over a period of 2 market-open days or more, which is quite useful to follow the changes in various stocks… etc., an example: Here the tickers are AA to EEEEE (OTC) and $GOLD / $SILVER for the spot gold / silver price (that isn't really a ticker). It is set to show the last 6 market days (one week+)...the '6' in '6&O'. You can change it in the URL above or change it on the site for the stocks you want... up to 25 in one chart but it gets really hard to tell them apart! By moving the slider just left of the ‘6’ at the bottom right corner of the chart, you can look at 2 days or more. For a specific time period in days, highlight the ‘6’ and type any number of market-open days you want (21 days = about one month, etc.). By setting a time period in days, and moving the entire slider, you can see how your stocks did in the last bull/bear run, as an example. The site has a full how-to, for this and the other types of charts they offer. The only problem is that many OTC stocks are not charted. Save the comparison charts you use regularly in a folder in your browser bookmarks. Blessings. I see the entire needed link isn't in blue... but you need it all.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"63848\",\n \"text\": \"The only way for a mutual fund to default is if it inflated the NAV. I.e.: it reports that its investments worth more than they really are. Then, in case of a run on the fund, it may end up defaulting since it won't have the money to redeem shares at the NAV it published. When does it happen? When the fund is mismanaged or is a scam. This happened, for example, to the fund Madoff was managing. This is generally a sign of a Ponzi scheme or embezzlement. How can you ensure the funds you invest in are not affected by this? You'll have to read the fund reports, check the independent auditors' reports and check for clues. Generally, this is the job of the SEC - that's what they do as regulators. But for smaller funds, and private (i.e.: not public) investment companies, SEC may not be posing too much regulations.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"545752\",\n \"text\": \"If your concern is scams, we should be talking about counterparties, not bitcoin itself. Unless you think the protocol itself is a scam, which imo it most certainly is not. You're conflating the trustworthiness of counterparties with the trustworthiness of the underlying protocol, which imo is not a very good model to operate by. You'll understand the situation better of you look at them independently. Bitcoin isn't trying to be a credit agency or the better business bureau, it's just trying to be digital money. Don't expect it to protect you from scams any more than cash will. That's not its job, and does not affect its trustworthiness as money.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"545789\",\n \"text\": \"\\\"How can I say this more clearly? SCAM, SCAM, SCAM! This is another one of the oldest scams out there, where you've won a prize or an inheritance has come in, and all you have to do is pay the taxes on it to claim it. Don't be a sucker! Ask yourself why the government couldn't (and wouldn't) just take the taxes due out of the funds they have and give the rest to the person they belong to? Wouldn't that be the smartest and easiest thing to do? As an example, let's say that you have $1,000 that belongs to me, and I owe you $100. Would you tell me to pay you the $100 and then you'll give me the $1,000 or would you take the $100 I owe you out of the $1,000 and give me the remaining $900? The fact this is someone you know from the internet and they want your \\\"\\\"help\\\"\\\" to claim their money should tell you how much of a scam this is. Stop talking to this person, and don't tell them anything personal about you. They are scam artists, and whatever you tell them could be used to steal your identity or take your money. Be careful, my friend!\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"42347\",\n \"text\": \"Something to consider is that in the case of the company you chose, on the OTC market, that stock is thinly traded and with such low volume, it can be easy for it to fluctuate greatly to have trades occur. This is why volume can matter for some people when it comes to buying shares. Some OTC stocks may have really low volume and thus may have bigger swings than other stocks that have higher volume.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"339268\",\n \"text\": \"\\\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \\\"\\\"T\\\"\\\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \\\"\\\"ANET\\\"\\\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \\\"\\\"P\\\"\\\" to the end for \\\"\\\"preferreds\\\"\\\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"597519\",\n \"text\": \"it looks like using an ADR is the way to go here. michelin has an ADR listed OTC as MGDDY. since it is an ADR it is technically a US company that just happens to be a shell company holding only shares of michelin. as such, there should not be any odd tax or currency implications. while it is an OTC stock, it should settle in the US just like any other US OTC. obviously, you are exposing yourself to exchange rate fluctuations, but since michelin derives much of it's income from the US, it should perform similarly to other multinational companies. notes on brokers: most US brokers should be able to sell you OTC stocks using their regular rates (e.g. etrade, tradeking). however, it looks like robinhood.com does not offer this option (yet). in particular, i confirmed directly from tradeking that the 75$ foreign settlement fee does not apply to MGDDY because it is an ADR, and not a (non-ADR) foreign security.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"225030\",\n \"text\": \"\\\"It's a scam. The cashier's check will be forged. Craigslist has a warning about it here (item #3). What kind of payment do you think is not fakable? Or at least not likely to be used in scams? When on craigslist - deal only locally and in person. You can ask to see the person's ID if you're being paid by check When being paid by check, how can seeing his/her ID help? In case the check isn't cashable, I can find that person by keeping record of his/her ID? If you're paid by check, the payers details should be printed on the check. By checking the ID you can verify that the details match (name/address), so you can find the payer later. Of course the ID can be faked too, but there's so much you can do to protect yourself. You'll get better protection (including verified escrow service) by selling on eBay. Is being paid by cash the safest way currently, although cash can be faked too, but it is the least common thing that is faked currently? Do you recommend to first deposit the cash into a bank (so that let the bank verify if the cash is faked), before delivering the good? For Craigslist, use cash and meet locally. That rules out most scams as a seller. What payment methods do you think are relatively safe currently? Then getting checks must be the least favorite way of being paid. Do you think cash is better than money order or cashier order? You should only accept cash. If it is a large transaction, you can meet them at your bank, have them get cash, and you receive the cash from the bank. Back to the quoted scam, how will they later manipulate me? Are they interested in my stuffs on moving sale, or in my money? They will probably \\\"\\\"accidentally\\\"\\\" overpay you and ask for a refund of some portion of the overpayment. In that case you will be out the entire amount that you send back to them and possibly some fees from your bank for cashing a bad check.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"346669\",\n \"text\": \"The OTC market is a marketplace, the location it definitely relied on the purchaser marketplace. The OTC market is mostly used to exchange bonds among the two occasions and all this technique are executed by way of manner of the third celebration. They are able to also be used to alternate equity, such because of the OTC QX and purple marketplaces within the USA. The minamargroup is the Florida, USA situated agency, who elements their purchase investor relation with to present organization into to make new ones. OTC way it's far a protection traded in some context other, changing between parties or groups inclusive of New York Stock trade.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"343518\",\n \"text\": \"\\\"This is clearly a scam, and you should stay away from it. Anyone reading this knew that from the title alone - and it seems that you know it too. Don't \\\"\\\"test\\\"\\\" whether something is a scam by putting your own money in it. That is exactly how these scammers make money, and how you lose it. How their scam works is irrelevant. The simple fact is that there is no way you can safely earn 20% return over the course of a year, let alone in 1 day*. You know this is true. Don't bother trying to figure out what makes it true in this case. There is no free lunch. Best case scenario, this is a hyper-risky investment strategy [on the level of putting your money down at a roulette wheel]. Worst case scenario, they simply steal your money. Either way, you won't come out ahead. Although I agree with others that this is likely a Ponzi scheme, that doesn't really matter. What matters is, there is no way they can guarantee those returns. Just go to a casino and throw your money away yourself, if you want that level of risk. *For reference, if you invested $100 for a year, earning 20% returns every day, you would have 6 million trillion trillion dollars by the end of the year. that's $6,637,026,647,624,450,000,000,000,000,000. that number doesn't even make sense. It's more money than exists on earth. So why would they need your $100?\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"263659\",\n \"text\": \"There are several red flags here. can they get my bank account info in any way from me transferring money to them? Probably yes. Almost all bank transactions are auditable, and intentionally cause a money track. This track can be followed from both sides. If they can use your bank account as if they were you, that is a bit deeper than what you are asking, but yes they (and the polish cops) can find you through that transfer. I did look up the company and didn't find any scam or complaints concerning them. Not finding scams or complains is good, but what did you find? Did you find good reviews, the company website, its register, etc, etc? How far back does the website goes (try the wayback machine) Making a cardboard front company is very easy, and if they are into identity theft the company is under some guy in guam that never heard of poland or paypal. As @Andrew said above, it is probably a scam. I'd add that this scam leverages on the how easier is to get a PayPal refund compared to a regular bank transfer. It is almost impossible to get the money back on an international transaction. Usually reverting a bank transfer requires the agreement in writing of the receiver and of both banks. As for paypal, just a dispute from the other user: You are responsible for all Reversals, Chargebacks, fees, fines, penalties and other liability incurred by PayPal, a PayPal User, or a third party caused by your use of the Services and/or arising from your breach of this Agreement. You agree to reimburse PayPal, a User, or a third party for any and all such liability. (source) Also, you might be violating the TOS: Allow your use of the Service to present to PayPal a risk of non-compliance with PayPal’s anti-money laundering, counter terrorist financing and similar regulatory obligations (including, without limitation, where we cannot verify your identity or you fail to complete the steps to lift your sending, receiving or withdrawal limit in accordance with sections 3.3, 4.1 and 6.3 or where you expose PayPal to the risk of any regulatory fines by European, US or other authorities for processing your transactions); (emphasis mine, source) So even if the PayPal transfer is not disputed, how can you be sure you are not laundering money? Are you being paid well enough to assume that risk?\",\n \"title\": \"\"\n },\n {\n \"docid\": \"282196\",\n \"text\": \"\\\"In general I don’t think you can blame the news stories. You can blame everyone’s preconceived notion that any sort of LBO or leveraged restructuring is the devil’s work. Every American is of course well-versed in the subject. From the Sealy example, you clearly have a journalist who has no idea what they are talking about. All you have is a cherry-picked summary of what took place. As such, the “finance scholars” jump in and explain how it’s all a giant scam. Bain LBO’d Sealy in 1997. As a part of that, it was saddled with ~$700m in debt. That of course is fodder for the \\\"\\\"finance scholars\\\"\\\" because they don't understand the benefits of debt and more generally how LBOs work, none of which are noted in the article. The article then notes that Sealy has recently encountered trouble. To the \\\"\\\"geniuses\\\"\\\" this is of course because of Romney's work and the ~$700m in debt. No one notices the fact that Bain unloaded this in 2004 for double what it paid for it. For those that did, the unloading was a textbook Bain scam. Bain unloaded this to KKR, perhaps the sharpest and most successful PE firm in history. Would KKR put $1.5b into this if it were a scam? According to the \\\"\\\"geniuses\\\"\\\", of course they would. How could Mitt Romney actually improve a business? No one looks at the fact that revenues were up considerably, margins had expanded tremendously, growth prospects were higher, and FCF yields were fantastic. This is why KKR bought the company, and this is what an LBO is supposed to be. I haven't done a ton of work on this case, it was before my time, but I would be very surprised if the growth wasn't accompanied by employee expansion as well. You also get the “I wish I had a way to just walk away from my debt” comment. I don’t even know where to begin explaining how asinine that is. Equity is subordinated to debt. That’s the definition of equity. The article also notes the one-sided-mattress idea, which is construed as Romney's giant scam to screw the average American while flipping this company and making his millions. The article of course didn't note that this one-sided mattress idea was a mere fraction of revenue. This was designed as an economy mattress, with an advertised shorter shelf life. Plus how can this be a scam? Would you go into the mattress store and pay the same amount for a mattress with only one side? If you would you deserve to get half of a mattress. So the crux of it is, this is in actuality an example of what an LBO should be. At least for Bain’s part. Bain took a business that was ripe for an LBO (reasonable steady FCF, low leverage), did the LBO, improved the business, and came out on top. What KKR did with it afterwords I have no idea. I would imagine it has more to do with deteriorating business conditions than the debt on its balance sheet. I work with restructurings over 100 hours a week. I of course don’t come up with the plans (I’m a lowly analyst building models and associated bitchwork) but I see just how brilliant these ideas are. In a lot of cases restructurings prevent the tripping of covenants and associated bankruptcy and allow for strategy to play out and for companies to grow. I can of course give a more detailed rant on the article, but I figured no one will read this anyway.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"593644\",\n \"text\": \"NSCC illiquid charges are charges that apply to the trading of low-priced over-the counter (OTC) securities with low volumes. Open net buy quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net buy quantity must be less than 5,000,000 shares per stock for your entire firm Basically, you can't hold a long position of more than 5 million shares in an illiquid OTC stock without facing a fee. You'll still be assessed this fee if you accumulate a long position of this size by breaking your purchase up into multiple transactions. Open net sell quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net sell quantity must be less than 10% percent of the 20-day average volume If you attempt to sell a number of shares greater than 10% of the stock's average volume over the last 20 days, you'll also be assessed a fee. The first link I included above is just an example, but it makes the important point: you may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. Technically, these fees are assessed to the clearing firm, not the individual investor, but usually the clearing firm will pass the fees along to the broker (and possibly add other charges as well), and the broker will charge a fee to the individual account(s) that triggered the restriction. Also, remember that when buying OTC/pink sheet stocks, your ability to buy or sell is also contingent on finding someone else to buy from/sell to. If you purchase 10,000 shares one day and attempt to sell them sometime in the future, but there aren't enough buyers to buy all 10,000 from you, you might not be able to complete your order at the desired price, or even at all.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"467352\",\n \"text\": \"Depends on how you measure liquidity. There's papers out there that approach this very question. Measured in order book spreads for a consolidated $100m trade, I'd say the second biggest market is FX swaps, followed or par'd by the money market (government bonds). If you disallow OTC venues, it's most definitely exchange listed government bonds. If, however, you happen to think in terms of sheer volume per time, the most liquid market phase could be considered the NYSE closing auction, as you can move billions in a matter of minutes, or expressed in speed terms: several m$/s (million dollars per second). You should pick a definition and we can provide you with a more accurate list of candidates and actual data.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"123511\",\n \"text\": \"\\\"What can I do to help him out, but at the same time protect myself from any potential scams? Find out why he can't do this himself. Whether your relative is being sincere or not, if he owns both accounts then he should be able to transfer money between them by himself. If you can find a way to solve that issue without involving your bank account, so much the better. Don't settle for \\\"\\\"something about authorized payees and expired cards.\\\"\\\" Get details, write them down. If possible, get documents. Then go to a bank or financial adviser you can trust and run those details by them to see what they have to say. Even if there's no scam, if what he's trying to do is illegal (even if he doesn't realize it himself) then you want to know before you get involved. You say you're willing to deal with \\\"\\\"other issues\\\"\\\" separately, but keep in mind that, even if there's no external scam here, those \\\"\\\"other issues\\\"\\\" could include hefty fees, censures on your own account, or jail time. Ask yourself: Does it make sense that this relative has an account overseas? I don't have any overseas accounts, because I don't do business in other countries. Is your relative a dual-citizen? Does he travel a lot? What country is the overseas account in? How long has he had this account? What bank is it with? Where the money is going is just as important as how it gets there (ie: through your account.) Arguably more so. Keep in mind that many scammers tell their marks not to share what's going on with anyone else. (Because doing so increases the odds of someone telling them to snap out of it.) It's entirely possible he's being scammed himself and just not telling you the whole story because the 419er is telling him to keep it quiet. (Check out that link for more details on common scams that your relative may be unwittingly part of, btw.) Get as many details as possible about what he's doing and why. If he's communicating with anyone else regarding this transfer, find out who. If there are emails, ask his permission to read them and watch for anything suspicious (ie: people who can't spell their own name consistently, constant pressure to act quickly, etc.)\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"432727\",\n \"text\": \"\\\"Shares sold to private investors are sold using private contracts and do not adhere to the same level of strict regulations as publicly traded shares. You may have different classes of shares in the company with different strings attached to them, depending on the deals made with the investors at the time. Since public cannot negotiate, the IPO prospectus is in fact the investment contract between the company and the public, and the requirements to what the company can put there are much stricter than private sales. Bob may not be able to sell his \\\"\\\"special\\\"\\\" stocks on the public exchange, as the IPO specifies which class of stock is being listed for trading, and Bob's is not the same class. He can sell it on the OTC market, which is less regulated, and then the buyer has to do his due diligence. Yes, OTC-sold stocks may have strings attached to them (for example a buy back option at a preset time and price).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"249643\",\n \"text\": \"In a perfect the world, the most ideal solution would be to find a way to pay back all of your debt so that your credit will not be affected any further. Unfortunately, it does not work this way most of the time. Debt settlement is where you work with a creditor to settle your a credit card debt for less than the full amount owed. This could be a very viable solution for you instead of filing for bankruptcy. However, there are many scams out there when it applies to debt settlement so you must tread carefully. Debt settlement can only occur when you're behind on your payments. If you are currently paying off your payments successfully, the creditor has no obligation to settle when they think you should be able to pay it fully back.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"517573\",\n \"text\": \"\\\"Affinity fraud. You see, Madoff really didn't have to sell himself, people recommended him to their friends. In a similar way, it's easy once a scammer reels in one sucker to keep him on the hook long enough to get 10 friends to invest as well. I've written about Mortgage Acceleration scams, and the common thread is that they are first sold to friends, relatives, neighbors. People tell their fellow church goer about it and pretty soon people's belief just takes over as they want it to work. Edit - the scam I referenced above was the \\\"\\\"Money Merge Account\\\"\\\" and its reincarnated \\\"\\\"Wealth Unlimited.\\\"\\\" It claimed to use sophisticated software to enable one to pay their mortgage in less than half the time while not changing their budget. The sellers of the product weren't able to explain how it was supposed to work, since it was nonsense anyway. You were supposed to be able to borrow against a HELOC at a rate higher than your mortgage, yet come out ahead, enough to cut the time in half or less. The link I posted above leads to a spreadsheet I wrote in a weekend, which was better at the math than their software and free. It also linked to 66 pages of accumulated writing I did over a number of months starting in 2008. In the end, I never saw any prosecution over this scam, I suppose people were too embarrassed once they realized they wasted $3500. How can I get scammed buying S&P ETFs through Schwab? Easy, I can't.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"319599\",\n \"text\": \"Well I'm not going to advise whether it's a good idea to invest in this company (though often OTC is pretty scary), but it DOES have a product (vivio, an ad blocker), it did post financials and it's trading on the OTC-QB (which is better than the pink sheets), so you need to look these over and study up on the product to decide if it is overpriced or not. What might have occurred (viz the Patriot Berry Farm becoming Cyberfort) is that the latter bought up the stock of the former (this is, I believe, called using a shell, which is not necessarily a bad thing) and is using this as a way to be registered, i.e. sell to non-accredited investors via the OTC market. So I'm really just answering your third question: yes, you have to do a lot of due diligence to see if buying this stock is a good deal or not. It might be the next big thing. Or it might not. It certainly is the case that low trading volume allows a relatively small trade to really change the stock price, so the penny stocks do tend to be easier to 'inflate'. Side comment: the bid/ask spreads are pretty big, with a best bid of 0.35 and best ask of 0.44.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"29571\",\n \"text\": \"how are the ways he could scam me? There are hundreds of different ways the scam can progress ... broadly;\",\n \"title\": \"\"\n },\n {\n \"docid\": \"214518\",\n \"text\": \"\\\"It is likely a scam. In fact the whole mystery shopping \\\"\\\"job\\\"\\\" may be a scam. There is a Snopes page about cashier's check scams, as well as a US government page which specifically mentions mystery shopping as a scam angle. As for how the scam works, from the occ.gov site I just linked: However, cashier’s checks lately have become an attractive vehicle for fraud when used for payments to consumers. Although, the amount of a cashier’s check quickly becomes \\\"\\\"available\\\"\\\" for withdrawal by the consumer after the consumer deposits the check, these funds do not belong to the consumer if the check proves to be fraudulent. It may take weeks to discover that a cashier’s check is fraudulent. In the meantime, the consumer may have irrevocably wired the funds to a scam artist or otherwise used the funds—only to find out later, when the fraud is detected—that the consumer owes the bank the full amount of the cashier’s check that had been deposited. It is somewhat unusual in that, from what you say, there has been no attempt thus far to get money back. However, your sister-in-law may have received that info separately, or received it as part of her mystery shopping job but didn't mention it to you with regard to this check. Typically the scam involves telling the recipient to transfer money to a third party (e.g., by buying goods as a mystery shopper, or via wire transfer to \\\"\\\"reimburse\\\"\\\" someone associated with a sham operation). By the time the cashier's check is revealed as fraudulent, the victim has already transferred away his/her own real money. It's probably worth taking the check to your or her bank and asking them about it. They may have more info. Also, banks usually want to know about scams like this because, in the long run, they accumulate data on them and share that with law enforcement and can eventually catch some of the scammers. Edit: Just to help anyone who may be reading this later. The letter you added confirms it is absolutely a scam. My boss was once contacted via a scam operation very similar to this. The huge red flag (in addition to others already mentioned) is that you are being \\\"\\\"given\\\"\\\" a check for over $2000, of which only $25 is purportedly for actual mystery shopping and $285 is payment for you, the mystery shopper. The whole rest of the $2000+ amount is for you to wire to \\\"\\\"another Mystery/Secret Shopper in order for them to complete their assignment\\\"\\\". They are giving you $2000 to give to someone else who is supposedly another one of their own employees/contractors. Ask yourself what sane business would conduct their operations in this way. If you work at a law office, or a hamburger stand, or a school, or anything you like, does your boss ever say \\\"\\\"Here is your paycheck for $5000. I know you only earned $1000, but I'm just going to give you the whole $5000, and you're supposed to use $4000 of it to pay your coworker Joe his wages.\\\"\\\" No. There is no reason to do that except that the \\\"\\\"other mystery shopper\\\"\\\" is actually the scammer.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"526073\",\n \"text\": \"Publicly traded companies perform dilution via an FPO (Follow-up Public Offer). It is a process similar to IPO, with announcements, prospectus, etc. You will know ahead of time when that happen. Stocks traded OTC are not required to file a lot of regulatory documents that publicly traded stocks are required to file, and may not disclose dilutions or additional issues. By buying OTC you agree to these terms. You will probably get a notice and a chance to vote on that in your proxy statement, but that happens when you already own the stock.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"208507\",\n \"text\": \"$15 being how much it costs to drive a car about 10 miles, and does not account for a driver's time. Hilarious shit, from the biggest payday loan scam the planet has ever seen. Because Uber is nothing but a scam where you work your ass off, to steal money from your future self, and give 25% of it to Uber! But if you think 6 cents a mile is a decent wage for a cab driver (which is what you can make, if you are lucky), then by all means, please sign up!\",\n \"title\": \"\"\n },\n {\n \"docid\": \"510163\",\n \"text\": \"\\\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \\\"\\\"IPO Date\\\"\\\" is wrong on this one. However, there are several companies that appear to do an \\\"\\\"IPO\\\"\\\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \\\"\\\"IPO\\\"\\\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \\\"\\\"IPO\\\"\\\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \\\"\\\"IPO\\\"\\\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \\\"\\\"Initial\\\"\\\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"496370\",\n \"text\": \"\\\"Yeah, I'll take the challenge...:) How trustworthy these are and what are their sources of income? These are in fact two separate questions, but the answers are related. How trustworthy? As trustworthy as they're clear about their own sources of income. If you cannot find any clue as to why, what for and how they're paying you - you probably should walk away. What's too good to be true usually is indeed too good to be true. For those of the sites that I know of their sources of income, it is usually advertisements and surveys. To get paid, you have to watch advertisements and/or answer surveys. I know of some sites who are legit, and pay people (not money, but gift cards, airline miles, etc) for participating in surveys. My own HMO (Kaiser in California) in fact pays (small amounts) to members who participate in enough surveys, so its legit. Are these sites worthwhile to consider for extra income? Not something you could live off, but definitely can get you enough gift cards for your weekly trip to Starbucks. What do I need to consider tax wise? Usually the amounts are very low, and are not paid in cash. While it is income, I doubt the IRS will chase you if you don't report the $20 Amazon gift card you got from there. It should, strictly speaking, be reported (probably as hobby income) on your tax return. Most people don't bother dealing with such small amounts though. In some cases (like the HMO I mentioned), its basically a rebate of the money paid (you pay your copays, deductibles etc. Since the surveys are only for members, you basically get your money back, not additional income). This is in fact similar to credit card rebates. Is there a best practice for handling the income? If we're talking about significant amounts (more than $20-30 a year), then you need to keep track of the income and related expenses, and report it as any other business income on your taxes, Schedule C. Is there a good test to determine what is and isn't a scam? As I said - if it looks too good to be true - it most likely is. If you're required to provide your personal/financial information without any explanation as to why, what it will be used for, and why and what for you're going to be paid - I'd walk away. Otherwise, you can also check Internet reviews, BBB ratings, FTC information and the relevant state agencies and consumer watchdogs (for example: http://www.scamadviser.com) whether they've heard of that particular site, and what is the information they have on it. A very good sign for a scam is contact information. Do they have a phone number to call to? Is it in your own country? If its not in your own country - definitely go away (for example the original link that was in the question pointed to a service whose phone number is in the UK, but listed address is in Los Angeles, CA. A clear sign of a scam). If they do have a phone number - try it, talk to them, call several times and see how many different people you're going to talk to. If its always the same person - run and hide. Do they have an address? If not - walk away. If they do - look it up. Is it a PMB/POB? A \\\"\\\"virtual\\\"\\\" office? Or do they have a proper office set up, which you can see on the map and in the listings as their office? And of course your guts. If your guts tell you its a scam - it very likely is.\\\"\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":2699,"cells":{"query_id":{"kind":"string","value":"9410"},"query":{"kind":"string","value":"What's the difference between shares outstanding and regular shares?"},"positive_passages":{"kind":"list like","value":[{"docid":"98654","text":"outstanding shares are the shares(regular shares) that are still tradable in the market, where the firm in question is listed. The term is primarily used to distinguish from shares held in treasury(treasury stock), which have been bought back(buybacks) from the market and aren't currently tradable in the market. Wikipedia is a bit more clearer and mentions the diluted outstanding shares(used for convertible bonds, warrants, etc) which is used to calculated diluted EPS.","title":""}],"string":"[\n {\n \"docid\": \"98654\",\n \"text\": \"outstanding shares are the shares(regular shares) that are still tradable in the market, where the firm in question is listed. The term is primarily used to distinguish from shares held in treasury(treasury stock), which have been bought back(buybacks) from the market and aren't currently tradable in the market. Wikipedia is a bit more clearer and mentions the diluted outstanding shares(used for convertible bonds, warrants, etc) which is used to calculated diluted EPS.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"313372","text":"\"There are a few other items that you should be aware of when getting options: The strike price is usually determined by an independent valuation of the common shares (called a 409a valuation). This should give you a sense on what the options are worth. Obviously you are hoping that the value becomes many multiple of that. There are two kinds in the US: Non-quals (NQO) and Incentive Stock Options (ISOs). The big difference is that when you exercise Non-quals, you have to pay the tax on the difference between the \"\"fair\"\" market value on the shares and what you paid for them (the strike price). This is important because if the company is private, you likely can not sell any shares until it is public. With ISOs, you don't pay any tax (except AMT tax) on the gain until you actually sell the shares. You should know what kind your getting. Some plans allow for early exercise, essentially allowing you to buy the shares early (and given back if you leave before they vest) which helps you establish capital gains treatment earlier as well as avoid AMT if you have ISOs. This is really complicated direction and you would want to talk to a tax professional. And always a good idea to know how many total shares outstanding in the Company. Very few people ask this question but it is helpful for you to understand the overall value of the options.\"","title":""},{"docid":"582736","text":"In Australia the ATO can determine if you are considered a shareholder or a share trader. The ATO defines a shareholder as: A shareholder is a person who holds shares for the purpose of earning income from dividends and similar receipts. Whilst they define a share trader as: A share trader is a person who carries out business activities for the purpose of earning income from buying and selling shares. To find out the differences between them you can refer to the following link describing The difference between a share trader and a shareholder. The ATO also describes: To be classed as a share trader, you may be asked to provide evidence that demonstrates you are carrying on a business of share trading, for example: the purchase of shares on a regular basis through a regular or routine method a trading plan use of share trading techniques in managing your share acquisitions, such as decisions based on thorough analysis of relevant market information a contingency plan in the event of a major shift in the market. Losses incurred in the business of share trading are treated the same as any other losses from business. If your activities change from investor to trader, your investment changes from a CGT (capital gains tax) asset to trading stock. This can trigger CGT event for any investments you currently hold as they change from CGT assets to trading stock. Once you have changed over to a trader you will not be entitled to the 50% CGT discount for stocks held over 12 months. You will, however, be able to count any paper losses at the end of Financial Year to reduce your other income.","title":""},{"docid":"427859","text":"\"I think it's easiest to illustrate it with an example... if you've already read any of the definitions out there, then you know what it means, but just don't understand what it means. So, we have an ice cream shop. We started it as partners, and now you and I each own 50% of the company. It's doing so well that we decide to take it public. That means that we will be giving up some of our ownership in return for a chance to own a smaller portion of a bigger thing. With the money that we raise from selling stocks, we're going to open up two more stores. So, without getting into too much of the nitty gritty accounting that would turn this into a valuation question, let's say we are going to put 30% of the company up for sale with these stocks, leaving you and me with 35% each. We file with the SEC saying we're splitting up the company ownership with 100,000 shares, and so you and I each have 35,000 shares and we sell 30,000 to investors. Then, and this depends on the state in the US where you're registering your publicly traded corporation, those shares must be assigned a par value that a shareholder can redeem the shares at. Many corporations will use $1 or 10 cents or something nominal. And we go and find investors who will actually pay us $5 per share for our ice cream shop business. We receive $150,000 in new capital. But when we record that in our accounting, $5 in total capital per share was contributed by investors to the business and is recorded as shareholder's equity. $1 per share (totalling $30,000) goes towards actual shares outstanding, and $4 per share (totalling $120,000) goes towards capital surplus. These amounts will not change unless we issue new stocks. The share prices on the open market can fluctuate, but we rarely would adjust these. Edit: I couldn't see the table before. DumbCoder has already pointed out the equation Capital Surplus = [(Stock Par Value) + (Premium Per Share)] * (Number of Shares) Based on my example, it's easy to deduce what happened in the case you've given in the table. In 2009 your company XYZ had outstanding Common Stock issued for $4,652. That's probably (a) in thousands, and (b) at a par value of $1 per share. On those assumptions we can say that the company has 4,652,000 shares outstanding for Year End 2009. Then, if we guess that's the outstanding shares, we can also calculate the implicit average premium per share: 90,946,000 ÷ 4,652,000 == $19.52. Note that this is the average premium per share, because we don't know when the different stocks were issued at, and it may be that the premiums that investors paid were different. Frankly, we don't care. So clearly since \"\"Common Stock\"\" in 2010 is up to $9,303 it means that the company released more stock. Someone else can chime in on whether that means it was specifically a stock split or some other mechanism... it doesn't matter. For understanding this you just need to know that the company put more stock into the marketplace... 9,303 - 4,652 == 4,651(,000) more shares to be exact. With the mechanics of rounding to the thousands, I would guess this was a stock split. Now. What you can also see is that the Capital Surplus also increased. 232,801 - 90,946 == 141,855. The 4,651,000 shares were issued into the market at an average premium of 141,855 ÷ 4,651 == $30.50. So investors probably paid (or were given by the company) an average of $31.50 at this split. Then, in 2011 the company had another small adjustment to its shares outstanding. (The Common Stock went up). And there was a corresponding increase in its Capital Surplus. Without details around the actual stock volumes, it's hard to get more exact. You're also only giving us a portion of the Balance Sheet for your company, so it's hard to go into too much more detail. Hopefully this answers your question though.\"","title":""},{"docid":"211343","text":"Investopedia has a good definition. Stock dividends are similar to cash dividends; however, instead of cash, a company pays out stock. Stock splits occur when a company perceives that its stock price may be too high. Stock splits are usually done to increase the liquidity of the stock (more shares outstanding) and to make it more affordable for investors to buy regular lots (a regular lot = 100 shares).","title":""},{"docid":"165855","text":"\"Treasury stock is not really represented in the Balance Sheet as a \"\"Treasury stock\"\" line item in the assets. Some companies will break out Treasury Shares as a line item in the \"\"Shareholders Equity\"\" heading of the balance sheet but Apple hides it in the \"\"Shares Issued and Outstanding\"\" counts under the \"\"Shareholders Equity\"\" heading. As of the most recent Q2 2017 quarterly report There are 5,205,815,000 shares issued against 5,336,166,000 shares outstanding. This indicates that Apple is retaining about 130,351,000 shares in treasury. On the Q1 10-Q you can see that Apple had 5,255,423,000 shares issued which indicates roughly 49mm shares were repurchased by the end of Q2. You can roughly verify this by looking at page 18 of the Q2 filing in the summary of the share repurchase program. Repurchased as part of an Accelerated Share Repurchase arrangement bleeds between quarters but from February 2017 through May 2017 there have been 17.5mm shares repurchased. 31mm shares were also repurchased on the open market in Q2. The \"\"shares issued\"\" total is on a downward trend as part of Apple's share repurchase initiative that has been underway for the last couple of years.\"","title":""},{"docid":"324470","text":"Broadly, there's a bunch of stuff you need to be accounting for that's not reflected in the above, which will impact the A/D profile of an acquisition: * Consideration paid (all cash on substantially the same terms is going to be more accretive than an all-stock transaction...because in the latter, your denominator is much bigger) * Shares outstanding (including repurchases, in-kind dividends and option exercise) * Financing / interest expense * Upside / base / downside case for all of your assumptions - best to have a toggle based on a CHOOSE function that will allow the user to easily toggle between these I'm not sure what EBITDA is getting you. EPS accretion/dilution typically looks at earnings, but you could also look at Cash EPS A/D which measures OCF/shares outstanding. The point is, this really depends on how back of the envelope you want the A/D computation to be. At a minimum, you need an earnings schedule projected over the next 2-3 years, and you need a schedule reflecting outstanding shares over the same time period. Your earnings buildout can have varying degrees of granularity. You can project cost synergies over the forecast period, which most obviously is going to affect your earnings, but you can also drill down further. Financing, transaction fees, etc. Your writeups and writedowns from your B/S combination may result in certain deferred tax items that will affect your bottom line over the forecast period. Your share schedule can also have varying degrees of complexity. One way to do it is to just presume that the company will not issue any more shares, and will not repurchase any shares, and that there will be no options exercised, over the forecast period. This is a bad series of assumptions. It is likely that as options vest, if in the money, they will be exercised, resulting in dilution for existing shareholders. It is also likely that certain preferred shareholders and optionholders are going to experience adjustments to the conversion prices based on antidilution provisions in their securities. These may be but are not always disclosed in the 10K. Last point - models are tools. What are you trying to build an accretion/dilution model for? This will affect and determine the degree of granularity you'll want to go into.","title":""},{"docid":"393439","text":"Now assume these shares are vested, held for at least 1 year, and are then sold for $5 each. Everything I've read implies that the grantee now owes long-term capital gains taxes on the difference, which would be 10k * ($5 - $1). No. That's exactly what the SO is NQ for. Read more on the differences between ISO and NQSO here. Now assume these shares are vested, held for at least 1 year, and are then sold for $5 each. Everything I've read implies that the grantee now owes long-term capital gains taxes on the difference, which would be 10k * ($5 - $1). At this point you no longer have NQSO, you have RSU. If you filed 83(b) when you exercised, then you pay capital gains tax when they vest. If you didn't - its ordinary income to you. NQSO is a red herring here since once exercised they no longer exist. If you didn't file 83(b), then when the stock vests the difference between the FMV at vest and the money you spent on it when exercising (if any) is considered wages and taxed as ordinary income (+FICA etc). From that point the RSU becomes a regular stock investment and the capital gains clock starts ticking.","title":""},{"docid":"467936","text":"For the case of spinoffs it reflects the market as activities as the specific steps that have to be followed take place. For example the spinoff of Leidos from SAIC in 2013. (I picked this one becasue I knew some of the details) On September 9, 2013, the Board of Directors of SAIC, Inc.(Ticker Symbol (NYSE):SAI) approved the following: The separation of its technical, engineering and enterprise information technology services business through the distribution of shares of SAIC Gemini, Inc. to stockholders. Each stockholder of record of SAIC, Inc. as of September 19, 2013 (Record Date) will receive one (1) share of SAIC Gemini, Inc. common stock for every seven (7) shares of SAIC, Inc. common stock held by such stockholder as of the Record Date. This distribution will be effective after market close on September 27, 2013 (Distribution Date). After the Distribution Date, SAIC Gemini, Inc. will be renamed Science Applications International Corporation (New SAIC). A one (1) for four (4) reverse stock split of the SAIC, Inc. common stock effective as of Distribution Date. After the Distribution Date, SAIC, Inc. will be renamed Leidos Holdings, Inc. (Leidos). Q 11: What are the different trading markets that may occur between Record Date and Distribution Date? A: Beginning two days prior to the Record Date of September 19, 2013 through the Distribution Date on September 27, 2013, there may be three different trading markets available with respect to SAIC, Inc. and the separation. Stock Ticker – SAI (Regular Way Trading with Due Bills): Shares of SAI common stock that trade on the regular-way market will trade with an entitlement to shares of the New SAIC common stock distributed on the Distribution Date. Purchasers in this market are purchasing both the shares of Leidos and New SAIC common stock. Form of Stock Ticker –SAIC (When Issued Trading): Shares of New SAIC common stock may be traded on a “when-issued” basis. These transactions are made conditionally because the security has been authorized, but not yet issued. Purchasers in this market are only purchasing the shares of New SAIC common stock distributed on the Distribution Date. Form of Stock Ticker – LDOS (Ex-Distribution Trading): Shares that trade on the ex-distribution market will trade without an entitlement to shares of New SAIC common stock distributed on the Distribution Date. Purchasers in this market are only purchasing the shares of Leidos common stock. So the stock price for New SAIC starts a few days before the record date of 19 September 2013, while LDOS (new name for the old SAIC) goes back much earlier. But the company didn't split until after the close of business on 27 September 2013. http://investors.saic.com/sites/saic.investorhq.businesswire.com/files/doc_library/file/GeneralStockholder-QuestionsandAnswers.pdf","title":""},{"docid":"56052","text":"What I think was being asked (and so this is how I interpreted it) is not the transition from public to private, but a corporation itself buying all its shares back, and as a result having no shareholders. In this case we could envision that all outstanding shares would be become treasury stock. My argument was that this would never happen in a practical setting. Obviously, if you interpret the question differently, for instance to be about all the shares of firm being purchased by someone else (as in a private equity buyout), you get very different answers about practicality. So I'm not disagreeing with you at all, I just read the question differently.","title":""},{"docid":"454224","text":"A mutual fund has several classes of shares that are charged different fees. Some shares are sold through brokers and carry a sales charge (called load) that compensates the broker in lieu of a fee that the broker would charge the client for the service. Vanguard does not have sales charge on its funds and you don't need to go through a broker to buy its shares; you can buy directly from them. Admiral shares of Vanguard funds are charged lower annual expenses than regular shares (yes, all mutual funds charge expenses for fund adninistration that reduce the return that you get, and Vanguard has some of the lowest expense ratios) but Admiral shares are available only for large investments, typically $50K or so. If you have invested in a Vanguard mutual fund, your shares can be set to automatically convert to Admiral shares when the investment reaches the right level. A mutual fund manager can buy and sell stocks to achieve the objectives of the fund, so what stockes you are invested in as a share holder in a mutual fund will typically be unknown to you on a day-to-day basis. On the other hand, Exchange-traded funds (ETFs) are fixed baskets of stocks, and you can buy shares in the ETF. These shares are bought and sold through a broker (so you pay a transaction fee each time) but expenses are lower since there is no manager to buy and sell stocks: the basket is fixed. Many ETFs follow specific market indexes (e.g. S&P 500). Another difference between ETFs and mutual funds is that you can buy and sell ETFs at any time of the day just as if you could if you held stocks. With mutual funds, any buy and sell requests made during the day are processed at the end of the day and the value of the shares that you buy or sell is determined by the closing price of the stocks held by the mutual fund. With ETFs, you are getting the intra-day price at the time the buy or sell order is executed by your broker.","title":""},{"docid":"581848","text":"During a stock split the only thing that changes is the number of shares outstanding. Typically a stock splits to lower its price per share. Sometimes if a company's value is falling it will do a reverse split where X shares will be exchanged for Y shares. This is typically done to avoid being de-listed from an exchange if the price per share falls below a certain threshold, usually $1. Again the only thing changing is the number of shares outstanding. A 20 for 1 reverse split means for every 20 shares outstanding the shareholder will be granted one new share. Example X Co. has 1,000,000 shares outstanding for a price of $100 per share. It does a 1 for 10 split. Now there are 10,000,000 shares outstanding for a price of $10 per share. Example Y Co has 1,000,000 shares outstanding for a price of $1 per share. It does a 10 for 1 reverse split. Now there are 100,000 shares outstanding for a price of $10. Quickly looking at the news for ASTI it looks like it underwent a 20 for 1 reverse split. You should probably look at your statements and ask your broker how the arithmetic worked in your case. Investopedia links for Reverse Stock Split and Stock Split","title":""},{"docid":"99947","text":"I have been asking myself a similar question about the financial statements of Weyerhaeuser. In response to Dheer's comment, whilst treasury shares are treated as a negative, it is issued shares less treasury shares (the negative) which gives the outstanding shares. So the original query remains unanswered. I've searched several sources and all state that outstanding shares will never be greater than issued shares. I've realized that the shares referred to are those authorized followed by those issued and outstanding (current year and prior year respectively) i.e. the shares that are both issued and outstanding as they must be issued in order to be outstanding This is supported in the example of Weyerhaeuser as there was a large increase in shares during Q1 2016 as a result of their merger with Plum Creek. Shares issued and outstanding are 510 million and 759 million respectively.","title":""},{"docid":"595796","text":"The Brokerage firm will purchase shares for the dividend paid in a omnibus account for the security of the issuer and then they will distribute fractional shares among all their clients that chose Div Reinvest. They will only have to buy 1 extra share to account for the fractional portion of what they allocate. The structure of the market does not permit trading of fractional shares. There is generally not any impact to the market place for Div Reinvest with the exception of certain securities that pay large dividends that are not liquid. sometimes this occurs in preferred securities where a large amount of Div reinvestment could create a large market order that has market impact. Most brokers place market orders for the opening on the day following the payment of the dividend. When you sell the fractional portion same process as full shares are sold into the market and the fractional if traded between you and the brokers omnibus account. if it creates a full share for the broker (omnibus has .6 shares and you sell him .5 they would likely flip that out to the street with the full share portion of your order. This would not have impact to outstanding shares and all cost are operational and with the broker handling the Div reinvestment service.","title":""},{"docid":"178519","text":"You can make a rough calculation of the annual turnover rate of stocks by calculating the institutional investors holding of that stock. Institutional investors are the only firms that are required to provide such data. The good this is they usually make the lion share of trading activity. On the other hand, this task might proof arduous A different ratio that could be used as a substitute Share Turnover which is calculated as: Share Turnover gives the number of shares traded as a fraction of the number of shares outstanding. For example, if you compare the results of stock turnover for three companies and the results came as follows: Company A-share turnover: 1.5 Times Company B share turnover: 3 times Company C share turnover: 0.3 times From the results, we can conclude that for a particular period, company C had the least activity and the number of shares traded for that period was only a small fraction of the shares outstanding while other traders of company C hold most shares and never trade them. If you make a cross sectional analysis of a list of businesses you intend to invest in, you could figure which one has the least number of rapidity in the shares traded.","title":""},{"docid":"472537","text":"The price of a share has two components: Bid: The highest price that someone who wants to buy shares is willing to pay for them. Ask: The lowest price that someone who has a share is willing to sell it for. The ask is always higher than the bid, since if they were equal the buyer and seller would have a deal, make a transaction, and that repeats until they are not equal. For stock with high volume, there is usually a very small difference between the bid and ask, but a stock with lower volume could have a major difference. When you say that the share price is $100, that could mean different things. You could be talking about the price that the shares sold for in the most recent transaction (and that might not even be between the current bid and ask), or you could be talking about any of the bid, the ask, or some value in between them. If you have shares that you are interested in selling, then the bid is what you could immediately sell a share for. If you sell a share for $100, that means someone was willing to pay you $100 for it. If after buying it, they still want to buy more for $100 each, or someone else does, then the bid is still $100, and you haven't changed the price. If no one else is willing to pay more than $90 for a share, then the price would drop to $90 next time a transaction takes place and thats what you would be able to immediately sell the next share for.","title":""},{"docid":"133760","text":"\"Buying pressure is when there are more buy orders than sell orders outstanding. Just because someone wants to buy a stock doesn't mean there's a seller ready to fill that order. When there's buying pressure, stock prices rise. When there's selling pressure, stock prices fall. There can be high volume where buying and selling are roughly equal, in which case share prices wouldn't move much. The market makers who actually fill buy and sell orders for stock will raise share prices in the face of buying pressure and lower them in the face of selling pressure. That's because they get to keep the margin between what they bought shares from a seller for and what they can sell them to a new buyer for. Here's an explanation from InvestorPlace.com about \"\"buying pressure\"\": Buying pressure can basically be defined as increasingly higher demand for a particular stock's shares. This demand for shares exceeds the supply and causes the price to rise. ... The strength or weakness of a stock determines how much buying or selling interest will be required to break support and resistance areas. I hope this helps!\"","title":""},{"docid":"303112","text":"\"The answer to your question has to do with the an explanation of \"\"shares authorized, issued and outstanding.\"\" Companies, in their Articles of Incorporation, specify a maximum number of shares they are authorized to issue. For example purposes let's assume Facebook is authorized to issue 100 shares. Let's pretend they have actually issued 75 shares, but only 50 are outstanding (aka Float, i.e. freely trading stock in the market) and stock options total 25 shares. So if someone owns 1 share, what percentage of Facebook do they own? You might think 1/100, or 1%; you might think 1/75, or 1.3%; or you might think 1/50, or 2%. 2% is the answer, but only on a NON-diluted basis. So today someone who owns 1 share owns 2% of Facebook. Tomorrow Facebook announces they just issued 15 shares to Whatsapp to buy the company. Now there are 65 shares outstanding and 90 issued. Now someone who owns 1 share of Facebook own only 1/65, or 1.5% (down from 2%)! P.S. \"\"Valuation\"\" can be thought of as the price of the stock at the time of the purchase announcement.\"","title":""},{"docid":"297032","text":"authorized 100,000,000 shares They cannot issue shares more than that so 102M isn't possible. Common stock - $.01 par value, authorized 100,000,000 shares, issued 51,970,721 and 51,575,743 shares If you look at the right 2 columns it become clear what it means. You missed the $ symbol and on the top (In thousands, except share amounts) ouststanding share 51,970,721 -> 520 On Sept 30, 2014 outstanding shares * 0.01 and rounded off to arrive at 520. ouststanding share 51,575,743 -> 516 On June 30, 2014 outstanding shares * 0.01 and rounded off to arrive at 516.","title":""},{"docid":"139094","text":"\"They are similar in the sense that they are transferring money from the company to shareholders, but that's about it. There is different tax treatment, yes, but that's because they are fundamentally different. Dividends transfer money equally to all shareholders, but that also reduces the value of each share by the same amount, since it's cash out the door, which drops the value of the company. Shareholders are taxed on dividends at the capital gains tax rate. A buyback returns the cash to shareholders who decide to sell. Other shareholders get a secondary benefit of now owning a slightly larger portion of the company since there are fewer shares outstanding. Shareholders only pay tax if they sell shares for a gain. It that means when company buyback their stock, the stock price will definitely go up? Not necessarily. It depends on the price that the company buys back the shares for and what the \"\"opportunity cost\"\" of that cash is - meaning what else could the company have done with the cash that would have been better? Buybacks often happen in mature companies with undervalued stock prices and fewer opportunities for further investment. If a company has an intrinsic value of $10 a share but its stock is trading at $8 a share, then it can instantly get a 25% \"\"return\"\" by buying back stock. I use the term \"\"return\"\" loosely since the company does not actually profit from the buyback, but from the shareholder's perspective the company is worth more per share.\"","title":""},{"docid":"64237","text":"All shares of the same class are considered equal. Each class of shares may have a different preference in order of repayment. After all company liabilities have been paid off [including bank debt, wages owing, taxes outstanding, etc etc.], the remaining cash value in a company is distributed to the shareholders. In general, there are 2 types of shares: Preferred shares, and Common shares. Preferred shares generally have 3 characteristics: (1) they get a stated dividend rate every year, sometimes regardless of company performance; (2) they get paid out first on liquidation; and (3) they can only receive their stated value on liquidation - that is, $1M of preferred shares will be redeemed for at most $1M on liquidation, assuming the corporation has at least that much cash left. Common Shares generally have 4 characteristics: (1) their dividends are not guaranteed (or may be based on a calculation relative to company performance), (2) they can vote for members of the Board of Directors who ultimately hire the CEO and make similar high level business decisions; (3) they get paid last on liquidation; and (4) they get all value remaining in the company once everyone else has been paid. So it is not the order of share subscription that matters, it is the class. Once you know how much each class gets, based on the terms listed in that share subscription, you simply divide the total class payout by number of shares, and pay that much for each share a person holds. For companies organized other-than as corporations, ie: partnerships, the calculation of who-gets-what will be both simpler and more complex. Simpler in that, generally speaking, a partnership interest cannot be of a different 'class', like shares can, meaning all partners are equal relative to the size of their partnership interest. More complex in that, if the initiation of the company was done in an informal way, it could easily become a legal fight as to who contributed what to the company.","title":""},{"docid":"1034","text":"\"What you are describing is a very specific case of the more general principle of how dividend payments work. Broadly speaking, if you own common shares in a corporation, you are a part owner of that corporation; you have the right to a % of all of that corporation's assets. The value in having that right is ultimately because the corporation will pay you dividends while it operates, and perhaps a final dividend when it liquidates at the end of its life. This is why your shares have value - because they give you ownership of the business itself. Now, assume you own 1k shares in a company with 100M shares, worth a total of $5B. You own 0.001% of the company, and each of your shares is worth $50; the total value of all your shares is $50k. Assume further that the value of the company includes $1B in cash. If the company pays out a dividend of $1B, it will now be only worth $4B. Your shares have just gone down in value by 20%! But, you have a right to 0.001% of the dividend, which equals a $10k cash payment to you. Your personal holdings are now $40k worth of shares, plus $10k in cash. Except for taxes, financial theory states that whether a corporation pays a dividend or not should not impact the value to the individual shareholder. The difference between a regular corporation and a mutual fund, is that the mutual fund is actually a pool of various investments, and it reports a breakdown of that pool to you in a different way. If you own shares directly in a corporation, the dividends you receive are called 'dividends', even if you bought them 1 minute before the ex-dividend date. But a payment from a mutual fund can be divided between, for example, a flow through of dividends, interest, or a return of capital. If you 'looked inside' your mutual fund you when you bought it, you would see that 40% of its value comes from stock A, 20% comes from stock B, etc etc., including maybe 1% of the value coming from a pile of cash the fund owns at the time you bought your units. In theory the mutual fund could set aside the cash it holds for current owners only, but then it would need to track everyone's cash-ownership on an individual basis, and there would be thousands of different 'unit classes' based on timing. For simplicity, the mutual fund just says \"\"yes, when you bought $50k in units, we were 1/3 of the year towards paying out a $10k dividend. So of that $10k dividend, $3,333k of it is assumed to have been cash at the time you bought your shares. Instead of being an actual 'dividend', it is simply a return of capital.\"\" By doing this, the mutual fund is able to pay you your owed dividend [otherwise you would still have the same number of units but no cash, meaning you would lose overall value], without forcing you to be taxed on that payment. If the mutual fund didn't do this separate reporting, you would have paid $50k to buy $46,667k of shares and $3,333k of cash, and then you would have paid tax on that cash when it was returned to you. Note that this does not \"\"falsely exaggerate the investment return\"\", because a return of capital is not earnings; that's why it is reported separately. Note that a 'close-ended fund' is not a mutual fund, it is actually a single corporation. You own units in a mutual fund, giving you the rights to a proportion of all the fund's various investments. You own shares in a close-ended fund, just as you would own shares in any other corporation. The mutual fund passes along the interest, dividends, etc. from its investments on to you; the close-ended fund may pay dividends directly to its shareholders, based on its own internal dividend policy.\"","title":""},{"docid":"29306","text":"No - there are additional factors involved. Note that the shares on issue of a company can change for various reasons (such as conversion/redemption of convertible securities, vesting of restricted employee shares, conversion of employee options, employee stock purchase programs, share placements, buybacks, mergers, rights issues etc.) so it is always worthwhile checking SEC announcements for the company if you want an exact figure. There may also be multiple classes of shares and preferred securities that have different levels of dividends present. For PFG, they filed a 10Q on 22 April 2015 and noted they had 294,385,885 shares outstanding of their common stock. They also noted for the three months ended March 31 2014 that dividends were paid to both common stockholders and preferred stockholders and that there were Series A preferred stock (3 million) and Series B preferred stock (10 million), plus a statement: In February 2015, our Board of Directors authorized a share repurchase program of up to $150.0 million of our outstanding common stock. Shares repurchased under these programs are accounted for as treasury stock, carried at cost and reflected as a reduction to stockholders’ equity. Therefore the exact amount of dividend paid out will not be known until the next quarterly report which will state the exact amount of dividend paid out to common and preferred shareholders for the quarter.","title":""},{"docid":"435798","text":"Well, you won't be double taxed based on what you described. Partners are taxed on income, typically distributions. Your gain in the partnership is not income. However, you were essentially given some money which you elected to invest in the partnership, so you need to pay tax on that money. The question becomes, are you being double taxed in another way? Your question doesn't explain how you invested, but pretty much the options are either a payroll deduction (some amount taken out of X paychecks or a bonus) or some other payment to you that was not treated as a payroll deduction. Given that you got a 1099, that suggests the latter. However, if the money was taken out as a payroll deduction - you've already paid taxes (via your W2)! So, I'd double check on that. Regarding why the numbers don't exactly match up - Your shares in the partnership likely transacted before the partnership valuation. Let's illustrate with an example. Say the partnership is currently worth $1000 with 100 outstanding shares. You put up $1000 and get 100 shares. Partnership is now worth $2000 with 200 outstanding shares. However, after a good year for the firm, it's valuation sets the firm's worth at $3000. Your gain is $1500 not $1000. You can also see if what happened was the firm's valuation went down, your gain would be less than your initial investment. If instead your shares transacted immediately after the valuation, then your gain and your cost to acquire the shares would be the same. So again, I'd suggest double checking on this - if your shares transacted after the valuation, there needs to be an explanation for the difference in your gain. For reference: http://smallbusiness.findlaw.com/incorporation-and-legal-structures/partnership-taxes.html And https://www.irs.gov/publications/p541/ar02.html Here you learn the purpose of the gain boxes on your K1 - tracking your capital basis should the partnership sell. Essentially, when the partnership is sold, you as a partner get some money. That money is then taxed. How much you pay will depend on what you received versus what the company was worth and whether your gain was long term or short term. This link doesn't go into that detail, but should give you a thread to pull. I'd also suggest reading more about partnerships and K1 and not just the IRS publications. Don't get me wrong, they're a good source of information, just also dense and sometimes tough to understand. Good luck and congrats.","title":""},{"docid":"34882","text":"Open Google finance and divide the Market Capitalization by the total price. That will give you the total number of shares outstanding. Now see the number of shares you could buy for $1000(40 shares of $25 each or 10 shares of 100 shares each). Now divide the number of shares you own, by the number of shares outstanding in the company and multiply it by 100(i.e (Shares you own/shares Outstanding) * 100). That will give you the percentage or stake of the company you own(With $1000, don't expect it to be a very large number). Now ask your self the question, Is it worth it if I can buy x % of this company for $1000? If the answer is yes, go ahead and buy it. To answer your question in short, NO! it does not matter whether you buy 10 shares for $100 or 40 shares for $25. Cheers","title":""},{"docid":"532171","text":"\"An important thing that many people fail to realize is that the number of shares outstanding in a stock, times the current market price of those shares, does not represent anything related to the total value of those shares. If a company has one million shares outstanding and its total value is $10 million, then the real worth of each share is $10. If few people feels like buying or selling, but a few people think the company is worth $50 million and offer $50/share, that could raise the market price to $50/share, but it wouldn't mean that the company became worth five times as much; it would merely mean the stock was overpriced. If, after the price went to $50/share, all the owners of the stock put in stop-loss orders at $45. Note that the real $10/share \"\"real value\"\" of their stock would never have changed. If the people who thought the stock was worth $50 decided to get out of the market, and nobody else was willing to offer more than $10, that would instantly drop the price to $10. The fact that a million shares of stock have stop-loss orders at $45 wouldn't magically generate buyers for those stocks at that price. Indeed, unchecked stop-loss orders would have the reverse effect, since many people who would have been willing if not eager to buy the stock if it had been available for less than $10/share would instead be trying to sell it below that price. It's too bad people think that the number of shares outstanding times the current market price represents some kind of \"\"meaningful quantity\"\". If the present cash value of all future payouts associated with a share of stock is $10, then someone who buys a share of stock for less than that makes money off the seller; someone who pays more loses money to the seller. Many people think they can lose money to the seller and still come out okay if the price goes higher, but what that really means is that they're hoping to find a bigger sucker--a game where it's guaranteed that some people will have losses they don't recoup.\"","title":""},{"docid":"179737","text":"Contrary to what you might have heard, moving money between mutual funds, whether or not in the same family of funds, is a taxable event, assuming, of course, that the funds are not in tax-deferred retirement accounts. About the only thing that is not taxable is moving funds between share classes in the same mutual fund, e.g. a conversion from what Vanguard refers to as Investor Shares to Admiral Shares in the same fund. In some cases, the Admiral Shares may have a considerably different price (for example, Vanguard Health Care Fund Investor Shares (VGHCX) and Admiral Shares (VGHAX) are priced at $215.83 and $91.04 respectively and so changing from one class to the other changes the number of shares owned considerably while the net value of the investment remains unchanged.","title":""},{"docid":"454610","text":"\"I wonder if ETF's are further removed from the actual underlying holdings or assets giving value to the fund, as compared to regular mutual funds. Not exactly removed. But slightly different. Whenever a Fund want to launch an ETF, it would buy the underlying shares; create units. Lets say it purchased 10 of A, 20 of B and 25 of C. And created 100 units for price x. As part of listing, the ETF company will keep the purchased shares of A,B,C with a custodian. Only then it is allowed to sell the 100 units into the market. Once created, units are bought or sold like regular stock. In case the demand is huge, more units are created and the underlying shares kept with custodian. So, for instance, would VTI and Total Stock Market Index Admiral Shares be equally anchored to the underlying shares of the companies within the index? Yes they are. Are they both connected? Yes to an extent. The way Vanguard is managing this is given a Index [Investment Objective]; it is further splitting the common set of assets into different class. Read more at Share Class. The Portfolio & Management gives out the assets per share class. So Vanguard Total Stock Market Index is a common pool that has VTI ETF, Admiral and Investor Share and possibly Institutional share. Is VTI more of a \"\"derivative\"\"? No it is not a derivative. It is a Mutual Fund.\"","title":""},{"docid":"495066","text":"\"Market Capitalization is the value the market attributes to the company shares calculated by multiplying the current trading price of these shares by the total amount of shares outstanding. So a company with 100 shares trading at $10 has a market cap of $1000. It is technically not the same as the value of a company (in the sense of how much someone would need to pay to acquire the company), Enterprise value is what you want to determine the net value of a company which is calculated as the market capitalization + company debt (as the acquirer has to take on this debt) - company cash (as the acquirer can pocket this for itself). The exact boundary for when a company belongs to a certain \"\"cap\"\" is up for debate. For a \"\"large cap\"\" a market capitalization of $10 billion+ is usually considered the cutoff (with $100+ billion behemoths being called \"\"mega caps\"\"). Anything between $10 billion and ~$1 billion is considered \"\"mid cap\"\", from ~$1billion to ~$200 million it's called a \"\"small cap\"\" and below $200 million is \"\"nano cap\"\". Worth noting that these boundaries change quite dramatically over time as the overall average market capitalization increases as companies grow, for example in the 80s a company with a market cap of $1 billion would be considered \"\"large cap\"\". The market \"\"determines\"\" what the market cap of company should be based (usually but certainly not always!) on the historical and expected profit a company makes, for a simple example let's say that our $1000 market cap company makes $100 a year, this means that this company's earnings per share is $1. If the company grows to make $200 a year you can reasonably expect the share price to rise from $10 to ~$20 with the corresponding increase in market cap. (this is all extremely simplified of course).\"","title":""},{"docid":"135216","text":"\"The market capitalization of a stock is the number of shares outstanding (of each stock class), times the price of last trade (of each stock class). In a liquid market (where there are lots of buyers and sellers at all price points), this represents the price that is between what people are bidding for the stock and what people are asking for the stock. If you offer any small amount more than the last price, there will be a seller, and if you ask any small amount less than the last price, there will be a buyer, at least for a small amount of stock. Thus, in a liquid market, everyone who owns the stock doesn't want to sell at least some of their stock for a bit less than the last trade price, and everyone who doesn't have the stock doesn't want to buy some of the stock for a bit more than the last trade price. With those assumptions, and a low-friction trading environment, we can say that the last trade value is a good midpoint of what people think one share is worth. If we then multiply it by the number of shares, we get an approximation of what the company is worth. In no way, shape or form does it not mean that there is 32 billion more invested in the company, or even used to purchase stock. There are situations where a 32 billion market cap swing could mean 32 billion more money was invested in the company: the company issues a pile of new shares, and takes in the resulting money. People are completely neutral about this gathering in of cash in exchange for dilluting shares. So the share price remains unchanged, the company gains 32 billion dollars, and there are now more shares outstanding. Now, in some sense, there is zero dollars currently invested in a stock; when you buy a stock, you no longer have the money, and the money goes to the person who no longer has the stock. The issue here is the use of the continuous tense of \"\"invested in\"\"; the investment was made at some point, but the money doesn't really stay in this continuous state of being. Unless you consider the investment liquid, and the option to take money out being implicit, it being a continuous action doesn't make much sense. Sometimes the money is invested in the company, when the company causes stocks to come into being and sells them. The owners of stocks has invested money in stocks in that they spent that money to buy the stocks, but the total sum of money ever spent on stocks for a given company is not really a useful value. The market capitalization is an approximation, which under the efficient market hypothesis (that markets find the correct price for things nearly instantly) is reasonably accurate, of the value the company has collectively to its shareholders. The efficient market hypothesis isn't accurate, but it is an acceptable rule of thumb. Now, this value -- market capitalization -- is arguably not the total value of a company: other stakeholders include bond holders, labour, management, various contract counter-parties, government and customers. Some companies are structured so that almost all value is captured not by the stock owners, but by contract counter-parties (this is sometimes used for hiding assets or debts). But for most large publically traded companies, it (in theory) shouldn't be far off.\"","title":""},{"docid":"327560","text":"Generally, when I run across this kind of situation, I look for the Investor Relations section of the corporate website for a 'Stock Information' (or similar) tab or link. This usually contains information explaining the different shares classes, how they relate (if at all), voting and/or dividend rights, and taxation differences for the different classes. However, I have trouble finding such a page on a central BYD corporate investor relations page. I did find this page detailing the HK1211 shares: http://www.byd.com/investor/base_information.html. I don't know what or why, but something tells me this is an older page. Searching on, I also found this page which looks newer and clarifies that the difference you are seeing is between 'A' and 'H' shares. http://www.byd.cn/BYDEnglish/basic/article.jsp?articleId=1524676. (I'm guessing but I'd think somewhere in the announcements on this byd.cn site, you may find more details of any structural differences between share classes -- I just didn't want to page through them all.)","title":""}],"string":"[\n {\n \"docid\": \"313372\",\n \"text\": \"\\\"There are a few other items that you should be aware of when getting options: The strike price is usually determined by an independent valuation of the common shares (called a 409a valuation). This should give you a sense on what the options are worth. Obviously you are hoping that the value becomes many multiple of that. There are two kinds in the US: Non-quals (NQO) and Incentive Stock Options (ISOs). The big difference is that when you exercise Non-quals, you have to pay the tax on the difference between the \\\"\\\"fair\\\"\\\" market value on the shares and what you paid for them (the strike price). This is important because if the company is private, you likely can not sell any shares until it is public. With ISOs, you don't pay any tax (except AMT tax) on the gain until you actually sell the shares. You should know what kind your getting. Some plans allow for early exercise, essentially allowing you to buy the shares early (and given back if you leave before they vest) which helps you establish capital gains treatment earlier as well as avoid AMT if you have ISOs. This is really complicated direction and you would want to talk to a tax professional. And always a good idea to know how many total shares outstanding in the Company. Very few people ask this question but it is helpful for you to understand the overall value of the options.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"582736\",\n \"text\": \"In Australia the ATO can determine if you are considered a shareholder or a share trader. The ATO defines a shareholder as: A shareholder is a person who holds shares for the purpose of earning income from dividends and similar receipts. Whilst they define a share trader as: A share trader is a person who carries out business activities for the purpose of earning income from buying and selling shares. To find out the differences between them you can refer to the following link describing The difference between a share trader and a shareholder. The ATO also describes: To be classed as a share trader, you may be asked to provide evidence that demonstrates you are carrying on a business of share trading, for example: the purchase of shares on a regular basis through a regular or routine method a trading plan use of share trading techniques in managing your share acquisitions, such as decisions based on thorough analysis of relevant market information a contingency plan in the event of a major shift in the market. Losses incurred in the business of share trading are treated the same as any other losses from business. If your activities change from investor to trader, your investment changes from a CGT (capital gains tax) asset to trading stock. This can trigger CGT event for any investments you currently hold as they change from CGT assets to trading stock. Once you have changed over to a trader you will not be entitled to the 50% CGT discount for stocks held over 12 months. You will, however, be able to count any paper losses at the end of Financial Year to reduce your other income.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"427859\",\n \"text\": \"\\\"I think it's easiest to illustrate it with an example... if you've already read any of the definitions out there, then you know what it means, but just don't understand what it means. So, we have an ice cream shop. We started it as partners, and now you and I each own 50% of the company. It's doing so well that we decide to take it public. That means that we will be giving up some of our ownership in return for a chance to own a smaller portion of a bigger thing. With the money that we raise from selling stocks, we're going to open up two more stores. So, without getting into too much of the nitty gritty accounting that would turn this into a valuation question, let's say we are going to put 30% of the company up for sale with these stocks, leaving you and me with 35% each. We file with the SEC saying we're splitting up the company ownership with 100,000 shares, and so you and I each have 35,000 shares and we sell 30,000 to investors. Then, and this depends on the state in the US where you're registering your publicly traded corporation, those shares must be assigned a par value that a shareholder can redeem the shares at. Many corporations will use $1 or 10 cents or something nominal. And we go and find investors who will actually pay us $5 per share for our ice cream shop business. We receive $150,000 in new capital. But when we record that in our accounting, $5 in total capital per share was contributed by investors to the business and is recorded as shareholder's equity. $1 per share (totalling $30,000) goes towards actual shares outstanding, and $4 per share (totalling $120,000) goes towards capital surplus. These amounts will not change unless we issue new stocks. The share prices on the open market can fluctuate, but we rarely would adjust these. Edit: I couldn't see the table before. DumbCoder has already pointed out the equation Capital Surplus = [(Stock Par Value) + (Premium Per Share)] * (Number of Shares) Based on my example, it's easy to deduce what happened in the case you've given in the table. In 2009 your company XYZ had outstanding Common Stock issued for $4,652. That's probably (a) in thousands, and (b) at a par value of $1 per share. On those assumptions we can say that the company has 4,652,000 shares outstanding for Year End 2009. Then, if we guess that's the outstanding shares, we can also calculate the implicit average premium per share: 90,946,000 ÷ 4,652,000 == $19.52. Note that this is the average premium per share, because we don't know when the different stocks were issued at, and it may be that the premiums that investors paid were different. Frankly, we don't care. So clearly since \\\"\\\"Common Stock\\\"\\\" in 2010 is up to $9,303 it means that the company released more stock. Someone else can chime in on whether that means it was specifically a stock split or some other mechanism... it doesn't matter. For understanding this you just need to know that the company put more stock into the marketplace... 9,303 - 4,652 == 4,651(,000) more shares to be exact. With the mechanics of rounding to the thousands, I would guess this was a stock split. Now. What you can also see is that the Capital Surplus also increased. 232,801 - 90,946 == 141,855. The 4,651,000 shares were issued into the market at an average premium of 141,855 ÷ 4,651 == $30.50. So investors probably paid (or were given by the company) an average of $31.50 at this split. Then, in 2011 the company had another small adjustment to its shares outstanding. (The Common Stock went up). And there was a corresponding increase in its Capital Surplus. Without details around the actual stock volumes, it's hard to get more exact. You're also only giving us a portion of the Balance Sheet for your company, so it's hard to go into too much more detail. Hopefully this answers your question though.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"211343\",\n \"text\": \"Investopedia has a good definition. Stock dividends are similar to cash dividends; however, instead of cash, a company pays out stock. Stock splits occur when a company perceives that its stock price may be too high. Stock splits are usually done to increase the liquidity of the stock (more shares outstanding) and to make it more affordable for investors to buy regular lots (a regular lot = 100 shares).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"165855\",\n \"text\": \"\\\"Treasury stock is not really represented in the Balance Sheet as a \\\"\\\"Treasury stock\\\"\\\" line item in the assets. Some companies will break out Treasury Shares as a line item in the \\\"\\\"Shareholders Equity\\\"\\\" heading of the balance sheet but Apple hides it in the \\\"\\\"Shares Issued and Outstanding\\\"\\\" counts under the \\\"\\\"Shareholders Equity\\\"\\\" heading. As of the most recent Q2 2017 quarterly report There are 5,205,815,000 shares issued against 5,336,166,000 shares outstanding. This indicates that Apple is retaining about 130,351,000 shares in treasury. On the Q1 10-Q you can see that Apple had 5,255,423,000 shares issued which indicates roughly 49mm shares were repurchased by the end of Q2. You can roughly verify this by looking at page 18 of the Q2 filing in the summary of the share repurchase program. Repurchased as part of an Accelerated Share Repurchase arrangement bleeds between quarters but from February 2017 through May 2017 there have been 17.5mm shares repurchased. 31mm shares were also repurchased on the open market in Q2. The \\\"\\\"shares issued\\\"\\\" total is on a downward trend as part of Apple's share repurchase initiative that has been underway for the last couple of years.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"324470\",\n \"text\": \"Broadly, there's a bunch of stuff you need to be accounting for that's not reflected in the above, which will impact the A/D profile of an acquisition: * Consideration paid (all cash on substantially the same terms is going to be more accretive than an all-stock transaction...because in the latter, your denominator is much bigger) * Shares outstanding (including repurchases, in-kind dividends and option exercise) * Financing / interest expense * Upside / base / downside case for all of your assumptions - best to have a toggle based on a CHOOSE function that will allow the user to easily toggle between these I'm not sure what EBITDA is getting you. EPS accretion/dilution typically looks at earnings, but you could also look at Cash EPS A/D which measures OCF/shares outstanding. The point is, this really depends on how back of the envelope you want the A/D computation to be. At a minimum, you need an earnings schedule projected over the next 2-3 years, and you need a schedule reflecting outstanding shares over the same time period. Your earnings buildout can have varying degrees of granularity. You can project cost synergies over the forecast period, which most obviously is going to affect your earnings, but you can also drill down further. Financing, transaction fees, etc. Your writeups and writedowns from your B/S combination may result in certain deferred tax items that will affect your bottom line over the forecast period. Your share schedule can also have varying degrees of complexity. One way to do it is to just presume that the company will not issue any more shares, and will not repurchase any shares, and that there will be no options exercised, over the forecast period. This is a bad series of assumptions. It is likely that as options vest, if in the money, they will be exercised, resulting in dilution for existing shareholders. It is also likely that certain preferred shareholders and optionholders are going to experience adjustments to the conversion prices based on antidilution provisions in their securities. These may be but are not always disclosed in the 10K. Last point - models are tools. What are you trying to build an accretion/dilution model for? This will affect and determine the degree of granularity you'll want to go into.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"393439\",\n \"text\": \"Now assume these shares are vested, held for at least 1 year, and are then sold for $5 each. Everything I've read implies that the grantee now owes long-term capital gains taxes on the difference, which would be 10k * ($5 - $1). No. That's exactly what the SO is NQ for. Read more on the differences between ISO and NQSO here. Now assume these shares are vested, held for at least 1 year, and are then sold for $5 each. Everything I've read implies that the grantee now owes long-term capital gains taxes on the difference, which would be 10k * ($5 - $1). At this point you no longer have NQSO, you have RSU. If you filed 83(b) when you exercised, then you pay capital gains tax when they vest. If you didn't - its ordinary income to you. NQSO is a red herring here since once exercised they no longer exist. If you didn't file 83(b), then when the stock vests the difference between the FMV at vest and the money you spent on it when exercising (if any) is considered wages and taxed as ordinary income (+FICA etc). From that point the RSU becomes a regular stock investment and the capital gains clock starts ticking.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"467936\",\n \"text\": \"For the case of spinoffs it reflects the market as activities as the specific steps that have to be followed take place. For example the spinoff of Leidos from SAIC in 2013. (I picked this one becasue I knew some of the details) On September 9, 2013, the Board of Directors of SAIC, Inc.(Ticker Symbol (NYSE):SAI) approved the following: The separation of its technical, engineering and enterprise information technology services business through the distribution of shares of SAIC Gemini, Inc. to stockholders. Each stockholder of record of SAIC, Inc. as of September 19, 2013 (Record Date) will receive one (1) share of SAIC Gemini, Inc. common stock for every seven (7) shares of SAIC, Inc. common stock held by such stockholder as of the Record Date. This distribution will be effective after market close on September 27, 2013 (Distribution Date). After the Distribution Date, SAIC Gemini, Inc. will be renamed Science Applications International Corporation (New SAIC). A one (1) for four (4) reverse stock split of the SAIC, Inc. common stock effective as of Distribution Date. After the Distribution Date, SAIC, Inc. will be renamed Leidos Holdings, Inc. (Leidos). Q 11: What are the different trading markets that may occur between Record Date and Distribution Date? A: Beginning two days prior to the Record Date of September 19, 2013 through the Distribution Date on September 27, 2013, there may be three different trading markets available with respect to SAIC, Inc. and the separation. Stock Ticker – SAI (Regular Way Trading with Due Bills): Shares of SAI common stock that trade on the regular-way market will trade with an entitlement to shares of the New SAIC common stock distributed on the Distribution Date. Purchasers in this market are purchasing both the shares of Leidos and New SAIC common stock. Form of Stock Ticker –SAIC (When Issued Trading): Shares of New SAIC common stock may be traded on a “when-issued” basis. These transactions are made conditionally because the security has been authorized, but not yet issued. Purchasers in this market are only purchasing the shares of New SAIC common stock distributed on the Distribution Date. Form of Stock Ticker – LDOS (Ex-Distribution Trading): Shares that trade on the ex-distribution market will trade without an entitlement to shares of New SAIC common stock distributed on the Distribution Date. Purchasers in this market are only purchasing the shares of Leidos common stock. So the stock price for New SAIC starts a few days before the record date of 19 September 2013, while LDOS (new name for the old SAIC) goes back much earlier. But the company didn't split until after the close of business on 27 September 2013. http://investors.saic.com/sites/saic.investorhq.businesswire.com/files/doc_library/file/GeneralStockholder-QuestionsandAnswers.pdf\",\n \"title\": \"\"\n },\n {\n \"docid\": \"56052\",\n \"text\": \"What I think was being asked (and so this is how I interpreted it) is not the transition from public to private, but a corporation itself buying all its shares back, and as a result having no shareholders. In this case we could envision that all outstanding shares would be become treasury stock. My argument was that this would never happen in a practical setting. Obviously, if you interpret the question differently, for instance to be about all the shares of firm being purchased by someone else (as in a private equity buyout), you get very different answers about practicality. So I'm not disagreeing with you at all, I just read the question differently.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"454224\",\n \"text\": \"A mutual fund has several classes of shares that are charged different fees. Some shares are sold through brokers and carry a sales charge (called load) that compensates the broker in lieu of a fee that the broker would charge the client for the service. Vanguard does not have sales charge on its funds and you don't need to go through a broker to buy its shares; you can buy directly from them. Admiral shares of Vanguard funds are charged lower annual expenses than regular shares (yes, all mutual funds charge expenses for fund adninistration that reduce the return that you get, and Vanguard has some of the lowest expense ratios) but Admiral shares are available only for large investments, typically $50K or so. If you have invested in a Vanguard mutual fund, your shares can be set to automatically convert to Admiral shares when the investment reaches the right level. A mutual fund manager can buy and sell stocks to achieve the objectives of the fund, so what stockes you are invested in as a share holder in a mutual fund will typically be unknown to you on a day-to-day basis. On the other hand, Exchange-traded funds (ETFs) are fixed baskets of stocks, and you can buy shares in the ETF. These shares are bought and sold through a broker (so you pay a transaction fee each time) but expenses are lower since there is no manager to buy and sell stocks: the basket is fixed. Many ETFs follow specific market indexes (e.g. S&P 500). Another difference between ETFs and mutual funds is that you can buy and sell ETFs at any time of the day just as if you could if you held stocks. With mutual funds, any buy and sell requests made during the day are processed at the end of the day and the value of the shares that you buy or sell is determined by the closing price of the stocks held by the mutual fund. With ETFs, you are getting the intra-day price at the time the buy or sell order is executed by your broker.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"581848\",\n \"text\": \"During a stock split the only thing that changes is the number of shares outstanding. Typically a stock splits to lower its price per share. Sometimes if a company's value is falling it will do a reverse split where X shares will be exchanged for Y shares. This is typically done to avoid being de-listed from an exchange if the price per share falls below a certain threshold, usually $1. Again the only thing changing is the number of shares outstanding. A 20 for 1 reverse split means for every 20 shares outstanding the shareholder will be granted one new share. Example X Co. has 1,000,000 shares outstanding for a price of $100 per share. It does a 1 for 10 split. Now there are 10,000,000 shares outstanding for a price of $10 per share. Example Y Co has 1,000,000 shares outstanding for a price of $1 per share. It does a 10 for 1 reverse split. Now there are 100,000 shares outstanding for a price of $10. Quickly looking at the news for ASTI it looks like it underwent a 20 for 1 reverse split. You should probably look at your statements and ask your broker how the arithmetic worked in your case. Investopedia links for Reverse Stock Split and Stock Split\",\n \"title\": \"\"\n },\n {\n \"docid\": \"99947\",\n \"text\": \"I have been asking myself a similar question about the financial statements of Weyerhaeuser. In response to Dheer's comment, whilst treasury shares are treated as a negative, it is issued shares less treasury shares (the negative) which gives the outstanding shares. So the original query remains unanswered. I've searched several sources and all state that outstanding shares will never be greater than issued shares. I've realized that the shares referred to are those authorized followed by those issued and outstanding (current year and prior year respectively) i.e. the shares that are both issued and outstanding as they must be issued in order to be outstanding This is supported in the example of Weyerhaeuser as there was a large increase in shares during Q1 2016 as a result of their merger with Plum Creek. Shares issued and outstanding are 510 million and 759 million respectively.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"595796\",\n \"text\": \"The Brokerage firm will purchase shares for the dividend paid in a omnibus account for the security of the issuer and then they will distribute fractional shares among all their clients that chose Div Reinvest. They will only have to buy 1 extra share to account for the fractional portion of what they allocate. The structure of the market does not permit trading of fractional shares. There is generally not any impact to the market place for Div Reinvest with the exception of certain securities that pay large dividends that are not liquid. sometimes this occurs in preferred securities where a large amount of Div reinvestment could create a large market order that has market impact. Most brokers place market orders for the opening on the day following the payment of the dividend. When you sell the fractional portion same process as full shares are sold into the market and the fractional if traded between you and the brokers omnibus account. if it creates a full share for the broker (omnibus has .6 shares and you sell him .5 they would likely flip that out to the street with the full share portion of your order. This would not have impact to outstanding shares and all cost are operational and with the broker handling the Div reinvestment service.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"178519\",\n \"text\": \"You can make a rough calculation of the annual turnover rate of stocks by calculating the institutional investors holding of that stock. Institutional investors are the only firms that are required to provide such data. The good this is they usually make the lion share of trading activity. On the other hand, this task might proof arduous A different ratio that could be used as a substitute Share Turnover which is calculated as: Share Turnover gives the number of shares traded as a fraction of the number of shares outstanding. For example, if you compare the results of stock turnover for three companies and the results came as follows: Company A-share turnover: 1.5 Times Company B share turnover: 3 times Company C share turnover: 0.3 times From the results, we can conclude that for a particular period, company C had the least activity and the number of shares traded for that period was only a small fraction of the shares outstanding while other traders of company C hold most shares and never trade them. If you make a cross sectional analysis of a list of businesses you intend to invest in, you could figure which one has the least number of rapidity in the shares traded.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"472537\",\n \"text\": \"The price of a share has two components: Bid: The highest price that someone who wants to buy shares is willing to pay for them. Ask: The lowest price that someone who has a share is willing to sell it for. The ask is always higher than the bid, since if they were equal the buyer and seller would have a deal, make a transaction, and that repeats until they are not equal. For stock with high volume, there is usually a very small difference between the bid and ask, but a stock with lower volume could have a major difference. When you say that the share price is $100, that could mean different things. You could be talking about the price that the shares sold for in the most recent transaction (and that might not even be between the current bid and ask), or you could be talking about any of the bid, the ask, or some value in between them. If you have shares that you are interested in selling, then the bid is what you could immediately sell a share for. If you sell a share for $100, that means someone was willing to pay you $100 for it. If after buying it, they still want to buy more for $100 each, or someone else does, then the bid is still $100, and you haven't changed the price. If no one else is willing to pay more than $90 for a share, then the price would drop to $90 next time a transaction takes place and thats what you would be able to immediately sell the next share for.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"133760\",\n \"text\": \"\\\"Buying pressure is when there are more buy orders than sell orders outstanding. Just because someone wants to buy a stock doesn't mean there's a seller ready to fill that order. When there's buying pressure, stock prices rise. When there's selling pressure, stock prices fall. There can be high volume where buying and selling are roughly equal, in which case share prices wouldn't move much. The market makers who actually fill buy and sell orders for stock will raise share prices in the face of buying pressure and lower them in the face of selling pressure. That's because they get to keep the margin between what they bought shares from a seller for and what they can sell them to a new buyer for. Here's an explanation from InvestorPlace.com about \\\"\\\"buying pressure\\\"\\\": Buying pressure can basically be defined as increasingly higher demand for a particular stock's shares. This demand for shares exceeds the supply and causes the price to rise. ... The strength or weakness of a stock determines how much buying or selling interest will be required to break support and resistance areas. I hope this helps!\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"303112\",\n \"text\": \"\\\"The answer to your question has to do with the an explanation of \\\"\\\"shares authorized, issued and outstanding.\\\"\\\" Companies, in their Articles of Incorporation, specify a maximum number of shares they are authorized to issue. For example purposes let's assume Facebook is authorized to issue 100 shares. Let's pretend they have actually issued 75 shares, but only 50 are outstanding (aka Float, i.e. freely trading stock in the market) and stock options total 25 shares. So if someone owns 1 share, what percentage of Facebook do they own? You might think 1/100, or 1%; you might think 1/75, or 1.3%; or you might think 1/50, or 2%. 2% is the answer, but only on a NON-diluted basis. So today someone who owns 1 share owns 2% of Facebook. Tomorrow Facebook announces they just issued 15 shares to Whatsapp to buy the company. Now there are 65 shares outstanding and 90 issued. Now someone who owns 1 share of Facebook own only 1/65, or 1.5% (down from 2%)! P.S. \\\"\\\"Valuation\\\"\\\" can be thought of as the price of the stock at the time of the purchase announcement.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"297032\",\n \"text\": \"authorized 100,000,000 shares They cannot issue shares more than that so 102M isn't possible. Common stock - $.01 par value, authorized 100,000,000 shares, issued 51,970,721 and 51,575,743 shares If you look at the right 2 columns it become clear what it means. You missed the $ symbol and on the top (In thousands, except share amounts) ouststanding share 51,970,721 -> 520 On Sept 30, 2014 outstanding shares * 0.01 and rounded off to arrive at 520. ouststanding share 51,575,743 -> 516 On June 30, 2014 outstanding shares * 0.01 and rounded off to arrive at 516.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"139094\",\n \"text\": \"\\\"They are similar in the sense that they are transferring money from the company to shareholders, but that's about it. There is different tax treatment, yes, but that's because they are fundamentally different. Dividends transfer money equally to all shareholders, but that also reduces the value of each share by the same amount, since it's cash out the door, which drops the value of the company. Shareholders are taxed on dividends at the capital gains tax rate. A buyback returns the cash to shareholders who decide to sell. Other shareholders get a secondary benefit of now owning a slightly larger portion of the company since there are fewer shares outstanding. Shareholders only pay tax if they sell shares for a gain. It that means when company buyback their stock, the stock price will definitely go up? Not necessarily. It depends on the price that the company buys back the shares for and what the \\\"\\\"opportunity cost\\\"\\\" of that cash is - meaning what else could the company have done with the cash that would have been better? Buybacks often happen in mature companies with undervalued stock prices and fewer opportunities for further investment. If a company has an intrinsic value of $10 a share but its stock is trading at $8 a share, then it can instantly get a 25% \\\"\\\"return\\\"\\\" by buying back stock. I use the term \\\"\\\"return\\\"\\\" loosely since the company does not actually profit from the buyback, but from the shareholder's perspective the company is worth more per share.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"64237\",\n \"text\": \"All shares of the same class are considered equal. Each class of shares may have a different preference in order of repayment. After all company liabilities have been paid off [including bank debt, wages owing, taxes outstanding, etc etc.], the remaining cash value in a company is distributed to the shareholders. In general, there are 2 types of shares: Preferred shares, and Common shares. Preferred shares generally have 3 characteristics: (1) they get a stated dividend rate every year, sometimes regardless of company performance; (2) they get paid out first on liquidation; and (3) they can only receive their stated value on liquidation - that is, $1M of preferred shares will be redeemed for at most $1M on liquidation, assuming the corporation has at least that much cash left. Common Shares generally have 4 characteristics: (1) their dividends are not guaranteed (or may be based on a calculation relative to company performance), (2) they can vote for members of the Board of Directors who ultimately hire the CEO and make similar high level business decisions; (3) they get paid last on liquidation; and (4) they get all value remaining in the company once everyone else has been paid. So it is not the order of share subscription that matters, it is the class. Once you know how much each class gets, based on the terms listed in that share subscription, you simply divide the total class payout by number of shares, and pay that much for each share a person holds. For companies organized other-than as corporations, ie: partnerships, the calculation of who-gets-what will be both simpler and more complex. Simpler in that, generally speaking, a partnership interest cannot be of a different 'class', like shares can, meaning all partners are equal relative to the size of their partnership interest. More complex in that, if the initiation of the company was done in an informal way, it could easily become a legal fight as to who contributed what to the company.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1034\",\n \"text\": \"\\\"What you are describing is a very specific case of the more general principle of how dividend payments work. Broadly speaking, if you own common shares in a corporation, you are a part owner of that corporation; you have the right to a % of all of that corporation's assets. The value in having that right is ultimately because the corporation will pay you dividends while it operates, and perhaps a final dividend when it liquidates at the end of its life. This is why your shares have value - because they give you ownership of the business itself. Now, assume you own 1k shares in a company with 100M shares, worth a total of $5B. You own 0.001% of the company, and each of your shares is worth $50; the total value of all your shares is $50k. Assume further that the value of the company includes $1B in cash. If the company pays out a dividend of $1B, it will now be only worth $4B. Your shares have just gone down in value by 20%! But, you have a right to 0.001% of the dividend, which equals a $10k cash payment to you. Your personal holdings are now $40k worth of shares, plus $10k in cash. Except for taxes, financial theory states that whether a corporation pays a dividend or not should not impact the value to the individual shareholder. The difference between a regular corporation and a mutual fund, is that the mutual fund is actually a pool of various investments, and it reports a breakdown of that pool to you in a different way. If you own shares directly in a corporation, the dividends you receive are called 'dividends', even if you bought them 1 minute before the ex-dividend date. But a payment from a mutual fund can be divided between, for example, a flow through of dividends, interest, or a return of capital. If you 'looked inside' your mutual fund you when you bought it, you would see that 40% of its value comes from stock A, 20% comes from stock B, etc etc., including maybe 1% of the value coming from a pile of cash the fund owns at the time you bought your units. In theory the mutual fund could set aside the cash it holds for current owners only, but then it would need to track everyone's cash-ownership on an individual basis, and there would be thousands of different 'unit classes' based on timing. For simplicity, the mutual fund just says \\\"\\\"yes, when you bought $50k in units, we were 1/3 of the year towards paying out a $10k dividend. So of that $10k dividend, $3,333k of it is assumed to have been cash at the time you bought your shares. Instead of being an actual 'dividend', it is simply a return of capital.\\\"\\\" By doing this, the mutual fund is able to pay you your owed dividend [otherwise you would still have the same number of units but no cash, meaning you would lose overall value], without forcing you to be taxed on that payment. If the mutual fund didn't do this separate reporting, you would have paid $50k to buy $46,667k of shares and $3,333k of cash, and then you would have paid tax on that cash when it was returned to you. Note that this does not \\\"\\\"falsely exaggerate the investment return\\\"\\\", because a return of capital is not earnings; that's why it is reported separately. Note that a 'close-ended fund' is not a mutual fund, it is actually a single corporation. You own units in a mutual fund, giving you the rights to a proportion of all the fund's various investments. You own shares in a close-ended fund, just as you would own shares in any other corporation. The mutual fund passes along the interest, dividends, etc. from its investments on to you; the close-ended fund may pay dividends directly to its shareholders, based on its own internal dividend policy.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"29306\",\n \"text\": \"No - there are additional factors involved. Note that the shares on issue of a company can change for various reasons (such as conversion/redemption of convertible securities, vesting of restricted employee shares, conversion of employee options, employee stock purchase programs, share placements, buybacks, mergers, rights issues etc.) so it is always worthwhile checking SEC announcements for the company if you want an exact figure. There may also be multiple classes of shares and preferred securities that have different levels of dividends present. For PFG, they filed a 10Q on 22 April 2015 and noted they had 294,385,885 shares outstanding of their common stock. They also noted for the three months ended March 31 2014 that dividends were paid to both common stockholders and preferred stockholders and that there were Series A preferred stock (3 million) and Series B preferred stock (10 million), plus a statement: In February 2015, our Board of Directors authorized a share repurchase program of up to $150.0 million of our outstanding common stock. Shares repurchased under these programs are accounted for as treasury stock, carried at cost and reflected as a reduction to stockholders’ equity. Therefore the exact amount of dividend paid out will not be known until the next quarterly report which will state the exact amount of dividend paid out to common and preferred shareholders for the quarter.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"435798\",\n \"text\": \"Well, you won't be double taxed based on what you described. Partners are taxed on income, typically distributions. Your gain in the partnership is not income. However, you were essentially given some money which you elected to invest in the partnership, so you need to pay tax on that money. The question becomes, are you being double taxed in another way? Your question doesn't explain how you invested, but pretty much the options are either a payroll deduction (some amount taken out of X paychecks or a bonus) or some other payment to you that was not treated as a payroll deduction. Given that you got a 1099, that suggests the latter. However, if the money was taken out as a payroll deduction - you've already paid taxes (via your W2)! So, I'd double check on that. Regarding why the numbers don't exactly match up - Your shares in the partnership likely transacted before the partnership valuation. Let's illustrate with an example. Say the partnership is currently worth $1000 with 100 outstanding shares. You put up $1000 and get 100 shares. Partnership is now worth $2000 with 200 outstanding shares. However, after a good year for the firm, it's valuation sets the firm's worth at $3000. Your gain is $1500 not $1000. You can also see if what happened was the firm's valuation went down, your gain would be less than your initial investment. If instead your shares transacted immediately after the valuation, then your gain and your cost to acquire the shares would be the same. So again, I'd suggest double checking on this - if your shares transacted after the valuation, there needs to be an explanation for the difference in your gain. For reference: http://smallbusiness.findlaw.com/incorporation-and-legal-structures/partnership-taxes.html And https://www.irs.gov/publications/p541/ar02.html Here you learn the purpose of the gain boxes on your K1 - tracking your capital basis should the partnership sell. Essentially, when the partnership is sold, you as a partner get some money. That money is then taxed. How much you pay will depend on what you received versus what the company was worth and whether your gain was long term or short term. This link doesn't go into that detail, but should give you a thread to pull. I'd also suggest reading more about partnerships and K1 and not just the IRS publications. Don't get me wrong, they're a good source of information, just also dense and sometimes tough to understand. Good luck and congrats.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"34882\",\n \"text\": \"Open Google finance and divide the Market Capitalization by the total price. That will give you the total number of shares outstanding. Now see the number of shares you could buy for $1000(40 shares of $25 each or 10 shares of 100 shares each). Now divide the number of shares you own, by the number of shares outstanding in the company and multiply it by 100(i.e (Shares you own/shares Outstanding) * 100). That will give you the percentage or stake of the company you own(With $1000, don't expect it to be a very large number). Now ask your self the question, Is it worth it if I can buy x % of this company for $1000? If the answer is yes, go ahead and buy it. To answer your question in short, NO! it does not matter whether you buy 10 shares for $100 or 40 shares for $25. Cheers\",\n \"title\": \"\"\n },\n {\n \"docid\": \"532171\",\n \"text\": \"\\\"An important thing that many people fail to realize is that the number of shares outstanding in a stock, times the current market price of those shares, does not represent anything related to the total value of those shares. If a company has one million shares outstanding and its total value is $10 million, then the real worth of each share is $10. If few people feels like buying or selling, but a few people think the company is worth $50 million and offer $50/share, that could raise the market price to $50/share, but it wouldn't mean that the company became worth five times as much; it would merely mean the stock was overpriced. If, after the price went to $50/share, all the owners of the stock put in stop-loss orders at $45. Note that the real $10/share \\\"\\\"real value\\\"\\\" of their stock would never have changed. If the people who thought the stock was worth $50 decided to get out of the market, and nobody else was willing to offer more than $10, that would instantly drop the price to $10. The fact that a million shares of stock have stop-loss orders at $45 wouldn't magically generate buyers for those stocks at that price. Indeed, unchecked stop-loss orders would have the reverse effect, since many people who would have been willing if not eager to buy the stock if it had been available for less than $10/share would instead be trying to sell it below that price. It's too bad people think that the number of shares outstanding times the current market price represents some kind of \\\"\\\"meaningful quantity\\\"\\\". If the present cash value of all future payouts associated with a share of stock is $10, then someone who buys a share of stock for less than that makes money off the seller; someone who pays more loses money to the seller. Many people think they can lose money to the seller and still come out okay if the price goes higher, but what that really means is that they're hoping to find a bigger sucker--a game where it's guaranteed that some people will have losses they don't recoup.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"179737\",\n \"text\": \"Contrary to what you might have heard, moving money between mutual funds, whether or not in the same family of funds, is a taxable event, assuming, of course, that the funds are not in tax-deferred retirement accounts. About the only thing that is not taxable is moving funds between share classes in the same mutual fund, e.g. a conversion from what Vanguard refers to as Investor Shares to Admiral Shares in the same fund. In some cases, the Admiral Shares may have a considerably different price (for example, Vanguard Health Care Fund Investor Shares (VGHCX) and Admiral Shares (VGHAX) are priced at $215.83 and $91.04 respectively and so changing from one class to the other changes the number of shares owned considerably while the net value of the investment remains unchanged.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"454610\",\n \"text\": \"\\\"I wonder if ETF's are further removed from the actual underlying holdings or assets giving value to the fund, as compared to regular mutual funds. Not exactly removed. But slightly different. Whenever a Fund want to launch an ETF, it would buy the underlying shares; create units. Lets say it purchased 10 of A, 20 of B and 25 of C. And created 100 units for price x. As part of listing, the ETF company will keep the purchased shares of A,B,C with a custodian. Only then it is allowed to sell the 100 units into the market. Once created, units are bought or sold like regular stock. In case the demand is huge, more units are created and the underlying shares kept with custodian. So, for instance, would VTI and Total Stock Market Index Admiral Shares be equally anchored to the underlying shares of the companies within the index? Yes they are. Are they both connected? Yes to an extent. The way Vanguard is managing this is given a Index [Investment Objective]; it is further splitting the common set of assets into different class. Read more at Share Class. The Portfolio & Management gives out the assets per share class. So Vanguard Total Stock Market Index is a common pool that has VTI ETF, Admiral and Investor Share and possibly Institutional share. Is VTI more of a \\\"\\\"derivative\\\"\\\"? No it is not a derivative. It is a Mutual Fund.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"495066\",\n \"text\": \"\\\"Market Capitalization is the value the market attributes to the company shares calculated by multiplying the current trading price of these shares by the total amount of shares outstanding. So a company with 100 shares trading at $10 has a market cap of $1000. It is technically not the same as the value of a company (in the sense of how much someone would need to pay to acquire the company), Enterprise value is what you want to determine the net value of a company which is calculated as the market capitalization + company debt (as the acquirer has to take on this debt) - company cash (as the acquirer can pocket this for itself). The exact boundary for when a company belongs to a certain \\\"\\\"cap\\\"\\\" is up for debate. For a \\\"\\\"large cap\\\"\\\" a market capitalization of $10 billion+ is usually considered the cutoff (with $100+ billion behemoths being called \\\"\\\"mega caps\\\"\\\"). Anything between $10 billion and ~$1 billion is considered \\\"\\\"mid cap\\\"\\\", from ~$1billion to ~$200 million it's called a \\\"\\\"small cap\\\"\\\" and below $200 million is \\\"\\\"nano cap\\\"\\\". Worth noting that these boundaries change quite dramatically over time as the overall average market capitalization increases as companies grow, for example in the 80s a company with a market cap of $1 billion would be considered \\\"\\\"large cap\\\"\\\". The market \\\"\\\"determines\\\"\\\" what the market cap of company should be based (usually but certainly not always!) on the historical and expected profit a company makes, for a simple example let's say that our $1000 market cap company makes $100 a year, this means that this company's earnings per share is $1. If the company grows to make $200 a year you can reasonably expect the share price to rise from $10 to ~$20 with the corresponding increase in market cap. (this is all extremely simplified of course).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"135216\",\n \"text\": \"\\\"The market capitalization of a stock is the number of shares outstanding (of each stock class), times the price of last trade (of each stock class). In a liquid market (where there are lots of buyers and sellers at all price points), this represents the price that is between what people are bidding for the stock and what people are asking for the stock. If you offer any small amount more than the last price, there will be a seller, and if you ask any small amount less than the last price, there will be a buyer, at least for a small amount of stock. Thus, in a liquid market, everyone who owns the stock doesn't want to sell at least some of their stock for a bit less than the last trade price, and everyone who doesn't have the stock doesn't want to buy some of the stock for a bit more than the last trade price. With those assumptions, and a low-friction trading environment, we can say that the last trade value is a good midpoint of what people think one share is worth. If we then multiply it by the number of shares, we get an approximation of what the company is worth. In no way, shape or form does it not mean that there is 32 billion more invested in the company, or even used to purchase stock. There are situations where a 32 billion market cap swing could mean 32 billion more money was invested in the company: the company issues a pile of new shares, and takes in the resulting money. People are completely neutral about this gathering in of cash in exchange for dilluting shares. So the share price remains unchanged, the company gains 32 billion dollars, and there are now more shares outstanding. Now, in some sense, there is zero dollars currently invested in a stock; when you buy a stock, you no longer have the money, and the money goes to the person who no longer has the stock. The issue here is the use of the continuous tense of \\\"\\\"invested in\\\"\\\"; the investment was made at some point, but the money doesn't really stay in this continuous state of being. Unless you consider the investment liquid, and the option to take money out being implicit, it being a continuous action doesn't make much sense. Sometimes the money is invested in the company, when the company causes stocks to come into being and sells them. The owners of stocks has invested money in stocks in that they spent that money to buy the stocks, but the total sum of money ever spent on stocks for a given company is not really a useful value. The market capitalization is an approximation, which under the efficient market hypothesis (that markets find the correct price for things nearly instantly) is reasonably accurate, of the value the company has collectively to its shareholders. The efficient market hypothesis isn't accurate, but it is an acceptable rule of thumb. Now, this value -- market capitalization -- is arguably not the total value of a company: other stakeholders include bond holders, labour, management, various contract counter-parties, government and customers. Some companies are structured so that almost all value is captured not by the stock owners, but by contract counter-parties (this is sometimes used for hiding assets or debts). But for most large publically traded companies, it (in theory) shouldn't be far off.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"327560\",\n \"text\": \"Generally, when I run across this kind of situation, I look for the Investor Relations section of the corporate website for a 'Stock Information' (or similar) tab or link. This usually contains information explaining the different shares classes, how they relate (if at all), voting and/or dividend rights, and taxation differences for the different classes. However, I have trouble finding such a page on a central BYD corporate investor relations page. I did find this page detailing the HK1211 shares: http://www.byd.com/investor/base_information.html. I don't know what or why, but something tells me this is an older page. Searching on, I also found this page which looks newer and clarifies that the difference you are seeing is between 'A' and 'H' shares. http://www.byd.cn/BYDEnglish/basic/article.jsp?articleId=1524676. (I'm guessing but I'd think somewhere in the announcements on this byd.cn site, you may find more details of any structural differences between share classes -- I just didn't want to page through them all.)\",\n \"title\": \"\"\n }\n]"}}}],"truncated":false,"partial":false},"paginationData":{"pageIndex":26,"numItemsPerPage":100,"numTotalItems":3240,"offset":2600,"length":100}},"jwt":"eyJhbGciOiJFZERTQSJ9.eyJyZWFkIjp0cnVlLCJwZXJtaXNzaW9ucyI6eyJyZXBvLmNvbnRlbnQucmVhZCI6dHJ1ZX0sImlhdCI6MTc1ODQyMDcyMCwic3ViIjoiL2RhdGFzZXRzL3Nza3RvcmEvbmZjb3JwdXMtc2NpZmFjdC1maXFhLWZldmVyLWhvdHBvdHFhLWNvbWJpbmUtNjQ4IiwiZXhwIjoxNzU4NDI0MzIwLCJpc3MiOiJodHRwczovL2h1Z2dpbmdmYWNlLmNvIn0.WXECmf9Ew6_6rWZth5CsGTq6qEd0LQvg9UK_l6oxjW80id_B-YUwddfKCAr8ZdD4IVi6CQ_hoimP1elK4ucXDQ","displayUrls":true},"discussionsStats":{"closed":0,"open":1,"total":1},"fullWidth":true,"hasGatedAccess":true,"hasFullAccess":true,"isEmbedded":false,"savedQueries":{"community":[],"user":[]}}">
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5ab73b5c554299110f219ad6
|
Between Rooney and Lostprophets, which group has more members?
|
[
{
"docid": "492820",
"text": "Lostprophets were a Welsh rock band from Pontypridd, Wales formed in 1997. Founded by lead vocalist and lyricist Ian Watkins, bassist (later guitarist) Mike Lewis, drummer Mike Chiplin and guitarist Lee Gaze, they were originally a side-project to hardcore punk band Public Disturbance. They were also part of the Cardiff music scene.",
"title": ""
},
{
"docid": "918821",
"text": "Rooney is the primary musical project of singer-songwriter Robert Schwartzman, evolving from its origin as an American rock band formed by high school friends in Los Angeles. Before Schwartzman decided to continue the project in a different direction, the band's most enduring line-up consisted of Schwartzman (lead vocals, guitar), Louie Stephens (keyboards, piano), Taylor Locke (lead guitar, backing vocals), Matthew Winter (bass guitar) and Ned Brower (drums, backing vocals). The band is named after Ed Rooney, the principal in \"Ferris Bueller's Day Off\".",
"title": ""
}
] |
[
{
"docid": "18625043",
"text": "Buchanan Ingersoll & Rooney PC is a large U.S. law firm and lobbying group based in Pittsburgh, Pennsylvania. The firm has more than 500 lawyers in offices in eighteen cities nationwide.",
"title": ""
},
{
"docid": "20002490",
"text": "Albert \"Al\" Rooney (1892-?) was an American gang leader and founder of the Fourteenth Street Gang. One of the independent gangs allied with Monk Eastman, most of them former members of the Humpty Jackson gang, Rooney led the group from the mid-to late 1900s (decade) until the New York City Police Department launched a four-year citywide campaign to break up the countless street gangs operating in the city between 1910 and 1914. Rooney was one of the first gang leaders to be imprisoned and, with his conviction of second degree murder in 1911, is considered one of the last generation gang captains of the \"Gangs of New York\" period.",
"title": ""
},
{
"docid": "54398673",
"text": "Group threat theory is a sociological theory which proposes that the larger the size of an outgroup, the more the corresponding ingroup perceives it to threaten its own interests, resulting in the ingroup members having more negative attitudes toward the outgroup. It is based on the work of Herbert Blumer and Hubert M. Blalock, Jr. in the 1950s and 1960s, and has since been supported by multiple studies. Other studies, however, have not found support for the theory. Its predictions are contrary to those of the contact hypothesis, which posits that greater proximity between racial/ethnic groups increases harmony between them.",
"title": ""
},
{
"docid": "10471105",
"text": "Mickey Rooney Jr. (born Joseph Yule III; July 3, 1945) is an American former actor, and the eldest son of the actor Mickey Rooney. He operates the Rooney Entertainment Group, a movie and TV production company. He is a born-again Christian, and he has an evangelical ministry in Hemet, California.",
"title": ""
},
{
"docid": "2140810",
"text": "Cory Rooney (born Mark Cory Rooney) is an Grammy Award Winning American songwriter, record producer, and C.E.O. of Cory Rooney Group. He has written, produced, and developed many successful songs and careers for artists including Mariah Carey, Mary J. Blige, Jessica Simpson, Jennifer Lopez, Marc Anthony, Thalia, Michael Jackson, and Destiny's Child.",
"title": ""
},
{
"docid": "43190994",
"text": "No Devotion are a Welsh/American alternative rock band formed in 2014. They are composed of American vocalist Geoff Rickly (of the band Thursday) from New Jersey, and former band members of the Welsh band Lostprophets. The band formed in the wake of Lostprophets' dissolution in 2013.",
"title": ""
},
{
"docid": "905619",
"text": "Geoffrey William \"Geoff\" Rickly (born March 8, 1979) is an American musician, best known as the lead singer and songwriter of rock band Thursday. Rickly is also a member of hardcore punk band United Nations, and the alternative rock group No Devotion with former members of Lostprophets, and is the founder of the record label Collect Records.",
"title": ""
},
{
"docid": "1196269",
"text": "Daniel Milton Rooney (July 20, 1932 – April 13, 2017) was chairman of the Pittsburgh Steelers, an American football team in the National Football League (NFL), and son of the Steelers' founder, Art Rooney. Dan Rooney was elected to the Pro Football Hall of Fame in 2000 for his contributions to the game. He was credited with spearheading a requirement that NFL teams with head coach and general manager vacancies interview at least one minority candidate, which has become known as the \"Rooney Rule\".",
"title": ""
},
{
"docid": "31092755",
"text": "The Mickey Rooney Show (also known as Hey, Mulligan) is an American sitcom that aired from 1954 to 1955 on NBC. The series stars Mickey Rooney (in his first television role) who was particularly remembered for his starring role in numerous Andy Hardy films made between 1937 and 1958, which overlapped with \"Hey Mulligan\".",
"title": ""
},
{
"docid": "3590967",
"text": "Ian David Karslake Watkins (born 30 July 1977) is a Welsh singer, musician, and convicted sex offender. He achieved prominence as a founding member, lead vocalist, and lyricist of the rock band Lostprophets. Lostprophets disbanded in 2013 after Watkins was charged with sexual offences in late 2012. In November 2013, he pleaded guilty to 13 charges, including the attempted rape and sexual assault of a child under 13; these offences were committed against the infant children of two women who were also convicted. He was subsequently jailed for 29 years and ordered to serve a further six years on extended licence.",
"title": ""
},
{
"docid": "34634004",
"text": "This is the complete list of songs by Welsh alternative rock band Lostprophets. Lostprophets have three EPs, five studio albums and sixteen singles.",
"title": ""
},
{
"docid": "30042974",
"text": "In the design of experiments, a between-group design is an experiment that has two or more groups of subjects each being tested by a different testing factor simultaneously. This design is usually used in place of, or in some cases in conjunction with, the within-subject design, which applies the same variations of conditions to each subject to observe the reactions. The simplest between-group design occurs with two groups; one is generally regarded as the treatment group, which receives the ‘special’ treatment, (that is, is treated with some variable) and the control group, which receives no variable treatment and is used as a reference (prove that any deviation in results from the treatment group is, indeed, a direct result of the variable.) The between-group design is widely used in psychological, economic, and sociological experiments, as well as in several other fields in the natural or social sciences.",
"title": ""
},
{
"docid": "1547062",
"text": "The Ringelmann effect is the tendency for individual members of a group to become increasingly less productive as the size of their group increases. This effect, discovered by French agricultural engineer Maximilien Ringelmann (1861–1931), illustrates the inverse relationship that exists between the size of a group and the magnitude of group members’ individual contribution to the completion of a task. While studying the relationship between process loss (i.e., reductions in performance effectiveness or efficiency) and group productivity, Ringelmann (1913) found that having group members work together on a task (e.g., pulling a rope) actually results in significantly less effort than when individual members are acting alone. Furthermore, Ringelmann discovered that as more and more people are added to a group, the group often becomes increasingly inefficient, ultimately violating the notion that group effort and team participation reliably leads to increased effort on behalf of the members.",
"title": ""
},
{
"docid": "39292021",
"text": "Patrick Rooney Jr. (born February 9, 1964) is a Republican member of the Florida House of Representatives, representing the 85th District, which includes northern Palm Beach County, since 2012, previously representing the 83rd District from 2010 to 2012.",
"title": ""
},
{
"docid": "295069",
"text": "The Exciters were an American pop music group of the 1960s. They were originally a girl group, with one male member being added afterwards. At the height of their popularity the group consisted of lead singer Brenda Reid, her husband Herb Rooney, Carolyn Johnson and Lillian Walker.",
"title": ""
},
{
"docid": "19107850",
"text": "Thomas Joseph Rooney (born November 21, 1970) is the U.S. Representative for Florida 's 17 congressional district , a post he has held since 2012. He previously represented Florida 's 16 congressional district from 2009 to 2013. He is a member of the Republican Party.",
"title": ""
},
{
"docid": "9691786",
"text": "Buddhism in Iceland has existed since the 1990s after immigration from countries with Buddhist populations, mainly Thailand. As of 2008, there are three Buddhist organizations in Iceland officially recognized as religious organizations by the Icelandic government. The oldest and largest is the Buddhist Association of Iceland, a Theravada group, which was recognized in 1996 and had 880 members in 2010. Another group, Zen in Iceland – Night Pasture, a Zen group, was recognized in 1999 and had 75 members in 2010. The most recent group is, SGI in Iceland, a Soka Gakkai group, which was recognized in 2008 with 135 members. Together, these three organizations represent approximately 0.3% of the population of Iceland. This is more than the Islamic groups but less than the pagan groups.",
"title": ""
},
{
"docid": "7509903",
"text": "William James McAuley III (born July 18, 1975), best known by his performing name, Bleu, is an American pop artist (singer-songwriter), professional songwriter and producer currently living in Los Angeles. Bleu graduated from the Berklee College of Music in Boston, Massachusetts. Along with his solo work, he is the lead singer and songwriter of the Electric Light Orchestra-style power pop band L.E.O., as well as a founding member of the power pop trio The Major Labels with Mike Viola and Ducky Carlisle, and is also a founding member of the Mutt Lange homage super-group LoudLion (featuring Taylor Locke of Rooney, Allison Robertson of The Donnas, Maclaine Diemer formerly of Bang Camaro, etc.). Bleu has toured the United States and internationally with bands such as John Mayer, Puffy AmiYumi, Hanson, Guster, Rooney, Mike Viola, Switchfoot, Alexz Johnson, and Toad the Wet Sprocket.",
"title": ""
},
{
"docid": "51097859",
"text": "The Popular Front for Justice in the Congo (French: Front populaire pour la justice au Congo , or FPJC) is an armed group operating in the south of Ituri Province in the Democratic Republic of the Congo (DRC), where it has participated in the Ituri conflict. It formed in September 2008 from a splintering of the Front for Patriotic Resistance in Ituri (FRPI) and coalescing of other armed actors, including combatants from the Nationalist and Integrationist Front, who had resisted national disarmament campaigns. The group has expressed opposition to a 2006 attempt to resolve the Ituri conflict, which granted amnesty to former participants in the conflict. In 2011, the group was estimated to have no more than 100 members. Whereas the FRPI was closely linked to the Ngiti ethnolinguistic group, the FPJC incorporated members of more varied ethnic backgrounds.",
"title": ""
},
{
"docid": "16243343",
"text": "The Malaysian Islamic Study Group (MISG) was founded in Peoria, Illinois in 1976 with the main objective to assist the Malaysian students in walking the path of success whilst they are in America/Canada, fulfilling their responsibilities as students, as members of their communities and as servants of God. After more than 30 years of its establishment, MISG has a sizeable number of members in almost each university in America which has Malaysian students.",
"title": ""
},
{
"docid": "422914",
"text": "Ozma is an American rock band from Pasadena, California. The band's sound is a mix of nostalgic new wave–influenced power pop and contrapuntal Casiotone-driven melodies sustained by heavy guitar riffs. Since their formation in September 1995, Ozma has released five studio albums and toured the U.S., Japan, and Canada more than thirty times, including extensive touring with stylistically similar groups including Weezer, Nada Surf, Rilo Kiley, Superdrag, The Rentals, and Rooney.",
"title": ""
},
{
"docid": "29018702",
"text": "The genus Epiophlebia is the sole member of the family Epiophlebiidae, which is itself the sole living representative of the Epiproctan infraorder Epiophlebioptera, and it contains only four species. The first two species were historically placed in their own suborder Anisozygoptera, considered intermediate between dragonflies and damselflies, mainly because the hind wings are very similar in size and shape to the forewings and held back over the body at rest, as in damselflies. It has more recently been recognized that the genus \"Epiophlebia\" shares a more recent ancestor with dragonflies (having become separated from these in and around the uplifting of the Himalayas), and the group has accordingly been reclassified as an infraorder within the dragonflies. Very recently a third species, \"Epiophlebia sinensis\", has been described from Heilongjiang province in northeast China, bridging the \"Epiophlebia\" distribution gap between Nepal and Japan. A fourth species is known only from larval material from South China.",
"title": ""
},
{
"docid": "31759631",
"text": "A massacre is the deliberate slaughter of members of one group by one or more members of another more powerful group. A massacre may be indiscriminate or highly methodical in application. A massacre is a single event, though it may occur during the course of an extended military campaign or war. A massacre is separate from a battle (an event in which opposing sides fight), but may follow in its immediate aftermath, when one side has surrendered or lost the ability to fight, yet the victors persist in killing their opponents.",
"title": ""
},
{
"docid": "49278669",
"text": "A massacre is the deliberate slaughter of members of one group by one or more members of another more powerful group. A massacre may be indiscriminate or highly methodical in application. A massacre is a single event, though it may occur during the course of an extended military campaign or war. A massacre is separate from a battle (an event in which opposing sides fight), but may follow in its immediate aftermath, when one side has surrendered or lost the ability to fight, yet the victors persist in killing their opponents.",
"title": ""
},
{
"docid": "32293746",
"text": "Michael Joseph Rooney (born April 2, 1962) is an American choreographer. He is the son of actor Mickey Rooney. Best known for his work on a number of music videos, Rooney has won MTV Video Music Award for Best Choreography five times.",
"title": ""
},
{
"docid": "40011771",
"text": "Borderline was an early-1970s band from Woodstock, New York, that fused elements of folk, rock, country and jazz. Consisting of brothers David Gershen (b. 1947) and Jon Gershen (b. 1950) as well as Jim Rooney (b. 1938), the trio recorded two albums, the second of which was not officially released until 2001, and then only in Japan, due to record company problems. Though the group did not enjoy a great deal of commercial success, it was part of the “Woodstock scene” of the early 1970s that included Van Morrison and the Band. Borderline was a forerunner of musical artists who would eventually be grouped under the “Americana” genre. Also notable is that their two albums featured some well-known backing musicians including members of the Band. After Borderline broke up in 1974, the Gershen brothers pursued various projects while Rooney became a successful producer in Nashville, working with artists including Iris DeMent, Nanci Griffith and John Prine.",
"title": ""
},
{
"docid": "3840635",
"text": "Paul Stretford is an English football agent. In 1987, he founded Proactive Sports Management, renamed Formation Group in 2004, which went on to represent, amongst others, England footballer and also step father to the England International Wayne Rooney. In 2010 Rooney revealed as part of his evidence during a court case that Stretford received 20% of his off-field earnings, an amount the player regarded as being fair.",
"title": ""
},
{
"docid": "570152",
"text": "Egalitarian communities are groups of people who have chosen to live together, with egalitarianism as one of their core values. A broad definition of egalitarianism is \"equal access to resources and to decision-making power.\" For example, decision-making is done by consensus or another system in which each person has a voice; it is not done hierarchically with only one or a few people making choices that will affect the whole group. If the group shares assets (income, vehicles, etc.), they are distributed equitably throughout the group, and each member has access to more-or-less the same resources as any other member. Egalitarian communities are a type of commune (some communal groups are not egalitarian in nature).",
"title": ""
},
{
"docid": "42131058",
"text": "Rooney were a British lo-fi band, that released three albums between 1998 and 2000.",
"title": ""
},
{
"docid": "45239873",
"text": "The Art Rooney Award is given annually by the National Football League recognizing outstanding sportsmanship on the playing field. Established in 2015, the award is named in honor of Art Rooney, Sr., the founding owner of the Pittsburgh Steelers and a member of the National Football League Hall of Fame.",
"title": ""
}
] |
6927
|
UK: How to *leave* self select stock and shares ISA (without selling the shares)?
|
[
{
"docid": "594040",
"text": "Your existing shares in their existing ISA(s) do not in any way impact on your future ISA allowances. The only thing that uses up your ISA allowance is you paying new cash into an ISA account. So you can leave your existing shares in their existing ISA(s) and simply open new ISA(s) for future contributions which suit your current plans.",
"title": ""
}
] |
[
{
"docid": "141141",
"text": "\"Something to note is that when a company announces a share buyback program there is usually a time frame and amount of shares that are important details as it isn't like the company will make one big buy back of stock generally. Rather it may take months or even years as noted in the Wikipedia article about share repurchases. Wikipedia covers some of the technical details here but to give a specific set of answers: When a company announces a share buyback program, who do they actually buy back the shares from? From the Wikipedia link: \"\"Under US corporate law there are five primary methods of stock repurchase: open market, private negotiations, repurchase 'put' rights, and two variants of self-tender repurchase: a fixed price tender offer and a Dutch auction.\"\" Thus, there are open market and a couple of other possibilities. Openly traded shares on a stock exchange? Possibly, though there are other options. Is there a fixed price that they buy back at? Sometimes. I'd think a \"\"fixed price tender offer\"\" would imply a fixed price though the open market way may take various prices. If I own shares in that company, can I get them to buy back my shares? Selective Buy-Backs is noted in Wikipedia as: \"\"In broad terms, a selective buy-back is one in which identical offers are not made to every shareholder, for example, if offers are made to only some of the shareholders in the company. In the US, no special shareholder approval of a selective buy-back is required. In the UK, the scheme must first be approved by all shareholders, or by a special resolution (requiring a 75% majority) of the members in which no vote is cast by selling shareholders or their associates. Selling shareholders may not vote in favor of a special resolution to approve a selective buy-back. The notice to shareholders convening the meeting to vote on a selective buy-back must include a statement setting out all material information that is relevant to the proposal, although it is not necessary for the company to provide information already disclosed to the shareholders, if that would be unreasonable.\"\" Thus it is possible, though how probable is another question. While not in the question, something to consider is how the buybacks can be done as a result of offsetting the dilution of employees who have stock options that may exercise them and spread the earnings over more shares, but this is more on understanding the employee stock option scenario that various big companies use when it comes to giving employees an incentive to help the stock price.\"",
"title": ""
},
{
"docid": "57646",
"text": "You can't actually transfer shares directly unless they were obtained as part of an employee share scheme - see the answers to questions 19 and 20 on this page: http://www.hmrc.gov.uk/isa/faqs.htm#19 Q. Can I put shares from my employee share scheme into my ISA? A. You can transfer any shares you get from into a stocks and shares component of an ISA without having to pay Capital Gains Tax - provided your ISA manager agrees to take them. The value of the shares at the date of transfer counts towards the annual limit. This means you can transfer up to £11,520 worth of shares in the tax year 2013-14 (assuming that you make no other subscriptions to ISAs, in those years). You must transfer the shares within 90 days from the day they cease to be subject to the Plan, or (for approved SAYE share option schemes) 90 days of the exercise of option date. Your employer should be able to tell you more. Q. Can I put windfall or inherited shares in my ISA? A. No. You can only transfer shares you own into an ISA if they have come from an employee share scheme. Otherwise, the ISA manager must purchase shares on the open market. The situation is the same if you have shares that you have inherited. You are not able to transfer them into an ISA.",
"title": ""
},
{
"docid": "206483",
"text": "Technically, the answer is no, you can't put more money in to that ISA in that tax year once you've transferred it (unless you've transferred it to a Stocks and Shares ISA). FAQs 7 and 8 from http://www.hmrc.gov.uk/isa/faqs.htm cover these cases: Q. I have transferred current year payments to my cash ISA to a stocks and shares ISA, can I make any further payments to a cash ISA in this tax year? A. Yes - provided you haven't already used up your annual ISA investment allowance (£11,520 in the tax year 2013-14). When you transfer current year payments to your cash ISA to a stocks and shares ISA it is as if that cash ISA had never existed. Any money you saved up to the date of transfer will be treated as if you had invested that money directly in the stocks and shares ISA. For example, if you had put £2,000 in a cash ISA and then transferred it to a stocks and shares ISA you would be able to make further payments totalling £9,520 in that tax year. You could either put all of the £9,520 in the stocks and shares ISA or you could put up to £5,760 in a cash ISA (with the same or a different ISA manager) and the remainder of the £9,520 in the stocks and shares ISA. Q. How many ISAs can I have? A. There are limits on the number of ISA accounts you can subscribe to each tax year. You can only put money into one cash ISA and one stocks and shares ISA. But in different years, you could choose to save with different managers. There are no limits on the number of different ISAs you can hold over time. However, in practice, if you transfer mid-year from Provider A to Provider B, Provider B has no way of telling whether you have already put money in to the ISA with Provider A that year or not, so you will be able to put more money in. I believe that ISA providers do report their subscriptions back to HMRC so they can check for multiple subscriptions (over the limit) in one tax year; but in the past, I have done exactly what you describe and it has never been picked up in any way or caused any problem at all. As long as you stick to total subscriptions within the limit, I'd guess you're unlikely to encounter a problem. (Of course I am not a financial advisor so you should take what I say with the same pinch of salt as you would take any other random advice from the internet).",
"title": ""
},
{
"docid": "574691",
"text": "Yes, this is fine: You can save up to £20,000 in one type of account or split the allowance across some or all of the other types. You can only pay £4,000 into your Lifetime ISA in a tax year ... Example You could save £11,000 in a cash ISA, £2,000 in a stocks and shares ISA, £3,000 in an innovative finance ISA and £4,000 in a Lifetime ISA in one tax year. https://www.gov.uk/individual-savings-accounts/how-isas-work You might want to consider whether it is wise to be fully invested in shares. If you're going to have to dip into them for things like holidays and a car, you're taking a risk that you might have to sell when the market is low. As a basic rate taxpayer, you have a £1 000 personal savings allowance. You don't need to chase the tax break with a cash ISA, which often have poor rates. However, you should consider keeping some of your savings in cash, for example in a current account that pays decent interest on the balance.",
"title": ""
},
{
"docid": "331850",
"text": "In order to compare the two, you need to compare your entire portfolio, which is not just how much money you have, but how much stock. In both scenarios, you start with (at least, but let's assume) £20 and 0 stock. In your scenario, you buy 10 shares, leaving you with £0 and 10 shares. You then sell it at £1.50/share to cut your losses, leaving you with £15 and 0 shares. That concludes the first transaction with a net loss of £5. In a second transaction, you then buy 10 shares again at £1/share, leaving you with £5 and 10 shares. You are still down £15 from the start, but you also still have 10 shares. Any further profit or loss depends on what you can get for those 10 shares in the future. In a short sale, you borrow 10 shares and sell them, leaving you with £40 (your initial £20 plus what you just made on the short sale) and -10 shares of stock. At the end of the contract, you must buy 10 shares to return them; you are able to do so at £1.50/share, leaving you with £25 and 0 shares. At this point, your exposure to the stock is complete, and you have a net gain of £5.",
"title": ""
},
{
"docid": "318823",
"text": "\"There are two different types of ISA; the \"\"Cash ISA\"\" for cash savings, and the \"\"Stocks and Shares ISA\"\" for stock market investing. You can transfer funds between these two different types of ISA. If your current cash ISA provider does not provide stocks and shares ISAs, then there may be a fee involved when transferring funds between two different providers. If I am reading your notation correctly, you have contributed the full allowance of GBP15,240 in both the current tax year and the previous tax year. Each year you can contribute GBP15,240 (currently) to your ISAs and this can be done in any combination of cash ISA and stocks and shares ISA. For example, you could put GBP5,240 into your cash ISA and GBP10,000 into your stocks and shares ISA. Regarding your questions : It is also important to understand that once you withdraw money from an ISA, it does not affect your previous contributions or allowances. For example, if you have used your full contribution allowance for the current year and chose to withdraw some funds, then you have still used your full contribution allowance and so you cannot redeposit these funds.\"",
"title": ""
},
{
"docid": "220147",
"text": "Options granted by an employer to an employee are generally different that the standardized options that are traded on public stock option exchanges. They may or may not have somewhat comparable terms, but generally the terms are fairly different. As a holder of an expiring employee option, you can only choose to exercise it by paying the specified price and receiving the shares, or not. It is common that the exercise system will allow you to exercise all the shares and simultaneously sell enough of the acquired shares to cover the option cost of all the shares, thus leaving you owning some of the stock without having to spend any cash. You will owe taxes on the gain on exercise, regardless of what you do with the stock. If you want to buy publicly-traded options, you should consider that completely separately from your employer options other than thinking about how much exposure you have to your company situation. It is very common for employees to be imprudently overexposed to their company's stock (through direct ownership or options).",
"title": ""
},
{
"docid": "36190",
"text": "First of all I recommend reading this short e-book that is aimed at young investors. The book is written for American investors but they same rules apply with different terms (e.g. the equivalent tax-free savings wrappers are called ISAs in the UK). If you don't anticipate needing the money any time soon then your best bet is likely a stocks and share ISA in an aggressive portfolio of assets. You are probably better off with an even more aggressive asset allocation than the one in the book, e.g. 0-15% bond funds 85-100% equity funds. In the long term, this will generate the most income. For an up-to-date table of brokers I recommend Monevator. If you are planning to use the money as a deposit on a mortgage then your best bet might be a Help to Buy ISA, you'll have to shop around for the best deals. If you would rather have something more liquid that you can draw into to cover expenses while at school, you can either go for a more conservative ISA (100% bond funds or even a cash ISA) or try to find a savings account with a comparable interest rate.",
"title": ""
},
{
"docid": "489640",
"text": "First I assume you are resident for tax purposes in the UK? 1 Put 2000 in a cash ISA as an emergency fund. 2 Buy shares in 2 or 3 of the big generalist Investment trusts as they have low charges and long track records – unless your a higher rate tax payer don’t buy the shares inside the ISA its not worth it You could use FTSE 100 tracker ETF's or iShares instead of Investment Trusts.",
"title": ""
},
{
"docid": "409402",
"text": "\"Your dec ision is actually rather more complex than it first appears. The problem is that the limits on what you can pay into the HTB ISA might make it less attractive - it will all depend. Currently, you can put £15k/year into a normal ISA (Either Cash, or Stocks and Share or a combination). The HTB ISA only allows £200/month = £2,400/year. Since you can only pay into one Cash ISA in any one year you are going to lose out on the other £12,600 that you could save and grow tax free. Having said that, the 25% contribution by the govt. is extremely attractive and probably outweighs any tax saving. It is not so clear whether you can contribute to a HTB ISA (cash) and put the rest of your allowance into a Stocks and Shares ISA - if you can, you should seriously consider doing so. Yes this exposes you to a riskier investment (shares can go down as well as up etc.) but the benefits can be significant (and the gains are tax free). As said above, the rules are that money you have paid into an ISA in earlier years is separate - you can't pay any more into the \"\"old\"\" one whilst paying into a \"\"new\"\" one but you don't have to do anything with the \"\"old\"\" ISA. But you might WANT to do something since institutions are amazingly mean (underhand) in their treatment of customers. You may well find that the interest rate you get on your \"\"old\"\" ISA becomes less competitive over time. You should (Must) check every year what rate you are getting and whether you can get a better rate in a different ISA - if there is a better rate ISA and if it allows transfers IN, you should arrange to make the trasnfer - you ABSOLUTELY MUST TRANSFER between ISAs - never even think of taking the money out and then trying to pay it in to another ISA, it must be transferred directly between ISAs. So overall, yes, stop paying into the \"\"old\"\" ISA, open a new HTB ISA next year and if you can pay in the maximum do so. But if you can afford to save more, you might be able to open a Stocks and Shares ISA as well and pay into that too (max £15k into the pair in one year). And then do not \"\"forget\"\" about the \"\"old\"\" ISA(s) you will probably need to move all the money you have in the \"\"old\"\" one(s) regualrly into new ISAs to obtain a sensible rate. You might do well to read up on all this a lot more - I strongly recommend the site http://www.moneysavingexpert.com/ which gives a lot of helpful advice about everything to do with money (no I don't have any association with them).\"",
"title": ""
},
{
"docid": "537212",
"text": "Yes, the newly bought shares will have a long-term holding period, regardless of when you sell them. In addition, it's only a wash sale if you sold the first shares for a loss; it's not a wash sale if you sold them for a gain. Wikipedia mentions this: When a wash sale occurs, the holding period for the replacement stock includes the period you held the stock you sold. Example: You've held shares of XYZ for 10 years. You sell it at a loss but then buy it back within the wash sale period. When you sell the replacement stock, your gain or loss will be long-term — no matter how soon you sell it. Charles Schwab also mentions this: Here's a quick example of a wash sale. On 9/30/XX, you buy 500 shares of ABC at $10 per share. One year later the stock price starts to drop, and you sell all your shares at $9 per share on 10/4/XY. Two days later, on 10/6, ABC bottoms out at $8 and you buy 500 shares again. This series of trades triggers a wash sale. The holding period of the original shares will be added to the holding period of the replacement shares, effectively leaving you with a long-term position.",
"title": ""
},
{
"docid": "417838",
"text": "\"The main thing is the percentage of the company represented by the shares. Number of shares is meaningless without total shares. If you compute percentage and total company value you can estimate the value of the grant. Or perhaps more useful for a startup is to multiple the percentage by some plausible \"\"exit\"\" value, such as how much the company might sell for or IPO for. Many grants expire when or soon after you leave the company if you don't \"\"cash out\"\" vested shares when you leave, this is standard, but do remember it when you leave. The other major thing is vesting. In the tech industry, vesting 1/4 after a year and then the rest quarterly over 3 more years is most common.\"",
"title": ""
},
{
"docid": "517323",
"text": "The stock market is just like any other market, but stocks are bought and sold here. Just like you buy and sell your electronics at the electronics market, this is a place where buyers and sellers come together to buy and sell shares or stocks or equity, no matter what you call it. What are these shares? A share is nothing but a portion of ownership of a company. Suppose a company has 100 shares issued to it, and you were sold 10 out of those, it literally means you are a 10% owner of the company. Why do companies sell shares? Companies sell shares to grow or expand. Suppose a business is manufacturing or producing and selling goods or services that are high in demand, the owners would want to take advantage of it and increase the production of his goods or services. And in order to increase production he would need money to buy land or equipment or labor, etc. Now either he could go get a loan by pledging something, or he could partner with someone who could give him money in exchange for some portion of the ownership of the company. This way, the owner gets the money to expand his business and make more profit, and the lender gets a portion of profit every time the company makes some. Now if the owner decides to sell shares rather than getting a loan, that's when the stock market comes into the picture. Why would a person want to trade stocks? First of all, please remember that stocks were never meant to be traded. You always invest in stocks. What's the difference? Trading is short term and investing is long term, in very simple language. It's the greed of humans which led to this concept of trading stocks. A person should only buy stocks if he believes in the business the company is doing and sees the potential of growth. Back to the question: a person would want to buy stocks of the company because: How does a stock market help society? Look around you for the answer to this question. Let me give you a start and I wish everyone reading this post to add at least one point to the answer. Corporations in general allow many people come together and invest in a business without fear that their investment will cause them undue liability - because shareholders are ultimately not liable for the actions of a corporation. The cornerstone North American case of how corporations add value is by allowing many investors to have put money towards the railroads that were built across America and Canada. For The stock market in particular, by making it easier to trade shares of a company once the company sells them, the number of people able to conveniently invest grows exponentially. This means that someone can buy shares in a company without needing to knock door to door in 5 years trying to find someone to sell to. Participating in the stock market creates 'liquidity', which is essentially the ease with which stocks are converted into cash. High liquidity reduces risk overall, and it means that those who want risk [because high risk often creates high reward] can buy shares, and those who want low risk [because say they are retiring and don't have a risk appetite anymore] can sell shares.",
"title": ""
},
{
"docid": "170863",
"text": "\"There are several reasons. One, mutual funds provide instant diversification. To build a diverse portfolio \"\"manually\"\" (by buying individual shares) requires a lot of time and effort. If your portfolio is not diverse, then it is wrong to say \"\"buying shares gives higher return\"\"; in many cases diversification will increase your returns. Two, mutual funds reduce transactions costs. If you buy individual shares, you pay transactions costs every time you buy or sell. If you buy and sell the shares of many companies, you must perform many transactions and thus incur heavy fees. With mutual funds, a single transaction gets you access to many companies. In addition, it is often possible to buy mutual funds without paying transactions costs at all (although you will still pay fund expenses). Three (sort of a combination of the previous two) it is just easier. Many people can easily buy mutual funds with no cost and little effort through their bank. It is also simple to set up auto-investment plans so that you automatically save money over time. All of these things are much more complicated if you try to buy many individual shares. Four, if you buy the right kinds of funds (low-cost index funds), it is probably more lucrative than buying individual shares. The odds that, through carefully selected stock-buying, you will earn more than the market average are small. Even professional stock-pickers consistently underperform broad market indexes. In short, it is not true that \"\"buying shares gives higher return\"\", and even if it were, the convenience and diversification of mutual funds would still be good reasons to use them.\"",
"title": ""
},
{
"docid": "457294",
"text": "You also need to remember that stock options usually become valueless if not exercised while an employee of the company. So if there is any chance that you will leave the company before an IPO, the effective value of the stock options is zero. That is the safest and least risky valuation of the stock options. With a Google or Facebook, stock options can be exercised and immediately sold, as they are publicly traded. In fact, they may give stock grants where you sell part of the grant to pay tax withholding. You can then sell the remainder of the grant for money at any time, even after you leave the company. You only need the option/grant to vest to take advantage of it. Valuing these at face value (current stock price) makes sense. That's at least a reasonable guess of future value. If you are absolutely sure that you will stay with the company until the IPO, then valuing the stock based on earnings can make sense. A ten million dollar profit can justify a hundred million dollar IPO market capitalization easily. Divide that by the number of shares outstanding and multiply by how many you get. If anything, that gives you a conservative estimate. I would still favor the big company offers though. As I said, they are immediately tradeable while this offer is effectively contingent on the IPO. If you leave before then, you get nothing. If they delay the IPO, you're stuck. You can't leave the company until then without sacrificing that portion of your compensation. That seems a big commitment to make.",
"title": ""
},
{
"docid": "344076",
"text": "The original owner of the shares can pledge their shares to be short, and they earn interest from lending their shares. The conditions of this arrangement are detailed in standard agreements all market participants sign with their broker, or clearinghouse, or with the exchange, or with the self regulatory agency. Stocks within the same class are identical, despite someone's sentiment to an old share certificate that their grandparents gave them, and as such can be sold and returned to the beneficial owner multiple times with no difference. That is how it is supposed to work anyway, as naked shorting involves selling fictional shares that have no beneficial owner. So there are market inefficiencies in this practice, but the agreements between market participants are sound and answers your question about how.",
"title": ""
},
{
"docid": "1203",
"text": "When you want to short a stock, you are trying to sell shares (that you are borrowing from your broker), therefore you need buyers for the shares you are selling. The ask prices represent people who are trying to sell shares, and the bid prices represent people who are trying to buy shares. Using your example, you could put in a limit order to short (sell) 1000 shares at $3.01, meaning that your order would become the ask price at $3.01. There is an ask price ahead of you for 500 shares at $3.00. So people would have to buy those 500 shares at $3.00 before anyone could buy your 1000 shares at $3.01. But it's possible that your order to sell 1000 shares at $3.01 never gets filled, if the buyers don't buy all the shares ahead of you. The price could drop to $1.00 without hitting $3.01 and you will have missed out on the trade. If you really wanted to short 1000 shares, you could use a market order. Let's say there's a bid for 750 shares at $2.50, and another bid for 250 shares at $2.49. If you entered a market order to sell 1000 shares, your order would get filled at the best bid prices, so first you would sell 750 shares at $2.50 and then you would sell 250 shares at $2.49. I was just using your example to explain things. In reality there won't be such a wide spread between the bid and ask prices. A stock might have a bid price of $10.50 and an ask price of $10.51, so there would only be a 1 cent difference between putting in a limit order to sell 1000 shares at $10.51 and just using a market order to sell 1000 shares and getting them filled at $10.50. Also, your example probably wouldn't work in real life, because brokers typically don't allow people to short stocks that are trading under $5 per share. As for your question about how often you are unable to make a short sale, it can sometimes happen with stocks that are heavily shorted and your broker may not be able to find any more shares to borrow. Also remember that you can only short stocks with a margin account, you cannot short stocks with a cash account.",
"title": ""
},
{
"docid": "200928",
"text": "Ignoring taxes, a share repurchase has exactly the same effect on the company and the shareholders' wealth as a cash dividend. In either case, the company is disbursing cash to its shareholders; in the former, in exchange for shares which shareholders happen to be selling on the market at the time; in the latter, equally to all shareholders. For those shareholders who do not happen to be selling their shares, a share repurchase by a company is equivalent to a shareholder's reinvestment of a cash dividend in additional shares of the same company. The only difference is the total number of shares left outstanding. Your shares after a share buyback represent ownership of a greater fraction of the company, since in effect the company is buying out other shareholders on your behalf. Theoretically, a share buyback leaves the price of the stock unchanged, whereas a cash dividend tends to reduce the price of the stock by exactly the amount of the dividend, (notwithstanding underlying earnings.) This is because a share buyback concentrates your ownership in the company, but at the same time, the company as a whole is devalued by the exact amount of cash disbursed to buy back shares. Taxwise, a share buyback generally allows you to treat your share of the company's profits as capital gains---and quite possibly defer taxes on it as long as you own the stock. You usually have to pay taxes on dividends at the time they are paid. However, dividends are sometimes seen as instilling discipline in management, because it's a very public and obvious sign of distress for a company to cut its dividend, whereas a share repurchase plan can often be quietly withdrawn without drawing that much attention. A third alternative to a dividend or a share repurchase is for the company to find profitable projects to reinvest its earnings in, and attempt to grow the company as a whole (in the hopes of even greater earnings in the future) rather than distribute current earnings back to shareholders. (A company may alse use its earnings to pay down or repurchase debt, as well.) As to your second question, the SEC has certain rules that regulate the timing and price of share repurchases on the open market.",
"title": ""
},
{
"docid": "535605",
"text": "You have a lot of different questions in your post - I am only responding to the request for how to value the ESPP. When valuing an ESPP, don't think about what you might sell the shares for in the future, think about what the market would charge you for that option today. In general, an option is worth much less than the underlying share itself. For the simplest example, assume you work at a public company, and your exercise price for your options is $.30, and you can only exercise those options until the end of today, and the cost of the shares on the public stock exchange is also $.30. You have the same 'strike price' as everyone else in the market, making your option worth nothing. In truth, holding that right to a specific strike price into the future does give you value, because it means you can realize the upside in share price gains, without risking any money on share losses. So, how do you value the options? If it's a public company with an active options market, you can easily compare your $.30 strike price with the value of call options in the market that have a $.30 strike price. That becomes the value to you of the option (caveat: it is unlikely you can find an exact match for the terms of your vesting period, but you should be able to find a good starting point). If it's a public company without an active options market, you will have to do a bit of estimation. If a current share is worth $.25 (so, close to your strike price), then your option is worth a little bit, but not much. Compare other shares in your industry / company size to get examples of the relative value between an option and a share. If the current share price is worth $.35, then your option is worth about $.05 [the $.05 profit you could get by immediately exercising and selling, plus a bit more for an option on a share that you can't buy in the open market]. If it's a private company, then you need to be very clear on how shares are to be valued, and what methods you have available to sell back to the company / other individuals. You can then consider as per above, how to value the option for a share, vs the share itself. Without a clear way to sell your shares of a private company [ideally through a sale directly back to the company that you are able to force them to agree on; ie: the company will buyback shares at 5x Net income for the previous year, or something like that], then the value of a small number of shares is very nebulous. There is an extremely limited market for shares of private companies, if you don't own enough to exert control. In your case, because the valuation appears to be $2/share [be sure that these are the same share classes you have the option to buy], your option would be worth a little more than $1.70, if you didn't have to wait 4 years to exercise it. This would be total compensation of about $10k, if you were able to exercise today. Many people don't end up working for an early job in their career for 4 years, so you need to consider whether how much that will reduce the value of the ESPP for you personally. Compared with salary of 90k, 10k worth of stock in 4 years may not be a heavy motivating compensation consideration. Note also that because the company is not public, the valuation of $2/share should be taken with a grain of salt.",
"title": ""
},
{
"docid": "447197",
"text": "See my answer here What is the dividend tax rate for UK stock The only tax from US stocks you'd need to worry about would be dividend withholding tax of 30%. If you contact your ISA provider they should be able to provide you with a W8-BEN form so that you can have this rate reduced to 15%. Just because there's a tax treaty does not mean you will automatically be charged 15% - you must provide a W8-BEN form and renew it when it expires. That last 15% is unfortunately unavoidable. If you were paying any UK taxes you could claim that 15% as a discount against your UK dividend tax liability, but as your US stock would be wrapped in an ISA there's no UK tax to pay which means no tax to reclaim from the tax treaty. Other than DWT though, you will pay absolutely no tax on US stocks held in an ISA to either the US or UK government.",
"title": ""
},
{
"docid": "279782",
"text": "\"Usually insiders are in a better position than you to understand their business, but that doesn't mean they will know the future with perfect accuracy. Sometimes they are wrong, sometimes life events force them to liquidate an otherwise promising investment, sometimes their minds change. So while it is indeed valuable information, as everything in fundamental analysis it must be taken with a grain of salt. Automatic Sell I think these refer to how the sell occurred. Often the employees don't get actual shares but options or warrants that can be converted to shares. Or there may be special predetermined arrangements regarding when and how the shares may be traded. Since the decision to sell here has nothing to do with the prospects of the business, but has to do with the personal situation of the employee, it's not quite the same as outright selling due to market concerns. Some people, for instance, are not interested in holding stock. Part of their compensation is given in stock, so they immediately sell the stock to avoid the headache of watching an investment. This obviously doesn't indicate that they expect the company will go south. I think automatic sell refers to these sorts of situations, but your broker should provide a more detailed definition. Disposition (Non Open Market) These days people trade through a broker, but there's nothing stopping you from taking the physical shares and giving them to someone in exchange for say a stack of cash. With a broker, you only \"\"sell\"\" without considering who is buying. The broker then finds buyers for you according to their own system. If selling without a broker you can also be choosy with who is buying, and it's not like anybody can just call up the CEO and ask to buy some stock, so it's a non-open market. Ultimately though it's still the insider selling. Just on a different exchange. So I would treat this as any insider sell - if they are selling, they may be expecting the stock to become less valuable. indirect ownership I think this refers to owning an entity that in turn owns the asset. For instance CEO of XYZ owns stock in ACME, but ACME holds shares of XYZ. This is a somewhat complicated situation, it comes down to whether you think they sold ACME because of the exposure to XYZ or because of some other risk that applies only to ACME and not XYZ. Generally speaking, I don't think you would find a rule like \"\"if insider transactions of so and so kinds > X then buy\"\" that provides guaranteed success. If such a rule was possible it would have been exploited already by the professionals. The more sensible option is to consider all data available to you and try to make a holistic evaluation. All of these insider activities can be bullish or bearish depending on many other factors.\"",
"title": ""
},
{
"docid": "100128",
"text": "Here's an excerpt from the Charles Schwab website which I think will help evaluate your position: The simple answer to your question is no, the value of a gift of stock for gift tax liability is NOT the donor's cost basis, but rather the fair market value of the stock at the time the gift is given. So let's say you purchased 100 shares of XYZ stock at $50 a share. Your cost basis is $5,000. Now the stock is $80 a share and you give it as a gift. The value of your gift for gift tax purposes is $8,000. In 2015, you can give up to $14,000 to an unlimited number of individuals each year without paying a gift tax or even reporting the gifts. If you give over that amount to any individual, however, you must report the gift on your tax return, but you don't have to pay taxes until you give away more than the current lifetime limit of $5,430,000—for the amount above and beyond $14,000 per person per year. So in the example above, there would be no gift tax liability. However, if the stock happened to be $150 a share, the value of the gift would be $15,000. You'd then have to report it and $1,000 would be applied toward your $5,430,000 lifetime exclusion. You will need to pay a gift tax on the current value of the stock. I'm not familiar with the tax laws in India, but if your brother was in the US, he wouldn't pay taxes on that gift until he sells the stock. The recipient doesn’t have to worry about gift taxes. It's when the recipient decides to sell the stock that the issue of valuation comes up—for income taxes. And this is where things can get a bit more complicated. In general, when valuing a gift of stock for capital gains tax liability, it's the donor's cost basis and holding period that rules. As an example, let's say you receive a gift of stock from your grandfather. He bought it for $10 a share and it's worth $15 a share on the day you receive it. If you then sell the stock, whether for a gain or a loss, your cost basis will be the same as your grandfather’s: $10 per share. Sell it at $25 and you'll pay tax (at the short- or long-term rate, depending on how long he owned the stock) on a gain of $15 a share; sell it at $8 and your capital loss will be $2 a share. Ultimately, with a gift this large that also crosses international borders, you really should hire a professional who is experienced with these types of transactions. Their fees/commission will be completely offset by the savings in risk and paperwork. http://www.schwab.com/public/schwab/nn/articles/How-Do-You-Value-a-Gift-of-Stock-It-Depends-on-Whether-You-re-the-Giver-or-the-Receiver",
"title": ""
},
{
"docid": "205280",
"text": "\"According to what little information is available currently, this fund is most akin to an actively managed exchange traded fund rather than an investment trust. An investment trust is an actively managed, closed-end fund that is tradeable on the stock market. \"\"Closed-end\"\" means that there are a fixed number of shares available for trading, so if you wish to buy or sell shares in a closed-end fund you need to find someone willing to sell or buy shares. \"\"Actively managed\"\" means that the assets are selected by the fund managers in the belief that they will perform well. This is in contrast to a \"\"passively managed\"\" fund which simply tracks an underlying index. The closed-end nature of investment trusts means that the share price is not well correlated to the value of the underlying assets. Indeed, almost all UK investment trusts trade at a significant discount to their net asset value. This reflects their historic poor performance and relatively weak liquidity. Of course there are some exceptions to this. Examples of open-end funds are unit trust (US = mutual funds) and ETFs (exchange traded funds). They are \"\"open-end\"\" funds in the sense that the number of shares/units available will change according to demand. Most importantly, the price of a share/unit will be strongly correlated to the net asset value of the underlying portfolio. In general, for an open-end fund, if the net asset value of the fund is X and there are Y shares/units outstanding, then the price of a share/unit will be X/Y. Historic data shows that passively managed funds (index trackers) \"\"always\"\" outperform actively managed funds in the long term. One of the big issues with actively managed funds is they have relatively high management fees. The Peoples Trust will be charging about 1% with a promise that this should come down over time. Compare this to a fee of 0.05% on a large, major market index tracking ETF. Further, the 1% headline fee being touted by Peoples Trust is a somewhat misleading, since they are paying their employees bonuses with shares in the fund. This will cause dilution of the net asset value per share and can be read as addition management fees by proxy. Since competent fund managers will demand high incomes, bonus shares could easily double the management fees, depending on the size of the fund. In summary, history has shown that the promises of active fund managers rarely (if ever) come to fruition. Personally, I would not consider this to be an attractive investment and would look more towards a passively managed major market index ETF with low management fees.\"",
"title": ""
},
{
"docid": "8974",
"text": "\"Firstly (and this part is rather opinion-based) I would absolutely not think of making more pension contributions when you are currently totaling 6% of salary as \"\"over contributing\"\". There are some who argue that you should be putting a minimum of 20% away for retirement throughout your working life; you don't say how old you are / how close to retirement you are, but a common rule of thumb is to halve your age and put away that % of your salary into your pension. So I would certainly start with upping those contributions. I actually don't think it makes much difference whether you go for just your workplace pension versus a separate private one - in general you end up paying management fees that are a % of the value, so whether it is in one place or split doesn't cost any less. The \"\"all eggs in one basket\"\" syndrome is a possible argument but equally if you change jobs a few times and end up with half a dozen pension pots it can be very hard to stay on top of them all. If you end up with everything in one pot and then transfer it when you change jobs, it's easier to manage. Other options: ISA as you mentioned; on the plus side these are tax free. On the minus side, you can either go for a cash ISA which at the moment has very low rates of return, and/or a stocks and shares ISA which exposes you to risks in the stock market. If you have debt, consider paying it off early / overpaying. Student loans may or may not be the exception to this depending on your personal situation. Certainly if you have a mortgage you can save a vast amount by overpaying early. Other investments - stocks and shares, BTL housing, fine wines, Bitcoin, there are almost limitless possibilities. But it makes sense to max out the tax-efficient options before you look into these.\"",
"title": ""
},
{
"docid": "427859",
"text": "\"I think it's easiest to illustrate it with an example... if you've already read any of the definitions out there, then you know what it means, but just don't understand what it means. So, we have an ice cream shop. We started it as partners, and now you and I each own 50% of the company. It's doing so well that we decide to take it public. That means that we will be giving up some of our ownership in return for a chance to own a smaller portion of a bigger thing. With the money that we raise from selling stocks, we're going to open up two more stores. So, without getting into too much of the nitty gritty accounting that would turn this into a valuation question, let's say we are going to put 30% of the company up for sale with these stocks, leaving you and me with 35% each. We file with the SEC saying we're splitting up the company ownership with 100,000 shares, and so you and I each have 35,000 shares and we sell 30,000 to investors. Then, and this depends on the state in the US where you're registering your publicly traded corporation, those shares must be assigned a par value that a shareholder can redeem the shares at. Many corporations will use $1 or 10 cents or something nominal. And we go and find investors who will actually pay us $5 per share for our ice cream shop business. We receive $150,000 in new capital. But when we record that in our accounting, $5 in total capital per share was contributed by investors to the business and is recorded as shareholder's equity. $1 per share (totalling $30,000) goes towards actual shares outstanding, and $4 per share (totalling $120,000) goes towards capital surplus. These amounts will not change unless we issue new stocks. The share prices on the open market can fluctuate, but we rarely would adjust these. Edit: I couldn't see the table before. DumbCoder has already pointed out the equation Capital Surplus = [(Stock Par Value) + (Premium Per Share)] * (Number of Shares) Based on my example, it's easy to deduce what happened in the case you've given in the table. In 2009 your company XYZ had outstanding Common Stock issued for $4,652. That's probably (a) in thousands, and (b) at a par value of $1 per share. On those assumptions we can say that the company has 4,652,000 shares outstanding for Year End 2009. Then, if we guess that's the outstanding shares, we can also calculate the implicit average premium per share: 90,946,000 ÷ 4,652,000 == $19.52. Note that this is the average premium per share, because we don't know when the different stocks were issued at, and it may be that the premiums that investors paid were different. Frankly, we don't care. So clearly since \"\"Common Stock\"\" in 2010 is up to $9,303 it means that the company released more stock. Someone else can chime in on whether that means it was specifically a stock split or some other mechanism... it doesn't matter. For understanding this you just need to know that the company put more stock into the marketplace... 9,303 - 4,652 == 4,651(,000) more shares to be exact. With the mechanics of rounding to the thousands, I would guess this was a stock split. Now. What you can also see is that the Capital Surplus also increased. 232,801 - 90,946 == 141,855. The 4,651,000 shares were issued into the market at an average premium of 141,855 ÷ 4,651 == $30.50. So investors probably paid (or were given by the company) an average of $31.50 at this split. Then, in 2011 the company had another small adjustment to its shares outstanding. (The Common Stock went up). And there was a corresponding increase in its Capital Surplus. Without details around the actual stock volumes, it's hard to get more exact. You're also only giving us a portion of the Balance Sheet for your company, so it's hard to go into too much more detail. Hopefully this answers your question though.\"",
"title": ""
},
{
"docid": "160464",
"text": "\"You have a large number of possible choices to make, and a lot of it does depend upon what interests you when you are older. The first thing to note is the difference between ISAs and pension-contribution schemes tax wise, which is of course the taxation point. When you contribute to your pensions scheme, it is done before taxation, which is why when you draw from your pension scheme you have to pay income tax. Conversely, your ISA is something you contribute to after you have already paid income tax - so besides the 10% tax on dividends if you hold any assets which may them, it is tax free when you draw on it regardless of how much you have accrued over the years. Now, when it comes to the question \"\"what is the best way to save\"\", the answer is almost certainly going to be filling your pension to the point where you're going to retire just on the edge of the limit, and then putting the rest into ISAs. This way you will not be paying the higher rates of tax associated with breaking the lifetime limit, but also get maximum contributions into your various schemes. There is an exception to this of course, which is the return on investment. If you do not have access to a SIPP (Self Invested Personal Pension), you may be able to receive a far higher return on investment when using a Stocks & Shares ISA, in which case the fact that you have to pay taxes prior to funding it may not make a significant difference. The other issue you have, as others have mentioned is rent. While now you may be enjoying London, it is in my opinion quite likely that will change when you get older, London has a very high-cost of living, even compared to the home counties, and many of its benefits are not relevant to someone who is retired. When you retire, it is quite possible that you will see it fit to take a large sum out of your various savings, and purchase a house, which means that regardless of how much you are drawing out you will be able to have somewhere to live. Renting is fine when you are working, but when you have a certain amount of (admittedly growing) funds that have to last you indefinitely, who knows if it will last you.\"",
"title": ""
},
{
"docid": "390817",
"text": "The worth of a share of stocks may be defined as the present cash value of all future dividends and liquidations associated therewith. Without a crystal ball, such worth may generally only be determined retrospectively, but even though it's generally not possible to know the precise worth of a stock in time for such information to be useful, it has a level of worth which is absolute and not--unlikely market price--is generally unaffected by people buying and selling the stock (except insofar as activities in company stock affect a company's ability to do business). If a particular share of stock is worth $10 by the above measure, but Joe sells it to Larry for $8, that means Joe gives Larry $2. If Larry sells it to Fred $12, Fred gives Larry $2. The only way Fred can come out ahead is if he finds someone else to give him $2 or more. If Fred can sell it to Adam for $13, then Adam will give Fred $3, leaving Fred $1 better off than he would be if he hadn't bought the stock, but Adam will be $3 worse off. The key point is that if you sell something for less than it's worth, or buy something for more that it's worth, you give money away. You might be able to convince other people to give you money in the same way you gave someone else money, but fundamentally the money has been given away, and it's not coming back.",
"title": ""
},
{
"docid": "438121",
"text": "\"During GM's Chapter 11 reorganization in 2009, a new company was formed, with new stock. The old General Motors Corporation was renamed to \"\"Motors Liquidation Company,\"\" and the new company was named \"\"General Motors Company.\"\" The new company purchased some of the assets from the old company, and the old company was left to sell off the remaining assets and settle the debts. None of the stock transferred from the old company to the new one; if you were a GM stockholder of the old company and didn't sell, it is now worthless. When the new company formed, the stock was not traded publicly. The company was primarily owned by the United States and Canadian governments; together, they owned 72.5%. In 2010, GM had an IPO, and the US government sold most of their stake. By the end of 2013, the US government sold the remaining stake; the government no longer has any ownership in GM. When we talk about voting rights for stockholders, we are mainly talking about voting for the members of the board of directors. And yes, the government did indeed have a hand in selecting the board of the new company. The Treasury Department selected 10 members of the board, and the Canadian government selected 1 member. There were 19 board members total. (Source) Unlike some companies, there are not \"\"voting\"\" and \"\"non-voting\"\" classes of GM stock. All the shares sold by the US government are voting shares. Additional Sources:\"",
"title": ""
},
{
"docid": "178497",
"text": "Stock options represent an option to buy a share at a given price. What you have been offered is the option to buy the company share at a given price ($5) starting a given date (your golden handcuffs aka vesting schedule). If the company's value doubles in 1 year and the shares are liquid (i.e. you can sell them) then you've just made $125k of profit. If the company's value has gone to zero in 1 year then you've lost nothing other than your hopes of getting rich. As others have mentioned, the mechanics of exercising the option and selling the shares can typically be accomplished without any cash involved. The broker will do both in a single transaction and use the proceeds of the sale to pay the cost of buying the shares. You should always at least cover the taxable portion of the transaction and typically the broker will withhold that tax anyways. Otherwise you could find yourself in a position where you have actually lost money due to tax being owed while the shares decline in value below that tax. You don't have to worry about that right now. Again as people have mentioned options will typically expire 10 years from vesting or 90 days from leaving your employment with the company. I'm sure there are some variations on the theme. Make sure you ask and all this should be part of some written contract. I'm sure you can ask to see it if you wish. Also typical is that stock option grants have to be approved by the board which is normally a technicality. Some general advice:",
"title": ""
},
{
"docid": "345943",
"text": "If you havent yet maxed out your ISA, then its a no-brainer. You get excellent tax rebates and its silly not to take advantage of these before considering self investing in shares. Note that even if your ISA is maxed out, the economic turbulence means that investing in individual stocks is an intimidating place for beginners right now. The FSA is also looking at revising the average percentages used for pension, from 7% for adventurous investments, down to 5% or 6%, so there is industry wide recognition that on average the stock market is going to be a little less lucrative than it was a few years ago. Thats not to say you cant still make a whopping profit, but the chances of you doing so as a first time investor are remote to say the least. My advice would be to look seriously into some of the social lending sites, where you can still easily get a 7% return with minimal risk. Whilst I do have a portfolio which is performing well overall (I am a very speculative investor), I am moving a lot of funds into Zopa.com, as I am averaging 7% return with a lot less time, effort and risk than the stockmarket. Whatever you decide, I think its time you thought about consulting an IFA. They can help you understand what sort of risk you are willing to tolerate, which is a very important aspect of investing.",
"title": ""
}
] |
3418
|
how much of foreign exchange (forex/fx) “deep liquidity” is really just unbacked leverage and what is the effect?
|
[
{
"docid": "429704",
"text": "\"First it is worth noting the two sided nature of the contracts (long one currency/short a second) make leverage in currencies over a diverse set of clients generally less of a problem. In equities, since most margin investors are long \"\"equities\"\" making it more likely that large margin calls will all be made at the same time. Also, it's worth noting that high-frequency traders often highly levered make up a large portion of all volume in all liquid markets ~70% in equity markets for instance. Would you call that grossly artificial? What is that volume number really telling us anyway in that case? The major players holding long-term positions in the FX markets are large banks (non-investment arm), central banks and corporations and unlike equity markets which can nearly slow to a trickle currency markets need to keep trading just for many of those corporations/banks to do business. This kind of depth allows these brokers to even consider offering 400-to-1 leverage. I'm not suggesting that it is a good idea for these brokers, but the liquidity in currency markets is much deeper than their costumers.\"",
"title": ""
},
{
"docid": "148141",
"text": "\"In essence the problem that the OP identified is not that the FX market itself has poor liquidity but that retail FX brokerage sometimes have poor counterparty risk management. The problem is the actual business model that many FX brokerages have. Most FX brokerages are themselves customers of much larger money center banks that are very well capitalized and provide ample liquidity. By liquidity I mean the ability to put on a position of relatively decent size (long EURUSD say) at any particular time with a small price impact relative to where it is trading. For spot FX, intraday bid/ask spreads are extremely small, on the order of fractions of pips for majors (EUR/USD/GBP/JPY/CHF). Even in extremely volatile situations it rarely becomes much larger than a few pips for positions of 1 to 10 Million USD equivalent notional value in the institutional market. Given that retail traders rarely trade that large a position, the FX spot market is essentially very liquid in that respect. The problem is that there are retail brokerages whose business model is to encourage excessive trading in the hopes of capturing that spread, but not guaranteeing that it has enough capital to always meet all client obligations. What does get retail traders in trouble is that most are unaware that they are not actually trading on an exchange like with stocks. Every bid and ask they see on the screen the moment they execute a trade is done against that FX brokerage, and not some other trader in a transparent central limit order book. This has some deep implications. One is the nifty attribute that you rarely pay \"\"commission\"\" to do FX trades unlike in stock trading. Why? Because they build that cost into the quotes they give you. In sleepy markets, buyers and sellers cancel out, they just \"\"capture\"\" that spread which is the desired outcome when that business model functions well. There are two situations where the brokerage's might lose money and capital becomes very important. In extremely volatile markets, every one of their clients may want to sell for some reason, this forces the FX brokers to accumulate a large position in the opposite side that they have to offload. They will trade in the institutional market with other brokerages to net out their positions so that they are as close to flat as possible. In the process, since bid/ask spreads in the institutional market is tighter than within their own brokerage by design, they should still make money while not taking much risk. However, if they are not fast enough, or if they do not have enough capital, the brokerage's position might move against them too quickly which may cause them lose all their capital and go belly up. The brokerage is net flat, but there are huge offsetting positions amongst its clients. In the example of the Swiss Franc revaluation in early 2015, a sudden pop of 10-20% would have effectively meant that money in client accounts that were on the wrong side of the trade could not cover those on the other side. When this happens, it is theoretically the brokerage's job to close out these positions before it wipes out the value of the client accounts, however it would have been impossible to do so since there were no prices in between the instantaneous pop in which the brokerage could have terminated their client's losing positions, and offload the risk in the institutional market. Since it's extremely hard to ask for more money than exist in the client accounts, those with strong capital positions simply ate the loss (such as Oanda), those that fared worse went belly up. The irony here is that the more leverage the brokerage gave to their clients, the less money would have been available to cover losses in such an event. Using an example to illustrate: say client A is long 1 contract at $100 and client B is short 1 contract at $100. The brokerage is thus net flat. If the brokerage had given 10:1 leverage, then there would be $10 in each client's account. Now instantaneously market moves down $10. Client A loses $10 and client B is up $10. Brokerage simply closes client A's position, gives $10 to client B. The brokerage is still long against client B however, so now it has to go into the institutional market to be short 1 contract at $90. The brokerage again is net flat, and no money actually goes in or out of the firm. Had the brokerage given 50:1 leverage however, client A only has $2 in the account. This would cause the brokerage close client A's position. The brokerage is still long against client B, but has only $2 and would have to \"\"eat the loss\"\" for $8 to honor client B's position, and if it could not do that, then it technically became insolvent since it owes more money to its clients than it has in assets. This is exactly the reason there have been regulations in the US to limit the amount of leverage FX brokerages are allowed to offer to clients, to assure the brokerage has enough capital to pay what is owed to clients.\"",
"title": ""
},
{
"docid": "229118",
"text": "I'd think that liquidity and speed are prioritized (even over retail brokers and in come cases over PoP) for institutional traders who by default have large positions. When the going gets tough, these guys are out and the small guys - trading through average retail brokers - are the ones left holding the empty bag.",
"title": ""
}
] |
[
{
"docid": "148948",
"text": "It ought to be possible to buy a foreign exchange future (aka forex future / FX future). Businesses use these futures to make sure their exchange rate is predictable: if they put a bunch of money into manufacturing things that'll be ready a year later, it helps to know that the currency exchange rate shifts won't wipe out all their profits. If you're willing to take on some of that risk, and if things go your way, you can make money. They are essentially contracts between two private parties to pay each other a certain amount of money based on the movement of the currencies, so the Chinese government doesn't actually need to be involved and no renminbi need to change hands, you can just trade the contracts. Note that the exchange rate is currently fixed by the Chinese government, so you're going to be subject to enhanced levels of political risk, and they may not be as widely available or readily tradable as other foreign exchange futures, so check with a broker before opening your account. I couldn't find them on my personal Etrade account, but a quick Google search reveals CME Group offering some. There are probably others. Foreign exchange futures are an advanced investing tool and carry risk. Be sure you understand the risk, in particular how much money you can end up on the hook for if things don't go your way. Also remember, futures expire: you're not just betting on the rate changing, but you're betting on it changing within a certain amount of time.",
"title": ""
},
{
"docid": "518721",
"text": "\"Unless you are buying a significant value of your goods in USD then the relative strength of USD versus your local currency will have little to no effect on what the value of your investments is worth to you. In fact only (de|in)flation will effect your purchasing power. If your investments are in your local currency and your future expenses (usage of the returns on the investments) will be in your local currency FX has no effect. To answer your question, however, since all investments involve flows of money there can be no investment (other than perhaps gold which is really a form of currency) that isn't bound to at least one currency. In general investments are expected to be valued against the investor's home currency (I tend to call it \"\"fund currency\"\" as I work with hedge funds) as the return on the investment will be paid out in the fund currency and returns will be compared on the same basis. If investments are to be made internationally then it is necessary to reduce, or \"\"hedge\"\" the exchange rate risk. This is normally done using FX swaps or futures that allow an exchange rate in the future to be locked in today. Far from being unbound from FX moves these derivatives are closely bound to any moves but crucially are bound in the opposite direction to the hoped for FX move. an example of this would be if I'm investing 100GBP (my local currency) in a US company XYZ corp which I expect to do well. Suppose I get 200USD for my 100GBP and so buy 1 * 200USD shares in XYZ. No matter what happens to XYZ stock any move in GBP/USD will affect my P&L so I buy a future that allows me to exchange 200USD for 100GBP in 6 month's time. If GBP rises I can sell the future and make money on both the higher exchange rate and the increase in XYZ corp. If GBP falls I can keep the future until maturity and exchange the 200USD from XYZ corp for 100GBP so I only take the foreign exchange hit on any profits. If I expect my profits to be 10USD I can even buy futures such that I can lock in the exchange rate for 110USD in 6 months so that I will lose even less of my profit from the exchange rate move.\"",
"title": ""
},
{
"docid": "35340",
"text": "Investopedia has a section in their article about currency trading that states: The FX market does not have commissions. Unlike exchange-based markets, FX is a principals-only market. FX firms are dealers, not brokers. This is a critical distinction that all investors must understand. Unlike brokers, dealers assume market risk by serving as a counterparty to the investor's trade. They do not charge commission; instead, they make their money through the bid-ask spread. Principals-only means that the only parties to a transaction are agents who actively bear risk by taking one side of the transaction. There are forex brokers who charge what's called a commission, based on the spread. Investopedia has another article about the commission structure in the forex market that states: There are three forms of commission used by brokers in forex. Some firms offer a fixed spread, others offer a variable spread and still others charge a commission based on a percentage of the spread. So yes, there are forex brokers who charge a commission, but this paragraph is saying mostly the same thing as the first paragraph. The brokers make their money through the bid-ask spread; how they do so varies, and sometimes they call this charge a commission, sometimes they don't. All of the information above differs from the stock markets, however, in which The broker takes the order to an exchange and attempts to execute it as per the customer's instructions. For providing this service, the broker is paid a commission when the customer buys and sells the tradable instrument. The broker isn't taking a side in the trade, so he's not making money on the spread. He's performing the service of taking the order to an exchange an attempting to execute it, and for that, he charges a commission.",
"title": ""
},
{
"docid": "93518",
"text": "\"It may seem weird but interest rates are set by a market. Risk is a very large component of the price that a saver will accept to deposit their money in a bank but not the only one. Essentially you are \"\"lending\"\" deposited cash to the bank that you put it in and they will lend it out at a certain risk to themselves and a certain risk to you. By diversifying who they lend to (corporations, home-buyers each other etc.) the banks mitigate a lot of the risk but lending to the bank is still a risky endeavour for the \"\"saver\"\" and the saver accepts a given interest rate for the amount of risk there is in having the money in that particular bank. The bank is also unable to diversify away all possible risk, but tries to do the best job it can. If a bank is seen to take bigger risks and therefore be in greater risk of failing (having a run on deposits) it must have a requisitely higher interest rates on deposits compared to a lower risk bank. \"\"Savers\"\" therefore \"\"shop around\"\" for the best interest rate for a given level of risk which sets the viable interest rate for that bank; any higher and the bank would not make a profit on the money that it lends out and so would not be viable as a business, any lower and savers would not deposit their money as the risk would be too high for the reward. Hence competition (or lack of it) will set the rate as a trade off between risk and return. Note that governments are also customers of the banking industry when they are issuing fixed income securities (bonds) and a good deal of the lending done by any bank is to various governments so the price that they borrow money at is a key determinant of what interest rate the bank can afford to give and are part of the competitive banking industry whether they want to be or not. Since governments in most (westernised) countries provide insurance for deposits the basic level of (perceived) risk for all of the banks in any given country is about the same. That these banks lend to each other on an incredibly regular basis (look into the overnight or repo money market if you want to see exactly how much, the rates that these banks pay to and receive from each other are governed by interbank lending rates called Libor and Euribor and are even more complicated than this answer) simply compounds this effect because it makes all of the banks reliant on each other and therefore they help each other to stay liquid (to some extent). Note that I haven't mentioned currency at all so far but this market in every country applies over a number of currencies. The way that this occurs is due to arbitrage; if I can put foreign money into a bank in a country at a rate that is higher than the rate in its native country after exchange costs and exchange rate risk I will convert all of my money to that currency and take the higher interest rate. For an ordinary individual's savings that is not really possible but remember that the large multinational banks can do exactly the same thing with billions of dollars of deposits and effectively get free money. This means that either the bank's interest rate will fall to a risk adjusted level or the exchange rate will move. Either of those moves will remove the potential for making money for nothing. In this case, therefore it is both the exchange rate risk (and costs) as well as the loan market in that country that set the interest rate in foreign currencies. Demand for loans in the foreign currency is not a major mover for the same reason. Companies importing from foreign entities need cash in foreign currencies to pay their bills and so will borrow money in other currencies to fulfil these operations which could come from deposits in the foreign currency if they were available at a lower interest rate than a loan in local currency plus the costs of exchange but the banks will be unwilling to loan to them for less than the highest return that they can get so will push up interest rates to their risk level in the same way that they did in the market before currencies were taken into account. Freedom of movement of foreign currencies, however, does move interest rates in foreign currencies as the banks want to be able to lend as much of currencies that are not freely deliverable as they can so will pay a premium for these currencies. Other political moves such as the government wanting to borrow large amounts of foreign currency etc. will also move the interest rate given for foreign currencies not just because loaning to the government is less risky but also because they sometimes pay a premium (in interest) for being able to borrow foreign currency which may balance this out. Speculation that a country may change its base interest rate will move short term rates, and can move long term rates if it is seen to be a part of a country's economic strategy. The theory behind this is deep and involved but the tl;dr answer would be the standard \"\"invisible hand\"\" response when anything market or arbitrage related is involved. references: I work in credit risk and got a colleague who is also a credit risk consultant and economist to look over it. Arbitrage theory and the repo markets are both fascinating so worth reading about!\"",
"title": ""
},
{
"docid": "80871",
"text": "long deep ITM calls is equivalent to owning the equity. You're going to pay alot and hence will start off in a hole already, and you aren't getting too much leverage there at all depending how deep ITM you go. Covariance scales, but assuming B-S in order to get nice scaling and ignoring the risks you are actually taking with options (unlimited down-size ie you can lose your entire investment in the option, people forget this) will screw you unless you really know what you are dong. Leverage means increasing your risk. long dep ITM is not obtaining much leverage and therefore not risking too much. but you aren't going ot get 3-4x leverage this way. you get leverage by saying: oh, i have 100, i could invest in 1 share of stock OR I could buy 100 worth of some option. If I pick a deep ITM (think strike = 0) it's identical to owing the stock. If i pick ATM, i have a ~50/50 chance of wining, so i should be able to double my upside. If I go OTM, i can increase my exposure to the upside while increasing hte chance that my options expire worthless. So really, i have no idea why deep ITM do what you are trying to do. and If you don't either, you probably shouldn't do it.",
"title": ""
},
{
"docid": "496857",
"text": "\"HSBC, Hang Seng, and other HK banks had a series of special savings account offers when I lived in HK a few years ago. Some could be linked to the performance of your favorite stock or country's stock index. Interest rates were higher back then, around 6% one year. What they were effectively doing is taking the interest you would have earned and used it to place a bet on the stock or index in question. Technically, one way this can be done, for instance, is with call options and zero coupon bonds or notes. But there was nothing to strategize with once the account was set up, so the investor did not need to know how it worked behind the scenes... Looking at the deposit plus offering in particular, this one looks a little more dangerous than what I describe. See, now we are in an economy of low almost zero interest rates. So to boost the offered rate the bank is offering you an account where you guarantee the AUD/HKD rate for the bank in exchange for some extra interest. Effectively they sell AUD options (or want to cover their own AUD exposures) and you get some of that as extra interest. Problem is, if the AUD declines, then you lose money because the savings and interest will be converted to AUD at a contractual rate that you are agreeing to now when you take the deposit plus account. This risk of loss is also mentioned in the fine print. I wouldn't recommend this especially if the risks are not clear. If you read the fine print, you may determine you are better off with a multicurrency account, where you can change your HK$ into any currency you like and earn interest in that currency. None of these were \"\"leveraged\"\" forex accounts where you can bet on tiny fluctuations in currencies. Tiny being like 1% or 2% moves. Generally you should beware anything offering 50:1 or more leverage as a way to possibly lose all of your money quickly. Since you mentioned being a US citizen, you should learn about IRS form TD F 90-22.1 (which must be filed yearly if you have over $10,000 in foreign accounts) and google a little about the \"\"foreign account tax compliance act\"\", which shows a shift of the government towards more strict oversight of foreign accounts.\"",
"title": ""
},
{
"docid": "342903",
"text": "Here is the technical guidance from the accounting standard FRS 23 (IAS 21) 'The Effects of Changes in Foreign Exchange Rates' which states: Exchange differences arising on the settlement of monetary items or on translating monetary items at rates different from those at which they were translated on initial recognition during the period or in previous financial statements shall be recognised in profit or loss in the period in which they arise. An example: You agree to sell a product for $100 to a customer at a certain date. You would record the sale of this product on that date at $100, converted at the current FX rate (lets say £1:$1 for ease) in your profit loss account as £100. The customer then pays you several $100 days later, at which point the FX rate has fallen to £0.5:$1 and you only receive £50. You would then have a realised loss of £50 due to exchange differences, and this is charged to your profit and loss account as a cost. Due to double entry bookkeeping the profit/loss on the FX difference is needed to balance the journals of the transaction. I think there is a little confusion as to what constitutes a (realised) profit/loss on exchange difference. In the example in your question, you are not making any loss when you convert the bitcoins to dollars, as there is no difference in the exchange rate between the point you convert them. Therefore you have not made either a profit or a loss. In terms of how this effects your tax position; you only pay tax on your profit and loss account. The example I give above is an instance where an exchange difference is recorded to the P&L. In your example, the value of your cash held is reflected in your balance sheet, as an asset, whatever its value is at the balance sheet date. Unfortunately, the value of the asset can rise/fall, but the only time where you will record a profit/loss on this (and therefore have an impact on tax) is if you sell the asset.",
"title": ""
},
{
"docid": "87057",
"text": "The currency market, more often referred as Forex or FX, is the decentralized market through which the currencies are exchanged. To trade currencies, you have to go through a broker or an ECN. There are a lot's of them, you can find a (small) list of brokers here on Forex Factory. They will allow you to take very simple position on currencies. For example, you can buy EUR/USD. By doing so, you will make money if the EUR/USD rate goes up (ie: Euro getting stronger against the US dollar) and lose money if the EUR/USD rate goes down (ie: US dollar getting stronger against the Euro). In reality, when you are doing such transaction the broker: borrows USD, sell it to buy EUR, and place it into an Euro account. They will charge you the interest rate on the borrowed currency (USD) and gives you the interest and the bought currency (EUR). So, if you bought a currency with high interest rate against one with low interest rate, you will gain the interest rate differential. But if you sold, you will lose the differential. The fees from the brokers are likely to be included in the prices at which you buy and sell currencies and in the interest rates that they will charge/give you. They are also likely to gives you big leverage to invest far more than the money that you deposited in their accounts. Now, about how to make money out of this market... that's speculation, there are no sure gains about it. And telling you what you should do is purely subjective. But, the Forex market, as any market, is directed by the law of supply and demand. Amongst what impacts supply and demands there are: Also, and I don't want to judge your friends, but from experience, peoples are likely to tell you about their winning transaction and not about their loosing ones.",
"title": ""
},
{
"docid": "60020",
"text": "I prefer to use a Foreign Exchange transfer service. You will get a good exchange rate (better than from Paypal or from your bank) and it is possible to set it up with no transfer fees on both ends. You can use an ACH transfer from your US bank account to the FX's bank account and then a SEPA transfer in Europe to get the funds into your bank account. Transfers can also go in the opposite direction (Europe to USA). I've used XE's service (www.xe.com) and US Forex's service (www.usforex.com). Transferwise (www.transferwise.com) is another popular service. US Forex's service calls you to confirm each transfer. They also charge a $5 fee on transfers under $1000. XE's service is more convenient: they do not charge fees for small transfers and do not call you to confirm the tramsfer. However, they will not let you set up a free ACH transfer from US bank accounts if you set up your XE account outside the US. In both cases, the transfer takes a few business days to complete. EDIT: In my recent (Summer 2015) experience, US Forex has offered slightly better rates than XE. I've also checked out Transferwise, and for transfers from the US it seems to be a bit of a gimmick with a fee added late in the process. For reference, I just got quotes from the three sites for converting 5000 USD to EUR:",
"title": ""
},
{
"docid": "114624",
"text": "Fx Pip partnership Limited is a reliable trading signal and consultancy provider with many years of experience and significant success in the field of investments. All the members of the team, utilizing in the best way their scientific background and their excellent professionalism, achieve the best results. The Fx Pip Signal which has at its disposal its Research and Development department, has an aim to offer the international community of traders, the most reliable solution to the most difficult daily questions, such as: which product do we buy and which do we sell, at what price do we enter the market and at what price do we exit? The employees have a long term experience in the international foreign exchange industry, which gives them the edge of competitiveness and professionalism. We guarantee independency at the selection of online trading options. The only obligation of fxpipsignal.com is to you, our customer. An ongoing training of our employee(s) is a priority, to have good knowledge and to meet your needs. Fx Pip Signal provides signals of major currency pairs as EUR/USD, GBP/USD, USD/JPY USD/CHF. It provides signals which suits almost all the market around the world.It has four packages named Trial, Standard, Premium, Premium Plus. It has well organised support team to provide 24/7 live support and forex consultancy to gain meaningful profit. It believes in transperancy , relaibility and accuracy. All the signals are provided in a flexible way so that the subscribers can easily execute them and their desire profit. Fx Pip Signal is available in almost all the countries of the world. It provides signals via sms, email and updated in the website.",
"title": ""
},
{
"docid": "172025",
"text": "I recommended Currency Trading For Dummies, in my answer to Layman's guide to getting started with Forex (foreign exchange trading)? The nature of the contract size points toward only putting up a fraction of the value. The Euro FX contract size is 125,000 Euro. If you wish to send the broker US$125K+ to trade this contract, go ahead. Most people trade it with a few thousand dollars.",
"title": ""
},
{
"docid": "450694",
"text": "\"Q: How do currency markets work? A: The FX (foreign exchange) market works very much like the stock market where potential buying parties bid $Y of country 1's currency to buy $1 in country 2's currency. Potential selling parties sell (ask) $1 of country 2's currency for $Y of country 1's currency. Like the stock market, there are also a swaps, futures and options in this market. Q: What factors are behind why currencies go up or down? A: Just like any open market, currencies go up and down based on supply and demand. Many factors affect the supply and demand of a particular currency. Some were listed well by the other posts. Q: What roles do governments, central banks, institutions, and traders have in the process? A: It's common practice that gov'ts intervene to \"\"control\"\" the value of currencies. For example, although it's not general public knowledge, the Canadian gov't is actively purchasing up US dollars in the FX market in an effort to stop the US/Canadian exchange rate from dropping further. This has dramatic economic consequences for the Canadian ecomony if the Canadian dollar were to strengthen too far and too quickly.\"",
"title": ""
},
{
"docid": "253847",
"text": "While most all Canadian brokers allow us access to all the US stocks, the reverse is not true. But some US brokers DO allow trading on foreign exchanges. (e.g. Interactive Brokers at which I have an account). You have to look and be prepared to switch brokers. Americans cannot use Canadian brokers (and vice versa). Trading of shares happens where-ever two people get together - hence the pink sheets. These work well for Americans who want to buy-sell foreign stocks using USD without the hassle of FX conversions. You get the same economic exposure as if the actual stock were bought. But the exchanges are barely policed, and liquidity can dry up, and FX moves are not necessarily arbitraged away by 'the market'. You don't have the same safety as ADRs because there is no bank holding any stash of 'actual' stocks to backstop those traded on the pink sheets.",
"title": ""
},
{
"docid": "265267",
"text": "\"Perhaps buying some internationally exchanged stock of China real-estate companies? It's never too late to enter a bubble or profit from a bubble after it bursts. As a native Chinese, my observations suggest that the bubble may exist in a few of the most populated cities of China such as Beijing, Shanghai and Shenzhen, the price doesn't seem to be much higher than expected in cities further within the mainland, such as Xi'an and Chengdu. I myself is living in Xi'an. I did a post about the urban housing cost of Xi'an at the end of last year: http://www.xianhotels.info/urban-housing-cost-of-xian-china~15 It may give you a rough idea of the pricing level. The average of 5,500 CNY per square meter (condo) hasn't fluctuated much since the posting of the entry. But you need to pay about 1,000 to 3,000 higher to get something desirable. For location, just search \"\"Xi'an, China\"\" in Google Maps. =========== I actually have no idea how you, a foreigner can safely and easily profit from this. I'll just share what I know. It's really hard to financially enter China. To prevent oversea speculative funds from freely entering and leaving China, the Admin of Forex (safe.gov.cn) has laid down a range of rigid policies regarding currency exchange. By law, any native individual, such as me, is imposed of a maximum of $50,000 that can be converted from USD to CNY or the other way around per year AND a maximum of $10,000 per day. Larger chunks of exchange must get the written consent of the Admin of Forex or it will simply not be cleared by any of the banks in China, even HSBC that's not owned by China. However, you can circumvent this limit by using the social ID of your immediate relatives when submitting exchange requests. It takes extra time and effort but viable. However, things may change drastically should China be in a forex crisis or simply war. You may not be able to withdraw USD at all from the banks in China, even with a positive balance that's your own money. My whole income stream are USD which is wired monthly from US to Bank of China. I purchased a property in the middle of last year that's worth 275,000 CNY using the funds I exchanged from USD I had earned. It's a 43.7% down payment on a mortgage loan of 20 years: http://www.mlcalc.com/#mortgage-275000-43.7-20-4.284-0-0-0.52-7-2009-year (in CNY, not USD) The current household loan rate is 6.12% across the entire China. However, because this is my first property, it is discounted by 30% to 4.284% to encourage the first house purchase. There will be no more discounts of loan rate for the 2nd property and so forth to discourage speculative stocking that drives the price high. The apartment I bought in July of 2009 can easily be sold at 300,000 now. Some of the earlier buyers have enjoyed much more appreciation than I do. To give you a rough idea, a house bought in 2006 is now evaluated 100% more, one bought in 2008 now 50% more and one bought in the beginning of 2009 now 25% more.\"",
"title": ""
},
{
"docid": "580757",
"text": "If you do not understand the volatility of the fx market, you need to stop trading it, immediately. There are many reasons that fx is riskier than other types of investing, and you bear those risks whether you understand them or not. Below are a number of reasons why fx trading has high levels of risk: 1) FX trades on the relative exchange rate between currencies. That means it is a zero-sum game. Over time, the global fx market cannot 'grow'. If the US economy doubles in size, and the European economy doubles in size, then the exchange rate between the USD and the EUR will be the same as it is today (in an extreme example, all else being equal, yes I know that value of currency /= value of total economy, but the general point stands). Compare that with the stock market - if the US economy doubles in size, then effectively the value of your stock investments will double in size. That means that stocks, bonds, etc. tied to real world economies generally increase when the global economy increases - it is a positive sum game, where many players can be winners. On the long term, on average, most people earn value, without needing to get into 'timing' of trades. This allows many people to consider long-term equity investing to be lower risk than 'day-trading'. With FX, because the value of a currency is in its relative position compared with another currency, 1 player is a winner, 1 player is a loser. By this token, most fx trading is necessarily short-term 'day-trading', which by itself carries inherent risk. 2) Fx markets are insanely efficient (I will lightly state that this is my opinion, but one that I am not alone in holding firmly). This means that public information about a currency [ie: economic news, political news, etc.] is nearly immediately acted upon by many, many people, so that the revised fx price of that currency will quickly adjust. The more efficient a market is, the harder it is to 'time a trade'. As an example, if you see on a news feed that the head of a central bank authority made an announcement about interest rates in that country [a common driver of fx prices], you have only moments to make a trade before the large institutional investors already factor it into their bid/ask prices. Keep in mind that the large fx players are dealing with millions and billions of dollars; markets can move very quickly because of this. Note that some currencies trade more frequently than others. The main currency 'pairs' are typically between USD and / or other G10 country-currencies [JPY, EUR, etc.]. As you get into currencies of smaller countries, trading of those currencies happens less frequently. This means that there may be some additional time before public information is 'priced in' to the market value of that currency, making that currency 'less efficient'. On the flip side, if something is infrequently traded, pricing can be more volatile, as a few relatively smaller trades can have a big impact on the market. 3) Uncertainty of political news. If you make an fx trade based on what you believe will happen after an expected political event, you are taking risk that the event actually happens. Politics and world events can be very hard to predict, and there is a high element of chance involved [see recent 'expected' election results across the world for evidence of this]. For something like the stock market, a particular industry may get hit every once in a while with unexpected news, but the fx market is inherently tied to politics in a way that may impact exchange rates multiple times a day. 4) Leveraging. It is very common for fx traders to borrow money to invest in fx. This creates additional risk because it amplifies the impact of your (positive or negative) returns. This applies to other investments as well, but I mention it because high degrees of debt leveraging is extremely common in FX. To answer your direct question: There are no single individual traders who spike fx prices - that is the impact you see of a very efficient market, with large value traders, reacting to frequent, surprising news. I reiterate: If you do not understand the risks associated with fx trade, I recommend that you stop this activity immediately, at least until you understand it better [and I would recommend personally that any amateur investor never get involved in fx at all, regardless of how informed you believe you are].",
"title": ""
},
{
"docid": "403948",
"text": "If you hold this money in USD and spend it in the US as USD, then there is no tax liability or reporting requirement at all. You are not subject to any tax on foreign exchange gains and losses because you have not performed any foreign exchange. CRA says a foreign exchange gain or loss happens when the fx transaction occurs—not as the currency’s value fluctuates while on deposit - and since you are never performing an fx transaction, no such issues will arise. The CRA is not interested in how you spend your money, only the money that you earn. The only possible tax liability that would arise in the circumstances that you describe would be the tax liability arising from interest earned while the cash in on deposit. If this interest exceeds the threshold of reportability, then your bank will issue you with a T-slip to be included in your tax return.",
"title": ""
},
{
"docid": "584223",
"text": "There are options on options. Some derivative instruments assets ARE options (some ETFs), and you are able to buy shares of those ETFs OR options on those ETFs. Secondly, options are just a contract, so you just need to write one up and find someone to buy the contract. The only thing is that the exchange won't facilitate it, so you will have liquidity issues. What you want to do is a diagonal / calendar spread. Buy the back month option, sell the front month option, this isn't a foreign concept and nobody is stopping you. Since you have extra leverage on your LEAPS, then you just need to change the balancing of your short leg to match the amount of leverage the leaps will provide. (so instead of buying,selling 1:1, you need to buy one leap and perhaps sell 5 puts)",
"title": ""
},
{
"docid": "476834",
"text": "Like most other investment decisions - it depends. Specifically in this case it depends upon your view of the FX (Foreign Exchange) market over the next few years, and how sensitive you are to losses. As you correctly note, a hedge has a cost, so it detracts from your overall return. But given that you need to repatriate the investment eventually to US Dollars, you need to be aware of the fluctuations of the dollar versus other currencies. If you believe that over your time horizon, the US dollar will be worth the same as now or less, then you should not buy the hedge. If the dollar is the same - the choice is/was obvious. If you believe the US dollar will be weaker in the future, that means that when you repatriate back to US dollars, you will purchase more dollars with your foreign currency. If on the other hand, you believe the US Dollar will get stronger, then you should certainly lock in some kind of hedge. That way, when your foreign currency would have effectively bought fewer US, you will have made money on the hedge to make up the difference. If you choose not to hedge now, you can likely hedge that exposure at any time in the future, separate from the initial investment purchase buy buying/selling the appropriate FX instrument. Good Luck",
"title": ""
},
{
"docid": "127894",
"text": "Disregarding leverage and things alike, I would like to know what's the difference between opening a position in Forex on a pair through a broker, for example, and effectively buy some currency in a traditional bank-to-bank transition The forex account may pay or charge you interest whereas converting your currency directly will not. Disregarding leverage, the difference would be interest.",
"title": ""
},
{
"docid": "528475",
"text": "\"This is an old post I feel requires some more love for completeness. Though several responses have mentioned the inherent risks that currency speculation, leverage, and frequent trading of stocks or currencies bring about, more information, and possibly a combination of answers, is necessary to fully answer this question. My answer should probably not be the answer, just some additional information to help aid your (and others') decision(s). Firstly, as a retail investor, don't trade forex. Period. Major currency pairs arguably make up the most efficient market in the world, and as a layman, that puts you at a severe disadvantage. You mentioned you were a student—since you have something else to do other than trade currencies, implicitly you cannot spend all of your time researching, monitoring, and investigating the various (infinite) drivers of currency return. Since major financial institutions such as banks, broker-dealers, hedge-funds, brokerages, inter-dealer-brokers, mutual funds, ETF companies, etc..., do have highly intelligent people researching, monitoring, and investigating the various drivers of currency return at all times, you're unlikely to win against the opposing trader. Not impossible to win, just improbable; over time, that probability will rob you clean. Secondly, investing in individual businesses can be a worthwhile endeavor and, especially as a young student, one that could pay dividends (pun intended!) for a very long time. That being said, what I mentioned above also holds true for many large-capitalization equities—there are thousands, maybe millions, of very intelligent people who do nothing other than research a few individual stocks and are often paid quite handsomely to do so. As with forex, you will often be at a severe informational disadvantage when trading. So, view any purchase of a stock as a very long-term commitment—at least five years. And if you're going to invest in a stock, you must review the company's financial history—that means poring through 10-K/Q for several years (I typically examine a minimum ten years of financial statements) and reading the notes to the financial statements. Read the yearly MD&A (quarterly is usually too volatile to be useful for long term investors) – management discussion and analysis – but remember, management pays themselves with your money. I assure you: management will always place a cherry on top, even if that cherry does not exist. If you are a shareholder, any expense the company pays is partially an expense of yours—never forget that no matter how small a position, you have partial ownership of the business in which you're invested. Thirdly, I need to address the stark contrast and often (but not always!) deep conflict between the concepts of investment and speculation. According to Seth Klarman, written on page 21 in his famous Margin of Safety, \"\"both investments and speculations can be bought and sold. Both typically fluctuate in price and can thus appear to generate investment returns. But there is one critical difference: investments throw off cash flow for the benefit of the owners; speculations do not. The return to the owners of speculations depends exclusively on the vagaries of the resale market.\"\" This seems simple and it is; but do not underestimate the profound distinction Mr. Klarman makes here. (and ask yourself—will forex pay you cash flows while you have a position on?) A simple litmus test prior to purchasing a stock might help to differentiate between investment and speculation: at what price are you willing to sell, and why? I typically require the answer to be at least 50% higher than the current salable price (so that I have a margin of safety) and that I will never sell unless there is a material operating change, accounting fraud, or more generally, regime change within the industry in which my company operates. Furthermore, I then research what types of operating changes will alter my opinion and how severe they need to be prior to a liquidation. I then write this in a journal to keep myself honest. This is the personal aspect to investing, the kind of thing you learn only by doing yourself—and it takes a lifetime to master. You can try various methodologies (there are tons of books) but overall just be cautious. Money lost does not return on its own. I've just scratched the surface of a 200,000 page investing book you need to read if you'd like to do this professionally or as a hobbyist. If this seems like too much or you want to wait until you've more time to research, consider index investing strategies (I won't delve into these here). And because I'm an investment professional: please do not interpret anything you've read here as personal advice or as a solicitation to buy or sell any securities or types of securities, whatsoever. This has been provided for general informational purposes only. Contact a financial advisor to review your personal circumstances such as time horizon, risk tolerance, liquidity needs, and asset allocation strategies. Again, nothing written herein should be construed as individual advice.\"",
"title": ""
},
{
"docid": "334495",
"text": "You have two problems, money exchange commissions and currency risk. Commissions are always exorbitant. First you must find the cheapest way to get your money converted to the foreign currency and into your brokerage account. The absolute cheapest way may involve some research and financial institution maneuvering. Also I'd forget about anything other than USD for the foreseeable future. Any other foreign currency will probably have higher commissions and a weaker market. Once you have that down, you must avoid needlessly exchanging currencies. Keep a balance in the foreign currency, keep all dividends and capital gains there, and only take local money out of your brokerage account right before using it. That means of course that you need to keep enough local currency to pay taxes on any gains, etc. As for currency risk, there are two solutions. One solution is to buy your risk away using forex. You sell an amount of USD/AED lots that is mostly equivalent to your current investments and then just make sure you don't get margin calls. I'm not sure just how cheap your rates would be in the UAE, but, on average, your investments should still have positive returns. The other solution is to just stop seeing exchange rate fluctuations as losses. If you had USD 100k and now you have USD 115k how are you losing money? Exchange rates can go the other way just fine, you know, and holding USD is a good way to hedge against your country going south.",
"title": ""
},
{
"docid": "279151",
"text": "\"What you're looking for are either FX Forwards or FX Futures. These products are traded differently but they are basically the same thing -- agreements to deliver currency at a defined exchange rate at a future time. Almost every large venue or bank will transact forwards, when the counterparty (you or your broker) has sufficient trust and credit for the settlement risk, but the typical duration is less than a year though some will do a single-digit multi-year forward on a custom basis. Then again, all forwards are considered custom contracts. You'll also need to know that forwards are done on currency pairs, so you'll need to pick the currency to pair your NOK against. Most likely you'll want EUR/NOK simply for the larger liquidity of that pair over other possible pairs. A quote on a forward will usually just be known by the standard currency pair ticker with a settlement date different from spot. E.g. \"\"EUR/NOK 12M\"\" for the 12 month settlement. Futures, on the other hand, are exchange traded and more standardized. The vast majority through the CME (Chicago Mercantile Exchange). Your broker will need access to one of these exchanges and you simply need to \"\"qualify\"\" for futures trading (process depends on your broker). Futures generally have highest liquidity for the next \"\"IMM\"\" expiration (quarterly expiration on well known standard dates), but I believe they're defined for more years out than forwards. At one FX desk I've knowledge of, they had 6 years worth of quarterly expirations in their system at any one time. Futures are generally known by a ticker composed of a \"\"globex\"\" or \"\"cme\"\" code for the currency concatenated with another code representing the expiration. For example, \"\"NOKH6\"\" is 'NOK' for Norwegian Krone, 'H' for March, and '6' for the nearest future date's year that ends in '6' (i.e. 2016). Note that you'll be legally liable to deliver the contracted size of Krone if you hold through expiration! So the common trade is to hold the future, and net out just before expiration when the price more accurately reflects the current spot market.\"",
"title": ""
},
{
"docid": "19367",
"text": "With your experience, I think you'd agree that trading over a standardized, regulated exchange is much more practical with the amount of capital you plan to trade with. That said, I'd highly advise you to consider FX futures at CME, cause spot forex at the bucket shops will give you a ton of avoidable operational risks.",
"title": ""
},
{
"docid": "179073",
"text": "Foreign stocks have two extra sources of risk attached to them; exchange rate and political. Exchange rate risk is obvious; if I buy a stock in a foreign currency and there is a currency movement that makes that investment worth less I lose money no matter what the stock does. This can be offset using exchange rate swaps. (This is ceteris paribus, of course; changes in exchange rate can give a comparative advantage to international and exporting companies that will improve the fundamentals and so increase the price of the stock relative to a local firm. The economics of the firms in particular are not explored in this answer as it would get too complicated and long if I did.) Political risk relates not only to the problems surrounding international politics such as a country deciding that foreign nationals may no longer own shares in their national industries or deciding to seize foreign nationals' assets as happens in some areas. Your home country may also decide to apply sanctions to the country in which you are invested thus making it impossible to get your money back even though the foreign country will allow you to redeem them or sell. Diplomatic relations and trade agreements tend to be difficult. There are further problems in lack of understanding of foreign countries' laws, tax code, customs etc. relating to investments and the necessity to find legal representation in a country you may never have visited if there are issues. There is also a hidden risk in that, as an individual investor, you are not likely to be reading the local financial news for that country regularly enough to spot company specific issues arising. By the time these issues get into international media its far too late as all of the local investors have sold out of their positions already. The risks are probably no different if you have the time to monitor international relations and the foreign country's news, and have FX swaps in place to counteract FX risk as the funds and investment banks do but as an individual investor the time required is not feasible.",
"title": ""
},
{
"docid": "151203",
"text": "A derivative in finance is simply any asset whose value is based on the value of another asset or based on the value of a group of assets. A derivative contract is a type of contract (usually a 'standardized contract') with specific payout instruction based on the price changes of a different asset. The basic idea is that it becomes easier to make a claim to an asset or property (and profit from this claim), without needing to physically transfer it (or even the title to said asset), and use much less capital to do so (reduce risk). They become problematic when multiple people may have claims to the real asset, or when the value of the derivatives changes very quickly or are hard to calculate. There are also liquidity problems the further you get from the real asset. This is not a problem for all kinds of derivatives contracts. And you must recognize that derivatives are used colloquially in a way that has nothing to do with reality to cause fear in people/investors that are not financially savvy. Many derivatives also have dubious or no economic purposes such that regulators don't allow them to be traded since they can't see how it is different from gambling. This is seen in financial markets that are less liberalized or cultures with puritanical backgrounds. Typically the trick is to convince regulators that the derivative or financial product helps with reducing risk and hedging and it will get approved. I've mentioned some terminology, but this depends specifically on what kind of derivatives contract you become interested in. Swaps, Credit Default Swaps, Futures, Options, Options on Futures, Leveraged Exchange Traded Funds, Inverse Leveraged Exchange Traded Funds, warrants, and more all have their own terminology. How to trade them in a simulation? It all depends on which financial product you really become interested in.",
"title": ""
},
{
"docid": "66119",
"text": "How can I calculate my currency risk exposure? You own securities that are priced in dollars, so your currency risk is the amount (all else being equal) that your portfolio drops if the dollar depreciates relative to the Euro between now and the time that you plan to cash out your investments. Not all stocks, though, have a high correlation relative to the dollar. Many US companies (e.g. Apple) do a lot of business in foreign countries and do not necessarily move in line with the Dollar. Calculate the correlation (using Excel or other statistical programs) between the returns of your portfolio and the change in FX rate between the Dollar and Euro to see how well your portfolio correlated with that FX rate. That would tell you how much risk you need to mitigate. how can I hedge against it? There are various Currency ETFs that will track the USD/EUR exchange rate, so one option could be to buy some of those to offset your currency risk calculated above. Note that ETFs do have fees associated with them, although they should be fairly small (one I looked at had a 0.4% fee, which isn't terrible but isn't nothing). Also note that there are ETFs that employ currency risk mitigation internally - including one on the Nasdaq 100 . Note that this is NOT a recommendation for this ETF - just letting you know about alternative products that MIGHT meet your needs.",
"title": ""
},
{
"docid": "24856",
"text": "\"In general, there should be a \"\"liquidity premium\"\" which means that less-liquid stocks should be cheaper. That's because to buy such a stock, you should demand a higher rate of return to compensate for the liquidity risk (the possibility that you won't be able to sell easily). Lower initial price = higher eventual rate of return. That's what's meant when Investopedia says the security would be cheaper (on average). Is liquidity good? It depends. Here's what illiquidity is. Imagine you own a rare piece of art. Say there are 10 people in the world who collect this type of art, and would appreciate what you own. That's an illiquid asset, because when you want to sell, maybe those 10 people aren't buying - maybe they don't want your particular piece, or they all happen to be short on funds. Or maybe worse, only one of them is buying, so they have all the negotiating leverage. You'll have to lower your price if you're really in a hurry to sell. Maybe if you lower your price enough, you can get one of the 10 buyers interested, even if none were initially. An illiquid asset is bad for sellers. Illiquid means there aren't enough buyers for you to get a bidding war going at the time of your choosing. You'll potentially have to wait around for buyers to turn up, or for a stock, maybe you'd have to sell a little bit at a time as buyers want the shares. Illiquid can be bad for buyers, too, if the buyer is for some reason in a hurry; maybe nobody is selling at any given time. But, usually buyers don't have to be in a hurry. An exception may be if you short sell something illiquid (brokers often won't let you do this, btw). In that case you could be a forced buyer and this could be very bad on an illiquid security. If there are only one or two sellers out there, they now have the negotiating leverage and they can ask whatever price they want. Illiquidity is very bad when mixed with margin or short sales because of the potential for forced trades at inopportune times. There are plenty of obscure penny stocks where there might be only one or two trades per day, or fewer. The spread is going to be high on these because the bids at a given time will just be lowball offers from buyers who aren't really all that interested, unless you want to give your stock away, in which case they'll take it. And the asks are going to be from sellers who want to get a decent price, but maybe there aren't really any buyers willing to pay, so the ask is just sitting there with no takers. The bids and asks may be limit orders that have been sitting open for 3 weeks and forgotten about. Contrast with a liquid asset. For example, a popular-model used car in good condition would be a lot more liquid than a rare piece of art, though not nearly as liquid as most stocks. You can probably find several people that want to buy it living nearby, and you're not going to have to drop the price to get a buyer to show up. You might even get those buyers in a bidding war. From illiquid penny stocks, there's a continuum all the way up to the most heavily-traded stocks such as those in the S&P500. With these at a given moment there will be thousands of buyers and sellers, so the spread is going to close down to nearly zero. If you think about it, just statistically, if there are thousands of bids and thousands of asks, then the closest bid-ask pair is going to be close together. That's a narrow spread. While if there are 3 bids and 2 asks on some illiquid penny stock, they might be dollars away from each other, and the number of shares desired might not match up. You can see how liquidity is good in some situations and not in others. An illiquid asset gives you more opportunity to get a good deal because there aren't a lot of other buyers and sellers around and there's some opportunity to \"\"negotiate\"\" within the wide spread. For some assets maybe you can literally negotiate by talking to the other party, though obviously not when trading stocks on an exchange. But an illiquid asset also means you might get a bad deal, especially if you need to sell quickly and the only buyers around are making lowball offers. So the time to buy illiquid assets is when you can take your time on both buying and selling, and will have no reason for a forced trade on a particular timeline. This usually means no debt is involved, since creditors (including your margin broker) can force you to trade. It also means you don't need to spend the money anytime soon, since if you suddenly needed the money you'd have a forced trade on your hands. If you have the time, then you put a price out there that's very good for you, and you wait for someone to show up and give you that price - this is how you get a good deal. One more note, another use of the term liquid is to refer to assets with low or zero volatility, such as money market funds. An asset with a lot of volatility around its intrinsic or true value is effectively illiquid even if there's high trade volume, in that any given point in time might not be a good time to sell, because the price isn't at the right level. Anyway, the general definition of a liquid investment is one that you'd be comfortable cashing out of at a moment's notice. In this sense, most stocks are not all that liquid, despite high trading volume. In different contexts people may use \"\"liquid\"\" in this sense or to mean a low bid-ask spread.\"",
"title": ""
},
{
"docid": "537711",
"text": "\"Before going into specific investments, I think it would be a good idea to assess how \"\"free\"\" is that $5000. How much do you have to rely on it in emergency? You always want to buy low and sell high. However, if you need to make unplanned withdraw from an investment, you risk unfavorable market conditions at the time when you need the money, and lose money that way. One common suggestion is to keep 3-6 months living expense in checking/saving/very, very liquid/short term investments. After that, you can invest the rest in more profitable ventures. Assuming that you are all set in that regard, next consideration is whether you have any goal for the money besides generating the maximum return. Is this for retirement, buying a house/apartment a few year down the road, graduate school, emergency cash store for the time between graduation and getting a job, or traveling a year in Europe after graduation? There are myriad of other possible goals. Knowing that you get a better idea of the time frame involved in the investment, and what you need to do with your money. If this is for retirement, you just need to generate the highest possible return for 40-50 years, while minimize taxes when you have to withdraw that money (there are more nuanced concerns, but large idea-wise that's what you need to do). If you want it for a trip to an exotic location in 2 year, then your primary goal will be to preserve the value of your capital, while assessing whether you need to manage foreign-exchange risk. The time frame also rule in or rule out certain types of investments. If you are planning to use the money to purchase a house in 5 years, IRAs probably would not be what you are looking for. If you are planning to retirement, short term CD would not be the most effective way. After figuring out a bit of what you are trying to do with the money, I think how you want to invest it will be much more clear to you. In case of retirement, people seem to generally recommend no load index funds, and mid-cap growth funds. Nothing is really off the table, since your investment time frame is so long, and you can tolerate risk. You might also be interested to check out https://www.wealthfront.com/ (I have no relation with them). A friend recommended it to me, and I think their pitch make sense. In other cases, it really is case dependent, and there might have more than one solution to any case. There is just one more potential investment venture that people you might not immediately thinking of, and that might be of interest to you. That is to use the $5000 as your own budget to build/maintain connections with people and network. Use it to take professors out to a meal to pick their brain, travel to keep in touch with old friends, network with potential future employers and peers to improve job prospect, or get opportunities to meet interesting people. I hope this helps.\"",
"title": ""
},
{
"docid": "373228",
"text": "\"Which was the foreign airline and what currency do they bill in? It's surprising to think there could be an FX exchange gain, after 30 days, considering the \"\"Thomas Cook\"\" high street spreads you (or your credit card company) ought to be being charged... In other words the rate would have to move at least 20% before you saw any FX gain from bid to offer.\"",
"title": ""
},
{
"docid": "393823",
"text": "Given that we live in a world rife with geopolitical risks such as Brexit and potential EU breakup, would you say it's advisable to keep some of cash savings in a foreign currency? Probably not. Primarily because you don't know what will happen in the fallout of these sorts of political shifts. You don't know what will happen to banking treaties between the various countries involved. If you can manage to place funds on deposit in a foreign bank/country in a currency other than your home currency and maintain the deposit insurance in that country and not spend too much exchanging your currency then there probably isn't a downside other than liquidity loss. If you're thinking I'll just wire some whatever currency to some bank in some foreign country in which you have no residency or citizenship consideration without considering deposit insurance just so you might protect some of your money from a possible future event I think you should stay away.",
"title": ""
}
] |
473
|
Financially Shielded Entity Separating Individuals Behind It From Risks
|
[
{
"docid": "466037",
"text": "You are describing a corporation. You can set up a corporation to perform business, but if you were using the money for any personal reasons the courts could Pierce the corporate veil and hold you personally liable. Also, setting up a corporation for purely personal reasons is fraud.",
"title": ""
}
] |
[
{
"docid": "540334",
"text": "\"There are TWO parts to an LLC or any company structure. This being the entire point of creating an LLC. The context is that a lawyer is after your LLC, and he's arguing that the LLC is not genuine, so he can go after your personal assets - your house, car, IRAs, tap your wife's salary etc. This is called \"\"piercing the corporate veil\"\". What would he use to claim the LLC is not genuine? The determination here is between you and the judge in a lawsuit. Suffice it to say, the way you withdraw money must consider the above issues, or you risk breaking the liability shield and becoming personally liable, which means you've been wasting the $25 every year to keep it registered. The IRS has a word for single member LLCs: \"\"Disregarded entity\"\". The IRS wants to know that the entity exists and it's connected to you. But for reporting tax numbers, they simply want the LLC's numbers folded into your personal numbers, because you are the same entity for tax purposes. The determination here is made by you. *LLCs are incredible versatile structures, and you can actually choose to have it taxed like a corporation where it is a separate \"\"person\"\" which files its own tax return. * The IRS doesn't care how you move money from the LLC to yourself, since it's all the same to them. The upshot is that while your own lawyer prohibits you from thinking of the assets as \"\"all one big pile\"\", IRS requires you to. Yes, it's enough to give you whiplash.\"",
"title": ""
},
{
"docid": "480472",
"text": "Of course not. You had another job for which you earned money. What does the corporation have to do with it? Corporation is a separate entity from your person, and since it was in no way involved in the transaction - there's no justification to funnel money through it. Doing so may pierce the corporate veil and expose you to liability which you created the corporation to shield yourself from. Not to mention the tax evasion, which is the reason you are asking the question to begin with....",
"title": ""
},
{
"docid": "348862",
"text": "I imagine that it wouldn't affect consumer debt significantly. Individuals are separate entities from their government like how stockholders are separate entities from a corporation. It would probably make it harder for the country to raise money through bonds. Who wants to purchase bonds from a country that won't pay you back?",
"title": ""
},
{
"docid": "103439",
"text": "The main problem I have with Uber is they represent themselves differently in some contexts than others. To most customers, Uber is Uber, not the individual who is driving. Conceptually, individuals not being able to shield themselves behind a corporation is an interesting idea, with both pros and cons.",
"title": ""
},
{
"docid": "361442",
"text": "From my Capital Markets and Institutions assignment on 2007 - 2008 Financial Crisis The subprime financial crisis that emerged in the summer of 2007 is much too intricate and interwoven to place the blame solely on one organisation or group of individuals. Each actor involved is responsible for and party to—in varying degrees—the events that transpired. Mortgage brokers (individuals) • First line of contact between an originator and a borrower • Out to get theirs; greedy • Disregard for borrowers, only want to originate as many mortgages as possible • Engaged in controversial practices – confusing, pressuring, lying to borrowers in order to secure a mortgage • Took advantage of 2/28 mortgages in order to collect new origination fees • Offered piggyback mortgages requiring no money down Mortgage originators (organisations) • Began lending to subprime borrowers during the 1990s – done through brokers to whom they paid a commission • Largely supplanted loans made by the FHA through traditional lenders • Many originators acquired by large investment banks • Cashed in on and espoused the “American dream” of home ownership • Different interest rates charged to borrowers • Use of statistical software and credit scores to evaluate borrowers • Popularised 2/28 mortgages • Allowed borrowers to take out mortgages with little or no documentation • Rapidly increased $ amount of mortgages issued • In charge of servicing mortgages issued – making reasonable efforts to collect principal and interest, able to foreclose on properties when delinquent • Profited from massive fees (late and other) added when loans were delinquent • First firms to suffer from the increase in foreclosures Investment banks • Often acquired mortgage originators to gain yet another revenue stream • Responsible for creating CDO entities, often registered in tax havens • CDOs took on large positions in MBSs and created subordinate obligations, also CDOs • CDO entities held assets of other CDOs, creating a complex interwoven situation • CDOs were also involved with positions in other securities • IB-controlled hedge funds often hedged risks through buying highly-rated MBSs • CDOs holding long-term debt were funded through the short-term commercial paper market – high ratings secured through IB lines of credit • Also pioneered SIVs – relied on highly-rated CP market; lines of credit combined with investor equity allowed IBs to keep SIVs off B/S • IBs heavily invested in MBSs/CDOs began to run into liquidity problems • Required capital investment to remain operational – often found abroad (e.g. Abu Dhabi, Chinese, Singaporean governments) • Largely responsible for the monetary policy pursued by the Fed during 2007/2008 • Conduct raised questions as to the regulation of the entire financial industry • Contrast with their responsibility for much innovation and engineering in the financial services industry Credit ratings agencies • Party to major conflicts of interest • Overwhelmingly gave AAA ratings to MBSs • Agencies loosened their rating criteria and perhaps over-rated MBSs in an effort to gain more business from originators • Agencies also rated the debt of institutions that held positions in MBSs • CDOs holding MBSs obtained high ratings as well – statistical models used indicated them to be safe • Based high ratings in the commercial paper market on IB lines of credit – obliged the IBs in order to gain more business • Agency downgrades of MBSs/CDOs resulted in large IB losses, setting in motion further developments • Ratings became less useful as the MBS market froze up, with even AAA-rated MBSs struggling to find a market • Previously championed as an alternative to government intervention in the market • Role of ratings agencies heavily questioned in aftermath • Also questioned was how ratings in general should be used • RAs deflected claims that they acted irresponsibly during the subprime boom • Criticised for the large proportion of AAA-ratings given to MBSs o Argued that historical defaults on MBSs were lower than similar corporate bonds • Conflicts inherent in having issuers pay for ratings o Committees that assigned ratings were separate from negotiations regarding fees • Emphasized benefits of giving all investors free access to ratings rather than them paying for them • Wave of downgrades in 2nd half of 2007 a result of unexpectedly poor performance of subprime mortgages originated in 2006 o Attributed to: laxer underwriting standards, declines in housing prices, more restrictive borrowing standards that prevented borrowers from refinancing Investors • Backbone of many institutions – shareholders • Owned stock in IBs and GSEs, two major players in subprime crisis • Driving force behind institutions taking on riskier investments (e.g. MBSs) • Unwilling to inject more capital/equity into firms required them to turn elsewhere for aid • Worries that the crisis could spread to other markets (e.g. credit cards) added to worries • Grouped with IBs in being seen as responsible for the crisis o US government would not allow higher sale price for Bear Stearns to avoid appearance of bailing out investors",
"title": ""
},
{
"docid": "269646",
"text": "I find that there are two violation of law , prima facie , if someone earns money by depositing in the online account and then not reporting it ( including in his total income for the year ) and not bringing in India. Income Tax Act violation 1. It is simply comcealment liable for penalty & prosecution under I.T.Act. 2. You should know that anyone who is resident of India as per income Tax Act and having taxable income ( gross total income exceeding exemption limit) will have to fill up the column in his/her income tax return whether Previously these column were not in the Income Tax Return. So , now anyone who is liable to file return of Income can be tried for false return if he has hiddne assets aborad. 2. FEMA violation RBI permits remittance under Liberalized Remittance Scheme. However this scheme can not be used for certain purpose . It is important to examine whether RBI prohibits use of remittance for any entity or business you have described. You can read following FAQ on RBI site Q. 30. What are the prohibited items under the Scheme? Ans. The remittance facility under the Scheme is not available for the following: i) Remittance for any purpose specifically prohibited under Schedule-I (like purchase of lottery tickets/sweep stakes, proscribed magazines, etc.) or any item restricted under Schedule II of Foreign Exchange Management (Current Account Transactions) Rules, 2000; ii) Remittance from India for margins or margin calls to overseas exchanges / overseas counter-party; iii) Remittances for purchase of FCCBs issued by Indian companies in the overseas secondary market; iv) Remittance for trading in foreign exchange abroad; v) Remittance by a resident individual for setting up a company abroad; vi) Remittances directly or indirectly to Bhutan, Nepal, Mauritius and Pakistan; vii) Remittances directly or indirectly to countries identified by the Financial Action Task Force (FATF) as “non co-operative countries and territories”, from time to time; and viii) Remittances directly or indirectly to those individuals and entities identified as posing significant risk of committing acts of terrorism as advised separately by the Reserve Bank to the banks. You will have to examine , if the remittance was NOT done for purpose not allowed by RBI under LRS . If you clear this , you can say there is no violation and your violation is restricted to I.T.Act only.",
"title": ""
},
{
"docid": "556668",
"text": "\"I think the key to this question is your last sentence, because it's applicable to everyone, high net-worth or not: How would one determine whether they are better off without insurance? In general, insurance is a net good when the coverage would prevent a 'catastrophic' event. If a catastrophic event doesn't happen, oh well, you wasted money on insurance. If it does happen, you just saved yourself from bankruptcy. These are two separate outcomes, so taking the 'average' cost of a catastrophic event (and weighing that against the more expensive insurance premiums) is not practical. This is a way of reducing risk, not of maximizing returns. Let the insurance company take the risk - they benefit from having a pool of people paying premiums, and you benefit because your own life has less financial risk. Now for something like cheap home electronics, insurance is a bad idea. This is because you now have a 'pool' of potential risks, and your own life experience could be close to the 'average' expected result. Meaning you'll pay more for insurance than you would just replacing broken things. This answer is another good resource on the topic. So to your question, at what point in terms of net-worth does someone's house become equivalent to you and your toaster? Remember that if you have home fire insurance, you are protecting the value of your house, because that loss would be catastrophic to you. But a high net-worth individual would also likely find the loss of their house catastrophic. Unless they are billionaires with multiple 10M+ mansions, then it is quite likely that regardless of wealth, a significant portion of their worth is tied up in their home. Even 10% of your net worth would be a substantial amount. As an example, would someone worth $1M have only a 100k home? Would someone worth $10M have only a $1M Home? Depends on where they live, and how extravagantly. Similarly, if you were worth $10M, you might not need extra insurance on your Toyota Camry, but you might want it if you drive a $1M Ferrari! Not to mention that things like auto insurance may cover you for liability, which could extend beyond the value of your car, into medical and disability costs for anyone in an accident. In fact, being high net-worth may make you more vulnerable to lawsuits, making this insurance even more important. In addition, high net-worth individuals have insurance that you or I have no need of. Things like kidnapping insurance; business operation insurance, life insurance used to secure bank loans. So yes, even high net-worth individuals may fear catastrophic events, and if they have so much money - why wouldn't they pay to reduce that risk? Insurance provides a service to them the same as to everyone else, it's just that the items they consider too 'cheap' too insure are more expensive than a toaster. Edit to counter concerns in some other answers, which say that insurance is \"\"always a bad idea\"\": Imagine you are in a kafka-esque episode of \"\"Let's Make a Deal\"\". Monty Hall shows you two parallel universes, each with 100 doors. You must choose your universe, then choose a door. The first universe is where you bought insurance, and behind every door is a penalty of $200. The second universe is where you didn't buy insurance, and behind 99 doors is nothing, with one random door containing a penalty of $10,000. On average, playing the game 99,999 times, you will come out ahead 2:1 by not buying insurance. But you play the game only maybe 3 times in your life. So which universe do you choose? Now, you might say \"\"pfft - I can cover the cost of a 10k penalty if it happens\"\". But this is exactly the point - insurance (unless already required by law) is a net good when it covers catastrophic losses. If you are wealthy enough to cover a particular loss, you typically shouldn't buy that insurance. That's why no one should insure their toaster. This is not a question of \"\"average returns\"\", it is a question of \"\"risk reduction\"\".\"",
"title": ""
},
{
"docid": "265948",
"text": "If I bought 1 percent share of company X, Most countries company X, is treated as a separate legal entity than individual. So max loss is what you have invested. However certain types of companies, generally called partnerships are not separate entities and you have to pay back the said loss. However such companies are not traded on stock exchanges. Is there an age requirements to enter the stock market? Depends on country. Generally a minor can hold an account with a guardian.",
"title": ""
},
{
"docid": "142645",
"text": "\"It is definitely legal, however none of such expenses will be allowed as a tax deduction for the corporation. Basically, you'll end up paying more to maintain the entity and pay taxes on its income (the rent you're paying to yourself as a corporation) at corporate rates, for no apparent benefit. Being the director/executive in the corporation will make you liable for whatever the corporation is liable, so liability isn't going away. The reason corporation is considered \"\"limited liability\"\" for owners is because shareholders are shielded from the corporate liability. Not directors or executives (which are explicitly not shielded).\"",
"title": ""
},
{
"docid": "368165",
"text": "This is business as usual, except that you need to keep in mind that the corporate entity is separate from the individual. As such - all the background checks and references should be with regards to the actual renter - the corporation. You should be cautious as it is not so easy to dissolve an individual (well... Not as easy, and certainly not as legal), as it is to dissolve the corporation. So you may end up with a tenant who doesn't pay and doesn't have to pay because the actual renter, the corporation, no longer exists. So check the corporation background - age, credit worthiness, tax returns/business activity, judgements against, etc etc, as you would do for an individual.",
"title": ""
},
{
"docid": "34887",
"text": "\"Paying yourself through a corporation requires an analysis of a variety of issues. First, a salary paid to yourself creates RRSP contribution room as well as CPP contributions. Paying yourself a dividend achieves neither of those. By having a corporation, you will have to file a corporate (T2) tax return. The corporation is considered a separate legal entity from you. As an individual, you will still need to file a personal (T1) tax return. Never just \"\"draw\"\" money out of a corporation. This can create messy transactions involving loans to shareholders. Interest is due on these amounts and any amounts not paid within one calendar year are considered as wages by Canada Revenue and would need to be reported as income on your next T1 return. You should never withhold EI premiums as the sole owner of a corporation. You are considered exempt from these costs by CRA. Any amounts that have been remitted to CRA can be reclaimed by submitting a formal request. The decision on whether to take a salary or dividends normally requires some detailed analysis. Your accountant or financial advisor should be able to assist in this matter.\"",
"title": ""
},
{
"docid": "163923",
"text": "I think you're mixing up being incorporated with being public. A corporation is just a financially separate organization from the owner(s). There might be only one owner, but the company's assets are separated from the person's. A public company is one entity whose ownership is on the market - a shareholder can sell his or her portion easily. A company that decides it no longer wants to be public just becomes a private corporation, with ownership of its own assets, but with a few owners, not many.",
"title": ""
},
{
"docid": "383252",
"text": "No, you can not use Schedule C for a Corporation. If you treat the business as a sole proprietorship, i.e.: not a separate legal entity and not a separate financial entity - then you can. If that's how you treat your corporation, then you can continue using Schedule C, but there's no reason whatsoever to continue being a corporation either since the corporate liability protection veil is likely to be long gone. Generally, corporations file form 1120, S-Corporations file form 1120S.",
"title": ""
},
{
"docid": "449279",
"text": "If bank B has a transfer limit set, you bet that there is a nice reason for that. Either risk of fraud, liability, client preferences, profiling, credit scoring, etc, etc. For a bank, the cost of denying something [1] is way lower than the potential damages and liabilities of allowing something to go through. Regarding your concerns for the ACH, here is the summarized transaction walkthrough source: An Originator– whether that’s an individual, a corporation or another entity– initiates either a Direct Deposit or Direct Payment transaction using the ACH Network. ACH transactions can be either debit or credit payments and commonly include Direct Deposit of payroll, government and Social Security benefits, mortgage and bill payments, online banking payments, person-to-person (P2P) and business-to-business (B2B) payments, to name a few. Instead of using paper checks, ACH entries are entered and transmitted electronically, making transactions quicker, safer and easier. The Originating Depository Financial institution (ODFI) enters the ACH entry at the request of the Originator. The ODFI aggregates payments from customers and transmits them in batches at regular, predetermined intervals to an ACH Operator. ACH Operators (two central clearing facilities: The Federal Reserve or The Clearing House) receive batches of ACH entries from the ODFI. The ACH transactions are sorted and made available by the ACH Operator to the Receiving Depository Financial Institution (RDFI). The Receiver’s account is debited or credited by the RDFI, according to the type of ACH entry. Individuals, businesses and other entities can all be Receivers. Each ACH credit transaction settles in one to two business days, and each debit transaction settles in just one business day, as per the Rules. Take heed of this like: The Originator initiates a direct deposit/payment transaction. In your scenario, the originator would be B. But since the transaction amount is higher than the limit, B would not even initiate the ACH transaction. The request would be denied. So the transaction would look like this: [1] Usually this cost comes down to just the processing costs of the denied transaction (and it is rather fail-fast like). For the other parties involved it may have additional costs (missed deadlines, penalties for not fulfilling an obligation, fines, etc), but for the bank that is irrelevant.",
"title": ""
},
{
"docid": "257168",
"text": "\"A tax return is a document you sign and file with the government to self-report your tax obligations. A tax refund is the payment you receive from the government if your payments into the tax system exceeded your obligations. As others have mentioned, if an extra $2K in income generated $5K in taxes, chances are your return was prepared incorrectly. The selection of an appropriate entity type for your business depends a lot on what you expect to see over the next several years in terms of income and expenses, and the extent to which you want or need to pay for fringe benefits or make pretax retirement contributions from your business income. There are four basic flavors of entity which are available to you: Sole proprietorship. This is the simplest option in terms of tax reporting and paperwork required for ongoing operations. Your net (gross minus expenses) income is added to your wage income and you'll pay tax on the total. If your wage income is less than approximately $100K, you'll also owe self-employment tax of approximately 15% in addition to income tax on your business income. If your business runs at a loss, you can deduct the loss from your other income in calculating your taxable income, though you won't be able to run at a loss indefinitely. You are liable for all of the debts and obligations of the business to the extent of all of your personal assets. Partnership. You will need at least two participants (humans or entities) to form a partnership. Individual items of income and expense are identified on a partnership tax return, and each partner's proportionate share is then reported on the individual partners' tax returns. General partners (who actively participate in the business) also must pay self-employment tax on their earnings below approximately $100K. Each general partner is responsible for all of the debts and obligations of the business to the extent of their personal assets. A general partnership can be created informally or with an oral agreement although that's not a good idea. Corporation. Business entities can be taxed as \"\"S\"\" or \"\"C\"\" corporations. Either way, the corporation is created by filing articles of incorporation with a state government (doesn't have to be the state where you live) and corporations are typically required to file yearly entity statements with the state where they were formed as well as all states where they do business. Shareholders are only liable for the debts and obligations of the corporation to the extent of their investment in the corporation. An \"\"S\"\" corporation files an information-only return similar to a partnership which reports items of income and expense, but those items are actually taken into account on the individual tax returns of the shareholders. If an \"\"S\"\" corporation runs at a loss, the losses are deductible against the shareholders' other income. A \"\"C\"\" corporation files a tax return more similar to an individual's. A C corporation calculates and pays its own tax at the corporate level. Payments from the C corporation to individuals are typically taxable as wages (from a tax point of view, it's the same as having a second job) or as dividends, depending on how and why the payments are made. (If they're in exchange for effort and work, they're probably wages - if they're payments of business profits to the business owners, they're probably dividends.) If a C corporation runs at a loss, the loss is not deductible against the shareholders' other income. Fringe benefits such as health insurance for business owners are not deductible as business expenses on the business returns for S corps, partnerships, or sole proprietorships. C corporations can deduct expenses for providing fringe benefits. LLCs don't have a predefined tax treatment - the members or managers of the LLC choose, when the LLC is formed, if they would like to be taxed as a partnership, an S corporation, or as a C corporation. If an LLC is owned by a single person, it can be considered a \"\"disregarded entity\"\" and treated for tax purposes as a sole proprietorship. This option is not available if the LLC has multiple owners. The asset protection provided by the use of an entity depends quite a bit on the source of the claim. If a creditor/plaintiff has a claim based on a contract signed on behalf of the entity, then they likely will not be able to \"\"pierce the veil\"\" and collect the entity's debts from the individual owners. On the other hand, if a creditor/plaintiff has a claim based on negligence or another tort-like action (such as sexual harassment), then it's very likely that the individual(s) involved will also be sued as individuals, which takes away a lot of the effectiveness of the purported asset protection. The entity-based asset protection is also often unavailable even for contract claims because sophisticated creditors (like banks and landlords) will often insist the the business owners sign a personal guarantee putting their own assets at risk in the event that the business fails to honor its obligations. There's no particular type of entity which will allow you to entirely avoid tax. Most tax planning revolves around characterizing income and expense items in the most favorable ways possible, or around controlling the timing of the appearance of those items on the tax return.\"",
"title": ""
},
{
"docid": "28894",
"text": "I don't know about the US, but in the UK this is common practice, even required in some situations, and not sketchy at all. It's perfectly legal, saves you tax, and protects you from a legal standpoint. (i.e. what if you break something and your employer wants to sue you?) This is what companies are for, they are legal entities that are separate from an individual. There is no requirement for a company to have more than one employee.",
"title": ""
},
{
"docid": "291749",
"text": "No, thanks to the principle of corporate personhood. The legal entity (company C) is the owner and parent of the private company (sub S). You and C are separate legal entities, as are C and S. This principle helps to legally insulate the parties for purposes such as liability, torts, taxes, and so forth. If company C is sued, you may be financially at stake (i.e. your investment in C is devalued or made worthless) but you are not personally being sued. However, the litigant may attach you as an additional litigant if the facts of the suit merit it. But without legal separateness of corporations, then potentially all owners and maybe a number of the employees would be sued any time somebody sued the business - which is messy for companies and messy for litigants. It's also far cleaner for lenders to lend to unified business entities rather than a variety of thousands of ever-shifting shareholders. Note that this is a separate analysis that assumes the companies are not treated as partnerships or disregarded entities (tax nothings) for tax purposes, in which case an owner may for some purposes be imputed to own the assets of C. I've also ignored the consolidated tax return, which would allow C and S to file a type of corporate joint return that for some purposes treats them similarly to common entity. For the simplest variation of your question, the answer is no. You do not own the assets of a corporation by virtue of owning a few of its shares. Edit: In light of your edit to include FB and Whatsapp, and the wrinkle about corporate books. If sub S is 100% owned by company C, then you do not have any inspection rights to S because you are not a shareholder. You also do not have virtual corporation inspection rights through company C. However, if a person has inspection rights to company C, and sub S appears on the books and financial records of C, then your C rights will do the job of seeing S information. However, Facebook is a public company, so they will make regular public filings and disclosures that should at least partly cover Whatsapp. So I hedge and clear my throat by averring that my securities training is limited, but I believe that the SEC filings of a public company will as a practical matter (maybe a matter of law?) moot the inspection rights. At the very least, I suspect you'd need a proper purpose (under DGCL, for example), to demand the inspection, and they will have already made extensive disclosures that I believe will be presumptively sufficient. I defer to more experienced securities experts on that question, but I don't believe inspection rights are designed for public companies.",
"title": ""
},
{
"docid": "287156",
"text": "Both a trust and an estate are separate, legal, taxpaying entities, just like any individual. Income earned by the trust or estate property (e.g., rents collected from real estate) is income earned by the trust or the estate. Who is liable for taxes on income earned by a trust depends on who receives or retains benefits from the trust. Who is liable for taxes on income received by an estate depends on how the income is classified (i.e., income earned by the decedent, income earned by the estate, income in respect of the decedent, or income distributed to beneficiaries). Generally, trusts and estates are taxed like individuals. General tax principles that apply to individuals therefore also apply to trusts and estates. A trust or estate may earn tax−exempt income and may deduct certain expenses. Each is allowed a small exemption ($300 for a simple trust, $100 for a complex trust, $600 for an estate). However, neither is allowed a standard deduction. The tax brackets for income taxable to a trust or estate are much more compressed and can result in higher taxes than for individuals. In short, the trust should have been paying taxes on its gains all along, when the money transfers to you it will be taxed as ordinary income.",
"title": ""
},
{
"docid": "528553",
"text": "As others have suggested, if you're considering taking a 50% discount on a revenue stream you feel is low risk because you're having cash flow issues paying those property taxes - I'd recommend you seriously separating these two unrelated concerns and deal with each in most financially astute manner individually. You'll keep more of your hard earned cash You don't have the hassle factor and uncertainty of trying to become proficient in an esoteric field of financial knowledge by Christmas!",
"title": ""
},
{
"docid": "325677",
"text": "Mods decided to leave it here, so I'll summarize some of my answers on this question given @OnStartups. You can find them here, here and here. Your options are : You and your business are one and the same. You report your income and expenses for taxes on a Schedule C (for each sole proprietorship a separate schedule), and taxed at your personal rates. There's no liability protection or legal separation between you and your business, and you don't need to have any bureaucratic overhead of managing an entity. You can use your own bank account and have checks written to you directly. You can register for DBA if you want a store-front name to be different from your own name. Depending on State, can cost a lot or close to nothing. Provides certain liability protection (depending on State, single-member and multi-member LLC's may have different liability protections). You can chose to be taxed as either a sole-proprietor (partnership, for multi-member) or as a corporation. You have to separate your activities, have a separate bank account, and some minimal bureaucracy is required to maintain the entity. Benefits include the limited liability, relatively easy to add partners to the business or sell it as a whole, and provides for separation of your personal and business finances. Drawbacks - bureaucracy, additional fees and taxes (especially in CA), and separation of assets. Corporation is an entirely separate entity from yourself, files its own tax returns, has separate bank accounts and is run by the board of directors (which in some cases may require more than 1 person to be on the board, check your state laws on that). As an officer of the corporation you'll have to pay salary to yourself. S-Corp has the benefit of pass-through taxation, C-Corp doesn't and has double taxation. Benefits - liability protection, can sell shares to investors, legally distinct entity. Disadvantages - have to deal with payroll, additional accounting, significant bureaucracy and additional layer of taxes for C-Corp (double taxation). Selling corporate assets is always a taxable event (although in your case it is probably not of an importance). You have to talk to a lawyer in your state about the options re the liability protection and how to form the entities. The formation process is usually simple and straight forward, but the LLC/Partnership operating agreements and Corporation charters/bylaws must be drafted by a lawyer if you're not going to be the sole owner (even if you are - better get a lawyer draft something for you, its just easier to fix and change things when you're the sole owner). You have to talk to a CPA/EA in your state about the taxes and how the choice of entity affects them.",
"title": ""
},
{
"docid": "59000",
"text": "Tax Shield would be known as: A tax shield is a reduction in taxable income for an individual or corporation achieved through claiming allowable deductions such as mortgage interest, medical expenses, charitable donations, amortization and depreciation. These deductions reduce a taxpayer's taxable income for a given year or defer income taxes into future years. Tax shields lower the overall amount of taxes owed by an individual taxpayer or a business. I know of various real estate investors that will use depreciation as noted above to reduce their tax liability though others can use other deductions. Fortune has this on Buffett's taxes in 2015: Here’s the breakdown of Buffett’s income taxes for 2015, according to the statement:",
"title": ""
},
{
"docid": "454563",
"text": "If you are tax-resident in the US, then you must report income from sources within and without the United States. Your foreign income generally must be reported to the IRS. You will generally be eligible for a credit for foreign income taxes paid, via Form 1116. The question of the stock transfer is more complicated, but revolves around the beneficial owner. If the stocks are yours but held by your brother, it is possible that you are the beneficial owner and you will have to report any income. There is no tax for bringing the money into the US. As a US tax resident, you are already subject to income tax on the gain from the sale in India. However, if the investment is held by a separate entity in India, which is not a US domestic entity or tax resident, then there is a separate analysis. Paying a dividend to you of the sale proceeds (or part of the proceeds) would be taxable. Your sale of the entity containing the investments would be taxable. There are look-through provisions if the entity is insufficiently foreign (de facto US, such as a Subpart-F CFC). There are ways to structure that transaction that are not taxable, such as making it a bona fide loan (which is enforceable and you must pay back on reasonable terms). But if you are holding property directly, not through a foreign separate entity, then the sale triggers US tax; the transfer into the US is not meaningful for your taxes, except for reporting foreign accounts. Please review Publication 519 for general information on taxation of resident aliens.",
"title": ""
},
{
"docid": "219398",
"text": "Bitcoin can facilitate this, despite the risks associated with using bitcoin exchanges and the price volatility at any given time. The speed of bitcoin can limit your exposure to the bitcoin network to one hour. Cyprus has a more advanced infrastructure than most countries to support bitcoin transactions, with Neo & Bee opening as a regulated bank/financial entity in Cyprus just two months ago, and ATM/Vending Machines existing for that asset. Anyway, you acquire bitcoin from an individual locally (in exchange for cash) or an exchange that does not require the same level of reporting as a bank account in Cyprus or Russia. No matter how you acquire the bitcoin, you transfer it to the exchange, sell bitcoin on the exchange for your desired currency (USD, EURO, etc), you instruct the exchange to wire the EURO to your cyprus bank account using your cyprus account's SWIFT code. The end. Depending on the combination of countries involved, the exchange may still encounter similar withdrawal limitations until certain regulatory requirements are resolved. Also, I'm unsure of the attitude toward bitcoin related answers on this site, so I tried to add a disclaimer about bitcoin's risks at the top, but that doesn't make this answer incorrect.",
"title": ""
},
{
"docid": "529835",
"text": "If I can play the Devil's avocado, though, these foreign-owned entities will still be subject to the laws of the country they operate in. I mean, if they're State-owned, there's little accountability because the government is largely shielded from being called out if they screw up, whereas a privately owned enterprise is accountable if they make mistakes.",
"title": ""
},
{
"docid": "334603",
"text": "\"If you have a single member LLC there is no need to separate expenses in this way since it is simply treated as part of the owner's normal tax returns. This is the way I've been operating. Owner of Single-Member LLC If a single-member LLC does not elect to be treated as a corporation, the LLC is a \"\"disregarded entity,\"\" and the LLC's activities should be reflected on its owner's federal tax return. If the owner is an individual, the activities of the LLC will generally be reflected on: Form 1040 Schedule C, Profit or Loss from Business (Sole Proprietorship) (PDF) Form 1040 Schedule E, Supplemental Income or Loss (PDF) Form 1040 Schedule F, Profit or Loss from Farming (PDF) An individual owner of a single-member LLC that operates a trade or business is subject to the tax on net earnings from self employment in the same manner as a sole proprietorship. If the single-member LLC is owned by a corporation or partnership, the LLC should be reflected on its owner's federal tax return as a division of the corporation or partnership. https://www.irs.gov/businesses/small-businesses-self-employed/single-member-limited-liability-companies\"",
"title": ""
},
{
"docid": "27425",
"text": "A Mortgage Backed Security or MBS is the security. It's not an entity, it's essentially a contract. As an investment they function more or less the same way a bond does. There is nothing wrong with the concept behind a Mortgage Backed Security. Functionally securities like these allows banks and other institutions to lend to high-risk borrowers. You package small slices of a wide range of risk from a large number of mortgages and the investor sill receive something similar to the average of the rates being charged. Essentially from a big pool of mortgages of varying risk you will create a different big pool of bonds that can be sold to investors based on some sort of expected return. For a frame of reference on a much smaller scale look at peer to peer lending sites like LendingClub and Prosper. The idea is lots of people of varying risk profiles make requests for loans of varying amounts. You bring your $2,500 and invest $25 in to 100 different loans. This way even if a few default you will still eek out a profit. It also allows you to include riskier borrowers without materially impacting your expected return.",
"title": ""
},
{
"docid": "584140",
"text": ">If banks did not have a big brother to bail them out of loans that went bust whenever they wanted, they would be a lot more careful in who they loaned money to. That's what they became, an avenue to offload risk. The reason those banks were making bad loans was the high demand for trading in mortgage backed securities, not because Freddie and Fannie were there. They wanted to make those loans anyway, so there'd be more paper to trade. If you could transfer half of the risk of a loan you already knew was shitty to another entity, but still keep all the profits and fuck around with the derivatives, then of course you'll take full advantage. The intention behind them was to help that margin of people that fell just below the banks' historically very high standards for home lending. Banks seek high profits. Fannie and freddie were to operate at break even or slim profit, but serve a population toward upward economic mobility(which benefits everyone). When the banks' lending standards dropped precipitously due to repeal of glass steagall, creation of new exotic financial instruments and appalling lack of regulatory enforcement, everything kind of went to shit. In my view, they're much more a casualty that's become a scapegoat than a causal force.",
"title": ""
},
{
"docid": "251392",
"text": "\"Here's a brief rundown: 1. You're not going to need a lot of capital or debt 2. You aren't in a high-liability or high (MM+) revenue industry unless you're making children's toys out of reclaimed dynamite or something 3. You are operating by yourself The first fact rules out S or C corp. The second fact dings LLC, and the third one rules out a LLP or GP by default, although you can always convert later if you get a partner. Benefits of sole proprietorship include very simple taxes! As a pass-through entity, the business's income is considered your own, and business expenses are tax deductible. You don't need separate tax returns for both. Additionally, if it's just your name, you might not even need a license depending on your state and municipality (figure this out). If you want a different name, you usually need to register \"\"doing business as [name]\"\" with your state or municipality. Lastly, you don't need to use business income in any special way, since you have no additional tax liability or general liability shield. With an LLC, there are a lot of rules and restrictions. Let me know if you have any specific questions.\"",
"title": ""
},
{
"docid": "168382",
"text": "\"In one personal finance book I read that if a company is located in a country with credit rating X it can't have credit rating better (lower - i.e. further from AAA level) than X. This is simply wrong. Real world evidence proves it wrong. Automatic Data Processing (ADP), Exxon Mobile (XOM), Johnson & Johnson (JNJ), and Microsoft (MSFT) all have a triple-A rating today, even though the United States doesn't. Toyota (TM) remained triple-A for many years even after Japanese debt was downgraded. The explanation was the following: country has rating X because risk of doing business with it is X and so risk of doing business with any company located in that country automatically can't be better than X. When reading financial literature, you should always be critical. Let's evaluate this statement. First off, a credit rating is not the \"\"risk of doing business.\"\" That is way too generic. Specifically, a credit rating attempts to define an individual or company's ability to repay it's obligations. Buying treasuries constitutes as doing business with the gov't, but you can argue that buying stamps at USPS is also doing business with the gov't, and a credit rating won't affect the latter too much. So a credit rating reflects the ability of an entity to repay it's obligations. What does the ability of a government to repay have to do with the ability of companies in that country to repay? Not much. Certainly, if a company keeps it's surplus cash all in treasuries, then downgrading the government will affect the company, but in general, the credit rating of a company determines the company's ability to pay.\"",
"title": ""
},
{
"docid": "531625",
"text": "Yep, this is a fact - and actually goes double for non-profits and the public sector. I'm significantly more shielded from this than if I was employed as a developer for a private entity. I once worked for a startup where I had to sign a contract to not create a competing service within 2 years of leaving the company. I've been very careful to never put myself in that position again.",
"title": ""
}
] |
7154
|
Tax Efficiency with Index Investing
|
[
{
"docid": "161019",
"text": "Your tax efficient reasoning is solid for where you want to distribute your assets. ETFs are often more tax efficient than their equivalent mutual funds but the exact differences would depend on the comparison between the fund and ETF you were considering. The one exception to this rule is Vanguard funds and ETFs which have the exact same tax-efficiency because ETFs are a share class of the corresponding mutual fund.",
"title": ""
}
] |
[
{
"docid": "403556",
"text": "I would open a taxable account with the same custodian that manages your Roth IRA (e.g., Vanguard, Fidelity, etc.). Then within the taxable account I would invest the extra money in low cost, broad market index funds that are tax efficient. Unlike in your 401(k) and Roth IRA, you will now have tax implications if your funds produce dividends or realize a capital gain. That is why tax-efficient funds are important to minimize this as much as possible. The 3-fund portfolio is a popular choice for taxable accounts because of simplicity and the tax efficiency of broad market index funds that are part of the three fund portfolio. The 3-fund portfolio normally consists of Depending on your tax bracket you may want to consider municipal bonds in your taxable instead of taxable bonds if your tax bracket is 25% or higher. Another option is to forgo bonds altogether in the taxable account and just hold bonds in retirement accounts while keeping tax efficient domestic and international tock funds in your taxable account. Then adjust the bond portion upward in your retirement accounts to account for the additional stocks in your taxable accounts. This will maintain the asset allocation that you've already chosen that is appropriate for your age and goals.",
"title": ""
},
{
"docid": "363753",
"text": "Don't over think about your choices. The most important thing to start now and keep adjusting and tuning your portfolio as you move along in your life. Each individual's situation is unique. Start with something simple and straight forward, like 100 - your age, in Total Stock market Index fund and the remaining total bond market index fund. For your 401k, at least contribute so much as to get the maximum employer match. Its always good if you can contribute the yearly maximum in your 401k or IRA. Once you have built up a substantial amount of assets (~ $50k+) then its time to think more about asset allocation and start buying into more specific investments as needed. Remember to keep your investment expenses low by using index funds. Also remember to factor in tax implications on your investment decisions. eg. buying an REIT fund in a tax advantaged account like 40k is more tax efficient than buying it in a normal brokerage account.",
"title": ""
},
{
"docid": "352987",
"text": "Does anyone know is it wise to invest money in NPS for tax saving ? This is primarily opinion based. NPS is efficient retirement plan, allows to invest into Index equities with almost NIL expense ratios. The additional tax breaks makes the overall returns attractive. The down side is 40% of corpus withdrawal is tax free, the balance 60% is taxable; alternatively one can buy annuity to make it tax free.",
"title": ""
},
{
"docid": "314056",
"text": "This question is indeed rather complicated. Let's simplify it a little bit. Paying down your mortgage makes sense if your expected return in the rest of your portfolio is less than the cost of the mortgage. In many cases, people may also decide to pay down their mortgage because they are risk-averse and do not like carrying debt. There's no tax benefit to doing so, though; Canada doesn't generally allow you to write off mortgage interest, unlike the U.S. As to keeping money in the corporation or not, I'm not going to address that. I don't have a firm enough understanding of corporate taxation. Canadian Couch Potato advises treating all of your investment assets as one large portfolio. That is what you are trying to do here. However, let's consider a different approach. If you do not have enough money to max out your RRSP or TFSA, you may choose to keep your TFSA for an emergency fund, where the money is kept highly liquid. Keep your cash in an interest-bearing TFSA, or perhaps invest it in the money market, inside your TFSA. Then, use your RRSP for the rest of your investment money, split according to your investment goals. This is not the most tax-efficient approach, but it is nice and simple. But you are looking for the most tax-efficient approach. So, let's assume you have enough to more than max out your TFSA and RRSP contributions, and all of your investments are going toward your retirement, which is at least a decade away. Because you are not taxed on your investment income from RRSPs (until you withdraw the money) or TFSA, it makes sense to hold the least tax-efficient investments there. Tax-advantaged investments such as Canadian equities should be held in your investment accounts outside of TFSA and RRSPs. Again, the Canadian Couch Potato has a great article on where to put your investment assets. That article covers interest, dividends, foreign dividends, and capital gains, as well as RRSPs, RESPs, and TFSAs. That article recommends holding Canadian equities in a taxable account, REITs in a tax-sheltered account (TFSA or RRSP), bonds, GICs, and money-market funds in a tax-sheltered account (as these count as interest). The article goes into rather more detail than this, and is worth checking out. It mentions the 15% withholding tax on US-listed ETFs, for example. In addition to that website, I recommend the following three books: The above three resources strongly advocate passive indexed investments, which I like but not everyone agrees with. All three specifically discuss tax implications, which is why I include them here.",
"title": ""
},
{
"docid": "135596",
"text": "This might be better suited to r/personalfinance but if you're looking to invest I'd say start with an index fund. The MER's (fees) for most other mutual funds take too heavy a chunk of returns to be worth it in a market where actively managed funds are either underperforming of performing at par with passive funds. Additionally if these are your first investments, make sure you're doing it with investment goals in mind. Is this money you're saving for short, medium, or long term? For medium and long term investing make sure you're doing it through a tax efficient instrument like an IRA or 401k.",
"title": ""
},
{
"docid": "437126",
"text": "The market is efficient, but it is not perfectly efficient. There are entities out there that consistently, legitimately, and significantly outperform the market because of asymmetric information (not necessarily insider trading) and their competitive advantage (access to data and proprietary, highly sophisticated models)*. I say this despite most hedge funds performing worse than their respective benchmarks. For most people (even very smart people) it makes a lot of sense to invest in index funds with a reasonable asset allocation (based on desired volatility, tax situation, rebalancing methods etc.). * The usual example that is cited is RT's Medallion Fund because it has enjoyed quite dramatic returns. Other groups that have been successful include Citadel and Soros Fund Management.",
"title": ""
},
{
"docid": "510328",
"text": "\"Liquidity is highly correlated to efficiency primarily because if an asset's price is not sampled during the time of a trade, it's price is unknown therefore inefficient. Past prices can be referenced, but they are not the price of the present. Prices of substitutes are even worse. SPY is extremely efficient for an equity. If permitted, it could easily trade with much lower ticks and still have potential for a locked market. Ideal exchange An ideal exchange has no public restrictions on trade. This is not to say that private restrictions would need to be put in place for various reasons, but one would only do that if it were responsible for its own survival instead of being too big to fail. In this market, trades would be approximately continuous for the largest securities and almost always locked because of continuous exchange fee competition with ever dropping minimum ticks. A market that can provide continuous locked orders with infinite precision is perfectly efficient from the point of view of the investor because the value of one's holdings are always known. EMH In terms of the theory the Efficient Market Hypothesis this is irrelevant to the rational investor. The rational investor will invest in the market at large of a given asset class, only increasing risk as wealth increases thus moving to more volatile asset classes when the volatility can be absorbed by excess wealth. Here, liquidity is also helpful, the \"\"two heads are better than one\"\" way of thinking. The more invested in an asset class, the lower the class's variance and vice versa. Bonds, the least variant, dwarf equities which dwarf options, all in order of the least variance. Believe it or not, there was a day when bonds were almost as risky as equities. For those concerned with EMH, liquidity is also believed to increase efficiency in some forms because liquidity is proportional to the number of individuals invested thus reducing the likelihood of an insufficient number of participants. External inefficiency In the case of ETFs that do not perfectly track their underlying index less costs at all times between index changes, this is because they are forbidden from directly trading in the market on their own behalf. If they were allowed and honest, the price would always be perfect and much more liquid than it otherwise should be since the combined frequency of all index members is much higher than any one alone. If one was dishonest, it would try to defraud with higher or lower numbers; however, if insider trading were permitted, both would fail due to the prisoner's dilemma that there is no honor among thieves. Here, the market would detect the problem much sooner because the insiders would arbitrage the false price away. Indirect internal efficiency Taking emerging market ETFs as an example, the markets that those are invested into are heavily restricted, so their ETF to underlying price inefficiencies are more pronounced even though the ETFs are actually working to make those underlying markets more efficient because a price for them altogether is known.\"",
"title": ""
},
{
"docid": "402046",
"text": "Ending up with nothing is an unlikely situation unless you invest 100% in a company stock and the company goes under. In order to give you a good answer we need to see what options your employer gives for 401k investments. The best advice would be to take a list of all options that your employer allows and talk with a financial advisor. Here are a few options that you may or may not have as an option from an employer: Definitions from wikipedia: A target-date fund – also known as a lifecycle, dynamic-risk or age-based fund – is a collective investment scheme, usually a mutual fund, designed to provide a simple investment solution through a portfolio whose asset allocation mix becomes more conservative as the target date (usually retirement) approaches. An index fund or index tracker is a collective investment scheme (usually a mutual fund or exchange-traded fund) that aims to replicate the movements of an index of a specific financial market... An exchange-traded fund (ETF) is an investment fund traded on stock exchanges, much like stocks.[1] An ETF holds assets such as stocks, commodities, or bonds, and trades close to its net asset value over the course of the trading day. Most ETFs track an index, such as a stock index or bond index. ETFs may be attractive as investments because of their low costs, tax efficiency, and stock-like features. The capital stock (or stock) of an incorporated business constitutes the equity stake of its owners. Which one can you lose everything in? You can lose everything in stocks by the company going under. In Index funds the entire market that it follows would have to collapse. The chances are slim here since the index made up of several companies. The S&P 500 is made up of 500 leading companies publicly traded in the U.S. A Pacific-Europe index such as MSCI EAFE Index is made up of 907 companies. The chances of losing everything in an ETF are also slim. The ETF that follows the S&P 500 is made up of 500 companies. An Pacific-Europe ETF such as MSCI EAFE ETF is made up of 871 companies. Target date funds are also slim to lose everything. Target date funds are made up of several companies like indexes and etfs and also mix in bonds and other investments depending on your age. What would I recommend? I would recommend the Index funds and/or ETFs that have the lowest fee that make up the following strategy for your age: Why Not Target Date Funds or Stocks? Target date funds have high fees. Later in life when you are closer to retirement you may want to add bonds to your portfolio. At that time if this is the only option to add bonds then you can change your elections. Stocks are too risky for you with your current knowledge. If your company matches by buying their stock you may want to consider reallocating that stock at certain points to your Index funds or ETFs.",
"title": ""
},
{
"docid": "370244",
"text": "Behind the scenes, mutual funds and ETFs are very similar. Both can vary widely in purpose and policies, which is why understanding the prospectus before investing is so important. Since both mutual funds and ETFs cover a wide range of choices, any discussion of management, assets, or expenses when discussing the differences between the two is inaccurate. Mutual funds and ETFs can both be either managed or index-based, high expense or low expense, stock or commodity backed. Method of investing When you invest in a mutual fund, you typically set up an account with the mutual fund company and send your money directly to them. There is often a minimum initial investment required to open your mutual fund account. Mutual funds sometimes, but not always, have a load, which is a fee that you pay either when you put money in or take money out. An ETF is a mutual fund that is traded like a stock. To invest, you need a brokerage account that can buy and sell stocks. When you invest, you pay a transaction fee, just as you would if you purchase a stock. There isn't really a minimum investment required as there is with a traditional mutual fund, but you usually need to purchase whole shares of the ETF. There is inherently no load with ETFs. Tax treatment Mutual funds and ETFs are usually taxed the same. However, capital gain distributions, which are taxable events that occur while you are holding the investment, are more common with mutual funds than they are with ETFs, due to the way that ETFs are structured. (See Fidelity: ETF versus mutual funds: Tax efficiency for more details.) That having been said, in an index fund, capital gain distributions are rare anyway, due to the low turnover of the fund. Conclusion When comparing a mutual fund and ETF with similar objectives and expenses and deciding which to choose, it more often comes down to convenience. If you already have a brokerage account and you are planning on making a one-time investment, an ETF could be more convenient. If, on the other hand, you have more than the minimum initial investment required and you also plan on making additional regular monthly investments, a traditional no-load mutual fund account could be more convenient and less expensive.",
"title": ""
},
{
"docid": "162562",
"text": "People ... are nearly twice as likely to ... feel confident Great, confidence is amazing. That and $5 will buy you a cup of coffee. 44% [who hired a pro] have $100K or more [vs.] 9% of DIYers There's no way to examine these numbers without a link to the source, but it stands to reason that if you have a plan that you're sticking to you'll save more money than if you are just investing haphazardly. It's too bad that we can't see what the returns are for those using a pro vs. DIYers. That would be much more valuable than an arbitrary dollar level. Unfortunately $100K isn't really that much money if you live in the US, so it's an irrelevant talking point. The real question is whether investment knowledge is readily available to the masses or if having a person who specializes in finance is required to make good decisions about investment. I think the fact that the conventional wisdom prefers index funds to actively managed funds demonstrates that investment professionals are less useful than they might have been even a decade or two ago. If money should be spent on professional advice, it's probably better spent on CPAs or other tax professionals who can help optimize your investments for tax efficiency, though even that is now available as more common knowledge.",
"title": ""
},
{
"docid": "88539",
"text": "There are two significant drawbacks to this type of transfer. They were the reasons why I kept my American 401(k) as-is and started funding my Canadian RRSP from zero balance. 1. Taxes - a large chunk of your 401(k) will be lost to taxes. There is probably no way to transfer the funds without making a 401(k)/IRA withdrawal, which will incur the US federal tax and the 10% early-withdrawal penalty. When the money went into the 401(k), you got a tax deduction in the US and the tax break is supposed be repaid later when you make a withdrawal (that's basically how tax deferral works). It's unlikely that any country will let you take a deduction first and send the payback to a foreign country. The withdrawal amount may also be taxable in Canada (Canadians generally pay taxes on their global income and that includes pensions and distributions from foreign retirement plans). Foreign tax credit will apply of course, to eliminate double taxation, but it's of little help if your marginal Canadian tax rate is higher than your average US tax rate. 2. Expenses. Your RRSP will have to be invested in something and mutual fund management expenses are generally higher in Canada than in the US. For example, my employer-sponsored RRSP has a Standard & Poor's stock index fund that charges 1.5% and that is considered low-cost. It also offers a number of managed funds with expenses in excess of 2% that I simply ignore. You can probably invest your American 401(k)/IRA in mutual funds more efficiently.",
"title": ""
},
{
"docid": "307716",
"text": "There are not always capital-efficient ways for a company to reinvest its own profits. This is why dividends exist. Imagine a company will reinvest 80% of its profits into a project with a huge projected return, but the other 20% of the company's profits cannot be reinvested efficiently because there are zero projects in which to reinvest the profits into that would return a better profit than what the company's shareholders could make by reinvesting those profits in their own way (ie: a benchmark market index like an S&P 500 index fund). Since the shareholders could make a better return with this than the company could with any company project, it would be irresponsible (technically maybe even illegal) for the company to reinvest that 20% of the profits. This reason for companies sometimes paying out profits to shareholders in the form of dividends is a market-efficient part of the economic system, and it really is great. If a CEO/CFO/anyone is paying out so much profit from a company that it is irresponsible to the company's investors, then that would also technically be illegal since the company is evading efficient project that would benefit its shareholders more than they could benefit themselves elsewhere in the market. (These legalities with shareholder laws are not explicitly put into action very often, but their effects are always there) It's also worth noting payout/plowback strategy is very important for the strategy and financing of a company, particularly for public investments.",
"title": ""
},
{
"docid": "476138",
"text": "I still don't see the point of this software; rebalancing frequently is a waste of money (through fees). If you invest in index funds, you don't have to rebalance at all--effectively, the fund is doing it for you, and since they can generally trade more efficiently than individual investors can, that's a win. The Coverdell ESA is a great example. There's a maximum contribution amount, just as there are for almost any tax-exempt account. A decent financial adviser could help you plan how much to contribute to which accounts, at what time, and when you can/should start to withdraw from them.",
"title": ""
},
{
"docid": "93129",
"text": "This is Rob Bennett, the fellow who developed the Valuation-Informed Indexing strategy and the fellow who is discussed in the comment above. The facts stated in that comment are accurate -- I went to a zero stock allocation in the Summer of 1996 because of my belief in Robert Shiller's research showing that valuations affect long-term returns. The conclusion stated, that I have said that I do not myself follow the strategy, is of course silly. If I believe in it, why wouldn't I follow it? It's true that this is a long-term strategy. That's by design. I see that as a benefit, not a bad thing. It's certainly true that VII presumes that the Efficient Market Theory is invalid. If I thought that the market were efficient, I would endorse Buy-and-Hold. All of the conventional investing advice of recent decades follows logically from a belief in the Efficient Market Theory. The only problem I have with that advice is that Shiller's research discredits the Efficient Market Theory. There is no one stock allocation that everyone following a VII strategy should adopt any more than there is any one stock allocation that everyone following a Buy-and-Hold strategy should adopt. My personal circumstances have called for a zero stock allocation. But I generally recommend that the typical middle-class investor go with a 20 percent stock allocation even at times when stock prices are insanely high. You have to make adjustments for your personal financial circumstances. It is certainly fair to say that it is strange that stock prices have remained insanely high for so long. What people are missing is that we have never before had claims that Buy-and-Hold strategies are supported by academic research. Those claims caused the biggest bull market in history and it will take some time for the widespread belief in such claims to diminish. We are in the process of seeing that happen today. The good news is that, once there is a consensus that Buy-and-Hold can never work, we will likely have the greatest period of economic growth in U.S. history. The power of academic research has been used to support Buy-and-Hold for decades now because of the widespread belief that the market is efficient. Turn that around and investors will possess a stronger belief in the need to practice long-term market timing than they have ever possessed before. In that sort of environment, both bull markets and bear markets become logical impossibilities. Emotional extremes in one direction beget emotional extremes in the other direction. The stock market has been more emotional in the past 16 years than it has ever been in any earlier time (this is evidenced by the wild P/E10 numbers that have applied for that entire time-period). Now that we are seeing the losses that follow from investing in highly emotional ways, we may see rational strategies becoming exceptionally popular for an exceptionally long period of time. I certainly hope so! The comment above that this will not work for individual stocks is correct. This works only for those investing in indexes. The academic research shows that there has never yet in 140 years of data been a time when Valuation-Informed Indexing has not provided far higher long-term returns at greatly diminished risk. But VII is not a strategy designed for stock pickers. There is no reason to believe that it would work for stock pickers. Thanks much for giving this new investing strategy some thought and consideration and for inviting comments that help investors to understand both points of view about it. Rob",
"title": ""
},
{
"docid": "272458",
"text": "\"Here are the few scenarios that may be worth noting in terms of using different types of accounts: Traditional IRA. In this case, the monies would grow tax-deferred and all monies coming out will be taxed as ordinary income. Think of it as everything is in one big black box and the whole thing is coming out to be taxed. Roth IRA. In this case, you could withdraw the contributions anytime without penalty. (Source should one want it for further research.) Past 59.5, the withdrawals are tax-free in my understanding. Thus, one could access some monies earlier than retirement age if one considers all the contributions that are at least 5 years old. Taxable account. In this case, each year there will be distributions to pay taxes as well as anytime one sells shares as that will trigger capital gains. In this case, taxes are worth noting as depending on the index fund one may have various taxes to consider. For example, a bond index fund may have some interest that would be taxed that the IRA could shelter to some extent. While index funds can be a low-cost option, in some cases there may be capital gains each year to keep up with the index. For example, small-cap indices and value indices would have stocks that may \"\"outgrow\"\" the index by either becoming mid-cap or large-cap in the case of small-cap or the value stock's valuation rises enough that it becomes a growth stock that is pulled out of the index. This is why some people may prefer to use tax-advantaged accounts for those funds that may not be as tax-efficient. The Bogleheads have an article on various accounts that can also be useful as dg99's comment referenced. Disclosure: I'm not an accountant or work for the IRS.\"",
"title": ""
},
{
"docid": "473658",
"text": "ETFs offer the flexibility of stocks while retaining many of the benefits of mutual funds. Since an ETF is an actual fund, it has the diversification of its potentially many underlying securities. You can find ETFs with stocks at various market caps and style categories. You can have bond or mixed ETFs. You can even get ETFs with equal or fundamental weighting. In short, all the variety benefits of mutual funds. ETFs are typically much less expensive than mutual funds both in terms of management fees (expense ratio) and taxable gains. Most of them are not actively managed; instead they follow an index and therefore have a low turnover. A mutual fund may actively trade and, if not balanced with a loss, will generate capital gains that you pay taxes on. An ETF will produce gains only when shifting to keep inline with the index or you yourself sell. As a reminder: while expense ratio always matters, capital gains and dividends don't matter if the ETF or mutual fund is in a tax-advantaged account. ETFs have no load fees. Instead, because you trade it like a stock, you will pay a commission. Commissions are straight, up-front and perfectly clear. Much easier to understand than the various ways funds might charge you. There are no account minimums to entry with ETFs, but you will need to buy complete shares. Only a few places allow partial shares. It is generally harder to dollar-cost average into an ETF with regular automated investments. Also, like trading stocks, you can do those fancy things like selling short, buying on margin, options, etc. And you can pay attention to the price fluctuations throughout the day if you really want to. Things to make you pause: if you buy (no-load) mutual funds through the parent company, you'll get them at no commission. Many brokerages have No Transaction Fee (NTF) agreements with companies so that you can buy many funds for free. Still look out for that expense ratio though (which is probably paying for that NTF advantage). As sort of a middle ground: index funds can have very low expense ratios, track the same index as an ETF, can be tax-efficient or tax-managed, free to purchase, easy to dollar-cost average and easier to automate/understand. Further reading:",
"title": ""
},
{
"docid": "327237",
"text": "The short answer to your question is yes. Index funds are about the easiest and most efficient diversified way to invest your money. Vanguard's are among the cheapest and best. Be aware, though, that passive income doesn't mean you do nothing for your money. In the case of investing, what you are doing is bearing risk. That is, you are being paid (on average) to put your money in a situation where you may lose money. If you keep your eye on the long-term prize, then when (not if) you sustain losses in your investment account, you will have the patience to leave the money in there. I'm a little confused by your wording about increasing your salary. Normally we think of index funds as a way to increase our wealth. If you are making new investments, presumably you have more salary than you need right now. Normal index funds will reinvest dividends automatically, so you will see the value of your investments rise but will not see any cash flows per se unless you are selling your holdings. If you want actual cash coming out of your investment, you can use ETF's to achieve the same type of investment and treat the dividends as a supplement to your income. Note, however, that some gains in your ETF will be in the form of capital gains and some will be dividends. Think more like 2% year per in dividend payments and the rest in capital gains. If your objective is to save for retirement, please consider investing through an IRA, Roth IRA, or through your 401(k). No need to give uncle sam a gift from your hard-earned money.",
"title": ""
},
{
"docid": "376485",
"text": "\"Congratulations on deciding to save money and choosing to invest it. One thing to know about mutual funds including index funds is that they typically require a minimum investment of a few thousand dollars, $3000 being a typical amount, unless the investment is in an IRA in which case $1000 might be a minimum. In some cases, automated monthly investments of $50 or $100 might need to be set up if you are beginning with a small balance. There is nothing wrong with your approach. You now should go and look at the various requirements for specific index funds. The Fidelity and Vanguard families are good choices and both offer very low-cost index funds to choose from, but different funds can have different requirements regarding minimum investments etc. You also have a choice of which index you want to follow, the S&P 500 Index, MidCap Indexes, Small-Cap Indexes, Total Stock Market Indexes etc., but your choice might be limited until you have more money to invest because of minimum investment rules etc. Most important, after you have made your choice, I urge you to not look every day, or even every month, to see how your investment is doing. You will save yourself a lot of anxiety and will save yourself from making wrong decisions. Far too many investors ignore the maxim \"\"Buy Low, Sell High\"\" and pull money out of what should be long-term investments at the first flicker of a downturn and end up buying high and selling low. Finally, the time is approaching when most stock funds will be declaring dividends and capital gains distributions. If you invest now, you may end up with a paper profit on which you will have to pay taxes (in non-tax-advantaged accounts) on your 2012 tax return (this is called \"\"buying a dividend\"\"), and so you might want to spend some time investigating now, but actually make the investment in late December after your chosen fund has made its distributions (the date for this will be on the fund's web site) or in early 2013.\"",
"title": ""
},
{
"docid": "569206",
"text": "\"I would let them get their hands dirty, learn by practicing. Below you can find a simple program to generate your own efficient frontier, just 29 lines' python. Depending on the age, adult could help in the activity but I would not make it too lecturing. With child-parent relationship, I would make it a challenge, no easy money anymore -- let-your-money work-for-you -attitude, create the efficient portfolio! If there are many children, I would do a competition over years' time-span or make many small competitions. Winner is the one whose portfolio is closest to some efficient portfolio such as lowest-variance-portfolio, I have the code to calculate things like that but it is trivial so build on the code below. Because the efficient frontier is a good way to let participants to investigate different returns and risk between assets classes like stocks, bonds and money, I would make the thing more serious. The winner could get his/her designed portfolio (to keep it fair in your budget, you could limit choices to index funds starting with 1EUR investment or to ask bottle-price-participation-fee, bring me a bottle and you are in. No money issue.). Since they probably don't have much money, I would choose free software. Have fun! Step-by-step instructions for your own Efficient Frontier Copy and run the Python script with $ python simple.py > .datSimple Plot the data with $ gnuplot -e \"\"set ylabel 'Return'; set xlabel 'Risk'; set terminal png; set output 'yourEffFrontier.png'; plot '.datSimple'\"\" or any spreadsheet program. Your first \"\"assets\"\" could well be low-risk candies and some easy-to-stale products like bananas -- but beware, notice the PS. Simple Efficient-frontier generator P.s. do not stagnate with collectibles, such as candies and toys, and retailer products, such as mangos, because they are not really good \"\"investments\"\" per se, a bit more like speculation. The retailer gets a huge percentage, for further information consult Bogleheads.org like here about collectible items.\"",
"title": ""
},
{
"docid": "216441",
"text": "Assuming this will be a taxable account (since you want to pull income off of it, although this will lower wealth growth), you could open a brokerage account at some place like Vanguard (free on their ETFs) and look at tax efficient index fund ETFs (such as total stock market or their 500 fund), including some international (foreign tax credit is nice in taxable) and muni funds for the (tax advantaged) income, although CDs are likely better for the income at this point.",
"title": ""
},
{
"docid": "62966",
"text": "when investing in index funds Index fund as the name suggests invests in the same proportion of the stocks that make up the index. You can choose a Index Fund that tracks NYSE or S&P etc. You cannot select individual companies. Generally these are passively managed, i.e. just follow the index composition via automated algorithms resulting in lower Fund Manager costs. is it possible to establish an offshore company Yes it is possible and most large organization or High Net-worth individuals do this. Its expensive and complicated for ordinary individuals. One needs and army of International Tax Consultants / International Lawyers / etc but do I have to pay taxes from the capital gains at the end of the year? Yes Canada taxes on world wide income and you would have to pay taxes on gains in Canada. Note depending on your tax residency status in US, you may have to pay tax in US as well.",
"title": ""
},
{
"docid": "162176",
"text": "If you're maxing out your 401k, just save in tax-efficient investments like stocks and tax efficient funds. If you live in a state with income taxes, look at municipal bond funds for some tax-free income. In 2011, be careful with bond funds and look for short duration funds.",
"title": ""
},
{
"docid": "2809",
"text": "\"I'm in a similar situation. First, a 529 plan can be use for \"\"qualifying\"\" international schools. There are 336 for 2015, which includes many well known schools but also excludes many schools, especially lower level or vocational schools and schools in non-English speaking countries. I ran 3 scenarios to see what the impact would be if you invested $3000 a year for 14 years in something tracking the S&P 500 Index: For each of these scenarios, I considered 3 cases: a state with 0% income tax, a state with the median income tax rate of 6% for the 25% tax bracket, and California with an income tax rate of 9.3% for the 25% tax bracket. California has an addition 2.5% penalty on unqualified distributions. Additionally, tax deductions taken on contributions that are part of unqualified distributions will be viewed as income and that portion of the distribution will be taxed as such at the state level. Vanguard's 500 Index Portfolio has a 10 year average return of 7.63%. Vanguard's S&P 500 Index fund has a 10 year average return of 7.89% before tax and 7.53% after taxes on distributions. Use a 529 as intended: Use a 529 but do not use as intended: Invest in a S&P 500 Index fund in a taxable account: Given similar investment options, using a 529 fund for something other than education is much worse than having an investment in a mutual fund in a taxable account, but there's also a clear advantage to using a 529 if you know with certainty you can use it for qualified expenses. Both the benefits for correct use of a 529 and the penalties for incorrect use increase with state tax rates. I live in a state with no income tax so the taxable mutual fund option is closer to the middle between correct and incorrect use of a 529. I am leaning towards the investment in a taxable account.\"",
"title": ""
},
{
"docid": "271825",
"text": "One of the things to consider is that most Vanguard funds are very tax efficient, that is they don't throw off much in the way of cap gains or taxable dividends while they grow. So if you do it right you won't have to pay much in the way of taxes on your investments even if they are in taxable accounts until retirement when at the very least you will have a lot more flexibility in managing your money and very likely be in a lower tax bracket. Roth is better if you are planning other types of investments, but if you are planning to hold an efficient Vanguard fund the difference isn't that bit.",
"title": ""
},
{
"docid": "312591",
"text": "\"Funds - especially index funds - are a safe way for beginning investors to get a diversified investment across a lot of the stock market. They are not the perfect investment, but they are better than the majority of mutual funds, and you do not spend a lot of money in fees. Compared to the alternative - buying individual stocks based on what a friend tells you or buying a \"\"hot\"\" mutual fund - it's a great choice for a lot of people. If you are willing to do some study, you can do better - quite a bit better - with common stocks. As an individual investor, you have some structural advantages; you can take significant (to you) positions in small-cap companies, while this is not practical for large institutional investors or mutual fund managers. However, you can also lose a lot of money quickly in individual stocks. It pays to go slow and to your homework, however, and make sure that you are investing, not speculating. I like fool.com as a good place to start, and subscribe to a couple of their newsletters. I will note that investing is not for the faint of heart; to do well, you may need to do the opposite of what everybody else is doing; buying when the market is down and selling when the market is high. A few people mentioned the efficient market hypothesis. There is ample evidence that the market is not efficient; the existence of the .com and mortgage bubbles makes it pretty obvious that the market is often not rationally valued, and a couple of hedge funds profited in the billions from this.\"",
"title": ""
},
{
"docid": "436904",
"text": "This is Ellie Lan, investment analyst at Betterment. To answer your question, American investors are drawn to use the S&P 500 (SPY) as a benchmark to measure the performance of Betterment portfolios, particularly because it’s familiar and it’s the index always reported in the news. However, going all in to invest in SPY is not a good investment strategy—and even using it to compare your own diversified investments is misleading. We outline some of the pitfalls of this approach in this article: Why the S&P 500 Is a Bad Benchmark. An “algo-advisor” service like Betterment is a preferable approach and provides a number of advantages over simply investing in ETFs (SPY or others like VOO or IVV) that track the S&P 500. So, why invest with Betterment rather than in the S&P 500? Let’s first look at the issue of diversification. SPY only exposes investors to stocks in the U.S. large cap market. This may feel acceptable because of home bias, which is the tendency to invest disproportionately in domestic equities relative to foreign equities, regardless of their home country. However, investing in one geography and one asset class is riskier than global diversification because inflation risk, exchange-rate risk, and interest-rate risk will likely affect all U.S. stocks to a similar degree in the event of a U.S. downturn. In contrast, a well-diversified portfolio invests in a balance between bonds and stocks, and the ratio of bonds to stocks is dependent upon the investment horizon as well as the individual's goals. By constructing a portfolio from stock and bond ETFs across the world, Betterment reduces your portfolio’s sensitivity to swings. And the diversification goes beyond mere asset class and geography. For example, Betterment’s basket of bond ETFs have varying durations (e.g., short-term Treasuries have an effective duration of less than six months vs. U.S. corporate bonds, which have an effective duration of just more than 8 years) and credit quality. The level of diversification further helps you manage risk. Dan Egan, Betterment’s Director of Behavioral Finance and Investing, examined the increase in returns by moving from a U.S.-only portfolio to a globally diversified portfolio. On a risk-adjusted basis, the Betterment portfolio has historically outperformed a simple DIY investor portfolio by as much as 1.8% per year, attributed solely to diversification. Now, let’s assume that the investor at hand (Investor A) is a sophisticated investor who understands the importance of diversification. Additionally, let’s assume that he understands the optimal allocation for his age, risk appetite, and investment horizon. Investor A will still benefit from investing with Betterment. Automating his portfolio management with Betterment helps to insulate Investor A from the ’behavior gap,’ or the tendency for investors to sacrifice returns due to bad timing. Studies show that individual investors lose, on average, anywhere between 1.2% to 4.3% due to the behavior gap, and this gap can be as high as 6.5% for the most active investors. Compared to the average investor, Betterment customers have a behavior gap that is 1.25% lower. How? Betterment has implemented smart design to discourage market timing and short-sighted decision making. For example, Betterment’s Tax Impact Preview feature allows users to view the tax hit of a withdrawal or allocation change before a decision is made. Currently, Betterment is the only automated investment service to offer this capability. This function allows you to see a detailed estimate of the expected gains or losses broken down by short- and long-term, making it possible for investors to make better decisions about whether short-term gains should be deferred to the long-term. Now, for the sake of comparison, let’s assume that we have an even more sophisticated investor (Investor B), who understands the pitfalls of the behavior gap and is somehow able to avoid it. Betterment is still a better tool for Investor B because it offers a suite of tax-efficient features, including tax loss harvesting, smarter cost-basis accounting, municipal bonds, smart dividend reinvesting, and more. Each of these strategies can be automatically deployed inside the portfolio—Investor B need not do a thing. Each of these strategies can boost returns by lowering tax exposure. To return to your initial question—why not simply invest in the S&P 500? Investing is a long-term proposition, particularly when saving for retirement or other goals with a time horizon of several decades. To be a successful long-term investor means employing the core principles of diversification, tax management, and behavior management. While the S&P might look like a ‘hot’ investment one year, there are always reversals of fortune. The goal with long-term passive investing—the kind of investing that Betterment offers—is to help you reach your investing goals as efficiently as possible. Lastly, Betterment offers best-in-industry advice about where to save and how much to save for no fee.",
"title": ""
},
{
"docid": "353337",
"text": "\"Whoa. These things are on two dimensions. It's like burger and fries, you can also have chicken sandwich and fries, or burger and onion rings. You can invest in an taxable brokerage account and/or an IRA. And then, within each of those... You can buy index funds and/or anything else. All 4 combinations are possible. If someone says otherwise, take your money and run. They are a shady financial \"\"advisor\"\" who is ripping you off by steering you only into products where they get a commission. Those products are more expensive because the commission comes out of your end. Not to mention any names. E.J. If you want financial advice that is honest, find a financial advisor who you pay for his advice, and who doesn't sell products at all. Or, just ask here. But I would start by listening to Suze Orman, Dave Ramsey, whomever you prefer. And read John Bogle's book. They can tell you all about the difference between money market, bonds, stocks, managed mutual funds (ripoff!) and index funds. IRA accounts, Roth IRA accounts and taxable accounts are all brokerage accounts. Within them, you can buy any security you want, including index funds. The difference is taxation. Suppose you earn $1000 and choose to invest it however Later you withdraw it and it has grown to $3000. Investing in a taxable account, you pay normal income tax on the $1000. When you later withdraw the $3000, you pay a tax on $2000 of income. If you invested more than a year, it is taxed at a much lower \"\"capital gains\"\" tax rate. With a traditional IRA account, you pay zero taxes on the initial $1000. Later, when you take the money out, you pay normal income tax on the full $3000. If you withdrew it before age 59-1/2, you also pay a 10% penalty ($300). With a Roth IRA account, you pay normal income tax on the $1000. When you withdraw the $3000 later, you pay NOTHING in taxes. Provided you followed the rules. You can invest in almost anything inside these accounts: Money market funds. Terrible return. You won't keep up with the market. Bonds. Low return but usually quite safe. Individual stocks. Good luck. Managed mutual funds. You're paying some genius stock picker to select high performing stocks. He has a huge staff of researchers and good social connections. He also charges you 1.5% per year overhead as an \"\"expense ratio\"\", which is a total loss to you. The fact is, he can usually pick stocks better than a monkey throwing darts. But he's not 1.5% better! Index funds. These just shrug and buy every stock on the market. There's no huge staff or genius manager, just some intern making small adjustments every week. As such, the expense ratio is extremely small, like 0.1%. If any of these investments pay dividends, you must pay taxes on them when they're issued, if you're not in an IRA account. This problem gets fixed in ETF's. Index ETF's. These are index funds packaged to behave like stocks. Dividends increase your stock's value instead of being paid out to you, which simplifies your taxes. If you buy index funds outside of an IRA, use these. Too many other options to get into here.\"",
"title": ""
},
{
"docid": "184820",
"text": "Maxing out an IRA would probably be step 1, if you exceed that probably just aim for saving in a taxable brokerage account. Just try and stick to ETFs if you're gonna index since they're slightly more tax efficient than a mutual fund",
"title": ""
},
{
"docid": "90858",
"text": "\"First, consider what causes taxes to apply to a mutual fund, index or actively managed. Dividends and capital gains are generally what will be distributed to shareholders given the nature of a mutual fund since the fund itself doesn't pay taxes. For funds held in IRAs or other tax-advantaged accounts, this isn't a concern and thus people may not have this concern for those situations which can account for a lot of investing situations as people may have 401(k)s and IRAs that hold their investments rather than taxable accounts. Second, there can be tax-managed funds so there can be cases where a fund is managed with taxes in mind that is worth noting here as what is referenced is a \"\"Dummies\"\" link that is making a generalization. For taxable accounts, it may make more sense to have a tax-managed fund rather than an index fund though I'd also argue to be careful of asset allocation as to maintain a purity of style can require selling of stocks that grow too big and thus trigger capital gains,e.g. small-cap and mid-cap funds that can't hold onto the winners as they would become mid-cap and large-cap instead of representing the proper asset class. A FUND THAT PLAYED IT SAFE--AND WAS SORRY would be a Businessweek story from 1998 of an actively managed fund that went mostly to cash and missed the rise of the stock market at that time if you want a specific example of what an actively managed fund can do that an index fund often cannot do. The index fund is to track the index and stay nearly all invested all the time.\"",
"title": ""
},
{
"docid": "216757",
"text": "\"Great question! While investing in individual stocks can be very useful as a learning experience, my opinion is that concentrating an entire portfolio in a few companies' stock is a mistake for most investors, and especially for a novice for several reasons. After all, only a handful of professional investors have ever beaten the market over the long term by picking stocks, so is it really worth trying? If you could, I'd say go work on Wall Street and good luck to you. Diversification For many investors, diversification is an important reason to use an ETF or index fund. If they were to focus on a few sectors or companies, it is more likely that they would have a lop-sided risk profile and might be subject to a larger downside risk potential than the market as a whole, i.e. \"\"don't put all your eggs in one basket\"\". Diversification is important because of the nature of compound investing - if you take a significant hit, it will take you a long time to recover because all of your future gains are building off of a smaller base. This is one reason that younger investors often take a larger position in equities, as they have longer to recover from significant market declines. While it is very possible to build a balanced, diversified portfolio from individual stocks, this isn't something I'd recommend for a new investor and would require a substantial college-level understanding of investments, and in any case, this portfolio would have a more discrete efficient frontier than the market as a whole. Lower Volatility Picking individual stocks or sectors would could also significantly increase or decrease the overall volatility of the portfolio relative to the market, especially if the stocks are highly cyclical or correlated to the same market factors. So if they are buying tech stocks, they might see bigger upswings and downswings compared to the market as a whole, or see the opposite effect in the case of utilities. In other words, owning a basket of individual stocks may result in an unintended volatility/beta profile. Lower Trading Costs and Taxes Investors who buy individual stocks tend to trade more in an attempt to beat the market. After accounting for commission fees, transaction costs (bid/ask spread), and taxes, most individual investors get only a fraction of the market average return. One famous academic study finds that investors who trade more trail the stock market more. Trading also tends to incur higher taxes since short term gains (<1 year) are taxed at marginal income tax rates that are higher than long term capital gains. Investors tend to trade due to behavioral failures such as trying to time the market, being overconfident, speculating on stocks instead of long-term investing, following what everyone else is doing, and getting in and out of the market as a result of an emotional reaction to volatility (ie buying when stocks are high/rising and selling when they are low/falling). Investing in index funds can involve minimal fees and discourages behavior that causes investors to incur excessive trading costs. This can make a big difference over the long run as extra costs and taxes compound significantly over time. It's Hard to Beat the Market since Markets are Quite Efficient Another reason to use funds is that it is reasonable to assume that at any point in time, the market does a fairly good job of pricing securities based on all known information. In other words, if a given stock is trading at a low P/E relative to the market, the market as a whole has decided that there is good reason for this valuation. This idea is based on the assumption that there are already so many professional analysts and traders looking for arbitrage opportunities that few such opportunities exist, and where they do exist, persist for only a short time. If you accept this theory generally (obviously, the market is not perfect), there is very little in the way of insight on pricing that the average novice investor could provide given limited knowledge of the markets and only a few hours of research. It might be more likely that opportunities identified by the novice would reflect omissions of relevant information. Trying to make money in this way then becomes a bet that other informed, professional investors are wrong and you are right (options traders, for example). Prices are Unpredictable (Behave Like \"\"Random\"\" Walks) If you want to make money as a long-term investor/owner rather than a speculator/trader, than most of the future change in asset prices will be a result of future events and information that is not yet known. Since no one knows how the world will change or who will be tomorrow's winners or losers, much less in 30 years, this is sometimes referred to as a \"\"random walk.\"\" You can point to fundamental analysis and say \"\"X company has great free cash flow, so I will invest in them\"\", but ultimately, the problem with this type of analysis is that everyone else has already done it too. For example, Warren Buffett famously already knows the price at which he'd buy every company he's interested in buying. When everyone else can do the same analysis as you, the price already reflects the market's take on that public information (Efficent Market theory), and what is left is the unknown (I wouldn't use the term \"\"random\"\"). Overall, I think there is simply a very large potential for an individual investor to make a few mistakes with individual stocks over 20+ years that will really cost a lot, and I think most investors want a balance of risk and return versus the largest possible return, and don't have an interest in developing a professional knowledge of stocks. I think a better strategy for most investors is to share in the future profits of companies buy holding a well-diversified portfolio for the long term and to avoid making a large number of decisions about which stocks to own.\"",
"title": ""
}
] |
3577
|
Avoiding Double-Reporting Income (1099-MISC plus 1099-K)
|
[
{
"docid": "57229",
"text": "Your clients should not send you 1099-MISC if they paid with a credit card. You can refer them to this text in the instructions for the form 1099-MISC: Payments made with a credit card or payment card and certain other types of payments, including third party network transactions, must be reported on Form 1099-K by the payment settlement entity under section 6050W and are not subject to reporting on Form 1099-MISC. See the separate Instructions for Form 1099-K. By sending out the 1099-MISC, your clients are essentially saying that they paid you directly (check or cash) in addition to the payment they made with a credit card (which will be reported on 1099-K). In case of an audit, you'll have trouble convincing the IRS that it didn't happen. I suggest asking the clients not to do this to you, since it may cost you significant amounts to fight the IRS later on. In any case, you report on your tax return what you really got, not what the 1099 says. If you have two 1099's covering the same income - there's no legal obligation to report the income twice. You do not have to pay twice the tax just because you have stupid clients. But you may have troubles explaining it to the IRS, especially if you're dealing with cash in your business. If you want to avoid matching issues, consider reporting all the 1099s, and then subtracting the duplicates and attaching a statement (the software will do it automatically when you add the description in the miscellaneous item) about what it is.",
"title": ""
}
] |
[
{
"docid": "277812",
"text": "There are many different types of 1099 forms. Since you are comparing it to a W-2, I'm assuming you are talking about a 1099-MISC form. Independent contractor income If you are a worker earning a salary or wage, your employer reports your annual earnings at year-end on Form W-2. However, if you are an independent contractor or self-employed you will receive a Form 1099-MISC from each client that pays you at least $600 during the tax year. For example, if you are a freelance writer, consultant or artist, you hire yourself out to individuals or companies on a contract basis. The income you receive from each job you take should be reported to you on Form 1099-MISC. When you prepare your tax return, the IRS requires you to report all of this income and pay income tax on it. So even if you receive a 1099-MISC form, you are required to pay taxes on it.",
"title": ""
},
{
"docid": "174025",
"text": "You are right that even if you do not receive a 1099-MISC, you still need to report all income to the IRS. Report the $40 on Schedule C or Schedule C-EZ. Since your net profit was less than $400, you do not need to file Schedule SE. From the IRS web site: Self-Employment Income It is a common misconception that if a taxpayer does not receive a Form 1099-MISC or if the income is under $600 per payer, the income is not taxable. There is no minimum amount that a taxpayer may exclude from gross income. All income earned through the taxpayer’s business, as an independent contractor or from informal side jobs is self-employment income, which is fully taxable and must be reported on Form 1040. Use Form 1040, Schedule C, Profit or Loss from Business, or Form 1040, Schedule C-EZ, Net Profit from Business (Sole Proprietorship) to report income and expenses. Taxpayers will also need to prepare Form 1040 Schedule SE for self-employment taxes if the net profit exceeds $400 for a year. Do not report this income on Form 1040 Line 21 as Other Income. Independent contractors must report all income as taxable, even if it is less than $600. Even if the client does not issue a Form 1099-MISC, the income, whatever the amount, is still reportable by the taxpayer.",
"title": ""
},
{
"docid": "434351",
"text": "You can and are supposed to report self-employment income on Schedule C (or C-EZ if eligible, which a programmer likely is) even when the payer isn't required to give you 1099-MISC (or 1099-K for a payment network now). From there, after deducting permitted expenses, it flows to 1040 (for income tax) and Schedule SE (for self-employment tax). See https://www.irs.gov/individuals/self-employed for some basics and lots of useful links. If this income is large enough your tax on it will be more than $1000, you may need to make quarterly estimated payments (OR if you also have a 'day job' have that employer increase your withholding) to avoid an underpayment penalty. But if this is the first year you have significant self-employment income (or other taxable but unwithheld income like realized capital gains) and your economic/tax situation is otherwise unchanged -- i.e. you have the same (or more) payroll income with the same (or more) withholding -- then there is a 'safe harbor': if your withholding plus estimated payments this year is too low to pay this year's tax but it is enough to pay last year's tax you escape the penalty. (You still need to pay the tax due, of course, so keep the funds available for that.) At the end of the first year when you prepare your return you will see how the numbers work out and can more easily do a good estimate for the following year(s). A single-member LLC or 'S' corp is usually disregarded for tax purposes, although you can elect otherwise, while a (traditional) 'C' corp is more complicated and AIUI out-of-scope for this Stack; see https://www.irs.gov/businesses/small-businesses-self-employed/business-structures for more.",
"title": ""
},
{
"docid": "42665",
"text": "I believe it's not only legal, but correct and required. A 1099 is how a business reports payments to others, and they're required by the IRS to send them for payments of $600 or more (for miscalleneous payments like this). The payment is an expense to the landlord and income to you, and the 1099 is how that's documented (although note that if they don't send you a 1099, it's still income to you and you still need to report it as such). It's similar to getting a 1099-INT for interest payments or a 1099-DIV for dividend payments. You'll get a 1099-MISC for a miscellaneous payment. If you were an employee they'd send you a W-2, not a 1099.",
"title": ""
},
{
"docid": "106684",
"text": "I'm not sure 1099-MISC is what you should expect. Equity means ownership, and in LLC context it means membership. As an LLC member, you'll get distributions and should receive a K-1 form for tax treatment, not 1099 or W2. If the CEO is talking about 1099 it means he's going to hire you as a contractor which contradicts the statement about equity allocation. That's an entirely different situation. 1) Specifically, would the 1099-MISC form be used in this case? 1099-MISC is used to describe various payments. Depending on which box is filled, the tax treatment may be as of employment income (subject to SE taxes) or passive income (royalties, rents, etc - subject to various limitations in the tax code). 3) If this is the only logical method of compensation (receiving a % of real estate sales), how would it be taxed? That would probably be a commission and taxed as employment income. I suggest to get a professional tax adviser consultation on this issue, with specific details, numbers, and kinds of deals involved. You can get gain or lose a lot of money just because you're characterized as a contractor and not LLC member or employee (each has its own benefits and disadvantages, and you have to consider them all). 4) Are there any advantages/disadvantages to acquiring and selling properties through the company as opposed to receiving a % of sales? Yes. There are advantages and there are disadvantages. For example, if you're using a corporation, you can get salary, if you're a contractor you cannot. There are a lot of issues hidden in this distinction (which I've just discussed with KeithS in this argument).",
"title": ""
},
{
"docid": "282681",
"text": "\"It is legal. They're probably going to give you a 1099-MISC, which is required of businesses for many cash payments over $600 in value to all sorts of counterparties. (Probably box 3 of 1099-MISC as is typical in \"\"cash for keys\"\" situations where one is paid to vacate early) A 1099-MISC is not necessarily pure income, but in this case, you do have money coming in. This money isn't a return of your security deposit or a gift. The payment could possibly be construed by you as a payment to make you whole, but the accounting for this would be on you. This is not a typical situation for IRS reporting. However, if you are uncomfortable with potentially explaining to the IRS how you implemented advice from strangers over the internet, the safest course is to report it all as income. Look at it this way: you did enter into a mutual contract, where you were paid consideration to release your leasehold interests in the property.\"",
"title": ""
},
{
"docid": "254151",
"text": "\"If you receive a 1099-MISC from YouTube, that tells you what they stated to the IRS and leads into most tax preparation software guided interviews or wizards as a topic for you to enter. Whether or not you have a 1099-MISC, this discussion from the IRS is pertinent to your question. You could probably elect to report the income as a royalty on your copyrighted work of art on Schedule E, but see this note: \"\"In most cases you report royalties in Part I of Schedule E (Form 1040). However, if you ... are in business as a self-employed writer, inventor, artist, etc., report your income and expenses on Schedule C or Schedule C-EZ (Form 1040).\"\" Whether reporting on Schedule E or C is more correct or better for your specific circumstances is beyond the advice you should take from strangers on the internet based on a general question - however, know that there are potentially several paths for you. Note that this is revenue from a business, so if you paid for equipment or services that are 100% dedicated to your YouTubing (PC, webcam, upgraded broadband, video editing software, vehicle miles to a shoot, props, etc.) then these are a combination of depreciable capital investments and expenses you can report against the income, reducing the taxes you may owe. If the equipment/services are used for business and personal use, there are further guidelines from the IRS as to estimating the split. These apply whether you report on Sch. E, Sch. C, or Sch C-EZ. Quote: \"\"Self-Employment Income It is a common misconception that if a taxpayer does not receive a Form 1099-MISC or if the income is under $600 per payer, the income is not taxable. There is no minimum amount that a taxpayer may exclude from gross income. All income earned through the taxpayer’s business, as an independent contractor or from informal side jobs is self-employment income, which is fully taxable and must be reported on Form 1040. Use Form 1040, Schedule C, Profit or Loss from Business, or Form 1040, Schedule C-EZ, Net Profit from Business (Sole Proprietorship) to report income and expenses. Taxpayers will also need to prepare Form 1040 Schedule SE for self-employment taxes if the net profit exceeds $400 for a year. Do not report this income on Form 1040 Line 21 as Other Income. Independent contractors must report all income as taxable, even if it is less than $600. Even if the client does not issue a Form 1099-MISC, the income, whatever the amount, is still reportable by the taxpayer. Fees received for babysitting, housecleaning and lawn cutting are all examples of taxable income, even if each client paid less than $600 for the year. Someone who repairs computers in his or her spare time needs to report all monies earned as self-employment income even if no one person paid more than $600 for repairs.\"\"\"",
"title": ""
},
{
"docid": "487728",
"text": "I strongly recommend that you talk to an accountant right away because you could save some money by making a tax payment by January 15, 2014. You will receive Forms 1099-MISC from the various entities with whom you are doing business as a contractor detailing how much money they paid you. A copy will go to the IRS also. You file a Schedule C with your Form 1040 in which you detail how much you received on the 1099-MISC forms as well as any other income that your contracting business received (e.g. amounts less than $600 for which a 1099-MISc does not need to be issued, or tips, say, if you are a taxi-driver running your own cab), and you can deduct various expenses that you incurred in generating this income, including tools, books, (or gasoline!) etc that you bought for doing the job. You will need to file a Schedule SE that will compute how much you owe in Social Security and Medicare taxes on the net income on Schedule C. You will pay at twice the rate that employees pay because you get to pay not only the employee's share but also the employer's share. At least, you will not have to pay income tax on the employer's share. Your net income on Schedule C will transfer onto Form 1040 where you will compute how much income tax you owe, and then add on the Social Security tax etc to compute a final amount of tax to be paid. You will have to pay a penalty for not making tax payments every quarter during 2013, plus interest on the tax paid late. Send the IRS a check for the total. If you talk to an accountant right away, he/she will likely be able to come up with a rough estimate of what you might owe, and sending in that amount by January 15 will save some money. The accountant can also help you set up for the 2014 tax year during which you could make quarterly payments of estimated tax for 2014 and avoid the penalties and interest referred to above.",
"title": ""
},
{
"docid": "477476",
"text": "Welcome to the wonderful but oft confusing world of self-employment. Your regular job will withhold income for you and give you a W2, which tells you and the government how much is withheld. At the end of the year uber will give you and the government a 1099-misc, which will tell you how much they paid you, but nothing will be withheld, which means you will owe the government some taxes. When it comes to taxes, you will file a 1040 (the big one, not a 1040EZ nor 1040A). In addition you will file a schedule C (self-employed income), where you will report the gross paid to you, deduct your expenses, and come up with your profit, which will be taxable. That profit goes into a line in the 1040. You need to file schedule SE. This says how much self-employment tax you will pay on your 1099 income, and it will be more than you expect. Self employment tax is SS/Medicare. There's a line for this on the 1040 as well. You can also deduct half of your self-employment tax on the 1040, there's a line for it. Now, you can pay quarterly taxes on your 1099 income by filing 1040-ES. That avoids a penalty (which usually isn't that large) for not withholding enough. As an alternative, you can have your regular W2 job withhold extra. As long as you don't owe a bunch at tax time, you won't be a fined. When you are self-employed your taxes aren't as simple. Sorry. You can either spend some time becoming an expert by studying the instructions for the 1040, pay for the expensive version of tax programs, or hire someone to do it for you. Self-employed taxes are painful, but take advantage of the upsides as well. You can start a solo 401(k) or SEP IRA, for example. Make sure you are careful to deduct every relevant business expense and keep good records in case you get audited.",
"title": ""
},
{
"docid": "4457",
"text": "From WePay (GoFundMe's payment processor) support. I received only gifts and donations. Will I receive a Form 1099-K? As of 2015, the IRS has clarified that WePay is not required to send a Form 1099-K with respect to payments that are made solely as gifts or donations. The purpose of Form 1099-K is to report payments for the provision of goods or services, which may be subject to tax. Gifts and donations typically are not reported as income by recipients, so it is not necessary to send them a Form 1099-K. https://support.wepay.com/hc/en-us/articles/203609483-Tax-Reporting",
"title": ""
},
{
"docid": "481459",
"text": "Do you get cash (or a deposit into your bank account) of your PhD stipend and then you immediately send the university a check to pay the tuition fee (which might be more than the cash you get from the University)? Or does the University simply keep the stipend money, transferring it from one pocket to another in essence, and say, OK, you have paid your tuition except for $X that you still owe us? Or does the university grant you a tuition waiver as part of your assistantship and reports this as income on Form 1099-MISC? In all of these cases, the money reported on Form 1099-MISC is not taxable income to you, and it is neither subject to Self-Employment tax (basically, Social Security and Medicare tax -- both the employee's share and the employer's share) nor to (Federal) income tax.",
"title": ""
},
{
"docid": "184698",
"text": "\"You can list it as other income reported on line 21 of form 1040. In TurboTax, enter at: - Federal Taxes tab (Personal in Home & Business) - Wages & Income -“I’ll choose what I work on” Button Scroll down to: -Less Common Income -Misc Income, 1099-A, 1099-C. -The next screen will give you several choices. Choose \"\"Other reportable Income\"\". You will reach a screen where you can type a description of the income and the amount. Type in the amount of income and categorize as Tutoring.\"",
"title": ""
},
{
"docid": "327078",
"text": "\"Does he need to file a tax return in this situation? Will the IRS be concerned that he did not file even if he received a 1099? No. However, if you don't file the IRS may come back asking why, or \"\"make up\"\" a return for you assuming that the whole amount on the 1099-MISC is your net earnings. So in the end, I suspect you'll end up filing even though you don't have to, just to prove that you don't have to. Bottom line - if you have 1099 income (or any other income reported to the IRS that brings you over the filing threshold), file a return.\"",
"title": ""
},
{
"docid": "417866",
"text": "\"Payment gateways such as Square do not normally withhold tax. It is up to you to pay the appropriate tax at tax time. That having been said, Square does report your payments to the IRS on a form 1099-K if your payments are large enough. According to Square, you'll get a 1099-K from them if your total payments for the year add up to $20,000 AND more than 200 transactions. Whether or not they report on a 1099-K, you are required to pay the appropriate taxes on your income. So now the question becomes, \"\"Do I have to pay income tax on the proceeds from my garage sale?\"\" And the answer to that question is usually not. When you sell something that you previously purchased, if you sell it for more than you paid for it, you have a capital gain and need to pay tax on that. However, generally you sell things in a garage sale at a loss, meaning that there is no tax due. If you make more than $20,000 at your garage sale and the IRS gets a 1099-K, the IRS might be curious as to how you did that with no capital gain. So if you sell any big ticket items (a bulldozer, for example), you should keep a record of what you paid for it, so you can show the loss to the IRS in the event of an audit.\"",
"title": ""
},
{
"docid": "196399",
"text": "I can't find specific information for Form 1099-DIV for this tax year. However, I found this quote for next tax season that talks about Form 1099-B: Due date for certain statements sent to recipients. The due date for furnishing statements to recipients for Forms 1099-B, 1099-S, and 1099-MISC (if amounts are reported in box 8 or 14) is February 15, 2018. [emphasis added] I know many brokerages bundle the 1099-DIV with the 1099-B, so one might assume that the deadlines are the same. February 15 seems consistent with the messages I got from my brokerages that said the forms will be mailed by mid-February.",
"title": ""
},
{
"docid": "454184",
"text": "I'm not sure how this gets entered in TurboTax, but this income from the company should be included in the Schedule C (or C-EZ) Line 1 Gross Receipts total, along with all of your 1099-MISC income from your business and any other income that your business took in. You don't need a 1099 from them, and the IRS doesn't care (at least from your perspective) if you got a 1099 or not; in fact, they probably expect you to have some non-1099 income. We don't know why the company chose not to issue 1099 forms, but luckily it isn't your concern. You can fill out your tax return properly without it. Note: This answer assumes that you didn't have any tax withheld from your checks from this company. If you did have tax withheld, you'll need to insist on a 1099 to show that.",
"title": ""
},
{
"docid": "345942",
"text": "Am I required to send form 1099 to non-US citizens who are not even residing in the US? Since they're not required to file US taxes, do I still have to send the form to them? That's tricky. You need to get W8/W9 from them, and act accordingly. You may need to withhold 30% (or different percentage, depending on tax treaty they claim on W8). If you withhold taxes, you also need to file form 1042. I suggest you talk to a tax professional. Is it fine to expose my ITIN (taxpayer identification number) to individuals or companies who I send the form to them. Since the form requires me to write my TIN/EIN, what would be the risks of this and what precautions should be taken to avoid inappropriate/illegal use? No, it is not OK. But if you pay these people directly - you don't have much choice, so deal with it. Get a good insurance for identity theft, and don't transact with people you don't trust. One alternative would be to pay through a payment processor (Paypal or credit cards) - see your next question. I send payments via PayPal and wire transfer. Should I send form 1099-MISC or 1099-K? Paypal is a corporation, so you don't need to send 1099 to Paypal. Whatever Paypal sends to others - it will issue the appropriate forms. Similarly if you use a credit card for payment. When you send money through Paypal - you don't send money directly to your business counterparts. You send money to Paypal.",
"title": ""
},
{
"docid": "357455",
"text": "\"MLP stands for master limited partnership. Investors who buy into one are limited partners, rather than shareholders, and have their taxable income reported on K-1s, rather than 1099s. MLPs are engaged in businesses (e.g. real estate, natural resources) that generate a lot of cash that doesn't need to be \"\"reinvested,\"\" or put back into the company. Because of this feature, the IRS will exempt it from corporate tax if it pays out at least 95% of its income in the form of dividends. The advantage is that you avoid the \"\"double taxation\"\" common to most corporations, and get a higher yield as a result. The disadvantage is that the company can't retain earnings for growth, and needs to borrow money if it wants to grow. In this regard, an MLP is much like a utility (except that a utility has to pay corporate taxes, and is otherwise heavily regulated by the Federal and/or state governments). You can look upon an MLP as an unregulated utility. This means that MLPs are most suitable for utility type investors who are more interested in current income, than capital gains. Because they are unregulated, they are riskier than utilities.\"",
"title": ""
},
{
"docid": "388713",
"text": "As a new (very!) small business, the IRS has lots of advice and information for you. Start at https://www.irs.gov/businesses/small-businesses-self-employed and be sure you have several pots of coffee or other appropriate aid against somnolence. By default a single-member LLC is 'disregarded' for tax purposes (at least for Federal, and generally states follow Federal although I don't know Mass. specifically), although it does have other effects. If you go this route you simply include the business income and expenses on Schedule C as part of your individual return on 1040, and the net SE income is included along with your other income (if any) in computing your tax. TurboTax or similar software should handle this for you, although you may need a premium version that costs a little more. You can 'elect' to have the LLC taxed as a corporation by filing form 8832, see https://www.irs.gov/businesses/small-businesses-self-employed/limited-liability-company-llc . In principle you are supposed to do this when the entity is 'formed', but in practice AIUI if you do it by the end of the year they won't care at all, and if you do it after the end of the year but before or with your first affected return you qualify for automatic 'relief'. However, deciding how to divide the business income/profits into 'reasonable pay' to yourself versus 'dividends' is more complicated, and filling out corporation tax returns in addition to your individual return (which is still required) is more work, in addition to the work and cost of filing and reporting the LLC itself to your state of choice. Unless/until you make something like $50k-100k a year this probably isn't worth it. 1099 Reporting. Stripe qualifies as a 'payment network' and under a recent law payment networks must annually report to IRS (and copy to you) on form 1099-K if your account exceeds certain thresholds; see https://support.stripe.com/questions/will-i-receive-a-1099-k-and-what-do-i-do-with-it . Note you are still legally required to report and pay tax on your SE income even if you aren't covered by 1099-K (or other) reporting. Self-employment tax. As a self-employed person (if the LLC is disregarded) you have to pay 'SE' tax that is effectively equivalent to the 'FICA' taxes that would be paid by your employer and you as an employee combined. This is 12.4% for Social Security unless/until your total earned income exceeds a cap (for 2017 $127,200, adjusted yearly for inflation), and 2.9% for Medicare with no limit (plus 'Additional Medicare' tax if you exceed a higher threshold and it isn't 'repealed and replaced'). If the LLC elects corporation status it has to pay you reasonable wages for your services, and withhold+pay FICA on those wages like any other employer. Estimated payments. You are required to pay most of your individual income tax, and SE tax if applicable, during the year (generally 90% of your tax or your tax minus $1,000 whichever is less). Most wage-earners don't notice this because it happens automatically through payroll withholding, but as self-employed you are responsible for making sufficient and timely estimated payments, and will owe a penalty if you don't. However, since this is your first year you may have a 'safe harbor'; if you also have income from an employer (reported on W-2, with withholding) and that withholding is sufficent to pay last year's tax, then you are exempt from the 'underpayment' penalty for this year. If you elect corporation status then the corporation (which is really just you) must always make timely payments of withheld amounts, according to one of several different schedules that may apply depending on the amounts; I believe it also must make estimated payments for its own liability, if any, but I'm not familiar with that part.",
"title": ""
},
{
"docid": "290045",
"text": "You should get a 1099-MISC for the $5000 you got. And your broker should send you a 1099-B for the $5500 sale of Google stock. These are two totally separate things as far as the US IRS is concerned. 1) You made $5000 in wages. You will pay income tax on this as well as FICA and other state and local taxes. 2) You will report that you paid $5000 for stock, and sold it for $5500 without holding it for one year. Since this was short term, you will pay tax on the $500 in income you made. These numbers will go on different parts of your tax form. Essentially in your case, you'll have to pay regular income tax rates on the whole $5500, but that's only because short term capital gains are treated as income. There's always the possibility that could change (unlikely). It also helps to think of them separately because if you held the stock for a year, you would pay different tax on that $500. Regardless, you report them in different ways on your taxes.",
"title": ""
},
{
"docid": "481284",
"text": "Typically that applies if the broker Form 1099-B reports an incorrect basis to the IRS. If the Form 1099-B shows incorrect basis relative to your records, then you can use 8949, column (g) to report the correct basis. The 8949 Instructions provide a brief example. http://www.irs.gov/pub/irs-prior/i8949--2013.pdf Although you have an obligation to report all income, and hence to report the true basis, as a practical matter this information will usually be correct as presented by the broker. If you have separate information or reports relating to your investments, and you are so inclined, then you can double-check the basis information in your 1099-B. If you aren't aware of basis discrepancies, then the adjustments probably don't apply to you and your investments can stick to Schedule D.",
"title": ""
},
{
"docid": "196920",
"text": "From the 1099 instructions: File Form 1099-MISC, Miscellaneous Income, for each person to whom you have paid during the year Your accounting method doesn't matter. You file 1099 for the year you paid the money.",
"title": ""
},
{
"docid": "175072",
"text": "\"If you are in the US, you legally must file taxes on any income whatsoever. How much you will pay in taxes, if any, will depend on your total taxable income. Now, for small transactions, the payments are often not reported to the IRS so some people do not file or pay. The threshold at which they payer is required to send a 1099 to the IRS is $600. Patreon considers each donation a separate transaction and therefore does not send a 1099 to the IRS unless you make more than $20,000 in a calendar year. If they do not report it, the IRS will not know about it unless they audit you or something. However, you are technically and legally responsible to report income whether the IRS knows about it or not. -------- EDIT ------- Note that the payer files a 1099, not the recipient. In order to report your patreon income you will either use schedule C or add it to the amount on 1040 line 21 (\"\"other income\"\") depending on whether you consider this a business or a hobby. If it's a business and it's a lot of money you should consider sending in quarterly payments using a 1040-ES in order to avoid a penalty for too little withholding.\"",
"title": ""
},
{
"docid": "158409",
"text": "You do not need to file 1099-MISC to yourself if you're running as a sole proprietor - you are yourself. However, you do not deduct this amount from your business income and report it as royalties either. Your self-published book is your business income subject to SE tax. You can only deduct the actual costs of producing/writing, and the remaining amount is your Schedule C income.",
"title": ""
},
{
"docid": "435405",
"text": "\"(Insert the usual disclaimer that I'm not any sort of tax professional; I'm just a random guy on the Internet who occasionally looks through IRS instructions for fun. Then again, what you're doing here is asking random people on the Internet for help, so here goes.) The gigantic book of \"\"How to File Your Income Taxes\"\" from the IRS is called Publication 17. That's generally where I start to figure out where to report what. The section on Royalties has this to say: Royalties from copyrights, patents, and oil, gas, and mineral properties are taxable as ordinary income. In most cases, you report royalties in Part I of Schedule E (Form 1040). However, if you hold an operating oil, gas, or mineral interest or are in business as a self-employed writer, inventor, artist, etc., report your income and expenses on Schedule C or Schedule C-EZ (Form 1040). It sounds like you are receiving royalties from a copyright, and not as a self-employed writer. That means that you would report the income on Schedule E, Part I. I've not used Schedule E before, but looking at the instructions for it, you enter this as \"\"Royalty Property\"\". For royalty property, enter code “6” on line 1b and leave lines 1a and 2 blank for that property. So, in Line 1b, part A, enter code 6. (It looks like you'll only use section A here as you only have one royalty property.) Then in column A, Line 4, enter the royalties you have received. The instructions confirm that this should be the amount that you received listed on the 1099-MISC. Report on line 4 royalties from oil, gas, or mineral properties (not including operating interests); copyrights; and patents. Use a separate column (A, B, or C) for each royalty property. If you received $10 or more in royalties during 2016, the payer should send you a Form 1099-MISC or similar statement by January 31, 2017, showing the amount you received. Report this amount on line 4. I don't think that there's any relevant Expenses deductions you could take on the subsequent lines (though like I said, I've not used this form before), but if you had some specific expenses involved in producing this income it might be worth looking into further. On Line 21 you'd subtract the 0 expenses (or subtract any expenses you do manage to list) and put the total. It looks like there are more totals to accumulate on lines 23 and 24, which presumably would be equally easy as you only have the one property. Put the total again on line 26, which says to enter it on the main Form 1040 on line 17 and it thus gets included in your income.\"",
"title": ""
},
{
"docid": "91466",
"text": "\"Gifts given and received between business partners or employers/employees are treated as income, if they are beyond minimal value. If your boss gives you a gift, s/he should include it as part of your taxable wages for payroll purposes - which means that some of your wages should be withheld to cover income, social security, and Medicare taxes on it. At the end of the year, the value of the gift should be included in Box 1 (wages) of your form W-2. Assuming that's the case, you don't need to do anything special. A 1099-MISC would not be appropriate because you are an employee of your boss - so the two of you need to address the full panoply of employment taxes, not just income tax, which would be the result if the payment were reported on 1099-MISC. If the employer wants to cover the cost to you of the taxes on the gift, they'll need to \"\"gross up\"\" your pay to cover it. Let's say your employer gives you a gift worth $100, and you're in a 25% tax bracket. Your employer has to give you $125 so that you end up with a gain of $100. But the extra $25 is taxable, too, so your employer will need to add on an extra $6.25 to cover the 25% tax on the $25. But, wait, now we've gotta pay 25% tax on the $6.25, so they add an extra $1.56 to cover that tax. And now they've gotta pay an extra $.39 . . . The formula to calculate the gross-up amount is: where [TAX RATE] is the tax rate expressed as a percentage. So, to get the grossed-up amount for a $100 gift in a 25% bracket, we'd calculate 1/(1-.25), or 1/.75, or 1.333, multiply that by the target gift amount of $100, and end up with $133.33. The equation is a little uglier if you have to pay state income taxes that are deductible on the federal return but it's a similar principle. The entire $133.33 would then be reported as income, but the net effect on the employee is that they're $100 richer after taxes. The \"\"gross-up\"\" idea can be quite complicated if you dig into the details - there are some circumstances where an additional few dollars of income can have an unexpected impact on a tax return, in a fashion not obvious from looking at the tax table. If the employer doesn't include the gift in Box 1 on the W-2 but you want to pay taxes on it anyway, include the amount in Line 7 on the 1040 as if it had been on a W-2, and fill out form 8919 to calculate the FICA taxes that should have been withheld.\"",
"title": ""
},
{
"docid": "406042",
"text": "Are the amounts in those boxes taxes that have already been removed? Yes. If they are, how do I report these totals? When I entered the information from the 1099-MISC, it only asked for the total, and didn't ask for (what I thought were) the taxes already taken out. It should appear on your 1040 line 64 (and similar line on your State tax return). If the program doesn't ask for all the 1099 fields (which is stupid), you can add it as additional taxes paid in the Credits section, somewhere in the area where they ask about estimated payments etc.",
"title": ""
},
{
"docid": "279538",
"text": "\"Yes, you can deduct up to your Adjusted Gross Income (AGI) or your contribution limit, whichever is lower. Note that this reduces your taxable income, not your taxes. This is self-employment income, which is included as compensation for IRA purposes. You still have to pay self-employment taxes (Social Security and Medicare) though. You pay those before calculating AGI. So this won't entirely shield your 1099 income from taxes, just from income taxes. Note that if you have both W-2 and 1099-MISC income, you don't get to pick which gets \"\"shielded\"\" from taxes. It all gets mixed together in the same bucket. There may be additional limitations if you are covered by a retirement plan at work.\"",
"title": ""
},
{
"docid": "537763",
"text": "Form 1099-misc reports PAYMENTS, not earnings. This does not imply the EARNINGS are not taxable in the year they were earned.",
"title": ""
},
{
"docid": "522619",
"text": "\"The Trustee has allowed me to act as his \"\"agent\"\", continuing to pay bills, and take care of much of the administrative affairs for my mother's estate since I did all of it for years before she passed away. I was not paid for any of this work. ... The expenses were more than $30K last year, and there is still a punch list to go this year. The trust should reimburse your expenses and deduct them on the trust tax return. Since the Trust owned the property in 2015, and I will receive ownership this month, can last year's expenses incurred for the Trust be deducted again future income for my property this year? Not exactly. The trust will file its own tax return and will report the income/loss attributed to the beneficiaries per the trust rules. What is attributed to you will flow to your Schedule E. From there you own it and if it is a passive activity where the loss is limited - you can carry it forward and offset with future gain. The trustee will have to deal with all the paperwork. Do 1099-misc forms need to be filed for the contractors who worked to get it ready for rental? It is my understanding that since 2010 (and before 2010) landlords who are not in real-estate trade or business are not required to send out 1099. But it won't hurt if you do, also. In any case - for all of these issues you should talk to a tax adviser (EA/CPA licensed in your State).\"",
"title": ""
}
] |
417
|
Female carriers of the Apolipoprotein E4 (APOE4) allele have shorter lifetime exposure to estrogen due to a decreased reproductive period.
|
[
{
"docid": "6309659",
"text": "CONTEXT Exogenous estrogen use may lower risk of dementia in postmenopausal women. A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied. OBJECTIVE To determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause. DESIGN AND SETTING The Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands. PARTICIPANTS A total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche, age at menopause, and type of menopause. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for development of dementia. MAIN OUTCOME MEASURES Incidence of dementia, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria, and AD, based on National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, compared by quartiles of reproductive period among women with natural menopause. RESULTS During 21 046 person-years of follow-up (median follow-up, 6.3 years), 199 women developed dementia, including 159 who developed AD. After adjusting for age, dementia was not clearly associated with length of reproductive period. However, after adjusting for multiple covariates, women with natural menopause and more reproductive years had an increased risk of dementia (adjusted rate ratio [RR] for women with >39 reproductive years [highest quartile] compared with <34 reproductive years [lowest quartile], 1.78; 95% confidence interval [CI], 1.12-2.84). The adjusted RR per year of increase was 1.04 (95% CI, 1.01-1.08). For risk of AD, the adjusted RRs were 1.51 (95% CI, 0.91-2.50) and 1.03 (95% CI, 1.00-1.07), respectively. Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers (adjusted RR for >39 reproductive years compared with <34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed. CONCLUSION Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause.",
"title": "Reproductive period and risk of dementia in postmenopausal women."
}
] |
[
{
"docid": "12443371",
"text": "OBJECTIVE To evaluate the association between apolipoprotein E (APOE) polymorphisms (E2, C/T Arg158Cys; E4, T/C Cys112Arg; and promoter, g-219t) and the history of concussion in college athletes. We hypothesized that carrying 1 or more APOE rare (or minor) allele assessed in this study would be associated with having a history of 1 or more concussions. DESIGN Multicenter cross-sectional study. SETTING University athletic facilities. PARTICIPANTS One hundred ninety-six male football (n = 163) and female soccer (n = 33) college athletes volunteered. INTERVENTIONS Written concussion history questionnaire and saliva samples for genotyping. MAIN OUTCOME MEASURES Self-reported history of a documented concussion and rare APOE genotype (E2, E4, promoter). RESULTS There was a significant association (Wald χ² = 3.82; P = 0.05; odds ratio = 9.8) between carrying all APOE rare alleles and the history of a previous concussion. There was also a significant association (Wald χ² = 3.96, P = 0.04, odds ratio = 8.4) between carrying the APOE promoter minor allele and experiencing 2 or more concussions. CONCLUSIONS Carriers of all 3 APOE rare (or minor) alleles assessed in this study were nearly 10 times more likely to report a previous concussion and may be at a greater risk of concussion versus noncarriers. Promoter minor allele carriers were 8.4 times more likely to report multiple concussions and may be at a greater risk of multiple concussions versus noncarriers. Research involving larger samples of individuals with multiple concussions and carriers of multiple APOE rare alleles is warranted.",
"title": "Apolipoprotein E genotype and concussion in college athletes."
},
{
"docid": "4709641",
"text": "Efforts to develop drugs for Alzheimer's disease (AD) have shown promise in animal studies, only to fail in human trials, suggesting a pressing need to study AD in human model systems. Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloid-β (Aβ) peptides, and that they displayed GABAergic neuron degeneration. ApoE4 increased Aβ production in human, but not in mouse, neurons. Converting ApoE4 to ApoE3 by gene editing rescued these phenotypes, indicating the specific effects of ApoE4. Neurons that lacked APOE behaved similarly to those expressing ApoE3, and the introduction of ApoE4 expression recapitulated the pathological phenotypes, suggesting a gain of toxic effects from ApoE4. Treatment of ApoE4-expressing neurons with a small-molecule structure corrector ameliorated the detrimental effects, thus showing that correcting the pathogenic conformation of ApoE4 is a viable therapeutic approach for ApoE4-related AD.",
"title": "Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector"
},
{
"docid": "37205759",
"text": "The Apolipoprotein (Apo) family is implicated in lipid metabolism. There are five types of Apo: Apoa, Apob, Apoc, Apod, and Apoe. Apoe has been demonstrated to play a central role in lipoprotein metabolism and to be essential for efficient receptor-mediated plasma clearance of chylomicron remnants and VLDL remnant particles by the liver. Apoe-deficient (Apoe(-/-)) mice develop atherosclerotic plaques spontaneously, followed by obesity. In this study, we investigated whether lipid deposition caused by Apoe knockout affects reproduction in female mice. The results demonstrated that Apoe(-/-) mice were severely hypercholesterolemic, with their cholesterol metabolism disordered, and lipid accumulating in the ovaries causing the ovaries to be heavier compared with the WT counterparts. In addition, estrogen and progesterone decreased significantly at D 100. Quantitative PCR analysis demonstrated that at D 100 the expression of cytochromeP450 aromatase (Cyp19a1), 3β-hydroxysteroid dehydrogenase (Hsd3b), mechanistic target of rapamycin (Mtor), and nuclear factor-κB (Nfkb) decreased significantly, while that of BCL2-associated agonist of cell death (Bad) and tuberous sclerosis complex 2 (Tsc2) increased significantly in the Apoe(-/-) mice. However, there was no difference in the fertility rates of the Apoe(-/-) and WT mice; that is, obesity induced by Apoe knockout has no significant effect on reproduction. However, the deletion of Apoe increased the number of ovarian follicles and the ratio of ovarian follicle atresia and apoptosis. We believe that this work will augment our understanding of the role of Apoe in reproduction.",
"title": "Obesity occurring in apolipoprotein E-knockout mice has mild effects on fertility."
},
{
"docid": "18852643",
"text": "In humans, apolipoprotein E (apoE) is a polymorphic multifunctional protein.1 It is coded by three alleles (e2, e3, e4) of a modulator gene (level, variability, and susceptibility gene) at the apoE locus on chromosome 19, determining six apoE genotypes and plasma phenotypes. Its pleiotropic effects are exerted on plasma lipoprotein metabolism, coagulation, oxidative processes, macrophage, glial cell and neuronal cell homeostasis, adrenal function, central nervous system physiology, inflammation, and cell proliferation.2,3 ApoE polymorphism modulates susceptibility to many diseases. It is, however, particularly notorious for its role in neurodegenerative disorders4 and atherosclerotic arterial disease.5,6 The e4 allele (phenotypes E4/4 and E4/3) that is associated with higher low density lipoprotein cholesterol (LDL-C) is considered proatherogenic, whereas the presence of the e2 allele (E3/2, E2/2), being associated with lower LDL-C levels, is deemed to have the opposite effect (although it may be associated with increased plasma triglycerides and lipoprotein remnants). This simple equation, however, is an oversimplification because these properties are subject to many environmental and genetic influences. ApoE has allele- and gender-dependent effects on reverse cholesterol transport, platelet aggregation, and oxidative processes that are likely to affect the overall atherogenic potential ascribed to modulation of lipoprotein metabolism.2,3,6 Notwithstanding the context dependency, a recent meta-analysis fully supports the presence of the e4 allele as a significant risk factor for coronary artery disease.7 Several mechanisms have been evoked to link apoE with atherosclerosis, but the relationship is not fully unraveled in humans. Nevertheless, some apoE mimetic peptides that promote LDL clearance are currently tested in animals for potential clinical applications.8,9 See page 436 The situation is relatively simpler in animals. The mouse model has been prominently useful to test mechanisms …",
"title": "Apolipoprotein E and atherosclerosis: beyond lipid effect."
},
{
"docid": "15669393",
"text": "Transient activation of estrogen receptors (ER) in the developing brain during a limited perinatal \"window of time\" is recognized as a key mechanism of defeminization of neural control of reproductive function and sexual behavior. Two major ER isoforms, alpha and beta, are present in neural circuits that govern ovarian cycle and sexual behavior. Using highly selective ER agonists, this study provides the first evidence for distinct contribution of individual ER isoforms to the process of estrogen dependent defeminization. Neonatal activation of the ERalpha in female rats resulted in abrogation of cyclic ovarian activity and female sexual behavior in adulthood. These effects are associated with male-like alterations in the morphology of the anteroventral periventricular (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN-POA), as well as refractoriness to estrogen-mediated induction of sexual receptivity. Exposure to an ERbeta-selective agonist induced persistent estrus and had a strong defeminizing effect on the hypothalamic gonadotropin \"surge generator\" AVPV. However, neonatal ERbeta activation failed to alter female sexual behavior, responsiveness to estrogens and morphometric features of the behaviorally relevant SDN-POA. Thus, although co-present in several brain regions involved in the control of female reproductive function, ER isoforms convey different, and probably not synergistic, chemical signals in the course of neonatal sex-specific brain organization.",
"title": "brain organization"
},
{
"docid": "30351165",
"text": "Cerebral apolipoprotein E (apoE) has been implicated in neuronal protection and repair. Due to the variable levels and types of estrogen receptors within different brain regions, the effect of estrogen on apoE and the mechanism of this effect may vary within different regions. Ovariectomized female C57BL/6 mice were treated with pharmacological levels of 17 beta-estradiol or placebo for 5 days, resulting in supraphysiological plasma levels of estradiol in the treated mice. ApoE and glial fibrillary acidic protein (GFAP) levels were measured in the cortex, hippocampus and diencephalon. 17 beta-Estradiol up-regulated apoE but not GFAP in the cortex and diencephalon, whereas in the hippocampus, GFAP and apoE were equally up-regulated. Treatment of estrogen receptor (ER) alpha knockout mice with 17 beta-estradiol or treatment of C57BL/6 mice with 17 alpha-estradiol, a poor estrogen receptor agonist, specifically induced apoE in the cortex, but not in the diencephalon. These results indicate that 17 beta-estradiol effects on apoE are either directly or indirectly mediated by ER alpha in the diencephalon, while the effects in the cortex may be mediated by a non-classical mechanism or by ER beta. Measurement of mRNA levels in estrogen versus placebo-treated wild-type mice indicated that the effect of 17 beta-estradiol on apoE was not associated with changes in apoE mRNA levels.",
"title": "Brain region-specific up-regulation of mouse apolipoprotein E by pharmacological estrogen treatments."
},
{
"docid": "20937018",
"text": "Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic beta A4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the beta A4 peptide are required. The gene for apolipoprotein E is located on chromosome 19q13.2, within the region previously associated with linkage of late-onset familial Alzheimer disease. Analysis of apolipoprotein E alleles in Alzheimer disease and controls demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014). A functional role of the apolipoprotein E-E4 isoform in the pathogenesis of late-onset familial Alzheimer disease is suggested.",
"title": "Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease."
},
{
"docid": "24906548",
"text": "The epsilon4 allele of the apolipoprotein E (APOE) gene has been linked to negative outcomes among adults with traumatic brain injury (TBI) across the spectrum of severity, with preliminary evidence suggesting a similar pattern among children. This study investigated the relationship of the APOE epsilon4 allele to outcomes in children with mild TBI. Participants in this prospective, longitudinal study included 99 children with mild TBI between the ages of 8 and 15 recruited from consecutive admissions to Emergency Departments at two large children's hospitals. Outcomes were assessed acutely in the Emergency Department and at follow-ups at 2 weeks, 3 months, and 12 months post-injury. Among the 99 participants, 28 had at least one epsilon4 allele. Children with and without an epsilon4 allele did not differ demographically. Children with an epsilon4 allele were significantly more likely than those without an epsilon4 allele to have a Glasgow Coma Scale score of less than 15, but the groups did not differ on any other measures of injury severity. Those with an epsilon4 allele exhibited better performance than children without an epsilon4 allele on a test of constructional skill, but the groups did not differ on any other neuropsychological tests. Children with and without an epsilon4 allele also did not differ on measures of post-concussive symptoms. Overall, the findings suggest that the APOE epsilon4 allele is not consistently related to the outcomes of mild TBI in children.",
"title": "Apolipoprotein E4 as a predictor of outcomes in pediatric mild traumatic brain injury."
},
{
"docid": "18340282",
"text": "BACKGROUND Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. METHODS We tested gene-environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). FINDINGS After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162.4 cm [95% CI 162.1-162.7] vs 163.1 cm [162.9-163.2]; p=0.01 after allowance for multiple testing). INTERPRETATION Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. FUNDING Cancer Research UK and the UK Medical Research Council.",
"title": "Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study"
},
{
"docid": "41380943",
"text": "During embryonic development, gonadal steroid hormones (androgens and estrogens) are thought to organize the sexual differentiation of the brain in the heterogametic sexes of higher vertebrates (males in mammals, females in birds). Brain differentiation of the homogametic sexes is thought to proceed by default, not requiring sex hormones for sex-specific organization. In gallinaceous birds such as the Japanese quail, female brain organization is thought to develop via estrogen-dependent demasculinization of a default male brain phenotype. We performed male donor-to-female host (MF), female-to-male (FM), male-to-male (MM), and female-to-female (FF) isotopic, isochronic transplantation of the forebrain primordium in Japanese quail embryos before gonadal differentiation had occurred; brain chimeras had a forebrain (including the hypothalamus) originating exclusively from donor cells. MM, FF, and MF chimeras all showed sexual behavior governed by the genetic sex of the host. In contrast, FM chimeras (genetically female forebrain, all other tissues genetically male) showed no mounting and only rudimentary crowing behavior. Although MM, FF, MF, and FM chimeras all showed host-typical production of steroid hormones during embryonic life, only FM chimeras were hypogonadal, had atypical low levels of circulating testosterone in adulthood, and showed reduction (crowing) or absence (mounting) of reproductive behaviors. Morphological features of the medial preoptic nucleus (a sexually dimorphic brain area) also were not male-like in FM males. These data demonstrate a brain-intrinsic, genetically determined component that organizes the sex-typical production of gonadal hormones in adulthood and call for a reevaluation of the mechanisms underlying brain sexual differentiation in other higher-vertebrate species.",
"title": "Male Japanese quails with female brains do not show male sexual behaviors."
},
{
"docid": "5145974",
"text": "STUDY QUESTION In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation? SUMMARY ANSWER Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation. WHAT IS KNOWN ALREADY Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E(2)) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development. STUDY DESIGN, SIZE AND DURATION Prospective preconception cohort study. One hundred and seventy-four women aged 18-45 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis. PARTICIPANTS/MATERIALS, SETTING AND METHODS Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) µg/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear dose-response association between increased urinary BPA concentrations and decreased number of oocytes (overall and mature), decreased number of normally fertilized oocytes and decreased E(2) levels (mean decreases of 40, 253 and 471 pg/ml for urinary BPA quartiles 2, 3 and 4, when compared with the lowest quartile, respectively; P-value for trend = 0.001). The mean number of oocytes and normally fertilized oocytes decreased by 24 and 27%, respectively, for the highest versus the lowest quartile of urinary BPA (trend test P < 0.001 and 0.002, respectively). Women with urinary BPA above the lowest quartile had decreased blastocyst formation (trend test P-value = 0.08). LIMITATIONS AND REASONS FOR CAUTION Potential limitations include exposure misclassification due to the very short half-life of BPA and its high variability over time; uncertainty about the generalizability of the results to the general population of women conceiving naturally and limited sample. WIDER IMPLICATIONS OF THE FINDINGS The results from this extended study, using IVF as a model to study early reproductive health outcomes in humans, indicate a negative dose-response association between urinary BPA concentrations and serum peak E(2) and oocyte yield, confirming our previous findings. In addition, we found significantly decreased metaphase II oocyte count and number of normally fertilizing oocytes and a suggestive association between BPA urinary concentrations and decreased blastocyst formation, thus indicating that BPA may alter reproductive function in susceptible women undergoing IVF. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. None of the authors has actual or potential competing financial interests. DISCLAIMER The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.",
"title": "Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF."
},
{
"docid": "12206390",
"text": "CONTEXT The long-term risk for developing hypertension is best described by the lifetime risk statistic. The lifetime risk for hypertension and trends in this risk over time are unknown. OBJECTIVES To estimate the residual lifetime risk for hypertension in older US adults and to evaluate temporal trends in this risk. DESIGN, SETTING, AND PARTICIPANTS Community-based prospective cohort study of 1298 participants from the Framingham Heart Study who were aged 55 to 65 years and free of hypertension at baseline (1976-1998). MAIN OUTCOME MEASURES Residual lifetime risk (lifetime cumulative incidence not adjusted for competing causes of mortality) for hypertension, defined as blood pressure of 140/90 mm Hg or greater or use of antihypertensive medications. RESULTS The residual lifetime risks for developing hypertension and stage 1 high blood pressure or higher (greater-than-or-equal to 140/90 mm Hg regardless of treatment) were 90% in both 55- and 65-year-old participants. The lifetime probability of receiving antihypertensive medication was 60%. The risk for hypertension remained unchanged for women, but it was approximately 60% higher for men in the contemporary 1976-1998 period compared with an earlier 1952-1975 period. In contrast, the residual lifetime risk for stage 2 high blood pressure or higher (greater-than-or-equal to 160/100 mm Hg regardless of treatment) was considerably lower in both sexes in the recent period (35%-57% in 1952-1975 vs 35%-44% in 1976-1998), likely due to a marked increase in treatment of individuals with substantially elevated blood pressure. CONCLUSION The residual lifetime risk for hypertension for middle-aged and elderly individuals is 90%, indicating a huge public health burden. Although the decline in lifetime risk for stage 2 high blood pressure or higher represents a major achievement, efforts should be directed at the primary prevention of hypertension.",
"title": "Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study."
},
{
"docid": "31851367",
"text": "Estrogens are key regulators of growth, differentiation, and the physiological functions of a wide range of target tissues, including the male and female reproductive tracts, breast, and skeletal, nervous, cardiovascular, digestive and immune systems. The majority of these biological activities of estrogens are mediated through two genetically distinct receptors, ERalpha and ERbeta, which function as hormone-inducible transcription factors. Over the past decade, it has become increasingly clear that the recruitment of coregulatory proteins to ERs is required for ER-mediated transcriptional and biological activities. These \"coactivator\" complexes enable the ERs to respond appropriately: 1) to hormones or pharmacological ligands, 2) interpret extra- and intra-cellular signals, 3) catalyze the process of chromatin condensation and 4) to communicate with the general transcription apparatus at target gene promoters. In addition to activating proteins, the existence of corepressors, proteins that function as negative regulators of ER activity in either physiological or pharmacological contexts, provides an additional level of complexity in ER action. This review also describes current efforts aimed at developing pharmaceutical agents that target ER-cofactor interactions as therapeutics for estrogen-associated pathologies.",
"title": "Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting."
},
{
"docid": "16734530",
"text": "BACKGROUND Breast cancer is the most common malignancy in women. There is increasing evidence suggesting that ORAI1, components of store-operated calcium channel, play a pivotal role in breast cancer progression and metastasis. METHODS A total of 384 female patients with breast cancer were included in this study. We selected five representative tagging ORAI1 SNPs from HapMap database with minimum allele frequency (MAF) >10%. Genotyping was performed using TaqMan allelic discrimination assay. Chi-square (χ²) test was used to analyze statistical differences among control and patient groups in genotype and allelic frequencies. RESULTS Two of the ORAI1 SNPs (rs12320939 and rs12313273) were associated with estrogen receptors positive in breast cancer patients under the recessive model. When the Bonferroni correction was performed, the significance still existed. In addition, rs12320939 also associated with the lymph nodal involvement. CONCLUSION We showed that genetic polymorphisms of ORAI1 associated strongly with lymph nodal involvement and estrogen receptors (ERs) positive breast cancer patients in a Taiwanese population.",
"title": "The Association between Single-Nucleotide Polymorphisms of ORAI1 Gene and Breast Cancer in a Taiwanese Population"
},
{
"docid": "11090688",
"text": "The weight lowering potential of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP-1R on body weight response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has not yet been evaluated. Fifty-seven obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m2) were assigned to liraglutide 1.2 mg QD s.c. for 12 weeks and classified as strong responders regarding weight loss if they lost 5 % or more of their initial body weight. They were genotyped for common GLP-1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of measures of obesity were measured before and at the end of the treatment. Twenty out of 57 subjects were strong responders and lost 7.38 ± 1.74 compared to 2.11 ± 2.17 kg lost in poor responders. Carriers of at least one polymorphic rs10305420 allele had poor treatment response compared to carriers of two wild type alleles (OR = 0.27, 95 % CI = 0.09–0.85, P = 0.025). Carriers of at least one polymorphic rs6923761 allele tended to have stronger treatment response compared to carriers of two wild type alleles (OR = 3.06, 95 % CI = 0.96–9.74, P = 0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT) comparably decreased in both groups when compared to baseline, whereas no within treatment differences were found in androgen profile. Gastrointestinal adverse events were transit and balanced between strong and poor responders. GLP-1R rs10305420 polymorphism explained some of the inter-individual differences in response to liraglutide regarding weight loss in obese PCOS women.",
"title": "Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study"
},
{
"docid": "43226130",
"text": "Multiple sclerosis (MS), a chronic inflammatory demyelina-ting and degenerative disease of the central nervous system, is a frequent cause of neurological disability in young adults. Female predominance has increased over the last decades. Although female gender carries a higher risk of developing relapsing remitting MS, being female and at child-bearing age also appears to provide some protection against cognitive decline and against progressive onset MS, an adverse predictive factor when considering long-term disability in MS. The risk of MS in women has been associated with an earlier age at menarche. In most studies, parity did not impact MS risk. However, the recently published association of higher parity and offspring number with a reduced risk of a first demyelinating event suggests a potential suppressive effect. Pregnancy in MS patients has been associated with a reduced relapse rate and a reduction of neurological symptoms, especially in the third trimester. Despite the increased relapse risk in the postpartum period, there is no indication of an adverse effect of childbirth on the long-term course of MS. Fertility treatment in MS has been associated with an increased relapse risk in the following 3-month period, especially when the procedure did not result in pregnancy and gonadotrophin-releasing hormone agonists were used. Altogether, there is substantial evidence to support a regulatory role of sex steroid hormones in MS. In the absence of correlations with single hormone blood levels, we can only speculate about the underlying mechanisms. In conclusion, the increased MS risk in women and the changes in relapse and progression risk in association with reproductive events suggest significant and complex interactions between immune, neuroendocrine and reproductive systems in MS.",
"title": "Female Gender and Reproductive Factors Affecting Risk, Relapses and Progression in Multiple Sclerosis"
},
{
"docid": "6540064",
"text": "BACKGROUND Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lowering by PCSK9 inhibitors, there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism. In particular, it is not known whether inhibition of PCSK9 has any effects on very low-density lipoprotein or intermediate-density lipoprotein (IDL) metabolism. Inhibition of PCSK9 also results in reductions of plasma lipoprotein (a) levels. The regulation of plasma Lp(a) levels, including the role of LDL receptors in the clearance of Lp(a), is poorly defined, and no mechanistic studies of the Lp(a) lowering by alirocumab in humans have been published to date. METHODS Eighteen (10 F, 8 mol/L) participants completed a placebo-controlled, 2-period study. They received 2 doses of placebo, 2 weeks apart, followed by 5 doses of 150 mg of alirocumab, 2 weeks apart. At the end of each period, fractional clearance rates (FCRs) and production rates (PRs) of apoB and apo(a) were determined. In 10 participants, postprandial triglycerides and apoB48 levels were measured. RESULTS Alirocumab reduced ultracentrifugally isolated LDL-C by 55.1%, LDL-apoB by 56.3%, and plasma Lp(a) by 18.7%. The fall in LDL-apoB was caused by an 80.4% increase in LDL-apoB FCR and a 23.9% reduction in LDL-apoB PR. The latter was due to a 46.1% increase in IDL-apoB FCR coupled with a 27.2% decrease in conversion of IDL to LDL. The FCR of apo(a) tended to increase (24.6%) without any change in apo(a) PR. Alirocumab had no effects on FCRs or PRs of very low-density lipoproteins-apoB and very low-density lipoproteins triglycerides or on postprandial plasma triglycerides or apoB48 concentrations. CONCLUSIONS Alirocumab decreased LDL-C and LDL-apoB by increasing IDL- and LDL-apoB FCRs and decreasing LDL-apoB PR. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition. The increase in apo(a) FCR during alirocumab treatment suggests that increased LDL receptors may also play a role in the reduction of plasma Lp(a). CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01959971.",
"title": "Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans"
},
{
"docid": "34228604",
"text": "Females live longer than males in many species, including humans. We have traced a possible explanation for this phenomenon to the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria from females produce fewer reactive oxygen species than those from males. Administering estrogens has serious drawbacks, however--they are feminizing (and thus cannot be administered to males) and may increase the incidence of serious diseases such as uterine cancer in postmenopausal women. Phytoestrogens, which are present in soy or wine, may have some of the favorable effects of estrogens without their undesirable effects. Study of gender differences in longevity may help us to understand the basic processes of aging and to devise practical strategies to increase the longevity of both females and males.",
"title": "Why females live longer than males: control of longevity by sex hormones."
},
{
"docid": "13956305",
"text": "Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.",
"title": "Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1"
},
{
"docid": "20280410",
"text": "Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07–1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner.",
"title": "A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability"
},
{
"docid": "21232018",
"text": "We investigated the capacity of young ovaries, transplanted into old ovariectomized CBA mice, to improve remaining life expectancy of the hosts. Donor females were sexually mature 2-month-olds; recipients were prepubertally ovariectomized at 3 weeks and received transplants at 5, 8 or 11 months of age. Relative to ovariectomized control females, life expectancy at 11 months was increased by 60% in 11-month recipient females and by 40% relative to intact control females. Only 20% of the 11-month transplant females died in the 300-day period following ovarian transplantation, whereas nearly 65% of the ovariectomized control females died during this same period. The 11-month-old recipient females resumed oestrus and continued to cycle up to several months beyond the age of control female reproductive senescence. Across the three recipient age groups, transplantation of young ovaries increased life expectancy in proportion to the relative youth of the ovary. Our results relate to recent findings on the gonadal input upon aging in Caenorhabditis elegans and may suggest how the mammalian gonad, including that of humans, could regulate aging and determine longevity.",
"title": "Age of ovary determines remaining life expectancy in old ovariectomized mice."
},
{
"docid": "6947286",
"text": "Recent biological studies indicate the importance of anterior-pharynx defective-1 (APH-1) proteins in Alzheimer's disease (AD) pathogenesis. We scanned APH-1 genes for the presence of sequence variations by denaturing high performance liquid chromatography and analyzed their distribution in an Italian sample of 113 AD patients and 132 controls. We found six different polymorphisms: three of them, all in APH-1b, predict an aminoacid substitution (T27I, V199L and F217L); the others are either silent or in non-coding regions. None of them is significantly associated with the disease; data stratification by the apolipoprotein E epsilon4 carrier status show a trend for coexistence of the transversion c+651T>G (F217L) with the epsilon4 allele. Our data suggest that polymorphisms in APH-1a/b coding regions are not linked with higher risk for sporadic AD in our Italian population sample.",
"title": "Association analysis between anterior-pharynx defective-1 genes polymorphisms and Alzheimer's disease."
},
{
"docid": "32534305",
"text": "OBJECTIVE Hyperinsulinemia may promote mammary carcinogenesis. Insulin resistance has been linked to an increased risk of breast cancer and is also characteristic of type 2 diabetes. We prospectively evaluated the association between type 2 diabetes and invasive breast cancer incidence in the Nurses' Health Study. RESEARCH DESIGN AND METHODS A total of 116,488 female nurses who were 30-55 years old and free of cancer in 1976 were followed through 1996 for the occurrence of type 2 diabetes and through 1998 for incident invasive breast cancer, verified by medical records and pathology reports. RESULTS During 2.3 million person-years of follow-up, we identified 6,220 women with type 2 diabetes and 5,189 incident cases of invasive breast cancer. Women with type 2 diabetes had a modestly elevated incidence of breast cancer (hazard ratio [HR] = 1.17; 95% CI 1.01-1.35) compared with women without diabetes, independent of age, obesity, family history of breast cancer, history of benign breast disease, reproductive factors, physical activity, and alcohol consumption. This association was apparent among postmenopausal women (1.16; 0.98-1.62) but not premenopausal women (0.83; 0.48-1.42). The association was predominant among women with estrogen receptor-positive breast cancer (1.22; 1.01-1.47). CONCLUSIONS Women with type 2 diabetes may have a slightly increased risk of breast cancer.",
"title": "Type 2 diabetes and subsequent incidence of breast cancer in the Nurses' Health Study."
},
{
"docid": "27408104",
"text": "Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico's population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW) Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA) software, based on the published data of the MTHFR C677T (rs1801133), ABCA1 Arg230Cys (rs9282541), APOE T388C (rs429358)/C526T (rs7412), LCT C-13910T (rs4988235) polymorphisms and AMY1 copy number variation (CNV). Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR) assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that may lead to a healthier dietary pattern.",
"title": "Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms"
},
{
"docid": "13069283",
"text": "BACKGROUND Estrogen receptor-positive breast cancer tumors depend on estrogen signaling for their growth and replication and can be treated by anti-estrogen therapy with tamoxifen. Polymorphisms of the CYP2D6 and CYP2C19 genes are associated with an impaired response to tamoxifen. The study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy. METHODS We studied 90 women with estrogen receptor-positive breast cancer, using the AmpliChip CYP450 test to determine CYP2D6 and CYP2C19 gene variants. Plasma levels of tamoxifen and its metabolites were quantified by high-performance liquid chromatography. RESULTS The CYP2D6 phenotype was extensive metabolizer in 80%, intermediate metabolizer in 12.2%, ultra-rapid metabolizer in 2.2%, and poor metabolizer in 5.6% of patients, and the allele frequency was 35.0% for allele (*)1, 21.0% for *2, and 18.9% for *4. All poor metabolizers in this series were *4/*4, and their endoxifen and 4-hydroxy tamoxifen levels were 25% lower than those of extensive metabolizers. CYP2C19*2 allele, which has been related to breast cancer outcomes, was detected in 15.6% of the studied alleles. CONCLUSION CYP2D6*4/*4 genotype was inversely associated with 4-hydroxy tamoxifen and endoxifen levels. According to these results, CYP2D6 and CYP2C19 genotyping appears advisable before the prescription of tamoxifen therapy.",
"title": "Influence of CYP2D6 Polymorphisms on Serum Levels of Tamoxifen Metabolites in Spanish Women with Breast Cancer"
},
{
"docid": "5864770",
"text": "Epidemiologic studies suggest that ovarian hormones contribute to the development of breast cancer at all stages. Early menopause and premenopausal obesity reduces the risk while postmenopausal obesity and menopausal estrogen replacement therapy increases the risk. Combined oral contraceptives and Depo-Provera do not reduce the risk. It appears that estrogens and progestogens act through and with proto-oncogenes and growth factors to affect breast cell proliferation and breast cancer etiology. Animal studies suggest that estrogen causes interlobular ductal cell division and progesterone causes increased terminal duct lobular unit cell division in the luteal phase. Most breast carcinomas originate from terminal duct lobular unit cells. During pregnancy, these cells fully multiply. Their reproduction is also increased during the luteal phase. Yet, there is considerable interpersonal variation. No studies examining breast cell division have compared cell division rates with serum hormone concentrations, however. The peak of mitosis occurs about 3 days before breast cell death in the late luteal and very early follicular phases. Other research suggests that breast stem cell proliferation is linked to breast cancer development. Endocrine therapy reduces mitotic activity, indicating the estrogen and progesterone receptor content of breast cancers. Hormone-dependent breast cancer cell lines are all estrogen-dependent. Progesterone can block the estrogen-dependent cell lines which act like endometrial cells. The results of the various breast cell proliferation studies in relation to breast cancer are unclear and research identifying a molecular explanation would help in understanding the different findings.",
"title": "Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk."
},
{
"docid": "36178047",
"text": "The same 15 male Wistar rats at the ages of 2.5, 6, 10, 14, 18, and 22 months were successively randomly mated with 2.5-month-old females. In a separate experiment, 15 male Wistar rats at the age of 2.5 months and 15 at the age of 23 months were simultaneously randomly mated with 2.5-month-old females. Offspring were evaluated in regard to the mean number per litter, sex ratio, frequency of gross external malformations, growth pattern, and mortality in the first 13 weeks of life and reproductive capacity at 13 weeks of age. They were also evaluated for spontaneous activity and emotionality with an open field test and for learning capacity with an avoidance conditioning test, both carried out between 10 and 13 weeks of age. Only learning capacity of the offspring, expressed in percentage of success for male or female, decreased consistently and significantly as the father's age increased. But females did not seem to be affected in the same way as males. The genetic implications are briefly discussed.",
"title": "Decrease of learning capacity in offspring with increasing paternal age in the rat."
},
{
"docid": "7209559",
"text": "CONTEXT The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth. Changes in physical activity or diet may therefore influence risk of forearm fracture. OBJECTIVE To determine whether there has been a change in the incidence of distal forearm fractures in children in recent years. DESIGN, SETTING, AND PATIENTS Population-based study among Rochester, Minn, residents younger than 35 years with distal forearm fractures in 1969-1971, 1979-1981, 1989-1991, and 1999-2001. MAIN OUTCOME MEASURE Estimated incidence of distal forearm fractures in 4 time periods. RESULTS Comparably age- and sex-adjusted annual incidence rates per 100 000 increased from 263.3 (95% confidence interval [CI], 231.1-295.4) in 1969-1971 to 322.3 (95% CI, 285.3-359.4) in 1979-1981 and to 399.8 (95% CI, 361.0-438.6) in 1989-1991 before leveling off at 372.9 (95% CI, 339.1-406.7) in 1999-2001. Age-adjusted incidence rates per 100 000 were 32% greater among male residents in 1999-2001 compared with 1969-1971 (409.4 [95% CI, 359.9-459.0] vs 309.4 [95% CI, 259.3-359.5]; P =.01) and 56% greater among female residents in the same time periods (334.3 [95% CI, 288.6-380.1] vs 214.6 [95% CI, 174.9-254.4]; P<.001). The peak incidence and greatest increase occurred between ages 11 and 14 years in boys and 8 and 11 years in girls. CONCLUSIONS There has been a statistically significant increase in the incidence of distal forearm fractures in children and adolescents, but whether this is due to changing patterns of physical activity, decreased bone acquisition due to poor calcium intake, or both is unclear at present. Given the large number of childhood fractures, however, studies are needed to define the cause(s) of this increase.",
"title": "Incidence of childhood distal forearm fractures over 30 years: a population-based study."
},
{
"docid": "1428840",
"text": "BACKGROUND It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. PURPOSE We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. METHODS The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. RESULTS High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. CONCLUSION High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. IMPLICATIONS Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.",
"title": "Case-control study of endogenous steroid hormones and endometrial cancer."
},
{
"docid": "3285322",
"text": "PURPOSE Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations. PATIENTS AND METHODS Tumor pathologic features and clinical characteristics were examined in 491 women with breast cancer who underwent genetic testing for BRCA mutations between 1997 and 2006. A retrospective review of medical records was conducted to determine clinical characteristics including ethnicity, age and clinical stage at diagnosis, age at parity, number of full-term pregnancies, use of oral contraceptives and hormone replacement therapy, and BRCA mutation status. Tumor pathology was reviewed to determine histologic type, tumor grade, and estrogen receptor, progesterone receptor, and HER-2/neu status. RESULTS Of the 491 patients with identified breast cancers, 391 patients were BRCA negative, and 86 patients were BRCA positive. Triple-negative breast cancer (ie, those with negative estrogen receptor, progesterone receptor, and HER-2/neu status) was diagnosed in 57.1% of the BRCA1-positive patients, 23.3% of the BRCA2-positive patients, and 13.8% of the BRCA-negative patients. BRCA1 mutation carriers had higher nuclear grade tumors than the other two groups (P < .001). Of the triple-negative cancer patients, BRCA2 mutation carriers were older when diagnosed than BRCA1 mutation carriers and noncarriers (P < .01). CONCLUSION These results suggest that tumors associated with BRCA1 mutations may be divided into two distinct groups, triple-negative and non-triple-negative groups. Future studies should seek to determine whether patients with BRCA1 mutations and triple-negative breast cancer respond to treatment better than BRCA-negative patients with similar tumor pathology.",
"title": "Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer."
}
] |
313
|
De novo assembly of sequence data has shorter contigs than unassembled sequence data.
|
[
{
"docid": "6173523",
"text": "IMPORTANCE Identification of the bacterium responsible for an outbreak can aid in disease management. However, traditional culture-based diagnosis can be difficult, particularly if no specific diagnostic test is available for an outbreak strain. OBJECTIVE To explore the potential of metagenomics, which is the direct sequencing of DNA extracted from microbiologically complex samples, as an open-ended clinical discovery platform capable of identifying and characterizing bacterial strains from an outbreak without laboratory culture. DESIGN, SETTING, AND PATIENTS In a retrospective investigation, 45 samples were selected from fecal specimens obtained from patients with diarrhea during the 2011 outbreak of Shiga-toxigenic Escherichia coli (STEC) O104:H4 in Germany. Samples were subjected to high-throughput sequencing (August-September 2012), followed by a 3-phase analysis (November 2012-February 2013). In phase 1, a de novo assembly approach was developed to obtain a draft genome of the outbreak strain. In phase 2, the depth of coverage of the outbreak strain genome was determined in each sample. In phase 3, sequences from each sample were compared with sequences from known bacteria to identify pathogens other than the outbreak strain. MAIN OUTCOMES AND MEASURES The recovery of genome sequence data for the purposes of identification and characterization of the outbreak strain and other pathogens from fecal samples. RESULTS During phase 1, a draft genome of the STEC outbreak strain was obtained. During phase 2, the outbreak strain genome was recovered from 10 samples at greater than 10-fold coverage and from 26 samples at greater than 1-fold coverage. Sequences from the Shiga-toxin genes were detected in 27 of 40 STEC-positive samples (67%). In phase 3, sequences from Clostridium difficile, Campylobacter jejuni, Campylobacter concisus, and Salmonella enterica were recovered. CONCLUSIONS AND RELEVANCE These results suggest the potential of metagenomics as a culture-independent approach for the identification of bacterial pathogens during an outbreak of diarrheal disease. Challenges include improving diagnostic sensitivity, speeding up and simplifying workflows, and reducing costs.",
"title": "A culture-independent sequence-based metagenomics approach to the investigation of an outbreak of Shiga-toxigenic Escherichia coli O104:H4."
}
] |
[
{
"docid": "14464451",
"text": "Next-generation-sequencing (NGS) has revolutionized the field of genome assembly because of its much higher data throughput and much lower cost compared with traditional Sanger sequencing. However, NGS poses new computational challenges to de novo genome assembly. Among the challenges, GC bias in NGS data is known to aggravate genome assembly. However, it is not clear to what extent GC bias affects genome assembly in general. In this work, we conduct a systematic analysis on the effects of GC bias on genome assembly. Our analyses reveal that GC bias only lowers assembly completeness when the degree of GC bias is above a threshold. At a strong GC bias, the assembly fragmentation due to GC bias can be explained by the low coverage of reads in the GC-poor or GC-rich regions of a genome. This effect is observed for all the assemblers under study. Increasing the total amount of NGS data thus rescues the assembly fragmentation because of GC bias. However, the amount of data needed for a full rescue depends on the distribution of GC contents. Both low and high coverage depths due to GC bias lower the accuracy of assembly. These pieces of information provide guidance toward a better de novo genome assembly in the presence of GC bias.",
"title": "Effects of GC Bias in Next-Generation-Sequencing Data on De Novo Genome Assembly"
},
{
"docid": "14185503",
"text": "BACKGROUND Genlisea aurea (Lentibulariaceae) is a carnivorous plant with unusually small genome size - 63.6 Mb - one of the smallest known among higher plants. Data on the genome sizes and the phylogeny of Genlisea suggest that this is a derived state within the genus. Thus, G. aurea is an excellent model organism for studying evolutionary mechanisms of genome contraction. RESULTS Here we report sequencing and de novo draft assembly of G. aurea genome. The assembly consists of 10,687 contigs of the total length of 43.4 Mb and includes 17,755 complete and partial protein-coding genes. Its comparison with the genome of Mimulus guttatus, another representative of higher core Lamiales clade, reveals striking differences in gene content and length of non-coding regions. CONCLUSIONS Genome contraction was a complex process, which involved gene loss and reduction of lengths of introns and intergenic regions, but not intron loss. The gene loss is more frequent for the genes that belong to multigenic families indicating that genetic redundancy is an important prerequisite for genome size reduction.",
"title": "The miniature genome of a carnivorous plant Genlisea aurea contains a low number of genes and short non-coding sequences"
},
{
"docid": "13123189",
"text": "BACKGROUND RNA-Seq is revolutionizing the way transcript abundances are measured. A key challenge in transcript quantification from RNA-Seq data is the handling of reads that map to multiple genes or isoforms. This issue is particularly important for quantification with de novo transcriptome assemblies in the absence of sequenced genomes, as it is difficult to determine which transcripts are isoforms of the same gene. A second significant issue is the design of RNA-Seq experiments, in terms of the number of reads, read length, and whether reads come from one or both ends of cDNA fragments. RESULTS We present RSEM, an user-friendly software package for quantifying gene and isoform abundances from single-end or paired-end RNA-Seq data. RSEM outputs abundance estimates, 95% credibility intervals, and visualization files and can also simulate RNA-Seq data. In contrast to other existing tools, the software does not require a reference genome. Thus, in combination with a de novo transcriptome assembler, RSEM enables accurate transcript quantification for species without sequenced genomes. On simulated and real data sets, RSEM has superior or comparable performance to quantification methods that rely on a reference genome. Taking advantage of RSEM's ability to effectively use ambiguously-mapping reads, we show that accurate gene-level abundance estimates are best obtained with large numbers of short single-end reads. On the other hand, estimates of the relative frequencies of isoforms within single genes may be improved through the use of paired-end reads, depending on the number of possible splice forms for each gene. CONCLUSIONS RSEM is an accurate and user-friendly software tool for quantifying transcript abundances from RNA-Seq data. As it does not rely on the existence of a reference genome, it is particularly useful for quantification with de novo transcriptome assemblies. In addition, RSEM has enabled valuable guidance for cost-efficient design of quantification experiments with RNA-Seq, which is currently relatively expensive.",
"title": "RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome"
},
{
"docid": "32770503",
"text": "Massively parallel sequencing of cDNA has enabled deep and efficient probing of transcriptomes. Current approaches for transcript reconstruction from such data often rely on aligning reads to a reference genome, and are thus unsuitable for samples with a partial or missing reference genome. Here we present the Trinity method for de novo assembly of full-length transcripts and evaluate it on samples from fission yeast, mouse and whitefly, whose reference genome is not yet available. By efficiently constructing and analyzing sets of de Bruijn graphs, Trinity fully reconstructs a large fraction of transcripts, including alternatively spliced isoforms and transcripts from recently duplicated genes. Compared with other de novo transcriptome assemblers, Trinity recovers more full-length transcripts across a broad range of expression levels, with a sensitivity similar to methods that rely on genome alignments. Our approach provides a unified solution for transcriptome reconstruction in any sample, especially in the absence of a reference genome.",
"title": "Full-length transcriptome assembly from RNA-Seq data without a reference genome."
},
{
"docid": "25041967",
"text": "Human artificial chromosomes have been used to model requirements for human chromosome segregation and to explore the nature of sequences competent for centromere function. Normal human centromeres require specialized chromatin that consists of alpha satellite DNA complexed with epigenetically modified histones and centromere-specific proteins. While several types of alpha satellite DNA have been used to assemble de novo centromeres in artificial chromosome assays, the extent to which they fully recapitulate normal centromere function has not been explored. Here, we have used two kinds of alpha satellite DNA, DXZ1 (from the X chromosome) and D17Z1 (from chromosome 17), to generate human artificial chromosomes. Although artificial chromosomes are mitotically stable over many months in culture, when we examined their segregation in individual cell divisions using an anaphase assay, artificial chromosomes exhibited more segregation errors than natural human chromosomes (P < 0.001). Naturally occurring, but abnormal small ring chromosomes derived from chromosome 17 and the X chromosome also missegregate more than normal chromosomes, implicating overall chromosome size and/or structure in the fidelity of chromosome segregation. As different artificial chromosomes missegregate over a fivefold range, the data suggest that variable centromeric DNA content and/or epigenetic assembly can influence the mitotic behavior of artificial chromosomes.",
"title": "Human artificial chromosomes with alpha satellite-based de novo centromeres show increased frequency of nondisjunction and anaphase lag."
},
{
"docid": "17447653",
"text": "BACKGROUND Sequence similarity searching is a very important bioinformatics task. While Basic Local Alignment Search Tool (BLAST) outperforms exact methods through its use of heuristics, the speed of the current BLAST software is suboptimal for very long queries or database sequences. There are also some shortcomings in the user-interface of the current command-line applications. RESULTS We describe features and improvements of rewritten BLAST software and introduce new command-line applications. Long query sequences are broken into chunks for processing, in some cases leading to dramatically shorter run times. For long database sequences, it is possible to retrieve only the relevant parts of the sequence, reducing CPU time and memory usage for searches of short queries against databases of contigs or chromosomes. The program can now retrieve masking information for database sequences from the BLAST databases. A new modular software library can now access subject sequence data from arbitrary data sources. We introduce several new features, including strategy files that allow a user to save and reuse their favorite set of options. The strategy files can be uploaded to and downloaded from the NCBI BLAST web site. CONCLUSION The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences. We have also improved the user interface of the command-line applications.",
"title": "BLAST+: architecture and applications"
},
{
"docid": "15478227",
"text": "The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.",
"title": "Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution"
},
{
"docid": "16626846",
"text": "Crude oils can be major contaminants of the marine ecosystem and microorganisms play a significant role in the degradation of its main constituents. To increase our understanding of the microbial hydrocarbon degradation process in the marine ecosystem, we collected crude oil from an active seep area located in the Santa Barbara Channel (SBC) and generated a total of about 52 Gb of raw metagenomic sequence data. The assembled data comprised ~500 Mb, representing ~1.1 million genes derived primarily from chemolithoautotrophic bacteria. Members of Oceanospirillales, a bacterial order belonging to the Deltaproteobacteria, recruited less than 2% of the assembled genes within the SBC metagenome. In contrast, the microbial community associated with the oil plume that developed in the aftermath of the Deepwater Horizon (DWH) blowout in 2010, was dominated by Oceanospirillales, which comprised more than 60% of the metagenomic data generated from the DWH oil plume. This suggests that Oceanospirillales might play a less significant role in the microbially mediated hydrocarbon conversion within the SBC seep oil compared to the DWH plume oil. We hypothesize that this difference results from the SBC oil seep being mostly anaerobic, while the DWH oil plume is aerobic. Within the Archaea, the phylum Euryarchaeota, recruited more than 95% of the assembled archaeal sequences from the SBC oil seep metagenome, with more than 50% of the sequences assigned to members of the orders Methanomicrobiales and Methanosarcinales. These orders contain organisms capable of anaerobic methanogenesis and methane oxidation (AOM) and we hypothesize that these orders - and their metabolic capabilities - may be fundamental to the ecology of the SBC oil seep.",
"title": "Metagenomic analysis of microbial consortium from natural crude oil that seeps into the marine ecosystem offshore Southern California"
},
{
"docid": "11244195",
"text": "MOTIVATION Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. RESULTS To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. AVAILABILITY AND IMPLEMENTATION STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.",
"title": "STAR: ultrafast universal RNA-seq aligner."
},
{
"docid": "15960670",
"text": "The centromere is a chromatin region that serves as the spindle attachment point and directs accurate inheritance of eukaryotic chromosomes during cell divisions. However, the mechanism by which the centromere assembles and stabilizes at a specific genomic region is not clear. The de novo formation of a human/mammalian artificial chromosome (HAC/MAC) with a functional centromere assembly requires the presence of alpha-satellite DNA containing binding motifs for the centromeric CENP-B protein. We demonstrate here that de novo centromere assembly on HAC/MAC is dependent on CENP-B. In contrast, centromere formation is suppressed in cells expressing CENP-B when alpha-satellite DNA was integrated into a chromosomal site. Remarkably, on those integration sites CENP-B enhances histone H3-K9 trimethylation and DNA methylation, thereby stimulating heterochromatin formation. Thus, we propose that CENP-B plays a dual role in centromere formation, ensuring de novo formation on DNA lacking a functional centromere but preventing the formation of excess centromeres on chromosomes.",
"title": "CENP-B Controls Centromere Formation Depending on the Chromatin Context"
},
{
"docid": "14275671",
"text": "The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. It has long been suggested that the resulting correlations among amino acid compositions at different sequence positions can be exploited to infer spatial contacts within the tertiary protein structure. Crucial to this inference is the ability to disentangle direct and indirect correlations, as accomplished by the recently introduced Direct Coupling Analysis (DCA) (Weigt et al. (2009) Proc Natl Acad Sci 106:67). Here we develop a computationally efficient implementation of DCA, which allows us to evaluate the accuracy of contact prediction by DCA for a large number of protein domains, based purely on sequence information. DCA is shown to yield a large number of correctly predicted contacts, recapitulating the global structure of the contact map for the majority of the protein domains examined. Furthermore, our analysis captures clear signals beyond intra- domain residue contacts, arising, e.g., from alternative protein conformations, ligand- mediated residue couplings, and inter-domain interactions in protein oligomers. Our findings suggest that contacts predicted by DCA can be used as a reliable guide to facilitate computational predictions of alternative protein conformations, protein complex formation, and even the de novo prediction of protein domain structures, provided the existence of a large number of homologous sequences which are being rapidly made available due to advances in genome sequencing.",
"title": "Direct-coupling analysis of residue co-evolution captures native contacts across many protein families"
},
{
"docid": "20045514",
"text": "Although important for gene regulation, most studies of genome organization use either fluorescence in situ hybridization (FISH) or chromosome conformation capture (3C) methods. FISH directly visualizes the spatial relationship of sequences but is usually applied to a few loci at a time. The frequency at which sequences are ligated together by formaldehyde cross-linking can be measured genome-wide by 3C methods, with higher frequencies thought to reflect shorter distances. FISH and 3C should therefore give the same views of genome organization, but this has not been tested extensively. We investigated the murine HoxD locus with 3C carbon copy (5C) and FISH in different developmental and activity states and in the presence or absence of epigenetic regulators. We identified situations in which the two data sets are concordant but found other conditions under which chromatin topographies extrapolated from 5C or FISH data are not compatible. We suggest that products captured by 3C do not always reflect spatial proximity, with ligation occurring between sequences located hundreds of nanometers apart, influenced by nuclear environment and chromatin composition. We conclude that results obtained at high resolution with either 3C methods or FISH alone must be interpreted with caution and that views about genome organization should be validated by independent methods.",
"title": "Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization."
},
{
"docid": "2576811",
"text": "Epithelial integrity is vitally important, and its deregulation causes early stage cancer. De novo formation of an adherens junction (AJ) between single epithelial cells requires coordinated, spatial actin dynamics, but the mechanisms steering nascent actin polymerization for cell-cell adhesion initiation are not well understood. Here we investigated real-time actin assembly during daughter cell-cell adhesion formation in human breast epithelial cells in 3D environments. We identify formin-like 2 (FMNL2) as being specifically required for actin assembly and turnover at newly formed cell-cell contacts as well as for human epithelial lumen formation. FMNL2 associates with components of the AJ complex involving Rac1 activity and the FMNL2 C terminus. Optogenetic control of Rac1 in living cells rapidly drove FMNL2 to epithelial cell-cell contact zones. Furthermore, Rac1-induced actin assembly and subsequent AJ formation critically depends on FMNL2. These data uncover FMNL2 as a driver for human epithelial AJ formation downstream of Rac1.",
"title": "Junctional actin assembly is mediated by Formin-like 2 downstream of Rac1"
},
{
"docid": "152245",
"text": "The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal termination codon has been replaced by a sense codon in the alphavirus genome. Evolutionary pressures appear to have maintained genomic sequences encoding both a stop codon (opal) and an open reading frame (arginine) as a general feature of the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts may determine predominance of a particular codon at this locus in the viral quasispecies. However, no systematic study has previously tested this hypothesis in whole animals. We report here the results of the first study to investigate in a natural mosquito host the functional significance of the opal stop codon in an alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4 nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a codon for the amino acid arginine at the corresponding position (39.8%). Although the frequency with which the opal virus disseminated from the mosquito midgut did not differ significantly from that of the arginine virus on days 8 and 10, dissemination did began earlier in mosquitoes infected with the opal virus. Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in Anopheles gambiae, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal. These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken together, these results suggest that the primary fitness advantage provided to ONNV by the presence of an opal codon between nsP3 and nsP4 is related to mosquito infectivity.",
"title": "Effects of an opal termination codon preceding the nsP4 gene sequence in the O'Nyong-Nyong virus genome on Anopheles gambiae infectivity."
},
{
"docid": "31634628",
"text": "Cell-free tumor DNA (ctDNA) has the potential to enable non-invasive diagnostic tests for personalized medicine in providing similar molecular information as that derived from invasive tumor biopsies. The histology-independent phase II SHIVA trial matches patients with targeted therapeutics based on previous screening of multiple somatic mutations using metastatic biopsies. To evaluate the utility of ctDNA in this trial, as an ancillary study we performed de novo detection of somatic mutations using plasma DNA compared to metastasis biopsies in 34 patients covering 18 different tumor types, scanning 46 genes and more than 6800 COSMIC mutations with a multiplexed next-generation sequencing panel. In 27 patients, 28 of 29 mutations identified in metastasis biopsies (97%) were detected in matched ctDNA. Among these 27 patients, one additional mutation was found in ctDNA only. In the seven other patients, mutation detection from metastasis biopsy failed due to inadequate biopsy material, but was successful in all plasma DNA samples providing three more potential actionable mutations. These results suggest that ctDNA analysis is a potential alternative and/or replacement to analyses using costly, harmful and lengthy tissue biopsies of metastasis, irrespective of cancer type and metastatic site, for multiplexed mutation detection in selecting personalized therapies based on the patient's tumor genetic content.",
"title": "Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types."
},
{
"docid": "19138874",
"text": "The biogenesis of the many functional compartments contained in the mammalian cell nucleus is poorly understood. More specifically, little is known regarding the initial nucleation step required for nuclear body formation. Here we show that RNA can function as a structural element and a nucleator of nuclear bodies. We find that several types of coding and noncoding RNAs are sufficient to de novo assemble, and are physiologically enriched in, histone locus bodies (with associated Cajal bodies), nuclear speckles, paraspeckles and nuclear stress bodies. Formation of nuclear bodies occurs through recruitment and accumulation of proteins resident in the nuclear bodies by nucleating RNA. These results demonstrate that transcription is a driving force in nuclear body formation and RNA transcripts can function as a scaffold in the formation of major nuclear bodies. Together, these data suggest that RNA-primed biogenesis of nuclear bodies is a general principle of nuclear organization.",
"title": "Nucleation of nuclear bodies by RNA"
},
{
"docid": "22186938",
"text": "Human artificial chromosomes (HACs) are autonomous molecules that can function and segregate as normal chromosomes in human cells. De novo HACs have successfully been used as gene expression vectors to complement genetic deficiencies in human cultured cells. HACs now offer the possibility of studying the regulation and expression of large genes in a variety of cell types from different tissues and correcting gene deficiencies caused by human inherited diseases. Complementary gene expression studies in mice, especially in mouse models of human genetic diseases, are also important in determining if large human transgenes can be expressed appropriately from artificial chromosomes. Toward this aim we are establishing artificial chromosomes in murine cells as novel gene expression vectors. Initially we transferred HAC vectors into murine cells, but were unable to generate de novo HACs at a reasonable frequency. We then transferred HACs previously established in human HT1080 cells to three different murine cell types by microcell fusion, followed by positive selection. We observed that the HACs in murine cells bound centromere protein C (CENP-C), a marker of active centromeres, and were detected under selection but rapidly lost when selection was removed. These results suggest that the HACs maintain at least a partially functional centromere complex in murine cells, but other factors are required for stability and segregation. Artificial chromosomes containing mouse centromeric sequences may be required for better stability and maintenance in murine cells.",
"title": "Human artificial chromosomes containing chromosome 17 alphoid DNA maintain an active centromere in murine cells but are not stable."
},
{
"docid": "18361917",
"text": "PURPOSE The adult newt can regenerate lens from pigmented epithelial cells (PECs) of the dorsal iris via dedifferentiation. The purpose of this research is to obtain sequence resources for a newt lens regeneration study and to obtain insights of dedifferentiation at the molecular level. METHODS mRNA was purified from iris during dedifferentiation and its cDNA library was constructed. From the cDNA library 10,449 clones were sequenced and analyzed. RESULTS From 10,449 reads, 780 contigs and 1,666 singlets were annotated. The presence of several cancer- and apoptosis-related genes during newt dedifferentiation was revealed. Moreover, several candidate genes, which might participate in reprogramming during dedifferentiation, were also found. CONCLUSIONS The expression of cancer- and apoptosis-related genes could be hallmarks during dedifferentiation. The expression sequence tag (EST) resource is useful for the future study of newt dedifferentiation, and the sequence information is available in GenBank (accession numbers; FS290155-FS300559).",
"title": "Expression profiles during dedifferentiation in newt lens regeneration revealed by expressed sequence tags"
},
{
"docid": "84784389",
"text": "When small RNA is sequenced on current sequencing machines, the resulting reads are usually longer than the RNA and therefore contain parts of the 3' adapter. That adapter must be found and removed error-tolerantly from each read before read mapping. Previous solutions are either hard to use or do not offer required features, in particular support for color space data. As an easy to use alternative, we developed the command-line tool cutadapt, which supports 454, Illumina and SOLiD (color space) data, offers two adapter trimming algorithms, and has other useful features. Cutadapt, including its MIT-licensed source code, is available for download at http://code.google.com/p/cutadapt/",
"title": "Cutadapt removes adapter sequences from high-throughput sequencing reads"
},
{
"docid": "15966318",
"text": "We have developed three computer programs for comparisons of protein and DNA sequences. They can be used to search sequence data bases, evaluate similarity scores, and identify periodic structures based on local sequence similarity. The FASTA program is a more sensitive derivative of the FASTP program, which can be used to search protein or DNA sequence data bases and can compare a protein sequence to a DNA sequence data base by translating the DNA data base as it is searched. FASTA includes an additional step in the calculation of the initial pairwise similarity score that allows multiple regions of similarity to be joined to increase the score of related sequences. The RDF2 program can be used to evaluate the significance of similarity scores using a shuffling method that preserves local sequence composition. The LFASTA program can display all the regions of local similarity between two sequences with scores greater than a threshold, using the same scoring parameters and a similar alignment algorithm; these local similarities can be displayed as a \"graphic matrix\" plot or as individual alignments. In addition, these programs have been generalized to allow comparison of DNA or protein sequences based on a variety of alternative scoring matrices.",
"title": "Improved tools for biological sequence comparison."
},
{
"docid": "140874",
"text": "It is thought that the H19 imprinting control region (ICR) directs the silencing of the maternally inherited Igf2 allele through a CTCF-dependent chromatin insulator. The ICR has been shown to interact physically with a silencer region in Igf2, differentially methylated region (DMR)1, but the role of CTCF in this chromatin loop and whether it restricts the physical access of distal enhancers to Igf2 is not known. We performed systematic chromosome conformation capture analyses in the Igf2/H19 region over >160 kb, identifying sequences that interact physically with the distal enhancers and the ICR. We found that, on the paternal chromosome, enhancers interact with the Igf2 promoters but that, on the maternal allele, this is prevented by CTCF binding within the H19 ICR. CTCF binding in the maternal ICR regulates its interaction with matrix attachment region (MAR)3 and DMR1 at Igf2, thus forming a tight loop around the maternal Igf2 locus, which may contribute to its silencing. Mutation of CTCF binding sites in the H19 ICR leads to loss of CTCF binding and de novo methylation of a CTCF target site within Igf2 DMR1, showing that CTCF can coordinate regional epigenetic marks. This systematic chromosome conformation capture analysis of an imprinting cluster reveals that CTCF has a critical role in the epigenetic regulation of higher-order chromatin structure and gene silencing over considerable distances in the genome.",
"title": "CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2."
},
{
"docid": "33920995",
"text": "No direct evidence has been reported whether the spatial organization of ICAM-1 on the cell surface is linked to its physiological function in terms of leukocyte adhesion and transendothelial migration (TEM). Here we observed that ICAM-1 by itself directly regulates the de novo elongation of microvilli and is thereby clustered on the microvilli. However, truncation of the intracellular domain resulted in uniform cell surface distribution of ICAM-1. Mutation analysis revealed that the C-terminal 21 amino acids are dispensable, whereas a segment of 5 amino acids ((507)RKIKK(511)) in the NH-terminal third of intracellular domain, is required for the proper localization and dynamic distribution of ICAM-1 and the association of ICAM-1 with F-actin, ezrin, and moesin. Importantly, deletion of the (507)RKIKK(511) significantly delayed the LFA-1-dependent membrane projection and decreased leukocyte adhesion and subsequent TEM. Endothelial cells treated with cell-permeant penetratin-ICAM-1 peptides comprising ICAM-1 RKIKK sequences inhibited leukocyte TEM. Collectively, these findings demonstrate that (507)RKIKK(511) is an essential motif for the microvillus ICAM-1 presentation and further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.",
"title": "RKIKK motif in the intracellular domain is critical for spatial and dynamic organization of ICAM-1: functional implication for the leukocyte adhesion and transmigration."
},
{
"docid": "1695604",
"text": "All eukaryotes have three nuclear DNA-dependent RNA polymerases, namely, Pol I, II, and III. Interestingly, plants have catalytic subunits for a fourth nuclear polymerase, Pol IV. Genetic and biochemical evidence indicates that Pol IV does not functionally overlap with Pol I, II, or III and is nonessential for viability. However, disruption of the Pol IV catalytic subunit genes NRPD1 or NRPD2 inhibits heterochromatin association into chromocenters, coincident with losses in cytosine methylation at pericentromeric 5S gene clusters and AtSN1 retroelements. Loss of CG, CNG, and CNN methylation in Pol IV mutants implicates a partnership between Pol IV and the methyltransferase responsible for RNA-directed de novo methylation. Consistent with this hypothesis, 5S gene and AtSN1 siRNAs are essentially eliminated in Pol IV mutants. The data suggest that Pol IV helps produce siRNAs that target de novo cytosine methylation events required for facultative heterochromatin formation and higher-order heterochromatin associations.",
"title": "Plant Nuclear RNA Polymerase IV Mediates siRNA and DNA Methylation-Dependent Heterochromatin Formation"
},
{
"docid": "143251",
"text": "Telomerase-negative tumor cells use an alternative lengthening of telomeres (ALT) pathway that involves DNA recombination and repair to maintain their proliferative potential. The cytological hallmark of this process is the accumulation of promyelocytic leukemia (PML) nuclear protein at telomeric DNA to form ALT-associated PML bodies (APBs). Here, the de novo formation of a telomeric PML nuclear subcompartment was investigated by recruiting APB protein components. We show that functionally distinct proteins were able to initiate the formation of bona fide APBs with high efficiency in a self-organizing and self-propagating manner. These included: (1) PML and Sp100 as the constituting components of PML nuclear bodies, (2) telomere repeat binding factors 1 and 2 (TRF1 and TRF2, respectively), (3) the DNA repair protein NBS1 and (4) the SUMO E3 ligase MMS21, as well as the isolated SUMO1 domain, through an interacting domain of another protein factor. By contrast, the repair factors Rad9, Rad17 and Rad51 were less efficient in APB nucleation but were recruited to preassembled APBs. The artificially created APBs induced telomeric extension through a DNA repair mechanism, as inferred from their colocalization with sites of non-replicative DNA synthesis and histone H2A.X phosphorylation, and an increase of the telomere repeat length. These activities were absent after recruitment of the APB factors to a pericentric locus and establish APBs as functional intermediates of the ALT pathway.",
"title": "De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation."
},
{
"docid": "21387297",
"text": "Cardiovascular disease is a leading cause of death worldwide. The limited capability of heart tissue to regenerate has prompted methodological developments for creating de novo cardiomyocytes, both in vitro and in vivo. Beyond uses in cell replacement therapy, patient-specific cardiomyocytes may find applications in drug testing, drug discovery, and disease modeling. Recently, approaches for generating cardiomyocytes have expanded to encompass three major sources of starting cells: human pluripotent stem cells (hPSCs), adult heart-derived cardiac progenitor cells (CPCs), and reprogrammed fibroblasts. We discuss state-of-the-art methods for generating de novo cardiomyocytes from hPSCs and reprogrammed fibroblasts, highlighting potential applications and future challenges.",
"title": "Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming."
},
{
"docid": "8989616",
"text": "The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.",
"title": "Genome Sequencing and Analysis of the Tasmanian Devil and Its Transmissible Cancer"
},
{
"docid": "4854076",
"text": "The rising incidence of obesity and associated metabolic diseases has increased the urgency in understanding all aspects of adipose tissue biology. This includes the function of adipocytes, how adipose tissue expands in obesity, and how expanded adipose tissues in adults can impact physiology. Here, we highlight the growing appreciation for the importance of de novo adipocyte differentiation to adipose tissue expansion in adult humans and animals. We detail recent efforts to identify adipose precursor populations that contribute to the physiological postnatal recruitment of white, brown, and beige adipocytes in mice, and summarize new data that reveal the complexity of adipose tissue development in vivo.",
"title": "The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment."
},
{
"docid": "14915566",
"text": "Debate exists over how to incorporate information from multipartite sequence data in phylogenetic analyses. Strict combined-data approaches argue for concatenation of all partitions and estimation of one evolutionary history, maximizing the explanatory power of the data. Consensus/independence approaches endorse a two-step procedure where partitions are analyzed independently and then a consensus is determined from the multiple results. Mixtures across the model space of a strict combined-data approach and a priori independent parameters are popular methods to integrate these methods. We propose an alternative middle ground by constructing a Bayesian hierarchical phylogenetic model. Our hierarchical framework enables researchers to pool information across data partitions to improve estimate precision in individual partitions while permitting estimation and testing of tendencies in across-partition quantities. Such across-partition quantities include the distribution from which individual topologies relating the sequences within a partition are drawn. We propose standard hierarchical priors on continuous evolutionary parameters across partitions, while the structure on topologies varies depending on the research problem. We illustrate our model with three examples. We first explore the evolutionary history of the guinea pig (Cavia porcellus) using alignments of 13 mitochondrial genes. The hierarchical model returns substantially more precise continuous parameter estimates than an independent parameter approach without losing the salient features of the data. Second, we analyze the frequency of horizontal gene transfer using 50 prokaryotic genes. We assume an unknown species-level topology and allow individual gene topologies to differ from this with a small estimable probability. Simultaneously inferring the species and individual gene topologies returns a transfer frequency of 17%. We also examine HIV sequences longitudinally sampled from HIV+ patients. We ask whether posttreatment development of CCR5 coreceptor virus represents concerted evolution from middisease CXCR4 virus or reemergence of initial infecting CCR5 virus. The hierarchical model pools partitions from multiple unrelated patients by assuming that the topology for each patient is drawn from a multinomial distribution with unknown probabilities. Preliminary results suggest evolution and not reemergence.",
"title": "Hierarchical phylogenetic models for analyzing multipartite sequence data."
},
{
"docid": "3662132",
"text": "MOTIVATION The enormous amount of short reads generated by the new DNA sequencing technologies call for the development of fast and accurate read alignment programs. A first generation of hash table-based methods has been developed, including MAQ, which is accurate, feature rich and fast enough to align short reads from a single individual. However, MAQ does not support gapped alignment for single-end reads, which makes it unsuitable for alignment of longer reads where indels may occur frequently. The speed of MAQ is also a concern when the alignment is scaled up to the resequencing of hundreds of individuals. RESULTS We implemented Burrows-Wheeler Alignment tool (BWA), a new read alignment package that is based on backward search with Burrows-Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps. BWA supports both base space reads, e.g. from Illumina sequencing machines, and color space reads from AB SOLiD machines. Evaluations on both simulated and real data suggest that BWA is approximately 10-20x faster than MAQ, while achieving similar accuracy. In addition, BWA outputs alignment in the new standard SAM (Sequence Alignment/Map) format. Variant calling and other downstream analyses after the alignment can be achieved with the open source SAMtools software package. AVAILABILITY http://maq.sourceforge.net.",
"title": "Fast and accurate short read alignment with Burrows–Wheeler transform"
},
{
"docid": "7059897",
"text": "The variable domain of an immunoglobulin (IG) sequence is encoded by multiple genes, including the variable (V) gene, the diversity (D) gene and the joining (J) gene. Analysis of IG sequences typically requires identification of each gene, as well as a comparison of sequence variations in the context of defined regions. General purpose tools, such as the BLAST program, have only limited use for such tasks, as the rearranged nature of an IG sequence and the variable length of each gene requires multiple rounds of BLAST searches for a single IG sequence. Additionally, manual assembly of different genes is difficult and error-prone. To address these issues and to facilitate other common tasks in analysing IG sequences, we have developed the sequence analysis tool IgBLAST (http://www.ncbi.nlm.nih.gov/igblast/). With this tool, users can view the matches to the germline V, D and J genes, details at rearrangement junctions, the delineation of IG V domain framework regions and complementarity determining regions. IgBLAST has the capability to analyse nucleotide and protein sequences and can process sequences in batches. Furthermore, IgBLAST allows searches against the germline gene databases and other sequence databases simultaneously to minimize the chance of missing possibly the best matching germline V gene.",
"title": "IgBLAST: an immunoglobulin variable domain sequence analysis tool"
}
] |
5ae717135542995703ce8bcd
|
Name the Swiss born Italian record producer, composer, musician and DJ, best known for his compostion 'Children' and who has worked with Frank Musker, the British songwriter and composer for artists such as Sheena Easton, Bucks Fizz and Lisa Stansfield?
|
[
{
"docid": "740408",
"text": "Roberto Concina (3 November 1969 – 9 May 2017), better known by his stage name Robert Miles, was a Swiss-born Italian record producer, composer, musician and DJ. He is best known for his composition \"Children\".",
"title": ""
},
{
"docid": "4891365",
"text": "Frank John Musker (born 1951) is a British songwriter and composer. Most prolific in the 1980s and 1990s, he worked with artists such as Sheena Easton, The Babys, Robert Miles, Jennifer Rush, Bucks Fizz, Air Supply, Lucio Battisti , Zucchero, Lisa Stansfield and Brian May (for the Queen song \"Too Much Love Will Kill You\"). His collaboration with May was awarded Best Song Musically and Lyrically at the 1997 Ivor Novello Awards.",
"title": ""
}
] |
[
{
"docid": "11328374",
"text": "Andrew Gerrard Hill (born 1957 in Bracknell, Berkshire, England) is an English record producer and songwriter, who was involved in creating many hits during the 1980s and 1990s. He is most famous for his work with Bucks Fizz.",
"title": ""
},
{
"docid": "13057305",
"text": "Matt Schwartz (born 26 October 1971) is an Israeli-British multi-instrumentalist record producer a songwriter, an artist, DJ, and a prolific audio engineer based in London. He has contributed to numerous records since 1995 as an engineer, producer, composer, musician and a songwriter, working with all the UK major record labels, he also had several club chart toppers and a few top 10 chart and airplay charts records in the UK, US and Europe as an artist.",
"title": ""
},
{
"docid": "2647583",
"text": "Jasun Martz is an American record producer, composer, musician, fine artist, creative director and sculptor who has worked on several #1 internationally best selling hit records but is probably best known for his contemporary classical symphonies. He has recorded with Michael Jackson, toured with Frank Zappa and helped arrange one of rock music's best selling hits: \"We Built this City\" by Starship.",
"title": ""
},
{
"docid": "1750863",
"text": "Thomas Bangalter (] ; born 3 January 1975) is a French musician, record producer, singer, songwriter, DJ, composer and film director, best known for being one half of the French house music duo Daft Punk, alongside Guy-Manuel de Homem-Christo. He has also recorded and released music as a member of the trio Stardust, the duo Together, and as a solo artist including compositions for the film \"Irréversible\". Bangalter's work has influenced a wide range of artists, many of whom are involved in different genres.",
"title": ""
},
{
"docid": "476237",
"text": "David Frank Paich (born June 25, 1954) is an Emmy and Grammy award-winning American keyboardist, singer, composer, recording producer, and arranger, best known for his work with the rock band Toto. With Toto, Paich has released 17 albums and sold over 30 million records. Additionally, Paich has contributed to a host of artists with his songwriting and arrangements including working with Boz Scaggs extensively in the 1970s and Michael Jackson in the 1980s.",
"title": ""
},
{
"docid": "28206161",
"text": "Joan Pla Parés; (born September 13, 1978) also known by his artist name \"Allone\", is a Catalan record producer, songwriter and composer. He has worked with well-known musicians such as James Czeiner, Joel Geddis and two-time Emmy-winning composer Neil Argo. He has release 2 full albums and 1 EP as a member of the Spanish band After Feed-Back and 1 album as a solo artist under his artistic name Allone. Joan Pla's credits include a list of TV commercials in the US, a feature film named \"Doctor Infierno\" in Spain, and several short films in different countries.",
"title": ""
},
{
"docid": "53912187",
"text": "Mike Willemsen (born (1996--) 27, 1996 ), better known by his stage name Mike Williams, is a Dutch DJ, record producer, musician and remixer. He is best known for working with Tiësto and as an artist of Spinnin' Records, who recognized him as an \"artist of the future\". He is regarded as a pioneer of the future house subgenre, \"future bounce\".",
"title": ""
},
{
"docid": "36309288",
"text": "Charles Goodan is an American, Los Angeles–based, Grammy Award winning musician, record producer, composer, singer, songwriter, engineer and multi-instrumentalist who has worked with many acclaimed artists such as Beck, The Rolling Stones, David Fincher, Morphine and Linkin Park. He is best known for his Grammy Award winning work on Santana's album \"Supernatural\", as well composing the Brit-Award nominated score for the film \"Fight Club\" and engineering the #1 Billboard song \"\"MMMBop\"\" by Hanson.",
"title": ""
},
{
"docid": "2430067",
"text": "Shinichi Osawa (Japanese: 大沢 伸一 , Hepburn: \"Ōsawa Shin'ichi\" , born 7 February 1967) , better known by his stage name Mondo Grosso, is a Japanese musician, DJ, record producer and composer currently signed onto Avex Trax's Rhythm Zone label. Previously he was signed to Sony Music Japan's FEARLESS RECORDS division and released albums under the title of \"Mondo Grosso\" (Italian for \"big world\"). Over the course of his career he has worked in genres from acid jazz to house, with strong influences of underground club music, though his recent work has been in the genre of electro house. HMV Japan rated Mondo Grosso at #95 on their \"Top 100 Japanese Pop Artists\" and Shinichi Osawa is ranked as Japan's #1 electro house DJ and Japan's #3 overall DJ by TopDeejays.com.",
"title": ""
},
{
"docid": "10310199",
"text": "David James Andrew Taylor, better known his stage name Switch, is a British DJ, songwriter, sound engineer, and record producer. He is best known for his work with M.I.A.. In the fidget house genre, Switch runs his own music label \"Dubsided\", as well as the label Counterfeet, established in 2006 with fellow producer Sinden. He has released various singles under his own name, and is also well known for remixing and producing for many major artists. He is a former member of the American electronic dancehall group Major Lazer.",
"title": ""
},
{
"docid": "14959649",
"text": "Nick Foster is a multiple BAFTA-winning British TV composer and music producer who has worked extensively over the past fifteen years. He is best known for composing music for television shows in the UK and US, such as The Cube, the Derren Brown programmes, Hank Zipzer, Penn & Teller,and for commercials. In his early career he was known for his work as a record producer and songwriter for acts including Gary Barlow, East 17, Toploader and S Club 7.",
"title": ""
},
{
"docid": "53190300",
"text": "Agundabweni Akweyu (also known Agunda) is Kenyan born record producer, Co - founder of record label Bwenieve, arranger, composer, songwriter, entrepreneur, audio engineer and a husband to a renown Kenyan gospel musician Evelyn Wanjiru .Based in Nairobi Kenya he is best known for producing hit songs for both established and uprising musicians as shown below, his unique style of production has seen a turn around in Kenyan gospel music in away that more musicians aspire to work with him.",
"title": ""
},
{
"docid": "35530215",
"text": "Tommy Asher Danvers, better known by his stage name TommyD, is a British producer, songwriter, arranger, DJ, and multi-instrumentalist. He is best known for his work with artists such as Right Said Fred, Catatonia, KT Tunstall, Corinne Bailey Rae, and Graffiti6. In addition, his career as a songwriter and/or producer has led him to work with a number of artists, including Kylie Minogue, Janet Jackson, Noel Gallagher, Sophie Ellis-Bextor, Kanye West, Jay Z, Beyoncé, Adele, Emeli Sandé, and fun.",
"title": ""
},
{
"docid": "10193216",
"text": "\"All Around the World\" is a song by English singer-songwriter Lisa Stansfield from her debut solo album \"Affection\" (1989). It was written by Stansfield, Ian Devaney and Andy Morris, and produced by Devaney and Morris. The song received favorable reviews from music critics. Songwriters, Stansfield, Devaney and Morris, received the 1989 Ivor Novello Award for Best Song Musically and Lyrically. \"All Around the World\" was also nominated for the Grammy Award for Best Female Pop Vocal Performance at the 33rd Annual Grammy Awards. Additionally, Stansfield was nominated for the Grammy Award for Best New Artist.",
"title": ""
},
{
"docid": "8516676",
"text": "Felix Bloxsom, was born in Sydney, Australia. He is a professional musician and songwriter, best known for his drumming and percussion playing and also as a DJ and record producer, working under the name 'Plastic Plates'.",
"title": ""
},
{
"docid": "34074005",
"text": "Robert Miles (1969–2017) was a Swiss-Italian record producer, composer, musician and DJ.",
"title": ""
},
{
"docid": "28569339",
"text": "Mario Fargetta (born 19 July 1962, Lissone, Milan, Italy) is an Italian house/electronic DJ, producer, recording artist, composer, and remixer. He is best known for his involvement with the groups The Tamperer featuring Maya, and, since 2005, Get Far, which is a pseudonym of both his last name and his desire to take his musical direction beyond the Italian Dance sound, of which he has been associated with since the late 1980s. As Get Far, he reached the top of US Hot Dance Airplay chart in August 2010 with the club hit \"The Radio\".",
"title": ""
},
{
"docid": "6000077",
"text": "Anni Hogan is a British musician, record producer, composer and Club DJ, born in 1961. Originally known for her association with British music artist Marc Almond, Hogan now collaborates with a diverse variety of artists including Rachel McFarlane and Cagedbaby.",
"title": ""
},
{
"docid": "15397786",
"text": "\"Strut\" is a song recorded by Sheena Easton for her album \"A Private Heaven\" (1984). It was released by EMI America in August 1984 as the album's lead single and peaked that November at #7 on the US \"Billboard\" Hot 100 (its \"Cash Box\" peak was #4). \"Strut\" was composed by singer/songwriter Charlie Dore (who had had a moderate solo hit of her own in the U.S. with \"Pilot of the Airwaves\" several years prior) and her longtime songwriting partner, Julian Littman.",
"title": ""
},
{
"docid": "29884635",
"text": "David Jost (born 12 August 1972) is an international music producer, singer-songwriter and DJ, born in Hamburg, Germany. His career as an international songwriter, music producer and remixer has a track record of 74 platinum & 108 gold records and 14 No. 1 hits. He has worked with platinum selling artist including Lady Gaga, Chris Brown, Tokio Hotel, Limp Bizkit, Selena Gomez, Nelly Furtado, Keri Hilson, Aura Dione, and Adam Lambert. For Tokio Hotel, David Jost has composed, produced and mixed six platinum selling #1 Hit Singles and three platinum selling #1 albums, he also has developed the band and is managing them. Tokio Hotel became the biggest international rock band to come out of Germany within two decades. Jost's work with Tokio Hotel lead to 87 media-awards, including 4 MTV European Music Awards, the MTV Video Music award Japan, 4 MTV Latin Music Awards including song of the year for \"Monsoon\" and also the US MTV Video Music Award (Moonman). Even though Jost managed several careers of big media artists, he only rarely answers interviews for the press and is known for principally never giving TV interviews. For his work as a songwriter, Jost was named Germany's best songwriter (Rock & Pop) by the GEMA (the German equivalent to the ASCAP/BMI). Jost is currently working in his Los Angeles studios.",
"title": ""
},
{
"docid": "26429034",
"text": "Eric M. Fowler is an American guitarist, singer, songwriter, composer and producer who is best known as a member of popular musical group Boxing Gandhis. Fowler is a featured musician on many popular recordings by artists such as Sting, UB40, Rosanne Cash, Taylor Dayne, General Public, Clint Black, Kelly Price and the Boxing Gandhis. He currently resides in Los Angeles California with his wife Colette and 3 children.",
"title": ""
},
{
"docid": "1907164",
"text": "Yak Bondy (born 8 July 1962 as Jerk Bondy in Germany) is a London-based music producer, songwriter, and composer. Bondy has been professionally involved in the music industry since 1990, when he was a musical director for Lisa Stansfield's world tour. Bondy works with the music licensing service, Hollywood Elite Music & Media in Los Angeles.",
"title": ""
},
{
"docid": "28647786",
"text": "Ian Kenneth Masterson is a British media composer, electronic musician and pop producer. Since the early 1990s he has produced and remixed songs for a range of pop acts including Dannii Minogue, Geri Halliwell, Kylie Minogue, Girls Aloud, Sheena Easton, Atomic Kitten, Bananarama, Sophie Ellis-Bextor, Lorie and the Pet Shop Boys.",
"title": ""
},
{
"docid": "205506",
"text": "Ryland Peter \"Ry\" Cooder (born March 15, 1947) is an American musician, songwriter, film score composer, and record producer. He is a multi-instrumentalist but is best known for his slide guitar work, his interest in roots music from the United States, and his collaborations with traditional musicians from many countries.",
"title": ""
},
{
"docid": "11884572",
"text": "Ming Freeman, born in Taiwan, of Chinese and Canadian descent, is a multi-keyboardist and pianist, musical director, composer and producer who has toured or recorded with artists such as Joni Mitchell, Yanni, Ronnie Laws, Chuck Negron, Jeffrey Osborne, Paula Abdul, Sheena Easton, Gladys Knight, Jean Carne and Michael Henderson. Freeman is a featured keyboard soloist in many of Yanni’s DVDs such as \"Tribute\" filmed in India and China, \"Yanni Live at Royal Albert Hall\" in London, \"Yanni Live! The Concert Event\", and \"Yanni Voices\". Freeman has been noted to handle the more advanced keyboard work during Yanni's shows.",
"title": ""
},
{
"docid": "7381387",
"text": "Kevin Porée (born 11 February 1965) is a British record producer, songwriter, composer, arranger and recording engineer. He is best known for his work with Mark Hole, Paul Young, Los Pacaminos, Senser, Joy Tobing, Hiding in Public, George Stiles and Anthony Drewe, Charlotte Gordon Cumming and for his associations with the composer / arranger Matheson Bayley and the eminent South African producer Neal Snyman.",
"title": ""
},
{
"docid": "41166336",
"text": "Matthieu Le Carpentier (born 22 September 1981 in Hérouville-Saint-Clair, Lower Normandy), better known by his stage name Skread (] ), is a French record producer, songwriter and musician. He has composed and produced for a great number of artists, notably Orelsan, Diam's, Booba, Rohff, Sinik and Nessbeal among others. He has worked on projects of young singer Isleym, rappers El Matador, Brasco and rap band Nysay. He is also co-founder of the record label 7th Magnitude, to which Orelsan and Nessbeal are signed, and has also appeared on many of Orelsan's music videos.",
"title": ""
},
{
"docid": "1789970",
"text": "Andrew Turner, known by the recording name Aim, is a British musician, DJ and producer, who was born in Barrow-in-Furness. Aim's sound is a blend of funky electronic music and hip hop beats, a sound which typified the Grand Central Records label. Much of Aim's work is instrumental, though his records include collaborations with other artists who provide vocals, including Stephen Jones of Babybird, Diamond D, Souls of Mischief, QNC and Kate Rogers.",
"title": ""
},
{
"docid": "48603237",
"text": "Montay Humphrey (known as DJ Montay) (born December 4, 1978) is an American DJ/turntablist, Grammy Award-nominated record producer and songwriter, who has worked with artists such as Flo Rida, T-Pain, Akon, and Ne-Yo. He has had his work featured on movies such as Step Up 3D, Stomp The Yard, and Norbit.",
"title": ""
},
{
"docid": "351071",
"text": "Christopher John \"Chris\" Spedding (born Peter Robinson, 17 June 1944) is an English musician, singer, guitarist, songwriter, multi-instrumentalist, composer, and record producer. In a career spanning more than 40 years, Spedding is best known for his studio session work. By the early 1970s, he had become one of the most sought-after session guitarists in England. Spedding has played on and produced many albums and singles. He has also been a member of eleven rock bands: The Battered Ornaments, Frank Ricotti Quartet, King Mob, Mike Batt and Friends, Necessaries, Nucleus, Ricky Norton, Sharks, Trigger, and The Wombles.",
"title": ""
}
] |
2049
|
How to tell if you can trust a loan company?
|
[
{
"docid": "233561",
"text": "Look for people who have done business with them. If you don't know anyone who has used their services, look for a company that at least has a brick and mortar branch in your area. Being able to deal with them face to face is a must. Have you checked with your local bank?",
"title": ""
}
] |
[
{
"docid": "217472",
"text": "As you own a company, you need to know what your role is. You can never just move money into or out of the company, you have to identify the role in which you are doing it, and do it properly. There is Company, and there is You, in three different roles. You are the sole shareholder and director of Company. You are the sole employee of Company. You are also just a private person. You need to keep these three roles separate. As the sole shareholder, you own the company. However, you don't own any assets of the company. The company is yours, but the money in its bank account isn't. As a private person, you give a loan to your company. You write on a sheet of paper that You personally, give a loan to the company, how much a loan is, what interest is paid, and when the loan will be paid back (that could be 'whenever You demands the money paid back'). Then you move the money from your private bank account to the company bank account, and the company has the money it needs to fund its operation. Assume it wasn't you who loaned the money, but I gave the loan to the company. You can imagine that I would have this loan written down and signed before I hand over the cash. And you must have exactly the same papers that I would have. How do you get money from the company? The company can pay back your loan. That should be written down again, in the same way as the loan itself was written down. Other than that, there are three ways how you can get money out of the company: The company can pay You, in your role as its employee, a salary, which it can deduct from its profits. The company can pay money into a pension of the company director (that's You in your role as company director) up to £40,000 or so a year; that money is deducted from its profits again. The company pays 20% tax on its remaining profits. Then the company can pay You, in your role as company director, a dividend, usually twice a year. Each of these payments has to be written down and given to HMRC properly. Best by far to use an accountant to do all the paper work for you and advice you what to do. You can lose a lot of money by just not getting the paperwork right, by filing late etc., which the accountant will get right. The accountant will also tell you what are the optimal amounts for salary and dividend (best is a small salary, about £10,000 a year, dividend of about £30,000 a year, pension as much as the company can afford, which is then all tax free to you). You can't pay more dividend then the company can afford (paying a dividend and then not being able to pay your suppliers is criminal), and if you want higher dividends, then you will have to pay taxes on them.",
"title": ""
},
{
"docid": "117429",
"text": "I'm going to give the succinct, plain language version of the answers: 1. Your oldest active credit agreement is not very old You don't have much experience or history for me to base my analysis on -- how do I know I can trust you to pay back the money? 2. You have no active credit card accounts Other people haven't trusted you with credit or you haven't trusted yourself with credit and there's no active good behavior of paying credit cards on time -- you want me to be the first one to go out on a limb and loan you money? How do I know I can trust you to pay back the money?",
"title": ""
},
{
"docid": "176830",
"text": "This is why we tell people not to co-sign unless they are able and willing to risk that money becoming a gift... or are able and willing to treat it as business rather than family. Unfortunately that advice is a bit late now to help you. When you cosigned, you promised the bank that you would make any payments he didn't. The bank doesn't care why he didn't, they just want their money on time. Getting him to repay you for covering this is strictly between the two of you, and unless you signed paperwork at the time establishing a contract other than the promise to cover his loan this becomes Extremely Messy. First step is to make the payments so the loan doesn't continue acquiring fees and hurting your credit rating, and keep it from falling behind again. Then you have to convince him to repay the money you have effectively given him. Depending on your relationship, and financial situations, you may decide to carry him for a while and trust that he'll pay you back when he can, or sic a lawyer on him. You need to make that decision, recognizing that it may be a matter of how much family drama you are willing to tolerate.",
"title": ""
},
{
"docid": "592510",
"text": "However, if you are employed by a company that exists in a tax haven and your services are provided to an employer by that tax haven company, it is the tax haven company that gets paid, not you. Under various schemes that company need not pay you at all. For example it may make you a loan which is not taxed (ie you don't pay tax on a loan, just as you don't pay tax on the money lent you by a mortgage company). You are bound by the terms of the loan agreement to repay that loan at a rate that the company finds acceptable. Indeed the company may find eventually that it is simply convenient to write off the loan as unrecoverable. if the owners/officers of he company write off your loans, how much tax will you have paid on the money you have had as loans? The taxman can of course state that this was simply set up to avoid tax (which is illegal) so you should have a balancing scheme to show that that the loans were taken to supplement income,just as one might take a bank loan / mortgage, not replace it entirely as a tax scam. Hiring tax counsel to provide this adequate proof to HMRC has a price. Frequently this kind of loophole exists because the number of people using it were sufficiently low not to warrant policing ( if the policing costs more than the tax recovered, then it is more efficient to ignore it) or because at some stage the scheme has been perfectly legal (as in the old offshore'education' trust recommended by the government a few decades ago). When Gordon Brown set out a 75% tax rate (for his possibly ideological reasons rather than financially based ones)for those who had these accounts , he encountered opposition from MPs who were going to be caught up paying high tax bills for what was effctively retrospective taxation, so there was a built in 'loophole' to allow the funds to be returned without undue penalty. If you think that is morally wrong, consider what the response would be if a future Chancellor was to declare all IAs the work of the devil and claim that retrospective tax would need to be paid on all ISA transactions over the last few decades.eg: tot up all the dividends and capital gains made on an ISA in any year and pay 40% tax on all of them, even if that took the ISA into negative territory because the value today was low/ underperfoming. Yet this has been sggested as a way of filling in the hole in the budget on the grounds that anyone with an ISA can be represented as 'rich' to a selected party of voters.",
"title": ""
},
{
"docid": "497901",
"text": "\"A \"\"leveraged/trade program\"\"? What exactly is that? So let me get this straight. You put just 10% of the total amount of what you're trading into an account with Citi (Citi's going to give you 10-1 leverage on your money...why?), and then in 90 days they'll give you your money back and a loan for ten times the amount? Either the heat has gotten to me or this is the craziest thing I've read today. You didn't specify what it is you'd be \"\"trading\"\", and if your \"\"acquaintance\"\" didn't share that with you either then it sounds beyond suspect -- it sounds like total fraud. I couldn't imagine a scenario whereby Citi would be involved in a scheme like this, whatever \"\"it\"\" is. I suspect that your \"\"friend\"\" has you opening an account at Citi because it makes the whole scam sound more legitimate by tying to a big bank name. It might be worth your time to actually call Citi (I looked up their number for you. It's 1-800-685-0935) and ask them about this particular idea. When they get done snickering, they'll tell you the same thing everyone else is -- RUN from this. You're very right to suspect that you can't leverage money without encumbering it. What would be the point for someone to essentially give you credit on a 10-to-1 basis and then not encumber the collateral? If you don't know anything about trading and how leverage works then it would be highly inadvisable for you to jump into something that you don't understand. Your \"\"acquaintance\"\" may have been sucked into investing their own money, and now they think they're doing you a \"\"favor\"\" by telling you about this \"\"incredible opportunity\"\". It's how most scams work. They get the suckers to sign up friends and relatives, because they're playing on the trust between those people. Stick to what you know or what someone can give you a clear and reasonable explanation of. And have someone you really know and trust (preferably a friend or family member who is reasonably successful in managing their own finances) to act as a sounding board when things like this come along to help keep you from doing something stupid that you'll really regret. Hope this helps. Good luck!\"",
"title": ""
},
{
"docid": "302691",
"text": "This are my opinions on the subject: -People are tired of the corrupt system of bankers who poorly manage money, Bitcoin is built on trust, and more people are starting to trust it. Can you trust a banker? NO. Can you trust computer systems built on strict code that will always do what you tell them too? YES. To understand why Bitcoin is safe, one must first understand the block-chain technology. MORE INFO -More companies are starting to accept Bitcoin as payment, which creates more trust in the system, which brings more people interest. LIST OF COMPANIES -Bitcoin is a worldwide coin, you can pay your friend in Japan with Bitcoin and the transaction is done in 10 minutes, as opposed to 5-7 business day if done through a bank. The banker fee is huge, the Bitcoin miner fee is minimal. -Bitcoin is like Gold but better, Bitcoin is not built for everyday transactions just like gold, its not built for buying coffee either, its built to retain value which is why there is a finite amount (21 million). -A huge benefit of bitcoin is anyone with a smartphone or a computer can download an App and start accepting Bitcoins as payments. Gold is not easily trade-able. Bitcoins is as simple as sending a picture message. (NOTE: More than 2 billion smartphone users around the world around 3.7 billion internet users around the world all capable of one day trading using bitcoin) LIVE INTERNET USERS -Keep in mind, there is more than one crypto currency, all built on different ideas and systems, all performing with incredible gains. MORE INFO",
"title": ""
},
{
"docid": "496540",
"text": "\"The question isn't \"\"fair\"\", it's \"\"how much do you have to give them in order to get them to trust you with the money for a year rather than doing something else with it, and does that exceed what you are willing/able to give them, and how sure are you that you can either do without the money or find it elsewhere?\"\" This has to be negotiated. There is no standard answer, since there is no standard company or lender. Heck, even a simple bank loan is a negotiation, though that usually takes the form of shopping around for an acceptable rate and their deciding whether they'll accept you rather than going back and forth on what rate would be the best compromise.\"",
"title": ""
},
{
"docid": "222232",
"text": "If an entity or individual has full rights to the land and land improvements, they can hold, transfer, delegate, or dispose of them on their terms. The only exception may be eminent domain. If the sovereignty meets the public necessity or public purpose tests they can assume or change the rights to your property in exchange for compensation. As others have said writing your own mortgage falls under the category of seller financing. A seller can write a mortgage with the help of a loan servicing company. Some loan service companies report to credit agencies, to help with buyer refinancing at a later point. Other forms of seller financing: Leasing Land contracts mineral contracts and more... Additionally, the seller can finance the minority of the property, called a junior mortgage. For example, the Bank finances 79% of the value, the seller finances 11%, and the buyer's 10% down payment covers the rest. If the buyer defaults, the superior mortgage (bank's) has collection priority. More commonly, the seller can option for a wrap-around mortgage or an 'all-inclusive mortgage'. The seller holds or refinances the existing mortgage and provides a junior mortgage in exchange for a secured promissory note and an all-inclusive trust deed. If the buyer defaults, the seller has foreclosure rights. It is not uncommon for entities or people to use financing strategies other than the traditional mortgage if they are unable to exclude the gain on sale. Check out section 1031 exchanges. In almost all cases I would tell people not to make decisions based on tax consequences alone, if your financial objective/goal for seller financing sounds like a 1031 exchange, take exception and carefully consider the tax consequences.",
"title": ""
},
{
"docid": "179175",
"text": "I just described its function. Tell me what they do other than what I described, and also tell me how much of drug companies' budgets are consumed in this process (preferably the unecessary parts of the process), especially compared to the rest of the drug spending and inordinate profits. Drug companies run ads, they have sales reps (pharma girls), they have tort cases (not a symptom of regulation), they have research, they have HUGE employee and CEO salaries and bonuses, they have distribution costs. Trust me when I say that regulation isn't the driving force here.",
"title": ""
},
{
"docid": "231188",
"text": "The government and local police is probably doing the same with all the cameras on highways and in city streets. I trust the IT security of a local civic government less than one of the largest e-commerce conglomerate. Besides, your Amazon profile is already pretty telling, if you're a prime member taking advantage of its benefits. You tell it your years of purchase preferences, your ebooks, music and audio tastes with prime video and music, your groceries can tell how big a family you have, they also have your home and very likely work addresses.",
"title": ""
},
{
"docid": "554465",
"text": "If you want to see a more academic version of this look up Weighted Average Cost of Capital (WACC). It's a formula that tells you how much it costs for a company to raise $1 of capital whether it be through issuing bonds or stocks. One thing you learn is that there are times that if you take on loans (even if you don't need it) you can raise shareholder value and therefore the total company netvalue. The thought process is (as it states in the article above) that a company can issue debt for cheaper than issue shares and it will have extra cash which it can use to get a better return than its net effective interest rate. I tried to give an example but I only ended up rehashing what it says in the article. Anyhow look up WACC and you'll understand the fundamentals.",
"title": ""
},
{
"docid": "305509",
"text": "Co-signing is not the same as owning. If your elderly lady didn't make any payments on the loan, and isn't on the ownership of the car, and there was no agreement that you would pay her anything, then you do not owe either her or her daughter any money. Also the loan is not affecting the daughter's credit, and the mother's credit is irrelevant (since she is dead). However you should be aware that the finance company will want to know about the demise of the mother, since they can no longer make a claim against her if you default. I would start by approaching the loan company, telling them about the mother's death, and asking to refinance in your name only. If you've really been keeping up the payments well this could be OK with them. If not I would find someone else who is prepared to co-sign a new loan with you, and still refinance. Then just tell the daughter that the loan her mother co-signed for has been discharged, and there is nothing for her to worry about.",
"title": ""
},
{
"docid": "463857",
"text": "A lot of this example is idealistic and the analysis stops right at the point the loan is issued. If you use generous interest rates you could just skirt by the bare minimum debt service coverage ratio for an asset-backed loan if you found a lender to approve it. However, he doesn't address any of the issues of running a business that will be insolvent if expenses rise more than about ~2% above the monthly average in a given month (those pesky 3-pay period months; equipment repairs; heating/cooling in winter/summer; etc.), or you have a similarly small sag in sales (selling dirtbikes in January?). Most companies doing LBOs have skin in it, and a plan to make the company more valuable, not run it exactly the way it is. This allows them to either acquire more debt capital than just a percentage of the collateral -- and so they can finance capital projects to improve the business, deal with fluctuations in cash flow, and/or implement plans to increase the free cash flows above how it was running previously. This site's advice is a bit like teaching someone the basics of how to take off in an airplane, and then telling them they're ready to fly.",
"title": ""
},
{
"docid": "127697",
"text": "SMSFs are generally prohibited from acquiring assets from related parties (whether it is purchased by the SMSF or contributed into the fund). There are some exceptions to the above rule for acquiring related party assets, including: • Listed securities (ie shares, units or bonds listed on an approved stock exchange, such as the ASX) acquired at market value. • Business real property (ie freehold or leasehold interests in real property used exclusively in one or more businesses) acquired at market value. • An in-house asset where the acquisition would not result in the level of the fund’s in-house assets exceeding 5%. • Units in a widely held unit trust, such as a retail ,managed fund. In-house asset rules An ‘in-house asset’ is generally defined as: • An investment by an SMSF in a related company or trust (ie a fund owns shares in a related company or units in a related trust). • An asset of an SMSF that is leased to a related party. • A loan made by an SMSF to a related company or trust. An investment, lease or loan that is an in-house asset is not prohibited, but is limited to 5% of the market value of the fund’s assets. The Answer: If your pre-owned Western Australian Rock Lobster fishery quota units are not included in the exceptions then you cannot transfer them into your SMSF.",
"title": ""
},
{
"docid": "454084",
"text": "If you are not open to changing the amount of money you are willing to spend, your options are limited. Why change your amounts and proportions? Your situation changed. You got married, divorced, purchased a new car, the company added free disability coverage. If the amount spent per year can't change, then you are asking how to review if your proportions are correct. The first thing is to look at what must you spend it on. If you have a mortgage or car loan, the bank will tell you the minimum amount. If you own a car the state will tell you the minimum amount for auto coverage. If there is any money left look at life, and disability. These can wreck the life of your dependents. When you have meet those needs, then increase auto and home to cover additional liability.",
"title": ""
},
{
"docid": "257980",
"text": "\"Here are some important things to think about. Alan and Denise Fields discuss them in more detail in Your New House. Permanent work. Where do you want to live? Are there suitable jobs nearby? How much do they pay? Emergency fund. Banks care that you have \"\"reserves\"\" (and/or an unsecured line of credit) in case you have a run of bad luck. This also helps with float the large expenses when closing a loan. Personal line of credit. Who are you building for? If you are not married, then you should consider whether building a home makes that easier, or harder. If you hope to have kids, you should consider whether your home will make it easier to have kids, or harder. If you are married (or seriously considering it), make sure that your spouse helps with the shopping, and is in agreement on the priorities and choices. If you are not married, then what will you do if/when you get married? Will you sell? expand? build another house on the same lot? rent the home out? Total budget. How much can the lot, utilities, permits, taxes, financing charges, building costs, and contingency allowance come to? Talk with a banker about how much you can afford. Talk with a build-on-your-lot builder about how much house you can get for that budget. Consider a new mobile or manufactured home. But if you do choose one, ask your banker how that affects what you can borrow, and how it affects your rates and terms. Talk with a good real estate agent about how much the resale value might be. Finished lot budget. How much can you budget for the lot, utilities, permits required to get zoning approval, fees, interest, and taxes before you start construction? Down payment. It sounds like you have a plan for this. Loan underwriting. Talk with a good bank loan officer about what their expectations are. Ask about the \"\"front-end\"\" and \"\"back-end\"\" Debt-To-Income ratios. In Oregon, I recommend Washington Federal for lot loans and construction loans. They keep all of their loans, and service the loans themselves. They use appraisers who are specially trained in evaluating new home construction. Their appraisers tend to appraise a bit low, but not ridiculously low like the incompetent appraisers used by some other banks in the area. (I know two banks with lots of Oregon branches that use an appraiser who ignores 40% of the finished, heated area of some to-be-built homes.) Avoid any institution (including USAA and NavyFed) that outsources their lending to PHH. Lot loan. In Oregon, Washington Federal offers lot loans with 30% down payments, 20-year amortization, and one point, on approved credit. The interest rate can be a fixed rate, but is typically a few percentage points per year higher than for a mortgage secured by a permanent house. If you have the financial wherewithal to start building within two years, Washington Federal also offers short-term lot loans. Ask about the costs of appraisals, points, and recording fees. Rent. How much will it cost to rent a place to live, between when you move back to Oregon, and when your new home is ready to move into? Commute. How much time will it take to get from your new home to work? How much will it cost? (E.g., car ownership, depreciation, maintenance, insurance, taxes, fuel? If public transportation is an option, how much will it cost?) Lot availability. How many are there to choose from? Can you talk a farmer into selling off a chunk of land? Can you homestead government land? How much does a lot cost? Is it worth getting a double lot (or an extra large lot)? Utilities. Do you want to live off the grid? Are you willing to make the choices needed to do that? (E.g., well, generator, septic system, satellite TV and telephony, fuel storage) If not, how much will it cost to connect to such systems? (For practical purposes, subtract twice the value of these installation costs from the cost of a finished lot, when comparing lot deals.) Easements. These provide access to your property, access for others through your property, and affect your rights. Utility companies often ask for far more rights than they need. Until you sign on the dotted line, you can negotiate them down to just what they need. Talk to a good real estate attorney. Zoning. How much will you be allowed to build? (In terms of home square footage, garage square footage, roof area, and impermeable surfaces.) How can the home be used? (As a business, as a farm, how many unrelated people can live there, etc.) What setbacks are required? How tall can the building(s) be? Are there setbacks from streams, swamps, ponds, wetlands, or steep slopes? Choosing a builder. For construction loans, banks want builders who will build what is agreed upon, in a timely fashion. If you want to build your own house, talk to your loan officer about what the bank expects in a builder. Plansets and permits. The construction loan process. If you hire a general contractor, and if you have difficulties with the contractor, you might be forced to refuse to accept some work as being complete. A good bank will back you up. Ask about points, appraisal charges, and inspection fees. Insurance during construction. Some companies have good plans -- if the construction takes 12 months or less. Some (but not all) auto insurance companies also offer good homeowners' insurance for homes under construction. Choose your auto insurance company accordingly. Property taxes. Don't forget to include them in your post-construction budget. Homeowners' insurance. Avoid properties that need flood insurance. Apply a sanity check to flood maps -- some of them are unrealistic. Strongly consider earthquake insurance. Don't forget to include these costs in your post-construction budget. Energy costs. Some jurisdictions require you to calculate how large a heating system you need. Do not trust their design temperatures -- they may not allow for enough heating during a cold snap, especially if you have a heat pump. (Some heat pumps work at -10°F -- but most lose their effectiveness between 10°F and 25°F.) You can use these calculations, in combination with the number of \"\"heating degree days\"\" and \"\"cooling degree days\"\" at your site, to accurately estimate your energy bills. If you choose a mobile or manufactured home, calculate how much extra its energy bills will be. Home design. Here are some good sources of ideas: A Pattern Language, by Christopher Alexander. Alexander emphasizes building homes and neighborhoods that can grow, and that have niches within niches within niches. The Not-So-Big House, by Sarah Susanka. This book applies many Alexander's design patterns to medium and large new houses. Before the Architect. The late Ralph Pressel emphasized the importance of plywood sheathing, flashing, pocket doors, wide hallways, wide stairways, attic trusses, and open-truss or I-joist floor systems. Lots of outlets and incandescent lighting are good too. (It is possible to have too much detail in a house plan, and too much room in a house. For examples, see any of his plans.) Tim Garrison, \"\"the builder's engineer\"\". Since Oregon is in earthquake country -- and the building codes do not fully reflect that risk -- emphasize that you want a building that would meet San Jose, California's earthquake code.\"",
"title": ""
},
{
"docid": "237043",
"text": "\"There are two ways that mortgages are sold: The loan is collateralized and sold to investors. This allows the bank to free up money for more loans. Of course sometime the loan may be treated like in the game of hot potato nobody want s to be holding a shaky loan when it goes into default. The second way that a loan is sold is through the servicing of the loan. This is the company or bank that collects your monthly payments, and handles the disbursement of escrow funds. Some banks lenders never sell servicing, others never do the servicing themselves. Once the servicing is sold the first time there is no telling how many times it will be sold. The servicing of the loan is separate from the collateralization of the loan. When you applied for the loan you should have been given a Servicing Disclosure Statement Servicing Disclosure Statement. RESPA requires the lender or mortgage broker to tell you in writing, when you apply for a loan or within the next three business days, whether it expects that someone else will be servicing your loan (collecting your payments). The language is set by the US government: [We may assign, sell, or transfer the servicing of your loan while the loan is outstanding.] [or] [We do not service mortgage loans of the type for which you applied. We intend to assign, sell, or transfer the servicing of your mortgage loan before the first payment is due.] [or] [The loan for which you have applied will be serviced at this financial institution and we do not intend to sell, transfer, or assign the servicing of the loan.] [INSTRUCTIONS TO PREPARER: Insert the date and select the appropriate language under \"\"Servicing Transfer Information.\"\" The model format may be annotated with further information that clarifies or enhances the model language.]\"",
"title": ""
},
{
"docid": "456526",
"text": "\"You're confusing between \"\"individual\"\" 401k (they're called \"\"Solo-401k\"\" and are intended for self-employed), and Individual Retirement Account (IRA). You can't open a solo-401k without being self employed. You can open an IRA and roll over money from your old 401k to it. You cannot get a loan from IRA. You can ask the 401k plan manager to reissue the checks to the new trust, shouldn't be a problem. Make sure the checks are issued to the trust, not to you, to avoid withholding and tax complications. This is what is called a \"\"direct\"\" rollover. You might be able to roll the money over to the 401k of your new employer, it is not always allowed and you should check. You can probably then take a loan from that 401k. However, it diminishes the value of your retirement savings and you should only do it if you have no other choice (being evicted from your home, your children are starving, can't pay for your chemo, etc... this kind of disasters). Otherwise, I'd suggest rolling over to IRA, investing in funds with significantly lower fees (Vanguard target retirements funds for example, or index funds/ETF's), and reassessing your spending and budgeting habits so that you won't need loans from your 401k. Re companies - ETrade is nice, consider also Scottrade, TDAmeriTrade, Vanguard, Fidelity, Sharebuilder, and may be others. These are all discount brokers with relatively low fees, but each has its own set of \"\"no-fee\"\" funds.\"",
"title": ""
},
{
"docid": "57211",
"text": "\"I am not sure how anyone is answering this unless they know what the loan was for. For instance if it is for a house you can put a lien on the house. If it is for the car in most states you can take over ownership of it. Point being is that you need to go after the asset. If there is no asset you need to go after you \"\"friend\"\". Again we need more specifics to determine the best course of action which could range from you suing and garnishing wages from your friend to going to small claims court. Part of this process is also getting a hold of the lending institution. By letting them know what is going on they may be able to help you - they are good at tracking people down for free. Also the lender may be able to give you options. For example if it is for a car a bank may help you clear this out if you get the car back plus penalty. If a car is not in the red on the loan and it is in good condition the bank turns a profit on the default. If they can recover it for free they will be willing to work with you. I worked in repo when younger and on more than a few occasions we had the cosigner helping. It went down like this... Co-signer gets pissed like you and calls bank, bank works out a plan and tells cosigner to default, cosigner defaults, banks gives cosigner rights to repo vehicle, cosigner helps or actually repos vehicle, bank gets car back, bank inspects car, bank asks cosigner for X amount (sometimes nothing but not usually), cosigner pays X, bank does not hit cosigners credit, bank releases loan and sells car. I am writing this like it is easy but it really requires that asset is still in good condition, that cosigner can get to the asset, and that the \"\"friend\"\" still is around and trusts cosigner. I have seen more than a few cosigners promise to deliver and come up short and couple conspiring with the \"\"friend\"\". I basically think most of the advice you have gotten so far is crap and you haven't provided enough info to give perfect advice. Seeking a lawyer is a joke. Going after a fleeing party could eat up 40-50 billable hours. It isn't like you are suing a business or something. The lawyer could cost as much as repaying the loan - and most lawyers will act like it is a snap of their fingers until they have bled you dry - just really unsound advice. For the most part I would suggest talking to the bank and defaulting but again need 100% of the details. The other part is cosigning the loan. Why the hell would you cosign a loan for a friend? Most parents won't cosign a loan for their own kids. And if you are cosigning a loan, you write up a simple contract and make the non-payment penalties extremely costly for your friend. I have seen simple contracts that include 30% interests rates that were upheld by courts.\"",
"title": ""
},
{
"docid": "317419",
"text": "I see you've marked an answer as accepted but I MUST tell you that STOPPING your 401k contribution all together is a bad idea. Your company match is 100% rate of return(or 50% depending on structure). I don't care what market you look at, or how bad a loan you take out, you will not receive 100% rate of return, or be charged 100% interest. Further, taking out a loan against your 401k effectively does two things: It is a loan that must be repaid according to the terms of your 401k AND in every 401k I've ever encountered, you cannot make contributions to the 401k until the loan is repaid. This in effect stops your contributions, and will almost certainly save you very little on your interest rates on your current loans. I have 4 potential solutions that may help achieve your goal without sacrificing your 401k match and transferring the debt from one lender to another, but they are conditional. Is your company match 100% up to 4% of your salary, or 50% of your contribution (up to a limit you have not yet reached)? This is important. If it is 100% up to 4%, stop committing the additional 4% and use that to pay down your debt...and after ward set up that 4% as auto pay into an IRA, not into the 401k. An IRA will make you more money because YOU have control over its management, not your employer. If it is 50% match, contribute until the match is met because you cannot get 50% rate of return anywhere, then take your additional monies and get an IRA. As far as your debt, in this scenario simply suck it up and pay it as is. You will lose far more than you gain by stopping your contributions. If you simply must reduce your expenses by 150$ month try refinancing the mortgage and rolling the 6500$ into it. If you get a big enough drop in the interest rate you could still end up paying less. OR If you cannot make the gain there, try snowballing the three payments. You do this by calling your student loan vendor and telling them you need to make much smaller payments, like even zero depending on the type of loan. Then take ALL of the money you are currently spending on the 3 loans and put into the car payment. When it's gone, roll the whole thing into the higher interest student loan, then finally roll it all into the last student loan. You'll pay it off faster, and student loans have lots of laws and regulations regarding working with payers to keep them paying something without breaking them. WHATEVER YOU DO, DO NOT STOP YOUR CONTRIBUTIONS. 50% OR 100%, THAT MONEY IS GUARANTEED AT A HIGHER RATE OF RETURN THAN YOU CAN GET ANYWHERE, ESPECIALLY GUARANTEED.",
"title": ""
},
{
"docid": "433066",
"text": "\"Consumer Reports offers a service that can tell you detailed actual cost to a dealer for a specific model and accessories -- real cost after rebates, not just invoice price. It costs a bit to order these reports, but if you are serious about buying a new car they are a highly recommended tool -- cu is independent and will give you the best info available, and simply walking into the dealership with the report in your hand can save huge amounts of negotiating. \"\"If you can give it to me for $500 over the real price, as shown here, I'll sign now.\"\" Of course, standard advice is that it's usually better to buy a recent-model used car. I believe cu has other reports that can help you determine what a fair price is in that case, but usually I just bring it to a trusted garage and pay them to tell me exactly how much work it needs and whether they think it's worth the asking price.\"",
"title": ""
},
{
"docid": "49059",
"text": "I said it in the comments, but I think it stands as a possible answer; if the bank's the only one telling you you are ineligible for HARP, get a second opinion. The bank is making lots of money off of you, at a time when the pickings are otherwise slim. The bank doesn't want you to refinance, and will do anything it can to convince you that you can't. Many of the big lenders have been taken to task (and to court) by the government for actively hindering these loan modification programs. So, don't trust the bank's word alone. Go to http://www.harpprogram.org and check the eligibility criteria, and if you think you meet them, fill out an application. The basic criteria are: Some caveats:",
"title": ""
},
{
"docid": "461233",
"text": "\"I think the answer to this question depends on how much you trust yourself. Most people are wonderful at deceiving themselves. I'd personally not trust myself; I'll use Liam's points for the pitfalls some people get into. You can pay off your loans with summer internships and retain the initial cash you had for additional activities that make college enjoyable, i.e - Fraternity/ Sorority, clubs, dinners, and social nights. This is actually the risk I've seen many people do. They'll blow their money in one semester under the assumption that 'they'll just earn more in Summer and keep it for expenses or the future.\"\" Another benefit to taking these loans would assist in building credit, No Credit (in the USA) is actually a good standing. Many sensible banks or credit unions will happily give people with No Credit a loan. This makes intuitive sense if you think about it. Imagine two people with the same income. One owes money regularly to multiple sources and the other has no debt obligations. Which one are you loaning money to? Simplifying things a lot: Great Credit is best, followed by No Credit, then Good Credit, and then Bad Credit. The advantage of Great Credit over No Credit is simply that some institutions in some sectors don't have the policies in place to process No Credit people (No Credit people plan to not apply for credit often, for self-explanatory reasons, so this is a mote point).\"",
"title": ""
},
{
"docid": "61196",
"text": "\"> If he's also a top notch electrician, I listen to him when he gives me electrical wiring advice, I just don't let him choose where we go for dinner. \"\"Now most folks will tell you that fuses are rated for 20 Amps, but they're just being over-cautious. I go to 25 and even 30 Amps all the time with no problem\"\" Do you trust *that* electrical opinion? Does his restaurant choice affect how you feel about it? Compare that to another friend who steered you away from another restaurant because he \"\"heard someone got sick there once.\"\" He also drives the car rated #1 for safety and can tell you exactly why. He always lectures you for riding a bicycle without a helmet, and offers to sharpen your kitchen knives because a sharp knife is less likely to slip and cut your finger. When *that* guy says you can go to 30A on a fuse, how do you feel about his opinion as an electrician? Still say that non-electrician decisions have zero bearing on how you feel about his abilities as an electrician? BTW, I'm done here. I've made my point. We can agree to disagree.\"",
"title": ""
},
{
"docid": "202749",
"text": "\"I don't mean to be discouraging, but that isn't necessarily always the case. Despite being the larger company, it is possible the other team will have a lower cost, or be more efficient, or depending on how the organizational structure works out may just simply be in a familiar reporting structure that \"\"trusts\"\" them more. I think that's why /u/RustbeltRoots suggested it is nearly impossible to tell.\"",
"title": ""
},
{
"docid": "581634",
"text": "There is a way to get a reasonable estimate of what you still owe, and then the way to get the exact value. When the loan started they should have given you amortization table that laid out each payment including the principal, interest and balance for each payment. If there are any other fees included in the payment those also should have been detailed. Determine how may payments you have maid: did you make the first payment on day one, or the start of the next month? Was the last payment the 24th, or the next one? The table will then tell you what you owe after your most recent payment. To get the exact value call the lender. The amount grows between payment due to the interest that is accumulating. They will need to know when the payment will arrive so they can give you the correct value. To calculate how much you will save do the following calculation: payment = monthly payment for principal and interest paymentsmade =Number of payments made = 24 paymentsremaining = Number of payments remaining = 60 - paymentsmade = 60-24 = 36 instantpayoff = number from loan company savings = (payment * paymentsremaining ) - instantpayoff",
"title": ""
},
{
"docid": "72240",
"text": "\"Lots of loans that are shady to say the least are advertised currently on TV in the UK. I'm happily in a situation where I don't need a loan but might be asked to be a guarantor. If anyone asked me to be a guarantor for a loan, I'd either be capable and willing to loan that money to the person myself, or I wouldn't guarantee. I'd never, ever in a million years be a guarantor. There is one company in particular offering loans \"\"the good old-fashioned way\"\" asking for 49.9% interest with a guarantor. That is an interest rate that can bankrupt the guarantor. If you take the loan with me as the guarantor, and you decide that you are not interested in paying back the loan, I'm stuck with this loan. So since the guarantor must trust you, if he or she is established in the UK, the best thing to do would be for them to take a loan from a bank (or any supermarket nowadays will give you a loan at a decent rate) in their own name, give the money to you, and hope that you pay back the money. I'm equally responsible for repayment whether I'm guarantor or whether the loan is in my name, so I'd get that loan at a decent rate from a reputable bank.\"",
"title": ""
},
{
"docid": "254500",
"text": "I'm leaning more towards trading it in can anyone give me some pointers on how to get the best deal? Information is key to getting the best deal possible. That is why I would strongly suggest getting a second opinion on the repairs. A misfire could be caused by many things. From cheap (bad spark plugs or cables) to mid-range cost (timing is off) to expensive (not getting proper compression in the cylinders due to mechanical issues that could require an engine rebuild). Also, car diagnostics is not an exact science, so it is definitely worth checking with another mechanic. You trust the first place you took it too, which is great. You taking it to another place does not represent a lack of trust, it represents knowing that humans are fallible and car repair diagnostics are not perfect either. Once you have quotes from 2 or 3 places for the repair work, you are in a much better position to negotiate. The next step is to see how much it will cost to replace the thing. Get actual quotes for trade-in from dealers, and you must disclose the engine troubles to them when getting this quote. $8,000 minus this amount is how much you are under water. Add that to the price of the car you would like to purchase to know how much of a loan you will have to take out (minus any downpayment). The next thing to consider is how you manage your risk from there. Your new car will be under-water too. Can you even get a loan? Will you need additional collateral or gap insurance to get the loan? What happens if you get in an accident the next day and total this car? Once you have all of this information, you are ready to really start thinking about the decision to be made. Things to consider: How reliable has the HHR been up to now? You don't want to put $3,500 into it now only to have to spend a few grand more in a month to replace the transmission. It is hard for us to know this as we don't know how long you have had it, what troubles you have had in the past, how well you have taken care of it (regular oil changes and maintenance). Keshlam is right about asking mechanics to check for other problems and scheduled maintenance that has not been done (e.g., timing belts replaced). Once you have made your decision, remember that everything is negotiable if you are wiling to walk away. If you decide to keep the car, try to get a better deal on the repairs by checking out other repair shops. If you decide to buy another car and get rid of this one, both the sale price of the new car and the trade-in price of the HHR are negotiable. Shop around and put in the work to buy something that will last a at a good price.",
"title": ""
},
{
"docid": "459724",
"text": "Danger. The affidavit is a legal document. Understand the risk of getting caught. If you are planning on using the condo to generate income the chances that you default on the loan are higher than an owner occupied property. That is why they demand more down payment (20%+) and charge a higher rate. The document isn't about making sure you spend 183+ nights a year in the property, it is making sure that it isn't a business, and you aren't letting a 3rd party live in the property. If you within the first year tell the mortgage company to send the bill to a new address, or you change how the property is insured, they will suspect that it is now a rental property. What can they do? Undo the loan; ask for penalty fee; limit your ability to get a mortgage in the future; or a percentage of the profits How likely is it? The exact penalty will be in the packet of documents you receive. It will depend on which government agency is involved in the loan, and the lenders plan to sell it on the secondary market. It can also depend on the program involved in the sale of the property. HUD and sister agencies lock out investors during the initial selling period, They don't want somebody to represent themselves as homeowner, but is actually an investor. Note: some local governments are interested not just in non-investors but in properties being occupied. Therefore they may offer tax discounts to residents living in their homes. Then they will be looking at the number of nights that you occupy the house in a year. If they detect that you aren't really a resident living in the house, that has tax penalties. Suggestion: If you don't want to wait a year buy the condo and let the loan officer know what your plan is. You will have to meet the down payment and interest rate requirements for an investment property. Your question implies that you will have enough money to pay the required 20% down payment. Then when you are ready buy the bigger house and move in. If you try and buy the condo with a non-investment loan you will have to wait a year. If you try and pay cash now, and then get a home equity loan later you will have to admit it is a rental. And still have to meet the investor requirements.",
"title": ""
},
{
"docid": "460357",
"text": "\"Tell them you will not loan them any more money until their existing debts are paid off. This is closer to how the real world works and it won't come across as vengeful or like your changing your initial \"\"contract\"\". If they protest, lovingly tell them that your money is not their money, and that an interest free loan from their father is a privilege, not a right. As far as charging interest on your loans, go for it! Charge them 5% or something small. Just don't do it on the existing loans or that will come across as changing your initial \"\"contract\"\" again, and perhaps once they've proven themselves to be reliable borrowers they can once again earn the privilege to have an interest free loan. The book \"\"The Millionaire Next Door\"\" has really good thoughts on this in its section on Economic Outpatient Care.\"",
"title": ""
}
] |
2965
|
What does a CFP do?
|
[
{
"docid": "204176",
"text": "A Certified Financial Planner has passed a licensing exam and will advise you and help you reach your financial goals. A good CFP can help you a lot, especially if you are unsure how to set up your insurance, investment, savings, and financial plans on your own. You do not need a CFP to get a life insurance policy. If you do get a CFP, he or she should help you above and beyond life insurance -- i.e. retirement planning, investment advice, education planning, etc. It's advantageous to you to pay a fixed price for services instead of a percentage or commission. Negotiate fees up front. For life insurance, in most cases a term policy will fit your needs. Whole life, universal life, etc., combine investments and life insurance into a single product and are big commission makers for the salesman. They make it sound like the best thing ever, so be aware. One of my rules of thumb is that, generally speaking, the larger the commission is for the salesperson, the worse the product is for the consumer. Welcome to life insurance pitches. Term life is far less expensive and provides a death benefit and nothing else. If you just had a baby and need to protect your family, for example, term life is often a good solution, easy to buy, and inexpensive. As you stated, any of the major providers will do just fine.",
"title": ""
},
{
"docid": "200468",
"text": "\"CFP stands for \"\"Certified Financial Planner\"\", and is a certification administered by the CFP board (a non-government non-profit entity). This has nothing to do with insurance, and CFP are not insurance agents. Many States require insurance agents to be explicitly licensed by the State as such, and only licensed insurance agents can advise on insurance products. When you're looking for an insurance policy as an investment vehicle, a financial adviser (CFP, or whatever else acronym on the business card - doesn't matter) may be helpful. But in any case, when dealing with insurance - talk to a licensed insurance agent. If your financial adviser is not a licensed tax adviser (EA/CPA licensed in your State) - talk to a licensed tax adviser about your options before making any decisions.\"",
"title": ""
}
] |
[
{
"docid": "314252",
"text": "\"A financial planner can help with investments, insurance, estate planning, budgeting, retirement planning, saving for college, tax planning/prep, and other money topics. One way to get a sense is to look at this Certified Financial Planner topic list. Another idea is to look at this book (my favorite I've read) which covers roughly a similar topic list in a concise form: http://www.amazon.com/Smart-Simple-Financial-Strategies-People/dp/0743269942 It could not hurt at all to read that before deciding to visit a planner, so you have baseline knowledge. By the way, look for the CFP certification which is a generalist certification. A CFP might also have a deeper cert in certain topics or connect you with someone who does. For example: You really want a generalist (CFP) who may have an additional credential as well. The idea is to holistically look at what you're trying to accomplish and all finance-related areas. Especially because there may be tradeoffs. The CFP would then refer you to or work with lawyers, accountants, etc. Importantly, some advisors are fiduciaries (must act in your interests) and some are not. In particular many stockbrokers are neither qualified planners (no CFP or equivalent) nor are they fiduciaries. Stay away. There are several models for paying a financial planner, including: There's an organization called NAPFA (napfa.org) for fiduciary non-commission-based planners. Membership there is a good thing to look for since it's a third party that defines what fee-only means and requires the no-commissions/fiduciary standard. Finally, the alternative I ended up choosing was to just take the CFP course myself. You can do it online via correspondence course, it costs about the same as 1 year of professional advice. I also took the exam, just to be sure I learned the stuff. This is the \"\"extreme DIY\"\" approach but it is cheaper over time and you know you are not going to defraud yourself. You still might do things that are counterproductive and not in your interests, but you know that already probably ;-) Anyway I think it's equivalent to about a quarter's worth of work at a decent college, or so. There are about 6 textbooks to dig through. You won't be an experienced expert at the end, but you'll know a lot. To get an actual CFP cert, you need 3 years experience on top of the courses and the exam - I haven't done that, just the book learning. Someone who puts \"\"CFP\"\" after their name will have the 3 years on top of the training. Some editorial: many planners emphasize investing, and many people looking for planners (or books on finance) emphasize investing. This is a big mistake, in my view. Investing is more or less a commodity and you just need someone who won't screw it up, overcharge, and/or lose your money on something idiotic or inappropriate. Some people are in plain-bad and inappropriate investments, don't get me wrong. But once you fix that and just get into anything decent, your biggest planning concerns are probably elsewhere. On investments, I'd look for a planner to just get you out of overpriced annuities and expensive mutual funds you may have been sold (anything you were sold by a salesperson is probably crap). And look for them to help you decide how much to invest, and how much in stocks vs. bonds. Those are the most important investment decisions.\"",
"title": ""
},
{
"docid": "461004",
"text": "you are on the right track. 7/66 will be legally necessary (most likely), and CFP is pretty much a professional necessity at this point. insurance license isn't a bad idea, but i would need to know the full scope of services offered to give you more info. as far as resources go, watch bloomberg in the morning and a bit before you hit the hay for futures and international movement. their website is pretty solid to check on throughout the day, too. beyond that, it's kind of all preference as to what sources you use. i'd recommend staying away from very obviously biased outlets. but there will be professional sources that are availed to you once you're up and running - your dad might have some subscriptions he can give to you. i check on the Atlantic, fivethirtyeight, and the economist regularly for context, as well. on a personal note, i would encourage you to really weigh your options before committing to taking on the practice. i am a professional (hold 7/63/66/9/10 and CFP) and can tell you that, in my opinion, it is very exhausting and largely unrewarding working with clients. i won't go into a pessimistic diatribe here, as i don't want to discourage you from doing something you want. but be really sure - unless you're an analyst, this sort of work experience does not lend itself to changing careers or type of work you do.",
"title": ""
},
{
"docid": "543042",
"text": "Not sure you read my post based on your word choice but.... CFP is more of a marketing ploy from a consumer behavior perspective. You don't need a CFP to have the technology or knowledge to utilize what is taught in the modules and plenty of CFPs will still give shit advice. When choosing an advisor it comes down to ethics, work ethic, knowledge, experience, and fee structure in that order. Not saying to never hire a CFP, but just because somebody has a CFP doesn't mean they'll actually be any better than any other advisor.",
"title": ""
},
{
"docid": "119059",
"text": "Being a successful CFP is 100% about convincing other people to give you their money. Managing 90% of people's finances is sticking to the foundationals and keeping them in the market long term. OP doesn't want to be a hedge fund or PE guy doing complex transactions, he wants CFP. He needs to be able to sell himself, because it's what he'll be doing his whole career.",
"title": ""
},
{
"docid": "458529",
"text": "\"Though @mehassee mentioned it in a comment, I would like to emphasize the point that the financial planner (CFP) you talked to said that he was a fiduciary. A fiduciary has an obligation to act in your best interests. According to uslegal.com, \"\"When one person does agree to act for another in a fiduciary relationship, the law forbids the fiduciary from acting in any manner adverse or contrary to the interests of the client, or from acting for his own benefit in relation to the subject matter\"\". So, any of these Stack Exchange community members may or may not have your best interest at heart, but the financial advisor you talked to is obligated to. You have to decide for yourself, is it worth 1% of your investment to have someone legally obligated to have your best financial interest in mind, versus, for example, someone who might steer you to an overpriced insurance product in the guise of an investment, just so they can make a buck off of you? Or versus wandering the internet trying to make sense of conflicting advice? In my opinion, a fiduciary (registered CFP) is probably the best person to answer your questions.\"",
"title": ""
},
{
"docid": "7882",
"text": "Well kind of hard to give an answer without seeing the underlying syllabus, but judging by the title of the majors here's what the career paths *might* be. Personal Financial Planning generally leads to a career in financial planning wherein clients come to you and explain to you their future goals and you have to devise an investment plan which adheres to their assets and liabilities structure. I'm getting a sense that the major is a precursor to the CFP certification; so check out the CFP Board's website. Finance Major is *probably* the major which leads to a career in investment banking or investment management (wherein you'll probably deal with institutional clients rather than individuals). It's worth noting that the two majors probably share courses.",
"title": ""
},
{
"docid": "458370",
"text": "\"I work in wealth management now - so it deviates from what you are looking to do long term, but what about getting your series 7 or 65? I'm 37 now, and before I started my own firm I got my 7/63 and worked for a big custodian to \"\"cut my teeth\"\" - which quite honestly was a glorified sales position, however it was invaluable for learning to \"\"speak the language\"\" for lack of a better term. I don't have a CFA (which I know is very challenging), but I am a CFP and ChFC (also not easy) and have a MS in statistics and MBA in finance. If you have any questions or wanted to do a mock interview I'd be glad to help.\"",
"title": ""
},
{
"docid": "59723",
"text": "Most of the organizations that financial advisors belong to have a function to find their members. The major ones are listed below: Advocis seems to be the largest organization, with CFPs (Certified Financial Planners) and some Insurance designations. The Advocis advisor search feature can be found here. FPSC is another organization that has a search for CFPs. Many of the same CFPs are in the Advocis database, but some aren't. The FPSC advisor search feature can be found here. IAFP is an organization of Registered Financial Planners (RFP). The database is smaller but the designation comes with prestige and is meant to be a mark of quality. The IAFP advisor search feature can be found here. Finally, there is a site — full disclosure, I am affiliated with it — called wealthprep.ca that has a large listing of advisors in Canada. You can filter by profession, specialties, and compensation type and there are ratings and reviews. Here is the page specifically for Toronto Financial Advisors.",
"title": ""
},
{
"docid": "595427",
"text": "\"It sounds like the kinds of planners you're talking to might be a poor fit, because they are essentially salespersons selling investments for a commission. Some thoughts on finding a financial planner The good kind of financial planner is going to be able to do a comprehensive plan - look at your whole life, goals, and non-investment issues such as insurance. You should expect to get a document with a Monte Carlo simulation showing your odds of success if you stick to the plan; for investments, you should expect to see a recommended asset allocation and an emphasis on low-cost no-commission (commission is \"\"load\"\") funds. See some of the other questions from past posts, for example What exactly can a financial advisor do for me, and is it worth the money? A good place to start for a planner might be http://napfa.org ; there's also a franchise of planners providing hourly advice called the Garrett Planning Network, I helped my mom hire someone from them and she was very happy, though I do think your results would depend mostly on the individual rather than the franchise. Anyway see http://www.garrettplanningnetwork.com/map.html , they do require planners to be fee-only and working on their CFP credential. You should really look for the Certified Financial Planner (CFP) credential. There are a lot of credentials out there, but many of them mean very little, and others might be hard to get but not mean the right thing. Some other meaningful ones include Chartered Financial Analyst (CFA) which would be a solid investment expert, though not necessarily someone knowledgeable in financial planning generally; and IRS Enrolled Agent, which means someone who knows a lot about taxes. A CPA (accountant) would also be pretty meaningful. A law degree (and estate law know-how) is very relevant to many planning situations, too. Some not-very-meaningful certifications include Certified Mutual Fund Specialist (which isn't bogus, but it's much easier to get than CFP or CFA); Registered Investment Adviser (RIA) which mostly means the person is supposed to understand securities fraud laws, but doesn't mean they know a lot about financial planning. There are some pretty bogus certifications out there, many have \"\"retirement\"\" or \"\"senior\"\" in the name. A good question for any planner is \"\"Are you a fiduciary?\"\" which means are they legally required to act in your interests and not their own. Most sales-oriented advisors are not fiduciaries; they wouldn't charge you a big sales commission if they were, and they are not \"\"on your side\"\" legally speaking. It's a good idea to check with your state regulators or the SEC to confirm that your advisor is registered and ask if they have had any complaints. (Small advisors usually register with the state and larger ones with the federal SEC). If they are registered, they may still be a salesperson who isn't acting in your interests, but at least they are following the law. You can also see if they've been in trouble in the past. When looking for a planner, one firm I found had a professional looking web site and didn't seem sketchy at all, but the state said they were not properly registered and not in compliance. Other ideas A good book is: http://www.amazon.com/Smart-Simple-Financial-Strategies-People/dp/0743269942 it's very approachable and you'd feel more confident talking to someone maybe with more background information. For companies to work with, stick to the ones that are very consumer-friendly and sell no-load funds. Vanguard is probably the one you'll hear about most. But T. Rowe Price, Fidelity, USAA are some other good names. Fidelity is a bit of a mixture, with some cheap consumer-friendly investments and other products that are less so. Avoid companies that are all about charging commission: pretty much anyone selling an annuity is probably bad news. Annuities have some valid uses but mostly they are a bad deal. Not knowing your specific situation in any detail, it's very likely that 60k is not nearly enough, and that making the right investment choices will make only a small difference. You could invest poorly and maybe end up with 50K when you retire, or invest well and maybe end up with 80-90k. But your goal is probably more like a million dollars, or more, and most of that will come from future savings. This is what a planner can help you figure out in detail. It's virtually certain that any planner who is for real, and not a ripoff salesperson, will talk a lot about how much you need to save and so forth, not just about choosing investments. Don't be afraid to pay for a planner. It's well worth it to pay someone a thousand dollars for a really thorough, fiduciary plan with your interests foremost. The \"\"free\"\" planners who get a commission are going to get a whole lot more than a thousand dollars out of you, even though you won't write a check directly. Be sure to convert those mutual fund expense ratios and sales commissions into actual dollar amounts! To summarize: find someone you're paying, not someone getting a commission; look for that CFP credential showing they passed a demanding exam; maybe read a quick and easy book like the one I mentioned just so you know what the advisor is talking about; and don't rush into anything! And btw, I think you ought to be fine with a solid plan. You and your husband have time remaining to work with. Good luck.\"",
"title": ""
},
{
"docid": "521835",
"text": "it depends on the area you want to focus in. to be sure, i will say that pretty much all certificates in finance can be achieved online now. CFP is a pretty ok one. i have it myself. there is quite a bit of material, but isn't too challenging. it focuses on financial planning/personal finance. certainly aids your technical knowledge but is kind of an analog to help boost your sales. most pure planners i know have this but moreover a series of more technical designations. you must have a bachelors to be given the right to use the CFP. CFA is a great one for your resume (and knowledge), but makes the CFP look like a summer vacation. it is for analysis, but has a broad range of potential uses. i know brokers, advisors, planners, and people leaders with these marks. if you are very smart, it will take you a minimum of 2.5 years (really 3yr) to complete due to their testing schedule. they also grade on a very steep curve. from what i understand, the amount of information and level of command you must demonstrate also necessitate this lengthy schedule. beyond that, you can look at getting FINRA licensed in a desired area (e.g. series 7/63 to be a broker). i would caution against this, unless you are very sure of where you want to go or need to meet the requirement for a job. typically jobs with license requirements will permit you 3-6 months to obtain them on company money. you risk spending a good bit of money that won't be reimbursed by getting licensed independently. keep in mind that you cannot actually use your licenses without a firm sponsor. finally, there are a variety of specialized designations like CWS and CMT that i would also caution against unless sure of desired position or meeting job requirements. it is better, in my opinion, to find yourself in a place where getting these will better position you for your current job rather than wasting time on them and finding yourself in a place where they hold no water.",
"title": ""
},
{
"docid": "480628",
"text": "Considering a CFP will likely use the same planning software as any other advisor...just hire an advisor with a clean broker check and solid educational background that doesn't come off as a sleazy sales person. Not to say that a CFP doesn't say ANYTHING about qualifications, but really it's just a marketing ploy from a business perspective.",
"title": ""
},
{
"docid": "397921",
"text": "I've already worked for a major broker dealer. I came to ask this question on Reddit for unbiased advice. I've asked multiple people the same question in industry and they always tell me something different. Since I will be registering in my home state of New York, I looked up what the regulations are and was even further confused. One website says >Licensing Requirements: Series 65, Series 66 and Series 7 combined, or one of the following acceptable professional designations: CFA, CFP, CIC, ChFC, PFS. Whereas another says > If you have taken the Series 65 or both the Series 66 and Series 7 within the last two years, you do not have to do anything. My confusion is the part where the first website says Series 65, Series 66, and Series 7 combined.",
"title": ""
},
{
"docid": "330711",
"text": "Great, thank you very much! I guess I will just do my 7/66 first and then worry about the others (CFP or CFA) later if I really want to get them. I just wanted to make sure I wasn’t doing something I didn’t *really* need to do.",
"title": ""
},
{
"docid": "494034",
"text": "I am a Certified Financial Planner and provide tactical advice on everything from budgeting to saving for retirement. You do not have to have any series exams or a CFP to do this work, although it helps give you credibility. As long as you DO NOT provide investment advice, you likely do not need to register as an investment advisor or need any certification.",
"title": ""
},
{
"docid": "530902",
"text": "\"I don't want to hate on those other comments but as a college student having a 4.0 and going to a \"\"target\"\" school are not realistic goals for everyone. The best advice I would give you is to be passionate about the field. It sounds dumb on its face but being involved in student investment clubs/funds or competing in investment competitions are great ways to get exposure and meet people in the field while building your resume. Internships are incredibly important because that's where you prove to yourself and others that you are a capable person. You also have a lot of options ahead of you. You can do research, client facing roles (CFP), and even corporate finance. I wasn't a finance major but I spent 3 years in college working in our student managed investment fund and it absolutely paid off (now doing corporate finance). You have to want to learn and grow. It's not realistic for a college student with limited resources to get your CFA level 1 or series exams, especially if it doesn't suit your field. Be open to different types of jobs and build relationships with your professors who are well connected. It does help to have stellar grades and it helps to be at a top school but our state school has put kids on the Street. You just have to be hungry and realistic about your talents and passion. Good luck to you.\"",
"title": ""
},
{
"docid": "106578",
"text": "I don't know what you mean by 'major'. Do you mean the fund company is a Fidelity or Vanguard, or that the fund is broad, as in an s&P fund? The problem starts with a question of what your goals are. If you already know the recommended mix for your age/risk, as you stated, you should consider minimizing the expenses, and staying DIY. I am further along, and with 12 year's income saved, a 1% hit would be 12% of a year's pay, I'd be working 1-1/2 months to pay the planner? In effect, you are betting that a planner will beat whatever metric you consider valid by at least that 1% fee, else you can just do it yourself and be that far ahead of the game. I've accepted the fact that I won't beat the average (as measured by the S&P) over time, but I'll beat the average investor. By staying in low cost funds (my 401(k) S&P fund charges .05% annual expense) I'll be ahead of the investors paying planner fees, and mutual fund fees on top of that. You don't need to be a CFP to manage your money, but it would help you understand the absurdity of the system.",
"title": ""
},
{
"docid": "188564",
"text": "\"as someone that works in finance, i will say it is really hard to get out of the sales web, regardless of where you are. i don't want to discourage you, but you will need to get advanced degrees/certification to get into analysis or fund management. there are plenty of broker/service roles available at large broker-dealers, but you will take a pay cut and likely only advance to your current pay in those roles. and you will still have some \"\"soft\"\" sales responsibilities. all that being said, if you want to go this route, go for it - and the sooner the better. if you are smart and hardworking, you can wrap up your bachelors in 2 years and then go for the CFA over the next 3. you'll need some luck to do the CFA in that amount of time (as there are 3 levels that take a minimum of 1 year each to complete), but you could potentially have some traction in 5-6 years. so it would be difficult, but achievable. the CFA will qualify you for some corporate finance roles as well. i have some friends that were hired to these positions after only passing the first or second levels of CFA, but i believe they had accounting/finance background already. i think that, regardless of your intermediate term plan, getting a bachelors is a great next move. it's a minimum in a growing number of financial roles. you can also look at getting the CFP, which is less demanding and quicker, but it will remove you less from the sales process. (you need a bachelors to qualify for the CFP, too)\"",
"title": ""
},
{
"docid": "74402",
"text": "You want CFP or CFA who is also a fiduciary, meaning that by law they have to put your interests ahead of their own. Financial planners who are not fiduciaries can, and often do, recommend investment vehicles that earn them the most commission with little regard of your financial goals. If you already have $500,000 to invest and racking up $100,000 a month you probably qualify for most institutions private client programs. That means that the firm/advisor will look at your financial situation and come up with a custom-tailored investment plan for you which should also include tax planning. I would start with whatever financial institutions you already work with - Schwab, your bank etc. Set up a meeting and see what they have to offer. Make sure you interrogate them about their fees, their licenses/certifications and above all if they are a fiduciary.",
"title": ""
},
{
"docid": "476678",
"text": "I took the exam and passed the first try. Although I did entirely self study with no exam prep course, I do not recommend that method. Dalton is the best option. It's very pricey, but they guarantee a refund if you don't pass. Don't forget that in addition to the Dalton fees, you will have the exam fee as well as if you pass, the CFP dues up front.",
"title": ""
},
{
"docid": "101184",
"text": "To charge money for investment advice the only prerequisite is the 65. Find out what licenses your father has. You can cover the 6, 63, 65, 66 and 7 with the 66 & 7. I would suggest: Life and Health, 66, 7, CFP. In that order. But you might also be able to get away with the L&H, 6 and 63 (this is more common among older product sales based advisors) to get up and running.",
"title": ""
},
{
"docid": "257757",
"text": "You can get an investment manager through firms like Fidelity or E*Trade to manage your account. It won't be someone dedicated exclusively to you, but you're in the range where they'd take you as a managed account customer. Another option would be to get a financial planner (CFP or something) help you to identify your needs and figure out what your investments portfolio should look like. This is not a whole lot of money, but is definitely enough to have an early retirement if managed and invested properly.",
"title": ""
},
{
"docid": "227364",
"text": "The bucket concept. What ever works. Some people literally use envelopes, putting cash into each category for there upcoming bills. I prefer not to mix my long term investments. My daughter's college fund is in a series of separate accounts from our retirement money. I won't criticize your CFP's comments, because advice is individual, her approach probably works well for her clients. The important thing isn't the focus on the words, but the end result. Spend less than you earn, save for each of your goals. I removed any IRA/US reference and comment on bucket concept.",
"title": ""
},
{
"docid": "133728",
"text": "You know there is a small group of individuals who focus on strictly planning without implementation. They are not securities licensed (no 7,6,66,63 license) so they cannot sell or discuss securities, but they do put together financial plans to help individuals recover from debt and rework spending/saving strategies. They also usually work hand in hand with a CFP or ChFc to do the implementation process. The hard part is making money at it. Financial Planners make most of their income on high net worth clients. You would be targeting low income or troubles income clients that would have a hard time paying money for the service. I am not saying it cannot be done, you just have your work cut out for you. But it is a noble career and you would be helping idividuals have a better life. That speaks volumes!",
"title": ""
},
{
"docid": "287192",
"text": "I should also add that the 7/63 won't do much for you. If you're really interested in finance, you have a few options. 1) Sales - in which case the 7/63 is about all you need. The rest is just time and practice. 2) A job as an analyst. Your best bet here is to pursue the CFA charter. 3) A financial planner/advisor. This job is kind of a subcategory of #1. I always like to say that an advisor's primary job is to sell, giving meaningful advice is secondary. Nonetheless, a CFP is helpful here. 4) A trader. CFA charter is helpful here as with #2. 5) High Frequency Trading - Masters/PhD in math or a quant discipline and C++ is a must.",
"title": ""
},
{
"docid": "55404",
"text": "There are a lot of certifications/designations you could look into if you're willing to put in the time to study. CFA, FRM, CFP, etc. Most financial companies will recognize these although some carry more weight than others.",
"title": ""
},
{
"docid": "56932",
"text": "A Random Walk Down Wall Street Barbarians at the Gate Liar's Poker King of Capital The Big Short No need to even consider CFP or CFA if you don't have a degree/full time job that requires it. They are costly.",
"title": ""
},
{
"docid": "457702",
"text": "\"The Financial Consumer Agency of Canada (FCAC) has a page specifically about working with a financial planner or advisor. It's a good starting point if you are thinking about getting a financial professional to help you plan and manage your investments. In the \"\"Where To Look\"\" section on that page, FCAC refers to a handful of industry associations. I'll specifically highlight the Financial Planning Standards Council's \"\"Find a planner\"\" page, which can help you locate a Certified Financial Planner (CFP). Choose financial advice carefully. Prefer certified professionals who charge a set fee for service over advisors who work on commission to push investment products. Commission-based advice is seldom unbiased. MoneySense magazine published a listing last year for where to find a fee-only financial planner, calling it \"\"The most comprehensive listing of Canadian fee-only financial planners on the web\"\" — but do note the caveat (near the bottom of the page) that the individuals & firms have not been screened. Do your own due diligence and check references.\"",
"title": ""
},
{
"docid": "143951",
"text": "Yea I know they are. I want to get them out of the way though and my firm gives me the support to take whatever. Cfp I'm looking at a year or more of studying. 9/10 I could crank out in a couple of months. Not sure if I want to go management or consultant route. But thank you!",
"title": ""
},
{
"docid": "303426",
"text": "If you like financial planning the CFP not the CFA will be your cup of tea. Screw books though. If you are really that interested just walk into an office like Schwab or Edward Jones or fidelity and start asking questions. They are usually happy to talk to new comers. Also if you are female you already have a leg up in the industry. Sad but true.",
"title": ""
},
{
"docid": "151442",
"text": "Not sure why people are suggesting CFP or CFA to someone who hasn't graduated with a BS yet. With that said, CFA had a claritas (fundamentals course) with like 20-20 page chapters going over basic finance and investment info. Pretty sure you can still get those pdfs for free. Investopedia is also great for general concepts for banking and investments. CFA is very expensive and I wouldn't touch it until you've taken general business classes and really built up your foundation.",
"title": ""
}
] |
5a846191554299123d8c222d
|
Community is an American television sitcom that follows an ensemble cast, including what actress who played Trudy Campbell in the AMC drama Mad Men?
|
[
{
"docid": "21998954",
"text": "Community is an American television sitcom created by Dan Harmon that aired on NBC and Yahoo! Screen from September 17, 2009 to June 2, 2015. The series follows an ensemble cast of characters played by Joel McHale, Gillian Jacobs, Danny Pudi, Yvette Nicole Brown, Alison Brie, Donald Glover, Ken Jeong, Chevy Chase, and Jim Rash at a community college in the fictional town of Greendale, Colorado. It makes heavy use of meta-humor and pop culture references, often parodying film and television clichés and tropes.",
"title": ""
},
{
"docid": "24382329",
"text": "Alison Brie Schermerhorn (born December 29, 1982 ) is an American actress and producer. She portrayed Annie Edison in the NBC/Yahoo! sitcom \"Community\" (2009–2015) and Trudy Campbell in the AMC drama \"Mad Men\" (2007–2015). Brie currently voices Diane Nguyen on the Netflix animated series \"BoJack Horseman\" (2014–present) and portrays Ruth Wilder on the Netflix comedy-drama series \"GLOW\" (2017). She has starred in several films, such as \"Scream 4\" (2011), \"The Five-Year Engagement\" (2012), \"The Lego Movie\" (2014), \"Get Hard\" (2015), \"Sleeping with Other People\" (2015), and \"How to Be Single\" (2016).",
"title": ""
}
] |
[
{
"docid": "28681645",
"text": "\"Chinese Wall\" is the eleventh episode of the fourth season of the American television drama series \"Mad Men\", and the 50th overall episode of the series. It aired on the AMC channel in the United States on October 3, 2010. Cara Buono, who played Dr. Faye Miller, received a nomination for Primetime Emmy Award for Outstanding Guest Actress in a Drama Series for this episode.",
"title": ""
},
{
"docid": "6617452",
"text": "John M. Slattery Jr. (born August 13, 1962) is an American actor and director. He is best known for his role as Roger Sterling in the AMC drama series \"Mad Men\" and for his role as Howard Stark in cameo appearances in the Marvel Cinematic Universe films \"Iron Man 2\", \"Ant-Man\", and \"\". He has received four Primetime Emmy Awards nominations and two Critics' Choice Television Awards for \"Mad Men\". He was also part of the \"Mad Men\" ensemble cast that won two SAG Awards.",
"title": ""
},
{
"docid": "28379233",
"text": "\"The Rejected\" is the fourth episode of the fourth season of the American television drama series \"Mad Men\", and the 43rd overall episode of the series. It was written by Keith Huff and series creator and executive producer Matthew Weiner, and directed by John Slattery, who portrays Roger Sterling on the show. It originally aired on the AMC channel in the United States on August 15, 2010. Reviews of the episode were generally positive, emphasizing particularly the emotional tension between Pete Campbell (Vincent Kartheiser) and Peggy Olson (Elisabeth Moss).",
"title": ""
},
{
"docid": "35515741",
"text": "\"Signal 30\" is the fifth episode of the fifth season of the American television drama series \"Mad Men\" and the 57th episode of the series overall. It was written by series creator and executive producer Matthew Weiner and writer Frank Pierson, and directed by main cast member John Slattery. It originally aired on the AMC channel in the United States on April 15, 2012.",
"title": ""
},
{
"docid": "28681660",
"text": "\"Blowing Smoke\" is the twelfth episode of the fourth season of the American television drama series \"Mad Men\", and the 51st overall episode of the series. It aired on the AMC channel in the United States on October 10, 2010. Robert Morse who plays Bertram Cooper received a nomination for the Primetime Emmy Award for Outstanding Guest Actor in a Drama Series for this episode at the 63rd Primetime Emmy Awards.",
"title": ""
},
{
"docid": "11951528",
"text": "Mad Men is an American period drama television series created by Matthew Weiner and produced by Lionsgate Television. The series premiered on July 19, 2007, on the cable network AMC. After seven seasons and 92 episodes, \"Mad Men's\" final episode aired on May 17, 2015.",
"title": ""
},
{
"docid": "37462175",
"text": "Jay Seals (born March 23, 1976) is an American actor, known for his recurring role in the television drama \"Mad Men\" on AMC from 2010 to 2015. Some of his other credits include the 2012 American television police procedural fantasy drama \"Awake\", as a police tech, Nat, who is considered to be a \"tech-savvy cop\". He also appeared in numerous other television series and films.",
"title": ""
},
{
"docid": "51388380",
"text": "\"For Those Who Think Young\" is the first episode of the second season of the American television drama series \"Mad Men\". It was written by series creator Matthew Weiner and directed by Tim Hunter. The episode originally aired on AMC in the United States on July 27, 2008.",
"title": ""
},
{
"docid": "53960323",
"text": "Carly Wray is an American television writer and producer. She is known for her writing on the AMC drama \"Mad Men\" and \"The Leftovers\" on HBO. She won a for \"Mad Men\" in 2016.",
"title": ""
},
{
"docid": "19067943",
"text": "Stephanie Courtney (born February 8, 1970) is an American actress and comedian, best known for playing the advertising character Flo in television and radio commercials for Progressive Corporation beginning in 2008, and noted for her recurring roles on several television series, including the voices of Renee the Receptionist and Joy Peters on the Adult Swim comedy \"Tom Goes to the Mayor\" (2004–06); Marge on the AMC drama \"Mad Men\" (2007); and Diane on the ABC comedy \"Cavemen\" (2007). She also appeared in the season 2 premiere of \"Men of a Certain Age\". Courtney is a member of The Groundlings, an improvisational and sketch comedy theater in Los Angeles, California.",
"title": ""
},
{
"docid": "3426205",
"text": "Christina Rene Hendricks (born May 3, 1975) is an American actress. She is best known for her role as Joan Holloway in the AMC drama television series \"Mad Men\", for which she was nominated for six Primetime Emmy Awards.",
"title": ""
},
{
"docid": "40920128",
"text": "Sarah Jocelyn \"Sadie\" Alexandru (born December 2, 1977) is an American actress and model. Alexandru is best known for playing Scarlett, the SCDP secretary on the hit AMC drama series \"Mad Men\".",
"title": ""
},
{
"docid": "29660233",
"text": "The first season of the American television drama series Mad Men premiered on July 19, 2007 and concluded on October 18, 2007. It consisted of thirteen episodes, each running approximately 47 minutes. AMC broadcast the first season on Thursdays at 10:00 pm in the United States. Actors Jon Hamm, Elisabeth Moss, Vincent Kartheiser, January Jones, Christina Hendricks, Bryan Batt, Michael Gladis, Aaron Staton, Rich Sommer, and Maggie Siff receive main cast billing.",
"title": ""
},
{
"docid": "3634471",
"text": "Jonathan Daniel Hamm (born March 10, 1971) is an American actor, director, and television producer best known for playing advertising executive Don Draper for the AMC television drama series, \"Mad Men\" (2007–2015).",
"title": ""
},
{
"docid": "18884302",
"text": "Todd London is an American television producer. He has worked on several series for HBO, including \"Carnivàle\", \"Rome\", and \"The Pacific\". He was a producer on the first series of AMC drama \"Mad Men\".",
"title": ""
},
{
"docid": "21184801",
"text": "Peter Dyckman \"Pete\" Campbell (born February 28, 1934) is a fictional character on AMC's television series \"Mad Men\". He is portrayed by Vincent Kartheiser.",
"title": ""
},
{
"docid": "83049",
"text": "Neve Adrianne Campbell ( ; born October 3, 1973) is a Canadian actress. She is best known for her role as Sidney Prescott in the horror film series \"Scream\". She got her start appearing in the Canadian television series \"Catwalk\", before she played Julia Salinger in the American drama series \"Party of Five\". She has starred in films such as \"The Craft\" (1996), \"Wild Things\" (1998), \"Panic\" (2000), and \"The Company\" (2003). Campbell has also made guest appearances on several television series, such as \"Medium\", \"Grey's Anatomy\" and \"Mad Men\", as well as a starring role in the fourth and fifth seasons of the critically acclaimed Netflix drama series \"House of Cards\".",
"title": ""
},
{
"docid": "13819121",
"text": "\"Babylon\" is the sixth episode of the first season of the American television drama series \"Mad Men\". It was written by Andre and Maria Jacquemetton and directed by Andrew Bernstein. The episode originally aired on the AMC channel in the United States on August 23, 2007.",
"title": ""
},
{
"docid": "47259104",
"text": "\"Person to Person\" is the series finale of the American television drama series \"Mad Men\" and the 92nd episode of the series overall. The episode was written and directed by series creator Matthew Weiner, and originally aired on AMC on May 17, 2015.",
"title": ""
},
{
"docid": "13818961",
"text": "\"Marriage of Figaro\" is the third episode of the first season of the American television drama series \"Mad Men\". It was written by Tom Palmer and directed by Ed Bianchi. The episode originally aired on the AMC channel in the United States on August 2, 2007.",
"title": ""
},
{
"docid": "13819044",
"text": "\"New Amsterdam\" is the fourth episode of the first season of the American television drama series \"Mad Men\". It was written by Lisa Albert and directed by Tim Hunter. The episode originally aired on the AMC channel in the United States on August 9, 2007.",
"title": ""
},
{
"docid": "51414886",
"text": "\"The Jet Set\" is the eleventh episode of the second season of the American television drama series \"Mad Men\". It was written by series creator Matthew Weiner and directed by Phil Abraham. The episode originally aired on AMC in the United States on October 12, 2008.",
"title": ""
},
{
"docid": "13819195",
"text": "\"Shoot\" is the ninth episode of the first season of the American television drama series \"Mad Men\". It was written by Chris Provenzano and series creator Matthew Weiner and was directed by Paul Feig. The episode originally aired on the AMC channel in the United States on September 13, 2007.",
"title": ""
},
{
"docid": "28681708",
"text": "\"Tomorrowland\" is the thirteenth and final episode of the fourth season of the American television drama series \"Mad Men\", and the 52nd overall episode of the series. It aired on the AMC channel in the United States on October 17, 2010. It was written by Jonathan Igla and Matthew Weiner and directed by Matthew Weiner.",
"title": ""
},
{
"docid": "35780472",
"text": "\"Lady Lazarus\" is the eighth episode of the fifth season of the American television drama series \"Mad Men\" and the 60th episode of the series overall. It was written by Matthew Weiner and directed by Phil Abraham. It originally aired on the AMC channel in the United States on May 6, 2012.",
"title": ""
},
{
"docid": "35876755",
"text": "\"Dark Shadows\" is the ninth episode of the fifth season of the American television drama series \"Mad Men\" and the 61st episode of the series overall. It was written by Erin Levy and directed by Scott Hornbacher and originally aired on the AMC channel in the United States on May 13, 2012.",
"title": ""
},
{
"docid": "28551368",
"text": "\"The Chrysanthemum and the Sword\" is the fifth episode of the fourth season of the American television drama series \"Mad Men\", and the 44th overall episode of the series. It was written by Erin Levy and directed by Lesli Linka Glatter, and it originally aired on the AMC channel in the United States on August 22, 2010.",
"title": ""
},
{
"docid": "35948696",
"text": "\"The Other Woman\" is the eleventh episode of the fifth season of the American television drama series \"Mad Men\" and the 63rd episode of the series overall. It is co-written by Semi Chellas and Matthew Weiner, and directed by Phil Abraham. It aired on AMC in the United States on May 27, 2012.",
"title": ""
},
{
"docid": "28681528",
"text": "\"The Beautiful Girls\" is the ninth episode of the fourth season of the American television drama series \"Mad Men\" and the 48th overall episode of the series. It first aired on the AMC channel in the United States on September 19, 2010. It was written by Dahvi Waller and Matthew Weiner and directed by Michael Uppendahl.",
"title": ""
},
{
"docid": "35894213",
"text": "\"Christmas Waltz\" is the tenth episode of the fifth season of the American television drama series \"Mad Men\" and the 62nd episode of the series overall. It is written by Victor Levin and Matthew Weiner, and directed by Michael Uppendahl. It originally aired on the AMC channel in the United States on May 20, 2012.",
"title": ""
}
] |
5ab47cb95542990594ba9c30
|
What city is the Clermont Longue, where The rock and roll band Low Cut Connie play, located?
|
[
{
"docid": "2446831",
"text": "The Clermont Lounge is Atlanta's first and longest continually operating strip club, opened in 1965. Located in the basement of the Clermont Motor Hotel at 789 Ponce De Leon Avenue, in the Poncey-Highland neighborhood, the Clermont has survived multiple attempts at being closed by the Atlanta city government, and has established a nationwide reputation for its kitschy atmosphere and unusual dancers. The Clermont has been featured on an episode of \"Insomniac with Dave Attell\", and celebrities including Marilyn Manson, Ashton Kutcher, Kid Rock, Skinny Lister, Lady Gaga, and Bombay Bicycle Club have been known to visit the Clermont when in Atlanta. Visitors to the Clermont usually alternate between a few handfuls of regulars and large numbers of college students, newcomers to town, and tourists lured in by tales of the Clermont's myriad charms.",
"title": ""
},
{
"docid": "43154528",
"text": "Low Cut Connie is an American rock and roll band based in Philadelphia, United States, which was formed in 2010. The band has been recognized by various media in the US for their records and high-energy live show, of which the \"Los Angeles Weekly\" said \"Their ferocious live show...is unmatched in all of rock right now.\" Frontman Adam Weiner plays a piano named \"Shondra,\" after a dancer at the Clermont Lounge in Atlanta.",
"title": ""
}
] |
[
{
"docid": "47597027",
"text": "Hi Honey is the third studio album by American rock and roll band Low Cut Connie. It was released on April 21, 2015 on Contender Records. Guests who appear on the album include Merrill Garbus of Tune-Yards, as well as Dean Ween and Greg Cartwright.",
"title": ""
},
{
"docid": "44077318",
"text": "Call Me Sylvia is the second album by rock and roll band Low Cut Connie, released on September 25, 2012. The band has described it as their first album recorded with the knowledge that they were really a band, whereas \"Get Out the Lotion,\" their debut album, was recorded under more informal circumstances. The song \"Boozophilia\" was released as a single from the album, accompanied by a music video which was filmed at Ray's Happy Birthday Bar in Philadelphia. In August 2015, \"Boozophilia\" was featured on Barack Obama's summer playlist.",
"title": ""
},
{
"docid": "43421950",
"text": "Get Out the Lotion is the debut album by Philadelphia-based indie rock band Low Cut Connie. The band self-released the album on January 1, 2011, after debuting it on New Year's Eve at Philadelphia's Old Swedes' Church.",
"title": ""
},
{
"docid": "4406181",
"text": "Big Hits and Nasty Cuts, The Best of Twisted Sister is a greatest hits compilation by American heavy metal band, Twisted Sister. It was released in 1992 by Atlantic Recording Corporation for the United States and by WEA International Inc. for the rest of the world. The track list consists solely of songs from their first three albums, omitting any material from \"Come Out and Play\" and \"Love Is for Suckers\", Except Australia where \"Bad boys of Rock 'n 'Roll\" was replaced with \"Be Chrool To Your Scuel\" from \"Come Out And Play\".",
"title": ""
},
{
"docid": "33007552",
"text": "Rock 'n' Roll Million Sellers is a studio album recorded by American entertainer Connie Francis. It was issued on the Contour label (2870 383) as \"Connie Francis Sings the Million Sellers\".",
"title": ""
},
{
"docid": "48916353",
"text": "What Do You Know About Rock 'N Roll? is the second studio album by Minneapolis shock rock band Slave Raider, released in the winter of 1988. It was the band's first album to be recorded for a major label. Despite snowballing success from a notoriously successful show at London's Marquee club, the album had little success outside of the bands dedicated fan base.",
"title": ""
},
{
"docid": "6557548",
"text": "\"Never\" is a song recorded by rock band Heart. It was written by Holly Knight, Gene Black and \"Connie\" (\"Connie\" is a combination of Ann Wilson, Nancy Wilson and Sue Ennis.) It was released as the second single from the band's self-titled 1985 album \"Heart\". The song is a rock song with an uplifting lyric to a person who has been discouraged by love. Like their previous single \"What About Love\", the music video for \"Never\" was placed in heavy rotation on MTV.",
"title": ""
},
{
"docid": "41385869",
"text": "Take the World by Storm is the debut studio album by the American glam metal band Slave Raider, released independently in 1986. In December 1987, the album was remixed and released to the public in 1988 through the Jive record label, suffering poor sales. The band did have a cult following in Minneapolis. The remixed \"Make Some Noise\" was released as a single and a promotional video was shot in The Twin Cities. In the remix, \"Make Some Noise\" was cut by around a minute and \"The Black Hole\" has a longer introduction. It was available scarcely on CD, cassette, and vinyl and was out of print until Divebomb Records reissued it and the band's sophomore release \"What Do You Know About Rock 'N Roll?\" in April 2015.",
"title": ""
},
{
"docid": "2200401",
"text": "Claremore Mound, a hill in present-day Rogers County, Oklahoma, is the site of the Battle of Strawberry Moon (a.k.a. Battle of Claremore Mound) where in 1817 a band Cherokees under Chief Spring Frog (\"Too-an-tuh\") wiped out Chief Clermont's band of Osage Indians. The hill is located north of Sageeyah near the south bank of the Verdigris River. The mound and the nearby city were both named in honor of Chief Clermont.",
"title": ""
},
{
"docid": "18520541",
"text": "Ming C. Lowe (born October 13, 1945) is an American painter of large-scale contemporary works on canvas and a fine art photographer. She emerged from the most embryonic 1960s rock 'n' roll scenes to become a unique voice in the Southern California desert, where her home was a gathering place for like-minded, creatively driven individuals of all genres of the arts seeking a place of peace and inspiration amid the turbulence of what was called the counter-culture.",
"title": ""
},
{
"docid": "1164711",
"text": "The Little Killers were an American rock and roll band who formed in New York City, New York, U.S. in 2001. They played punky garage rock inspired by the likes of Chuck Berry, the New York Dolls, and Johnny Burnette's Rock & Roll Trio.",
"title": ""
},
{
"docid": "23629873",
"text": "\"Rock & Roll Band\" is a song written by Tom Scholz and first released by the rock band Boston on the band's eponymous debut album. It is one of six songs Scholz worked on in his basement in 1974 and 1975 before Boston got its record contract, five of which eventually appeared on the \"Boston\" album. The \"Rock and Roll Band\" demo was finished in 1974, along with three of the six. However, Scholz had begun writing the song years earlier, in the early 1970s. The drum parts of this and other early Boston songs were developed by Jim Masdea, but this is the only song on the \"Boston\" album on which Masdea plays drums. Scholz plays clavinet and all the guitar parts, including bass guitar, and Brad Delp sings the vocals. Boston would consistently open with \"Rock and Roll Band\" while playing at live concerts.",
"title": ""
},
{
"docid": "25036",
"text": "Pub rock is a style of Australian rock and roll popular throughout the 1970s and 1980s, and still influencing contemporary Australian music in the 2000s (decade). The term came from the venues where most of these bands originally played — inner-city and suburban pubs. These often noisy, hot, small and crowded venues were not always ideal as music venues and favoured loud, simple songs based on drums and electric guitar riffs.",
"title": ""
},
{
"docid": "6956542",
"text": "Leviathan was a hard rock band that formed in New York City, N.Y. in 2001. During their career, they've played with Glenn Danzig, The Exploited, Nuclear Assault, Body Count, Jello Biafra, Clutch, Michale Graves, The Misfits, Hirax, Six Feet Under, and Testament, Agent Orange to name a few. Before their hiatus, Caustic Truths Magazine named the band alongside Sum 41 and The Hellacopters as one of the fifty \"hardest touring bands in the USA\" in 2004, and they're listed in the \"New Wave Of North American Heavy Metal\", published in 2005. By mixing traditional metal distortion and heavy beats with horror punk, funk, and hard rock, the band is very versatile within what are usually very exclusionary micro-genre factions of rock & roll, able to open for many varying headliners.",
"title": ""
},
{
"docid": "1747801",
"text": "The Low Spark of High Heeled Boys is the fifth studio album by English rock band Traffic, released in 1971. As with other Traffic albums, \"The Low Spark of High Heeled Boys\" featured different forms and offshoots of rock including jazz rock, progressive rock, as well as classic rock and roll. The name of the album's title track was suggested by the actor Michael J. Pollard.",
"title": ""
},
{
"docid": "10109240",
"text": "First Blood... Last Cuts is the first compilation album by the American heavy metal band W.A.S.P.. Released in 1993, it was the first time the song, \"Animal (Fuck Like a Beast)\", previously only released as a single in 1984, was released on an album. The album also included two new songs, \"Sunset and Babylon\" and \"Rock and Roll to Death\". \"Rock and Roll to Death\" was later released on \"Still Not Black Enough\", with \"Sunset and Babylon\" remaining exclusive to this CD, while others songs were re-mixed for the album.",
"title": ""
},
{
"docid": "5593842",
"text": "\"Dolls (Sweet Rock and Roll)\" (sometimes referred to as \"Dolls\" or \"Dolls (Sweet Rock n Roll)\") is a song by Scottish band Primal Scream. It was released as the second single from the band's eighth album, \"Riot City Blues\", on 7 August 2006, and reached number forty on the UK Singles Chart. It also features the vocals of Alison Mosshart (VV) from the British/American rock band, The Kills.",
"title": ""
},
{
"docid": "6533442",
"text": "Conny Bloom is the stage name for Ulf Conny Blomqvist, (born 23 November 1964 in Stockholm) who is a Swedish guitarist and songwriter. He is best known as the frontman for the funk metal band, Electric Boys. Bloom also served a stint as a guitarist of the Finnish rock band Hanoi Rocks and in Silver Ginger 5",
"title": ""
},
{
"docid": "10444128",
"text": "The Eskigümüş rock cut monastery, located off the Kayseri-Niğde road near to the city of Niğde in Turkey, is famed for having what is believed to be the only fresco with a smiling Theotokos.",
"title": ""
},
{
"docid": "25121285",
"text": "The Blue Angel is a nightclub in Liverpool, England. It is located where Seel Street meets Berry Street in Liverpool City Centre. It is a venue in Liverpool in which the Beatles, Rolling Stones, Bob Dylan and many other bands played at in the 1960s. It was historically a jazz club, but it now plays pop music.",
"title": ""
},
{
"docid": "1355368",
"text": "The Templars are an Oi! band formed in Long Island, New York in April 1991. Composed of black and white members, their musical influences include Oi!, punk rock, glam rock and rock and roll. They have tended to purposely use low-quality recording techniques (their Acre Studios is a garage).",
"title": ""
},
{
"docid": "23722277",
"text": "Long Hair In Three Stages is the debut full-length studio album by the Chicago-based experimental rock quartet U.S. Maple. The band formed in early 1995 seeking to \"deconstruct rock, only to \"erase rock and roll entirely from [their] collective minds\" and \"then set out to devise a working method for reorganizing the rock and rock, keeping what we feel areits most important core elements.\" After recording a debut single, they recorded the album in late 1995 at the Solid Sound Studios in Illinois with producer Jim O'Rourke. It was O'Rourke's first recording session with a rock band. The album is often said to \"deconstruct\" rock music, and in the words of Allmusic, contains \"angular guitar attacks, odd skronks, jazzy tones, and a generally deconstructive approach to music into a sound of unparalleled idiosyncrasy.\" It is also characterized by the unique set up of Todd Rittmann's \"low\" guitar complimenting Mark Shippy's \"high\" guitar.",
"title": ""
},
{
"docid": "6338932",
"text": "Roll with It is the fifth solo studio album by English blue-eyed soul artist Steve Winwood, released on 21 June 1988. It topped the album charts in the United States, and has sold over three million copies. The title cut topped the pop and rock singles charts. The success led the subsequent songs to serve as singles, \"Don't You Know What the Night Can Do?\" and \"Holding On\". \"Don't You Know What the Night Can Do?\" had been written by Winwood to be featured in an ad campaign for Michelob which began running on American television on the day of the \"Roll With It\" album's US release. Two other tracks from \"Roll With It\": \"Hearts on Fire\" and \"Put on Your Dancing Shoes\", also achieved radio airplay.",
"title": ""
},
{
"docid": "38696417",
"text": "Hay Mucho Rock'n Roll is a compilation series by Spanish rock band Platero y Tú. Most of the songs are re-recorded and remastered due to the low quality audio in previous releases.",
"title": ""
},
{
"docid": "3208972",
"text": "Clermont Foot 63 (Occitan: \"Clarmont d'Auvèrnhe\"; commonly referred to as Clermont Foot or simply Clermont) is a French association football club based in Clermont-Ferrand. The first incarnation of the club was formed in 1911 and the current club was created in 1990 as a result of a merger. Clermont currently play in Ligue 2, the second level of French football having achieved promotion to the league after winning the 2006–07 edition of the Championnat National. The club plays its home matches at the Stade Gabriel Montpied located within the city. Clermont is managed by Corinne Diacre and captained by Cameroonian Eugène Ekobo.",
"title": ""
},
{
"docid": "2578184",
"text": "\"Rock 'n' Roll Star\" is a song by English rock band Oasis. It is the opening track from their record breaking debut album, \"Definitely Maybe\". Like the majority of the band's songs from this era, it was written by lead guitarist Noel Gallagher. Noel said that \"Rock 'n' Roll Star\" was one of only three songs in which he wanted to say something: \"I've pretty much summed up everything I wanted to say in \"Rock 'n' Roll Star\", \"Live Forever\" and \"Cigarettes & Alcohol\", after that I'm repeating myself, but in a different way\". It became a fan favourite and was often played to close the band's gigs.",
"title": ""
},
{
"docid": "38973382",
"text": "The Sex, Love and Rock 'n' Roll Tour was a concert tour by Social Distortion. It was on this tour, that they have played the most concerts. It was also the first tour where the band started adding old country songs like \"Send Her Back\" to their setlist. At one point, they played \"Moral Threat\", a song they haven't performed in more than 20 years. They also premiered a new song, \"Diamond In the Rough\" in London. They also played another song from 1992, a forgotten song which was originally titled \"Ready for Love\". They rearranged the song differently and renamed it \"That's Alright\". It was also their first time in London in seven years. At first, the band had Rancid (band) bassist Matt Freeman the fill in for the recently departured John Maurer. About late 2004, Matt Freeman left the band and current bassist Brent Harding joined the band.",
"title": ""
},
{
"docid": "44464909",
"text": "The Masroor Rock Cut Temple or Himalayan Pyramid is a complex of temples located in Masroor (or Masrur) in Kangra Valley, which is 40 km from Kangra city in Kangra district of the Indian state of Himachal Pradesh. It is now known as 'Thakurwada', meaning \"Vaishnavite temples\". It is a complex of monolithic rock cut temples, in shikhara (raising tower) style of classical Indian architectural style, dated by art historians to 6–8th centuries. Such an architectural style is unique to the northern part of India while there are many places in western and southern India where such rock-cut structures exist at number of locations. There is a lake or pond called Masroor lake in front of this edifice which shows partial reflection of the temples. A legend attributes its construction to the Pandavas of Mahabharata fame who resided here during their \"incognito\" exile (Ajnatavasa) from their kingdom.",
"title": ""
},
{
"docid": "43100452",
"text": "\"Rock 'n' Roll Cities\" is a song by the British rock group, the Kinks. The song appeared on the band's 1986 album, \"Think Visual\", and, unlike most other Kinks songs, it was written by Dave Davies rather than his brother, Ray.",
"title": ""
},
{
"docid": "50321621",
"text": "Jeremy & The Harlequins are a five-piece rock band from New York City. Drawing influence from classic ‘50s and ‘60s rock & roll, they released their first album in 2015 after two years of recording. The members of the band are Jeremy Fury (lead vocals), Craig Bonich (guitar), Patrick Meyer (guitar), Steve Fury (drums), and Bobby Ever (bass guitar). After releasing their first album, \"American Dreamer\" (2015), Jeremy & The Harlequins signed with Yep Roc Records. In August 2016, the label released their second album, \"Into the Night.\"<br> Jeremy and his brother, drummer Steve Fury, had played music together for years (they cut an album in 2006 as members of the group We Are the Fury, and when Steve returned from a sojourn in Europe, he soon teamed up with Jeremy and Craig. <br>",
"title": ""
}
] |
5a81c9ac5542990a1d231eb8
|
Benjamin Sulsky plays poker under the aliases Sauce123 and Sauce1234 on Full Tilt Poker on PokerStars an online poker cardroom owned by what group?
|
[
{
"docid": "44612329",
"text": "Benjamin Sulsky (born November 22, 1987) is an American professional poker player from Durham, New Hampshire, currently considered one of the best online cash game players in the world. Sulsky plays under the aliases Sauce123 on PokerStars and Sauce1234 on Full Tilt Poker. He specializes in Pot Limit Omaha (PLO) and No-Limit hold'em (NLHE).",
"title": ""
},
{
"docid": "3528947",
"text": "PokerStars is an online poker cardroom owned by The Stars Group. It can be accessed through downloadable poker clients for the Windows, macOS, Android and iOS.",
"title": ""
}
] |
[
{
"docid": "3817869",
"text": "Full Tilt Poker is an Irish online poker card room and online casino that opened in June 2004. Formerly privately owned by Tiltware, LLC and later by the Rational Entertainment Group, the site was acquired by The Stars Group (then known as Amaya Gaming Group) in a deal where Amaya acquired all of Rational's assets, including PokerStars. A statement by Amaya said the takeover would not affect the activities of Full Tilt Poker. The deal was closed on August 1, 2014.",
"title": ""
},
{
"docid": "44613210",
"text": "Jens \"Jeans89\" Kyllönen (born 1989) is a Finnish professional poker player who won the European Poker Tour Copenhagen in February 2009. Kyllönen was the second Finnish EPT winner since Patrik Antonius's victory in 2005. He is an online cash game specialist and plays under the aliases Jeans89 on PokerStars and Ingenious89 on Full Tilt Poker.",
"title": ""
},
{
"docid": "5853494",
"text": "Mark Vos (born 20 October 1983), also known as 'pokerbok', is a professional poker player from Australia. Vos was born in Cape Town, South Africa, and attended Waldorf High School in Constantia. He excelled at mathematics olympiads while in high school, and represented his province in the interprovincial olympiad. Vos permanently deferred his actuarial studies at Macquarie University, to play poker full-time. Starting out online with limit hold'em in mid-2004, Vos soon turned his attention to no-limit games, and in short time, earned a reputation as being one of the world's top online poker players, such that he can often be found playing in the most expensive cash games and tournaments online. When not travelling the world playing poker, Vos plans to divide his time between Australia and South Africa. In January 2006, Vos finished 8th in the main event of the Crown Australian Poker Championship, winning A$83,600. As of May 2006, Vos represents the Full Tilt Poker online poker cardroom as a friend of Full Tilt Poker. His name is reflected in red on Full Tilt tables.",
"title": ""
},
{
"docid": "31526583",
"text": "United States v. Scheinberg, 10 Cr. 336 (2011), is a United States federal criminal case against the founders of the three largest online poker companies, PokerStars, Full Tilt Poker and Cereus (Absolute Poker/Ultimatebet), and a handful of their associates, which alleges that the defendants violated the Unlawful Internet Gambling Enforcement Act (UIGEA) and engaged in bank fraud and money laundering to process transfers to and from their customers. A companion civil case, United States v. PokerStars, et al., 11 Civ. 2564 (2011), includes Full Tilt and Cereus as defendants and seeks the recovery of forfeiture equalling approximately $3 billion in assets belonging to the companies. After the indictment was unsealed on April 15, 2011, a date quickly dubbed Black Friday by the online poker community, PokerStars and Full Tilt stopped offering real money play to their United States customers.",
"title": ""
},
{
"docid": "49792361",
"text": "Alexander Kostritsyn (born 1986) is a Russian professional poker player considered among the best online cash game players in the world. Kostritsyn plays under the alias joiso on PokerStars and PostflopAction on Full Tilt Poker.",
"title": ""
},
{
"docid": "26264677",
"text": "Viktor Blom (born 26 September 1990) is a Swedish high-stakes online poker player, best known by the online poker name Isildur1. His rise to fame drew considerable attention around the poker world in late 2009, when he took part in all ten of the largest pots in online poker history. In December 2010, it was announced that then-anonymous Isildur1 had joined Team PokerStars Pro. Blom's identity was revealed by PokerStars on January 8, 2011, at the PokerStars Caribbean Adventure. Blom parted ways with PokerStars in August 2012 and was quickly signed-up by Full Tilt Poker on October 15, 2012, along with rival high-stakes player Tom Dwan.",
"title": ""
},
{
"docid": "44591440",
"text": "Alexander Millar (born 29 July 1985) is a British professional poker player who specializes in online high-stakes heads-up cash games, specifically No Limit Hold'em, playing under the alias Kanu7 on PokerStars and IReadYrSoul on Full Tilt Poker.",
"title": ""
},
{
"docid": "14442986",
"text": "The Full Tilt Online Poker Series (FTOPS) is an online poker tournament series sponsored by Full Tilt Poker. It was established in August 2006",
"title": ""
},
{
"docid": "44810948",
"text": "Vladimir Shchemelev (born 1972 or 1973) is a Russian banker and professional poker player from St. Petersburg, Russia. He is an online cash game player earning over $1,600,000 playing under the alias GVOZDIKA55 on PokerStars and NEKOTYAN on Full Tilt Poker. He specializes in mixed games.",
"title": ""
},
{
"docid": "6941845",
"text": "Johnny Lodden (born 1 June 1985 in Jørpeland, Norway) is a Norwegian professional poker player prominently known for his online success. He frequently played under the alias \"bad_ip\" on Prima network online high-stakes games (up to $40,000 buy-in NLHE), and for a brief time he was considered the biggest winner in the largest online cash games in the world (before Full Tilt Poker expanded to include larger games). Lodden has also been known to occasionally play on PokerStars under the alias \"Lars-Magne\". He is sponsored by PokerStars today, and will play for them in the forthcoming EPT events.",
"title": ""
},
{
"docid": "2534387",
"text": "The World Championship of Online Poker (WCOOP) is an online poker tournament series sponsored by PokerStars. It is played on the PokerStars site in September.",
"title": ""
},
{
"docid": "8094431",
"text": "Full Tilt Poker Championship at Red Rock (also FullTiltPoker.Net Championship at Red Rock) was a seven-week televised shootout poker tournament played at the Red Rock Resort Spa and Casino in Summerlin near Las Vegas, Nevada. The tournament was sponsored by online poker website Full Tilt Poker and aired by Fox Sports Net. In each of the first six episodes, six professional poker player affiliated with Full Tilt Poker played a single-table freezeout tournament. The winner of each freezeout won US$25,000 and advanced to the seven-handed final table. The seventh seat at the final table was filled by Stefan Rehn, an Internet qualifier. Tournaments featured a speed poker format, with players having 30 seconds to act on their hands with one 60-second time extension per match.",
"title": ""
},
{
"docid": "17073343",
"text": "Thomas Dwan Jr. (born July 30, 1986) is an American professional poker player who played online in the highest-stakes No-Limit Texas hold 'em and Pot-Limit Omaha games, primarily on Full Tilt Poker under the screen name \"durrrr\". Dwan has won prize money in live poker tournaments and has appeared on NBC's \"National Heads-Up Poker Championship\", the fourth, fifth, sixth, and seventh seasons of \"Poker After Dark\", the third, fourth and fifth seasons of Full Tilt Poker's \"Million Dollar Cash Game\", and the fifth and sixth seasons of GSN's \"High Stakes Poker\".",
"title": ""
},
{
"docid": "31091860",
"text": "Peter Jetten (born March 26, 1985) is a Canadian professional poker player. Jetten is known for playing online poker under the screen name \"Apathy\". He has over $2,000,000 in live poker tournament winnings, and in early 2011 signed a sponsorship deal with Full Tilt Poker.",
"title": ""
},
{
"docid": "2403789",
"text": "Prahlad S. Friedman (born May 20, 1978) is an American professional poker player from Los Angeles, California. He has played under the screen names \"Spirit Rock\" on Full Tilt Poker, \"Mahatma\" on Ultimate Bet, \"Zweig\" on Prima Network, and \"Prefontaine\" on PokerStars.",
"title": ""
},
{
"docid": "18862338",
"text": "Planet Poker was the first real-money cardroom for playing online poker, opening in 1998.",
"title": ""
},
{
"docid": "13902524",
"text": "Cereus Poker Network was an online poker network comprising Absolute Poker and Ultimate Bet. The site is now insolvent and not processing player withdrawals. Cereus is owned by a private company, Blanca Games. Blanca Games bought all Network assets in August 2010 from Tokwiro Enterprises. The Cereus network was one of the world's ten largest online poker cardrooms prior to losing the majority of its player base in the wake of the April 15, 2011 online poker indictments.",
"title": ""
},
{
"docid": "44748697",
"text": "David Benefield (born May 17, 1986) is an American professional poker player considered a high-stakes online cash game specialist who has earnings of over $900,000 from online winnings playing under his name on Full Tilt Poker. He made the World Series of Poker Main Event final table in 2013 finishing 8th.",
"title": ""
},
{
"docid": "31419508",
"text": "Daniel Cates (born November 14, 1989) also known as jungleman12 or w00ki3z. is a professional poker player from the United States, considered to be one of the best heads-up No Limit Texas Hold 'em players in the world. As of 2014, his online cash game earnings at Full Tilt Poker and PokerStars are over $11,000,000. In 2010, he won over $5,000,000 making him the biggest winner for the year.",
"title": ""
},
{
"docid": "22050544",
"text": "The Spring Championship of Online Poker - All Stakes (SCOOP) is an online poker tournament series sponsored by PokerStars. It was established in 2009.",
"title": ""
},
{
"docid": "12186343",
"text": "The Poker Players Alliance (PPA) is an American nonprofit Interest group formed to emphasize the rights of poker players, and to protect the players' liberties.\" The PPA formed to serve as an advocacy group to Washington to establish rights and protections for U.S. poker players. Within the first year of its existence, the PPA garnered over 600,000 members. In April 2008, the PPA claimed to have signed up its one millionth member. Membership growth has been due in part to promotional activities by online poker cardrooms like Party Poker.",
"title": ""
},
{
"docid": "47453288",
"text": "The PlayWCOOP (PlayWorld Championship of Online Poker) is a series of poker tournaments taking place every year in online poker room PokerStars.net. It is dedicated to amateur players and is considered the largest Play Money series of tournaments in the world. Its creation was based on WCOOP (World Championship of Online Poker), which also occurs in the PokerStars room. The first edition of PlayWCOOP took place in 2014 and featured 66 events.",
"title": ""
},
{
"docid": "1296513",
"text": "The European Poker Tour (EPT) was a series of poker tournaments similar to those in the World Poker Tour (WPT), created by John Duthie, winner of the inaugural Poker Million tournament. It began in 2004 as part of the worldwide explosion in Texas Hold 'em popularity. Since 2011 the EPT has been sponsored and wholly owned and controlled by PokerStars the online casino and taped by Sunset + Vine for television broadcast across Europe.",
"title": ""
},
{
"docid": "6391613",
"text": "Steve Paul-Ambrose (born 1983) is a poker player from Ontario, Canada who won the 2006 PokerStars Caribbean Poker Adventure (PCA), earning $1,388,600. At the time a World Poker Tour event, he won his PCA entry through an online $102 satellite tournament on PokerStars. He used to be a member of PokerStars Team Pro.",
"title": ""
},
{
"docid": "14528322",
"text": "TheV0id is the screen name used by an unnamed poker player who won the PokerStars 2007 World Championship of Online Poker, beating a field of 2998 players to the first place and $1,378,331.00 on October 1, 2007, then the largest ever online poker prize.",
"title": ""
},
{
"docid": "6261786",
"text": "Mike Schneider (born November 29, 1983) is a professional poker player from Eagan, Minnesota who, at the age of 22, won the \"PartyPoker.com Million V\" for $1,000,000. He is also a member of Team CardRunners a group of sponsored professional poker players on Full Tilt Poker.",
"title": ""
},
{
"docid": "37026945",
"text": "Andrew Feldman (born 16 July 1987, Watford) is an English poker player. He started playing poker on the Internet when he was 18 through his older brother and then received sponsorship from Full Tilt Poker.",
"title": ""
},
{
"docid": "25735006",
"text": "Alan \"Boston\" Dvorkis is an online poker professional playing predominantly at Full Tilt Poker. He is a specialist at Seven-card stud. He has over a decade of experience at the WSOP, where he has achieved many money finishes, including a runner-up finish in a Seven-card stud event. Boston claims to be an expert on handicapping college basketball. In 2007, he appeared on Poker After Dark.",
"title": ""
},
{
"docid": "27682078",
"text": "John-Paul Kelly, known as J.P. Kelly, is a professional poker player from Aylesbury, England. Kelly is a two time World Series of Poker bracelet winner, having won the 2009 World Series of Poker $1,500 Pot Limit Hold'em event in Las Vegas and then later that same year won another bracelet at the 2009 World Series of Poker Europe in the £1,000 No Limit Hold'em event in London. He was a member of team PokerStars Pro, playing under the screen name \"jp Kelly\" However, his association with PokerStars has since ended.",
"title": ""
},
{
"docid": "4812187",
"text": "The PokerStars Caribbean Adventure is an annual televised poker tournament. The event was first held in 2004 and was originally co-sponsored by PokerStars and the World Poker Tour. In 2008, the event moved from the WPT to the European Poker Tour. In 2010, the event was moved again and served as the inauagural event of the North American Poker Tour. In 2017 the tournament was the inaugural event of the new PokerStars Championship tour and renamed PokerStars Championship Bahamas. The name was changed back to the PCA for 2018 and the buy-in restored to $10,000.",
"title": ""
}
] |
9
|
32% of liver transplantation programs required patients to discontinue methadone treatment in 2001.
|
[
{
"docid": "44265107",
"text": "ContextChronic hepatitis C is the leading cause for liver transplantation in the United States. Intravenous drug use, the major risk factor, accounts for approximately 60% of hepatitis C virus transmission. Information from the United Network of Organ Sharing (UNOS) does not address substance use among liver transplantation patients. ObjectiveTo identify addiction-related criteria for admission to the UNOS liver transplantation waiting list and posttransplantation problems experienced by patients who are prescribed maintenance methadone. Design, Setting, and ParticipantsMail survey of all 97 adult US liver transplantation programs (belonging to UNOS) in March 2000 with telephone follow-up conducted in May and June 2000.Main Outcome MeasuresPrograms' acceptance and management of patients with past or present substance use disorder. ResultsOf the 97 programs surveyed, 87 (90%) responded. All accept applicants with a history of alcoholism or other addictions, including heroin dependence. Eighty-eight percent of the responding programs require at least 6 months of abstinence from alcohol; 83% from illicit drugs. Ninety-four percent have addiction treatment requirements. Consultations from substance abuse specialists are obtained by 86%. Patients receiving methadone maintenance are accepted by 56% of the responding programs. Approximately 180 patients receiving methadone maintenance are reported to have undergone liver transplantation. ConclusionsMost liver transplantation programs have established policies for patients with substance use disorders. Opiate-dependent patients receiving opiate replacement therapy seem underrepresented in transplantation programs. Little anecdotal evidence for negative impact of opiate replacement therapy on liver transplantation outcome was found. Policies requiring discontinuation of methadone in 32% of all programs contradict the evidence base for efficacy of long-term replacement therapies and potentially result in relapse of previously stable patients.",
"title": "Liver transplantation and opioid dependence."
}
] |
[
{
"docid": "25182647",
"text": "Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) are rare but major disorders of the third trimester of pregnancy. Over a 10-year period, 46 women (median age, 30 years; range, 17-41 years) developed hepatic dysfunction severe enough to require transfer to our Liver Failure Unit. Three quarters of the women were nulliparous, and 5 had twin pregnancies; the median gestational age was 35 weeks (range, 24-40 weeks). At admission, 32 patients (70%) were preeclamptic and 21 (46%) were encephalopathic and/or ventilated. Thirty-two patients (70%) had clinical features and laboratory values consistent with AFLP, and 7 (15%) had HELLP syndrome. One patient had preeclamptic liver rupture requiring liver transplantation. In 6 other patients, causes of severe liver dysfunction unrelated to pregnancy were found. Infectious complications occurred in 17 of the patients with AFLP (53%) and in 2 of those with HELLP syndrome (29%). Major intra-abdominal bleeding occurred in 12 women (10 with AFLP), 9 of whom required laparotomies for clot evacuation. Four patients with AFLP (12.5%) had a fatal outcome, with a corresponding perinatal mortality rate of 9%. There were no maternal or perinatal deaths associated with HELLP syndrome. In contrast to results of many previous studies, the results of this large series suggest a relatively favorable maternal and perinatal outcome in severe AFLP and HELLP syndrome. Further improvements in outcome are likely to be achieved through the prevention of the bleeding and infectious complications associated with these disorders.",
"title": "Maternal and perinatal outcome in severe pregnancy-related liver disease."
},
{
"docid": "24700152",
"text": "Injection drug users (IDUs) are at increased risk for HIV, viral hepatitis, and tuberculosis, and making up more than a quarter of the incarcerated population in the United States. Methadone maintenance treatment of opiate addiction is highly effective at reducing drug use, drug-related criminal activity, and risk of HIV transmission. Recently released inmates are at particularly high risk for overdose and disease transmission. Linkage to methadone treatment immediately upon release from incarceration is a promising opportunity to combat disease transmission, facilitate reentry into the community, and reduce recidivism.",
"title": "Linkage with methadone treatment upon release from incarceration: a promising opportunity."
},
{
"docid": "8190282",
"text": "CONTEXT Noninvasive ventilation (NIV) has been associated with lower rates of endotracheal intubation in populations of patients with acute respiratory failure. OBJECTIVE To compare NIV with standard treatment using supplemental oxygen administration to avoid endotracheal intubation in recipients of solid organ transplantation with acute hypoxemic respiratory failure. DESIGN AND SETTING Prospective randomized study conducted at a 14-bed, general intensive care unit of a university hospital. PATIENTS Of 238 patients who underwent solid organ transplantation from December 1995 to October 1997, 51 were treated for acute respiratory failure. Of these, 40 were eligible and 20 were randomized to each group. INTERVENTION Noninvasive ventilation vs standard treatment with supplemental oxygen administration. MAIN OUTCOME MEASURES The need for endotracheal intubation and mechanical ventilation at any time during the study, complications not present on admission, duration of ventilatory assistance, length of hospital stay, and intensive care unit mortality. RESULTS The 2 groups were similar at study entry. Within the first hour of treatment, 14 patients (70%) in the NIV group, and 5 patients (25%) in the standard treatment group improved their ratio of the PaO2 to the fraction of inspired oxygen (FIO2). Over time, a sustained improvement in PaO2 to FIO2 was noted in 12 patients (60%) in the NIV group, and in 5 patients (25%) randomized to standard treatment (P = .03). The use of NIV was associated with a significant reduction in the rate of endotracheal intubation (20% vs 70%; P = .002), rate of fatal complications (20% vs 50%; P = .05), length of stay in the intensive care unit by survivors (mean [SD] days, 5.5 [3] vs 9 [4]; P = .03), and intensive care unit mortality (20% vs 50%; P = .05). Hospital mortality did not differ. CONCLUSIONS These results indicate that transplantation programs should consider NIV in the treatment of selected recipients of transplantation with acute respiratory failure.",
"title": "Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial."
},
{
"docid": "16737210",
"text": "CONTEXT Blood type and crossmatch incompatibility will exclude at least one third of patients in need from receiving a live donor kidney transplant. Kidney paired donation (KPD) offers incompatible donor/recipient pairs the opportunity to match for compatible transplants. Despite its increasing popularity, very few transplants have resulted from KPD. OBJECTIVE To determine the potential impact of improved matching schemes on the number and quality of transplants achievable with KPD. DESIGN, SETTING, AND POPULATION We developed a model that simulates pools of incompatible donor/recipient pairs. We designed a mathematically verifiable optimized matching algorithm and compared it with the scheme currently used in some centers and regions. Simulated patients from the general community with characteristics drawn from distributions describing end-stage renal disease patients eligible for renal transplantation and their willing and eligible live donors. MAIN OUTCOME MEASURES Number of kidneys matched, HLA mismatch of matched kidneys, and number of grafts surviving 5 years after transplantation. RESULTS A national optimized matching algorithm would result in more transplants (47.7% vs 42.0%, P<.001), better HLA concordance (3.0 vs 4.5 mismatched antigens; P<.001), more grafts surviving at 5 years (34.9% vs 28.7%; P<.001), and a reduction in the number of pairs required to travel (2.9% vs 18.4%; P<.001) when compared with an extension of the currently used first-accept scheme to a national level. Furthermore, highly sensitized patients would benefit 6-fold from a national optimized scheme (2.3% vs 14.1% successfully matched; P<.001). Even if only 7% of patients awaiting kidney transplantation participated in an optimized national KPD program, the health care system could save as much as $750 million. CONCLUSIONS The combination of a national KPD program and a mathematically optimized matching algorithm yields more matches with lower HLA disparity. Optimized matching affords patients the flexibility of customizing their matching priorities and the security of knowing that the greatest number of high-quality matches will be found and distributed equitably.",
"title": "Kidney paired donation and optimizing the use of live donor organs."
},
{
"docid": "37699461",
"text": "Beta-cell replacement is considered to be the most promising approach for treatment of type 1 diabetes. Its application on a large scale is hindered by a shortage of cells for transplantation. Activation of insulin expression, storage, and regulated secretion in stem/progenitor cells offers novel ways to overcome this shortage. We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells. FH cells possess a considerable replication capacity, and this was further extended by introduction of the gene for the catalytic subunit of human telomerase. Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose. When transplanted into hyperglycemic immunodeficient mice, the cells restored and maintained euglycemia for prolonged periods. Quantitation of human C-peptide in the mouse serum confirmed that the glycemia was normalized by the transplanted human cells. This approach offers the potential of a novel source of cells for transplantation into patients with type 1 diabetes.",
"title": "Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells."
},
{
"docid": "26067999",
"text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l",
"title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement"
},
{
"docid": "21186109",
"text": "Low case detection rates of new smear-positive pulmonary tuberculosis (PTB) patients globally are a cause for concern. The aim of this study was to determine for patients registered for TB in Malawi the number and percentage who lived in a neighbouring country and the registration, recording and reporting practices for these 'foreign' patients. All 44 non-private hospitals, which register and treat all TB patients in the public health sector in Malawi, were visited. Ten (23%) hospitals in 2001 and 14 (32%) in 2002 maintained a separate register for cross-border TB cases. Patients recorded in these registers were not formally reported to the Malawi National TB Programme (NTP), the neighbouring country's NTP, nor to WHO. They therefore constitute missing cases. In Malawi, the number of cross-border new smear-positive PTB cases was 77 in 2001 and 91 in 2002, constituting about 3% of missing smear-positive cases in those hospitals that maintain cross-border registers and about 1% of missing cases nationally.",
"title": "The missing cases of tuberculosis in Malawi: the contribution from cross-border registrations."
},
{
"docid": "24916604",
"text": "BACKGROUND The use of bisphosphonates for the prevention of skeletal related events in women with bone metastases from breast cancer is well established. We undertook an evaluation of bisphosphonate use in clinical practice in three Canadian cancer centres. In addition we assessed whether or not physicians at these centres are following their local treatment guidelines and funding policies. METHODS Charts and electronic files of patients who had received either clodronate or pamidronate at any time between January 2000 and December 2001 at three Canadian cancer centres were retrospectively reviewed. RESULTS There has been a marked improvement in the time between the diagnosis of bone metastases and the commencement of bisphosphonates from a median of 155 days in 1998 to 24 days in 2001. However, despite a local funding policy requiring that oral clodronate be the first bisphosphonate used, this was the case in only 67% of patients. In addition, despite one centre's guidelines recommending that bisphosphonates be stopped once the patient was progressing, 90% of their patients remained on bisphosphonates until they died. CONCLUSIONS A considerable amount of effort is spent on the creation of \"evidence based\" treatment guidelines. Funding agencies develop policies based on these treatment guidelines, but often funding is more restrictive than the treatment guideline would suggest. It is clear from this review that physicians still appear to manage a substantial proportion of patients outside of funding policies, but within evidence based recommendations. Therefore, a need exists for either the creation of guidelines and policies that physicians will follow or the implementation of methods to ensure that restrictive policies are actually followed.",
"title": "Do physicians follow systemic treatment and funding policy guidelines?"
},
{
"docid": "14647747",
"text": "Strategies to prevent organ transplant rejection whilst minimizing long-term immunosuppression are currently under intense investigation with regulatory T cells (Tregs) nearing clinical application. The clinical trial, ThRIL, recently commenced at King's College London, proposes to use Treg cell therapy to induce tolerance in liver transplant recipients, the success of which has the potential to revolutionize the management of these patients and enable a future of drug-free transplants. This is the first report of the manufacture of clinical grade Tregs from prospective liver transplant recipients via a CliniMACS-based GMP isolation technique and expanded using anti-CD3/CD28 beads, IL-2 and rapamycin. We report the enrichment of a pure, stable population of Tregs (>95% CD4(+)CD25(+)FOXP3(+)), reaching adequate numbers for their clinical application. Our protocol proved successful in, influencing the expansion of superior functional Tregs, as compared to freshly isolated cells, whilst also preventing their conversion to Th17 cells under pro-inflammatory conditions. We conclude with the manufacture of the final Treg product in the clinical research facility (CRF), a prerequisite for the clinical application of these cells. The data presented in this manuscript together with the much-anticipated clinical results from ThRIL, will undoubtedly inform the improved management of the liver transplant recipient.",
"title": "Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation"
},
{
"docid": "3578380",
"text": "Importance Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. Objectives To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Design and Setting Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Exposures Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time. Main Outcomes and Measures A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. Results From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near–regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Conclusions and Relevance Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near–regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.",
"title": "Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010"
},
{
"docid": "21859699",
"text": "Providing transplantation opportunities for patients with incompatible live donors through kidney paired donation (KPD) is seen as one of the important strategies for easing the crisis in organ availability. It has been estimated that an additional 1000-2000 transplants per year could be accomplished if a national KPD program were implemented in the United States. While most of these transplants could be arranged within the participants' local or regional area, patients with hard-to-match blood types or broad HLA sensitization would benefit from matching across larger geographic areas. In this case, either patients or organs would need to travel in order to obtain maximum benefit from a national program. In this study, we describe how a triple KPD enabled a highly sensitized patient (PRA 96%) to receive a well-matched kidney from a live donor on the opposite coast. The kidney was removed in San Francisco and transported to Baltimore where it was reperfused 8 h later. The patient had prompt function and 1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint for solving some of the complexities that are inherent in the implementation of a national KPD program in a large country like the United States.",
"title": "Successful three-way kidney paired donation with cross-country live donor allograft transport."
},
{
"docid": "25816994",
"text": "BACKGROUND Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.",
"title": "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial."
},
{
"docid": "7034001",
"text": "Donor kidney exchange is an established method to overcome incompatibility of donor-recipient pairs (DRP). A computerized algorithm was devised to exchange donor kidney and was tested in a multicenter setting. The algorithm was made according to the consensus of participating centers. It makes all possible exchange combinations not only between two incompatible DRP but also circularly among three DRP and selects an optimum set of exchange combinations, considering several factors that can affect the outcome of the exchanged transplant. The algorithm was implemented as a web-based program, and matching was performed five times. Fifty-three DRP were enrolled from five transplant centers. The numbers of DRP that were enrolled in each matching were 38 (25:13), 39 (34:5), 33 (31:2), 32 (28:4), and 34 (30:4) (carryover:newcomer). The numbers of generated exchange combinations were 4:11, 3:17, 2:12, 2:3, and 2:3 (two-pair exchange:three-pair exchange), and the numbers of DRP in selected exchange combinations were six, 12, six, five, and four in each matching. The numbers of DRP with blood type O recipient or AB donor were five and one, respectively, in selected exchange combinations. Six DRP of two-pair exchange combinations and six DRP of three-pair exchange combinations underwent transplantation successfully. Computerized algorithm of donor kidney exchange was tried not only between two incompatible DRP but also circularly among three DRP. It showed that the algorithm has potential to improve the outcome of donor kidney exchange, especially for disadvantaged DRP with blood type O recipients or AB donors.",
"title": "Outcome of multipair donor kidney exchange by a web-based algorithm."
},
{
"docid": "39985001",
"text": "We retrospectively studied the long-term (2-year) outcome of 50 consecutive patients admitted to our inpatient headache program because of chronic daily headache (CDH) associated with the overuse of analgesics, ergotamine, or both. They had been detoxified, given repetitive intravenous dihydroergotamine (IV DHE) and prophylactic medications as part of the program, and had become headache-free on this regimen. At the time of admission, 37 of the 50 patients had transformed migraine (TM), 12 had new daily persistent headache (NDPH), and 1 had chronic tension-type headache; 29 of the patients with TM, 7 of those with NDPH, and the single patient with chronic tension-type headache had coexistent migraine. Substances abused, alone or in combination, included: caffeine in 39 patients (av. 441 mg/d), acetaminophen in 32 (av. 2187 mg/d), aspirin in 24 (av. 1807 mg/d), ibuprofen in 9 (av. 1156 mg/d), narcotics in 7 (av. 10.1 mg morphine equivalents/d) and ergotamine in 11 (av. 2.3 mg/d). Twenty patients were using preventive medication at the time of admission. Follow-up evaluations were performed at 3, 6, 12, and 24 months after discharge. Forty-three patients were analyzed at 3 months. Of these, 44% had an excellent or good result and 28% a fair result; 3 were overusing analgesics. At 24 months, 39 patients were analyzed: 59% had a good or excellent result and 28% a fair result; 5 were overusing analgesics, 4 of whom were doing poorly.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Chronic daily headache: long-term prognosis following inpatient treatment with repetitive IV DHE."
},
{
"docid": "3471191",
"text": "IMPORTANCE The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab. OBJECTIVE To characterize the association of pembrolizumab with tumor response and overall survival among patients with advanced melanoma. DESIGN, SETTINGS, AND PARTICIPANTS Open-label, multicohort, phase 1b clinical trials (enrollment, December 2011-September 2013). Median duration of follow-up was 21 months. The study was performed in academic medical centers in Australia, Canada, France, and the United States. Eligible patients were aged 18 years and older and had advanced or metastatic melanoma. Data were pooled from 655 enrolled patients (135 from a nonrandomized cohort [n = 87 ipilimumab naive; n = 48 ipilimumab treated] and 520 from randomized cohorts [n = 226 ipilimumab naive; n = 294 ipilimumab treated]). Cutoff dates were April 18, 2014, for safety analyses and October 18, 2014, for efficacy analyses. EXPOSURES Pembrolizumab 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks continued until disease progression, intolerable toxicity, or investigator decision. MAIN OUTCOMES AND MEASURES The primary end point was confirmed objective response rate (best overall response of complete response or partial response) in patients with measurable disease at baseline per independent central review. Secondary end points included toxicity, duration of response, progression-free survival, and overall survival. RESULTS Among the 655 patients (median [range] age, 61 [18-94] years; 405 [62%] men), 581 had measurable disease at baseline. An objective response was reported in 194 of 581 patients (33% [95% CI, 30%-37%]) and in 60 of 133 treatment-naive patients (45% [95% CI, 36% to 54%]). Overall, 74% (152/205) of responses were ongoing at the time of data cutoff; 44% (90/205) of patients had response duration for at least 1 year and 79% (162/205) had response duration for at least 6 months. Twelve-month progression-free survival rates were 35% (95% CI, 31%-39%) in the total population and 52% (95% CI, 43%-60%) among treatment-naive patients. Median overall survival in the total population was 23 months (95% CI, 20-29) with a 12-month survival rate of 66% (95% CI, 62%-69%) and a 24-month survival rate of 49% (95% CI, 44%-53%). In treatment-naive patients, median overall survival was 31 months (95% CI, 24 to not reached) with a 12-month survival rate of 73% (95% CI, 65%-79%) and a 24-month survival rate of 60% (95% CI, 51%-68%). Ninety-two of 655 patients (14%) experienced at least 1 treatment-related grade 3 or 4 adverse event (AE) and 27 of 655 (4%) patients discontinued treatment because of a treatment-related AE. Treatment-related serious AEs were reported in 59 patients (9%). There were no drug-related deaths. CONCLUSIONS AND RELEVANCE Among patients with advanced melanoma, pembrolizumab administration was associated with an overall objective response rate of 33%, 12-month progression-free survival rate of 35%, and median overall survival of 23 months; grade 3 or 4 treatment-related AEs occurred in 14%. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01295827.",
"title": "Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma."
},
{
"docid": "28419824",
"text": "Two hundred patients who were taking daily symptomatic or immediate relief medications, often in excessive quantities, yet suffering from daily or near daily severe headaches were studied. One hundred and sixteen (58%) of them were also taking concomitant prophylactic medications and they were ineffective. Low tyramine, low caffeine dietary instructions and biofeedback training were given to all patients. The effect of continuing symptomatic medications, discontinuing symptomatic medications, and adding or changing prophylactic medications were studied in the various treatment groups. It is concluded that; 1.) Daily use of symptomatic or immediate relief medications result in chronic daily headache. 2.) Discontinuing daily symptomatic medications itself result in improvement of headache. 3.) Concomitant use of symptomatic medications nullifies the effect of prophylactic medications. 4.) Discontinuing daily symptomatic medications enhances the beneficial effect of prophylactic medications.",
"title": "Drug induced refractory headache--clinical features and management."
},
{
"docid": "21700295",
"text": "Importance More than 240 million individuals worldwide are infected with chronic hepatitis B virus (HBV). Among individuals with chronic HBV infection who are untreated, 15% to 40% progress to cirrhosis, which may lead to liver failure and liver cancer. Observations Pegylated interferon and nucleos(t)ide analogues (lamivudine, adefovir, entecavir, tenofovir disoproxil, and tenofovir alafenamide) suppress HBV DNA replication and improve liver inflammation and fibrosis. Long-term viral suppression is associated with regression of liver fibrosis and reduced risk of hepatocellular carcinoma in cohort studies. The cure (defined as hepatitis B surface antigen loss with undetectable HBV DNA) rates after treatment remain low (3%-7% with pegylated interferon and 1%-12% with nucleos[t]ide analogue therapy). Pegylated interferon therapy can be completed in 48 weeks and is not associated with the development of resistance; however, its use is limited by poor tolerability and adverse effects such as bone marrow suppression and exacerbation of existing neuropsychiatric symptoms such as depression. Newer agents (entecavir, tenofovir disoproxil, and tenofovir alafenamide) may be associated with a significantly reduced risk of drug resistance compared with older agents (lamivudine and adefovir) and should be considered as the first-line treatment. Conclusions and Relevance Antiviral treatment with either pegylated interferon or a nucleos(t)ide analogue (lamivudine, adefovir, entecavir, tenofovir disoproxil, or tenofovir alafenamide) should be offered to patients with chronic HBV infection and liver inflammation in an effort to reduce progression of liver disease. Nucleos(t)ide analogues should be considered as first-line therapy. Because cure rates are low, most patients will require therapy indefinitely.",
"title": "Chronic Hepatitis B Infection: A Review"
},
{
"docid": "7209559",
"text": "CONTEXT The incidence of distal forearm fractures in children peaks around the time of the pubertal growth spurt, possibly because physical activity increases at the time of a transient deficit in cortical bone mass due to the increased calcium demand during maximal skeletal growth. Changes in physical activity or diet may therefore influence risk of forearm fracture. OBJECTIVE To determine whether there has been a change in the incidence of distal forearm fractures in children in recent years. DESIGN, SETTING, AND PATIENTS Population-based study among Rochester, Minn, residents younger than 35 years with distal forearm fractures in 1969-1971, 1979-1981, 1989-1991, and 1999-2001. MAIN OUTCOME MEASURE Estimated incidence of distal forearm fractures in 4 time periods. RESULTS Comparably age- and sex-adjusted annual incidence rates per 100 000 increased from 263.3 (95% confidence interval [CI], 231.1-295.4) in 1969-1971 to 322.3 (95% CI, 285.3-359.4) in 1979-1981 and to 399.8 (95% CI, 361.0-438.6) in 1989-1991 before leveling off at 372.9 (95% CI, 339.1-406.7) in 1999-2001. Age-adjusted incidence rates per 100 000 were 32% greater among male residents in 1999-2001 compared with 1969-1971 (409.4 [95% CI, 359.9-459.0] vs 309.4 [95% CI, 259.3-359.5]; P =.01) and 56% greater among female residents in the same time periods (334.3 [95% CI, 288.6-380.1] vs 214.6 [95% CI, 174.9-254.4]; P<.001). The peak incidence and greatest increase occurred between ages 11 and 14 years in boys and 8 and 11 years in girls. CONCLUSIONS There has been a statistically significant increase in the incidence of distal forearm fractures in children and adolescents, but whether this is due to changing patterns of physical activity, decreased bone acquisition due to poor calcium intake, or both is unclear at present. Given the large number of childhood fractures, however, studies are needed to define the cause(s) of this increase.",
"title": "Incidence of childhood distal forearm fractures over 30 years: a population-based study."
},
{
"docid": "42800527",
"text": "BACKGROUND Adverse effects of metformin are primarily related to gastrointestinal (GI) intolerance that could limit titration to an efficacious dose or cause discontinuation of the medication. Because some metformin side effects may be attributable to shifts in the GI microbiome, we tested whether a GI microbiome modulator (GIMM) used in combination with metformin would ameliorate the GI symptoms. METHODS A 2-period crossover study design was used with 2 treatment sequences, either placebo in period 1 followed by GIMM in period 2 or vice versa. Study periods lasted for 2 weeks, with a 2-week washout period between. During the first week, type 2 diabetes patients (T2D) who experienced metformin GI intolerance took 500 mg metformin along with their assigned NM504 (GIMM) or placebo treatment with breakfast and with dinner. In the second week, the 10 subjects took 500 mg metformin (t.i.d.), with GIMM or placebo consumed with the first and third daily metformin doses. Subjects were permitted to discontinue metformin dosing if it became intolerable. RESULTS The combination of metformin and GIMM treatment produced a significantly better tolerance score to metformin than the placebo combination (6.78 ± 0.65 [mean ± SEM] versus 4.45 ± 0.69, P = .0006). Mean fasting glucose levels were significantly (P < .02) lower with the metformin-GIMM combination (121.3 ± 7.8 mg/dl) than with metformin-placebo (151.9 ± 7.8 mg/dl). CONCLUSION Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.",
"title": "Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels."
},
{
"docid": "25121903",
"text": "The number of cancer survivors continues to increase due to the aging and growth of the population and improvements in early detection and treatment. In order for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborated to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results (SEER) program registries. In addition, current treatment patterns for the most common cancer types are described based on information in the National Cancer Data Base and the SEER and SEER-Medicare linked databases; treatment-related side effects are also briefly described. Nearly 14.5 million Americans with a history of cancer were alive on January 1, 2014; by January 1, 2024, that number will increase to nearly 19 million. The 3 most common prevalent cancers among males are prostate cancer (43%), colorectal cancer (9%), and melanoma (8%), and those among females are cancers of the breast (41%), uterine corpus (8%), and colon and rectum (8%). The age distribution of survivors varies substantially by cancer type. For example, the majority of prostate cancer survivors (62%) are aged 70 years or older, whereas less than one-third (32%) of melanoma survivors are in this older age group. It is important for clinicians to understand the unique medical and psychosocial needs of cancer survivors and to proactively assess and manage these issues. There are a growing number of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship.",
"title": "Cancer treatment and survivorship statistics, 2014."
},
{
"docid": "44048701",
"text": "IMPORTANCE The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing. OBJECTIVE To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck. DESIGN, SETTING, AND PARTICIPANTS A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck. Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data. The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis. INTERVENTIONS Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques. Nonsurgical treatment was sling immobilization. Standardized outpatient and community-based rehabilitation was provided to both groups. MAIN OUTCOMES AND MEASURES Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months. Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score. Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality. RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points. There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points]; P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27). Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay. CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence. These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus. TRIAL REGISTRATION isrctn.com Identifier: ISRCTN50850043.",
"title": "Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial."
},
{
"docid": "7613033",
"text": "Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50% or more reduction in the risk of CRC commencing five years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin's anticancer effect require further investigation.",
"title": "Aspirin in the chemoprevention of colorectal neoplasia: an overview."
},
{
"docid": "6477536",
"text": "OBJECTIVE To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery. DESIGN Cross sectional observational study of registered and published trials. SETTING Randomised controlled trials of interventions in patients undergoing a surgical procedure. DATA SOURCES The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword \"surgery\". Recruitment status was extracted from the ClinicalTrials.gov database. A systematic search for studies published in peer reviewed journals was performed; if they were not found, results posted on the ClinicalTrials.gov results database were sought. Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed. MAIN OUTCOME MEASURES Trial discontinuation before completion and non-publication after completion. Logistic regression was used to determine the effect of funding source on publication status, with adjustment for intervention type and trial size. RESULTS Of 818 registered trials found using the keyword \"surgery\", 395 met the inclusion criteria. Of these, 21% (81/395) were discontinued early, most commonly owing to poor recruitment (44%, 36/81). The remaining 314 (79%) trials proceeded to completion, with a publication rate of 66% (208/314) at a median time of 4.9 (interquartile range 4.0-6.0) years from study completion to publication search. A further 6% (20/314) of studies presented results on ClinicalTrials.gov without a corresponding peer reviewed publication. Industry funding did not affect the rate of discontinuation (adjusted odds ratio 0.91, 95% confidence interval 0.54 to 1.55) but was associated with a lower odds of publication for completed trials (0.43, 0.26 to 0.72). Investigators' email addresses for trials with an uncertain fate were identified for 71.4% (10/14) of discontinued trials and 83% (101/122) of unpublished studies. Only 43% (6/14) and 20% (25/122) replies were received. Email responses for completed trials indicated 11 trials in press, five published studies (four in non-indexed peer reviewed journals), and nine trials remaining unpublished. CONCLUSIONS One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks. To promote future efficiency and transparency, changes are proposed to research governance frameworks to overcome these concerns.",
"title": "Discontinuation and non-publication of surgical randomised controlled trials: observational study"
},
{
"docid": "17119869",
"text": "The pancreas emerges independently from dorsal and ventral domains of embryonic gut endoderm. Gene inactivation experiments in mice have identified factors required for dorsal pancreas development, but factors that initiate the ventral pancreas have remained elusive. In this study, we investigated the hypothesis that the emergence of the ventral pancreas is related to the emergence of the liver. We find that the liver and ventral pancreas are specified at the same time and in the same general domain of cells. Using embryo tissue explantation experiments, we find that the default fate of the ventral foregut endoderm is to activate the pancreas gene program. FGF signalling from the cardiac mesoderm diverts this endoderm to express genes for liver instead of those for pancreas. No evidence was found to indicate that the cell type choice for pancreas or liver involves a selection for growth or viability. Cardiac mesoderm or FGF induces the local expression of sonic hedgehog, which in turn is inhibitory to pancreas but not to liver. The bipotential precursor cell population for pancreas and liver in embryonic development and its fate selection by FGF has features that appear to be recapitulated in the adult pancreas and are reflected in the evolution of these organs.",
"title": "A bipotential precursor population for pancreas and liver within the embryonic endoderm."
},
{
"docid": "26105746",
"text": "Solid organ transplant recipients receiving chronic immunosuppressive agents are at increased risk to acquire influenza virus despite vaccination. Myocarditis is a known but rare complication of influenza infection. We present the first adult liver transplant recipient who received prophylactic vaccination but developed influenza A myocarditis. This may occur in solid organ transplant recipients, because they have reduced response to protein vaccines, which may leave them vulnerable to infections. Studies are needed to evaluate if antiviral chemoprophylaxis in solid organ transplant recipients during influenza season would be an effective preventive therapy against influenza in this high-risk population.",
"title": "Influenza A myocarditis developing in an adult liver transplant recipient despite vaccination: a case report and review of the literature."
},
{
"docid": "2496002",
"text": "Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a fatal clinical disorder characterized by extracellular deposition of abnormal fibrils derived from misfolded, normally soluble transthyretin (TTR) molecules. The disease is most commonly caused by a point mutation within the TTR gene inherited in an autosomal dominant fashion. Over 100 of such mutations have been identified, leading to destabilization of the physiological TTR tetramer. As a result, many monomers originate with a tendency for spontaneous conformational changes and self-aggregation. The main clinical feature of TTR-FAP is progressive sensorimotor and autonomic neuropathy. In the beginning, this polyneuropathy predominantly involves small unmyelinated nerve fibers with the result of dissociated sensory loss disproportionately affecting sensation of pain and temperature. Autonomic neuropathy typically accompanies sensory deficits early in the disease course. The symptoms include orthostatic hypotension, constipation alternating with diarrhea, erectile dysfunction, anhydrosis, and urinary retention or incontinence. Later, involvement of motor fibers causes rapidly progressive weakness and gait disturbances. In addition to the peripheral nervous system, the heart and the gut are frequently affected. Onset of symptoms is bimodal, with one peak at age 33 years (early onset) and another distinct peak in the sixth decade of life (late onset). The course of TTR-FAP is uniformly progressive and fatal. Death occurs an average of 10.8 years after the onset of symptoms in Portuguese patients, and 7.3 years in late-onset Japanese patients. Common causes include cachexia, cardiac failure, arrhythmia, and secondary infections. Liver transplantation is the standard therapy for patients who are in a clinical condition good enough to tolerate this intervention because it stops progression of neuropathy by removing the main source of mutant TTR. Recently, orally administered tafamidis meglumine has been approved by European authorities for treatment of FAP. The substance has been shown to stabilize the TTR tetramer, thereby improving the outcome of patients with TTR-FAP. Various other strategies have been studied in vitro to prevent TTR amyloidosis, including gene therapy, immunization, dissolution of TTR aggregates, and free radical scavengers, but none of them is ready for clinical use so far.",
"title": "Familial amyloidotic polyneuropathy: current and emerging treatment options for transthyretin-mediated amyloidosis"
},
{
"docid": "25104843",
"text": "We report on a patient treated with hemoperfusion-hemodialysis (HP-HD) for severe paraquat poisoning. This procedure was adopted since the combination of adsorption and dialysis may improve overall drug removal. On admission blood paraquat was 15.8 micrograms/ml. He received conventional treatment and combined HP-HD which started within 3 hours after ingestion of the chemical and lasted 5 hours. Blood samples were obtained during and after HP-HD. The samples during HP-HD were taken before the charcoal column, between the charcoal column and the artificial kidney and after the artificial kidney. Blood clearances of paraquat were 116 +/- 32 ml/min (n=6) for the charcoal column (HP), 90 +/- 54 ml/min (n=6) for the artificial kidney (HD) and 151 +/- 37 ml/min (n=6) for the combined systems (HP-HD). After HP-HD a limited rebound of blood paraquat level was seen. One day after admission renal and hepatic failure had developed, and the patient died after 5 days. Tissue paraquat levels (microgram/g wet tissue) were: skeletal muscle 9.4, pancreas 6.0, prostate 5.6, thyroid 4.2, lungs 4.0, bone marrow 4.0, kidney 3.1, spleen 2.9, adrenal 2.9, heart 2.8, liver 2.3, stomach and testis below 1.0. Measurements of blood levels demonstrated the efficient clearances of paraquat with HP-HD from the central (plasma) compartment. However, the present results confirmed those previously reported which suggest that the efficiency of short HP-HD in treating severe paraquat poisoning is questionable since paraquat levels in the peripheral (tissue) compartment remain elevated.",
"title": "Hemoperfusion-hemodialysis ineffective for paraquat removal in life-threatening poisoning?"
},
{
"docid": "31562330",
"text": "BACKGROUND The increased caloric requirements of HIV-positive individuals, undesirable side effects of treatment that may be worsened by malnutrition (but alleviated by nutritional support), and associated declines in adherence and possible increased drug resistance are all justifications for developing better interventions to strengthen the nutrition security of individuals receiving antiretroviral treatment. OBJECTIVE To highlight key benefits and challenges relating to interventions aimed at strengthening the nutrition security of people living with HIV who are receiving antiretroviral treatment. METHODS Qualitative research was undertaken on a short-term nutrition intervention linked to the provision of free antiretroviral treatment for people living with HIV in western Kenya in late 2005 and early 2006. RESULTS Patients enrolled in the food program while on treatment regimens self-reported greater adherence to their medication, fewer side effects, and a greater ability to satisfy increased appetite. Most clients self-reported weight gain, recovery of physical strength, and the resumption of labor activities while enrolled in dual (food supplementation and treatment) programs. Such improvements were seen to catalyze increased support from family and community. CONCLUSIONS These findings provide further empirical support to calls for a more holistic and comprehensive response to the coexistence of AIDS epidemics with chronic nutrition insecurity. Future work is needed to clarify ways of bridging the gap between short-term nutritional support to individuals and longer-term livelihood security programming for communities affected by AIDS. Such interdisciplinary research will need to be matched by intersectoral action on the part of the agriculture and health sectors in such environments.",
"title": "Integrating nutrition security with treatment of people living with HIV: lessons from Kenya."
},
{
"docid": "27188320",
"text": "OBJECTIVE This longitudinal study conducted path analyses to examine the relationships between treatment processes and outcomes among patients in community-based drug treatment programs. METHODS A total of 1,939 patients from 36 outpatient drug-free and residential treatment programs in 13 California counties were assessed at intake, discharge, three months after admission, and nine months after admission. Path analyses were conducted to relate the quantity and quality of services that were received in the first three months of treatment to treatment retention and outcomes at the nine-month follow-up. Patients were determined to have a favorable outcome if for at least 30 days before the follow-up assessment they did not use drugs, were not involved in criminal activity, and lived in the community. The path analyses controlled for patients' baseline characteristics. RESULTS Greater service intensity and satisfaction were positively related to either treatment completion or longer treatment retention, which in turn was related to favorable treatment outcomes. Patients with greater problem severity received more services and were more likely to be satisfied with treatment. These patterns were similar for patients regardless of whether they were treated in outpatient drug-free programs or residential programs. CONCLUSIONS The positive association between process measures-that is, greater levels of service intensity, satisfaction, and either treatment completion or retention-and treatment outcome strongly suggests that improvements in these key elements of the treatment process will improve treatment outcomes.",
"title": "Relationship between drug treatment services, retention, and outcomes."
},
{
"docid": "32787042",
"text": "AIM To determine the outcome of patients that underwent liver resection for metastases from uveal melanoma. METHODS Over a 9-year period, patients referred with uveal melanoma metastases were included. Following treatment of primary uveal melanoma, high-risk patients were offered to be enrolled into a 6-monthly non-contrast liver magnetic resonance imaging (MRI) surveillance. Following detection of liver metastases, patients were staged with a contrast-enhanced (Primovist(®)) liver MRI, computer tomography (CT) of the thorax and staging laparoscopy. RESULTS 155 patients were referred with uveal melanoma liver metastases, of which 17 (11.0%) patients had liver resection and one patient was treated with percutaneous radio-frequency ablation. The majority of patients undergoing liver resection were treated with multiple metastectomies (n = 8) and three patients had major liver resections. The overall median survival for patients treated with surgery/ablation was 27 (14-90) months, and this was significantly better compared to patients treated palliatively [median = 8(1-30) months, P < 0.001]. Following surgery, 11 patients had recurrent disease [median = 13(6-36) months]. Patients who had undergone a major liver resection had a significantly poorer disease-free survival (P = 0.037). CONCLUSIONS Patients who can undergo surgical resection for metastatic uveal melanoma have a more favorable survival compared to those who do not.",
"title": "The Liverpool uveal melanoma liver metastases pathway: outcome following liver resection."
}
] |
PLAIN-1701
|
natural toxins
|
[
{
"docid": "MED-3487",
"text": "Weight loss supplements often contain powerful pharmacoactive ingredients with the potential to cause harm. Trials used to determine product safety and effectiveness, meanwhile, tend to be small, of short duration, and frequently lack financial conflict of interest disclosures. These factors could conspire to place consumers at risk, especially when published research cited in advertising cloaks products with the suggestion that their safety and effectiveness have been proven by science. Examples of current and former weight loss products backed by potentially conflicted or low quality research include Metabolife-356, Hydroxycut, Xenadrine and LeptiCore. Published research, especially in the field of weight loss supplements, needs better conflict of interest disclosure, and regulators should consider how research findings are used in marketing claims.",
"title": "Science of weight loss supplements: Compromised by conflicts of interest?"
},
{
"docid": "MED-3488",
"text": "Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity.",
"title": "Aloe-induced Toxic Hepatitis"
},
{
"docid": "MED-4912",
"text": "Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.",
"title": "Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain."
},
{
"docid": "MED-4914",
"text": "As one of the major agricultural crops, the cultivated potato is consumed each day by millions of people from diverse cultural backgrounds. A product of global importance, the potato tuber contains toxic glycoalkaloids (GAs) that cause sporadic outbreaks of poisoning in humans, as well as many livestock deaths. This article will discuss some aspects of the potato GAs, including their toxic effects and risk factors, methods of detection of GAs and biotechnological aspects of potato breeding. An attempt has been made to answer a question of vital importance - are potato GAs dangerous to humans and animals and, if so, to what extent?",
"title": "Potato glycoalkaloids: true safety or false sense of security?"
},
{
"docid": "MED-4620",
"text": "Phytochemicals are recognized as playing an important role in cancer prevention by fruits and vegetables. The avocado is a widely grown and consumed fruit that is high in nutrients and low in calories, sodium, and fats. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with chloroform from avocado fruits target multiple signaling pathways and increase intracellular reactive oxygen leading to apoptosis. This review summarizes the reported phytochemicals in avocado fruit and discusses their molecular mechanisms and targets. These studies suggest that individual and combinations of phytochemicals from the avocado fruit may offer an advantageous dietary strategy in cancer prevention.",
"title": "Chemopreventive characteristics of avocado fruit."
},
{
"docid": "MED-5022",
"text": "The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.",
"title": "Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana."
},
{
"docid": "MED-3490",
"text": "Liquid dietary supplements represent a fast growing market segment, including botanically-based beverages containing mangosteen, acai, and noni. These products often resemble fruit juice in packaging and appearance, but may contain pharmacologically active ingredients. While little is known about the human health effects or safety of consuming such products, manufacturers make extensive use of low-quality published research to promote their products. This report analyzes the science-based marketing claims of two of the most widely consumed mangosteen liquid dietary supplements, and compares them to the findings of the research being cited. The reviewer found that analyzed marketing claims overstate the significance of findings, and fail to disclose severe methodological weaknesses of the research they cite. If this trend extends to other related products that are similarly widely consumed, it may pose a public health threat by misleading consumers into assuming that product safety and effectiveness are backed by rigorous scientific data.",
"title": "Science in Liquid Dietary Supplement Promotion: The Misleading Case of Mangosteen Juice"
},
{
"docid": "MED-5023",
"text": "Infection by unicellular green algae has not been described in humans. A case is reported in a 30-year-old woman who developed persistent infection of a healing operative wound on the dorsum of the right foot, after possible contamination by river water while canoeing. The wound was debrided 2 months later. Histologically, infected tissues contained mixed suppurative and granulomatous inflammation associated with endosporulating, round to oval microorganisms, ranging from 6-9 microns in diameter. Many of these organisms contained multiple, strongly periodic acid-Schiff, Gomori methenamine-silver, and Gridley fungus-positive granules in the cytoplasm. The organisms in tissue did not stain with fluorescent antibody conjugates specific for the two known pathogenic Prototheca species. In some organisms, electron microscopy revealed membranous cytoplasmic profiles considered to be remnants of degenerated chloroplasts. These findings are consistent with the presence of a green algal infection.",
"title": "Green algal infection in a human."
},
{
"docid": "MED-3489",
"text": "OBJECTIVE: To examine in overweight humans the short-term safety and efficacy for weight loss of an herbal supplement containing Ma Huang, Guarana and other ingredients. DESIGN: An 8 week randomized, double-blind placebo controlled study of a herbal dietary supplement (72 mg/day ephedrine alkaloids and 240 mg/day caffeine). SUBJECTS: Overweight men and women (body mass index, > or =29 and < or =35 kg/m2). MEASUREMENTS: The primary outcome variable was body weight change. Secondary variables included anthropometric, metabolic and cardiovascular changes. RESULTS: Sixty-seven subjects were randomized to either placebo (n=32) or active Ma Huang/Guarana (n=35). Twenty-four subjects in each group completed the study. Active treatment produced significantly (P<0.006) greater loss of weight (X+/-s.d.,-4.0+/-3.4 kg) and fat (-2.1+/-3.0% fat) over the 8-week treatment period than did placebo (-0.8+/-2.4 kg and 0.2+/-2.3% fat). Active treatment also produced greater reductions in hip circumference and serum triglyceride levels. Eight of the 35 actively treated subjects (23%) and none of the 32 placebo-treated control subjects withdrew from the protocol because of potential treatment-related effects. Dry mouth, insomnia and headache were the adverse symptoms reported most frequently by the herbal vs placebo group at the final evaluation visit. CONCLUSIONS: This herbal mixture of Ma Huang and Guarana effectively promoted short-term weight and fat loss. Safety with long-term use requires further investigation.",
"title": "An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial."
},
{
"docid": "MED-4415",
"text": "Cinnamon has been used as a spice and as traditional herbal medicine for centuries. The available in vitro and animal in vivo evidence suggests that cinnamon has anti-inflammatory, antimicrobial, antioxidant, antitumor, cardiovascular, cholesterol-lowering, and immunomodulatory effects. In vitro studies have demonstrated that cinnamon may act as an insulin mimetic, to potentiate insulin activity or to stimulate cellular glucose metabolism. Furthermore, animal studies have demonstrated strong hypoglycemic properties. However, there are only very few well-controlled clinical studies, a fact that limits the conclusions that can be made about the potential health benefits of cinnamon for free-living humans. The use of cinnamon as an adjunct to the treatment of type 2 diabetes mellitus is the most promising area, but further research is needed before definitive recommendations can be made.",
"title": "Cinnamon and health."
},
{
"docid": "MED-5024",
"text": "An adult dog with ataxia and a lingual mass, previously diagnosed as protothecosis, was euthanized. At the postmortem examination, the lingual mass, regions of the lungs and hilar lymph nodes, liver, mesenteric and sublumbar lymph nodes, and spinal meninges had pronounced green discoloration. Histologically, pyogranulomatous inflammation and algal organisms were found in the tongue, spinal meninges, hilar and mesenteric lymph nodes, liver, and lung. The algae had cell walls positive for periodic acid-Schiff and cytoplasmic granules. Ultrastructurally, the algae had a well-defined cell wall, stacks of grana and thylakoid membrane, and dense bodies, typical of starch granules. The organisms were identified as Chlorella, a green alga, based on the results of histochemistical and electron microscopic examination. To the author's knowledge this is the first report of disseminated Chlorella infection and the first report in a companion animal.",
"title": "Disseminated chlorellosis in a dog."
},
{
"docid": "MED-4959",
"text": "Tetrodotoxin is a neurotoxin that occurs in select species of the family Tetraodontidae (puffer fish). It causes paralysis and potentially death if ingested in sufficient quantities. In 2007, two individuals developed symptoms consistent with tetrodotoxin poisoning after ingesting home-cooked puffer fish purchased in Chicago. Both the Chicago retailer and the California supplier denied having sold or imported puffer fish but claimed the product was monkfish. However, genetic analysis and visual inspection determined that the ingested fish and others from the implicated lot retrieved from the supplier belonged to the family Tetraodontidae. Tetrodotoxin was detected at high levels in both remnants of the ingested meal and fish retrieved from the implicated lot. The investigation led to a voluntary recall of monkfish distributed by the supplier in three states and placement of the supplier on the U.S. Food and Drug Administration's Import Alert for species misbranding. This case of tetrodotoxin poisoning highlights the need for continued stringent regulation of puffer fish importation by the U.S. Food and Drug Administration, education of the public regarding the dangers of puffer fish consumption, and raising awareness among medical providers of the diagnosis and management of foodborne toxin ingestions and the need for reporting to public health agencies.",
"title": "Public health response to puffer fish (Tetrodotoxin) poisoning from mislabeled product."
},
{
"docid": "MED-5025",
"text": "Gel filtration chromatography, ultra-filtration, and solid-phase extraction silica gel clean-up were evaluated for their ability to remove microcystins selectively from extracts of cyanobacteria Spirulina samples after using the reversed-phase octadecylsilyl ODS cartridge for subsequent analysis by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The reversed-phase ODS cartridge/silica gel combination were effective and the optimal wash and elution conditions were: H(2)O (wash), 20% methanol in water (wash), and 90% methanol in water (elution) for the reversed-phase ODS cartridge, followed by 80% methanol in water elution in the silica gel cartridge. The presence of microcystins in 36 kinds of cyanobacteria Spirulina health food samples obtained from various retail outlets in China were detected by LC-MS/MS, and 34 samples (94%) contained microcystins ranging from 2 to 163 ng g(-1) (mean = 14 +/- 27 ng g(-1)), which were significantly lower than microcystins present in blue green alga products previously reported. MC-RR - which contains two molecules of arginine (R) - (in 94.4% samples) was the predominant microcystin, followed by MC-LR - where L is leucine - (30.6%) and MC-YR - where Y is tyrose - (27.8%). The possible potential health risks from chronic exposure to microcystins from contaminated cyanobacteria Spirulina health food should not be ignored, even if the toxin concentrations were low. The method presented herein is proposed to detect microcystins present in commercial cyanobacteria Spirulina samples.",
"title": "Detection of the hepatotoxic microcystins in 36 kinds of cyanobacteria Spirulina food products in China."
},
{
"docid": "MED-4865",
"text": "Despite its antioxidant capacity and well-known health benefits, yerba mate tea (Ilex paraguariensis) has been shown to possess some genotoxic and mutagenic activities and to increase incidence of some types of cancer. The aim of this study was to estimate the cyto- and genotoxicity of mate tea in human peripheral lymphocytes in vitro. We found that yerba mate extract induced a concentration-dependent, statistically significant increase in the level of apoptotic and necrotic cells and a decrease in the nuclear division index (NDI). Mate-exposed lymphocytes had a reduced transcriptional rDNA activity, which may be due to the stress conditions, and showed an elevated production of micronuclei. The FISH technique revealed the appearance of an acrocentric signal in mate-induced micronuclei, which suggests that under these conditions yerba mate extract may display aneugenic activity. Since caffeine is one of the most abundant compounds found in the dry mass of mate, we conducted additional experiments with caffeine alone. We showed that caffeine used at the same concentrations manifests a more potent cyto- and genotoxic effect that may account, at least in part, for the disadvantageous effects observed for yerba mate extract.",
"title": "Evaluation of the cyto- and genotoxic activity of yerba mate (Ilex paraguariensis) in human lymphocytes in vitro."
},
{
"docid": "MED-5021",
"text": "We have previously discovered that star fruit can induce oliguric acute renal failure. To investigate the mechanisms of star fruit-associated acute oxalate nephropathy, the nephrotoxic effect of star fruit was examined in both cellular experiments and animal models. We evaluated renal function, pathological changes in kidney tissues and apoptotic effects using terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay in four groups of rats -- a control group (CG), fed with tap water (1); a star fruit group (SG), fed with star fruit juice naturally containing 0.2M oxalate (2); and oxalate groups (OxG), fed with 0.2M (3) or 0.4M (4) oxalate solution. The effects of both star fruit juice and oxalate on MDCK cells were also analyzed by flow cytometry. We found that the mean creatinine clearance was significantly lower in the SG, 0.2M OxG and 0.4M OxG. Dose-dependent apoptotic effects were evident from the TUNEL assay, and flow cytometry analysis of treated MDCK cells showed dose- and time-dependent effects. Our findings suggest that star fruit juice produces acute renal injury, not only through the obstructive effect of calcium oxalate crystals, but also by inducing apoptosis of renal epithelial cells, which may be caused by the levels of oxalate in the fruit.",
"title": "Mechanisms of star fruit-induced acute renal failure."
},
{
"docid": "MED-4913",
"text": "Potatoes are a source of glycoalkaloids (GAs) represented primarily by alpha-solanine and alpha-chaconine (about 95%). Content of GAs in tubers is usually 10-100 mg/kg and maximum levels do not exceed 200 mg/kg. GAs can be hazardous for human health. Poisoning involve gastrointestinal ailments and neurological symptoms. A single intake of >1-3 mg/kg b.w. is considered a critical effect dose (CED). Probabilistic modelling of acute and chronic (usual) exposure to GAs was performed in the Czech Republic, Sweden and The Netherlands. National databases on individual consumption of foods, data on concentration of GAs in tubers (439 Czech and Swedish results) and processing factors were used for modelling. Results concluded that potatoes currently available at the European market may lead to acute intakes >1 mg GAs/kg b.w./day for upper tail of the intake distribution (0.01% of population) in all three countries. 50 mg GAs/kg raw unpeeled tubers ensures that at least 99.99% of the population does not exceed the CED. Estimated chronic (usual) intake in participating countries was 0.25, 0.29 and 0.56 mg/kg b.w./day (97.5% upper confidence limit). It remains unclear if the incidence of GAs poisoning is underreported or if assumptions are the worst case for extremely sensitive persons.",
"title": "Probabilistic modelling of exposure doses and implications for health risk characterization: glycoalkaloids from potatoes."
},
{
"docid": "MED-4618",
"text": "Persea americana is much sought after both for the nutritional value of its fruit and the medicinal values of its various plant parts. A chromosomal aberration assay was undertaken to evaluate the potential genotoxicity of crude extracts from avocado fruits and leaves. Chromosomal aberrations were observed in cultured human peripheral lymphocytes exposed to separately increasing concentrations of 50% methanolic extracts of Persea americana fruit and leaves. The groups exposed to leaf and fruit extracts, respectively, showed a concentration-dependent increase in chromosomal aberrations as compared to that in a control group. The mean percentage total aberrant metaphases at 100 mg/kg, 200 mg/kg, and 300 mg/kg concentrations of leaf extract were found respectively to be 58 ± 7.05, 72 ± 6.41, and 78 ± 5.98, which were significantly higher (p < 0.0001 each) than that in the control group (6 ± 3.39). The mean percentage total aberrant metaphases at 100 mg/kg, 200 mg/kg, and 300 mg/kg concentrations of fruit extract were found to be 18 ± 5.49, 40 ± 10.00, and 52 ± 10.20, respectively, which were significantly higher (p = 0.033, p < 0.0001, and p < 0.0001, respectively) than that for control (6 ± 3.39). Acrocentric associations and premature centromeric separation were the two most common abnormalities observed in both the exposed groups. The group exposed to leaf extracts also showed a significant number of a variety of other structural aberrations, including breaks, fragments, dicentrics, terminal deletion, minutes, and Robertsonian translocations. The group exposed to leaf extract showed higher frequency of all types of aberrations at equal concentrations as compared to the group exposed to fruit extract.",
"title": "In vitro evaluation of genotoxicity of avocado (Persea americana) fruit and leaf extracts in human peripheral lymphocytes."
},
{
"docid": "MED-3493",
"text": "We present a case of a 14-year-old previously healthy boy with acute hepatotoxicity after noni berry juice consumption. As the popularity of noni berry consumption continues to increase, heightened awareness of the relation between noni berry consumption and acute hepatotoxicity is important.",
"title": "Acute hepatotoxicity after ingestion of Morinda citrifolia (Noni Berry) juice in a 14-year-old boy."
},
{
"docid": "MED-4999",
"text": "Curcumin (Cur), a component of turmeric (Curcuma longa), has been reported to exhibit antimetastatic activities, but the mechanisms remain unclear. Other curcuminoids present in turmeric, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) have not been investigated whether they exhibit antimetastatic activity to the same extent as curcumin. The regulation of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) play important role in cancer cell invasion by cleavage of extracellular matrix (ECM). In this line, we comparatively examined the influence of Cur, DMC and BDMC on the expressions of uPA, MMP-2, MMP-9, membrane Type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-2), and in vitro invasiveness of human fibrosarcoma cells. The results indicate that the differential potency for inhibition of cancer cell invasion was BDMC> or =DMC>Cur, whereas the cell migration was not affected. Zymography analysis exhibited that curcumin, DMC and BDMC significantly decreased uPA, active-MMP-2 and MMP-9 but not pro-MMP-2 secretion from the cells in a dose-dependent manner, in which BDMC and DMC show higher potency than curcumin. The suppression of active MMP-2 level correlated with inhibition of MT1-MMP and TIMP-2 protein levels involved in pro-MMP-2 activation. Importantly, BDMC and DMC at 10 microM reduced MT1-MMP and TIMP-2 protein expression, but curcumin slightly reduced only MT1-MMP but not TIMP-2. In addition, three forms of curcuminoids significantly inhibited collagenase, MMP-2, and MMP-9 but not uPA activity. In summary, these data demonstrated that DMC and BDMC show higher antimetastasis potency than curcumin by the differentially down-regulation of ECM degradation enzymes.",
"title": "Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA."
},
{
"docid": "MED-4418",
"text": "Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.",
"title": "Toxicology and risk assessment of coumarin: focus on human data."
},
{
"docid": "MED-4416",
"text": "Cinnamon, the dry bark and twig of Cinnamomum spp., is a rich botanical source of polyphenolics that has been used for centuries in Chinese medicine and has been shown to affect blood glucose and insulin signaling. Cinnamon's effects on blood glucose have been the subject of many clinical and animal studies; however, the issue of cinnamon intake's effect on fasting blood glucose (FBG) in people with type 2 diabetes and/or prediabetes still remains unclear. A meta-analysis of clinical studies of the effect of cinnamon intake on people with type 2 diabetes and/or prediabetes that included three new clinical trials along with five trials used in previous meta-analyses was done to assess cinnamon's effectiveness in lowering FBG. The eight clinical studies were identified using a literature search (Pub Med and Biosis through May 2010) of randomized, placebo-controlled trials reporting data on cinnamon and/or cinnamon extract and FBG. Comprehensive Meta-Analysis (Biostat Inc., Englewood, NJ, USA) was performed on the identified data for both cinnamon and cinnamon extract intake using a random-effects model that determined the standardized mean difference ([i.e., Change 1(control) - Change 2(cinnamon)] divided by the pooled SD of the post scores). Cinnamon intake, either as whole cinnamon or as cinnamon extract, results in a statistically significant lowering in FBG (-0.49±0.2 mmol/L; n=8, P=.025) and intake of cinnamon extract only also lowered FBG (-0.48 mmol/L±0.17; n=5, P=.008). Thus cinnamon extract and/or cinnamon improves FBG in people with type 2 diabetes or prediabetes.",
"title": "Cinnamon intake lowers fasting blood glucose: meta-analysis."
},
{
"docid": "MED-4714",
"text": "This study investigated the association between pickled vegetable consumption and the risk of breast cancer using a validated food frequency questionnaire. A total of 358 patients with breast cancer who were matched to 360 healthy controls by age (using a 5-yr age distribution) were recruited from the National Cancer Center in South Korea. After adjusting for nondietary risk factors, total vegetable intake was inversely associated with risk of breast cancer. However, unlike nonpickled vegetables, pickled vegetable intake and its proportion relative to total vegetables were positively associated with the risk of breast cancer, and this association was more profound and consistent when pickled vegetable intake was considered as a proportion relative to total vegetables (odds ratio [OR] = 6.24, 95% confidence interval [CI] = 3.55-10.97; P for trend <0.001 for highest vs. lowest quartiles of intake) than as the absolute consumed amount (OR = 2.47, 95% CI = 1.45-4.21; P for trend = 0.015 for highest vs. lowest quartiles of intake). These results suggest that not only the amount of total vegetable intake but also the amounts of different types of vegetable (i.e., pickled or nonpickled) and their proportions relative to total vegetables are significantly associated with the risk of breast cancer.",
"title": "Vegetables, but not pickled vegetables, are negatively associated with the risk of breast cancer."
},
{
"docid": "MED-4916",
"text": "Agaritine (N-(gamma-L(+)-glutamyl)-4-hydroxymethyl-phenylhydrazine) was identified and quantified by high-pressure liquid chromatography and used as a marker for the occurrence of phenylhydrazine derivatives in the cultivated Agaricus bitorquis and A. garicus hortensis mushrooms. Although relatively high levels of agaritine (around 700 mg kg(-1)) could be found in freshly harvested A. bitorquis from early flushes, samples from supermarkets contained less agaritine. The content of 28 samples varied between 165 and 457 mg kg(-1), on average being 272 +/- 69 mg kg(-1). The highest amounts of agaritine were found in the skin of the cap and in the gills, the lowest being in the stem. There was no significant difference in agaritine content of the two mushroom species in our study. Pronounced reduction in agaritine content was observed during storage of mushrooms in the refrigerator or freezer, as well as during drying of the mushrooms. The degree of reduction was dependent on the length and condition of storage and was usually in the region 20-75%. No reduction in agaritine content was observed during freeze-drying. Depending on the cooking procedure, household processing of cultivated Agaricus mushrooms reduced the agaritine content to various degrees. Boiling extracted around 50% of the agaritine content into the cooking broth within 5min and degraded 20-25% of the original agaritine content of the mushrooms. Prolonged boiling, as when preparing a sauce, reduced the content in the solid mushroom further (around 10% left after 2h). Dry baking of the cultivated mushroom, a process similar to pizza baking, reduced the agaritine content by approximately 25%, whereas frying in oil or butter or deep frying resulted in a more marked reduction (35-70%). Microwave processing of the cultivated mushrooms reduced the agaritine content to one-third of the original level. Thus, the exposure to agaritine was substantially less when consuming processed Agaricus mushrooms as compared with consuming the raw mushrooms. However, it is not yet known to what extent agaritine and other phenylhydrazine derivatives occurring in the cultivated mushroom are degraded into other biologically active compounds during the cooking procedure.",
"title": "Influence of storage and household processing on the agaritine content of the cultivated Agaricus mushroom."
},
{
"docid": "MED-3492",
"text": "AIM: The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. METHODS: A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. RESULTS: At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. CONCLUSION: The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.",
"title": "Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extrac..."
},
{
"docid": "MED-4619",
"text": "Avocados have a high content of phytochemicals with potential chemopreventive activity. Previously we reported that phytochemicals extracted from avocado meat into a chloroform partition (D003) selectively induced apoptosis in cancer but not normal, human oral epithelial cell lines. In the present study, we observed that treatment of human oral cancer cell lines containing high levels of reactive oxygen (ROS) with D003 increased ROS levels twofold to threefold and induced apoptosis. In contrast, ROS levels increased only 1.3-fold, and apoptosis was not induced in the normal cell lines containing much lower levels of basal ROS. When cellular ROS levels in the malignant cell lines were reduced by N-acetyl-l-cysteine (NAC), cells were resistant to D003 induced apoptosis. NAC also delayed the induction of apoptosis in dominant negative FADD-expressing malignant cell lines. D003 increased ROS levels via mitochondrial complex I in the electron transport chain to induce apoptosis. Normal human oral epithelial cell lines transformed with HPV16 E6 or E7 expressed higher basal levels of ROS and became sensitive to D003. These data suggest that perturbing the ROS levels in human oral cancer cell lines may be a key factor in selective apoptosis and molecular targeting for chemoprevention by phytochemicals.",
"title": "Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism."
},
{
"docid": "MED-3491",
"text": "Background Muscletech Hydroxycut® (Iovate Health Sciences Research, Oakville, Ontario) was a popular weight loss supplement that was recalled by the manufacturer in May 2009 based on reports of hepatotoxicity associated with this supplement. Objective To characterize the clinical presentation of Hydroxycut®-associated liver injury and to adjudicate these cases for causal association with Hydroxycut®. Design Case series. Setting Academic tertiary care hospitals and FDA databases. Measurements Assessment of causality and grading of severity of liver injury using methodology developed by the Drug-Induced Liver Injury Network (DILIN) study. Results Eight patients who developed liver injury after taking Hydroxycut treated at different medical centers were identified. All were hospitalized and 3 of 8 patients required liver transplantation. Nine other cases with adequate clinical information were obtained from the FDA MedWatch database including one fatal case of acute liver failure. Usual symptoms were jaundice, fatigue, nausea, vomiting and abdominal pain. Most patients exhibited a hepatocellular pattern of injury. Adjudication for causality revealed 8 cases as definite, 5 highly likely, 2 probable and 2 were considered as possible. Conclusions Hydroxycut® has been clearly implicated as a cause for severe liver injury that may lead to acute liver failure and death. Weight loss supplements represent a class of dietary supplements that should be regarded as capable of causing severe hepatic toxicity when the usual causes of identified liver injury cannot be otherwise elucidated.",
"title": "Hepatotoxicity Due To Hydroxycut®: A Case Series"
},
{
"docid": "MED-4621",
"text": "The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD50) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD50 could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.",
"title": "Acute and Sub-Acute Toxicological Assessment of the Aqueous Seed Extract of Persea Americana Mill (Lauraceae) in Rats"
},
{
"docid": "MED-4998",
"text": "Curcumin has been reported to have the potential to prevent obesity as well as cancers. The downstream targets regulated by AMP-activated protein kinase (AMPK) for inhibiting adipocyte differentiation or cancer cell proliferation of curcumin were investigated. The activation of AMPK by curcumin was crucial for the inhibition of differentiation or growth in both adipocytes and cancer cells. Stimulation of AMPK by curcumin resulted in the down-regulation of PPAR (peroxisome proliferator-activated receptor)-gamma in 3T3-L1 adipocytes and the decrease in COX-2 in MCF-7 cells. Application of a synthetic AMPK activator also supported the evidence that AMPK acts as an upstream signal of PPAR-gamma in 3T3-L1 adipocytes. In cancer cells, AMPK was found to act as a regulator of ERK1/2, p38, and COX-2. Regulation of AMPK and its downstream targets such as PPAR-gamma, Mapkinases, and COX-2 by curcumin appears to be important in controlling adipocytes and cancerous cells.",
"title": "Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 i..."
},
{
"docid": "MED-5000",
"text": "BACKGROUND: High oxalate intake resulting from consuming supplemental doses of cinnamon and turmeric may increase risk of hyperoxaluria, a significant risk factor for urolithiasis. OBJECTIVE: This study assessed urinary oxalate excretion from supplemental doses of cinnamon and turmeric as well as changes in fasting plasma glucose, cholesterol, and triacylglycerol concentrations. DESIGN: Eleven healthy subjects, aged 21-38 y, participated in an 8-wk, randomly assigned, crossover study that involved the ingestion of supplemental doses of cinnamon and turmeric for 4-wk periods that provided 55 mg oxalate/d. Oxalate load tests, which entailed the ingestion of a 63-mg dose of oxalate from the test spices, were performed after each 4-wk experimental period and at the study onset with water only (control treatment). Fasting plasma glucose and lipid concentrations were also assessed at these time points. RESULTS: Compared with the cinnamon and control treatments, turmeric ingestion led to a significantly higher urinary oxalate excretion during the oxalate load tests. There were no significant changes in fasting plasma glucose or lipids in conjunction with the 4-wk periods of either cinnamon or turmeric supplementation. CONCLUSIONS: The percentage of oxalate that was water soluble differed markedly between cinnamon (6%) and turmeric (91%), which appeared to be the primary cause of the greater urinary oxalate excretion/oxalate absorption from turmeric. The consumption of supplemental doses of turmeric, but not cinnamon, can significantly increase urinary oxalate levels, thereby increasing risk of kidney stone formation in susceptible individuals.",
"title": "Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects."
},
{
"docid": "MED-5001",
"text": "We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.",
"title": "Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer."
},
{
"docid": "MED-4417",
"text": "AIMS: To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes. METHODS: 58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks. RESULTS: After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups. CONCLUSIONS: Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.",
"title": "Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-contr..."
},
{
"docid": "MED-4961",
"text": "While fish consumption is considered a component of a heart-healthy diet, many illnesses have been associated with eating contaminated fish. The authors describe two cases of muscle weakness and rhabdomyolysis that occurred after eating salmon. Cases of rhabdomyolysis and muscle weakness after consumption of fresh water fish have rarely been reported in the United States but have been frequently reported from the Baltic region. This illness is known as Haff disease. While the etiology is unknown, it is felt to be a toxin. Palytoxin, found in marine fish, has been associated with rhabdomyolysis, and may serve as a model for further study of the suspected toxin responsible for rhabdomyolysis after consumption of fresh water fish. If a case of Haff disease is suspected, contact the Centers for Disease Control and Prevention and collect any uneaten fish, which may be sent for laboratory analysis.",
"title": "Haff disease after eating salmon."
},
{
"docid": "MED-4926",
"text": "PURPOSE OF REVIEW: To explore the role of iron physiology in the brain of healthy adults and review how increased brain iron deposition has been associated with common neurodegenerative diseases that affect the elderly. RECENT FINDINGS: Because iron plays a role in oxygen transportation, myelin synthesis, neurotransmitter production, and electron transfers, it serves as a crucial cofactor in normal central nervous metabolism. However, an increased level of brain iron may promote neurotoxicity due to free radical formation, lipid peroxidation, and ultimately, cellular death. Advanced neuroimaging techniques and pathological studies have demonstrated increased brain iron with aging, and increased iron deposition has also been observed in patients with a constellation of neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. SUMMARY: Pathologic and neurologic imaging coupled with experimentation have increased our understanding of the link between iron and neurodegeneration. A potential implication is that disease-modifying therapies aimed at removing excess iron may one day be part of the armamentarium employed by clinicians to decrease the burden of neurodegenerative diseases in the elderly.",
"title": "Role of iron in neurotoxicity: a cause for concern in the elderly?"
},
{
"docid": "MED-4915",
"text": "A quantitative human dietary risk assessment was conducted using the glycoalkaloid concentrations measured from tubers of plants defoliated by Colorado potato beetles and undefoliated (control). There was a significantly greater production of glycoalkaloids for defoliated plants compared to control plants for both skin and inner tissue of tubers. The dietary risk posed to different human subgroups associated with the consumption of potatoes was estimated for the 50th, 95th, and 99.9th percentile US national consumption values. Exposures were compared to a toxic threshold of 1.0mg/kg body weight. Defoliation by Colorado potato beetles increased dietary risk by approximately 48%. Glycoalkaloid concentrations within the inner tissue of tubers, including undefoliated controls, exceeded the toxic threshold for all human subgroups at less than the 99.9th percentile of exposure, but not the 95th percentile.",
"title": "A human dietary risk assessment associated with glycoalkaloid responses of potato to Colorado potato beetle defoliation."
},
{
"docid": "MED-3486",
"text": "The Dietary Supplements Information Expert Committee (DSI-EC) of the United States Pharmacopeial Convention (USP) reviews the safety of dietary supplements and dietary supplement ingredients for the purpose of determining whether they should be admitted as quality monographs into the United States Pharmacopeia and National Formulary (USP-NF). The United States Food and Drug Administration (FDA) has enforcement authority to pursue a misbranding action in those instances where a dietary supplement product indicates that it conforms to USP standards but fails to so conform. Recently DSI-EC undertook a safety evaluation of spirulina, a widely used dietary ingredient. DSI-EC reviewed information from human clinical trials, animal studies, and regulatory and pharmacopeial sources and analyzed 31 adverse event reports regarding spirulina to assess potential health concerns. At the conclusion of this review, DSI-EC assigned a Class A safety rating for Spirulina maxima and S. platensis, thereby permitting the admission of quality monographs for these dietary supplement ingredients in USP-NF. DSI-EC continually monitors reports concerning the safety of dietary supplements and dietary supplement ingredients for which USP dietary supplement monographs are developed. The DSI-EC may revisit the safety classification of spirulina as new information on this dietary ingredient becomes available.",
"title": "United States pharmacopeia safety evaluation of spirulina."
},
{
"docid": "MED-5017",
"text": "BACKGROUND: Betel-nut use is associated with metabolic syndrome and obesity. However, the association between betel-nut chewing and risk for chronic kidney disease (CKD) is unknown. The present study was conducted to determine the association between betel-nut chewing and CKD in men. METHODS: We retrospectively reviewed health-check records of 3264 men in a hospital-based cross-sectional screening programme from 2003 to 2006. CKD was defined as estimated glomerular filtration rate less than 60 ml/min/1.73 m2 calculated by the Modification of Diet in Renal Disease formula. Risk factors for CKD including diabetes, hypertension, BMI, smoking, alcohol consumption and age were also considered. RESULTS: A total of 677 (20.7 %) men were found to have CKD and 427 (13.1 %) participants reported a history of betel-nut use. The prevalence (24.8 %) of CKD in betel-nut users was significantly higher than that (11.3 %) of participants without betel-nut use (P = 0.026). In multivariate logistic regression analysis with adjustments for age, hypertension, diabetes and hyperlipidaemia, betel-nut use was independently associated with CKD (P < 0.001). The adjusted odds ratio for betel-nut use was 2.572 (95 % CI 1.917, 3.451). CONCLUSIONS: Betel-nut use is associated with CKD in men. The association between betel-nut use and CKD is independent of age, BMI, smoking, alcohol consumption, hypertension, diabetes and hyperlipidaemia.",
"title": "Association between betel-nut chewing and chronic kidney disease in men."
},
{
"docid": "MED-4958",
"text": "Biogenic amines are non-volatile amines formed by decarboxylation of amino acids. Although many biogenic amines have been found in fish, only histamine, cadaverine, and putrescine have been found to be significant in fish safety and quality determination. Despite a widely reported association between histamine and scombroid food poisoning, histamine alone appears to be insufficient to cause food toxicity. Putrescine and cadaverine have been suggested to potentiate histamine toxicity. With respect to spoilage on the other hand, only cadaverine has been found to be a useful index of the initial stage of fish decomposition. The relationship between biogenic amines, sensory evaluation, and trimethylamine during spoilage are influenced by bacterial composition and free amino acid content. A mesophilic bacterial count of log 6-7 cfu/g has been found to be associated with 5 mg histamine/100 g fish, the Food and Drug Administration (FDA) maximum allowable histamine level. In vitro studies have shown the involvement of cadaverine and putrescine in the formation of nitrosamines, nitrosopiperidine (NPIP), and nitrosopyrrolidine (NPYR), respectively. In addition, impure salt, high temperature, and low pH enhance nitrosamine formation, whereas pure sodium chloride inhibits their formation. Understanding the relationships between biogenic amines and their involvement in the formation of nitrosamines could explain the mechanism of scombroid poisoning and assure the safety of many fish products.",
"title": "Biogenic amines in fish: roles in intoxication, spoilage, and nitrosamine formation--a review."
},
{
"docid": "MED-5122",
"text": "BACKGROUND: Drinking mate has been associated with cancers of the esophagus, oropharynx, larynx, lung, kidney, and bladder. We conducted this study to determine whether drinking mate could lead to substantial exposure to polycyclic aromatic hydrocarbons (PAH), including known carcinogens, such as benzo[a]pyrene. METHODS: The concentrations of 21 individual PAHs were measured in dry leaves of eight commercial brands of yerba mate and in infusions made with hot (80 degrees C) or cold (5 degrees C) water. Measurements were done using gas chromatography/mass spectrometry, with deuterated PAHs as the surrogates. Infusions were made by adding water to the leaves, removing the resulting infusion after 5 min, and then adding more water to the remaining leaves. This process was repeated 12 times for each infusion temperature. RESULTS: The total concentrations of the 21 PAHs in different brands of yerba mate ranged from 536 to 2,906 ng/g dry leaves. Benzo[a]pyrene concentrations ranged from 8.03 to 53.3 ng/g dry leaves. For the mate infusions prepared using hot water and brand 1, 37% (1,092 of 2,906 ng) of the total measured PAHs and 50% (25.1 of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. Similar results were obtained for other hot and cold infusions. CONCLUSION: Very high concentrations of carcinogenic PAHs were found in yerba mate leaves and in hot and cold mate infusions. Our results support the hypothesis that the carcinogenicity of mate may be related to its PAH content.",
"title": "High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks."
},
{
"docid": "MED-4930",
"text": "The growing popularity and availability of over-the-counter (OTC) health products, including vitamins, raises serious concern about vitamin toxicity. We report a case of cirrhosis in a patient with habitual daily ingestion of an OTC dietary supplement that contained 13,000 microg vitamin A and was associated with marked clinical improvement after discontinuation. This case highlights the potential for liver damage that may be associated with long-term intake of OTC vitamin supplements, and indicates the need for medical supervision of such products.",
"title": "Potential liver damage associated with over-the-counter vitamin supplements."
},
{
"docid": "MED-4960",
"text": "Seafood-borne illnesses are a common but under recognised source of morbidity. We report the case of an 80-year-old woman who presented to hospital after collapsing in a restaurant following lunch consisting of mackerel fish. A detailed food history and clinical exclusion helped diagnose the condition as scombroid poisoning. The patient made a complete recovery following antihistamine therapy.",
"title": "A fishy cause of sudden near fatal hypotension."
}
] |
[
{
"docid": "MED-1570",
"text": "Ciguatera is an important form of human poisoning caused by the consumption of seafood. The disease is characterised by gastrointestinal, neurological and cardiovascular disturbances. In cases of severe toxicity, paralysis, coma and death may occur. There is no immunity, and the toxins are cumulative. Symptoms may persist for months or years, or recur periodically. The epidemiology of ciguatera is complex and of central importance to the management and future use of marine resources. Ciguatera is an important medical entity in tropical and subtropical Pacific and Indian Ocean regions, and in the tropical Caribbean. As reef fish are increasingly exported to other areas, it has become a world health problem. The disease is under-reported and often misdiagnosed. Lipid-soluble, polyether toxins known as ciguatoxins accumulated in the muscles of certain subtropical and tropical marine finfish cause ciguatera. Ciguatoxins arise from biotransformation in the fish of less polar ciguatoxins (gambiertoxins) produced by Gambierdiscus toxicus, a marine dinoflagellate that lives on macroalgae, usually attached to dead coral. The toxins and their metabolites are concentrated in the food chain when carnivorous fish prey on smaller herbivorous fish. Humans are exposed at the end of the food chain. More than 400 species of fish can be vectors of ciguatoxins, but generally only a relatively small number of species are regularly incriminated in ciguatera. Ciguateric fish look, taste and smell normal, and detection of toxins in fish remains a problem. More than 20 precursor gambiertoxins and ciguatoxins have been identified in G. toxicus and in herbivorous and carnivorous fish. The toxins become more polar as they undergo oxidative metabolism and pass up the food chain. The main Pacific ciguatoxin (P-CTX-1) causes ciguatera at levels=0.1 microg/kg in the flesh of carnivorous fish. The main Caribbean ciguatoxin (C-CTX-1) is less polar and 10-fold less toxic than P-CTX-1. Ciguatoxins activate sodium ion (Na ) channels, causing cell membrane excitability and instability. Worldwide coral bleaching is now well documented, and there is a strong association between global warming and the bleaching and death of coral. This, together with natural environmental factors such as earthquakes and hurricanes, and man-made factors such as tourism, dock construction, sewage and eutrophication, may create more favourable environments for G. toxicus. While low levels of G. toxicus are found throughout tropical and subtropical waters, the presence of bloom numbers is unpredictable and patchy. Only certain genetic strains produce ciguatoxins, and environmental triggers for increasing toxin production are unknown.",
"title": "Ciguatera: recent advances but the risk remains."
},
{
"docid": "MED-1144",
"text": "Public risk perceptions and demand for safer food are important factors shaping agricultural production practices in the United States. Despite documented food safety concerns, little attempt has been made to elicit consumers' subjective risk judgments for a range of food safety hazards or to identify factors most predictive of perceived food safety risks. In this study, over 700 conventional and organic fresh produce buyers in the Boston area were surveyed for their perceived food safety risks. Survey results showed that consumers perceived relatively high risks associated with the consumption and production of conventionally grown produce compared with other public health hazards. For example, conventional and organic food buyers estimated the median annual fatality rate due to pesticide residues on conventionally grown food to be about 50 per million and 200 per million, respectively, which is similar in magnitude to the annual mortality risk from motor vehicle accidents in the United States. Over 90% of survey respondents also perceived a reduction in pesticide residue risk associated with substituting organically grown produce for conventionally grown produce, and nearly 50% perceived a risk reduction due to natural toxins and microbial pathogens. Multiple regression analyses indicate that only a few factors are consistently predictive of higher risk perceptions, including feelings of distrust toward regulatory agencies and the safety of the food supply. A variety of factors were found to be significant predictors of specific categories of food hazards, suggesting that consumers may view food safety risks as dissimilar from one another. Based on study findings, it is recommended that future agricultural policies and risk communication efforts utilize a comparative risk approach that targets a range of food safety hazards.",
"title": "Perceived risks of conventional and organic produce: pesticides, pathogens, and natural toxins."
},
{
"docid": "MED-4380",
"text": "Domoic acid is a potent neurotoxin that is naturally produced by several diatom species of the genus Pseudo-nitzschia. The toxin acts as a glutamate agonist and is excitotoxic in the vertebrate central nervous system and other glutamate receptor-rich organs. Human exposure to domoic acid occurs via the consumption of contaminated shellfish that have accumulated the toxin while filter feeding on toxigenic phytoplankton during blooms. The first reported human domoic acid poisoning event occurred in Canada in 1987 during which clinical signs of acute toxicity such as gastrointestinal distress, confusion, disorientation, memory loss, coma and death were observed. The illness was named amnesic shellfish poisoning (ASP) and due to effective seafood monitoring programs there have been no documented ASP cases since 1987. However, domoic acid poisoning has a significant effect on marine wildlife and multiple poisoning events have occurred in marine birds and mammals over the last few decades. Currently, domoic acid producing diatom blooms are thought to be increasing in frequency world wide, posing an increasing threat to wildlife and human health. Of particular concern are the potential impacts of long-term low-level exposure in \"at risk\" human populations. The impacts of repetitive low-level domoic acid exposure are currently unknown. This review provides a basic description of the mechanism of action of domoic acid as well as a synthesis of information pertaining to domoic acid exposure routes, toxin susceptibility, and the importance of effective monitoring programs. The importance of investigating the potential human health impacts of long-term low-level domoic acid exposure in \"at risk\" human populations is also discussed. Published by Elsevier Ltd.",
"title": "Domoic acid and human exposure risks: a review."
},
{
"docid": "MED-1569",
"text": "Biopsy-proved polymyositis subsequently developed in two patients who were severely poisoned by ciguatera fish toxin. Ciguatera toxin may have several mechanisms of action and may represent more than one toxin. The patients' clinical courses and the unlikelihood of coincidence of contracting both diseases suggested to us a causal relationship. Although we cannot prove this relationship, we suggest a mechanism by which the toxin predisposed the muscle to inflammation.",
"title": "Polymyositis after ciguatera toxin exposure."
},
{
"docid": "MED-943",
"text": "A heat stable toxin present in needles of ponderosa pine was found to be soluble in methanol, ethanol, chloroform hexanes and 1-butanol. The embryotoxic effects of fresh green pine needles and a chloroform/methanol extract were determined by measuring embryo resorption in pregnant mice. Autoclaving the needles and extract for 1 hour prior to feeding enhanced the embryoresorptive effect by 28% and 32%, respectively. The results of this study revealed that the embryo resorptive dose (ERD50) of heat stable toxin for 1 mouse was 8.95 gms. for fresh green pine needles and 6.46 gms. for autoclaved green pine needles. In addition to embryocidal effects, feeding of the toxin resulted in significant weight loss in adult mice.",
"title": "Embryotoxic effects of pine needles and pine needle extracts."
},
{
"docid": "MED-1749",
"text": "Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada."
},
{
"docid": "MED-1266",
"text": "There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis). The non-protein amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer’s disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin.",
"title": "The Cyanobacteria Derived Toxin Beta-N-Methylamino-L-Alanine and Amyotrophic Lateral Sclerosis"
},
{
"docid": "MED-1272",
"text": "Cyanobacteria produce many neurotoxins including beta-methylamino-L-alanine (BMAA) that has been liked to amyotrophic lateral sclerosis (ALS) and neurodegenerative disease. A number of ALS cases have been diagnosed among residents of Enfield, NH, a town encompassing a lake with a history of cyanobacteria algal blooms. To investigate an association between toxic cyanobacterial blooms in New Hampshire and development of ALS, we reviewed records from our institution and other community databases to obtain demographic information on patients diagnosed with ALS within New England. We identified nine ALS patients who lived near Lake Mascoma in Enfield, NH, an incidence of sporadic ALS that is 10 to 25 times the expected incidence of 2/100,000/year. We suggest that the high incidence of ALS in this potential cluster could be directly related to chronic exposure to cyanobacterial neurotoxins such as BMAA. Possible routes of toxin exposure include inhalation of aerosolized toxins, consuming fish, or ingestion of lake water. Further investigation, including analysis of brain tissue for cyanobacterial toxins, will be helpful to test for an association between BMAA and ALS.",
"title": "A cluster of amyotrophic lateral sclerosis in New Hampshire: a possible role for toxic cyanobacteria blooms."
},
{
"docid": "MED-4807",
"text": "To determine the presence of Shiga toxin-producing Escherichia coli (STEC) and other potentially diarrheagenic E. coli strains in retail meats, 7,258 E. coli isolates collected by the U.S. National Antimicrobial Resistance Monitoring System (NARMS) retail meat program from 2002 to 2007 were screened for Shiga toxin genes. In addition, 1,275 of the E. coli isolates recovered in 2006 were examined for virulence genes specific for other diarrheagenic E. coli strains. Seventeen isolates (16 from ground beef and 1 from a pork chop) were positive for stx genes, including 5 positive for both stx1 and stx2, 2 positive for stx1, and 10 positive for stx2. The 17 STEC strains belonged to 10 serotypes: O83:H8, O8:H16, O15:H16, O15:H17, O88:H38, ONT:H51, ONT:H2, ONT:H10, ONT:H7, and ONT:H46. None of the STEC isolates contained eae, whereas seven carried enterohemorrhagic E. coli (EHEC) hlyA. All except one STEC isolate exhibited toxic effects on Vero cells. DNA sequence analysis showed that the stx2 genes from five STEC isolates encoded mucus-activatable Stx2d. Subtyping of the 17 STEC isolates by pulsed-field gel electrophoresis (PFGE) yielded 14 distinct restriction patterns. Among the 1,275 isolates from 2006, 11 atypical enteropathogenic E. coli (EPEC) isolates were identified in addition to 3 STEC isolates. This study demonstrated that retail meats, mainly ground beef, were contaminated with diverse STEC strains. The presence of atypical EPEC strains in retail meat is also of concern due to their potential to cause human infections.",
"title": "Presence and Characterization of Shiga Toxin-Producing Escherichia coli and Other Potentially Diarrheagenic E. coli Strains in Retail Meats"
},
{
"docid": "MED-4967",
"text": "BACKGROUND: From 2003 through 2007, Vibrio cholerae serogroup O75 strains possessing the cholera toxin gene were isolated from 6 patients with severe diarrhea, including 3 in Georgia, 2 in Alabama, and 1 in South Carolina. These reports represent the first identification of V. cholerae O75 as a cause of illness in the United States. V. cholerae O75 was isolated from a water sample collected from a pond in Louisiana in 2004. Subsequently, 3 V. cholerae isolates from Louisiana (2 from patients with diarrhea in 2000 and 1 from a water sample collected in 1978) that had been previously reported as serogroup O141 were also discovered to be serogroup O75. RESULTS: All 8 patients who were infected with V. cholerae O75 were adults who became ill after consuming seafood; 2 had eaten raw oysters traced back to the Gulf Coast of the United States. All 10 isolates possessed the cholera toxin gene and were susceptible to 10 antimicrobials. One clinical isolate and 1 environmental (water) isolate had the same pulsed-field gel electrophoresis pattern; 4 clinical isolates shared a common pulsed-field gel electrophoresis pattern. CONCLUSIONS: The occurrence of these cases over many years and the concurrent identification of V. cholerae O75 in water from a Gulf Coast state suggest that these strains may survive for long periods in this environment. The patients' exposure histories suggest that infection can be acquired from consumption of raw oysters from the Gulf Coast. Clinicians and public health authorities should be vigilant for the occurrence of new toxigenic serogroups of V. cholerae that are capable of causing severe diarrhea.",
"title": "Severe diarrhea caused by cholera toxin-producing vibrio cholerae serogroup O75 infections acquired in the southeastern United States."
},
{
"docid": "MED-3515",
"text": "Cluster headache (CH) is a primary headache syndrome that is classified with the trigeminal autonomic cephalalgias. CH treatment involves three steps: acute attack management, transitional therapy, and preventive therapy. Greater occipital nerve block has been shown to be an effective alternative bridge therapy to oral steroids in CH. Botulinum toxin type A has recently been studied as a new preventive treatment for patients with chronic CH, with limited success.",
"title": "The role of nerve blocks and botulinum toxin injections in the management of cluster headaches."
},
{
"docid": "MED-1572",
"text": "Ciguatera fish poisoning results from the bioconcentration of a variety of toxins produced by marine dinoflagellates. Signs and symptoms vary widely, but it usually presents as gastrointestinal and neurologic complaints beginning shortly after the ingestion of fish containing the toxins. Symptoms may persist for months and sometimes even years. Although cases have been reported throughout the United States, epidemics are most common along tropical and subtropical coasts and usually involve the ingestion of large carnivorous fish. We review the literature and report the first epidemic of 25 cases of ciguatera fish poisoning presenting to area hospitals in Southern California that were successfully tracked by the Department of Health Services and isolated to fish caught off the coast of Baja California, Mexico.",
"title": "Ciguatera fish poisoning. A southern California epidemic."
},
{
"docid": "MED-4525",
"text": "The red sap obtained by slashing the bark of Croton urucurana Baill. (Euphorbiaceae), also known as dragon's blood, was screened for a possible antidiarrhoeal activity on castor oil-induced diarrhoea in rats, cholera toxin-induced intestinal secretion in mice and on small intestinal transit in mice. Dragon's blood at an oral dose of 600 mg/kg caused in marked inhibition of the diarrhoeal response following castor oil administration as well as the intestinal fluid accumulation promoted by cholera toxin. At a similar dose the red sap significantly inhibited the small intestinal transit which was, however, found to be independent of the opioid mechanism. These results suggest a potential usefulness of the red sap from Croton urucurana Baill. in the control of secretory diarrhoea associated pathologies. Copyright 2001 John Wiley & Sons, Ltd.",
"title": "Studies on the antidiarrhoeal effect of dragon's blood from Croton urucurana."
},
{
"docid": "MED-4640",
"text": "BACKGROUND: The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. AIM: To define normal function of the gut and immune system and describe available methods of measuring it. RESULTS: We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be \"improved\". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo. measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens. determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.",
"title": "PASSCLAIM--gut health and immunity."
},
{
"docid": "MED-4797",
"text": "The objectives of this study were to compare the prevalence of Clostridium difficile (Cd) among different age and production groups of swine in a vertically integrated swine operation in Texas in 2006 and to compare our isolates to other animal and human isolates. Results are based on 131 Cd isolates from 1008 swine fecal samples and pork trim samples (overall prevalence of 13%). The prevalence (number positive/number tested in production type) of Cd was different between the groups (P<or=0.001), and was highest among suckling piglets at 50.0% (61/122), followed by 23.8% (34/143) for lactating sows and effluent from the farrowing barn, 8.4% (10/119) for nursery, 6.5% (4/62) for pork products, 3.9% (15/382) for grower-finisher, and 3.9% (7/180) for breeding boars and sows. Of the 131 isolates, 122 were positive by PCR for both toxins A (tcdA) and B (tcdB) genes, 129 isolates harbored a 39 base pair deletion in the tcdC gene, 120 isolates were toxinotype V, and all 131 of the isolates were positive for the binary toxin gene cdtB. All isolates were resistant to cefoxitin, ciprofloxacin, and imipenem, whereas all were sensitive to metronidazole, piperacillin/tazobactam, amoxicillin/clavulanic acid, and vancomycin. The majority of isolates were resistant to clindamycin; resistant or intermediate to ampicillin; and sensitive to tetracycline and chloramphenicol. There was an increased (P</=0.001) number of isolates for the timeframe of September to February compared to March to August.",
"title": "Varied prevalence of Clostridium difficile in an integrated swine operation."
},
{
"docid": "MED-4360",
"text": "Ciguatera is a type of food poisoning associated with the consumption of contaminated marine fish. We report two cases in which painful ejaculation in an affected male and dyspareunia in an unaffected female following her partner's ejaculation suggest the sexual transfer of the responsible agent, ciguatoxin (CTX). Immunoassay of semen samples for CTX were not diagnostic, but the sensitivity and timing of the test employed may have precluded detection of small quantities of the toxin. We conclude that CTX may be present in the semen of men affected with ciguatera toxicity and be capable of producing symptomatology in both males and females during sexual intercourse.",
"title": "Can ciguatera be a sexually transmitted disease?"
},
{
"docid": "MED-5101",
"text": "When making food choices, consumers are faced with the dilemma of reconciling differences between health benefits and exposure to potential toxins. Analyses to estimate likely intake and exposure outcomes for young children and women of child-bearing age shows that seafood, chicken, and beef, while approximately equivalent in protein, vary in key nutrients of importance as well as in levels of certain contaminants. Increasing the variety of choices among meats, poultry, and seafood and consuming them in amounts consistent with current dietary guidelines and advisories will contribute toward meeting nutritional needs while reducing exposure to any single type of contaminant.",
"title": "Nutrient and contaminant tradeoffs: exchanging meat, poultry, or seafood for dietary protein."
},
{
"docid": "MED-4968",
"text": "Vibrios are ubiquitous in the aquatic environment and are commonly present in or on shellfish and other seafood. A small subset of strains/species are able to cause human disease, including the cholera toxin-producing strains of Vibrio cholerae that are responsible for epidemic/pandemic cholera; thermostable direct hemolysin-producing strains of Vibrio parahaemolyticus; and Vibrio vulnificus, which can cause fulminant sepsis. Cholera outbreaks can be initiated by transmission of \"epidemic\" V. cholerae strains from their environmental reservoir to humans through seafood or other environmentally related food or water sources. \"Nonepidemic\" strains of V. cholerae and strains of other Vibrio species, including V. parahaemolyticus and V. vulnificus, are generally acquired by eating seafood (particularly raw oysters/oysters on the half shell). Although the primary clinical manifestation of infection with these strains is gastroenteritis, they can also cause wound infections and (particularly for V. vulnificus) septicemia in persons who have liver disease or are immunocompromised.",
"title": "Cholera and other types of vibriosis: a story of human pandemics and oysters on the half shell."
},
{
"docid": "MED-2165",
"text": "Death of dopaminergic neurons in Parkinson's disease (PD) may partially be caused by synthesis and accumulation of endogenous and exogenous toxins. Because of structural similarity to MPTP, beta-carbolines, like norharman and harman, have been proposed as putative neurotoxins. In vivo they may easily be formed by cyclization of indoleamines with e.g. aldehydes. For further elucidation of the role of beta-carbolines in neurodegenerative disorders harman and norharman levels in cerebrospinal fluid (CSF) were measured in 14 patients with PD and compared to an age- and sex-matched control group (n = 14). CSF levels of norharman and harman in PD were significantly higher compared to controls. These results may suggest a possible role of harman and norharman or its N-methylated carbolinium ions in the pathophysiological processes initiating PD. However the origin of increased levels of these beta-carbolines remains unclear. On the one hand one may speculate, that unknown metabolic processes induce the increased synthesis of harman and norharman in PD. On the other hand a possible impact of exogenous sources may also be possible.",
"title": "Elevated levels of harman and norharman in cerebrospinal fluid of parkinsonian patients."
},
{
"docid": "MED-2327",
"text": "A wide variety of phytochemicals present in our diet, including fruits, vegetables, and spices, have been shown to possess a broad range of health-beneficial properties. The cytoprotective and restorative effects of dietary phytochemicals are likely to result from the modulation of several distinct cellular signal transduction pathways. Many dietary phytochemicals that are synthesized as secondary metabolites function as toxins, that is, \"phytoalexins,\" and hence protect plants against insects and other damaging organisms and stresses. However, at the relatively low doses consumed by humans and other mammals, these same toxic plant-derived chemicals, as mild stressors, activate adaptive cellular response signaling, conferring stress resistance and other health benefits. This phenomenon has been referred to as xenohormesis. This review highlights the xenohormesis mechanisms underlying chemopreventive effects of some dietary chemopreventive phytochemicals, with special focus on the nuclear transcription factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) as a key player. © 2011 New York Academy of Sciences.",
"title": "Xenohormesis mechanisms underlying chemopreventive effects of some dietary phytochemicals."
},
{
"docid": "MED-1274",
"text": "Sharks are among the most threatened groups of marine species. Populations are declining globally to support the growing demand for shark fin soup. Sharks are known to bioaccumulate toxins that may pose health risks to consumers of shark products. The feeding habits of sharks are varied, including fish, mammals, crustaceans and plankton. The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) has been detected in species of free-living marine cyanobacteria and may bioaccumulate in the marine food web. In this study, we sampled fin clips from seven different species of sharks in South Florida to survey the occurrence of BMAA using HPLC-FD and Triple Quadrupole LC/MS/MS methods. BMAA was detected in the fins of all species examined with concentrations ranging from 144 to 1836 ng/mg wet weight. Since BMAA has been linked to neurodegenerative diseases, these results may have important relevance to human health. We suggest that consumption of shark fins may increase the risk for human exposure to the cyanobacterial neurotoxin BMAA.",
"title": "Cyanobacterial Neurotoxin β-N-Methylamino-L-alanine (BMAA) in Shark Fins"
},
{
"docid": "MED-2173",
"text": "MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes selective destruction of dopaminergic neurons of the nigrostriatal pathway in humans and other primates. It is less specific and much less potent in mice and has only slight effects in rats. Differences in rates and sites of metabolism of MPTP to its active, toxic, highly polar metabolite, MPP+ (1-methyl-4-phenylpyridine), appear to influence species specificity. In rats, type B monoamine oxidase (MAO-B), which mediates the conversion of MPTP to MPP+, may act as an enzymatic barrier at brain microvessels, whereas in primates the enzyme, present mainly in astrocytes, appears important for bioactivation of MPTP into the toxic metabolite. MPP+ is a substrate for catecholamine uptake sites and is concentrated in these neurons. The molecular mechanism of MPP+ toxicity has not been established definitively, but conversion to a free radical or uptake by mitochondria and inhibition of mitochondrial respiratory enzymes, leading to calcium release and cell death have been suggested. The discovery of toxin which causes an animal model of Parkinson's disease has stimulated new research on environmental factors that might contribute to this progressive degenerative disorder and provides a means for assessing new approaches to therapy.",
"title": "MPTP: an industrial chemical and contaminant of illicit narcotics stimulates a new era in research on Parkinson's disease."
},
{
"docid": "MED-5156",
"text": "Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.",
"title": "Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas."
},
{
"docid": "MED-1140",
"text": "Consumer concern over the quality and safety of conventional food has intensified in recent years, and primarily drives the increasing demand for organically grown food, which is perceived as healthier and safer. Relevant scientific evidence, however, is scarce, while anecdotal reports abound. Although there is an urgent need for information related to health benefits and/or hazards of food products of both origins, generalized conclusions remain tentative in the absence of adequate comparative data. Organic fruits and vegetables can be expected to contain fewer agrochemical residues than conventionally grown alternatives; yet, the significance of this difference is questionable, inasmuch as actual levels of contamination in both types of food are generally well below acceptable limits. Also, some leafy, root, and tuber organic vegetables appear to have lower nitrate content compared with conventional ones, but whether or not dietary nitrate indeed constitutes a threat to human health is a matter of debate. On the other hand, no differences can be identified for environmental contaminants (e.g. cadmium and other heavy metals), which are likely to be present in food from both origins. With respect to other food hazards, such as endogenous plant toxins, biological pesticides and pathogenic microorganisms, available evidence is extremely limited preventing generalized statements. Also, results for mycotoxin contamination in cereal crops are variable and inconclusive; hence, no clear picture emerges. It is difficult, therefore, to weigh the risks, but what should be made clear is that 'organic' does not automatically equal 'safe.' Additional studies in this area of research are warranted. At our present state of knowledge, other factors rather than safety aspects seem to speak in favor of organic food.",
"title": "Organic food: buying more safety or just peace of mind? A critical review of the literature."
},
{
"docid": "MED-1271",
"text": "Background Dietary exposure to the cyanotoxin BMAA is suspected to be the cause of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and North America, this toxin has been identified in the marine environment of amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures have been described. Objectives We aimed at identifying cluster(s) of amyotrophic lateral sclerosis in the Hérault district, a coastal district from Southern France, and to search, in the identified area(s), for the existence of a potential dietary source of BMAA. Methods A spatio-temporal cluster analysis was performed in the district, considering all incident amyotrophic lateral sclerosis cases identified from 1994 to 2009 by our expert center. We investigated the cluster area with serial collections of oysters and mussels that were subsequently analyzed blind for BMAA concentrations. Results We found one significant amyotrophic lateral sclerosis cluster (p = 0.0024), surrounding the Thau lagoon, the most important area of shellfish production and consumption along the French Mediterranean coast. BMAA was identified in mussels (1.8 µg/g to 6.0 µg/g) and oysters (0.6 µg/g to 1.6 µg/g). The highest concentrations of BMAA were measured during summer when the highest picocyanobacteria abundances were recorded. Conclusions While it is not possible to ascertain a direct link between shellfish consumption and the existence of this ALS cluster, these results add new data to the potential association of BMAA with sporadic amyotrophic lateral sclerosis, one of the most severe neurodegenerative disorder.",
"title": "Dietary BMAA Exposure in an Amyotrophic Lateral Sclerosis Cluster from Southern France"
},
{
"docid": "MED-329",
"text": "Elevated phosphate (P) levels are seen in advanced renal failure and, together with dysregulated calcium, parathyroid hormone and vitamin D levels, contribute to the complex of chronic kidney disease-mineral and bone disease (CKD-MBD). Converging evidence from in vitro, clinical and epidemiological studies suggest that increased P is associated with vascular calcification and mortality. When vessels are exposed to high P conditions in vitro, they develop apoptosis, convert to bone-like cells and develop extensive calcification. Clinical studies in children on dialysis show that high P is associated with increased vessel wall thickness, arterial stiffness and coronary calcification. Epidemiological studies in adult dialysis patients demonstrate a significant and independent association between raised P and mortality. Importantly, raised P is associated with cardiovascular changes even in pre-dialysis CKD, and also in subjects with normal renal function but high P. All P binders can effectively reduce serum P, and this decrease is linked to improved survival. Raised serum P triggers the release of fibroblast growth factor 23 (FGF-23), which has the beneficial effect of increasing P excretion in early CKD, but is increased several 1,000-fold in dialysis, and may be an independent cardiovascular risk factor. Both FGF-23 and its co-receptor Klotho may have direct effects on the vasculature leading to calcification. Fascinatingly, disturbances in FGF-23-Klotho and raised P have also been associated with premature aging. These data suggest that high P levels have adverse vascular effects and that maintaining the serum P levels in the normal range reduces cardiovascular risk and mortality.",
"title": "Phosphate is a vascular toxin."
},
{
"docid": "MED-4299",
"text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.",
"title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention."
},
{
"docid": "MED-838",
"text": "Docosahexaenoic acid (DHA) is an omega-3 fatty acid that comprises 22 carbons and 6 alternative double bonds in its hydrocarbon chain (22:6omega3). Previous studies have shown that DHA from fish oil controls the growth and development of different cancers; however, safety issues have been raised repeatedly about contamination of toxins in fish oil that makes it no longer a clean and safe source of the fatty acid. We investigated the cell growth inhibition of DHA from the cultured microalga Crypthecodinium cohnii (algal DHA [aDHA]) in human breast carcinoma MCF-7 cells. aDHA exhibited growth inhibition on breast cancer cells dose-dependently by 16.0% to 59.0% of the control level after 72-h incubations with 40 to 160 microM of the fatty acid. DNA flow cytometry shows that aDHA induced sub-G(1) cells, or apoptotic cells, by 64.4% to 171.3% of the control levels after incubations with 80 mM of the fatty acid for 24, 48, and 72 h. Western blot studies further show that aDHA did not modulate the expression of proapoptotic Bax protein but induced the downregulation of anti-apoptotic Bcl-2 expression time-dependently, causing increases of Bax/Bcl-2 ratio by 303.4% and 386.5% after 48- and 72-h incubations respectively with the fatty acid. Results from this study suggest that DHA from the cultured microalga is also effective in controlling cancer cell growth and that downregulation of antiapoptotic Bcl-2 is an important step in the induced apoptosis.",
"title": "Docosahexaenoic acid from a cultured microalga inhibits cell growth and induces apoptosis by upregulating Bax/Bcl-2 ratio in human breast carcinoma..."
},
{
"docid": "MED-1598",
"text": "Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered – Thirdhand smoke (THS) – the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.",
"title": "Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health"
},
{
"docid": "MED-2166",
"text": "Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors are likely to play important etiological roles. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. Previously, elevated blood harmane concentrations were demonstrated in ET cases compared to controls, but these observations were all been cross-sectional, assessing each subject at only one time point. Thus, no one has ever repeat-assayed blood harmane in the same subjects twice. Whether the observed case-control difference persists at a second time point, years later, is unknown. The current goal was to re-assess a sample of our ET cases and controls to determine whether blood harmane concentration remained elevated in ET at a second time point. Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method in 63 ET cases and 70 controls. A mean of approximately 6 years elapsed between the initial and this subsequent blood harmane determination. The mean log blood harmane concentration was significantly higher in cases than controls (0.30 ± 0.61 g−10/ml vs. 0.08 ± 0.55 g−10/ml), and the median value in cases was double that of controls: 0.22 g−10/ml vs. 0.11 g−10/ml. The log blood harmane concentration was highest in cases with a family history of ET. Blood harmane concentration was elevated in ET cases compared to controls when re-assessed at a second time point several years later, indicating what seems to be a stable association between this environmental toxin and ET.",
"title": "Blood Harmane (1-methyl-9h-pyrido[3,4-b]indole) Concentrations in Essential Tremor: Repeat Observation in Cases and Controls in New York"
}
] |
PLAIN-1032
|
dishwashing detergent
|
[
{
"docid": "MED-1160",
"text": "Washing is the most practical way to remove pesticide residues in fruits and vegetables. Two commonly used kitchen dishwashing liquids (detergents) in Chinese market were tested for enhanced removal of chlorpyrifos (CHP) and chlorothalonil (CHT) in cherry tomatoes by soaking the cherry tomatoes in the detergent solutions. The critical micelle concentrations of detergent A and detergent B were about 250 mg L(-1) and 444 mg L(-1), respectively. Detergent A had a higher solubilizing ability for pesticides and hence washing effectiveness than detergent B. The apparent solubility of CHP increased with increasing detergent concentration, while that of CHT remained comparatively invariant independent of detergent concentration within the tested range. The apparent solubility of CHP was also consistently higher in solutions of both detergents as compared to CHT. Due probably to its lower logKow value, CHT was more readily washed off cherry tomatoes than CHP. In terms of washing, a duration of 10-20 min was sufficient for removal of pesticides on cherry tomatoes in distilled water and detergent solutions. The effectiveness of removing pesticides increased with increasing detergent concentration from 50 mg L(-1) to 5 g L(-1), with up to 80% CHT and 42% CHP removed. Multiple washing further increased pesticide removal. Adding 10% acetic acid to lower pH or increasing washing temperature favored pesticide removal, but 10% NaCl produced the shielding effect and substantially reduced the effectiveness of detergent A for pesticide removal. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Effectiveness of dishwashing liquids in removing chlorothalonil and chlorpyrifos residues from cherry tomatoes."
},
{
"docid": "MED-1181",
"text": "Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.",
"title": "Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses"
},
{
"docid": "MED-1581",
"text": "Crohn's disease is a life-long idiopathic inflammatory disease which affects the entire gastrointestinal tract and occasionally extra-intestinal organs. CD is thought to result from complex interactions between environmental factors, the gut microbes, and the genetic background and the immune system of the host. In the last decades research on these pathogenetic components, and especially on mucosal immunity, has led to the development of biologic agents and therapeutic strategies that have improved dramatically the treatment of CD but we are still far away from curing the disease. If there is a treatment for CD that will probably evolve through methodical steps towards integrating research on all the components involved in the pathogenesis of CD. This holistic and global approach may aid at unravelling the mysteries of CD and developing novel agents and therapeutic strategies which by targeting multiple pathogenetic pathways and at different stages of disease may lead hopefully to cure. Copyright © 2014 Elsevier Ltd. All rights reserved.",
"title": "When can we cure Crohn's?"
},
{
"docid": "MED-1158",
"text": "The efficiencies of acidic solutions (radish, citric acid, ascorbic acid, acetic acid and hydrogen peroxide), neutral solutions (sodium chloride) and alkaline solution (sodium carbonate) as well as tap water in the elimination of organochlorine and organophosphorus pesticides from naturally contaminated potatoes were examined. The results indicated that acidic solutions were more effective than neutral and alkaline solutions in the elimination of the organochlorine compounds under investigation, Radish solutions eliminated pesticides completely, except o,p'-DDE (73.1% loss), followed by citric and ascorbic acid solutions. On the other hand, organophosphorus pesticides (pirimphos methyl, malathion and profenofos) were eliminated more by acidic, neutral and alkaline solutions than by organochlorines. The percentage of removal ranged from 98.5 to 100% for pirimphos methyl, 87.9 to 100% for malathion and 100% for profenofos.",
"title": "Behaviour of some organophosphorus and organochlorine pesticides in potatoes during soaking in different solutions."
},
{
"docid": "MED-1165",
"text": "The cooking-induced changes in the levels of polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB), and 16 polycyclic aromatic hydrocarbons (PAHs) in various foodstuffs were investigated. Foods included fish (sardine, hake and tuna), meat (veal steak, loin of pork, breast and thigh of chicken, and steak and rib of lamb), string bean, potato, rice, and olive oil. For each food item, raw and cooked (fried, grilled, roasted, boiled) samples were analyzed. There were some variations in the concentrations of PBDEs before and after cooking. However, they depended not only on the cooking process, but mainly on the specific food item. The highest HCB concentrations were found in sardine, being lower in cooked samples. All cooking processes enhanced HCB levels in hake, while very scarce differences could be noted in tuna (raw and cooked). In general terms, the highest PAH concentrations were found after frying by being the values especially notable in fish, excepting hake, where the highest total PAH levels corresponded to roasted samples. The results of this study show that, in general, cooking processes are only of a limited value as a means of reducing PBDE, HCB and PAH concentrations in food.",
"title": "Concentrations of polybrominated diphenyl ethers, hexachlorobenzene and polycyclic aromatic hydrocarbons in various foodstuffs before and after coo..."
},
{
"docid": "MED-1161",
"text": "Pesticides are one of the major inputs used for increasing agricultural productivity of crops. The pesticide residues, left to variable extent in the food materials after harvesting, are beyond the control of consumer and have deleterious effect on human health. The presence of pesticide residues is a major bottleneck in the international trade of food commodities. The localization of pesticides in foods varies with the nature of pesticide molecule, type and portion of food material and environmental factors. The food crops treated with pesticides invariably contain unpredictable amount of these chemicals, therefore, it becomes imperative to find out some alternatives for decontamination of foods. The washing with water or soaking in solutions of salt and some chemicals e.g. chlorine, chlorine dioxide, hydrogen peroxide, ozone, acetic acid, hydroxy peracetic acid, iprodione and detergents are reported to be highly effective in reducing the level of pesticides. Preparatory steps like peeling, trimming etc. remove the residues from outer portions. Various thermal processing treatments like pasteurization, blanching, boiling, cooking, steaming, canning, scrambling etc. have been found valuable in degradation of various pesticides depending upon the type of pesticide and length of treatment. Preservation techniques like drying or dehydration and concentration increase the pesticide content many folds due to concentration effect. Many other techniques like refining, fermentation and curing have been reported to affect the pesticide level in foods to varied extent. Milling, baking, wine making, malting and brewing resulted in lowering of pesticide residue level in the end products. Post harvest treatments and cold storage have also been found effective. Many of the decontamination techniques bring down the concentration of pesticides below MRL. However, the diminution effect depends upon the initial concentration at the time of harvest, substrate/food and type of pesticide. There is diversified information available in literature on the effect of preparation, processing and subsequent handling and storage of foods on pesticide residues which has been compiled in this article.",
"title": "Effect of handling and processing on pesticide residues in food- a review"
},
{
"docid": "MED-1579",
"text": "Crohn's disease is an autoimmune disorder that affects nearly 1.4 million Americans. The etiology of Crohn's disease is not completely understood, however, research has suggested a genetic link. There is currently no known cure for Crohn's disease and, as a result, most government-funded research is being conducted to increase the quality of life of afflicted patients (i.e. reducing chronic inflammation and alleviating growth impairment in pediatric patients). A number of treatment options are available including an alpha-4 integrin inhibitor and several TNF-alpha inhibitors. Furthermore, research is being conducted on several alternative treatment options to help understand exactly which cellular mechanisms (i.e. inducing apoptosis in leukocytes) are required for clinical efficacy. This review seeks to chronicle the current available treatment options for patients affected by Crohn's disease to aid in understanding potential cellular mechanistic requirements for an efficacious drug, and shed light on potential options for future treatment. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.",
"title": "Crohn's disease: a review of treatment options and current research."
},
{
"docid": "MED-1580",
"text": "Background Crohn's disease is common in developed nations where the typical diet is low in fibre and high in processed food. Primary lesions overlie Peyer's patches and colonic lymphoid follicles where bacterial invasion through M-cells occurs. We have assessed the effect of soluble non-starch polysaccharide (NSP) and food emulsifiers on translocation of Escherichia coli across M-cells. Methods To assess effects of soluble plant fibres and food emulsifiers on translocation of mucosa-associated E coli isolates from Crohn's disease patients and from non-Crohn's controls, we used M-cell monolayers, generated by co-culture of Caco2-cl1 and Raji B cells, and human Peyer's patches mounted in Ussing chambers. Results E coli translocation increased across M-cells compared to parent Caco2-cl1 monocultures; 15.8-fold (IQR 6.2–32.0) for Crohn's disease E coli (N=8) and 6.7-fold (IQR 3.7–21.0) for control isolates (N=5). Electron microscopy confirmed E coli within M-cells. Plantain and broccoli NSP markedly reduced E coli translocation across M-cells at 5 mg/ml (range 45.3–82.6% inhibition, p<0.01); apple and leek NSP had no significant effect. Polysorbate-80, 0.01% vol/vol, increased E coli translocation through Caco2-cl1 monolayers 59-fold (p<0.05) and, at higher concentrations, increased translocation across M-cells. Similarly, E coli translocation across human Peyer's patches was reduced 45±7% by soluble plantain NSP (5 mg/ml) and increased 2-fold by polysorbate-80 (0.1% vol/vol). Conclusions Translocation of E coli across M-cells is reduced by soluble plant fibres, particularly plantain and broccoli, but increased by the emulsifier Polysorbate-80. These effects occur at relevant concentrations and may contribute to the impact of dietary factors on Crohn's disease pathogenesis.",
"title": "Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers"
},
{
"docid": "MED-1575",
"text": "Background Epithelial barrier function is impaired in Crohn's disease. Aim To define the underlying cellular mechanisms with special attention to tight junctions. Methods Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling and 4′,6‐diamidino‐2‐phenylindole staining. Results Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore‐forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor α. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. Conclusion Upregulation of pore‐forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.",
"title": "Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease"
},
{
"docid": "MED-1578",
"text": "Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic and microbial factors involved in the development of the disease. A remarkable feature of this disease in childhood is the effective response to exclusive enteral nutrition (EEN) therapy and the need for complete exclusion of normal diet required for success (principle of exclusivity). EEN or dietary interventions might act through removal of dietary components, which affect microbial composition, decrease a proinflammatory response and promote restitution of the epithelial barrier, likewise allowing termination of this vicious disease-forming cycle before a critical threshold is reached. Multiple traditional and nontraditional dietary components may affect the microbiome, mucous layer, intestinal permeability, or adherence and translocation of pathobionts. We review the epidemiological data, as well as data from animal models and cell lines, and propose a model for pathogenesis we have termed the 'bacterial penetration cycle', whereby dietary components such as animal fat, high sugar intake and gliadin, and consumption of emulsifiers, maltodextrin as well as low-fiber diets may be able to cause a localized acquired bacterial clearance defect, leading to bacterial adhesion and penetration, and subsequently inflammation in the gut. © 2014 S. Karger AG, Basel.",
"title": "Dietary clues to the pathogenesis of Crohn's disease."
},
{
"docid": "MED-1582",
"text": "Background & Aims Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn’s disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses’ Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusion Based on data from the Nurses’ Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.",
"title": "A Prospective Study of Long-term Intake of Dietary Fiber and Risk of Crohn’s Disease and Ulcerative Colitis"
},
{
"docid": "MED-1576",
"text": "OBJECTIVES: The incidence of inflammatory bowel disease (IBD) is increasing. Dietary factors such as the spread of the \"Western\" diet, high in fat and protein but low in fruits and vegetables, may be associated with the increase. Although many studies have evaluated the association between diet and IBD risk, there has been no systematic review. METHODS: We performed a systematic review using guideline-recommended methodology to evaluate the association between pre-illness intake of nutrients (fats, carbohydrates, protein) and food groups (fruits, vegetables, meats) and the risk of subsequent IBD diagnosis. Eligible studies were identified via structured keyword searches in PubMed and Google Scholar and manual searches. RESULTS: Nineteen studies were included, encompassing 2,609 IBD patients (1,269 Crohn's disease (CD) and 1,340 ulcerative colitis (UC) patients) and over 4,000 controls. Studies reported a positive association between high intake of saturated fats, monounsaturated fatty acids, total polyunsaturated fatty acids (PUFAs), total omega-3 fatty acids, omega-6 fatty acids, mono- and disaccharides, and meat and increased subsequent CD risk. Studies reported a negative association between dietary fiber and fruits and subsequent CD risk. High intakes of total fats, total PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of UC. High vegetable intake was associated with a decreased risk of UC. CONCLUSIONS: High dietary intakes of total fats, PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of CD and UC. High fiber and fruit intakes were associated with decreased CD risk, and high vegetable intake was associated with decreased UC risk.",
"title": "Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature."
},
{
"docid": "MED-1577",
"text": "Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the brain caused by a ubiquitous polyomavirus, JC virus. PML is almost always associated with some underlying immunosuppression and acquired immune deficiency syndrome has been the most common predisposing disorder. Recently, different pharmacological agents have been demonstrated to increase the risk of PML. Therapies that predispose people to PML can be classified into three categories: therapies that uniquely increase the risk for the disorder, such as the monoclonal antibodies natalizumab and efalizumab; therapies that appear to increase the risk in individuals already at risk of PML due to pre-existing conditions, such as rituximab and mycophenolate mofetil; and therapies with a mechanism of action that might suggest a potential for increased PML risk and/or with which rare cases of PML have been observed. Unlike the latter two classes, therapeutic agents uniquely increasing the risk of PML are associated with a much greater prevalence of the disorder and a latent interval from the time of drug initiation to the development of PML. PML development with pharmacological agents has provided new insight into the pathogenesis of this devastating disorder. This review focuses on the risks of PML with multiple pharmacological agents, the proposed pathogenesis with these agents, and potential risk mitigation strategies.",
"title": "Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps"
},
{
"docid": "MED-1157",
"text": "In 1997 this laboratory initiated a research program with the objective of examining the effect that rinsing of produce with tap water would have on pesticide residues. Samples were obtained from local markets and/or grown at our experimental farm. Because approximately 35% of produce from retail sources contains pesticide residues, growing and treating produce at an experimental farm had the advantage that all such samples contain pesticide residues. Pesticides were applied under normal field conditions to a variety of food crops and the vegetation was allowed to undergo natural weathering prior to harvest. The resulting samples contained field-incurred or \"field-fortified\" residues. This experimental design was employed to mimic as closely as possible real world samples. Crops were treated, harvested, and divided into equal subsamples. One subsample was processed unwashed, whereas the other was rinsed under tap water. The extraction and analysis method used was a multi-residue method developed in our laboratory. Twelve pesticides were included in this study: the fungicides captan, chlorothalonil, iprodione, and vinclozolin; and the insecticides endosulfan, permethrin, methoxychlor, malathion, diazinon, chlorpyrifos, bifenthrin, and DDE (a soil metabolite of DDT). Statistical analysis of the data using the Wilcoxon signed-rank test showed that rinsing removed residues for nine of the twelve pesticides studied. Residues of vinclozolin, bifenthrin, and chlorpyrifos were not reduced. The rinsability of a pesticide is not correlated with its water solubility.",
"title": "Reduction of pesticide residues on produce by rinsing."
},
{
"docid": "MED-1164",
"text": "We assessed organophosphorus (OP) pesticide exposure from diet by biological monitoring among Seattle, Washington, preschool children. Parents kept food diaries for 3 days before urine collection, and they distinguished organic and conventional foods based on label information. Children were then classified as having consumed either organic or conventional diets based on analysis of the diary data. Residential pesticide use was also recorded for each home. We collected 24-hr urine samples from 18 children with organic diets and 21 children with conventional diets and analyzed them for five OP pesticide metabolites. We found significantly higher median concentrations of total dimethyl alkylphosphate metabolites than total diethyl alkylphosphate metabolites (0.06 and 0.02 micro mol/L, respectively; p = 0.0001). The median total dimethyl metabolite concentration was approximately six times higher for children with conventional diets than for children with organic diets (0.17 and 0.03 micro mol/L; p = 0.0003); mean concentrations differed by a factor of nine (0.34 and 0.04 micro mol/L). We calculated dose estimates from urinary dimethyl metabolites and from agricultural pesticide use data, assuming that all exposure came from a single pesticide. The dose estimates suggest that consumption of organic fruits, vegetables, and juice can reduce children's exposure levels from above to below the U.S. Environmental Protection Agency's current guidelines, thereby shifting exposures from a range of uncertain risk to a range of negligible risk. Consumption of organic produce appears to provide a relatively simple way for parents to reduce their children's exposure to OP pesticides.",
"title": "Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets."
},
{
"docid": "MED-2494",
"text": "Background In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. Methods We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2–4 years, n=207), school-age children (5–7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. Results Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. Conclusions Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake.",
"title": "Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment"
},
{
"docid": "MED-1162",
"text": "Consumers are frequently urged to avoid imported foods as well as specific fruits and vegetables due to health concerns from pesticide residues and are often encouraged to choose organic fruits and vegetables rather than conventional forms. Studies have demonstrated that while organic fruits and vegetables have lower levels of pesticide residues than do conventional fruits and vegetables, pesticide residues are still frequently detected on organic fruits and vegetables; typical dietary consumer exposure to pesticide residues from conventional fruits and vegetables does not appear to be of health significance. Similarly, research does not demonstrate that imported fruits and vegetables pose greater risks from pesticide residues than do domestic fruits and vegetables or that specific fruits and vegetables singled out as being the most highly contaminated by pesticides should be avoided in their conventional forms.",
"title": "Pesticide residues in imported, organic, and \"suspect\" fruits and vegetables."
},
{
"docid": "MED-1574",
"text": "Crohn's disease (CD) is associated with intestinal dysbiosis evidenced by an altered microbiome forming thick biofilms on the epithelium. Additionally, adherent-invasive E. coli (AIEC) strains are frequently isolated from ileal lesions of CD patients indicating a potential role for these strains in disease pathogenesis. The composition and characteristics of the host microbiome are influenced by environmental factors, particularly diet. Polysaccharides added to food as emulsifiers, stabilizers or bulking agents have been linked to bacteria-associated intestinal disorders. The escalating consumption of polysaccharides in Western diets parallels an increased incidence of CD during the latter 20th century. In this study, the effect of a polysaccharide panel on adhesiveness of the CD-associated AIEC strain LF82 was analyzed to determine if these food additives promote disease-associated bacterial phenotypes. Maltodextrin (MDX), a polysaccharide derived from starch hydrolysis, markedly enhanced LF82 specific biofilm formation. Biofilm formation of multiple other E. coli strains was also promoted by MDX. MDX-induced E. coli biofilm formation was independent of polysaccharide chain length indicating a requirement for MDX metabolism. MDX exposure induced type I pili expression, which was required for MDX-enhanced biofilm formation. MDX also increased bacterial adhesion to human intestinal epithelial cell monolayers in a mechanism dependent on type 1 pili and independent of the cellular receptor CEACAM6, suggesting a novel mechanism of epithelial cell adhesion. Analysis of mucosa-associated bacteria from individuals with and without CD showed increased prevalence of malX, a gene essential for MDX metabolism, uniquely in the ileum of CD patients. These findings demonstrate that the ubiquitous dietary component MDX enhances E. coli adhesion and suggests a mechanism by which Western diets rich in specific polysaccharides may promote dysbiosis of gut microbes and contribute to disease susceptibility.",
"title": "Crohn's Disease-Associated Adherent-Invasive Escherichia coli Adhesion Is Enhanced by Exposure to the Ubiquitous Dietary Polysaccharide Maltodextrin"
}
] |
[
{
"docid": "MED-3651",
"text": "Thirteen sites in each of 60 domestic kitchens were examined for Salmonella and Campylobacter spp. following the preparation of a chicken for cooking and the application of different hygiene regimes. During food preparation bacteria became widely disseminated to hand and food contact surfaces. Where cleaning was carried out with detergent and hot water using a prescribed routine there was no significant decrease in the frequency of contaminated surfaces. Where hypochlorite was used in addition, a significant reduction in the number of contaminated sites was observed. The study suggests that there is a need to better understand and promote effective hygiene procedures for the domestic kitchen.",
"title": "The effectiveness of hygiene procedures for prevention of cross-contamination from chicken carcases in the domestic kitchen."
},
{
"docid": "MED-1038",
"text": "We examined effects of fiber on stool output, since this is one of the primary mediating variables for the hypothesized relationship between fiber and disease. Total neutral detergent fiber in the dietary fiber source was predictive of stool weight but not frequency. Substantial individual differences in stool output remained when dietary factors were controlled. Personality measures were used to predict stool weight and frequency independently of diet, and accounted for about as much variance in stool output as did dietary fiber. These results suggest that personality factors predispose some persons to low stool output. These individuals may benefit particularly from dietary fiber.",
"title": "Dietary fiber and personality factors as determinants of stool output."
},
{
"docid": "MED-4798",
"text": "OBJECTIVE To review the evidence for the efficacy of products used for environmental or hand cleaning on the rates of Clostridium difficile–associated diarrhea (CDAD). QUALITY OF EVIDENCE MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched for articles pertinent to the efficacy of cleaning products against C difficile or studies with outcomes related to rates of CDAD. Evidence was level II. MAIN MESSAGE Minimizing the incidence of CDAD in geriatric rehabilitation units is essential to achieving the goals of increasing patient function and independence for discharge into the community. Attention to environmental control of C difficile and its spores by health care workers and patient visitors is an important secondary prevention strategy. CONCLUSION Chlorine-releasing agents are more effective than detergents for killing spores produced by C difficile. No level I evidence is available to determine if the use of chlorine-releasing agents has an effect on rates of CDAD. Hand-washing is currently the recommended strategy for reducing transmission of C difficile. Alcohol gels do not inactivate C difficile spores; however, increased use of alcohol hand gel has not been associated with higher rates of CDAD. Résumé OBJECTIF Examiner les preuves indiquant que les produits utilisés pour nettoyer l’environnement et les mains sont efficaces pour réduire le taux de diarrhée due au Clostridium difficile (DDCD). QUALITÉ DES PREUVES On a consulté MEDLINE, EMBASE et la Cochrane Database of Systematic Reviews en retenant les articles portant sur l’efficacité des agents de nettoyage contre le C difficile ou les études traitant de questions liées aux taux de DDCD. Les preuves étaient de niveau II. PRINCIPAL MESSAGE La réduction de l’incidence de la DDCD dans les unités de réadaptation gériatrique est une condition essentielle pour accroître l’état fonctionnel et l’indépendance des patients qui retournent dans la communauté. Pour les intervenants et pour les visiteurs des patients, le contrôle du C difficile et de ses spores dans l’environnement est primordial comme stratégie de prévention secondaire. Les agents qui libèrent du chlore sont plus efficaces que les détergents pour tuer les spores du C difficile. Il n’existe pas de preuves de niveau I indiquant que l’utilisation d’agents libérant du chlore influence les taux de DDCD. Le lavage des mains est la stratégie présentement recommandée pour réduire la transmission du C difficile. Les gels d’alcool n’inactivent pas les spores du C difficile; toutefois, une utilisation accrue de gels d’alcool n’a pas entraîné d’augmentation du taux de DDCD.",
"title": "Efficacy of cleaning products for C difficile"
},
{
"docid": "MED-3658",
"text": "The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute migraine drugs. Soon, seven different triptans will be clinically available at 13 different oral doses, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis. We wished to provide an evidence-based foundation for using triptans in clinical practice, and to review the methodological issues surrounding triptan trials. We asked pharmaceutical companies and the principal investigators of company-independent trials for the 'raw patient data' of all double-blind, randomized, controlled, clinical trials with oral triptans in migraine. All data were cross-checked with published or presented data. We calculated summary estimates across studies for important efficacy and tolerability parameters, and compared these with those from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials, 53 (12 not yet published) involving 24089 patients met the criteria for inclusion. Mean results (and 95% confidence intervals) for sumatriptan 100 mg, the first available and most widely prescribed oral triptan, are 59% (57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post-dose), and 67% (63-70) for consistency (response in at least two out of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) are 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data: rizatriptan 10 mg shows better efficacy and consistency, and similar tolerability; eletriptan 80 mg shows better efficacy, similar consistency, but lower tolerability; almotriptan 12.5 mg shows similar efficacy at 2 h but better sustained pain-free response, consistency, and tolerability; sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show lower efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 40 mg, and rizatriptan 5 mg show very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest substantially lower efficacy. The major methodological issues involve the choice of the primary endpoint, consistency over multiple attacks, how to evaluate headache recurrence, use of placebo-subtracted proportions to control for across-study differences, and the difference between tolerability and safety. In addition, there are a number of methodological issues specific for direct comparator trials, including encapsulation and patient selection. At marketed doses, all oral triptans are effective and well tolerated. Differences among them are in general relatively small, but clinically relevant for individual patients. Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success. Sumatriptan features the longest clinical experience and the widest range of formulations. All triptans are contra-indicated in the presence of cardiovascular disease.",
"title": "Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials."
},
{
"docid": "MED-4783",
"text": "INTRODUCTION: Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. METHODS: In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. RESULTS: Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. DISCUSSION: Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.",
"title": "Childhood soy intake and breast cancer risk in Asian American women."
},
{
"docid": "MED-2893",
"text": "Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.",
"title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis."
},
{
"docid": "MED-2397",
"text": "Background Studies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs). Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking. Objectives This study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers. Methods The cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status. Results DDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status. Conclusions This study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.",
"title": "Organochlorine Exposure and Incidence of Diabetes in a Cohort of Great Lakes Sport Fish Consumers"
},
{
"docid": "MED-1258",
"text": "Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.",
"title": "The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia."
},
{
"docid": "MED-4496",
"text": "BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.",
"title": "The effect of fruit and vegetable intake on risk for coronary heart disease."
},
{
"docid": "MED-957",
"text": "Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to \"negative\" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)",
"title": "Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powde..."
},
{
"docid": "MED-927",
"text": "OBJECTIVE: To assess the effects of krill oil on blood lipids, specifically total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). METHODS: A multi-center, three-month, prospective, randomized study followed by a three-month, controlled follow-up of patients treated with 1 g and 1.5 g krill oil daily. Patients with hyperlipidemia able to maintain a healthy diet and with blood cholesterol levels between 194 and 348 mg per dL were eligible for enrollment in the trial. A sample size of 120 patients (30 patients per group) was randomly assigned to one of four groups. Group A received krill oil at a body mass index (BMI)-dependent daily dosage of 2-3 g daily. Patients in Group B were given 1-1.5 g krill oil daily, and Group C was given fish oil containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) per gram of oil at a dose of 3 g daily. Group D was given a placebo containing microcrystalline cellulose. The krill oil used in this study was Neptune Krill Oil, provided by Neptune Technologies and Bioresources, Laval, Quebec, Canada. OUTCOME MEASURES: Primary parameters tested (baseline and 90-day visit) were total blood cholesterol, triglycerides, LDL, HDL, and glucose. RESULTS: Krill oil 1-3 g per day (BMI-dependent) was found to be effective for the reduction of glucose, total cholesterol, triglycerides, LDL, and HDL, compared to both fish oil and placebo. CONCLUSIONS: The results of the present study demonstrate within high levels of confidence that krill oil is effective for the management of hyperlipidemia by significantly reducing total cholesterol, LDL, and triglycerides, and increasing HDL levels. At lower and equal doses, krill oil was significantly more effective than fish oil for the reduction of glucose, triglycerides, and LDL levels.",
"title": "Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia."
},
{
"docid": "MED-5224",
"text": "Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.",
"title": "Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye"
},
{
"docid": "MED-1693",
"text": "Diet is believed to play a complex role in the development of cardiovascular disease, the leading cause of death in the Western world. Tomatoes, the second most produced and consumed vegetable nationwide, are a rich source of lycopene, beta-carotene, folate, potassium, vitamin C, flavonoids, and vitamin E. The processing of tomatoes may significantly affect the bioavailability of these nutrients. Homogenization, heat treatment, and the incorporation of oil in processed tomato products leads to increased lycopene bioavailability, while some of the same processes cause significant loss of other nutrients. Nutrient content is also affected by variety and maturity. Many of these nutrients may function individually, or in concert, to protect lipoproteins and vascular cells from oxidation, the most widely accepted theory for the genesis of atherosclerosis. This hypothesis has been supported by in vitro, limited in vivo, and many epidemiological studies that associate reduced cardiovascular risk with consumption of antioxidant-rich foods. Other cardioprotective functions provided by the nutrients in tomatoes may include the reduction of low-density lipoprotein (LDL) cholesterol, homocysteine, platelet aggregation, and blood pressure. Because tomatoes include several nutrients associated with theoretical or proven effects and are widely consumed year round, they may be considered a valuable component of a cardioprotective diet.",
"title": "Tomatoes and cardiovascular health."
},
{
"docid": "MED-3462",
"text": "Immediate and delayed-onset muscle soreness differ mainly in chronology of presentation. Both conditions share the same quality of pain, eliciting and relieving activities and a varying degree of functional deficits. There is no single mechanism for muscle soreness; instead, it is a culmination of 6 different mechanisms. The developing pathway of DOMS begins with microtrauma to muscles and then surrounding connective tissues. Microtrauma is then followed by an inflammatory process and subsequent shifts of fluid and electrolytes. Throughout the progression of these events, muscle spasms may be present, exacerbating the overall condition. There are a multitude of modalities to manage the associated symptoms of immediate soreness and DOMS. Outcomes of each modality seem to be as diverse as the modalities themselves. The judicious use of NSAIDs and continued exercise are suggested to be the most reliable methods and recommended. This review article and each study cited, however, represent just one part of the clinician's decisionmaking process. Careful affirmation of temporary deficits from muscle soreness is not to be taken lightly, nor is the advisement and medical management of muscle soreness prescribed by the clinician.",
"title": "Muscle soreness and delayed-onset muscle soreness."
},
{
"docid": "MED-4629",
"text": "In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.",
"title": "Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?"
},
{
"docid": "MED-3744",
"text": "Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.",
"title": "Antioxidant and antiproliferative activities of common fruits."
},
{
"docid": "MED-3026",
"text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.",
"title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data"
},
{
"docid": "MED-2792",
"text": "Two populations of immigrants to London and to the West Indies from the Indian subcontinent have higher than expected morbidity and mortality from atherosclerosis but do not show the commonly accepted major risk factors. This study investigated the hypothesis that ghee, a clarified butter product prized in Indian cooking, contains cholesterol oxides and could therefore be an important source of dietary exposure to cholesterol oxides and an explanation for the high atherosclerosis risk. Substantial amounts of cholesterol oxides were found in ghee (12.3% of sterols), but not in fresh butter, by thin-layer and high-performance-liquid chromatography. Dietary exposure to cholesterol oxides from ghee may offer a logical explanation for the high frequency of atherosclerotic complications in these Indian populations.",
"title": "Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations."
},
{
"docid": "MED-3946",
"text": "The fruit of Euterpe oleraceae, commonly known as acai, has been demonstrated to exhibit significantly high antioxidant capacity in vitro, especially for superoxide and peroxyl scavenging, and, therefore, may have possible health benefits. In this study, the antioxidant capacities of freeze-dried acai fruit pulp/skin powder (OptiAcai) were evaluated by different assays with various free radical sources. It was found to have exceptional activity against superoxide in the superoxide scavenging (SOD) assay, the highest of any food reported to date against the peroxyl radical as measured by the oxygen radical absorbance capacity assay with fluorescein as the fluorescent probe (ORACFL), and mild activity against both the peroxynitrite and hydroxyl radical by the peroxynitrite averting capacity (NORAC) and hydroxyl radical averting capacity (HORAC) assays, respectively. The SOD of acai was 1614 units/g, an extremely high scavenging capacity for O2*-, by far the highest of any fruit or vegetable tested to date. Total phenolics were also tested as comparison. In the total antioxidant (TAO) assay, antioxidants in acai were differentiated into \"slow-acting\" and \"fast-acting\" components. An assay measuring inhibition of reactive oxygen species (ROS) formation in freshly purified human neutrophils showed that antioxidants in acai are able to enter human cells in a fully functional form and to perform an oxygen quenching function at very low doses. Furthermore, other bioactivities related to anti-inflammation and immune functions were also investigated. Acai was found to be a potential cyclooxygenase (COX)-1 and COX-2 inhibitor. It also showed a weak effect on lipopolysaccharide (LPS)-induced nitric oxide but no effect on either lymphocyte proliferation and phagocytic capacity.",
"title": "Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai)."
},
{
"docid": "MED-4585",
"text": "The total phenolic content of 13 commercially available fruit juices and juice drinks, selected to represent the most popular juice flavors in the United Kingdom, were analyzed using the Folin-Ciocalteu assay. Individual phenolic compounds were identified and quantified using HPLC-PDA-MS2. The catechin content and degree of polymerization of proanthocyanidins were also analyzed. Purple grape juice contained the largest number of individual phenolic compounds and also the highest concentration of total phenolics. The main components were flavan-3-ols, anthocyanins, and hydroxycinnamates, which accounted for 93% of the total phenolic content. In contrast, white grape juice, which contained principally hydroxycinnamates, had the lowest total phenolic content. Antioxidant activity was measured using the ORAC and FRAP assays, and the data obtained were in broad agreement with total phenol content. In view of the recent findings of the Kame project indicating that long-term fruit juice consumption can provide protection against Alzheimer's disease (Dai et al. Am. J. Med. 2006, 379, 464-475), it is suggested that the protective effects may be enhanced by consumption of a combination of juices rich in phenolics and containing a diverse variety of individual phenolic compounds, namely, juices derived from purple grapes, grapefruit, cranberries, and apples.",
"title": "Evaluation of phenolic compounds in commercial fruit juices and fruit drinks."
},
{
"docid": "MED-1781",
"text": "BACKGROUND: Saturated fat intake has been associated with both cardiovascular disease and cancer risk, and a newly published study found an association between saturated fat intake and a lower sperm concentration in infertile men. OBJECTIVE: The objective was to examine the association between dietary fat intake and semen quality among 701 young Danish men from the general population. DESIGN: In this cross-sectional study, men were recruited when they were examined to determine their fitness for military service from 2008 to 2010. They delivered a semen sample, underwent a physical examination, and answered a questionnaire comprising a quantitative food-frequency questionnaire to assess food and nutrient intakes. Multiple linear regression analyses were performed with semen variables as outcomes and dietary fat intakes as exposure variables, adjusted for confounders. RESULTS: A lower sperm concentration and total sperm count in men with a high intake of saturated fat was found. A significant dose-response association was found, and men in the highest quartile of saturated fat intake had a 38% (95% CI: 0.1%, 61%) lower sperm concentration and a 41% (95% CI: 4%, 64%) lower total sperm count than did men in the lowest quartile. No association between semen quality and intake of other types of fat was found. CONCLUSIONS: Our findings are of potentially great public interest, because changes in diet over the past decades may be part of the explanation for the recently reported high frequency of subnormal human sperm counts. A reduction in saturated fat intake may be beneficial for both general and reproductive health.",
"title": "High dietary intake of saturated fat is associated with reduced semen quality among 701 young Danish men from the general population."
},
{
"docid": "MED-2153",
"text": "Background: Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer. Methods: We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results: We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables. Conclusion: Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.",
"title": "Nut consumption and risk of pancreatic cancer in women"
},
{
"docid": "MED-4918",
"text": "Background & Aims The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. Methods This study included 9,133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 sex-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n=5,558) or age at sampling (n=7,210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. Results Of 9,133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio=3.9; 95% CI, 2.0–7.5; P<.001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts (respectively) than in the Air Force cohort (both P ≤ .0001). Conclusions During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD appears to have increased dramatically in the United States during the past 50 years.",
"title": "Increased Prevalence and Mortality in Undiagnosed Celiac Disease"
},
{
"docid": "MED-1241",
"text": "PURPOSE: With little scientific evidence to support use of aromatherapy for postoperative nausea and/or vomiting (PONV) symptoms, this study evaluated controlled breathing with peppermint aromatherapy (AR) and controlled breathing alone (CB) for PONV relief. DESIGN: A single blind randomized control trial design was used. METHODS: On initial PONV complaint, symptomatic subjects received either CB (n = 16) or AR (n = 26) intervention based on randomization at enrollment. A second treatment was repeated at 5 minutes if indicated. Final assessment occurred 10 minutes post initial treatment. Rescue medication was offered for persistent symptoms. FINDINGS: Among eligible subjects, PONV incidence was 21.4% (42/196). Gender was the only risk factor contributing to PONV symptoms (P = .0024). Though not statistically significant, CB was more efficacious than AR, 62.5% versus 57.7%, respectively. CONCLUSIONS: CB can be initiated without delay as an alternative to prescribed antiemetics. Data also support use of peppermint AR in conjunction with CB for PONV relief. Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.",
"title": "Controlled breathing with or without peppermint aromatherapy for postoperative nausea and/or vomiting symptom relief: a randomized controlled trial."
},
{
"docid": "MED-2215",
"text": "We investigated the relationship between animal product consumption and evidence of dementia in two cohort substudies. The first enrolled 272 California residents matched for age, sex, and zip code (1 vegan, 1 lacto-ovo-vegetarian, and 2 'heavy' meat eaters in each of 68 quartets). This design ensured a wide range of dietary exposure. The second included 2,984 unmatched subjects who resided within the Loma Linda, California area. All subjects were enrolled in the Adventist Health Study. The matched subjects who ate meat (including poultry and fish) were more than twice as likely to become demented as their vegetarian counterparts (relative risk 2.18, p = 0.065) and the discrepancy was further widened (relative risk 2.99, p = 0.048) when past meat consumption was taken into account. There was no significant difference in the incidence of dementia in the vegetarian versus meat-eating unmatched subjects. There was no obvious explanation for the difference between the two substudies, although the power of the unmatched sub-study to detect an effect of 'heavy' meat consumption was unexpectedly limited. There was a trend towards delayed onset of dementia in vegetarians in both substudies.",
"title": "The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study."
},
{
"docid": "MED-4938",
"text": "Objective To test the effect of four polychlorinated biphenyl congeners (PCB-77, PCB-105, PCB 153 and PCB 180) on expression of three adhesion markers, TGF-β1, VEGF, and type I collagen in normal human peritoneal and adhesion fibroblasts Design Cell culture study Settings University Research Laboratory Patients Primary cultures of normal peritoneal and adhesion fibroblasts were established from three patients. Interventions Fibroblasts were treated with PCB-77, PCB-105, PCB-153 or PCB-180, 20 ppm for 24 hours. Total RNA was extracted from each treatment and subjected to real-time RT/PCR. Main Outcome and Measures mRNA levels of type I collagen, VEGF and TGF-β1. Results Normal human peritoneal fibroblasts expressed type I collagen, VEGF and TGF-β1. Exposure of normal human fibroblasts to PCB-77, PCB-105, PCB-153 or PCB-180 did not affect mRNA levels of β-actin, the house keeping gene used to normalized RNA levels for the real-time RT/PCR, nor did it affect cell viability as assessed by trypan blue exclusion. PCB treatments, compared to control, resulted in no significant change for TGF-β1 or VEGF mRNA levels, in normal peritoneal and adhesion fibroblasts. In marked contrast, type I collagen mRNA levels were markedly increased in response to the brief 24 hrs exposure to each PCB, treatment each (P<0.0001) in both cell types. Conclusion The finding that PCB-77, PCB-105, PCB-153 or PCB-180 increased the expression of type I collagen in human normal peritoneal and adhesion fibroblasts is the first demonstration of involvement of organochlorines in the pathogenesis of tissue fibrosis. This may implicate organochlorine exposure as an etiologic factor in a wide variety of previously unlinked human ailments characterized by fibrosis.",
"title": "PCBs Enhance Collagen I Expression from Human Peritoneal Fibroblasts"
},
{
"docid": "MED-1420",
"text": "PURPOSE OF REVIEW: To highlight mechanisms whereby diet affects colonic function and disease patterns. RECENT FINDINGS: Topical nutrients are preferentially used by the gut mucosa to maintain structure and function. With the colon, topical nutrients are generated by the colonic microbiota to maintain mucosal health. Most importantly, short chain fatty acids control proliferation and differentiation, thereby reducing colon cancer risk. In patients with massive loss of small intestine, short chain fatty acid production supports survival by releasing up to 1000 kcal energy/day. Human studies show that the microbiota synthesizes a large pool of utilizable folate which may support survival in impoverished populations. Unfortunately, the microbiota may also elaborate toxic products from food residues such as genotoxic hydrogen sulfide by sulfur-reducing bacteria in response to a high-meat diet. The employment of culture-free techniques based on 16S regions of DNA has revealed that our colons harbor over 800 bacterial species and 7000 different strains. Evidence suggests that the diet directly influences the diversity of the microbiota, providing the link between diet, colonic disease, and colon cancer. The microbiota, however, can determine the efficiency of food absorption and risk of obesity. SUMMARY: Our investigations have focused on a small number of bacterial species: characterization of microbiota and its metabolism can be expected to provide the key to colonic health and disease.",
"title": "Nutrition and colonic health: the critical role of the microbiota."
},
{
"docid": "MED-2435",
"text": "Breast cancer is the leading cause of cancer-related deaths in women in the United States and many other countries. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for many cancers, especially for breast cancer. Natural products are being tested with a hope of identifying novel potent molecules as anticancer agents. Phytochemicals and dietary compounds have been used for the treatment of various illnesses throughout history due to their safety, low toxicity, and general availability. Currently, many active phytochemicals are in clinical trials. Preclinical and clinical studies have indicated that daily consumption of dietary phytochemicals reduces the risk of several cancers. Phytochemicals can inhibit, delay, or reverse carcinogenesis by inducing detoxifying and antioxidant enzymes, by regulating inflammatory/proliferative signaling pathways, and by inducing apoptosis. This review article describes some of the potential natural cancer preventive compounds, along with a mechanistic discussion of their interactions with key cellular signal transduction pathways as well as their contribution to the suppression of breast cancer cell growth.",
"title": "Chemoprevention of breast cancer by dietary compounds."
},
{
"docid": "MED-2382",
"text": "BACKGROUND: Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal allergic reactions in the United States, and the prevalence appears to be increasing. OBJECTIVES: We sought to determine the US prevalence of self-reported peanut, TN, and sesame allergy in 2008 and compare results with comparable surveys conducted in 1997 and 2002. METHODS: A nationwide, cross-sectional, random telephone survey for peanut and TN allergy was conducted with a previously used questionnaire, with additional questions about sesame. RESULTS: A total of 5,300 households (13,534 subjects) were surveyed (participation rate, 42% vs 52% in 2002 and 67% in 1997). Peanut allergy, TN allergy, or both was reported by 1.4% of subjects (95% CI, 1.2% to 1.6%) compared with 1.2% in 2002 and 1.4% in 1997. For adults, the prevalence was 1.3% (95% CI, 1.1% to 1.6%), which was not significantly different from prior surveys. However, the prevalence of peanut or TN allergy for children younger than 18 years was 2.1% (95% CI, 1.6% to 2.7%) compared with 1.2% in 2002 (P = .007) and 0.6% in 1997 (P < .001). The prevalence of peanut allergy in children in 2008 was 1.4% (95% CI, 1.0% to 1.9%) compared with 0.8% in 2002 (P = not significant) and 0.4% in 1997 (P < .0001). The prevalence of childhood TN allergy increased significantly across the survey waves (1.1% in 2008, 0.5% in 2002, and 0.2% in 1997). Sesame allergy was reported by 0.1% (95% CI, 0.0% to 0.2%). CONCLUSIONS: Although caution is required in comparing surveys, peanut allergy, TN allergy, or both continue to be reported by more than 1% of the US population (eg, >3 million subjects) and appear to be increasingly reported among children over the past decade. Sesame allergy is reported much less commonly. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.",
"title": "US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up."
},
{
"docid": "MED-1192",
"text": "Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.",
"title": "Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies"
}
] |
5ae3ce955542994393b9e76b
|
Pamela Morgan Halpert, is a fictional character on the U.S. television sitcom "The Office", played by Jenna Fischer, an American actress, and is widely known for her portrayal as Pam Beesly, on which organization?
|
[
{
"docid": "2303476",
"text": "Regina Marie \"Jenna\" Fischer (born March 7, 1974) is an American actress. She is widely known for her portrayal as Pam Beesly on the NBC sitcom \"The Office\", for which she received critical acclaim and was nominated for the Primetime Emmy Award for Outstanding Supporting Actress in a Comedy Series in 2007.",
"title": ""
},
{
"docid": "3721290",
"text": "Pamela Morgan Halpert (née Beesly; born March 25, 1979) is a fictional character on the U.S. television sitcom \"The Office\", played by Jenna Fischer. Her counterpart in the original UK series of \"The Office\" is Dawn Tinsley. Her character is initially the receptionist at the paper distribution company Dunder Mifflin, before becoming a saleswoman and eventually office administrator until her termination in the series finale. Her character is shy, growing assertive but amiable, and artistically inclined, and shares romantic interest with Jim Halpert, whom she begins dating in the fourth season and marries and starts a family with as the series continues.",
"title": ""
}
] |
[
{
"docid": "9846918",
"text": "\"The Negotiation\" (originally titled \"Labor Negotiation\") is the nineteenth episode of the third season of the American comedy television series \"The Office\", and the show's forty-seventh episode overall. The series depicts the everyday lives of office employees in the Scranton branch of the fictional Dunder Mifflin Paper Company. In this episode, Roy Anderson (David Denman) tries to attack Jim Halpert (John Krasinski) for kissing Pam Beesly (Jenna Fischer) on Casino Night, only to be pepper-sprayed by Dwight Schrute (Rainn Wilson). Jim repeatedly tries to thank Dwight for his actions, but each attempt is rejected. Meanwhile, with Roy fired, Darryl Philbin (Craig Robinson) asks for a raise and is astounded when he learns that this raise would cause him to be paid more than his boss, Michael Scott (Steve Carell).",
"title": ""
},
{
"docid": "2221234",
"text": "Dawn Tinsley is a fictional character in the BBC sitcom \"The Office\", played by Lucy Davis. She is a receptionist for paper merchants Wernham Hogg and was originally engaged to warehouse worker Lee. Her American \"The Office\" equivalent is Pam Beesly. She is also the inspiration for Laetitia Kadiri in the French version of the show, \"Le Bureau\", and Anne Viens in the Québécois version, \"La Job\".",
"title": ""
},
{
"docid": "7422946",
"text": "Pamela Barnes Ewing is a fictional character from the CBS primetime soap opera, \"Dallas\". Pamela is portrayed by actress Victoria Principal, first appearing on the show in the first episode, entitled \"Digger's Daughter\", which was first broadcast on April 2, 1978. \"Dallas\" follows the trials of the wealthy Ewing oil family in the city of Dallas, Texas, which Pam has married into. Principal played Pam until the end of the tenth season of \"Dallas\" in 1987, when the character crashes into a truck carrying butane and propane and her body is severely burned. After this, she is briefly played by actress Margaret Michaels in an attempt to write the character out. Pamela's storylines in season 1 focus on her relationship with her new husband, Bobby Ewing (Patrick Duffy), and her fight against the considerable suspicion and hostility from within the Ewing family, due to Pamela being a member of the Barnes family. Pamela's love for Bobby remains a strong character trait throughout her tenure on the show, noted for its similarities to \"Romeo and Juliet\", with two people from hostile families falling in love.",
"title": ""
},
{
"docid": "24896769",
"text": "Kelly Erin Hannon (born May 1, 1986) is a fictional character from the U.S. comedy television series \"The Office\". She is the office receptionist for the Scranton branch of the Dunder Mifflin Paper Company, Inc., a position previously held by Pam Halpert before she quit to go work for the Michael Scott Paper Company.",
"title": ""
},
{
"docid": "860047",
"text": "Pamela Dawber (born October 18, 1951) is an American actress best known for her lead television sitcom roles as Mindy McConnell in \"Mork & Mindy\" (1978–1982) and Samantha Russell in \"My Sister Sam\" (1986–1988).",
"title": ""
},
{
"docid": "29392021",
"text": "\"Christening\" is the seventh episode of the seventh season of the American version of the comedy television series \"The Office\" and the show's 133rd episode overall. Written by Peter Ocko and directed by Alex Hardcastle, the episode aired on November 4, 2010 on NBC in the United States. The episode guest stars Linda Purl as Helene Beesly, Rick Overton as William Beesly, Robert Pine as Mr. Halpert, Perry Smith as Betsy Halpert, Bobby Ray Shafer as Bob Vance, and Peggy Stewart as Sylvia.",
"title": ""
},
{
"docid": "7792247",
"text": "Jenna Krebbs (maiden name Wade; formerly Marchetta) is a fictional character on the popular American television series \"Dallas\", played, most notably, by Priscilla Presley from 1983 to 1988. Jenna was also briefly played by Morgan Fairchild in 1978 and Francine Tacker in 1980.",
"title": ""
},
{
"docid": "4701806",
"text": "Jennifer Ann Celotta (born November 11, 1971 in Gaithersburg, Maryland) is an American television producer and writer. Among her credits are \"Home Improvement\", \"Malcolm in the Middle\", \"The Newsroom\", \"Greg the Bunny\", \"Andy Richter Controls The Universe\" and \"The Office\". She has directed two episodes of \"The Office\": \"Crime Aid\" and \"The Promotion.\" By the fifth season, Celotta was serving as an \"Office\" producer and one of the series show runners, along with fellow writer Paul Lieberstein. Celotta and Lieberstein wrote the fifth season finale \"Company Picnic\", which ended with character Pam Beesly learning she is pregnant. In May 2009, Celotta said the sixth season would include a wedding for Jim and Pam, although at the time she said the specifics of it had not been worked out yet.",
"title": ""
},
{
"docid": "3721286",
"text": "Jim Halpert (born October 1, 1978) is a fictional character in the U.S. version of the television sitcom \"The Office\", portrayed by John Krasinski. The character is based on Tim Canterbury from the original version of \"The Office\". The character is named after a childhood friend of executive producer Greg Daniels. He is introduced as a sales representative at the Scranton branch of paper distribution company Dunder Mifflin, before transferring to the Stamford branch in the third season. Upon the merger of Scranton and Stamford branches, he becomes Assistant Regional Manager, and later co-manager alongside Michael Scott during the sixth season episode arc from \"The Promotion\" to \"The Manager and the Salesman\". After Dunder Mifflin is bought by Sabre Corporation, Jim is very briefly the sole regional manager of the branch, before returning to the Sales department until his requested termination in the series finale.",
"title": ""
},
{
"docid": "675980",
"text": "Jennifer Mary Elfman (born Jennifer Mary Butala; September 30, 1971) is an American television and film actress. She is best known for her role as Dharma on the 1997–2002 American television sitcom \"Dharma & Greg\".",
"title": ""
},
{
"docid": "2144612",
"text": "Ta-Tanisha (born Shirley Cummings on January 15, 1953 in the Bronx, New York) is an African American character actress, best known for her role as Pam Simpson on the television series \"Room 222\", which she played from 1970 to 1972.",
"title": ""
},
{
"docid": "13544548",
"text": "Pamela Kosh, also known as Pam Kosh, is an English television and film actress best known for her roles as Miss Peach in \"Days of Our Lives\", Flora in \"The King of Queens\", Miss Simpson in \"Saved by the Bell\" and Martha in \"Dr. Quinn, Medicine Woman\".",
"title": ""
},
{
"docid": "45644792",
"text": "Mary Virginia Skinner (May 24, 1925 – March 2, 2015), known professionally as Jenna McMahon, was an American writer, producer, actress and comedian. She was best known for her Emmy Award-winning work as a writer on the variety/sketch comedy program \"The Carol Burnett Show\" and for co-creating the television sitcoms \"It's a Living\", \"The Facts of Life\", and \"Mama's Family\" along with her writing partner Dick Clair.",
"title": ""
},
{
"docid": "4342943",
"text": "Alice Hirson (born March 10, 1929) is an American actress best known for her roles on television. She began her career on stage, before roles on the daytime soap operas. She is best known for her roles as Mavis Anderson in the CBS prime time soap opera, \"Dallas\", and as Lois Morgan, the mother of the title character on the ABC sitcom, \"Ellen\".",
"title": ""
},
{
"docid": "2015421",
"text": "Rosario Inés Consuelo Yolanda Salazar (previously McFarland; also known as \"Rosie\" and \"Ro-Ro\") is a fictional character on the American television sitcom \"Will & Grace\", portrayed by actress Shelley Morrison. Originally due to appear just once, her popularity caused her to be a semi-regular character.",
"title": ""
},
{
"docid": "964638",
"text": "Lindsay Jean Wagner (born June 22, 1949) is an American film and television actress, model, author, singer, acting coach, and adjunct professor. Wagner is best known for her portrayal of the 1970s television leading female science fiction action character Jaime Sommers, who takes on special high-risk government missions using her superhuman bionic powers in the American television series \"The Bionic Woman\" (1976–1978). She first played this role on the 1970s American television series \"The Six Million Dollar Man\". The Jaime Sommers character also became a pop culture icon of the 1970s. In the late 1980s and early 1990s, she reprised the role in several bionic reunion television movies.",
"title": ""
},
{
"docid": "818798",
"text": "Patricia Castle Richardson (born February 23, 1951) is an American television and film actress best known for her portrayal of Jill Taylor on the sitcom \"Home Improvement\", for which she was nominated four times for the Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series and two times for the Golden Globe Award for Best Actress in a Television Series - Comedy or Musical.",
"title": ""
},
{
"docid": "2304773",
"text": "Bree Weston (née Mason, previously Van de Kamp and Hodge) is a fictional character and one of the four protagonists on the ABC television series \"Desperate Housewives\". She is played by actress Marcia Cross, who has received multiple awards and nominations for her portrayal, including an Emmy Award nomination, three Golden Globe Award nominations, and two Screen Actors Guild Awards. Cross' portrayal of Bree has been widely praised by critics and fans.",
"title": ""
},
{
"docid": "6669787",
"text": "Fleur Saville (born 14 July 1984, in Auckland) is a New Zealand television actress best known for her roles in the television sitcoms \"Being Eve\" and \"The Tribe\" in which she became known to international audiences for her portrayal of Ruby. Saville previously acted on New Zealand soap opera \"Shortland Street\", playing the personal assistant Libby Jeffries for the CEO of Shortland Street Hospital.",
"title": ""
},
{
"docid": "4342732",
"text": "Francine Tacker (born September 15, 1946) is an American actress known for appearing as Jenna Wade in 2 episodes of the soap opera \"Dallas\" in 1980. Tacker was the second actress to play the character, succeeding Morgan Fairchild and preceding Priscilla Presley. She was also a regular on the television series \"The Paper Chase\", playing Elizabeth Logan during the 1978–1979 season and on \"Empire\" in 1984. In 1980, she played reporter Camille Rittenhouse, a woman who shared an attic apartment with three other women, on the short-lived comedy series, \"Goodtime Girls\".",
"title": ""
},
{
"docid": "1869238",
"text": "Pamela Fionna Adlon (\"née\" Segall; born July 9, 1966) is an American actress, voice actress, screenwriter, producer, and director. Adlon voiced Bobby Hill on \"King of the Hill\", for which she won an Emmy Award, and the title character from the \"Pajama Sam\" video games. She is also known for playing Dolores in \"Grease 2\" and Ashley Spinelli on the animated series \"Recess\", and for her appearances on \"Californication\" and \"Louie\", on which she is also a consulting producer. Adlon currently stars in and writes the FX comedy television series \"Better Things\", which has won a Peabody Award, which she co-created with Louis C.K.",
"title": ""
},
{
"docid": "4802498",
"text": "Pamela Willis (also Beresford) is a fictional character from the Australian soap opera \"Neighbours\", played by Sue Jones. Pam was introduced by executive producer Don Battye as the matriarch of the newly introduced Willis family. Jones was offered the role after a screen test. She made her first screen appearance during the episode broadcast on 6 August 1990.",
"title": ""
},
{
"docid": "12115190",
"text": "Pamela Baird (born Pamela Beaird on April 6, 1945) is an American former actress, best known for her role as \"Mary Ellen Rogers\", the girlfriend of \"Wally Cleaver\" on the classic sitcom, \"Leave It to Beaver\". She appeared in seven of the show's 235 episodes, but her name was mentioned in many other segments. Mary Ellen and Wally eventually wed, as they were shown as a married couple in the 1983 reunion movie \"Still the Beaver\" and the subsequent \"The New Leave It to Beaver\" series (in which Janice Kent played \"Mary Ellen\").",
"title": ""
},
{
"docid": "1845368",
"text": "John Burke Krasinski ( ; born October 20, 1979) is an American actor and filmmaker. He is widely known for his role as Jim Halpert on the NBC sitcom \"The Office\" (2005–2013), for which he received critical acclaim and won numerous awards. He also served as a producer and occasional director of the show.",
"title": ""
},
{
"docid": "7812080",
"text": "Pamela Douglas is a fictional character from the CBS soap opera, \"The Bold and the Beautiful\", portrayed by Alley Mills. She made her first appearance during the episode broadcast on December 1, 2006. Pam was introduced as the sister of established character Stephanie Forrester (Susan Flannery). She is a receptionist at Forrester Creations.",
"title": ""
},
{
"docid": "1025499",
"text": "Jenna von Oÿ (born May 2, 1977) is an American actress and country music singer. She is perhaps best known for her role as Six LeMeure on the NBC sitcom \"Blossom\". She also had a voicing role in \"Pepper Ann\" as well as the role of Stevie Van Lowe on the UPN sitcom \"The Parkers\".",
"title": ""
},
{
"docid": "2504374",
"text": "Wanda Ventham (born 5 August 1935) is an English actress, known primarily for her role as Colonel Virginia Lake in the 1970s science-fiction television series \"UFO\", and for her recurring role as Cassandra Trotter's mother Pamela Parry in the sitcom \"Only Fools and Horses\" from 1989–92. She also appeared in two episodes of \"The Saint\" alongside Roger Moore.",
"title": ""
},
{
"docid": "643545",
"text": "Beth Alison Broderick (born February 24, 1959) is an American actress notable for her portrayal of the character Zelda Spellman in the television sitcom \"Sabrina the Teenage Witch\" from 1996 to 2003 on ABC and then the Warner Bros. network. She recently starred as the recurring character Rose Twitchell on the Stephen King and Steven Spielberg TV series \"Under the Dome\".",
"title": ""
},
{
"docid": "39942",
"text": "Jennifer Joanna Aniston (born February 11, 1969) is an American actress, producer, and businesswoman. She is the daughter of Greek-born actor John Aniston and American actress Nancy Dow. Aniston gained worldwide recognition for portraying Rachel Green on the television sitcom \"Friends\" (1994–2004), a role which earned her a Primetime Emmy Award, a Golden Globe Award, and a Screen Actors Guild Award. The character was widely popular during the airing of the series and was later recognized as one of the 100 greatest female characters in United States television.",
"title": ""
},
{
"docid": "89689",
"text": "Loretta Jane Swit (born November 4, 1937) is an American stage and television actress known for her character roles. Swit is best known for her portrayal of Major Margaret \"Hot Lips\" Houlihan on \"M*A*S*H\", for which she won two Emmy Awards.",
"title": ""
}
] |
96
|
Algerian physicians constitue the largest component of sub-Saharan Africa-trained physicians in the United States.
|
[
{
"docid": "14500725",
"text": "BACKGROUND The large-scale emigration of physicians from sub-Saharan Africa (SSA) to high-income nations is a serious development concern. Our objective was to determine current emigration trends of SSA physicians found in the physician workforce of the United States. METHODS AND FINDINGS We analyzed physician data from the World Health Organization (WHO) Global Health Workforce Statistics along with graduation and residency data from the 2011 American Medical Association Physician Masterfile (AMA-PM) on physicians trained or born in SSA countries who currently practice in the US. We estimated emigration proportions, year of US entry, years of practice before emigration, and length of time in the US. According to the 2011 AMA-PM, 10,819 physicians were born or trained in 28 SSA countries. Sixty-eight percent (n = 7,370) were SSA-trained, 20% (n = 2,126) were US-trained, and 12% (n = 1,323) were trained outside both SSA and the US. We estimated active physicians (age ≤ 70 years) to represent 96% (n = 10,377) of the total. Migration trends among SSA-trained physicians increased from 2002 to 2011 for all but one principal source country; the exception was South Africa whose physician migration to the US decreased by 8% (-156). The increase in last-decade migration was >50% in Nigeria (+1,113) and Ghana (+243), >100% in Ethiopia (+274), and >200% (+244) in Sudan. Liberia was the most affected by migration to the US with 77% (n = 175) of its estimated physicians in the 2011 AMA-PM. On average, SSA-trained physicians have been in the US for 18 years. They practiced for 6.5 years before US entry, and nearly half emigrated during the implementation years (1984-1999) of the structural adjustment programs. CONCLUSION Physician emigration from SSA to the US is increasing for most SSA source countries. Unless far-reaching policies are implemented by the US and SSA countries, the current emigration trends will persist, and the US will remain a leading destination for SSA physicians emigrating from the continent of greatest need. Please see later in the article for the Editors' Summary.",
"title": "Physician Emigration from Sub-Saharan Africa to the United States: Analysis of the 2011 AMA Physician Masterfile"
}
] |
[
{
"docid": "3662510",
"text": "OBJECTIVE To estimate the lost investment of domestically educated doctors migrating from sub-Saharan African countries to Australia, Canada, the United Kingdom, and the United States. DESIGN Human capital cost analysis using publicly accessible data. SETTINGS Sub-Saharan African countries. PARTICIPANTS Nine sub-Saharan African countries with an HIV prevalence of 5% or greater or with more than one million people with HIV/AIDS and with at least one medical school (Ethiopia, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe), and data available on the number of doctors practising in destination countries. MAIN OUTCOME MEASURES The financial cost of educating a doctor (through primary, secondary, and medical school), assuming that migration occurred after graduation, using current country specific interest rates for savings converted to US dollars; cost according to the number of source country doctors currently working in the destination countries; and savings to destination countries of receiving trained doctors. RESULTS In the nine source countries the estimated government subsidised cost of a doctor's education ranged from $21,000 (£13,000; €15,000) in Uganda to $58,700 in South Africa. The overall estimated loss of returns from investment for all doctors currently working in the destination countries was $2.17bn (95% confidence interval 2.13bn to 2.21bn), with costs for each country ranging from $2.16m (1.55m to 2.78m) for Malawi to $1.41bn (1.38bn to 1.44bn) for South Africa. The ratio of the estimated compounded lost investment over gross domestic product showed that Zimbabwe and South Africa had the largest losses. The benefit to destination countries of recruiting trained doctors was largest for the United Kingdom ($2.7bn) and United States ($846m). CONCLUSIONS Among sub-Saharan African countries most affected by HIV/AIDS, lost investment from the emigration of doctors is considerable. Destination countries should consider investing in measurable training for source countries and strengthening of their health systems.",
"title": "The financial cost of doctors emigrating from sub-Saharan Africa: human capital analysis"
},
{
"docid": "6085365",
"text": "BACKGROUND Few studies have examined whether physician knowledge, attitudes, or practice patterns might contribute to gender disparities in the primary prevention of coronary heart disease (CHD), including among physicians caring for the largest number of reproductive-age women, obstetricians and gynecologists (OB/GYNs). We sought to identify barriers affecting the provision of recommended coronary risk factor therapies in women. METHODS We surveyed internists and OB/GYNs who attended Grand Rounds presentations developed for the New York State Women and Heart Disease Physician Education Initiative. This program was designed to improve screening and management of coronary risk factors in women. Attendees were asked to complete a 7-minute questionnaire. RESULTS The mean age of the 529 respondents was 40.3 years (standard deviation = 12.3), 75.1% were internists (n=378), and 42.7% (n=226) were women. Physicians correctly responded to 71.5% of the 13 questions assessing knowledge of coronary risk prevention (range, 4-13). Almost one third of internists and half of the OB/GYNs did not know that tobacco use was the leading cause of myocardial infarction in young women. For patients who smoked tobacco, only two thirds of internists and 55.4% of OB/GYNs reported suggesting a quit date (p=.007). After controlling for covariates, physicians who did not perceive time as a barrier were more likely to discuss smoking cessation (odds ratio=1.7 [1.1-2.7]). CONCLUSIONS Among the internists and OB/GYNs surveyed, time was perceived as a barrier to implementing risk prevention. These physicians also underestimated the impact of tobacco use as a risk factor for CHD in young women. To lessen gender disparities in CHD prevention, both specialties need time-efficient educational programs that reflect specialty differences.",
"title": "Physician knowledge levels and barriers to coronary risk prevention in women: survey results from the Women and Heart Disease Physician Education Initiative."
},
{
"docid": "20999249",
"text": "BACKGROUND Falciparum malaria or malaria tropica is one of the leading causes of childhood mortality worldwide. Malaria-related deaths occur mainly in sub-Saharan Africa, where an estimated 365 million clinical cases of Plasmodium falciparum malaria occur each year. In Europe, imported malaria cases occur due to returning travellers or immigration mostly from African countries. Children are more at risk than adults. The objective of this study was to identify high risk groups for imported childhood malaria in Europe in order to guide development of strategies for prevention, early recognition and management. METHODS In the period May 2003-January 2005 we reviewed all cases of paediatric malaria in the Netherlands notified by the Dutch Paediatric Surveillance System (Nederland Signalerings Centrum Kindergeneeskunde, NSCK) and the literature on imported malaria in children in Europe published between 1996 and 2006. RESULTS Malaria occurred mainly in children of long-term (n = 15, 47%) and new (n = 8, 25%) immigrants and was mostly acquired in sub-Saharan Africa. The dominant species was P. falciparum. Only one quarter of children had used adequate malaria chemoprophylaxis. Complicated disease occurred in 10 (31%) of cases. We also reviewed the literature and found 6082 reported cases of imported malaria among children in Europe; among these, four died and only one was reported to develop neurological sequelae. CONCLUSION Imported malaria in children remains an important problem and is unlikely to decrease unless the reasons for inadequate prophylaxis are addressed.",
"title": "Imported malaria in children: a national surveillance in the Netherlands and a review of European studies."
},
{
"docid": "25953438",
"text": "Understanding of the age- and season- dependence of malaria mortality is an important prerequisite for epidemiologic models of malaria immunity. However, most studies of malaria mortality have aggregated their results into broad age groups and across seasons, making it hard to predict the likely impact of interventions targeted at specific age groups of children. We present age-specific mortality rates for children aged < 15 years for the period of 2001-2005 in 7 demographic surveillance sites in areas of sub-Saharan Africa with stable endemic Plasmodium falciparum malaria. We use verbal autopsies (VAs) to estimate the proportion of deaths by age group due to malaria, and thus calculate malaria-specific mortality rates for each site, age-group, and month of the year. In all sites a substantial proportion of deaths (ranging from 20.1% in a Mozambican site to 46.2% in a site in Burkina Faso) were attributed to malaria. The overall age patterns of malaria mortality were similar in the different sites. Deaths in the youngest children (< 3 months old) were only rarely attributed to malaria, but in children over 1 year of age the proportion of deaths attributed to malaria was only weakly age-dependent. In most of the sites all-cause mortality rates peaked during the rainy season, but the strong seasonality in malaria transmission in these sites was not reflected in strong seasonality in the proportion of deaths attributed to malaria, except in the two sites in Burkina Faso. Improvement in the specificity of malaria verbal autopsies would make it easier to interpret the age and season patterns in such data.",
"title": "Patterns of age-specific mortality in children in endemic areas of sub-Saharan Africa."
},
{
"docid": "14395738",
"text": "Studies from sub-Saharan Africa indicate that children made vulnerable by poverty have been disproportionately affected by HIV with many exposed via mother-to-child transmission. For youth living with HIV, adherence to life-saving treatment regimens are likely to be affected by the complex set of economic and social circumstances that challenge their families and also exacerbate health problems. Using baseline data from the National Institute of Child and Human Development (NICHD) funded Suubi+Adherence study, we examined the extent to which individual and composite measures of equity predict self-reported adherence among Ugandan adolescents aged 10-16 (n = 702) living with HIV. Results showed that greater asset ownership, specifically familial possession of seven or more tangible assets, was associated with greater odds of self-reported adherence (OR 1.69, 95% CI: 1.00-2.85). Our analyses also indicated that distance to the nearest health clinic impacts youth's adherence to an ARV regimen. Youth who reported living nearest to a clinic were significantly more likely to report optimal adherence (OR 1.49, 95% CI: 0.92-2.40). Moreover, applying the composite equity scores, we found that adolescents with greater economic advantage in ownership of household assets, financial savings, and caregiver employment had higher odds of adherence by a factor of 1.70 (95% CI: 1.07-2.70). These findings suggest that interventions addressing economic and social inequities may be beneficial to increase antiretroviral therapy (ART) uptake among economically vulnerable youth, especially in sub-Saharan Africa. This is one of the first studies to address the question of equity in adherence to ART among economically vulnerable youth with HIV.",
"title": "Equity in adherence to antiretroviral therapy among economically vulnerable adolescents living with HIV in Uganda"
},
{
"docid": "1606628",
"text": "CONTEXT One key target of the United Nations Millennium Development goals is to reduce the prevalence of underweight among children younger than 5 years by half between 1990 and 2015. OBJECTIVE To estimate trends in childhood underweight by geographic regions of the world. DESIGN, SETTING, AND PARTICIPANTS Time series study of prevalence of underweight, defined as weight 2 SDs below the mean weight for age of the National Center for Health Statistics and World Health Organization (WHO) reference population. National prevalence rates derived from the WHO Global Database on Child Growth and Malnutrition, which includes data on approximately 31 million children younger than 5 years who participated in 419 national nutritional surveys in 139 countries from 1965 through 2002. MAIN OUTCOME MEASURES Linear mixed-effects modeling was used to estimate prevalence rates and numbers of underweight children by region in 1990 and 2015 and to calculate the changes (ie, increase or decrease) to these values between 1990 and 2015. RESULTS Worldwide, underweight prevalence was projected to decline from 26.5% in 1990 to 17.6% in 2015, a change of -34% (95% confidence interval [CI], -43% to -23%). In developed countries, the prevalence was estimated to decrease from 1.6% to 0.9%, a change of -41% (95% CI, -92% to 343%). In developing regions, the prevalence was forecasted to decline from 30.2% to 19.3%, a change of -36% (95% CI, -45% to -26%). In Africa, the prevalence of underweight was forecasted to increase from 24.0% to 26.8%, a change of 12% (95% CI, 8%-16%). In Asia, the prevalence was estimated to decrease from 35.1% to 18.5%, a change of -47% (95% CI, -58% to -34%). Worldwide, the number of underweight children was projected to decline from 163.8 million in 1990 to 113.4 million in 2015, a change of -31% (95% CI, -40% to -20%). Numbers are projected to decrease in all subregions except the subregions of sub-Saharan, Eastern, Middle, and Western Africa, which are expected to experience substantial increases in the number of underweight children. CONCLUSIONS An overall improvement in the global situation is anticipated; however, neither the world as a whole, nor the developing regions, are expected to achieve the Millennium Development goals. This is largely due to the deteriorating situation in Africa where all subregions, except Northern Africa, are expected to fail to meet the goal.",
"title": "Estimates of global prevalence of childhood underweight in 1990 and 2015."
},
{
"docid": "9274291",
"text": "PURPOSE To compare expectations for cancer survivorship care between patients and their physicians and between primary care providers (PCPs) and oncologists. METHODS Survivors and their physicians were surveyed to evaluate for expectations regarding physician participation in primary cancer follow-up, screening for other cancers, general preventive health, and management of comorbidities. RESULTS Of 992 eligible survivors and 607 physicians surveyed, 535 (54%) and 378 (62%) were assessable, respectively. Among physician respondents, 255 (67%) were PCPs and 123 (33%) were oncologists. Comparing patients with their oncologists, expectations were highly discrepant for screening for cancers other than the index one (agreement rate, 29%), with patients anticipating significantly more oncologist involvement. Between patients and their PCPs, expectations were most incongruent for primary cancer follow-up (agreement rate, 35%), with PCPs indicating they should contribute a much greater part to this aspect of care. Expectations between patients and their PCPs were generally more concordant than between patients and their oncologists. PCPs and oncologists showed high discordances in perceptions of their own roles for primary cancer follow-up, cancer screening, and general preventive health (agreement rates of 3%, 44%, and 51%, respectively). In the case of primary cancer follow-up, both PCPs and oncologists indicated they should carry substantial responsibility for this task. CONCLUSION Patients and physicians have discordant expectations with respect to the roles of PCPs and oncologists in cancer survivorship care. Uncertainties around physician roles and responsibilities can lead to deficiencies in care, supporting the need to make survivorship care planning a standard component in cancer management.",
"title": "Comparisons of patient and physician expectations for cancer survivorship care."
},
{
"docid": "12258338",
"text": "CONTEXT Pharmacist review of medication orders in the intensive care unit (ICU) has been shown to prevent errors, and pharmacist consultation has reduced drug costs. However, whether pharmacist participation in the ICU at the time of drug prescribing reduces adverse events has not been studied. OBJECTIVE To measure the effect of pharmacist participation on medical rounds in the ICU on the rate of preventable adverse drug events (ADEs) caused by ordering errors. DESIGN Before-after comparison between phase 1 (baseline) and phase 2 (after intervention implemented) and phase 2 comparison with a control unit that did not receive the intervention. SETTING A medical ICU (study unit) and a coronary care unit (control unit) in a large urban teaching hospital. PATIENTS Seventy-five patients randomly selected from each of 3 groups: all admissions to the study unit from February 1, 1993, through July 31, 1993 (baseline) and all admissions to the study unit (postintervention) and control unit from October 1, 1994, through July 7, 1995. In addition, 50 patients were selected at random from the control unit during the baseline period. INTERVENTION A senior pharmacist made rounds with the ICU team and remained in the ICU for consultation in the morning, and was available on call throughout the day. MAIN OUTCOME MEASURES Preventable ADEs due to ordering (prescribing) errors and the number, type, and acceptance of interventions made by the pharmacist. Preventable ADEs were identified by review of medical records of the randomly selected patients during both preintervention and postintervention phases. Pharmacists recorded all recommendations, which were then analyzed by type and acceptance. RESULTS The rate of preventable ordering ADEs decreased by 66% from 10.4 per 1000 patient-days (95% confidence interval [CI], 7-14) before the intervention to 3.5 (95% CI, 1-5; P<.001) after the intervention. In the control unit, the rate was essentially unchanged during the same time periods: 10.9 (95% CI, 6-16) and 12.4 (95% CI, 8-17) per 1000 patient-days. The pharmacist made 366 recommendations related to drug ordering, of which 362 (99%) were accepted by physicians. CONCLUSIONS The presence of a pharmacist on rounds as a full member of the patient care team in a medical ICU was associated with a substantially lower rate of ADEs caused by prescribing errors. Nearly all the changes were readily accepted by physicians.",
"title": "Pharmacist participation on physician rounds and adverse drug events in the intensive care unit."
},
{
"docid": "18268012",
"text": "OBJECTIVES To estimate the present value of current and future funding needed for HIV treatment and prevention in 9 sub-Saharan African (SSA) countries that account for 70% of HIV burden in Africa under different scenarios of intervention scale-up. To analyse the gaps between current expenditures and funding obligation, and discuss the policy implications of future financing needs. DESIGN We used the Goals module from Spectrum, and applied the most up-to-date cost and coverage data to provide a range of estimates for future financing obligations. The four different scale-up scenarios vary by treatment initiation threshold and service coverage level. We compared the model projections to current domestic and international financial sources available in selected SSA countries. RESULTS In the 9 SSA countries, the estimated resources required for HIV prevention and treatment in 2015-2050 range from US$98 billion to maintain current coverage levels for treatment and prevention with eligibility for treatment initiation at CD4 count of <500/mm(3) to US$261 billion if treatment were to be extended to all HIV-positive individuals and prevention scaled up. With the addition of new funding obligations for HIV--which arise implicitly through commitment to achieve higher than current treatment coverage levels--overall financial obligations (sum of debt levels and the present value of the stock of future HIV funding obligations) would rise substantially. CONCLUSIONS Investing upfront in scale-up of HIV services to achieve high coverage levels will reduce HIV incidence, prevention and future treatment expenditures by realising long-term preventive effects of ART to reduce HIV transmission. Future obligations are too substantial for most SSA countries to be met from domestic sources alone. New sources of funding, in addition to domestic sources, include innovative financing. Debt sustainability for sustained HIV response is an urgent imperative for affected countries and donors.",
"title": "Long-term financing needs for HIV control in sub-Saharan Africa in 2015-2050: a modelling study."
},
{
"docid": "12009265",
"text": "CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer. OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men. DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled. INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. MAIN OUTCOME MEASURES Prostate and total cancer. RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk. CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.",
"title": "Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial."
},
{
"docid": "30741007",
"text": "The distribution of insecticide-treated bednets to help combat the burden of malaria in sub-Saharan Africa has accelerated in the past 5 years. Additionally, many countries are also considering, or have already begun, indoor residual spraying campaigns. These are positive developments, since vector control has repeatedly proven to be an effective means of reducing malaria transmission. However, the sustainability of these insecticide-based interventions relies on the continuing susceptibility of the anopheles vectors to the limited number of available insecticides. Continual monitoring for early signs of insecticide resistance and the adoption of carefully considered resistance management strategies are therefore required. Regrettably, this essential monitoring component is frequently given a low priority in the push to meet ambitious coverage targets. We outline the key requirements for establishing an insecticide resistance surveillance system and urge all those involved in malaria vector control, either directly or as facilitators, to ensure that these measures are incorporated into control programmes. Failure to act now will inevitably lead to a future breakdown in disease control and jeopardise hopes of eradicating this major public-health problem.",
"title": "Lessons from the past: managing insecticide resistance in malaria control and eradication programmes."
},
{
"docid": "12672066",
"text": "IMPORTANCE In 2011, the Centers for Medicare & Medicaid Services (CMS) approved intensive behavioral weight loss counseling for approximately 14 face-to-face, 10- to 15-minute sessions over 6 months for obese beneficiaries in primary care settings, when delivered by physicians and other CMS-defined primary care practitioners. OBJECTIVE To conduct a systematic review of behavioral counseling for overweight and obese patients recruited from primary care, as delivered by primary care practitioners working alone or with trained interventionists (eg, medical assistants, registered dietitians), or by trained interventionists working independently. EVIDENCE REVIEW We searched PubMed, CINAHL, and EMBASE for randomized controlled trials published between January 1980 and June 2014 that recruited overweight and obese patients from primary care; provided behavioral counseling (ie, diet, exercise, and behavioral therapy) for at least 3 months, with at least 6 months of postrandomization follow-up; included at least 15 participants per treatment group and objectively measured weights; and had a comparator, an intention-to-treat analysis, and attrition of less than 30% at 1 year or less than 40% at longer follow-up. FINDINGS Review of 3304 abstracts yielded 12 trials, involving 3893 participants, that met inclusion-exclusion criteria and prespecified quality ratings. No studies were found in which primary care practitioners delivered counseling that followed the CMS guidelines. Mean 6-month weight changes from baseline in the intervention groups ranged from a loss of 0.3 kg to 6.6 kg. In the control group, mean change ranged from a gain of 0.9 kg to a loss of 2.0 kg. Weight loss in both groups generally declined with longer follow-up (12-24 months). Interventions that prescribed both reduced energy intake (eg, ≥ 500 kcal/d) and increased physical activity (eg, ≥150 minutes a week of walking), with traditional behavioral therapy, generally produced larger weight loss than interventions without all 3 specific components. In the former trials, more treatment sessions, delivered in person or by telephone by trained interventionists, were associated with greater mean weight loss and likelihood of patients losing 5% or more of baseline weight. CONCLUSIONS AND RELEVANCE Intensive behavioral counseling can induce clinically meaningful weight loss, but there is little research on primary care practitioners providing such care. The present findings suggest that a range of trained interventionists, who deliver counseling in person or by telephone, could be considered for treating overweight or obesity in patients encountered in primary care settings.",
"title": "Behavioral treatment of obesity in patients encountered in primary care settings: a systematic review."
},
{
"docid": "2138843",
"text": "Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition to ensuring the adequate delivery of glucose to the tissues of the body, treatment of diabetes attempts to decrease the likelihood that the tissues of the body are harmed by hyperglycemia. The importance of protecting the body from hyperglycemia cannot be overstated; the direct and indirect effects on the human vascular tree are the major source of morbidity and mortality in both type 1 and type 2 diabetes. Generally, the injurious effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy). It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding. ### Diabetic retinopathy Diabetic retinopathy may be the most common microvascular complication of diabetes. It is responsible for ∼ 10,000 new cases of blindness every year in the United States alone.1 The risk of developing diabetic retinopathy or other microvascular complications of diabetes depends on both the duration and the severity of hyperglycemia. Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both severity of hyperglycemia and presence of hypertension in the U.K. Prospective Diabetes Study (UKPDS), and most patients with type 1 diabetes develop evidence of retinopathy within 20 years of diagnosis.2,3 Retinopathy may begin to develop as early as 7 years before the diagnosis of diabetes in patients with type 2 diabetes.1 There are several proposed pathological mechanisms by which diabetes may lead …",
"title": "Microvascular and Macrovascular Complications of Diabetes"
},
{
"docid": "34198460",
"text": "BACKGROUND Given the high value placed on children in sub-Saharan Africa, previous research suggests that infertility increases the risk of psychological distress and marital conflict, encourages risky sexual behavior and deprives infertile individuals and couples of an important source of economic and social capital. This paper explores the implications of infertility for women in Ghana, West Africa. METHODS Semi-structured interview data collected from 107 women (aged 21-48 years, mean 33 years) seeking treatment in gynecological and obstetric clinics in Accra, Ghana, are analyzed. Based on iterative open coding of the interviews, the focus of the analysis is on mental health, marital instability, social interaction and gendered experiences. RESULTS Infertile women report facing severe social stigma, marital strain and a range of mental health difficulties. Many women feel that they shoulder a disproportionate share of the blame for infertility and, by extension, face greater social consequences than male partners for difficulties conceiving. Women who do not self-identify as infertile corroborate these findings, asserting that the social consequences of infertility are severe, particularly for women. CONCLUSIONS Infertility in Ghana has important consequences for social interactions, marital stability and mental health. These consequences are not perceived to be shared equally by Ghanaian men.",
"title": "'Zero is not good for me': implications of infertility in Ghana."
},
{
"docid": "37248570",
"text": "After a lapse of almost 40 years, malaria eradication is back on the global health agenda. Inspired by the Gates Malaria Forum in October 2007,1,2 key organizations are starting to debate the pros and cons of redefining eradication as an explicit goal of malaria control efforts. Attempts to eliminate malaria in southern Africa3 and Pacific Island states,4 and WHO’s Global Malaria Programme agenda and field manual for malaria elimination,5,6 foreshadow this movement towards another global attempt at eradication. When marking 60 years of WHO’s commitment to fighting malaria, we must ask what has been achieved, but also what can we learn from the past. We now know so much more about the biology of parasite-host responses, the determinants of endemicity and transmission dynamics, the social, economic and cultural implications of malaria at household, community and national levels, and the demands made upon health systems in endemic countries. We do not yet know how to synthesize and integrate this knowledge to achieve elimination in different settings. Regional malaria elimination campaigns were first conducted in the late 1940s, preparing the ground for the Global Malaria Eradication Program in 1955. This campaign succeeded in eliminating malaria from Europe, North America, the Caribbean and parts of Asia and South-Central America.7 But no major success occurred in sub-Saharan Africa, which accounts for 80% of today’s burden of malaria.8 When the aspiration of global eradication was abandoned in 1969, the main reasons for failure were technical challenges of executing the strategy especially in Africa. The post-eradication era from 1969 to 1991 focused on technical issues, and research and development for new tools, leading to advances in drug and vaccine development, vector control and insecticide-treated nets. These decades also brought a better understanding of the social, economic and cultural dimensions of malaria. There was little global support provided specifically for malaria control in the newly independent states of Africa that were struggling to establish broad-based health systems and primary health care. By 1992, the combination of a worsening malaria situation and promising technical developments led to renewed global focus on malaria control. The Roll Back Malaria initiative, launched by WHO in 1998, led to the Abuja Declaration in 2000, which defined progressive intervention coverage targets for control designed to eliminate malaria as a public health problem, while emphasizing that this could only be achieved through vastly strengthened local health systems.9 Increased resources through the Global Fund to Fight AIDS, Tuberculosis and Malaria, the World Bank’s Booster Program, the US President’s Malaria Initiative and many others has meant that this page is finally beginning to turn as intervention coverage is rising.10 It is against this background that we hear this call for elimination/eradication. The challenges remain formidable. We all know that elimination in Africa is not possible with current tools. But efforts must focus beyond simply developing better tools, to include how existing and future tools can be strategically combined for maximum synergistic effectiveness when integrated into different health and social systems prevailing in endemic areas. Aiming at elimination and eradication further implies the need for effective surveillance strategies to monitor progress (again a challenge for health systems). This in turn requires a better understanding of malaria transmission heterogeneity in a globalized world with rapidly changing dynamics in environment, climate, migration and transnational cooperation. Maintaining long-term momentum in the face of success in regional elimination while waiting to achieve final eradication will be a major challenge. Shrinking the map by starting on the malaria margins with the “easy-to-eliminate” settings will boost morale initially but may bring marginal benefits to such areas at the expense of those where the burden of malaria is highest. Any strategic plan – and here we learn again from the past – needs to be a synchronous global effort, locally adapted in all endemic areas. Although we lack sufficient knowledge, systems and tools to eradicate malaria today, we do have a window of political will and financial resources to refocus on the goal of effective control through universal coverage of appropriate interventions. The prerequisites for a successful start are: (i) a process of inclusive discourse to agree on global vision, goals and strategy; and (ii) a global plan for all endemic areas describing how, where and when we move from control towards elimination. What must distinguish the new era, especially in Africa, is a real rather than rhetorical emphasis on health systems. ■",
"title": "Malaria eradication back on the table."
},
{
"docid": "409280",
"text": "BACKGROUND Few data have evaluated physician adherence to cardiovascular disease (CVD) prevention guidelines according to physician specialty or patient characteristics, particularly gender. METHODS AND RESULTS An online study of 500 randomly selected physicians (300 primary care physicians, 100 obstetricians/gynecologists, and 100 cardiologists) used a standardized questionnaire to assess awareness of, adoption of, and barriers to national CVD prevention guidelines by specialty. An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high-, intermediate-, or low-risk patients. Intermediate-risk women, as assessed by the Framingham risk score, were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles (P<0.0001), and trends were similar for obstetricians/gynecologists and cardiologists. Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy. After adjustment for risk assignment, the impact of patient gender on preventive care was not significant except for less aspirin (P<0.01) and more weight management recommended (P<0.04) for intermediate-risk women. Physicians did not rate themselves as very effective in their ability to help patients prevent CVD. Fewer than 1 in 5 physicians knew that more women than men die each year from CVD. CONCLUSIONS Perception of risk was the primary factor associated with CVD preventive recommendations. Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men. Educational interventions for physicians are needed to improve the quality of CVD preventive care and lower morbidity and mortality from CVD for men and women.",
"title": "National study of physician awareness and adherence to cardiovascular disease prevention guidelines."
},
{
"docid": "7285256",
"text": "COPD continues to cause a heavy health and economic burden both in the United States and around the world. Some of the risk factors for COPD are well-known and include smoking, occupational exposures, air pollution, airway hyperresponsiveness, asthma, and certain genetic variations, although many questions, such as why < 20% of smokers develop significant airway obstruction, remain. Precise definitions of COPD vary and are frequently dependent on an accurate diagnosis of the problem by a physician. These differences in the definition of COPD can have large effects on the estimates of COPD in the population. Furthermore, evidence that COPD represents several different disease processes with potentially different interventions continues to emerge. In most of the world, COPD prevalence and mortality are still increasing and likely will continue to rise in response to increases in smoking, particularly by women and adolescents. Resources aimed at smoking cessation and prevention, COPD education and early detection, and better treatment will be of the most benefit in our continuing efforts against this important cause of morbidity and mortality.",
"title": "COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity."
},
{
"docid": "25499612",
"text": "Despite its key role in determining the stability and intensity of malaria transmission, the infectiousness of human populations to mosquitoes has rarely been estimated. Field-based analyses of malaria transmission have frequently relied on the prevalence of asexual parasites or gametocytes as proxies for infectiousness. We now summarize empirical data on human infectiousness from Africa and Papua New Guinea. Over a wide range of transmission intensities there is little relationship between the infectiousness of human populations to vector mosquitoes and mosquito-to-human transmission intensity. We compare these data with the predictions of a stochastic simulation model of Plasmodium falciparum epidemiology. This model predicted little variation in the infectiousness of the human population for entomologic inoculation rates (EIRs) greater than approximately 10 infectious bites per year, demonstrating that the lack of relationship between the EIR and the infectious reservoir can be explained without invoking any effects of acquired transmission-blocking immunity. The near absence of field data from areas with an EIR < 10 per year precluded validation of the model predictions for low EIR values. These results suggest that interventions reducing mosquito-to-human transmission will have little or no effect on human infectiousness at the levels of transmission found in most rural areas of sub-Saharan Africa. Unless very large reductions in transmission can be achieved, measures to prevent mosquito-to-human transmission need to be complemented with interventions that reduce the density or infectiousness of blood stage parasites.",
"title": "Infectiousness of malaria-endemic human populations to vectors."
},
{
"docid": "24077493",
"text": "BACKGROUND With increasing restrictions placed on physician-industry interactions, industry marketing may target other health professionals. Recent health policy developments confer even greater importance on the decision making of non-physician clinicians. The purpose of this systematic review is to examine the types and implications of non-physician clinician-industry interactions in clinical practice. METHODS AND FINDINGS We searched MEDLINE and Web of Science from January 1, 1946, through June 24, 2013, according to PRISMA guidelines. Non-physician clinicians eligible for inclusion were: Registered Nurses, nurse prescribers, Physician Assistants, pharmacists, dieticians, and physical or occupational therapists; trainee samples were excluded. Fifteen studies met inclusion criteria. Data were synthesized qualitatively into eight outcome domains: nature and frequency of industry interactions; attitudes toward industry; perceived ethical acceptability of interactions; perceived marketing influence; perceived reliability of industry information; preparation for industry interactions; reactions to industry relations policy; and management of industry interactions. Non-physician clinicians reported interacting with the pharmaceutical and infant formula industries. Clinicians across disciplines met with pharmaceutical representatives regularly and relied on them for practice information. Clinicians frequently received industry \"information,\" attended sponsored \"education,\" and acted as distributors for similar materials targeted at patients. Clinicians generally regarded this as an ethical use of industry resources, and felt they could detect \"promotion\" while benefiting from industry \"information. \" Free samples were among the most approved and common ways that clinicians interacted with industry. Included studies were observational and of varying methodological rigor; thus, these findings may not be generalizable. This review is, however, the first to our knowledge to provide a descriptive analysis of this literature. CONCLUSIONS Non-physician clinicians' generally positive attitudes toward industry interactions, despite their recognition of issues related to bias, suggest that industry interactions are normalized in clinical practice across non-physician disciplines. Industry relations policy should address all disciplines and be implemented consistently in order to mitigate conflicts of interest and address such interactions' potential to affect patient care. Please see later in the article for the Editors' Summary.",
"title": "Interactions between Non-Physician Clinicians and Industry: A Systematic Review"
},
{
"docid": "72180760",
"text": "To determine physicians' perceptions of the effects that the companions of cancer patients have on physician-patient communication, semistructured interviews were conducted with 12 oncologists (6 medical, 4 surgical, and 2 radiation) from a total population of 21 oncologists. The physicians estimated that threefourths of their patients brought companions with them to consultations and said that these consultations were more complex for the physician. The behaviors of the companions varied from domination to passive note taking, and the companions who were young professional men or older women who accompanied their husbands were the most assertive and asked the most questions. All possible coalitions were observed during medical visits. The physicians perceived that companions and patients often had different agendas and noted differences in the companions' behaviors according to their gender and whether they lived in rural or urban areas.",
"title": "Oncologists' perceptions of the effects of cancer patients' companions on physician-patient interactions"
},
{
"docid": "4883040",
"text": "BACKGROUND Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection. METHODS AND FINDINGS PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count. Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). CONCLUSIONS Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic. REVIEW REGISTRATION International Prospective Register of Systematic Reviews CRD42011001209 Please see later in the article for the Editors' Summary.",
"title": "Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis"
},
{
"docid": "34818263",
"text": "As time passes, the AIDS pandemic continues to spike, affecting an estimated 38.6 million people worldwide. In response, a satellite health clinic is being d esigned by two Cal Poly students to serve the Maasai people living in the Kajiado district in Southern Kenya. The Maasai have traditionally lived as pastoralists, surviving off of their cattle with which they share their water, increasing the risk for contamination. However, as the population of Kenya increases, the land the Maasai have traditionally used for grazing is shrink ing. For this reason, some have turned to farming to maintain their liveli hood. These factors have contributed to the desertification and deforestation of their region. As the lifestyle of the Maasai evolves, they rely more on maize than meat and dairy products for their nutrients. All of these changes have contributed to the evolution of the Maasai culture. We will address these changes in order to better understand the Maasai, as well as highlight pos sible further aid needed to support their survival.",
"title": "Current Health and Environmental Status of the Maasai People in Sub-Saharan Africa"
},
{
"docid": "116556376",
"text": "BACKGROUND Little information is available on physician characteristics and patient presentations that may influence compliance with evidence-based guidelines for acute low back pain. OBJECTIVE To assess whether physicians' management decisions are consistent with the Agency for Health Research Quality's guideline and whether responses varied with the presentation of sciatica or by physician characteristics. DESIGN Cross-sectional study using a mailed survey. PARTICIPANTS Participants were randomly selected from internal medicine, family practice, general practice, emergency medicine, and occupational medicine specialties. MEASUREMENTS A questionnaire asked for recommendations for 2 case scenarios, representing patients without and with sciatica, respectively. RESULTS Seven hundred and twenty surveys were completed (response rate=25%). In cases 1 (without sciatica) and 2 (with sciatica), 26.9% and 4.3% of physicians fully complied with the guideline, respectively. For each year in practice, the odds of guideline noncompliance increased 1.03 times (95% confidence interval [CI]=1.01 to 1.05) for case 1. With occupational medicine as the referent specialty, general practice had the greatest odds of noncompliance (3.60, 95% CI=1.75 to 7.40) in case 1, followed by internal medicine and emergency medicine. Results for case 2 reflected the influence of sciatica with internal medicine having substantially higher odds (vs case 1) and the greatest odds of noncompliance of any specialty (6.93, 95% CI=1.47 to 32.78), followed by family practice and emergency medicine. CONCLUSIONS A majority of primary care physicians continue to be noncompliant with evidence-based back pain guidelines. Sciatica dramatically influenced clinical decision-making, increasing the extent of noncompliance, particularly for internal medicine and family practice. Physicians' misunderstanding of sciatica's natural history and belief that more intensive initial management is indicated may be factors underlying the observed influence of sciatica.",
"title": "Physicians' initial management of acute low back pain versus evidence-based guidelines. Influence of sciatica."
},
{
"docid": "25069745",
"text": "OBJECTIVE To describe the epidemiology of urban malaria, an emerging problem in sub-Saharan Africa. METHOD Cross-sectional surveys of communities in Accra and Kumasi, Ghana, determining risk factors for malaria infection and anaemia in children aged 6-60 months. RESULTS Malaria prevalence rates ranged from 2% to 33% between urban communities. 47.1% of children were anaemic (Hb<11.0 g/dl). Factors associated with malaria prevalence were low socio-economic status, age and anaemia. The attributable risks of anaemia and severe anaemia (Hb<8.0 g/dl) caused by malaria were 5% and 23% respectively. CONCLUSIONS Malaria in urban areas displayed a heterogeneity and complexity that differed from the rural environment, which has important implications for malaria control. Marked intra-city variation indicates the importance of targeting specific areas or districts. The most vulnerable group, the urban poor, should be prioritized when designing control measures. This would require careful assessment of the malaria risk pattern in any city to guide an integrated control program.",
"title": "Urban malaria and anaemia in children: a cross-sectional survey in two cities of Ghana."
},
{
"docid": "30844602",
"text": "PROBLEM/CONDITION Since 1973, CDC has maintained a collaborative surveillance program for collection and periodic reporting of data on the occurrence and causes of foodborne-disease outbreaks (FBDOs) in the United States. REPORTING PERIOD COVERED This summary reviews data from January 1993 through December 1997. DESCRIPTION OF SYSTEM The Foodborne-Disease Outbreak Surveillance System reviews data concerning FBDOs, defined as the occurrence of two or more cases of a similar illness resulting from the ingestion of a common food. State and local public health departments have primary responsibility for identifying and investigating FBDOs. State, local, and territorial health departments use a standard form to report these outbreaks to CDC. RESULTS During 1993-1997, a total of 2,751 outbreaks of foodborne disease were reported (489 in 1993, 653 in 1994, 628 in 1995, 477 in 1996, and 504 in 1997). These outbreaks caused a reported 86,058 persons to become ill. Among outbreaks for which the etiology was determined, bacterial pathogens caused the largest percentage of outbreaks (75%) and the largest percentage of cases (86%). Salmonella serotype Enteritidis accounted for the largest number of outbreaks, cases, and deaths; most of these outbreaks were attributed to eating eggs. Chemical agents caused 17% of outbreaks and 1% of cases; viruses, 6% of outbreaks and 8% of cases; and parasites, 2% of outbreaks and 5% of cases. INTERPRETATION The annual number of FBDOs reported to CDC did not change substantially during this period or from previous years. During this reporting period, S. Enteritidis continued to be a major cause of illness and death. In addition, multistate outbreaks caused by contaminated produce and outbreaks caused by Escherichia coli O157:H7 remained prominent. ACTIONS TAKEN Current methods to detect FBDOs are improving, and several changes to improve the ease and timeliness of reporting FBDO data are occurring (e.g., a revised form to simplify FBDO reporting by state health departments and electronic reporting methods). State and local health departments continue to investigate and report FBDOs as part of efforts to better understand and define the epidemiology of foodborne disease in the United States. At the regional and national levels, surveillance data provide an indication of the etiologic agents, vehicles of transmission, and contributing factors associated with FBDOs and help direct public health actions to reduce illness and death caused by FBDOs.",
"title": "Surveillance for foodborne-disease outbreaks--United States, 1993-1997."
},
{
"docid": "13959707",
"text": "BACKGROUND Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. METHODS AND FINDINGS Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR) = 2.7 (95% CI 1.42, 5.01, P = 0.002) but not in those without detectable parasitaemia (HR = 1.0 (95% CI 0.74, 1.42, P = 0.9). CONCLUSIONS We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection.",
"title": "The Ratio of Monocytes to Lymphocytes in Peripheral Blood Correlates with Increased Susceptibility to Clinical Malaria in Kenyan Children"
},
{
"docid": "79231308",
"text": "as compared with 103 (8.2 percent) in the control group; the Kaplan-Meier estimates of the likelihood of freedom from deep-vein thrombosis or pulmonary embolism at 90 days were 94.1 percent (95 percent confidence interval, 92.5 to 95.4 percent) and 90.6 percent (95 percent confidence interval, 88.7 to 92.2 percent), respectively (P 0.001). The computer alert reduced the risk of deep-vein thrombosis or pulmonary embolism at 90 days by 41 percent (hazard ratio, 0.59; 95 percent confidence interval, 0.43 to 0.81; P 0.001). CONCLUSIONS The institution of a computer-alert program increased physicians’ use of prophylaxis and markedly reduced the rates of deep-vein thrombosis and pulmonary embolism among hospitalized patients at risk. Editorial Comment: Most hospitals have adopted electronic systems to alert physicians of drug interactions or possible substitutions, as well as other measures designed to improve the quality of care and decrease expenses. This approach was taken one step further by these authors, who evaluated whether notifying physicians that their patients were at increased risk for venous thromboembolism would decrease the incidence of deep vein thrombosis or pulmonary embolism. The premise was that simply notifying the physician would increase the use of appropriate prophylactic measures. Major surgery (defined as anything requiring general anesthesia), cancer and age greater than 75 years were included among the risk factors, each of which frequently applies to a urology population. In fact, more than 13% of the patients in the intervention group had a known diagnosis of a genitourinary cancer. The computer alert decreased the risk of deep vein thrombosis or pulmonary embolism by 41%. There are 2 lessons urologists can learn from this study. First, many urology patients are at increased risk for venous thromboembolism and appropriate prophylaxis should be used. In addition, although computer alert systems may seem intrusive at times, clinicians can expect to see more and more of them if there is further documentation that they improve the quality of care.",
"title": "Role of Computerized Physician Order Entry Systems in Facilitating Medication Errors"
},
{
"docid": "1349033",
"text": "Based on sensitivity analysis of the MacDonald-Ross model, it has long been argued that the best way to reduce malaria transmission is to target adult female mosquitoes with insecticides that can reduce the longevity and human-feeding frequency of vectors. However, these analyses have ignored a fundamental biological difference between mosquito adults and the immature stages that precede them: adults are highly mobile flying insects that can readily detect and avoid many intervention measures whereas mosquito eggs, larvae and pupae are confined within relatively small aquatic habitats and cannot readily escape control measures. We hypothesize that the control of adult but not immature mosquitoes is compromised by their ability to avoid interventions such as excito-repellant insecticides. We apply a simple model of intervention avoidance by mosquitoes and demonstrate that this can substantially reduce effective coverage, in terms of the proportion of the vector population that is covered, and overall impact on malaria transmission. We review historical evidence that larval control of African malaria vectors can be effective and conclude that the only limitations to the effective coverage of larval control are practical rather than fundamental. Larval control strategies against the vectors of malaria in sub-Saharan Africa could be highly effective, complementary to adult control interventions, and should be prioritized for further development, evaluation and implementation as an integral part of Rolling Back Malaria.",
"title": "Advantages of larval control for African malaria vectors: Low mobility and behavioural responsiveness of immature mosquito stages allow high effective coverage"
},
{
"docid": "8593263",
"text": "An observational prospective cohort study assessed malaria risk perception, knowledge and prophylaxis practices among individuals of African ethnicity living in Paris and travelling to their country of origin to visit friends or relatives (VFR). The study compared two groups of VFR who had visited a travel clinic (TC; n=122) or a travel agency (TA; n=69) before departure. Of the 47% of VFR citing malaria as a health concern, 75% knew that malaria is mosquito-borne and that bed nets are an effective preventive measure. Perception of high malaria risk was greater in the TA group (33%) than in the TC group (7%). The availability of a malaria vaccine was mentioned by 35% of VFR, with frequent confusion between yellow fever vaccine and malaria prevention. Twenty-nine percent took adequate chemoprophylaxis with complete adherence, which was higher among the TC group (41%) than the TA group (12%). Effective antivector protection measures used were bed nets (16%), wearing long clothes at night (14%) and air conditioning (8%), with no differences between the study groups except in the use of impregnated bed nets (11% of the TC group and none of the TA group). Media coverage, malaria chemoprophylaxis repayment and cultural adaptation of preventive messages should be improved to reduce the high rate of inadequate malaria prophylaxis in VFR.",
"title": "Malaria risk perception, knowledge and prophylaxis practices among travellers of African ethnicity living in Paris and visiting their country of origin in sub-Saharan Africa."
},
{
"docid": "24916604",
"text": "BACKGROUND The use of bisphosphonates for the prevention of skeletal related events in women with bone metastases from breast cancer is well established. We undertook an evaluation of bisphosphonate use in clinical practice in three Canadian cancer centres. In addition we assessed whether or not physicians at these centres are following their local treatment guidelines and funding policies. METHODS Charts and electronic files of patients who had received either clodronate or pamidronate at any time between January 2000 and December 2001 at three Canadian cancer centres were retrospectively reviewed. RESULTS There has been a marked improvement in the time between the diagnosis of bone metastases and the commencement of bisphosphonates from a median of 155 days in 1998 to 24 days in 2001. However, despite a local funding policy requiring that oral clodronate be the first bisphosphonate used, this was the case in only 67% of patients. In addition, despite one centre's guidelines recommending that bisphosphonates be stopped once the patient was progressing, 90% of their patients remained on bisphosphonates until they died. CONCLUSIONS A considerable amount of effort is spent on the creation of \"evidence based\" treatment guidelines. Funding agencies develop policies based on these treatment guidelines, but often funding is more restrictive than the treatment guideline would suggest. It is clear from this review that physicians still appear to manage a substantial proportion of patients outside of funding policies, but within evidence based recommendations. Therefore, a need exists for either the creation of guidelines and policies that physicians will follow or the implementation of methods to ensure that restrictive policies are actually followed.",
"title": "Do physicians follow systemic treatment and funding policy guidelines?"
}
] |
PLAIN-1688
|
nasal cavity cancer
|
[
{
"docid": "MED-2602",
"text": "In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.",
"title": "Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53."
},
{
"docid": "MED-4037",
"text": "In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 μg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 μg m(-3)) and Western (21.47 ± 11.44 μg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 μg m(-3)), followed by Western (0.86 ± 1.43 μg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 μg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6). Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.",
"title": "Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions."
},
{
"docid": "MED-2598",
"text": "Death receptors belong to the TNF receptor family and are characterised by an intracellular death domain that serves to recruit adapter proteins such as TRADD and FADD and cysteine proteases such as Caspase-8. Activation of Caspase-8 on the aggregated receptor leads to apoptosis. Triggering of death receptors is mediated through the binding of specific ligands of the TNF family, which are homotrimeric type-2 membrane proteins displaying three receptor binding sites. There are various means of modulating the activation of death receptors. The status of the ligand (membrane-bound vs. soluble) is critical in the activation of Fas and of TRAIL receptors. Cleavage of membrane-bound FasL to a soluble form (sFasL) does not affect its ability to bind to Fas but drastically decreases its cytotoxic activity. Conversely, cross-linking epitope-tagged sFasL with anti-tag antibodies to mimic membrane-bound ligand results in a 1000-fold increase in cytotoxicity. This suggests that more than three Fas molecules need to be aggregated to efficiently signal apoptosis. Death receptors can also be regulated by decoy receptors. The cytotoxic ligand TRAIL interacts with five receptors, only two of which (TRAIL-R1 and -R2) have a death domain. TRAIL-R3 is anchored to the membrane by a glycolipid and acts as a dominant negative inhibitor of TRAIL-mediated apoptosis when overexpressed on TRAIL-sensitive cells. Intracellular proteins interacting with the apoptotic pathway are potential modulators of death receptors. FLIP resembles Caspase-8 in structure but lacks protease activity. It interacts with both FADD and Caspase-8 to inhibits the apoptotic signal of death receptors and, at the same time, can activate other signalling pathways such as that leading to NF-kappa B activation.",
"title": "Apoptosis induced by death receptors."
},
{
"docid": "MED-2604",
"text": "Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.",
"title": "Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?"
},
{
"docid": "MED-4433",
"text": "BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund."
},
{
"docid": "MED-2605",
"text": "Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is known to inhibit proliferation of cancer cells by arresting them at various phases of the cell cycle and to induce apoptosis in tumor cells. Curcumin-induced apoptosis mainly involves the activation of caspase-3 and mitochondria-mediated pathway in various cancer cells of different tissue origin. In the present study, the induction of apoptosis and cytotoxicity by curcumin in colon cancer colo 205 cells was investigated by using flow cytometry. The results demonstrated that curcumin induced cytotoxicity and apoptosis dose- and time-depedently. Curcumin induced the production of reactive oxygen species (ROS) and Ca+2, decreased the levels of mitochondria membrane potential and induced caspase-3 activity. Curcumin also promoted the expression of Bax, cytochrome C, p53 and p21 but inhibited the expression of Bcl-2. These observations suggest that curcumin may have a possible therapeutic potential in colon cancer patients.",
"title": "Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3."
},
{
"docid": "MED-2603",
"text": "FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "FADD: a regulator of life and death."
},
{
"docid": "MED-2599",
"text": "Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.",
"title": "Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upre..."
},
{
"docid": "MED-4038",
"text": "We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes. The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS). The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period. In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.",
"title": "IMPACT OF BARBECUED MEAT CONSUMED IN PREGNANCY ON BIRTH OUTCOMES ACCOUNTING FOR PERSONAL PRENATAL EXPOSURE TO AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS. BIRTH COHORT STUDY IN POLAND"
},
{
"docid": "MED-2601",
"text": "It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.",
"title": "Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pat..."
},
{
"docid": "MED-4976",
"text": "Airborne cooking by-products from frying beef (hamburgers), pork (bacon strips) and soybean-based food (tempeh burgers) were collected, extracted, tested for mutagenicity and chemically analysed. The fumes generated by frying pork and beef were mutagenic, with 4900 and 1300 revertants/g of food cooked, respectively. No mutagenicity was detected in fumes from frying tempeh burgers. Bacon fried to a well-done but non-charred state was eight times more mutagenic in a microsuspension Ames/Salmonella test (TA98 with S-9) than hamburgers and about 350 times more mutagenic than tempeh burgers. Among food samples cooked to a well-done, non-charred state, bacon strips had almost 15-fold more mass (109.5 ng/g) than that of the beef, whereas no heterocyclic amine (HCA) was detected in the fried tempeh burgers. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HCA, followed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). No 2-amino-9H-pyrido[2,3-b]indole (A alpha C) was detected in the food samples fried at about 200 degrees C, although it was present in the collected airborne products. The total amounts of HCAs in the smoke condensates were 3 ng/g from fried bacon, 0.37 ng/g from fried beef and 0.177 ng/g from fried soy-based food. This study indicates that cooks are potentially exposed to relatively high levels of airborne mutagens and carcinogens and that long-term sampling inside restaurants and kitchens may be warranted in order to assess the potential risk of prolonged exposure.",
"title": "Airborne mutagens produced by frying beef, pork and a soy-based food."
},
{
"docid": "MED-4818",
"text": "Clinical and ecological evidence supporting an association between human papillomavirus (HPV)-related tumors and dietary factors are presented. Abstinence from high intake of fried pork (600-1,000 g/day) was associated with regression of an urethral condyloma in a healthy 19-year-old man treated with interferon gamma. International correlations suggest that pork intake is positively associated with incidence of cervical cancer, a disease also related to HPV. Pork meat or dietary factors associated with pork meat consumption may be involved in the development of HPV-related diseases.",
"title": "Pork intake and human papillomavirus-related disease."
},
{
"docid": "MED-4819",
"text": "We previously studied mortality up to 1989 in 2,639 members of a local union who had ever worked in poultry slaughtering and processing plants, because they were exposed to oncogenic viruses present in poultry. In this report, cancer mortality was updated to the year 2003 for 2,580 of the 2,639 subjects who worked exclusively in poultry plants. Mortality in poultry workers was compared with that in the US general population through the estimation of proportional mortality and standardized mortality ratios separately for each race/sex group and for the whole cohort. Compared to the US general population, an excess of cancers of the buccal and nasal cavities and pharynx (base of the tongue, palate and other unspecified mouth, tonsil and oropharynx, nasal cavity/middle ear/accessory sinus), esophagus, recto-sigmoid/rectum/anus, liver and intrabiliary system, myelofibrosis, lymphoid leukemia and multiple myeloma was observed in particular subgroups or in the entire poultry cohort. We hypothesize that oncogenic viruses present in poultry, and exposure to fumes, are candidates for an etiologic role to explain the excess occurrence of at least some of these cancers in the poultry workers. Larger studies which can control for confounding factors are urgently needed to determine the significance of these findings.",
"title": "Mortality from malignant diseases-update of the Baltimore union poultry cohort."
},
{
"docid": "MED-2607",
"text": "Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications.",
"title": "New perspectives of curcumin in cancer prevention"
}
] |
[
{
"docid": "MED-3767",
"text": "BACKGROUND: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day). PATIENTS AND METHODS: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010. RESULTS: We included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors. CONCLUSIONS: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.",
"title": "Light alcohol drinking and cancer: a meta-analysis."
},
{
"docid": "MED-3516",
"text": "1. Topical application of capsaicin to the human nasal mucosa induced a burning sensation and sneezing. A dose-dependent seromucous nasal secretion was also observed. Capsaicin (75 micrograms) was more potent than methacholine (50 mg) in producing nasal secretion, while topical histamine (200 micrograms), substance P (135 micrograms) and calcitonin gene-related peptide (36 micrograms) did not induce rhinorrhea. 2. Pretreatment with either topical ipratropium bromide, systemic dexchlorpheniramine or indomethacin did not influence the effects induced by capsaicin. Topical pretreatment with lidocaine inhibited the painful sensation but failed to block the rhinorrhea. Desensitization to the effects of capsaicin occurred following 4-5 subsequent applications, and full recovery was observed within 30-40 days. 3. It is proposed that the effects of capsaicin in human nasal mucosa are due to excitation of primary afferent neurones that (a) convey burning and painful sensation, (b) evoke a sneezing reflex and (c) induce nasal secretion by releasing transmitter(s) from their peripheral terminals.",
"title": "Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man."
},
{
"docid": "MED-4142",
"text": "Swine confinement buildings in eastern Canada are enclosed and equipped with modern production systems to manage waste. Bioaerosols of these swine confinement buildings could be contaminated by human pathogens and antimicrobial resistant bacteria which could colonize exposed workers. We therefore wanted to analyze bioaerosols of swine confinement buildings and nasal flora of Canadian hog producers to evaluate possible colonization with human pathogens and tetracycline-resistant bacteria. Culturable and non-culturable human pathogens and tet genes were investigated in the bioaerosols of 18 barns. The nasal passages of 35 hog producers were sampled and total DNA was extracted from the calcium-alginate swabs to detect, by PCR, Campylobacter, C. perfringens, Enterococcus, E. coli, Y. enterocolitica, tetA/tetC, tetG and ribosomal protection protein genes. Airborne culturable C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were present in the bioaerosols of 16, 17, 11 and 6 of the 18 facilities. Aerosolized total (culturable/non culturable) Campylobacter, C. perfringens, Enterococcus, E. coli and Y. enterocolitica were detected in 10, 6, 15, 18 and 2 barns, respectively. Tet genes were found in isolates of culturable human pathogens. TetA/tetC, tetG and ribosomal protection protein genes were detected in the bioaerosols of all 18 studied buildings. Campylobacter, C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were found respectively in 4, 9, 17, 14 and one nasal flora of workers. One and 10 workers were positive for tetA/tetC and tetG genes, respectively. In swine confinement buildings, hog producers are exposed to aerosolized human pathogens and tetracycline-resistant bacteria that can contaminate the nasal flora. Copyright © 2010 Elsevier GmbH. All rights reserved.",
"title": "Human pathogens and tetracycline-resistant bacteria in bioaerosols of swine confinement buildings and in nasal flora of hog producers."
},
{
"docid": "MED-3517",
"text": "Preliminary studies have shown that repeated nasal applications of capsaicin prevented the occurrence of cluster headache attacks. The present study was designed to verify the difference in efficacy of treatment with nasal capsaicin, depending on the side of application. Fifty-two patients affected by episodic form were divided into 2 groups, one receiving the treatment on the same side where the attacks occurred (ipsilateral side), the other on the controlateral side. Eighteen patients with a chronic form alternately received both ipsilateral and controlateral treatments. Seventy percent of the episodic patients, treated on the ipsilateral side, showed a marked amelioration whereas no improvement was noted in the patients treated on the contralateral side. The efficacy of ipsilateral treatment was emphasized by the results obtained in chronic patients. However, in these patients, the maximum period of amelioration lasted no more than 40 days. The difference between the effects of the 2 treatments (contralateral and ipsilateral) was statistically significant in both episodic and chronic sufferers. The efficacy of repeated nasal applications of capsaicin in cluster headache is congruent with previous reports on the therapeutic effect of capsaicin in other pain syndromes (post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia) and supports the use of the drug to produce a selective analgesia.",
"title": "Preventative effect of repeated nasal applications of capsaicin in cluster headache."
},
{
"docid": "MED-4023",
"text": "INTRODUCTION: The aim of the study was to determine the potential relation between vegetarian diet and tooth erosion and abrasion. MATERIAL/METHODS: The examination included 46 vegetarians and the same number in the control group. Clinical research was carried out in order to detect the presence of abrasive and erosive changes and the level of hygiene in oral cavities. The questionnaire survey concerned dietary and hygienic habits. Statistical analysis of the data was conducted with Chi-square test and Mann-Whitney U test. The relations between following a vegetarian diet and the occurrence of non-carious cavities was tested with models of logistic regression. RESULTS: Tooth erosion was present among 39.1% of vegetarians and 23.9% of controls, while abrasion appeared among 26.1% and 10.9%, respectively, and the differences were statistically insignificant. The distribution of the changes was similar in both groups. Among vegetarians, significantly more frequent consumption of sour products (predominantly raw vegetables and fruit and tomatoes) was observed. The level of oral hygiene and hygienic habits were similar in both groups. The analysis of statistical regression did not reveal any relations between following a vegetarian diet and the occurrence of tooth erosion and abrasion. DISCUSSION: The results did not reveal any direct influence of vegetarian diet on the occurrence of erosive and abrasive changes. However, in the vegetarian group, more frequent consumption of some sour products and more commonly used horizontal brushing method were observed, with a slightly higher occurrence of non-carious cavities. Further research is required to obtain unambiguous conclusions.",
"title": "Assessment of the influence of vegetarian diet on the occurrence of erosive and abrasive cavities in hard tooth tissues."
},
{
"docid": "MED-4741",
"text": "BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.",
"title": "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay."
},
{
"docid": "MED-2449",
"text": "BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.",
"title": "An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis."
},
{
"docid": "MED-4565",
"text": "OBJECTIVES/HYPOTHESIS: This study aimed to assess the clinical relevance of contamination of nasal irrigation bottles in patients with recalcitrant chronic rhinosinusitis (CRS). Secondary investigations to identify the presence of bacterial biofilms on the inner surface of the bottles and to assess different sterilization methods were also undertaken. STUDY DESIGN: Prospective, observational. METHODS: Eleven patients with recalcitrant CRS who were already using nasal irrigation as part of their treatment regimen were examined every 2 weeks for a period of 6 weeks. At each visit, a culture sample was taken from their irrigation bottle and middle meatus, and they were given a new irrigation bottle. Irrigation bottles from six patients were analyzed with scanning electron microscopy (SEM) to detect biofilm formation. Finally, new bottles were inoculated with different strains of Staphylococcus aureus and then cleaned with different methods. The bottles were cultured immediately after cleaning and 48 hours later. RESULTS: Overall, 42 of 43 (97%) bottles collected demonstrated bacterial growth. Concurrent sinonasal and bottle infection with S. aureus was seen in 51% of patients during the study. Bacterial biofilms were demonstrated on the inner surface of four of the six irrigation bottles tested. Treatment with Milton's solution (1% NaOCl plus 19% NaCl) and microwaving were found to be effective methods for sterilizing the bottles both initially after the cleaning and 48 hours later. CONCLUSIONS: Patients who irrigate their nose and sinuses commonly contaminate their irrigation bottle, most often with S. aureus, which can be in the biofilm form. Simple cleaning methods could reduce contamination of the bottles.",
"title": "The clinical significance of nasal irrigation bottle contamination."
},
{
"docid": "MED-1567",
"text": "INTRODUCTION: American Seventh-day Adventists have been reported to have lower cancer mortality and incidence than the general population. Adventists do not consume tobacco, alcohol or pork, and many adhere to a lacto-ovo-vegetarian lifestyle. Baptists discourage excessive use of alcohol and tobacco. In this study, we investigated whether the incidence of cancer in a large cohort of Danish Adventists and Baptists was different compared to the general Danish population. MATERIAL AND METHODS: We followed 11,580 Danish Adventists and Baptists in the nationwide Danish Cancer Registry, which contains information on cases of cancer for 1943-2008. Cancer incidence in the cohort was compared with that in the general Danish population as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), and within-cohort comparisons were made with a Cox model. RESULTS: Lower cancer incidences were observed for both Seventh-day Adventist men (SIR, 66; 95% CI, 60-72) and women (85; 80-91). The same result was observed for Baptists although not as low. The differences were most pronounced for smoking-related cancers such as those of the buccal cavity and lung (SIR, 20; 13-30 for Seventh-day Adventist men and 33; 22-49 for Seventh-day Adventist women). The incidences of other lifestyle-related cancers, such as of stomach, rectum, liver and cervix, were also decreased. In general, the SIRs were lower for men than for women, and Adventists had lower hazard rates than Baptists. DISCUSSION: Our findings point to the benefits of compliance with public health recommendations and indicate that lifestyle changes in the population might change the cancer risks of individuals. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Cancer incidence among Danish Seventh-day Adventists and Baptists."
},
{
"docid": "MED-5172",
"text": "The prevalence of allergic rhinitis is increasing globally due to various causes. It affects the quality life of a large group of people in all around the world. Allergic rhinitis still remains inadequately controlled with present medical means. The need of continuous medical therapy makes individuals anxious about the side effects of the drugs. So there is a need for an alternative strategy. Effects of spirulina, tinospora cordifolia and butterbur were investigated recently on allergic rhinitis in just very few investigations. Spirulina represents a blue-green alga that is produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. This double blind, placebo controlled study, evaluated the effectiveness and tolerability of spirulina for treating patients with allergic rhinitis. Spirulina consumption significantly improved the symptoms and physical findings compared with placebo (P < 0.001***) including nasal discharge, sneezing, nasal congestion and itching. Spirulina is clinically effective on allergic rhinitis when compared with placebo. Further studies should be performed in order to clarify the mechanism of this effect.",
"title": "The effects of spirulina on allergic rhinitis."
},
{
"docid": "MED-3764",
"text": "Increasing evidence suggests that acetaldehyde, the first and genotoxic metabolite of ethanol, mediates the carcinogenicity of alcoholic beverages. Ethanol is also contained in a number of ready-to-use mouthwashes typically between 5 and 27% vol. An increased risk of oral cancer has been discussed for users of such mouthwashes; however, epidemiological evidence had remained inconclusive. This study is the first to investigate acetaldehyde levels in saliva after use of alcohol-containing mouthwashes. Ready-to-use mouthwashes and mouthrinses (n = 13) were rinsed in the mouth by healthy, nonsmoking volunteers (n = 4) as intended by the manufacturers (20 ml for 30 sec). Saliva was collected at 0.5, 2, 5 and 10 min after mouthwash use and analyzed using headspace gas chromatography. The acetaldehyde content in the saliva was 41 +/- 15 microM, range 9-85 microM (0.5 min), 52 +/- 14 microM, range 11-105 microM (2 min), 32 +/- 7 microM, range 9-67 microM (5 min) and 15 +/- 7 microM, range 0-37 microM (10 min). The contents were significantly above endogenous levels and corresponding to concentrations normally found after alcoholic beverage consumption. A twice-daily use of alcohol-containing mouthwashes leads to a systemic acetaldehyde exposure of 0.26 microg/kg bodyweight/day on average, which corresponds to a lifetime cancer risk of 3E-6. The margin of exposure was calculated to be 217,604, which would be seen as a low public health concern. However, the local acetaldehyde contents in the saliva are reaching concentrations associated with DNA adduct formation and sister chromatid exchange in vitro, so that concerns for local carcinogenic effects in the oral cavity remain.",
"title": "Salivary acetaldehyde increase due to alcohol-containing mouthwash use: a risk factor for oral cancer."
},
{
"docid": "MED-3763",
"text": "The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity."
},
{
"docid": "MED-4032",
"text": "AIM: The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. METHODS: A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. RESULTS: The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. CONCLUSION: In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.",
"title": "Oral implications of the vegan diet: observational study."
},
{
"docid": "MED-2208",
"text": "BACKGROUND: Bikunin, a Kunitz-type protease inhibitor, specifically inhibits tumor invasion and metastasis. METHODS: The authors initially evaluated the therapeutic efficacy of once-daily oral administration of different doses of bikunin against human ovarian carcinoma HRA cells growing in the peritonea of nude mice. For the in vivo studies, female 7-week-old nude mice were randomized to 1 of 4 groups: bikunin-treated groups (n = 9 in each group) received 3, 10, or 30 microg/g body weight per day bikunin for 7 days via gastrointestinal gavage, and a control group (n = 9) received the vehicle solution (phosphate-buffered saline) via gastrointestinal gavage. On Day 9, the abdominal cavity was examined by two observers who were blinded to treatment. RESULTS: After oral administration, intact bikunin was detectable in mouse serum specimens at 3 and 6 hours. This was followed by a decline at 12 hours. The mice given bikunin at the highest dose level had a 40% decrease in tumor load. The highest uptake in the tumor was obtained with [125I]bikunin 12 hours postadministration. No effect on either food intake or body weight was observed in the treated versus sham groups. The current study was the first to report the potent activity of once-daily oral administration of bikunin against ovarian carcinoma. Next, the authors performed a Phase I trial to determine the maximum-tolerated dose (MTD) and safety of a once-daily oral administration schedule. The indication was locally advanced uterine cervical carcinoma after definitive treatment. An escalating dose (3, 10, and 30 mg/kg per day) of bikunin was administered orally to nine patients for 7 days. There were no dose-limiting toxicities and the MTD of the bikunin schedule was not defined. The authors also obtained preliminary data on its effect on urokinase-type plasminogen activator expression at the highest dose level. CONCLUSIONS: Once-daily oral administration of bikunin was found to be safe in humans and exhibited signs of biologic activity. Copyright 2004 American Cancer Society.",
"title": "Therapeutic efficacy of once-daily oral administration of a Kunitz-type protease inhibitor, bikunin, in a mouse model and in human cancer."
},
{
"docid": "MED-1759",
"text": "Background Livestock-Associated MRSA (LA-MRSA) belonging to ST398 lineage, common among pigs and other animals, emerged in Central and Northern Europe, becoming a new risk factor for MRSA among farm workers. Strains belonging to ST398 can be responsible for human colonization and infection, mainly in areas with high livestock-farming. The aim of this study was to investigate the occurrence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) human colonization and infections in an area of the Lombardy Region (Italy), the Italian region with the highest density of pig farming. Methods In the period March-April 2010, 879 nasal swabs were taken from subjects at admission to a local hospital serving an area of the Lombardy Region devoted to agriculture and farming. In the period March 2010-February 2011, all MRSA strains from community-acquired infection (CAI) observed in the same hospital, were collected. Molecular characterization of the isolates included SCCmec typing, spa typing and multilocus sequence typing (MLST). Results Out of 879 nasal swabs examined, 9 (1%) yielded MRSA. Five strains were assigned to sequence type (ST)398 (spa t899, 3 isolates; t108 and t2922, 1 isolate each) and were therefore categorized as LA-MRSA. The other 4 isolates were likely of hospital origin. No strains were positive for Panton-Valentine Leukocidin genes. Twenty MRSA isolates were detected from CAI, 17 were from skin and soft-tissue infections and 3 from other infections. An MRSA isolate from otitis externa was t899/ST398 and PVL-negative, hence categorized as LA-MRSA. Four isolates were assigned to t127/ST1. Eight strains were PVL-positive community acquired (CA)-MRSA and belonged to different clones, the most frequent being ST8. Conclusions In an area of Italy with high density of pig farming, LA-MRSA is able to colonize the population and rarely to produce infections. Typical CA-MRSA is more common than LA-MRSA among CAI.",
"title": "Livestock-associated methicillin-resistant Staphylococcus aureus responsible for human colonization and infection in an area of Italy with high density of pig farming"
},
{
"docid": "MED-4563",
"text": "BACKGROUND: The use of nasal irrigation for the treatment of nose and sinus complaints has its foundations in yogic and homeopathic traditions. There has been increasing use of saline irrigation, douches, sprays and rinsing as an adjunct to the medical management of chronic rhinosinusitis. Treatment strategies often include the use of topical saline from once to more than four times a day. Considerable patient effort is often involved. Any additional benefit has been difficult to discern from other treatments. OBJECTIVES: To evaluate the effectiveness and safety of topical saline in the management of chronic rhinosinusitis. SEARCH STRATEGY: Our search included the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4 2006), MEDLINE (1950 to 2006) and EMBASE (1974 to 2006). The date of the last search was November 2006. SELECTION CRITERIA: Randomised controlled trials in which saline was evaluated in comparison with either no treatment, a placebo, as an adjunct to other treatments or against treatments. The comparison of hypertonic versus isotonic solutions was also compared. DATA COLLECTION AND ANALYSIS: Trials were graded for methodological quality using the Cochrane approach (modification of Chalmers 1990). Only symptom scores from saline versus no treatment and symptom and radiological scores from the hypertonic versus isotonic group could be pooled for statistical analysis. A narrative overview of the remaining results is presented. MAIN RESULTS: Eight trials were identified that satisfied the inclusion criteria. Three studies compared topical saline against no treatment, one against placebo, one as an adjunct to and one against an intranasal steroid spray. Two studies compared different hypertonic solutions against isotonic saline. There is evidence that saline is beneficial in the treatment of the symptoms of chronic rhinosinusitis when used as the sole modality of treatment. Evidence also exists in favour of saline as a treatment adjunct. No superiority was seen when saline was compared against a reflexology 'placebo'. Saline is not as effective as an intranasal steroid. Some evidence suggests that hypertonic solutions improve objective measures but the impact on symptoms is less clear. AUTHORS' CONCLUSIONS: Saline irrigations are well tolerated. Although minor side effects are common, the beneficial effect of saline appears to outweigh these drawbacks for the majority of patients. The use of topical saline could be included as a treatment adjunct for the symptoms of chronic rhinosinusitis.",
"title": "Nasal saline irrigations for the symptoms of chronic rhinosinusitis."
},
{
"docid": "MED-855",
"text": "Hydrogen peroxide is an oxidising agent that is used in a number of household products, including general-purpose disinfectants, chlorine-free bleaches, fabric stain removers, contact lens disinfectants and hair dyes, and it is a component of some tooth whitening products. In industry, the principal use of hydrogen peroxide is as a bleaching agent in the manufacture of paper and pulp. Hydrogen peroxide has been employed medicinally for wound irrigation and for the sterilisation of ophthalmic and endoscopic instruments. Hydrogen peroxide causes toxicity via three main mechanisms: corrosive damage, oxygen gas formation and lipid peroxidation. Concentrated hydrogen peroxide is caustic and exposure may result in local tissue damage. Ingestion of concentrated (>35%) hydrogen peroxide can also result in the generation of substantial volumes of oxygen. Where the amount of oxygen evolved exceeds its maximum solubility in blood, venous or arterial gas embolism may occur. The mechanism of CNS damage is thought to be arterial gas embolisation with subsequent brain infarction. Rapid generation of oxygen in closed body cavities can also cause mechanical distension and there is potential for the rupture of the hollow viscus secondary to oxygen liberation. In addition, intravascular foaming following absorption can seriously impede right ventricular output and produce complete loss of cardiac output. Hydrogen peroxide can also exert a direct cytotoxic effect via lipid peroxidation. Ingestion of hydrogen peroxide may cause irritation of the gastrointestinal tract with nausea, vomiting, haematemesis and foaming at the mouth; the foam may obstruct the respiratory tract or result in pulmonary aspiration. Painful gastric distension and belching may be caused by the liberation of large volumes of oxygen in the stomach. Blistering of the mucosae and oropharyngeal burns are common following ingestion of concentrated solutions, and laryngospasm and haemorrhagic gastritis have been reported. Sinus tachycardia, lethargy, confusion, coma, convulsions, stridor, sub-epiglottic narrowing, apnoea, cyanosis and cardiorespiratory arrest may ensue within minutes of ingestion. Oxygen gas embolism may produce multiple cerebral infarctions. Although most inhalational exposures cause little more than coughing and transient dyspnoea, inhalation of highly concentrated solutions of hydrogen peroxide can cause severe irritation and inflammation of mucous membranes, with coughing and dyspnoea. Shock, coma and convulsions may ensue and pulmonary oedema may occur up to 24-72 hours post exposure. Severe toxicity has resulted from the use of hydrogen peroxide solutions to irrigate wounds within closed body cavities or under pressure as oxygen gas embolism has resulted. Inflammation, blistering and severe skin damage may follow dermal contact. Ocular exposure to 3% solutions may cause immediate stinging, irritation, lacrimation and blurred vision, but severe injury is unlikely. Exposure to more concentrated hydrogen peroxide solutions (>10%) may result in ulceration or perforation of the cornea. Gut decontamination is not indicated following ingestion, due to the rapid decomposition of hydrogen peroxide by catalase to oxygen and water. If gastric distension is painful, a gastric tube should be passed to release gas. Early aggressive airway management is critical in patients who have ingested concentrated hydrogen peroxide, as respiratory failure and arrest appear to be the proximate cause of death. Endoscopy should be considered if there is persistent vomiting, haematemesis, significant oral burns, severe abdominal pain, dysphagia or stridor. Corticosteroids in high dosage have been recommended if laryngeal and pulmonary oedema supervene, but their value is unproven. Endotracheal intubation, or rarely, tracheostomy may be required for life-threatening laryngeal oedema. Contaminated skin should be washed with copious amounts of water. Skin lesions should be treated as thermal burns; surgery may be required for deep burns. In the case of eye exposure, the affected eye(s) shod eye(s) should be irrigated immediately and thoroughly with water or 0.9% saline for at least 10-15 minutes. Instillation of a local anaesthetic may reduce discomfort and assist more thorough decontamination.",
"title": "Hydrogen peroxide poisoning."
},
{
"docid": "MED-4564",
"text": "Rhinosinusitis is one of the most common conditions for which patients seek medical care. Subtypes of rhinosinusitis include acute, subacute, recurrent acute, and chronic. Acute rhinosinusitis is further specified as bacterial or viral. Most cases of acute rhinosinusitis are caused by viral infections associated with the common cold. Symptomatic treatment with analgesics, decongestants, and saline nasal irrigation is appropriate in patients who present with nonsevere symptoms (e.g., mild pain, temperature less than 101°F [38.3°C]). Narrow-spectrum antibiotics, such as amoxicillin or trimethoprim/sulfamethoxazole, are recommended in patients with symptoms or signs of acute rhinosinusitis that do not improve after seven days, or that worsen at any time. Limited evidence supports the use of intranasal corticosteroids in patients with acute rhinosinusitis. Radiographic imaging is not recommended in the evaluation of uncomplicated acute rhinosinusitis. Computed tomography of the sinuses should not be used for routine evaluation, although it may be used to define anatomic abnormalities and evaluate patients with suspected complications of acute bacterial rhinosinusitis. Rare complications of acute bacterial rhinosinusitis include orbital, intracranial, and bony involvement. If symptoms persist or progress after maximal medical therapy, and if computed tomography shows evidence of sinus disease, referral to an otolaryngologist is warranted.",
"title": "Acute rhinosinusitis in adults."
},
{
"docid": "MED-5031",
"text": "Background Sleep quality is thought to be an important predictor of immunity and in turn susceptibility to the common cold. This article examines whether sleep duration and efficiency in the weeks preceding viral exposure are associated with cold susceptibility. Methods Participants were 153 healthy men and women volunteers, ages 21–55. For 14 consecutive days, they reported their sleep duration and sleep efficiency (percent of time in bed actually asleep) for the previous night, and whether they felt rested. Average scores for each sleep variable were calculated over the 14-day baseline. Subsequently, participants were administered nasal drops containing a rhinovirus, quarantined and monitored on the day before and for five days following exposure for development of a clinical cold (infection in the presence of objective signs of illness). Results There was a graded association with average sleep duration, with those with <7 hours sleep 2.94 times (CI[95%]=1.18–7.30) more likely to develop a cold than those with ≥ 8 hours. The association with sleep efficiency was also graded with those with < 92% efficiency 5.50 times (CI[95%]=2.08–14.48) more likely to develop a cold than those with efficiencies ≥98%. These relations could not be explained by differences in pre-challenge virus-specific antibody, demographics, season of the year, body mass, socioeconomic status, psychological variables or health practices. Percent of days feeling rested was not associated with colds. Conclusions Poorer sleep efficiency and shorter sleep duration in the weeks preceding an exposure to a rhinovirus were associated with lower resistance to illness.",
"title": "Sleep Habits and Susceptibility to the Common Cold"
},
{
"docid": "MED-2095",
"text": "During the last few years, there has been increasing interest in buccal epithelial cells for cytogenetic evaluation of different materials. In the present study, the use of these cells and peripheral lymphocytes for cytogenetic evaluation of chlorhexidine digluconate (CHX) with comet assay (single cell gel electrophoresis, or SCGE) is reported. This technique detects DNA strand breaks in individual cells in alkaline conditions. Thirteen volunteers were requested to rinse their mouths with 0.12% CHX solution for 18 days. Buccal epithelial cells and peripheral blood lymphocytes were obtained from all participants at baseline and the end of the experimental period. One hundred cells per subject were analysed for the DNA damage. A statistical increase was observed in the damaged buccal and blood cells after the CHX application. The mean grade of damage in buccal cells was statistically different from that in blood cells. Due to minimal absorption of chlorhexidine into the tissues and low concentrations of free chlorhexidine in the oral cavity, the DNA damage produced by chlorhexidine in lymphocytes was lower than in buccal epithelial cells. As chlorhexidine does not accumulate in the body, the frequencies of DNA damage could be transient. Detected DNA damage after CHX use might be the indication of an earlier effect, before DNA repair begins, and could be reversible.",
"title": "Monitoring of buccal epithelial cells by alkaline comet assay (single cell gel electrophoresis technique) in cytogenetic evaluation of chlorhexidine."
},
{
"docid": "MED-3637",
"text": "There are over 750 species of bacteria that inhabit the human oral cavity, but only a small fraction of those are attributed to causing plaque-related diseases such as caries. Streptococcus mutans is accepted as the main cariogenic agent and there is substantial knowledge regarding the specific virulence factors that render the organism a pathogen. There has been rising interest in alternative, target-specific treatment options as opposed to nonspecific mechanical plaque removal or application of broad-spectrum antibacterials that are currently in use. The impact of diet on oral health is undeniable, and this is directly observable in populations that consume high quantities of polyphenol-rich foods or beverages. Such populations have low caries incidence and better overall oral health. Camellia sinensis, the plant from which various forms of tea are derived, and Vaccinium macrocarpon (American cranberry fruit) have received notable attention both for their prevalence in the human diet as well as for their unique composition of polyphenols. The biologically active constituents of these plants have demonstrated potent enzyme-inhibitory properties without being bactericidal, a key quality that is important in developing therapies that will not cause microorganisms to develop resistance. The aim of this review is to consider studies that have investigated the feasibility of tea, cranberry, and other select plant derivatives as a potential basis for alternative therapeutic agents against Streptococcus mutans and to evaluate their current and future clinical relevance.",
"title": "Antimicrobial Traits of Tea- and Cranberry-Derived Polyphenols against Streptococcus mutans"
},
{
"docid": "MED-4507",
"text": "Recent studies surprisingly show that dietary inorganic nitrate, abundant in vegetables, can be metabolized in vivo to form nitrite and then bioactive nitric oxide. A reduction in blood pressure was recently noted in healthy volunteers after dietary supplementation with nitrate; an effect consistent with formation of vasodilatory nitric oxide. Oral bacteria have been suggested to play a role in bioactivation of nitrate by first reducing it to the more reactive anion nitrite. In a cross-over designed study in seven healthy volunteers we examined the effects of a commercially available chlorhexidine-containing antibacterial mouthwash on salivary and plasma levels of nitrite measured after an oral intake of sodium nitrate (10mg/kg dissolved in water). In the control situation the salivary and plasma levels of nitrate and nitrite increased greatly after the nitrate load. Rinsing the mouth with the antibacterial mouthwash prior to the nitrate load had no effect on nitrate accumulation in saliva or plasma but abolished its conversion to nitrite in saliva and markedly attenuated the rise in plasma nitrite. We conclude that the acute increase in plasma nitrite seen after a nitrate load is critically dependent on nitrate reduction in the oral cavity by commensal bacteria. The removal of these bacteria with an antibacterial mouthwash will very likely attenuate the NO-dependent biological effects of dietary nitrate.",
"title": "The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash."
},
{
"docid": "MED-1413",
"text": "The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated.",
"title": "Human gut microbiota: does diet matter?"
},
{
"docid": "MED-1218",
"text": "There has been a recent increase in community-associated infections linked to methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile. It is established that both pathogens can be recovered from retail pork, although it is unclear to what degree contamination is acquired at the farm in comparison to that acquired during processing. To address this gap, the following study reports on the carriage of MRSA and C. difficile on pigs from birth through to the end of processing. C. difficile was isolated from 28 (93%) of 30 pigs at 1 day of age, but prevalence declined sharply to 1 of 26 by market age (188 days). MRSA prevalence peaked at 74 days of age, with 19 (68%) of 28 pigs testing positive, but declined to 3 of 26 at 150 days of age, with no pig being detected as positive at market age. At the processing facility, C. difficile was isolated from the holding area, with a single carcass testing positive for the pathogen at preevisceration. MRSA was primarily isolated from nasal swabs with 8 (31%) carcasses testing positive at postbleed, which increased to 14 (54%) positive at postscald tanks. Only one carcass (sampled at postbleed) tested positive for MRSA, with no recovery of the pathogen from environmental samples taken. C. difficile ribotype 078 predominated in the longitudinal portion of the study, accounting for all of the 68 isolates recovered from pigs. Only three C. difficile isolates, which were identified as ribotype 078, were recovered at the slaughterhouse. MRSA spa type 539 (t034) predominated in pigs on the farm and samples taken at the slaughterhouse, accounting for 80% of all isolates recovered. The study demonstrated that both C. difficile and MRSA acquired on the farm can be transferred through to processing, although no evidence for significant cross-contamination between carcasses or the slaughterhouse environment was evident.",
"title": "Longitudinal study of Clostridium difficile and Methicillin-resistant Staphylococcus aureus associated with pigs from weaning through to the end of..."
},
{
"docid": "MED-899",
"text": "Heiner syndrome (HS) is a food hypersensitivity pulmonary disease that affects primarily infants, and is mostly caused by cow's milk (CM). Only a few reports have been published, which may be due to its misdiagnosis. We review here a series of eight cases. When first diagnosed they were 4-29 months of age. They were fed CM from birth and their chronic respiratory symptoms began at age 1-9 months. The symptoms were in the form of cough in seven, wheezing in three, hemoptysis in two, nasal congestion in three, dyspnea in one, recurrent otitis media (OM) in three, recurrent fever in four, anorexia, vomiting, colic or diarrhea in five, hematochezia in one, and failure to thrive (FTT) in two. All had radiologic evidence of pulmonary infiltrates. High titers of precipitating antibodies to CM proteins were demonstrated in six of six and milk-specific immunoglobulin E (IgE) was positive in one of two. Pulmonary hemosiderosis (PH) was confirmed in one patient who showed iron-laden macrophages (ILM) in the bronchoalveolar lavage (BAL), gastric washing, and open lung biopsy. Additional findings, in a descending frequency, were eosinophilia, anemia, and elevated level of total IgM, IgE or IgA. Milk elimination resulted in remarkable improvement in symptoms within days and clearing of the pulmonary infiltrate within weeks. Parents consented to milk challenge in only three cases, all of whom developed recurrence of symptoms. After 2 yr of milk avoidance in one patient, milk challenge was tolerated for 2 months, and then the patient developed symptoms, serum milk precipitins, pulmonary infiltrate, and ILM. The HS should be suspected in young children with chronic pulmonary disease of obscure cause. The diagnosis is supported with a positive milk precipitin test and improvement on a trial of milk elimination. Severe cases may be complicated with PH, which should be suspected in the presence of anemia or hemoptysis and be confirmed with the demonstration of ILM.",
"title": "Milk-induced pulmonary disease in infants (Heiner syndrome)."
},
{
"docid": "MED-1977",
"text": "Reports have documented colonization of swine in Europe, North America and more recently in China with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA). Contamination of pig farmers, veterinarians and abattoir workers with these strains has been observed. However, although contamination levels of 10% of retail pork were reported from the Netherlands and Canada, there are limited data of contamination rates of workers handling raw meat. We investigated the rates of MRSA contamination of local butchers working in wet markets, where recently slaughtered pigs are cut up. Nasal swabs collected from 300 pork butchers at markets throughout Hong Kong were enriched in brain heart infusion broth with 5% salt and cultured on MRSASelect(®) . Isolates were confirmed as Staphylococcus aureus and susceptibility testing performed. The presence of mecA was confirmed, SCCmec and spa type determined and relatedness investigated by PFGE. Subjects completed a questionnaire on MRSA carriage risk factors. Seventeen samples (5.6%) yielded MRSA, 15 harbouring SCCmec IVb. Ten strains were t899 (CC9), previously reported from local pig carcasses. Five strains were healthcare associated: SCCmec type II, t701(CC6), colonizing two subjects at the same establishment, and single isolates of t008 (CC8), t002 (CC5) and t123 (CC45). The remaining isolates were t359 (CC97), previously reported from buffaloes, and t375 (CC5), reported from bovine milk. None of these butchers reported recent hospitalization or a healthcare worker in the family. Two had recently received antibiotics, one for a skin infection. Four reported wound infections within the last year. All were exposed to meat for >9 h per day. Carriage of MRSA was higher in butchers than in the general community. Although five strains were probably of healthcare origin, the high incidence of t899 (CC9) suggests that cross-contamination from pork occurs frequently. Washing of hands after touching raw pork is advised. © 2012 Blackwell Verlag GmbH.",
"title": "Colonization of butchers with livestock-associated methicillin-resistant Staphylococcus aureus."
},
{
"docid": "MED-3355",
"text": "OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.",
"title": "Recent fat intake modulates fat taste sensitivity in lean and overweight subjects."
},
{
"docid": "MED-3703",
"text": "OBJECTIVE: To provide an overview of what is currently known about the relationship between allergies and cancer. DATA SOURCES: Publications were selected from a systematic review of the English-language literature from established databases (eg, MEDLINE, EBSCO) and the references of materials identified through these databases. STUDY SELECTION: Publications assessing the association between asthma, hay fever, or other allergy-related diseases and cancer were included in this review. RESULTS: Individuals with any type of allergy have a decreased risk for cancer (compared with the general population), including glioma, colorectal cancer, cancer of the larynx, non-Hodgkin lymphoma, cancer of the esophagus, oral cancer, pancreatic cancer, stomach cancer, and uterine body cancer. However, an increased risk for bladder cancer, lymphoma, myeloma, and prostate cancer exists among those with allergies. Studies that involve breast cancer, leukemia, lung cancer, melanoma, and thyroid cancer have shown no association or conflicting results related to allergies. More research is needed before conclusions can be made about the relation between allergies and Kaposi sarcoma, liver cancer, and cancer of the ovaries. CONCLUSIONS: The association between allergies and cancer is site specific. Further research is needed to verify these results and to determine why such associations exist.",
"title": "The association between allergies and cancer: what is currently known?"
},
{
"docid": "MED-1721",
"text": "Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Main outcome measures Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.",
"title": "Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study"
},
{
"docid": "MED-3699",
"text": "BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.",
"title": "Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk o..."
}
] |
5abdcc6755429965af743e55
|
What profession does Adrian Brunel and Richard Oswald have in common?
|
[
{
"docid": "3061175",
"text": "Richard Oswald (5 November 1880 – 11 September 1963) was an Austrian director, producer, and screenwriter.",
"title": ""
},
{
"docid": "28504180",
"text": "Adrian Brunel (4 September 1892 – 18 February 1958) was an English film director and screenwriter. Brunel's directorial career started in the silent era, and reached its peak in the latter half of the 1920s. His surviving work from the 1920s, both full-length feature films and shorts, is highly regarded by silent film historians for its distinctive innovation, sophistication and wit. With the arrival of talkies, Brunel's career ground to a halt and he was absent from the screen for several years before returning in the mid-1930s with a flurry of quota quickie productions, a majority of which are now classed as lost. Brunel's last credit as director was in a 1940 wartime propaganda short film, although he worked for a few years more as a \"fixer-up\" for films directed or produced by friends in the industry.",
"title": ""
}
] |
[
{
"docid": "28221731",
"text": "Richard Alexander Oswald (17 February 1771 – 19 June 1841) was a Scottish Liberal Party politician who sat in the House of Commons from 1832 to 1835.",
"title": ""
},
{
"docid": "37918379",
"text": "The Cost of a Kiss is a 1917 British silent drama film directed by Adrian Brunel and starring Bertram Wallis, Marjorie Day and Edward Cooper. It marked the feature film debut of Brunel who went on to become a leading British director of the 1920s. It was the only film produced by Mirror Films, a company set up by Brunel and the screenwriter H. Fowler Mear.",
"title": ""
},
{
"docid": "1666780",
"text": "David William Ferrie (March 28, 1918 – February 22, 1967) was an American pilot who was alleged by New Orleans District Attorney Jim Garrison to have been involved in a conspiracy to assassinate President John F. Kennedy. Garrison also alleged that Ferrie knew Lee Harvey Oswald. Ferrie denied any involvement in a conspiracy and said he never knew Oswald. Decades later, photos emerged establishing that Ferrie had been in the same Civil Air Patrol unit as Oswald in the 1950s, but critics have argued this does not prove that either Ferrie or Oswald was involved in an assassination plot.",
"title": ""
},
{
"docid": "29122903",
"text": "Vanity is a 1935 British comedy film directed by Adrian Brunel and starring Jane Cain, Percy Marmont and John Counsell. The plot concerns a conceited actress, convinced of the general adoration in which she is held, faking her own death in order to gratify herself by observing the depth of grief caused by her demise. However the actual reactions to the \"news\" prove to be far from what she had expected.",
"title": ""
},
{
"docid": "28525801",
"text": "The Man Without Desire is a 1923 British silent film fantasy drama, directed by Adrian Brunel and starring Ivor Novello, who also co-produced the film along with Miles Mander. The film was Brunel's feature-length directorial debut and has been described as \"one of the stranger films to emerge from Britain in the 1920s\". The film's theme of loss of sexual desire, and by implication impotence, was exceptionally frank for its time; oddly however, it appears to have been passed for release without interference by the British film censors, who at this period has a reputation for extreme zealousness where sexual matters in film were concerned.",
"title": ""
},
{
"docid": "957653",
"text": "\"It does exactly what it says on the tin\" (often quoted as \"does what it says on the tin\") was originally an advertising slogan in the United Kingdom, which then became a common idiomatic phrase. It colloquially means that the name of something is an accurate description of its qualities. It is akin to the previously existing phrases \"by name and by nature\" and \"it lives up to its name\".",
"title": ""
},
{
"docid": "38923844",
"text": "The Trial of Lee Harvey Oswald is a 1964 American film from Larry Buchanan. It is the first speculative trial drama to be produced about Lee Harvey Oswald only a few months after the assassination of John F. Kennedy along with the assassination of Lee Harvey Oswald himself. The film was made in Dallas, and served as an idea of what the trial would have been like had it occurred, if Oswald hadn't been killed by Jack Ruby. In the film, the prosecution asserts Oswald committed the crime for political reasons due to his Marxist beliefs, while Oswald's attorney presents an insanity defense, claiming he suffered from untreated paranoid schizophrenia since adolescence. Since the viewer acts as a juror, no verdict is given.",
"title": ""
},
{
"docid": "37921381",
"text": "The Girl Who Forgot is a 1940 British comedy film directed by Adrian Brunel and starring Elizabeth Allan, Ralph Michael and Enid Stamp-Taylor. It was made at the Nettlefold Studios in Walton-on-Thames, based on a novel by Gertrude E. Jennings. A young woman loses her memory. It was the final film of Brunel, who had been a leading director during the silent era.",
"title": ""
},
{
"docid": "588603",
"text": "\"The Reeve's Tale\" is the third story told in Geoffrey Chaucer's \"The Canterbury Tales\". The reeve, named Oswald in the text, is the manager of a large estate who reaped incredible profits for his master and himself. He is described in the \"Tales\" as skinny and bad-tempered. The Reeve had once been a carpenter, a profession mocked in the previous \"Miller's Tale\". Oswald responds with a tale that mocks the Miller's profession.",
"title": ""
},
{
"docid": "53595798",
"text": "The Ginger Tree is a BBC's four-part TV adaptation, based on Oswald Wynd's novel of the same name, adapted by Christopher Hampton and directed by Anthony Garner and Morimasa Matsumoto. Originally aired on BBC1 from 26 November to 17 December 1989, starring Samantha Bond as Mary MacKenzie, Daisuke Ryu as Count Kentaro Kurihama and Adrian Rawlins as Captain Richard Collingsworth.",
"title": ""
},
{
"docid": "18267561",
"text": "The Trial of Lee Harvey Oswald is an American two-part television film shown on ABC-TV in September 1977. The film starred Ben Gazzara, Lorne Greene and John Pleshette in the title role. It is an example of alternative history. The hypothesis is what might have happened if Lee Harvey Oswald had not been killed by Jack Ruby and had stood trial for the murder of President John F. Kennedy.",
"title": ""
},
{
"docid": "37923948",
"text": "Love at Sea is a 1936 British comedy film directed by Adrian Brunel and starring Rosalyn Boulter, Carl Harbord and Aubrey Mallalieu. During production a major fire broke out at Elstree Studios where the film was being shot. Brunel moved production to another studio and managed to complete the film on time. The screenplay concerns a woman travelling on a cruise ship who falls in love with a suspected thief on board.",
"title": ""
},
{
"docid": "4500480",
"text": "Richard Hume Adrian, 2nd Baron Adrian FRS (16 October 1927 – 4 April 1995) was a British peer and physiologist.",
"title": ""
},
{
"docid": "13228745",
"text": "\"New York City\" is the first single by the musical group Emigrate. The promo version of the single has an alternative cover. The gas mask has a burning building instead of a woman reflected in lenses. It has been considered the band's most successful song, so far. Richard, in the music video, can be seen walking through New York City and sitting down and singing. The song has been credited by many as a phenomenon, as Richard Z. Kruspe does not show his guitar skills, like he does with Rammstein, but now sings as the main vocalist and does what Till Lindemann states as \"[An] incredible job at singing and makes the song perfect in every way, who would have known my fellow German guitarist would now be singing in great American dialect, I'm very proud of Rick\".",
"title": ""
},
{
"docid": "48427038",
"text": "Taxi to Paradise is a 1933 British comedy film directed by Adrian Brunel and starring Binnie Barnes, Garry Marsh and Henry Wilcoxon. It was made as a quota quickie at Wembley Studios.",
"title": ""
},
{
"docid": "3665046",
"text": "Dehe (Syriac: ܪܗܐ ) is an Assyrian Christian village located at the western end of Mateena Mountains in the Sapna valley that separates the Sapna and Barwali Bala districts in the Dohuk Governorate of Iraqi Kurdistan. The village does not have very fertile soil due to its mountainous nature, so instead the village economy is based upon fruit trees. What distinguishes the village most are its olive trees, vineyards, and apple orchards. It is one of the only villages in the area where growing olive tree is the main profession of the inhabitants.",
"title": ""
},
{
"docid": "55180561",
"text": "Drosophila sulfurigaster is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. It was first described by Oswald Duda in 1923. According to the \"Catalogue of Life\" \"D. sulfurigaster\" does not have subspecies.",
"title": ""
},
{
"docid": "30624204",
"text": "Salvage with a Smile is a 1940 British, black-and-white, sponsored war film, directed by Adrian Brunel and starring Ronald Shiner as the Dustman. It was produced by Ealing Studios and the Ministry of Supply for the Ministry of Information.",
"title": ""
},
{
"docid": "37917900",
"text": "I'm an Explosive is a 1933 British comedy film directed by Adrian Brunel and starring William Hartnell, Gladys Jennings and Eliot Makeham. In the film, the son of an inventor accidentally drinks an explosive liquid.",
"title": ""
},
{
"docid": "37920768",
"text": "Lovers in Araby is a 1924 British silent adventure film directed by Adrian Brunel and starring Annette Benson, Miles Mander and Norman Penrose. Much of the film was shot on location in North Africa.",
"title": ""
},
{
"docid": "34741978",
"text": "Isle of Missing Men is a 1942 American drama film directed by Richard Oswald and starring John Howard, Helen Gilbert and Gilbert Roland. In the film, a young woman receives an invitation from the Governor of an island prison to spend a week with him. She does so, but conceals the fact that her husband is being held as a convict on the island.",
"title": ""
},
{
"docid": "2524990",
"text": "A stereotype is a generalized idea or image about a particular person or thing that is often oversimplified and offensive. Stereotypes are victim of prejudice when negative portrayals of a group are untrue of individual members. Nursing has been stereotyped throughout the history of the profession. A common misconception is that all nurses are female; this has led to the stereotype of male nurses as effeminate. These generalized ideas of the nursing profession have formed a skewed image of nurses in the media. The image of a nurse projected by the media is typically of a young white single female being over-sexualized as well as diminished intellectually; this idea is then portrayed in get-well cards, television shows and novels. The over-sexualized nurse is commonly referred to as a naughty nurse and is shown as a sex symbol or nymphomaniac. Along with these common stereotypes, studies have identified several other popular images used in media such as handmaiden, angel, torturer, homosexual male, alcoholic, buffoon and woman in white. Common stereotypes of nursing and portrayal of these misconceptions have fueled a discussion on the effects they have on the profession, harmful or good.",
"title": ""
},
{
"docid": "1533505",
"text": "Sir Richard Empson (c.1450 – 17 August 1510), minister of Henry VII, was a son of Peter Empson. Educated as a lawyer, he soon attained considerable success in his profession, and in 1491 was a Knight of the Shire for Northamptonshire in Parliament, and Speaker of the House of Commons.",
"title": ""
},
{
"docid": "55125386",
"text": "Adrian Delia (born August 1969, Sliema, Malta) is a Maltese politician, and lawyer by profession. He is the leader of the Nationalist Party since September 2017.",
"title": ""
},
{
"docid": "492117",
"text": "Horseless carriage is a term for early automobiles; at the time it was common that carriages were pulled by animals, typically horses, but the automobiles were not. In 2010, the term was compared to other transitional terms, like cordless phone and wireless phone. These are cases in which a new technology is described by what it does not have, compared to an older technology.",
"title": ""
},
{
"docid": "29076918",
"text": "City of Beautiful Nonsense is a 1919 British silent film drama directed by Henry Edwards, who also starred in the film with Chrissie White. The film is based on the best-selling 1909 novel of the same name by E. Temple Thurston and is a tale of a woman intending to marry for financial gain and security, who realises at the last minute that to be true to herself and to have the prospect of a happy future she must instead marry for love. A sound version of the same story was made in 1935 by Adrian Brunel.",
"title": ""
},
{
"docid": "28809393",
"text": "Important People is a 1934 British comedy film directed by Adrian Brunel and starring Stewart Rome, Dorothy Boyd and Jack Raine. In the film, a bickering couple stand against each other as candidates in a local council election.",
"title": ""
},
{
"docid": "37917773",
"text": "Variety is a 1935 British musical film directed by Adrian Brunel and starring George Carney, Barry Livesey, Sam Livesey. The film follows a revue show format, with a number of performers playing themselves. It was made at Cricklewood Studios.",
"title": ""
},
{
"docid": "31243296",
"text": "Bullying in the legal profession is believed to be more common than in some other professions. It is believed that its adversarial, hierarchical tradition contributes towards this. Women, trainees and solicitors who have been qualified for five years or less are more impacted, as are ethnic minority lawyers and lesbian, gay and bisexual lawyers.",
"title": ""
},
{
"docid": "31137405",
"text": "The Vortex is a 1928 British drama film directed by Adrian Brunel and starring Ivor Novello, Willette Kershaw and Simeon Stuart. It was an adaptation of the Noël Coward play \"The Vortex\" and was made by Gainsborough Studios. The film's sets were designed by Clifford Pember.",
"title": ""
}
] |
970
|
PrimPol generates short DNA replication intermediates on the leading strand during DNA replication.
|
[
{
"docid": "19356271",
"text": "Prim-pol is a recently identified DNA primase-polymerase belonging to the archaeao-eukaryotic primase (AEP) superfamily. Here, we characterize a previously unrecognized prim-pol in human cells, which we designate hPrimpol1 (human primase-polymerase 1). hPrimpol1 possesses primase and DNA polymerase activities in vitro, interacts directly with RPA1 and is recruited to sites of DNA damage and stalled replication forks in an RPA1-dependent manner. Cells depleted of hPrimpol1 display increased spontaneous DNA damage and defects in the restart of stalled replication forks. Both RPA1 binding and the primase activity of hPrimpol1 are required for its cellular function during DNA replication. Our results indicate that hPrimpol1 is a novel factor involved in the response to DNA replication stress.",
"title": "hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the maintenance of genome integrity."
},
{
"docid": "17368516",
"text": "We describe a second primase in human cells, PrimPol, which has the ability to start DNA chains with deoxynucleotides unlike regular primases, which use exclusively ribonucleotides. Moreover, PrimPol is also a DNA polymerase tailored to bypass the most common oxidative lesions in DNA, such as abasic sites and 8-oxoguanine. Subcellular fractionation and immunodetection studies indicated that PrimPol is present in both nuclear and mitochondrial DNA compartments. PrimPol activity is detectable in mitochondrial lysates from human and mouse cells but is absent from mitochondria derived from PRIMPOL knockout mice. PRIMPOL gene silencing or ablation in human and mouse cells impaired mitochondrial DNA replication. On the basis of the synergy observed with replicative DNA polymerases Polγ and Polε, PrimPol is proposed to facilitate replication fork progression by acting as a translesion DNA polymerase or as a specific DNA primase reinitiating downstream of lesions that block synthesis during both mitochondrial and nuclear DNA replication.",
"title": "PrimPol, an Archaic Primase/Polymerase Operating in Human Cells"
}
] |
[
{
"docid": "28904104",
"text": "DNA replication forks that collapse during the process of genomic duplication lead to double-strand breaks and constitute a threat to genomic stability. The risk of fork collapse is higher in the presence of replication inhibitors or after UV irradiation, which introduces specific modifications in the structure of DNA. In these cases, fork progression may be facilitated by error-prone translesion synthesis (TLS) DNA polymerases. Alternatively, the replisome may skip the damaged DNA, leaving an unreplicated gap to be repaired after replication. This mechanism strictly requires a priming event downstream of the lesion. Here we show that PrimPol, a new human primase and TLS polymerase, uses its primase activity to mediate uninterrupted fork progression after UV irradiation and to reinitiate DNA synthesis after dNTP depletion. As an enzyme involved in tolerance to DNA damage, PrimPol might become a target for cancer therapy.",
"title": "Repriming of DNA synthesis at stalled replication forks by human PrimPol"
},
{
"docid": "15077696",
"text": "DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) light-damaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol η-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player in replication fork progression in eukaryotic cells.",
"title": "PrimPol Bypasses UV Photoproducts during Eukaryotic Chromosomal DNA Replication"
},
{
"docid": "11401602",
"text": "The effects of topoisomerases I and II on the replication of SV40 DNA were examined using an in vitro replication system of purified proteins that constitutes the monopolymerase system. In the presence of the two topoisomerases, two distinct nascent DNAs were formed. One product arising from the replication of the leading template strand was approximately half the size of the template DNA, whereas the other product derived from the lagging template strand consisted of short DNAs. These products were synthesized from both SV40 naked DNA and SV40 chromosomes. For the replication of SV40 naked DNA, either topoisomerase I or II maintained replication fork movement and supported complete leading strand synthesis. When SV40 chromosomes were replicated with the same proteins, reactions containing only topoisomerase I produced shorter leading strands. However, mature size DNA products accumulated in reactions supplemented with topoisomerase II, as well as in reactions containing only topoisomerase II. In the presence of crude extracts of HeLa cells, VP-16, a specific inhibitor of topoisomerase II, blocked elongation of the nascent DNA during the replication of SV40 chromosomes. These results indicate that topoisomerase II plays a crucial role as a swivelase in the late stage of SV40 chromosome replication in vitro.",
"title": "Topoisomerase II plays an essential role as a swivelase in the late stage of SV40 chromosome replication in vitro."
},
{
"docid": "41314611",
"text": "Numerous agents attack DNA, forming lesions that impair normal replication. Specialized DNA polymerases transiently replace the replicative polymerase and copy past lesions, thus generating mutations, the major initiating cause of cancer. We monitored, in Escherichia coli, the kinetics of replication of both strands of DNA molecules containing a single replication block in either the leading or lagging strand. Despite a block in the leading strand, lagging-strand synthesis proceeded further, implying transient uncoupling of concurrent strand synthesis. Replication through the lesion requires specialized DNA polymerases and is achieved with similar kinetics and efficiencies in both strands.",
"title": "Uncoupling of leading- and lagging-strand DNA replication during lesion bypass in vivo."
},
{
"docid": "2758012",
"text": "Based on its in vitro unwinding activity on G-quadruplex (G4) DNA, the Bloom syndrome-associated helicase BLM is proposed to participate in telomere replication by aiding fork progression through G-rich telomeric DNA. Single molecule analysis of replicated DNA (SMARD) was used to determine the contribution of BLM helicase to telomere replication. In BLM-deficient cells, replication forks initiating from origins within the telomere, which copy the G-rich strand by leading strand synthesis, moved slower through the telomere compared with the adjacent subtelomere. Fork progression through the telomere was further slowed in the presence of a G4 stabilizer. Using a G4-specific antibody, we found that deficiency of BLM, or another G4-unwinding helicase, the Werner syndrome-associated helicase WRN, resulted in increased G4 structures in cells. Importantly, deficiency of either helicase led to greater increases in G4 DNA detected in the telomere compared with G4 seen genome-wide. Collectively, our findings are consistent with BLM helicase facilitating telomere replication by resolving G4 structures formed during copying of the G-rich strand by leading strand synthesis.",
"title": "BLM helicase facilitates telomere replication during leading strand synthesis of telomeres"
},
{
"docid": "37328025",
"text": "Cells cope with blockage of replication fork progression in a manner that allows DNA synthesis to be completed and genomic instability minimized. Models for resolution of blocked replication involve fork regression to form Holliday junction structures. The human RecQ helicases WRN and BLM (deficient in Werner and Bloom syndromes, respectively) are critical for maintaining genomic stability and thought to function in accurate resolution of replication blockage. Consistent with this notion, WRN and BLM localize to sites of blocked replication after certain DNA-damaging treatments and exhibit enhanced activity on replication and recombination intermediates. Here we examine the actions of WRN and BLM on a special Holliday junction substrate reflective of a regressed replication fork. Our results demonstrate that, in reactions requiring ATP hydrolysis, both WRN and BLM convert this Holliday junction substrate primarily to a four-stranded replication fork structure, suggesting they target the Holliday junction to initiate branch migration. In agreement, the Holliday junction binding protein RuvA inhibits the WRN- and BLM-mediated conversion reactions. Importantly, this conversion product is suitable for replication with its leading daughter strand readily extended by DNA polymerases. Furthermore, binding to and conversion of this Holliday junction are optimal at low MgCl(2) concentrations, suggesting that WRN and BLM preferentially act on the square planar (open) conformation of Holliday junctions. Our findings suggest that, subsequent to fork regression events, WRN and/or BLM could re-establish functional replication forks to help overcome fork blockage. Such a function is highly consistent with phenotypes associated with WRN- and BLM-deficient cells.",
"title": "The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) holliday junctions to functional replication forks."
},
{
"docid": "31514338",
"text": "The eukaryotic replisome is a crucial determinant of genome stability, but its structure is still poorly understood. We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components. Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle. These findings indicate that coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process.",
"title": "A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome."
},
{
"docid": "7151961",
"text": "Double-strand breaks (DSBs) occur frequently during DNA replication. They are also caused by ionizing radiation, chemical damage or as part of the series of programmed events that occur during meiosis. In yeast, DSB repair requires RAD52, a protein that plays a critical role in homologous recombination. Here we describe the actions of human RAD52 protein in a model system for single-strand annealing (SSA) using tailed (i.e. exonuclease resected) duplex DNA molecules. Purified human RAD52 protein binds resected DSBs and promotes associations between complementary DNA termini. Heteroduplex intermediates of these recombination reactions have been visualized by electron microscopy, revealing the specific binding of multiple rings of RAD52 to the resected termini and the formation of large protein complexes at heteroduplex joints formed by RAD52-mediated annealing.",
"title": "Visualization of recombination intermediates produced by RAD52-mediated single-strand annealing."
},
{
"docid": "4444861",
"text": "Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of replication fork protection, highlighting the complexities by which tumour cells evade chemotherapeutic interventions and acquire drug resistance.",
"title": "Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells"
},
{
"docid": "16217855",
"text": "The product of the gene mutated in Bloom's syndrome, BLM, is a 3′–5′ DNA helicase belonging to the highly conserved RecQ family. In addition to a conventional DNA strand separation activity, BLM catalyzes both the disruption of non-B-form DNA, such as G-quadruplexes, and the branch migration of Holliday junctions. Here, we have characterized a new activity for BLM: the promotion of single-stranded DNA (ssDNA) annealing. This activity does not require Mg2+, is inhibited by ssDNA binding proteins and ATP, and is dependent on DNA length. Through analysis of various truncation mutants of BLM, we show that the C-terminal domain is essential for strand annealing and identify a 60 amino acid stretch of this domain as being important for both ssDNA binding and strand annealing. We present a model in which the ssDNA annealing activity of BLM facilitates its role in the processing of DNA intermediates that arise during repair of damaged replication forks.",
"title": "The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA"
},
{
"docid": "6812319",
"text": "Chromosomal instability (CIN) is a hallmark of tumour initiation and progression. Some genomic regions are particularly unstable under replication stress, notably common fragile sites (CFSs) whose rearrangements in tumour cells contribute to cancer development. Recent work has shown that the Fanconi anaemia (FANC) pathway plays a role in preventing defective chromosome segregation and CIN under conditions of replication stress. Strikingly, FANCD2 is recruited to regions hosting CFSs on metaphase chromosomes. To decipher the mechanisms protecting CFSs in G2/M, we searched for proteins that co-localize with FANCD2 on mitotic chromosomes, and identified XPF–ERCC1 and MUS81–EME1, two structure-specific endonucleases. We show that depletion of either ERCC1 or MUS81–EME1 affects accurate processing of replication intermediates or under-replicated DNA that persist at CFSs until mitosis. Depletion of these endonucleases also leads to an increase in the frequency of chromosome bridges during anaphase that, in turn, favours accumulation of DNA damage in the following G1 phase.",
"title": "ERCC1 and MUS81–EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis"
},
{
"docid": "25787749",
"text": "The evolutionarily conserved G-quadruplexes (G4s) are faithfully inherited and serve a variety of cellular functions such as telomere maintenance, gene regulation, DNA replication initiation, and epigenetic regulation. Different from the Watson-Crick base-pairing found in duplex DNA, G4s are formed via Hoogsteen base pairing and are very stable and compact DNA structures. Failure of untangling them in the cell impedes DNA-based transactions and leads to genome instability. Cells have evolved highly specific helicases to resolve G4 structures. We used a recombinant nuclear form of Saccharomyces cerevisiae Pif1 to characterize Pif1-mediated DNA unwinding with a substrate mimicking an ongoing lagging strand synthesis stalled by G4s, which resembles a replication origin and a G4-structured flap in Okazaki fragment maturation. We find that the presence of G4 may greatly stimulate the Pif1 helicase to unwind duplex DNA. Further studies reveal that this stimulation results from G4-enhanced Pif1 dimerization, which is required for duplex DNA unwinding. This finding provides new insights into the properties and functions of G4s. We discuss the observed activation phenomenon in relation to the possible regulatory role of G4s in the rapid rescue of the stalled lagging strand synthesis by helping the replicator recognize and activate the replication origin as well as by quickly removing the G4-structured flap during Okazaki fragment maturation.",
"title": "G-quadruplexes significantly stimulate Pif1 helicase-catalyzed duplex DNA unwinding."
},
{
"docid": "3512154",
"text": "CRISPR-Cas (clustered, regularly interspaced short palindromic repeats coupled with CRISPR-associated proteins) is a bacterial immunity system that protects against invading phages or plasmids. In the process of CRISPR adaptation, short pieces of DNA ('spacers') are acquired from foreign elements and integrated into the CRISPR array. So far, it has remained a mystery how spacers are preferentially acquired from the foreign DNA while the self chromosome is avoided. Here we show that spacer acquisition is replication-dependent, and that DNA breaks formed at stalled replication forks promote spacer acquisition. Chromosomal hotspots of spacer acquisition were confined by Chi sites, which are sequence octamers highly enriched on the bacterial chromosome, suggesting that these sites limit spacer acquisition from self DNA. We further show that the avoidance of self is mediated by the RecBCD double-stranded DNA break repair complex. Our results suggest that, in Escherichia coli, acquisition of new spacers largely depends on RecBCD-mediated processing of double-stranded DNA breaks occurring primarily at replication forks, and that the preference for foreign DNA is achieved through the higher density of Chi sites on the self chromosome, in combination with the higher number of forks on the foreign DNA. This model explains the strong preference to acquire spacers both from high copy plasmids and from phages.",
"title": "CRISPR adaptation biases explain preference for acquisition of foreign DNA"
},
{
"docid": "19165076",
"text": "Replication protein A [RPA; also known as replication factor A (RFA) and human single-stranded DNA-binding protein] is a single-stranded DNA-binding protein that is required for multiple processes in eukaryotic DNA metabolism, including DNA replication, DNA repair, and recombination. RPA homologues have been identified in all eukaryotic organisms examined and are all abundant heterotrimeric proteins composed of subunits of approximately 70, 30, and 14 kDa. Members of this family bind nonspecifically to single-stranded DNA and interact with and/or modify the activities of multiple proteins. In cells, RPA is phosphorylated by DNA-dependent protein kinase when RPA is bound to single-stranded DNA (during S phase and after DNA damage). Phosphorylation of RPA may play a role in coordinating DNA metabolism in the cell. RPA may also have a role in modulating gene expression.",
"title": "Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism."
},
{
"docid": "12909503",
"text": "DNA damage encountered by DNA replication forks poses risks of genome destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause cell cycle arrest, promote repair and induce programed cell death when damage is severe. Checkpoints are critical parts of the DNA damage response network that act to suppress cancer. DNA damage and perturbation of replication machinery causes replication stress, characterized by accumulation of single-stranded DNA bound by replication protein A (RPA), which triggers activation of ataxia telangiectasia and Rad3 related (ATR) and phosphorylation of the RPA32, subunit of RPA, leading to Chk1 activation and arrest. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) [a kinase related to ataxia telangiectasia mutated (ATM) and ATR] has well characterized roles in DNA double-strand break repair, but poorly understood roles in replication stress-induced RPA phosphorylation. We show that DNA-PKcs mutant cells fail to arrest replication following stress, and mutations in RPA32 phosphorylation sites targeted by DNA-PKcs increase the proportion of cells in mitosis, impair ATR signaling to Chk1 and confer a G2/M arrest defect. Inhibition of ATR and DNA-PK (but not ATM), mimic the defects observed in cells expressing mutant RPA32. Cells expressing mutant RPA32 or DNA-PKcs show sustained H2AX phosphorylation in response to replication stress that persists in cells entering mitosis, indicating inappropriate mitotic entry with unrepaired damage.",
"title": "Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress"
},
{
"docid": "2679511",
"text": "Werner's syndrome (WS) and Bloom's syndrome (BS) are cancer predisposition disorders caused by loss of function of the RecQ helicases WRN or BLM, respectively. BS and WS are characterized by replication defects, hyperrecombination events and chromosomal aberrations, which are hallmarks of cancer. Inefficient replication of the G-rich telomeric strand contributes to chromosome aberrations in WS cells, demonstrating a link between WRN, telomeres and genomic stability. Herein, we provide evidence that BLM also contributes to chromosome-end maintenance. Telomere defects (TDs) are observed in BLM-deficient cells at an elevated frequency, which is similar to cells lacking a functional WRN helicase. Loss of both helicases exacerbates TDs and chromosome aberrations, indicating that BLM and WRN function independently in telomere maintenance. BLM localization, particularly its recruitment to telomeres, changes in response to replication dysfunction, such as in WRN-deficient cells or after aphidicolin treatment. Exposure to replication challenge causes an increase in decatenated deoxyribonucleic acid (DNA) structures and late-replicating intermediates (LRIs), which are visible as BLM-covered ultra-fine bridges (UFBs) in anaphase. A subset of UFBs originates from telomeric DNA and their frequency correlates with telomere replication defects. We propose that the BLM complex contributes to telomere maintenance through its activity in resolving LRIs.",
"title": "The BLM helicase contributes to telomere maintenance through processing of late-replicating intermediate structures"
},
{
"docid": "8577229",
"text": "Recombination-dependent DNA replication, often called break-induced replication (BIR), was initially invoked to explain recombination events in bacteriophage but it has recently been recognized as a fundamentally important mechanism to repair double-strand chromosome breaks in eukaryotes. This mechanism appears to be critically important in the restarting of stalled and broken replication forks and in maintaining the integrity of eroded telomeres. Although BIR helps preserve genome integrity during replication, it also promotes genome instability by the production of loss of heterozygosity and the formation of nonreciprocal translocations, as well as in the generation of complex chromosomal rearrangements.",
"title": "Break-induced DNA replication."
},
{
"docid": "28271439",
"text": "Completion of genome duplication is challenged by structural and topological barriers that impede progression of replication forks. Although this can seriously undermine genome integrity, the fate of DNA with unresolved replication intermediates is not known. Here, we show that mild replication stress increases the frequency of chromosomal lesions that are transmitted to daughter cells. Throughout G1, these lesions are sequestered in nuclear compartments marked by p53-binding protein 1 (53BP1) and other chromatin-associated genome caretakers. We show that the number of such 53BP1 nuclear bodies increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. Conversely, 53BP1 nuclear bodies are partially suppressed by knocking down SMC2, a condensin subunit required for mechanical stability of mitotic chromosomes. Finally, we provide evidence that 53BP1 nuclear bodies shield chromosomal fragile sites sequestered in these compartments against erosion. Together, these data indicate that restoration of DNA or chromatin integrity at loci prone to replication problems requires mitotic transmission to the next cell generations.",
"title": "53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress"
},
{
"docid": "25842866",
"text": "Most eukaryotic telomeres contain a repeating motif with stretches of guanine residues that form a 3'-terminal overhang extending beyond the telomeric duplex region. The telomeric repeat of hypotrichous ciliates, d(T(4)G(4)), forms a 16-nucleotide 3'-overhang. Such sequences can adopt parallel-stranded as well as antiparallel-stranded quadruplex conformations in vitro. Although it has been proposed that guanine-quadruplex conformations may have important cellular roles including telomere function, recombination, and transcription, evidence for the existence of this DNA structure in vivo has been elusive to date. We have generated high-affinity single-chain antibody fragment (scFv) probes for the guanine-quadruplex formed by the Stylonychia telomeric repeat, by ribosome display from the Human Combinatorial Antibody Library. Of the scFvs selected, one (Sty3) had an affinity of K(d) = 125 pM for the parallel-stranded guanine-quadruplex and could discriminate with at least 1,000-fold specificity between parallel or antiparallel quadruplex conformations formed by the same sequence motif. A second scFv (Sty49) bound both the parallel and antiparallel quadruplex with similar (K(d) = 3--5 nM) affinity. Indirect immunofluorescence studies show that Sty49 reacts specifically with the macronucleus but not the micronucleus of Stylonychia lemnae. The replication band, the region where replication and telomere elongation take place, was also not stained, suggesting that the guanine-quadruplex is resolved during replication. Our results provide experimental evidence that the telomeres of Stylonychia macronuclei adopt in vivo a guanine-quadruplex structure, indicating that this structure may have an important role for telomere functioning.",
"title": "In vitro generated antibodies specific for telomeric guanine-quadruplex DNA react with Stylonychia lemnae macronuclei."
},
{
"docid": "36606083",
"text": "Many fundamental aspects of DNA replication, such as the exact locations where DNA synthesis is initiated and terminated, how frequently origins are used, and how fork progression is influenced by transcription, are poorly understood. Via the deep sequencing of Okazaki fragments, we comprehensively document replication fork directionality throughout the S. cerevisiae genome, which permits the systematic analysis of initiation, origin efficiency, fork progression, and termination. We show that leading-strand initiation preferentially occurs within a nucleosome-free region at replication origins. Using a strain in which late origins can be induced to fire early, we show that replication termination is a largely passive phenomenon that does not rely on cis-acting sequences or replication fork pausing. The replication profile is predominantly determined by the kinetics of origin firing, allowing us to reconstruct chromosome-wide timing profiles from an asynchronous culture.",
"title": "Quantitative, genome-wide analysis of eukaryotic replication initiation and termination."
},
{
"docid": "29851836",
"text": "We show that DNA replication activity in extracts of human HeLa cells decreases following UV irradiation. Alterations in replication activity in vitro parallel the UV-induced block in cell cycle progression of these cells in culture. UV irradiation also induces specific changes in the pattern of phosphorylation of the 34 kDa subunit of a DNA replication protein, human single-stranded DNA-binding protein (hSSB). The appearance of a hyperphosphorylated form of hSSB correlates with reduced in vitro DNA replication activity in extracts of UV-irradiated cells. Replication activity can be restored to these extracts in vitro by addition of purified hSSB. These results suggest that UV-induced DNA synthesis arrest may be mediated in part through phosphorylation-related alterations in the activity of hSSB, an essential component of the DNA replication apparatus.",
"title": "UV light-induced DNA synthesis arrest in HeLa cells is associated with changes in phosphorylation of human single-stranded DNA-binding protein."
},
{
"docid": "9379687",
"text": "DNA polymerase ε (Pol ε) is involved in DNA replication, repair, and cell-cycle checkpoint control in eukaryotic cells. Although the roles of replicative Pol α and Pol δ in chromosomal DNA replication are relatively well understood and well documented, the precise role of Pol ε in chromosomal DNA replication is not well understood. This study uses a Xenopus egg extract DNA replication system to further elucidate the replicative role(s) played by Pol ε. Previous studies show that the initiation timing and elongation of chromosomal DNA replication are markedly impaired in Pol ε-depleted Xenopus egg extracts, with reduced accumulation of replicative intermediates and products. This study shows that normal replication is restored by addition of Pol ε holoenzyme to Pol ε-depleted extracts, but not by addition of polymerase-deficient forms of Pol ε, including polymerase point or deletion mutants or incomplete enzyme complexes. Evidence is also provided that Pol ε holoenzyme interacts directly with GINS, Cdc45p and Cut5p, each of which plays an important role in initiation of chromosomal DNA replication in eukaryotic cells. These results indicate that the DNA polymerase activity of Pol ε holoenzyme plays an essential role in normal chromosomal DNA replication in Xenopus egg extracts. These are the first biochemical data to show the DNA polymerase activity of Pol ε holoenzyme is essential for chromosomal DNA replication in higher eukaryotes, unlike in yeasts.",
"title": "The DNA polymerase activity of Pol ε holoenzyme is required for rapid and efficient chromosomal DNA replication in Xenopus egg extracts"
},
{
"docid": "39637840",
"text": "BLM, WRN, and p53 are involved in the homologous DNA recombination pathway. The DNA structure-specific helicases, BLM and WRN, unwind Holliday junctions (HJ), an activity that could suppress inappropriate homologous recombination during DNA replication. Here, we show that purified, recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind synthetic HJ in vitro. The p53 248W mutant reduces abilities of both to bind HJ and inhibit helicase activities, whereas the p53 273H mutant loses these abilities. Moreover, full-length p53 and a C-terminal polypeptide (residues 373-383) inhibit the BLM and WRN helicase activities, but phosphorylation at Ser(376) or Ser(378) completely abolishes this inhibition. Following blockage of DNA replication, Ser(15) phospho-p53, BLM, and RAD51 colocalize in nuclear foci at sites likely to contain DNA replication intermediates in cells. Our results are consistent with a novel mechanism for p53-mediated regulation of DNA recombinational repair that involves p53 post-translational modifications and functional protein-protein interactions with BLM and WRN DNA helicases.",
"title": "The processing of Holliday junctions by BLM and WRN helicases is regulated by p53."
},
{
"docid": "4393153",
"text": "RNA polymerase (Pol) II catalyses DNA-dependent RNA synthesis during gene transcription. There is, however, evidence that Pol II also possesses RNA-dependent RNA polymerase (RdRP) activity. Pol II can use a homopolymeric RNA template, can extend RNA by several nucleotides in the absence of DNA, and has been implicated in the replication of the RNA genomes of hepatitis delta virus (HDV) and plant viroids. Here we show the intrinsic RdRP activity of Pol II with only pure polymerase, an RNA template–product scaffold and nucleoside triphosphates (NTPs). Crystallography reveals the template–product duplex in the site occupied by the DNA–RNA hybrid during transcription. RdRP activity resides at the active site used during transcription, but it is slower and less processive than DNA-dependent activity. RdRP activity is also obtained with part of the HDV antigenome. The complex of transcription factor IIS (TFIIS) with Pol II can cleave one HDV strand, create a reactive stem-loop in the hybrid site, and extend the new RNA 3′ end. Short RNA stem-loops with a 5′ extension suffice for activity, but their growth to a critical length apparently impairs processivity. The RdRP activity of Pol II provides a missing link in molecular evolution, because it suggests that Pol II evolved from an ancient replicase that duplicated RNA genomes.",
"title": "Molecular basis of RNA-dependent RNA polymerase II activity"
},
{
"docid": "39225849",
"text": "The Bloom syndrome helicase (BLM) is critical for genomic stability. A defect in BLM activity results in the cancer-predisposing Bloom syndrome (BS). Here, we report that BLM-deficient cell lines and primary fibroblasts display an endogenously activated DNA double-strand break checkpoint response with prominent levels of phosphorylated histone H2AX (gamma-H2AX), Chk2 (p(T68)Chk2), and ATM (p(S1981)ATM) colocalizing in nuclear foci. Interestingly, the mitotic fraction of gamma-H2AX foci did not seem to be higher in BLM-deficient cells, indicating that these lesions form transiently during interphase. Pulse labeling with iododeoxyuridine and immunofluorescence microscopy showed the colocalization of gamma-H2AX, ATM, and Chk2 together with replication foci. Those foci costained for Rad51, indicating homologous recombination at these replication sites. We therefore analyzed replication in BS cells using a single molecule approach on combed DNA fibers. In addition to a higher frequency of replication fork barriers, BS cells displayed a reduced average fork velocity and global reduction of interorigin distances indicative of an elevated frequency of origin firing. Because BS is one of the most penetrant cancer-predisposing hereditary diseases, it is likely that the lack of BLM engages the cells in a situation similar to precancerous tissues with replication stress. To our knowledge, this is the first report of high ATM-Chk2 kinase activation and its linkage to replication defects in a BS model.",
"title": "Endogenous gamma-H2AX-ATM-Chk2 checkpoint activation in Bloom's syndrome helicase deficient cells is related to DNA replication arrested forks."
},
{
"docid": "26083387",
"text": "The Saccharomyces cerevisiae DNA helicase Rrm3p is needed for normal fork progression through >1000 discrete sites scattered throughout the genome. Here we show that replication of all yeast chromosomes was markedly delayed in rrm3 cells. Delayed replication was seen even in a region that lacks any predicted Rrm3p-dependent sites. Based on the pattern of replication intermediates in two-dimensional gels, the rate of fork movement in rrm3 cells appeared similar to wild-type except at known Rrm3p-dependent sites. These data suggest that although Rrm3p has a global role in DNA replication, its activity is needed only or primarily at specific, difficult-to-replicate sites. By the criterion of chromatin immunoprecipitation, Rrm3p was associated with both Rrm3p-dependent and -independent sites, and moved with the replication fork through both. In addition, Rrm3p interacted with Pol2p, the catalytic subunit of DNA polymerase epsilon, in vivo. Thus, rather than being recruited to its sites of action when replication forks stall at these sites, Rrm3p is likely a component of the replication fork apparatus.",
"title": "The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes."
},
{
"docid": "45875990",
"text": "Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes. Unexpectedly, cyclin A2 controlled Mre11 abundance through a C-terminal RNA binding domain that selectively and directly binds Mre11 transcripts to mediate polysome loading and translation. These data reveal cyclin A2 as a mechanistically diverse regulator of DNA replication combining multifaceted kinase-dependent functions with a kinase-independent, RNA binding–dependent role that ensures adequate repair of common replication errors.",
"title": "Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation"
},
{
"docid": "38131471",
"text": "DNA damage is a relatively common event in the life of a cell and may lead to mutation, cancer, and cellular or organismic death. Damage to DNA induces several cellular responses that enable the cell either to eliminate or cope with the damage or to activate a programmed cell death process, presumably to eliminate cells with potentially catastrophic mutations. These DNA damage response reactions include: (a) removal of DNA damage and restoration of the continuity of the DNA duplex; (b) activation of a DNA damage checkpoint, which arrests cell cycle progression so as to allow for repair and prevention of the transmission of damaged or incompletely replicated chromosomes; (c) transcriptional response, which causes changes in the transcription profile that may be beneficial to the cell; and (d) apoptosis, which eliminates heavily damaged or seriously deregulated cells. DNA repair mechanisms include direct repair, base excision repair, nucleotide excision repair, double-strand break repair, and cross-link repair. The DNA damage checkpoints employ damage sensor proteins, such as ATM, ATR, the Rad17-RFC complex, and the 9-1-1 complex, to detect DNA damage and to initiate signal transduction cascades that employ Chk1 and Chk2 Ser/Thr kinases and Cdc25 phosphatases. The signal transducers activate p53 and inactivate cyclin-dependent kinases to inhibit cell cycle progression from G1 to S (the G1/S checkpoint), DNA replication (the intra-S checkpoint), or G2 to mitosis (the G2/M checkpoint). In this review the molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed.",
"title": "Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints."
},
{
"docid": "11568270",
"text": "Human TopBP1 is a major player in the control of the DNA replication checkpoint. In this study, we identified MDC1, a key checkpoint protein involved in the cellular response to DNA double-strand breaks, as a TopBP1-associated protein. The specific TopBP1-MDC1 interaction is mediated by the fifth BRCT domain of TopBP1 and the Ser-Asp-Thr (SDT) repeats of MDC1. In addition, we demonstrated that TopBP1 accumulation at stalled replication forks is promoted by the H2AX/MDC1 signaling cascade. Moreover, MDC1 is important for ATR-dependent Chk1 activation in response to replication stress. Collectively, our data suggest that MDC1 facilitates several important steps in both cellular DNA damage response and the DNA replication checkpoint.",
"title": "MDC1 collaborates with TopBP1 in DNA replication checkpoint control"
},
{
"docid": "17628888",
"text": "Modification of proteins by SUMO is essential for the maintenance of genome integrity. During DNA replication, the Mms21-branch of the SUMO pathway counteracts recombination intermediates at damaged replication forks, thus facilitating sister chromatid disjunction. The Mms21 SUMO ligase docks to the arm region of the Smc5 protein in the Smc5/6 complex; together, they cooperate during recombinational DNA repair. Yet how the activity of the SUMO ligase is controlled remains unknown. Here we show that the SUMO ligase and the chromosome disjunction functions of Mms21 depend on its docking to an intact and active Smc5/6 complex, indicating that the Smc5/6-Mms21 complex operates as a large SUMO ligase in vivo. In spite of the physical distance separating the E3 and the nucleotide-binding domains in Smc5/6, Mms21-dependent sumoylation requires binding of ATP to Smc5, a step that is part of the ligase mechanism that assists Ubc9 function. The communication is enabled by the presence of a conserved disruption in the coiled coil domain of Smc5, pointing to potential conformational changes for SUMO ligase activation. In accordance, scanning force microscopy of the Smc5-Mms21 heterodimer shows that the molecule is physically remodeled in an ATP-dependent manner. Our results demonstrate that the ATP-binding activity of the Smc5/6 complex is coordinated with its SUMO ligase, through the coiled coil domain of Smc5 and the physical remodeling of the molecule, to promote sumoylation and chromosome disjunction during DNA repair.",
"title": "ATPase-Dependent Control of the Mms21 SUMO Ligase during DNA Repair"
}
] |
5a859cbb5542992a431d1b71
|
Which record producer and engineer worked for the English heavy metal band formed in 1977 in South Yorkshire?
|
[
{
"docid": "11518033",
"text": "Herman Frank (born 1959) is a German heavy metal guitarist best known for his work with Accept and Victory. In 2009, he released his first solo album called \"Loyal to None\". Frank has also recorded with Hazzard, Sinner, Moon'Doc, Saeko, Thomsen and Poison Sun. As a record producer and engineer, he has worked for Saxon, Rose Tattoo, Crown of Creation, Molly Hatchet, gutworm, and several others.",
"title": ""
},
{
"docid": "510249",
"text": "Saxon are an English heavy metal band formed in 1977, in South Yorkshire. As one of the leaders of the new wave of British heavy metal, they had eight UK Top 40 albums in the 1980s including four UK Top 10 albums and two Top 5 albums. The band also had numerous singles in the UK Singles Chart and chart success all over Europe and Japan, as well as success in the US. During the 1980s Saxon established themselves as one of Europe's biggest metal acts. The band tours regularly and have sold more than 15 million albums worldwide. They are considered one of the classic metal acts and have influenced many bands such as Metallica, Mötley Crüe, Pantera, Sodom.",
"title": ""
}
] |
[
{
"docid": "24440080",
"text": "Lifescreen is an English heavy-rock band from Leeds, West Yorkshire, formed in 2007. The band is made up of two former members of the alternative-metal band Nerve Engine. It is influenced by bands including Alice in Chains, Tool and King's X.",
"title": ""
},
{
"docid": "3098225",
"text": "Colin Richardson is a British record producer, mixer and recording engineer. He has worked on over 100 albums, and is most frequently associated with heavy metal and its subgenres. Some of the bands he has worked for include:",
"title": ""
},
{
"docid": "1850514",
"text": "Rock Goddess are an English all-female heavy metal band formed in Wandsworth, South London, in 1977 by sisters Jody Turner and Julie Turner.",
"title": ""
},
{
"docid": "33736283",
"text": "Alvacast was a heavy metal band formed in Uruguay in 1985. They were one of the most influential bands of the thrash metal scene in South America, in the 1980s, alongside bands such as Pentagram, Massakre and Volcano. The band moved to Canada later in their career and recorded in English.",
"title": ""
},
{
"docid": "37887147",
"text": "Jesters of Destiny is a heavy metal band from Los Angeles, California, which was formed in 1984 by Bruce Duff (bass/vocals, who had been booted from 45 Grave earlier in the year) and guitarist Ray Violet. Evolving from a recording project spearheaded by Violet, who was working as the house engineer for Dawnbreaker studio in San Fernando, CA (previously owned by Seals and Crofts), the band recorded what would be the first two Jesters songs during the project,which was instigated in order to come up with commercial jingles. The songs were \"Diggin' That Grave\" and \"End of Time.\" The band presented the songs to Metal Blade Records, who included \"End of Time\" on Metal Massacre V collection. It closed the LP, which include early tracks by Overkill, Fates Warning, Voi Vod and Metal Church. The band then signed to Metal Blade, but due to the band not being strictly heavy metal, the label created a subsidiary, Dimension Records, which released the band's debut album, \"Fun at the Funeral\", in 1986, and an EP, \"In a Nostalgic Mood\", in 1987, during their first tenure. Following \",,\"Mood,\"\" Metal Blade dropped the band. They demo-ed a number of songs for a planned third LP to be titled, \"No Laughing Matter,\" but we're unable to land a new recording contract. They broke up in 1988. During their run, a number of lead guitarists and drummers were part of the band, including on drums, David Buzzelli (Doktor Stixx), Louie Schilling, Walin' Jennings Morgan, Dave Kuzma, Blaze; and on guitar, Sickie Wifebeater, Michael Montano and Brian Butler.",
"title": ""
},
{
"docid": "7192328",
"text": "Atomic Mass was an English hard rock/heavy metal band from Sheffield, who formed in 1977 as part of the new wave of British heavy metal movement. The group's core members along with newly recruited singer Joe Elliott later became Def Leppard, eventually becoming one of the UK's top-selling hard rock bands.",
"title": ""
},
{
"docid": "5080698",
"text": "Rattlebone was a punk/heavy metal band formed in Los Angeles, California in 1992. The group signed with Hollywood Records that same year. They recorded two albums with veteran producer Dave Jerden, who has also worked with bands such as Jane's Addiction, Alice in Chains, and The Offspring.",
"title": ""
},
{
"docid": "23294374",
"text": "Gravestone was a German heavy metal band, formed in 1977 as originally a progressive rock outfit, before going in to the heavy metal genre.",
"title": ""
},
{
"docid": "2327604",
"text": "Nathan Jonas \"Joey\" Jordison (born April 26, 1975), is an American musician, songwriter, record producer and multi-instrumentalist, best known for his work as the former drummer and co-songwriter for the American heavy metal band Slipknot as well as guitarist in the American horror punk band Murderdolls. Jordison played in Slipknot since their formation in 1995 until his departure from the band in December 2013. He was the drummer and founder of the American heavy metal band Scar the Martyr which formed in 2013 and disbanded in 2016. He grew up in Waukee, Iowa with his parents and two sisters, and was given his first drum kit at the age of 8. He performed in several bands until joining in the summer of 1995 with the group The Pale Ones, which would later change their name to Slipknot. Of Slipknot's nine-member lineup which lasted from 1999–2010, Joey was the third to join the band.",
"title": ""
},
{
"docid": "16868163",
"text": "Jean-François Dagenais (born October 16, 1975) is a Canadian Juno Award-winning record producer, recording engineer, mixer, guitarist, and songwriter. He is best known as guitarist for the death metal band Kataklysm and for producing and mixing many heavy metal albums and its subgenres.",
"title": ""
},
{
"docid": "24413422",
"text": "Disillusion (撃剣霊化 , Gekken reika ) is the fourth studio album by Japanese heavy metal band Loudness. It was recorded, mixed and mastered in London, England, in 1983 and released at the beginning of 1984. The sound engineer chosen for the recording sessions was the expert Julian Mendelsohn, who had previously worked with acts like Yes, Elton John, Jimmy Page and Bob Marley. The original Japanese version was licensed and released by Music for Nations in the UK and Roadrunner Records in Europe. Attention by major US labels for the band and the need to make their work accessible to Western audiences, prompted a new release of the album with vocal tracks sung in English on July 1, 1984. The English version opened the album with the instrumental \"Anthem (Loudness Overture)\" by Akira Takasaki, which was missing in the original Japanese release.",
"title": ""
},
{
"docid": "43409647",
"text": "Canadian heavy metal music has a long history. Going back to the late 1960s, Canada has produced metal bands that have and continue to influence metal bands to this day. In 1964, Toronto-based band The Sparrows was formed. This band later changed their name to Steppenwolf and featured Canadians John Kay, Goldy McJohn and Jerry Edmonton. Steppenwolf's 1968 single \"Born to be Wild\" was the first use of the words 'heavy metal' in a song's lyric. In 1970, Woodstock, Ontario based Warpig released their metal music debut, which, although never reaching mainstream success like fellow heavy metal bands Black Sabbath and Blue Cheer, has become a cult favourite within the Doom metal scene.",
"title": ""
},
{
"docid": "2996701",
"text": "Jari Mäenpää (born 23 December 1977) is a Finnish heavy metal multi-instrumentalist and songwriter. He is the founder of Wintersun for which he records all instruments. Before forming Wintersun, Mäenpää was best known for his role in the folk metal band Ensiferum, which he joined in 1996 after leaving his prior band named \"Immemorial\". Wintersun was initially planned as a parallel project alongside Ensiferum, but in January, 2004 he was forced to leave Ensiferum due to clashes between their touring schedule and the studio recording time he had booked for Wintersun.",
"title": ""
},
{
"docid": "45462993",
"text": "Mirage was a heavy metal band which was formed in 1983 from the ashes of two Welsh Rock/ Metal bands: 'Rough Justice' and 'Exit'. The band were based in the valleys of South East Wales, UK. Its members were Richard Morgan (aka \"Wretch) on vocals, Richard Price on guitar, Carl Skinner on bass and Gerry Turner on drums. In 1984, they released one track 'Blind Fury' on a compilation album produced by local record company 'Notepad Productions'. This came to the attention of Malc Macmillan, author of the Encyclopaedia of New Wave of British Heavy Metal (NWoBHM) who described their track 'Blind Fury' as \"truly one of the classic tracks of the entire NWoBHM genre\" The rare Notepad Productions VOLUME I album remains highly sought after by collectors - featured in Record Collector Magazine in January 2015. The band has enjoyed some recent attention from High Roller Records who have re-released the band's tracks Blind Fury/ Twilight Zone on black and white vinyl. The cover features Richard Price's original 1979 Fender Stratocaster guitar alongside a Turner family artefact from World War II.",
"title": ""
},
{
"docid": "12632318",
"text": "March of the Saint is the first album by American heavy metal band Armored Saint. It was released in 1984 on Chrysalis Records and recorded with producer Michael James Jackson who previously worked for Kiss. The debut album yielded a minor MTV hit with \"Can U Deliver\", but Joey Vera and John Bush later recalled the album's recording as a frustrating and disappointing experience, explaining that Jackson's approach was much more commercial than the heavy metal sound the band had wanted. As Vera recalled in 2006: \"At the end of the record we were very unhappy with the production, the mix, the way we worked and who we worked with. And the producer and our manager let us spend over ($)300,000 on our first record. To this day we are still in debt for that one.\"",
"title": ""
},
{
"docid": "1165746",
"text": "Angel Witch are a British heavy metal band which formed in London, England in 1977 as part of the new wave of British heavy metal movement. Despite critical acclaim in the music press, their only UK chart action consisted of a single week at No. 75 (the lowest position in the charts) in 1980.",
"title": ""
},
{
"docid": "8729045",
"text": "Eric Wagner (born April 24, 1959) is an American heavy metal singer who is best known for his work with doom metal band Trouble, which he formed in 1979 when he was 20 years old. He briefly left Trouble in the mid-nineties and formed Lid with guitarist Danny Cavanagh, resulting in 1997's \"In The Mushroom\". Wagner rejoined Trouble in 2002 to record Simple Mind Condition. He also appeared on Dave Grohl's heavy metal side project \"Probot\" in 2004 with the song My Tortured Soul.",
"title": ""
},
{
"docid": "9573445",
"text": "Thunderstorm was a doom metal band from Bergamo, Italy. Formed in the early 1990s as a classic heavy metal band, with touches of a down tuned sound. During this early incarnation, they released two demos, \"Thunderstorm\" (1992) and \"Force of Evil\" (1994). In 1998, the band split up due to musical incompatibility issues between members. Their leader and vocalist Fabio \"Thunder\" Bellan met drummer Massimo Tironi and formed a new Thunderstorm band, this time geared the sound toward classic doom metal in style of Black Sabbath, Candlemass, and Trouble, and called themselves Sad Symphony. Joining the band soon after was bassist Omar Roncalli, after which the named was then switched back to the original moniker Thunderstorm, and a second guitarist, Sandro Mazzoleni, joined the band. In 1999, this line-up produced a demo called \"Sad Symphony\", which generated interest among record labels, and the band was signed to Northwind Records.",
"title": ""
},
{
"docid": "12187524",
"text": "Heavy Load was a Swedish heavy metal band from Stockholm. The band is often hailed as the first Swedish heavy metal band, and were known for their Viking themes. The Wahlquist brothers, who founded the band in 1976 along with Michael Backler, were later producers and owners of Thunderload Records in Sweden, were at one point producing Veni Domine, and also were considering releasing a new album, though that never occurred. Misfortune struck when Thunderload Studios got severely damaged due to a water leakage in the 2000s, which meant a halt to its official existence. After the breakup, the members then went on and performed with other bands.",
"title": ""
},
{
"docid": "2201996",
"text": "Rata Blanca (White Rat in English) is a heavy metal band from Argentina, formed in 1986. It is considered the most famous metal band in its country, and one of the most important of the genre in South America.",
"title": ""
},
{
"docid": "3550764",
"text": "Sami Kristian Karppinen is a Finnish drummer. He is a former drummer of Swedish heavy metal band Therion (1998–2001) and Finnish industrial metal band Ruoska (2002-2008), sound engineer and producer in Modern Art Studio, and session drummer. He has been working as drum tech for Therion, after he left the band.",
"title": ""
},
{
"docid": "20907",
"text": "Motörhead ( ) were an English rock band formed in June 1975 by bassist, singer, and songwriter Ian Fraser \"Lemmy\" Kilmister, who was the sole constant member, guitarist Larry Wallis and drummer Lucas Fox. The band are often considered a precursor to the new wave of British heavy metal, which re-energised heavy metal in the late 1970s and early 1980s. Though several guitarists and drummers have played in Motörhead, most of their best-selling albums and singles feature the work of \"Fast\" Eddie Clarke on guitar and Phil \"Philthy Animal\" Taylor on drums.",
"title": ""
},
{
"docid": "528779",
"text": "Diamond Head are an English heavy metal band formed in 1976 in Stourbridge, England. The band is recognised as one of the leading members of the new wave of British heavy metal movement and is acknowledged by thrash metal bands such as Metallica and Megadeth as an important early influence.",
"title": ""
},
{
"docid": "7879780",
"text": "Wrought is a band based in the town of Fayetteville, Arkansas; it was formed on Halloween of 2004, but played its first venue on March 22, 2005. Wrought's merging of vocals, solos and rhythms over a southern-metal hump has proven to be popular with heavy metal fans. The release of their eponymous EP in the summer of 2005 caused a surge in popularity that was followed by their first full-length release (\"Hand Crafted Metal\" in 2006), both of which were completely self-recorded, produced, and promoted.",
"title": ""
},
{
"docid": "20816998",
"text": "Baby Tuckoo was an English hard rock band, formed in Bradford, West Yorkshire, England in 1982. Their name is taken from the James Joyce novel \"A Portrait of the Artist as a Young Man\". They were generally considered a part of the new wave of British heavy metal.",
"title": ""
},
{
"docid": "24219579",
"text": "Salem is a hard rock/heavy metal band from Hull, England. The band was formed following the split of the new wave of British heavy metal band Ethel The Frog. Salem recorded three demos and a single in the early 1980s; a compilation album of these recordings was released in 2010.",
"title": ""
},
{
"docid": "33920182",
"text": "Boize was a Canadian heavy metal and glam metal band based in Montreal, Quebec. The band was formed in the spring of 1989 in Laval, Quebec when vocalist Perry Blainey responded to an advertisement placed in the Montreal Gazette newspaper by bassist and keyboardist Stéphane Fania and guitarist Robert Kourie. Boize was associated with record label Aquarius Records and was managed by Canadian musician star and recording studio owner Bill Hill, under his music production company and management agency Bill Hill Productions. The band also had a brief association with South American heavy metal legend Alvacast, when singer Carlos \"Charly\" Lopez joined Boize as new vocalist in the fall of 1992.",
"title": ""
},
{
"docid": "2105746",
"text": "Fallout was a heavy metal band formed in 1979 based out of Brooklyn, New York, USA. The band contained future Type O Negative members Peter Steele (then billed under his birth name, Peter Ratajczyk) on bass and vocals and Josh Silver on keyboards, as well as John Campos on guitars and Agnostic Front drummer Louie Beateaux (then billed as Lou Beato) on drums. Fallout released only one record before the band's demise in 1982, the \"Rock Hard\" 7\" single, released in 1981 on Silver Records and limited to 500 copies. This record was produced by Richard Termini and William Wittman.",
"title": ""
},
{
"docid": "838930",
"text": "Living Sacrifice is an American heavy metal band that formed in September 1989 in Little Rock, Arkansas. The band has released eight studio albums, out of which the first three were recorded under R.E.X. Records with their original vocalist Darren Johnson as a more thrash metal and death metal oriented band. The band evolved into a groove metal/metalcore style beginning with \"Reborn\" (1997) under Solid State Records with the original guitarist Bruce Fitzhugh on vocals. In 2003, the group split up, due to other projects and later their label, Solid State, released their best-of album, \"In Memoriam\" (2005). In 2008, Living Sacrifice reformed and released a two-song digital only single called \"Death Machine\". They then began working on \"The Infinite Order\" which was released on January 26, 2010. Lance Garvin and Bruce Fitzhugh are the two remaining original members.",
"title": ""
},
{
"docid": "3064598",
"text": "Nitro II: H.W.D.W.S. (\"Hot, Wet, Drippin' with Sweat\") is the second studio album by American heavy metal band Nitro. Recorded at the Platinum Post Full Sail Center for Recording Arts in Orlando, Florida, it was produced by the band's vocalist Jim Gillette and co-produced by engineer Gary Platt. The album was released on March 21, 1992 by Rampage Records, a division of Rhino Entertainment. The band's cover of Ted Nugent's \"Cat Scratch Fever\" was issued as the album's only single.",
"title": ""
}
] |
5ae685b45542996d980e7bd7
|
On what date did the German offensive of which the First Battle of Villers-Bretonneux was a part begin?
|
[
{
"docid": "502983",
"text": "The 1918 Spring Offensive or Kaiserschlacht (\"Kaiser's Battle\"), also known as the Ludendorff Offensive, was a series of German attacks along the Western Front during the First World War, beginning on 21 March 1918, which marked the deepest advances by either side since 1914. The Germans had realised that their only remaining chance of victory was to defeat the Allies before the overwhelming human and matériel resources of the United States could be fully deployed. They also had the temporary advantage in numbers afforded by the nearly 50 divisions freed by the Russian surrender (the Treaty of Brest-Litovsk).",
"title": ""
},
{
"docid": "19493670",
"text": "The First Battle of Villers-Bretonneux (30 March – 5 April 1918), took place during Operation Michael, part of the German Spring Offensive on the Western Front. The offensive began against the British Fifth Army and the Third Army on the Somme and pushed back the British and French reinforcements on the north side of the Somme. The capture of Villers-Bretonneux, close to Amiens, a strategically-important road- and rail-junction, would have brought the Germans within artillery-range. In late March, Australian troops were brought south from Belgium as reinforcements to help shore up the line and in early April the Germans launched an attack to capture Villers-Bretonneux. After a determined defence by British and Australian troops, the attackers were close to success until a counter-attack by the 9th Australian Infantry Brigade and British troops late in the afternoon of 4 April restored the situation and halted the German advance on Amiens.",
"title": ""
}
] |
[
{
"docid": "5076856",
"text": "The Battle of the Avre (4–5 April 1918), part of the First Battle of Villers-Bretonneux, constituted the final German attack towards Amiens in World War I. It was the point at which the Germans got the closest to Amiens. It was fought between attacking German troops and defending Australian and British troops. The attack was an attempt to take Amiens, where other aspects of Operation Michael had failed. The Avre marked the beginning of the end for Ludendorf's March Offensive.",
"title": ""
},
{
"docid": "46544577",
"text": "Hangard Wood is a locality south of Villers-Bretonneux northern France. It was the site of Hangard village and a battle in World War I. The battle of Hangard Wood was part of the German offensive Operation Michael, in the Arras - St-Quentin-La Fére sector of the Somme fought in March 1918. The battle of Hangard Wood was more specifically part of the larger second battle of Villers-Bretonneux, fought between Canadian British/Australian/French and German armies.",
"title": ""
},
{
"docid": "19493708",
"text": "The Second Battle of Villers-Bretonneux took place during the Battle of the Lys, 24–27 April 1918, when an assault was launched against the Allied lines to the east of Amiens. It is notable for the first major use of tanks by the Germans, who deployed fourteen of their twenty A7Vs, and for the first tank-versus-tank battle in history.",
"title": ""
},
{
"docid": "25605511",
"text": "The Australian National Memorial, Villers–Bretonneux is the main memorial to Australian military personnel killed on the Western Front during World War I. It is located on the Route Villiers-Bretonneux (D 23), between the towns of Fouilloy and Villers-Bretonneux, in the Somme département, France. The memorial lists 10,773 names of soldiers of the Australian Imperial Force with no known grave who were killed between 1916, when Australian forces arrived in France and Belgium, and the end of the war. The location was chosen to commemorate the role played by Australian soldiers in the Second Battle of Villers-Bretonneux (24–27 April 1918).",
"title": ""
},
{
"docid": "28802370",
"text": "The Gare de Villers-Bretonneux (Villers-Bretonneux station) is a railway station located in the commune of Villers-Bretonneux in the Somme department, France. The station is served by TER Picardie trains (Amiens - Saint-Quentin).",
"title": ""
},
{
"docid": "30860300",
"text": "Operation \"Michael\" was a major German military offensive during the First World War that began the Spring Offensive on 21 March 1918. It was launched from the Hindenburg Line, in the vicinity of Saint-Quentin, France. Its goal was to break through the Allied (Entente) lines and advance in a north-westerly direction to seize the Channel ports, which supplied the British Expeditionary Force (BEF) and to drive the BEF into the sea. Two days later General Ludendorff, the Chief of the German General Staff, changed his plan and pushed for an offensive due west, along the whole of the British front north of the River Somme. This was designed to separate the French and British Armies and crush the British forces by pushing them into the sea. The offensive ended at Villers-Bretonneux, to the east of the Allied communications centre at Amiens, where the Allies managed to halt the German advance; the German Armies had suffered many casualties and were unable to maintain supplies to the advancing troops.",
"title": ""
},
{
"docid": "8828728",
"text": "The Battle of Amiens or Battle of Villers-Bretonneux was fought on 27 November 1870 during the Franco-Prussian War, ending in a Prussian victory.",
"title": ""
},
{
"docid": "3300973",
"text": "Villers-Bretonneux is a commune in the Somme department in Hauts-de-France in northern France.",
"title": ""
},
{
"docid": "4824633",
"text": "The East Prussian Offensive was a strategic offensive by the Red Army against the German \"Wehrmacht\" on the Eastern Front (World War II). It lasted from 13 January to 25 April 1945, though some German units did not surrender until 9 May. The Battle of Königsberg was a major part of the offensive, which ended in victory for the Red Army.",
"title": ""
},
{
"docid": "17193189",
"text": "This is the order of battle for the Battle of Villers-Bocage, a World War II battle on 13 June 1944 between British and German forces in Normandy, France as part of Operation Perch.",
"title": ""
},
{
"docid": "1328501",
"text": "The Hundred Days Offensive was the final period of the First World War, during which the Allies launched a series of offensives against the Central Powers on the Western Front from 8 August to 11 November 1918, beginning with the Battle of Amiens. The offensive essentially pushed the Germans out of France, forcing them to retreat beyond the Hindenburg Line, and was followed by an armistice. The term \"Hundred Days Offensive\" does not refer to a specific battle or unified strategy, but rather the rapid series of Allied victories starting with the Battle of Amiens.",
"title": ""
},
{
"docid": "46217753",
"text": "The First Rzhev-Sychyovka Offensive Operation was part of a series of battles that lasted 15 months in the center of the Eastern Front. In Soviet historiography, the operation is officially defined as spanning 30 July to 23 August 1942. However, it is widely documented that the fighting continued undiminished into September and did not finally cease until the beginning of October 1942. The Red Army suffered massive casualties for little gain during the fighting, giving the battle a notoriety reflected in its sobriquet: \"The Rzhev Meat Grinder\".",
"title": ""
},
{
"docid": "7622742",
"text": "The First Battle of Champagne (French: \"1ère Bataille de Champagne\" ) was fought from 20 December 1914 – 17 March 1915 in World War I in the Champagne region of France and was the second offensive by the Allies against the Germans since mobile warfare had ended after the First Battle of Ypres in Flanders(19 October – 22 November 1914). The battle was fought by the French Fourth Army and the German 3rd Army. The offensive was part of a strategy by the French army to attack the Noyon Salient, a large bulge in the new Western Front, which ran from Switzerland to the North Sea. The First Battle of Artois began on the northern flank of the salient on 17 December and the offensive against the southern flank in Champagne began three days later.",
"title": ""
},
{
"docid": "2792534",
"text": "The Nivelle Offensive of 1917, was a Franco-British offensive on the Western Front in the First World War. The French part of the offensive was intended to be strategically decisive, by breaking through the German defences on the Aisne front within 48 hours, with casualties expected to be around 10,000 men. A preliminary attack was to be made by the French Third Army at St. Quentin and the British First, Third and Fifth armies at Arras, to capture high ground and divert German reserves from the French fronts on the Aisne and in Champagne. The main offensive was to be delivered by the French on the Chemin des Dames ridge (the Second Battle of the Aisne, \"La bataille du Chemin des Dames\" , \"Seconde bataille de l'Aisne\" and \"Doppelschlacht Aisne-Champagne\" ), with a subsidiary attack by the Fourth Army (the Third Battle of Champagne, the Battle of the Hills or Battle of the Hills of Champagne). The final stage of the offensive was to follow the meeting of the British and French armies, having broken through the German lines, with a pursuit of the defeated German armies towards the German frontier.",
"title": ""
},
{
"docid": "22704839",
"text": "The Battle of Vimy Ridge was a military engagement fought as part of the Battle of Arras, in the Nord-Pas-de-Calais region of France, during the First World War. The main combatants were the Canadian Corps against three divisions of the German Sixth Army. The battle was part of the opening phase of the Battle of Arras, part Nivelle Offensive and took place from 9–12 April 1917. The objective of the Canadian Corps was to take control of the German-held high ground, along an escarpment at the northernmost end of the Arras Offensive. This would ensure that the southern flank could advance without suffering German enfilade fire.",
"title": ""
},
{
"docid": "204517",
"text": "The Battle of Villers-Bocage took place during the Second World War on 13 June 1944, one week after the Normandy Landings by the Western Allies that began the conquest of German-occupied France. The battle was the result of a British attempt to improve their position, by exploiting a gap in the German defences west of the city of Caen. After one day of fighting in and around the small town of Villers-Bocage and a second day defending a position outside the town, the British force retired.",
"title": ""
},
{
"docid": "70435",
"text": "The Battle of Vimy Ridge was a military engagement fought primarily as part of the Battle of Arras, in the Nord-Pas-de-Calais region of France, during the First World War. The main combatants were the Canadian Corps, of four divisions, against three divisions of the German Sixth Army. The battle, which took place from 9 to 12 April 1917, was part of the opening phase of the British-led Battle of Arras, a diversionary attack for the French Nivelle Offensive.",
"title": ""
},
{
"docid": "5060085",
"text": "The Battle of Broodseinde was fought on 4 October 1917 near Ypres in Flanders, at the east end of the Gheluvelt plateau, by the British Second and Fifth armies and the German 4th Army. The battle was the most successful Allied attack of the Battle of Passchendaele. Using \"bite-and-hold\" tactics, with objectives limited to what could be held against German counter-attacks, the British devastated the German defence, which prompted a crisis among the German commanders and caused a severe loss of morale in the German 4th Army. Preparations were made by the Germans for local withdrawals and planning began for a greater withdrawal, which would entail the loss for the Germans of the Belgian coast, one of the strategic aims of the British offensive.",
"title": ""
},
{
"docid": "24541356",
"text": "The Battle of Grand Couronné (French: \"Bataille du Grand Couronné\" ) took place in France after the Battle of the Frontiers, at the beginning of World War I. After the German victories of Sarrebourg and Morhange, the German pursuit by the 6th and 7th armies took four days to regain contact with the French. The Germans attacked to break through French defences on the Moselle, from 24 August – 13 September in three phases, the Battle of the Trouée de Charmes (24–28 August), when the German offensive was met by a French counter-offensive, a period of preparation from 28 August – 3 September, when part of the French eastern armies was moved westwards towards Paris and then a final German attack against the Grand Couronné de Nancy. The battle was fought day and night from 4–13 September 1914, by the German 6th Army commanded by Crown Prince Rupprecht of Bavaria and the French Second Army commanded by Noël de Castelnau.",
"title": ""
},
{
"docid": "24436088",
"text": "The Second Battle of Bapaume was a battle of the First World War that took place at Bapaume in France, from 21 August 1918 to 3 September 1918. It was a continuation of the Battle of Albert and is also referred to as the second phase of that battle. The British and Dominion attack was part of what was later known as the Allies' Hundred Days Offensive.",
"title": ""
},
{
"docid": "2912026",
"text": "The Battle of Radzymin was one of a series of engagements between the Red Army's 1st Byelorussian Front and the German Army's XXXIXth Panzer Corps that occurred as part of the Lublin-Brest Offensive between 1 and 10 August 1944 at the conclusion of the Belorussian strategic offensive operation near the town of Radzymin in the vicinity of Warsaw, part of which entailed a large tank battle at Wołomin. It was the largest tank battle on the territories of Poland during World War II .",
"title": ""
},
{
"docid": "40738529",
"text": "This is the order of battle for Operation Michael, part of the German Spring Offensive fought from 21 March to 5 April 1918 as one of the main engagements of the First World War. It was fought between mixed French, British and Dominion forces and the",
"title": ""
},
{
"docid": "672675",
"text": "The Korsun–Shevchenkovsky Offensive led to the Battle of the Korsun–Cherkasy Pocket which took place from 24 January to 16 February 1944. The offensive was part of the Dnieper–Carpathian Offensive. In it, the 1st and 2nd Ukrainian Fronts, commanded, respectively, by Nikolai Vatutin and Ivan Konev, encircled German forces of Army Group South in a pocket near the Dnieper River. During weeks of fighting, the two Red Army Fronts tried to eradicate the pocket. The encircled German units attempted a breakout in coordination with a relief attempt by other German forces, resulting in heavy casualties, estimates of which vary.",
"title": ""
},
{
"docid": "6861741",
"text": "The Battle of Zborov (\"Зборовское сражение\" in Russian, \"Schlacht bei Zborów\" in German, \"bitva u Zborova\" in Czech, \"bitka pri Zborove\" in Slovak) was a part of the Kerensky Offensive, (the last Russian offensive in World War I, taking place in July 1917). The battle was the first significant action of the Czechoslovak Legions (volunteers fighting against the Central Powers) on the Eastern Front and the only successful engagement of the failed Russian offensive.",
"title": ""
},
{
"docid": "6164558",
"text": "The second Battle of Smolensk (7 August–2 October 1943) was a Soviet strategic offensive operation conducted by the Red Army as part of the Summer-Autumn Campaign of 1943. Staged almost simultaneously with the Lower Dnieper Offensive (13 August–22 September), the offensive lasted two months and was led by General Andrei Yeremenko, commanding the Kalinin Front, and Vasily Sokolovsky, commanding the Western Front. Its goal was to clear the German presence from the Smolensk and Bryansk regions. Smolensk had been under German occupation since the first Battle of Smolensk in 1941.",
"title": ""
},
{
"docid": "21975800",
"text": "The Battle of Podu Iloaiei was part of the First Jassy–Kishinev Offensive of World War II fought between the Romanians along with their German allies and the Soviets. The battle was a reaction to the Soviet defeat at the First Battle of Târgu Frumos. It consisted mainly of a tank battle near Scobâlțeni where the First Romanian Armored Division (Divizia 1 Blindată) held off the Soviet tanks for a single day. At the end of the battle, the Germans joined to drive the Soviets back to the positions they held before the battle.",
"title": ""
},
{
"docid": "4363893",
"text": "The Battle of Krasny Bor was part of the Soviet offensive Operation \"Polyarnaya Zvezda\". It called for a pincer attack near Leningrad, to build on the success of Operation \"Iskra\" and completely lift the Siege of Leningrad, encircling a substantial part of the German 18th Army. The offensive near \"Krasny Bor\", formed the western arm of the pincer. The Soviet offensive began on Wednesday, 10 February 1943. It produced noticeable gains on the first day, but rapidly turned into a stalemate. The strong defense of the 250th (Spanish) Infantry Division led by General Emilio Esteban Infantes and the 4th SS Police Division gave the German forces time to reinforce their positions. By February 13, the Soviet forces had stopped their offensive in this sector.",
"title": ""
},
{
"docid": "5809606",
"text": "The Battle of Aubers Ridge was a British offensive on the Western Front on 9 May 1915 during World War I. The battle was part of the British contribution to the Second Battle of Artois, a Franco-British offensive intended to exploit the German diversion of troops to the Eastern Front. The French Tenth Army was to attack the German 6th Army north of Arras and capture Vimy Ridge, preparatory to an advance on Cambrai and Douai. The British First Army on the left (northern) flank of the Tenth Army, was to attack on the same day and widen the gap in the German defences expected to be made by the Tenth Army and to prevent German troops from being moved south of La Bassée canal.",
"title": ""
},
{
"docid": "2659661",
"text": "The Second Battle of the Somme of 1918 was fought during the First World War on the Western Front from late August to early September, in the basin of the River Somme. It was part of a series of successful counter-offensives in response to the German Spring Offensive, after a pause for redeployment and supply.",
"title": ""
},
{
"docid": "34823997",
"text": "The Battle of Tulkarm took place on 19 September 1918, beginning of the Battle of Sharon, which along with the Battle of Nablus formed the set piece Battle of Megiddo fought between 19 and 25 September in the last months of the Sinai and Palestine Campaign of the First World War. During the infantry phase of the Battle of Sharon the British Empire 60th Division, XXI Corps attacked and captured the section of the front line nearest the Mediterranean coast under cover of an intense artillery barrage including a creeping barrage and naval gunfire. This Egyptian Expeditionary Force (EEF) victory over the entrenched Ottoman Eighth Army, composed of German and Ottoman soldiers, began the Final Offensive, ultimately resulting in the destruction of the equivalent of one Ottoman army, the retreat of what remained of two others, and the capture of many thousands of prisoners and many miles of territory from the Judean Hills to the border of modern-day Turkey. After the end of the battle of Megiddo, the Desert Mounted Corps pursued the retreating soldiers to Damascus, six days later. By the time an Armistice of Mudros was signed between the Allies and the Ottoman Empire five weeks later, Aleppo had been captured.",
"title": ""
}
] |
6995
|
Can I use losses from sale of stock to offset capital gains from sale of property
|
[
{
"docid": "236254",
"text": "Capital losses from the sale of stocks can be used to offset capital gains from the sale of a house, assuming that house was a rental property the whole time. If it was your principal residence, the capital gains are not taxed. If you used it as both a rental and a principal residence, then it gets more complicated: http://www.cra-arc.gc.ca/tx/ndvdls/tpcs/ncm-tx/rtrn/cmpltng/rprtng-ncm/lns101-170/127/rsdnc/menu-eng.html",
"title": ""
}
] |
[
{
"docid": "195767",
"text": "@BlackJack does a good answer of addressing the gains and when you are taxed on them and at what kind of rate. Money held in a brokerage account will usually be in a money-market fund, so you would own taxes on the interest it earned. There is one important consideration that must be understood for capitol Losses. This is called the Wash Sale Rule. This rule comes into affect if you sell a stock at a LOSS, and buy shares of the same stock within 30 days (before or after) the sale. A common tactic used to minimize taxes paid is to 'capture losses' when they occur, since these can be used to offset gains and lower your taxes. This is normally done by selling a stock in which you have a LOSS, and then either buying another similar stock, or waiting and buying back the stock you sold. However, if you are intending to buy back the same stock, you must not 'trigger' the Wash Sale Rule or you are forbidden to take the loss. Examples. Lets presume you own 1000 shares of a stock and it's trading 25% below where you bought it, and you want to capture the loss to use on your taxes. This can be a very important consideration if trading index ETF's if you have a loss in something like a S&P500 ETF, you would likely incur a wash sale if you sold it and bought a different S&P500 ETF from another company since they are effectively the same thing. OTOH, if you sold an S&P500 ETF and bought something like a 'viper''total stock market' ETF it should be different enough to not trigger the wash sale rule. If you are trying to minimize the taxes you pay on stocks, there are basically two rules to follow. 1) When a gain is involved, hold things at least a year before selling, if at all possible. 2) Capture losses when they occur and use to offset gains, but be sure not to trigger the wash sale rule when doing so.",
"title": ""
},
{
"docid": "411375",
"text": "\"Because the returns are not good. One of the big drivers in Australia is \"\"negative gearing\"\": if your investment loses money you can offset losses against your tax on other income. Institutional investors and corporations are in the business of making money: not losing it. Housing market investors are betting that these year to year revenue losses will ultimately be made up in a big capital gain: for which individuals get a huge tax break that is also not available to corporations. Capital gains are not guaranteed. Australia has benefited from 25+ years of economic, employment and wages growth: a result of good government planning, strong corporate governance and a fair slice of luck. If this were to end housing prices would plateau at best and crash at worst. A person who has negative cash flow investments has to sell them urgently if they lose their job. A glut of mortgagee sales and property prices could easily come off 20-30%. Rental yields on residential property in Sydney are about 4% with a capital gain of currently 10% but this has been flat or negative within the last 5 years and no doubt will be again within the next 5. Rental yields for residential property are constrained by mortgage rates: if it significantly cheaper to buy then to rent, why would anyone rent? In contrast, industrial and commercial property gets a yield of about 7% and gets exactly the same capital gain. This is because land is land and if the price of industrial land doesn't grow at the same rate as the residential land next door eventually one will be converted into the other. Retail rentals are even higher. In addition commercial tenants are responsible for more outgoings and have fewer legal rights than residential tenants. Further, individual residential properties are horribly illiquid and have large transaction costs. While it is possible to bundle them up into property trusts so that units can be sold on the stock exchange it is far more common to do this with office and retail buildings. This is what companies like Westfield and AMP Capital do. Notwithstanding, heavily geared property trusts can get into deep water because of the illiquid nature of property as the failure of Centro illustrates. That said, there are plenty of companies that develop residential houses and units for sale to owner occupiers or investors because that's where the money is.\"",
"title": ""
},
{
"docid": "568064",
"text": "\"As long as the IRS treats bitcoin as property, then whenever you use bitcoin to buy anything you are supposed to consider the capital gain or capital loss. There is no \"\"until it's converted to fiat\"\". You are paying local sales tax and capital gains, or paying local sales tax and reporting capital loss. As long as you are consistent, you can use either the total cost basis, or individual lot purchases. The same as other property like stocks (except without stock specific regulations like wash-sale rules :D ). There are a lot of perks or unintentional loopholes for speculators, with the property designation. There are a lot of disadvantages for consumers trying to use it like a currency. Someone mixing investment and spending funds across addresses is going to have complicated tax issues, but fortunately the exchanges have records of purchase times and prices, which you can compare with the addresses you control. Do note, after that IRS guideline, another federal agency designated Bitcoin as a commodity, which is a subset of \"\"property\"\" with its own more favorable but different tax guidelines.\"",
"title": ""
},
{
"docid": "97348",
"text": "\"While you'd need to pay tax if you realized a capital gain on the sale of your car, you generally can't deduct any loss arising from the sale of \"\"personal use property\"\". Cars are personal use property. Refer to Canada Revenue Agency – Personal-use property losses. Quote: [...] if you have a capital loss, you usually cannot deduct that loss when you calculate your income for the year. In addition, you cannot use the loss to decrease capital gains on other personal-use property. This is because if a property depreciates through personal use, the resulting loss on its disposition is a personal expense. There are some exceptions. Read up at the source links.\"",
"title": ""
},
{
"docid": "171819",
"text": "\"There some specific circumstances when you would have a long-term gain. Option 1: If you meet all of these conditions: Then you've got a long-term gain on the stock. The premium on the option gets rolled into the capital gain on the stock and is not taxed separately. From the IRS: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010630 Option 2: If you didn't hold the underlying and the exercise of the call that you wrote resulted in a short position, you might also be able to get to a long-term gain by buying the underlying while keeping your short position open and then \"\"crossing\"\" them to close both positions after one year. (In other words, don't \"\"buy to cover\"\" just \"\"buy\"\" so that your account shows both a long and a short position in the same security. Your broker probably allows this, but if not you, could buy in a different account than the one with the short position.) That would get you to this rule: As a general rule, you determine whether you have short-term or long-term capital gain or loss on a short sale by the amount of time you actually hold the property eventually delivered to the lender to close the short sale. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010586 Option 1 is probably reasonably common. Option 2, I would guess, is uncommon and likely not worthwhile. I do not think that the wash sale rules can help string along options from expiration to expiration though. Option 1 has some elements of what you wrote in italics (I find that paragraph a bit confusing), but the wash sale does not help you out.\"",
"title": ""
},
{
"docid": "552255",
"text": "The loss for B can be used to write off the gain for A. You will fill out a schedule 3 with cost base and proceeds of disposition. This will give you a $0 capital gain for the year and an amount of $5 (50% of the $10 loss) you can carry forward to offset future capital gains. You can also file a T1-a and carry the losses back up to 3 years if you're so inclined. It can't be used to offset other income (unless you die). Your C and D trades can't be on income account except for very unusual circumstances. It's not generally acceptable to the CRA for you to use 2 separate accounting methods. There are some intricacies but you should probably just use capital gains. There is one caveat that if you do short sales of Canadian listed securities, they will be on income account unless you fill out form T-123 and elect to have them all treated as capital gains. I just remembered one wrinkle in carrying forward capital losses. They don't reduce your capital gains anymore, but they reduce your taxable income. This means your net income won't be reduced and any benefits that are calculated from that (line 236), will not get an increase.",
"title": ""
},
{
"docid": "468047",
"text": "Don't let tax considerations be the main driver. That's generally a bad idea. You should keep tax in mind when making the decision, but don't let it be the main reason for an action. selling the higher priced shares (possibly at a loss even) - I think it's ok to do that, and it doesn't necessarily have to be FIFO? It is OK to do that, but consider also the term. Long term gain has much lower taxes than short term gain, and short term loss will be offsetting long term gain - means you can lose some of the potential tax benefit. any potential writeoffs related to buying a home that can offset capital gains? No, and anyway if you're buying a personal residence (a home for yourself) - there's nothing to write off (except for the mortgage interest and property taxes of course). selling other investments for a capital loss to offset this sale? Again - why sell at a loss? anything related to retirement accounts? e.g. I think I recall being able to take a loan from your retirement account in order to buy a home You can take a loan, and you can also withdraw up to 10K without a penalty (if conditions are met). Bottom line - be prepared to pay the tax on the gains, and check how much it is going to be roughly. You can apply previous year refund to the next year to mitigate the shock, you can put some money aside, and you can raise your salary withholding to make sure you're not hit with a high bill and penalties next April after you do that. As long as you keep in mind the tax bill and put aside an amount to pay it - you'll be fine. I see no reason to sell at loss or pay extra interest to someone just to reduce the nominal amount of the tax. If you're selling at loss - you're losing money. If you're selling at gain and paying tax - you're earning money, even if the earnings are reduced by the tax.",
"title": ""
},
{
"docid": "274278",
"text": "\"The only \"\"authoritative document\"\" issued by the IRS to date relating to Cryptocurrencies is Notice 2014-21. It has this to say as the first Q&A: Q-1: How is virtual currency treated for federal tax purposes? A-1: For federal tax purposes, virtual currency is treated as property. General tax principles applicable to property transactions apply to transactions using virtual currency. That is to say, it should be treated as property like any other asset. Basis reporting the same as any other property would apply, as described in IRS documentation like Publication 550, Investment Income and Expenses and Publication 551, Basis of Assets. You should be able to use the same basis tracking method as you would use for any other capital asset like stocks or bonds. Per Publication 550 \"\"How To Figure Gain or Loss\"\", You figure gain or loss on a sale or trade of property by comparing the amount you realize with the adjusted basis of the property. Gain. If the amount you realize from a sale or trade is more than the adjusted basis of the property you transfer, the difference is a gain. Loss. If the adjusted basis of the property you transfer is more than the amount you realize, the difference is a loss. That is, the assumption with property is that you would be using specific identification. There are specific rules for mutual funds to allow for using average cost or defaulting to FIFO, but for general \"\"property\"\", including individual stocks and bonds, there is just Specific Identification or FIFO (and FIFO is just making an assumption about what you're choosing to sell first in the absence of any further information). You don't need to track exactly \"\"which Bitcoin\"\" was sold in terms of exactly how the transactions are on the Bitcoin ledger, it's just that you bought x bitcoins on date d, and when you sell a lot of up to x bitcoins you specify in your own records that the sale was of those specific bitcoins that you bought on date d and report it on your tax forms accordingly and keep track of how much of that lot is remaining. It works just like with stocks, where once you buy a share of XYZ Corp on one date and two shares on another date, you don't need to track the movement of stock certificates and ensure that you sell that exact certificate, you just identify which purchase lot is being sold at the time of sale.\"",
"title": ""
},
{
"docid": "169240",
"text": "You can keep the cash in your account as long as you want, but you have to pay a tax on what's called capital gains. To quote from Wikipedia: A capital gain is a profit that results from investments into a capital asset, such as stocks, bonds or real estate, which exceeds the purchase price. It is the difference between a higher selling price and a lower purchase price, resulting in a financial gain for the investor.[1] Conversely, a capital loss arises if the proceeds from the sale of a capital asset are less than the purchase price. Thus, buying/selling stock counts as investment income which would be a capital gain/loss. When you are filing taxes, you have to report net capital gain/loss. So you don't pay taxes on an individual stock sale or purchase - you pay tax on the sum of all your transactions. Note: You do not pay any tax if you have a net capital loss. Taxes are only on capital gains. The amount you are taxed depends on your tax bracket and your holding period. A short term capital gain is gain on an investment held for less than one year. These gains are taxed at your ordinary income tax rate. A long term capital gain is gain on an investment held for more than one year. These gains are taxed at a special rate: If your income tax rate is 10 or 15%, then long term gains are taxed at 0% i.e. no tax, otherwise the tax rate is 15%. So you're not taxed on specific stock sales - you're taxed on your total gain. There is no tax for a capital loss, and investors sometimes take profits from good investments and take losses from bad investments to lower their total capital gain so they won't be taxed as much. The tax rate is expected to change in 2013, but the current ratios could be extended. Until then, however, the rate is as is. Of course, this all applies if you live in the United States. Other countries have different measures. Hope it helps! Wikipedia has a great chart to refer to: http://en.wikipedia.org/wiki/Capital_gains_tax_in_the_United_States.",
"title": ""
},
{
"docid": "444405",
"text": "Here's how capital gains are totaled: Long and Short Term. Capital gains and losses are either long-term or short-term. It depends on how long the taxpayer holds the property. If the taxpayer holds it for one year or less, the gain or loss is short-term. Net Capital Gain. If a taxpayer’s long-term gains are more than their long-term losses, the difference between the two is a net long-term capital gain. If the net long-term capital gain is more than the net short-term capital loss, the taxpayer has a net capital gain. So your net long-term gains (from all investments, through all brokers) are offset by any net short-term loss. Short term gains are taxed separately at a higher rate. I'm trying to avoid realizing a long term capital gain, but at the same time trade the stock. If you close in the next year, one of two things will happen - either the stock will go down, and you'll have short-term gains on the short, or the stock will go up, and you'll have short-term losses on the short that will offset the gains on the stock. So I don;t see how it reduces your tax liability. At best it defers it.",
"title": ""
},
{
"docid": "212394",
"text": "\"I'll try to answer using your original example. First, let me restate your assumptions, slightly modified: The mutual fund has: Note that I say the \"\"mutual fund has\"\" those gains and losses. That's because they occur inside the mutual fund and not directly to you as a shareholder. I use \"\"realized\"\" gains and losses because the only gains and losses handled this way are those causes by actual asset (stock) sales within the fund (as directed by fund management). Changes in the value of fund holdings that are not sold are not included in this. As a holder of the fund, you learn the values of X, Y, and Z after the end of the year when the fund management reports the values. For gains, you will also typically see the values reported on your 1099-DIV under \"\"capital gains distributions\"\". For example, your 1099-DIV for year 3 will have the value Z for capital gains (besides reporting any ordinary dividends in another box). Your year 1 1099 will have $0 \"\"capital gains distributions\"\" shown because of the rule you highlighted in bold: net realized losses are not distributed. This capital loss however can later be used to the mutual fund holder's tax advantage. The fund's internal accounting carries forward the loss, and uses it to offset later realized gains. Thus your year 2 1099 will have a capital gain distribution of (Y-X), not Y, thus recognizing the loss which occurred. Thus the loss is taken into account. Note that for capital gains you, the holder, pay no tax in year 1, pay tax in year 2 on Y-X, and pay tax in year 3 on Z. All the above is the way it works whether or not you sell the shares immediately after the end of year 3 or you hold the shares for many more years. Whenever you do sell the shares, you will have a gain or loss, but that is different from the fund's realized losses we have been talking about (X, Y, and Z).\"",
"title": ""
},
{
"docid": "11122",
"text": "\"Disclaimer: I am neither a lawyer nor a tax-expert This page on the HMRC site lists several pages that appear to be relevant, starting with CG78401 - Foreign currency: delayed remittances and on to CG78408 - Foreign currency: example which seems pertinent to your case [paraphrased]: A property bought in 1983 is sold for a [taxable] gain in one tax-year (1986/87) but the proceeds cannot be released/remitted to the UK until later (1991/92), by which time currency fluctuations have created a second [taxable] gain. The size of the first gain (selling the property) is determined by the exchange rate in effect at the time of the sale but because of local restrictions, this can be deferred. The size of the second gain (currency movement) is determined by the change in exchange-rate between the time of the sale and the time of conversion. In your case, the first \"\"gain\"\" was actually a loss, so I believe you should be able to use this to offset any tax due second gain. This page states that losses can be claimed up to four years after the end of the tax-year in which they were incurred, so you are probably still OK. (The example makes application under TCGA92/S279 to defer the gain made on the original sale [because of the inability to transfer funds], but as I understand it, this is primarily to avoid a tax liability in that year. Since you made a loss on the sale, there wouldn't have been a tax liability, so there would be no need to defer it).\"",
"title": ""
},
{
"docid": "591157",
"text": "Sale of a stock creates a capital gain. It can be offset with losses, up to $3000 more than the gains. It can be deferred when held within a retirement account. When you gift appreciated stock, the basis follows. So when I gifted my daughter's trust shares, there was still tax due upon sale. The kiddy tax helped reduce but not eliminate it. And there was no quotes around ownership. The money is gone, her account is for college. No 1031 exchange exists for stock.",
"title": ""
},
{
"docid": "385121",
"text": "\"Books would be considered Personal-Use Property according to Canada's income tax laws. The most detailed IT I was able to find is IT-332R, which says: GAINS AND LOSSES 3. A gain on the disposition of personal-use property is normally a capital gain within the meaning of paragraph 39(1)(a). Where the property is a principal residence, the gain > is computed under paragraph 40(2)(b) or (c). 4. Under subparagraph 40(2)(g)(iii), a loss on a disposition of personal-use property, other than listed personal property, is deemed to be nil. [...] This part of the bulletin indicates that a gain might be considered a capital gain - not income. However, you don't get to book a loss as a capital loss. This is the first hint that your book sale - which is actually an exempt capital loss - shouldn't go on your tax return unless it's one of the \"\"listed\"\" items: LISTED PERSONAL PROPERTY 7. Listed personal property is defined in paragraph 54(e) to mean personal-use property that is all or any portion of, or any interest in or right to, any (a) print, etching, drawing, painting, sculpture, or other similar work of art, (b) jewellery, (c) rare folio, rare manuscript, or rare book, (d) stamp, or (e) coin. So unless you're selling rare books, the disposition (sale) of them is essentially exempt as income, regardless of whether you sold it at a profit or at a loss. If it is rare, then you might be able to consider it a capital loss, which doesn't help you much unless you had other capital gains, but you can carry over capital losses to future years. There's also a newer IT related to hobbies and \"\"collecting\"\" items, IT-334R2. This one says: 11. In order for any activity or pursuit to be regarded as a source of income, there must be a reasonable expectation of profit. Where such an expectation does not exist (as is the case with most hobbies), neither amounts received nor expenses incurred are included in the income computation for tax purposes and any excess of expenses over receipts is a personal or living expense, the deduction of which is denied by paragraph 18(1)(h). On the other hand, if the hobby or pastime results in receipts of revenue in excess of expenses, that fact is a strong indication that the hobby is a venture with an expectation of profit; if so, the net income may be taxable as income from a business. The current version of IT-504, Visual Artists and Writers, discusses the concept of \"\"a reasonable expectation of profit\"\" in greater detail. Where a hobby consists of collecting personal-use property or listed personal property, dispositions should be accounted for as described in the current version of IT-332, Personal-Use Property. (emphasis mine) In other words, if it's not the type of thing where you'd make a tax deduction when you bought it in the first place, then you clearly don't need to report it as income when you sell it. Just to be absolutely clear here: The fact that you are selling them at a loss is not actually what's important here. What's important is that, if the books aren't collectibles, then you would have had no expectation of profit. If you did have that expectation then you could have made a tax deduction when you first purchased them. So in this case, it is probably not necessary for you to report the income; however, for the benefit of other readers, in some cases you might need to report it under \"\"other income\"\" or book it as a capital gain/loss, depending on what those personal items are and whether or not you made a net profit.\"",
"title": ""
},
{
"docid": "318321",
"text": "My understanding is that losses are first deductible against any capital gains you may have, then against your regular income (up to $3,000 per year). If you still have a loss after that, the loss may be carried over to offset capital gains or income in subsequent years As you suspect, a short term capital loss is deductible against short term capital gains and long term losses are deductible against long term gains. So taking the loss now MIGHT be beneficial from a tax perspective. I say MIGHT because there are a couple scenarios in which it either may not matter, or actually be detrimental: If you don't have any short term capital gains this year, but you have long term capital gains, you would have to use the short term loss to offset the long term gain before you could apply it to ordinary income. So in that situation you lose out on the difference between the long term tax rate (15%) and your ordinary income rate (potentially higher). If you keep the stock, and sell it for a long term loss next year, but you only have short-term capital gains or no capital gains next year, then you may use the long term loss to offset your short-term gains (first) or your ordinary income. Clear as mud? The whole mess is outlined in IRS Publication 550 Finally, if you still think the stock is good, but just want to take the tax loss, you can sell the stock now (to realize the loss) then re-buy it in 30 days. This is called Tax Loss Harvesting. The 30 day delay is an IRS requirement for being allowed to realize the loss.",
"title": ""
},
{
"docid": "507276",
"text": "\"Are these all of the taxes or is there any additional taxes over these? Turn-over tax is not for retail investors. Other taxes are paid by the broker as part of transaction and one need not worry too much about it. Is there any \"\"Income tax\"\" to be paid for shares bought/holding shares? No for just buying and holding. However if you buy and sell; there would be a capital gain or loss. In stocks, if you hold a security for less than 1 year and sell it; it is classified as short term capital gain and taxes at special rate of 15%. The loss can be adjusted against any other short term gain. If held for more than year it is long term capital gain. For stock market, the tax is zero, you can't adjust long term losses in stock markets. Will the money received from selling shares fall under \"\"Taxable money for FY Income tax\"\"? Only the gain [or loss] will be tread as income not the complete sale value. To calculate gain, one need to arrive a purchase price which is price of stock + Brokerage + STT + all other taxes. Similar the sale price will be Sales of stock - Brokerage - STT - all other taxes. The difference is the gain. Will the \"\"Dividend/Bonus/Buy-back\"\" money fall under taxable category? Dividend is tax free to individual as the company has already paid dividend distribution tax. Bonus is tax free event as it does not create any additional value. Buy-Back is treated as sale of shares if you have participated. Will the share-holder pay \"\"Dividend Distribution Tax\"\"? Paid by the company. What is \"\"Capital Gains\"\"? Profit or loss of buying and selling a particular security.\"",
"title": ""
},
{
"docid": "14768",
"text": "No. The gain on RSU is not a capital gain, it is considered wages and treated as part of your salary, for tax purposes. You cannot offset it with capital losses in excess of $3000 a year. If you have RSUs left after they vest, and you then sell them at gain, the gain (between the vesting price and the sale price) is capital gain and can be offset by your prior years' capital losses.",
"title": ""
},
{
"docid": "360193",
"text": "AS PER IRS PUBLICATION: Question: Is money received from the sale of inherited property considered taxable income? Answer: To determine if the sale of inherited property is taxable, you must first determine your basis in the property. The basis of property inherited from a decedent is generally one of the following: For information on the FMV of inherited property on the date of the decedent’s death, contact the executor of the decedent’s estate. Also, note that in 2015, Congress passed a new law that, under certain circumstances, requires an executor to provide a statement identifying the FMV of certain inherited property to the individual receiving that property. Check IRS.gov for updates on final rules being promulgated to implement the new law. If you or your spouse gave the property to the decedent within one year before the decedent's death, see Publication 551, Basis of Assets. Report the sale on Schedule D (Form 1040), Capital Gains and Losses, and on Form 8949, Sales and Other Dispositions of Capital Assets: Under the new law passed by Congress in 2015, an accuracy-related penalty may apply if an individual reporting the sale of certain inherited property uses a basis in excess of that property’s final value for federal estate tax purposes. Again, check IRS.gov for updates on final rules being promulgated to implement the new law. For estates of decedents who died in 2010, basis is generally determined as described above. However, the executor of a decedent who died in 2010 may elect out of the estate tax rules for 2010 and use the modified carryover of basis rules. Under this special election, the basis of property inherited from a decedent who died during 2010 is generally the lesser of: Under this special election for estates of decedents who died in 2010, the executor of the decedent’s estate may increase the basis of certain property that beneficiaries acquire from a decedent by up to $1.3 million (plus certain unused built-in losses and loss carryovers, if applicable), but the increased basis cannot exceed the FMV of the property at the date of the decedent’s death. The executor may also increase the basis of certain property that the surviving spouse acquires from a decedent by up to an additional $3 million, but the increased basis cannot exceed the FMV of the property at the date of the decedent’s death. The executor of the decedent’s estate is required to provide a statement to all heirs listing the decedent’s basis in the property, the FMV of the property on the date of the decedent’s death, and the additional basis allocated to the property. Contact the executor to determine what the basis of the asset is. Report the sale on Schedule D (Form 1040) and on Form 8949, as described above. Additional Information:",
"title": ""
},
{
"docid": "217781",
"text": "The harvested losses are capital losses. See this IRS page: Generally, realized capital losses are first offset against realized capital gains. Any excess losses can be deducted against ordinary income up to $3,000 ($1,500 if married filing separately) on line 13 of Form 1040. Losses in excess of this limit can be carried forward to later years to reduce capital gains or ordinary income until the balance of these losses is used up. This means that your harvested losses can be used to offset ordinary income --- up to $3000 in a single year, and with extra losses carried forward to future years. It is pretty close to a free lunch, provided that you have some losses somewhere in your portfolio. This free lunch is available to anyone, but for a human, it can be quite a chore to decide when to sell what, keep track of the losses, and avoid the wash sale rules. The advantage of robo-advisors is that they eat that kind of bookkeeping for breakfast, so they can take advantage of tax loss harvesting opportunities that would be too cumbersome for a human to bother with.",
"title": ""
},
{
"docid": "107045",
"text": "Rich's answer captures the basic essence of short selling with example. I'd like to add these additional points: You typically need a specially-privileged brokerage account to perform short selling. If you didn't request short selling when you opened your account, odds are good you don't have it, and that's good because it's not something most people should ever consider doing. Short selling is an advanced trading strategy. Be sure you truly grok selling short before doing it. Consider that when buying stock (a.k.a. going long or taking a long position, in contrast to short) then your potential loss as a buyer is limited (i.e. stock goes to zero) and your potential gain unlimited (stock keeps going up, if you're lucky!) Whereas, with short selling, it's reversed: Your loss can be unlimited (stock keeps going up, if you're unlucky!) and your potential gain is limited (i.e. stock goes to zero.) The proceeds you receive from a short sale – and then some – need to stay in your account to offset the short position. Brokers require this. Typically, margin equivalent to 150% the market value of the shares sold short must be maintained in the account while the short position is open. The owner of the borrowed shares is still expecting his dividends, if any. You are responsible for covering the cost of those dividends out of your own pocket. To close or cover your short position, you initiate a buy to cover. This is simply a buy order with the intention that it will close out your matching short position. You may be forced to cover your short position before you want to and when it is to your disadvantage! Even if you have sufficient margin available to cover your short, there are cases when lenders need their shares back. If too many short sellers are forced to close out positions at the same time, they push up demand for the stock, increasing price and deepening their losses. When this happens, it's called a short squeeze. In the eyes of the public who mostly go long buying stock, short sellers are often reviled. However, some people and many short sellers believe they are providing balance to the market and preventing it sometimes from getting ahead of itself. [Disambiguation: A short sale in the stock market is not related to the real estate concept of a short sale, which is when a property owner sells his property for less than he owes the bank.] Additional references:",
"title": ""
},
{
"docid": "299211",
"text": "\"-Alain Wertheimer I'm a hobbyist... Most (probably all) of those older items were sold both prior to my establishing the LLC This is a hobby of yours, this is not your business. You purchased all of these goods for your pleasure, not for their future profit. The later items that you bought after your LLC was establish served both purposes (perks of doing what you love). How should I go about reporting this income for the items I don't have records for how much I purchased them for? There's nothing you can do. As noted above, these items (if you were to testify in court against the IRS). \"\"Losses from the sale of personal-use property, such as your home or car, aren't tax deductible.\"\" Source Do I need to indicate 100% of the income because I can't prove that I sold it at a loss? Yes, if you do not have previous records you must claim a 100% capital gain. Source Addition: As JoeTaxpayer has mentioned in the comments, the second source I posted is for stocks and bonds. So at year begin of 2016, I started selling what I didn't need on eBay and on various forums [January - September]. Because you are not in the business of doing this, you do not need to explain the cost; but you do need to report the income as Gross Income on your 1040. Yes, if you bought a TV three years ago for a $100 and sold it for $50, the IRS would recognize you earning $50. As these are all personal items, they can not be deducted; regardless of gain or loss. Source Later in the year 2016 (October), I started an LLC (October - December) If these are items that you did not record early in the process of your LLC, then it is reported as a 100% gain as you can not prove any business expenses or costs to acquire associated with it. Source Refer to above answer. Refer to above answer. Conclusion Again, this is a income tax question that is split between business and personal use items. This is not a question of other's assessment of the value of the asset. It is solely based on the instruments of the IRS and their assessment of gains and losses from businesses. As OP does not have the necessary documents to prove otherwise, a cost basis of $0 must be assumed; thus you have a 100% gain on sale.\"",
"title": ""
},
{
"docid": "207788",
"text": "\"You have a sequence of questions here, so a sequence of answers: If you stopped at the point where you had multiple wins with a net profit of $72, then you would pay regular income tax on that $72. It's a short term capital gain, which does not get special tax treatment, and the fact that you made it on multiple transactions does not matter. When you enter your next transaction that takes the hypothetical loss the question gets more complicated. In either case, you are paying a percentage on net gains. If you took a two year view in the second case and you don't have anything to offset your loss in the second year, then I guess you could say that you paid more tax than you won in the total sequence of trades over the two years. Although you picked a sequence of trades where it does not appear to play, if you're going to pursue this type of strategy then you are likely at some point to run into a case where the \"\"wash sale\"\" rules apply, so you should be aware of that. You can find information on this elsewhere on this site and also, for example, here: http://www.marketwatch.com/story/understanding-the-wash-sale-rules-2015-03-02 Basically these rules require you to defer recording a loss under some circumstances where you have rapid wins and losses on \"\"substantially identical\"\" securities. EDIT A slight correction, you can take part of your losses in the second year even if you have no off-setting gain. From the IRS: If your capital losses exceed your capital gains, the amount of the excess loss that you can claim on line 13 of Form 1040 to lower your income is the lesser of $3,000, ($1,500 if you are married filing separately)\"",
"title": ""
},
{
"docid": "193485",
"text": "\"A nondividend distribution is typically a return of capital; in other words, you're getting money back that you've contributed previously (and thus would have been taxed upon in previous years when those funds were first remunerated to you). Nondividend distributions are nontaxable, so they do not represent income from capital gains, but do effect your cost basis when determining the capital gain/loss once that capital gain/loss is realized. As an example, publicly-traded real estate investment trusts (REITs) generally distribute a return of capital back to shareholders throughout the year as a nondividend distribution. This is a return of a portion of the shareholder's original capital investment, not a share of the REITs profits, so it is simply getting a portion of your original investment back, and thus, is not income being received (I like to refer to it as \"\"new income\"\" to differentiate). However, the return of capital does change the cost basis of the original investment, so if one were to then sell the shares of the REIT (in this example), the basis of the original investment has to be adjusted by the nondividend distributions received over the course of ownership (in other words, the cost basis will be reduced when the shares are sold). I'm wondering if the OP could give us some additional information about his/her S-Corp. What type of business is it? In the course of its business and trade activity, does it buy and sell securities (stocks, etc.)? Does it sell assets or business property? Does it own interests in other corporations or partnerships (sales of those interests are one form of capital gain). Long-term capital gains are taxed at rates lower than ordinary income, but the IRS has very specific rules as to what constitutes a capital gain (loss). I hate to answer a question with a question, but we need a little more information before we can weigh-in on whether you have actual capital gains or losses in the course of your S-Corporation trade.\"",
"title": ""
},
{
"docid": "437907",
"text": "The dividend tax credit is not applicable to foreign dividend income, so you would be taxed fully on every dollar of that income. When you sell a stock, there will be a capital gain or capital loss depending on if it gained or lost value, after accounting for the Adjusted Cost Base. You only pay income tax on half of the amount earned through capital gains, and if you have losses, you can use them to offset other investments that had capital gains (or carry forward to offset gains in the future). The dividends from US stocks are subject to a 15% withholding tax that gets paid to the IRS automatically when the dividends are issued. If the stocks are held in an RRSP, they are exempt from the withholding tax. If held in a non-registered account, you can be reimbursed for the tax by claiming the foreign tax credit that you linked to. If held in a TFSA or RESP, the withholding tax cannot be recovered. Also, if you are not directly holding the stocks, and instead buy a mutual fund or ETF that directly holds the stocks, then the RRSP exemption no longer applies, but the foreign tax credit is still claimable for a non-registered account. If the mutual fund or ETF does not directly hold stocks, and instead holds one or more ETFs, there is no way to recover the withholding tax in any type of account.",
"title": ""
},
{
"docid": "536610",
"text": "\"The wash sale rule only applies when the sale in question is at a loss. So the rule does not apply at all to your cases 3, 4, 7, 8, 11, 12, 15, and 16, which all start with a gain. You get a capital gain at the first sale and then a separately computed gain / loss at the second sale, depending on the case, BUT any gain or loss in the IRA is not a taxable event due to the usual tax-advantaged rules for the IRA. The wash sale does not apply to \"\"first\"\" sales in your IRA because there is no taxable gain or loss in that case. That means that you wouldn't be seeking a deduction anyway, and there is nothing to get rolled into the repurchase. This means that the rule does not apply to 1-8. For 5-8, where the second sale is in your brokerage account, you have a \"\"usual\"\" capital gain / loss as if the sale in the IRA didn't happen. (For 1-4, again, the second sale is in the IRA, so that sale is not taxable.) What's left are 9-10 (Brokerage -> IRA) and 13-14 (Brokerage -> Brokerage). The easier two are 13-14. In this case, you cannot take a capital loss deduction for the first sale at a loss. The loss gets added to the basis of the repurchase instead. When you ultimately close the position with the second sale, then you compute your gain or loss based on the modified basis. Note that this means you need to be careful about what you mean by \"\"gain\"\" or \"\"loss\"\" at the second sale, because you need to be careful about when you account for the basis adjustment due to the wash sale. Example 1: All buys and sells are in your brokerage account. You buy initially at $10 and sell at $8, creating a $2 loss. But you buy again within the wash sale window at $9 and sell that at $12. You get no deduction after the first sale because it's wash. You have a $1 capital gain at the second sale because your basis is $11 = $9 + $2 due to the $2 basis adjustment from wash sale. Example 2: Same as Example 1, except that final sale is at $8 instead of at $12. In this case you appear to have taken a $2 loss on the first buy-sell and another $1 loss on the second buy-sell. For taxes however, you cannot claim the loss at the first sale due to the wash. At the second sale, your basis is still $11 (as in Example 1), so your overall capital loss is the $3 dollars that you might expect, computed as the $8 final sale price minus the $11 (wash-adjusted) basis. Now for 9-10 (Brokerage->IRA), things are a little more complicated. In the IRA, you don't worry about the basis of individual stocks that you hold because of the way that tax advantages of those accounts work. You do need to worry about the basis of the IRA account as a whole, however, in some cases. The most common case would be if you have non-deductable contributions to your traditional IRA. When you eventually withdraw, you don't pay tax on any distributions that are attributable to those nondeductible contributions (because you already paid tax on that part). There are other cases where basis of your account matters, but that's a whole question in itself - It's enough for now to understand 1. Basis in your IRA as a whole is a well-defined concept with tax implications, and 2. Basis in individual holdings within your account don't matter. So with the brokerage-IRA wash sale, there are two questions: 1. Can you take the capital loss on the brokerage side? 2. If no because of the wash sale, does this increase the basis of your IRA account (as a whole)? The answer to both is \"\"no,\"\" although the reason is not obvious. The IRS actually put out a Special Bulletin to answer the question specifically because it was unclear in the law. Bottom line for 9-10 is that you apparently are losing your tax deduction completely in that case. In addition, if you were counting on an increase in the basis of your IRA to avoid early distribution penalties, you don't get that either, which will result in yet more tax if you actually take the early distribution. In addition to the Special Bulletin noted above, Publication 550, which talks about wash sale rules for individuals, may also help some.\"",
"title": ""
},
{
"docid": "426960",
"text": "\"Since you did not treat the house as a QBU, you have to use USD as your functional currency. To calculate capital gains, you need to calculate the USD value at the time of purchase using the exchange rate at the time of purchase and the USD value at the time of sale using the exchange rate at the time of sale. The capital gain / loss is then the difference between the two. This link describes it in more detail and provides some references: http://www.maximadvisors.com/2013/06/foreign-residence/ That link also discusses additional potential complications if you have a mortgage on the house. This link gives more detail on the court case referenced in the above link: http://www.uniset.ca/other/cs5/93F3d26.html The court cases references Rev. Rul 54-105. This link from the IRS has some details from that (https://www.irs.gov/pub/irs-wd/0303021.pdf): Rev. Rul. 54-105, 1954-1 C.B. 12, states that for purposes of determining gain, the basis and selling price of property acquired by a U.S. citizen living in a foreign country should be expressed in United States dollars at the rates of exchange prevailing as of the dates of purchase and sale of the property, respectively. The text of this implies it is for U.S. citizen is living in a foreign country, but the court case makes it clear that it also applies in your scenario (house purchased while living abroad but now residing in the US): Appellants agree that the 453,374 pounds received for their residence should be translated into U.S. dollars at the $1.82 exchange rate prevailing at the date of sale. They argue, however, that the 343,147 pound adjusted cost basis of the residence, consisting of the 297,500 pound purchase price and the 45,647 pounds paid for capital improvements, likewise should be expressed in U.S. dollar terms as of the date of the sale. Appellants correctly state that, viewed “in the foreign currency in which it was transacted,” the purchase generated a 110,227 pound gain as of the date of the sale, which translates to approximately $200,000 at the $1.82 per pound exchange rate. ... However fair and reasonable their argument may be, it amounts to an untenable attempt to convert their “functional currency” from the U.S. dollar to the pound sterling. ... Under I.R.C. § 985(b)(1), use of a functional currency other than the U.S. dollar is restricted to qualified business units (\"\"QBU\"\"s). ... appellants correctly assert that their residence was purchased “for a pound-denominated value” while they were “living and working in a pound-denominated economy,” ... And since appellants concede that the purchase and sale of their residence was not carried out by a QBU, the district court properly rejected their plea to treat the pound as their functional currency.\"",
"title": ""
},
{
"docid": "366560",
"text": "Your question is missing too much to be answered directly. Instead - here are some points to consider. Short term gains taxed at your marginal rates, whereas long term gains have preferable capital gains rates (up to 20% tax rate, instead of your marginal rate). So if you're selling at gain, you might want to consider to sell FIFO and pay lower capital gains tax rate instead of the short term marginal rate. If you're selling at loss and have other short term gains, you would probably be better selling LIFO, so that the loss could offset other short term gains that you might have. If you're selling at loss and don't have short term gains to offset, you can still offset your long term gains with short term losses, but the tax benefit will be lower. In this case - FIFO might be a better choice again. If you're selling at loss, beware of the wash sale rules, as you might not be able to deduct the loss if you buy/sell within too short a window.",
"title": ""
},
{
"docid": "350555",
"text": "Capital gain distribution is not capital gain on sale of stock. If you have stock sales (Schedule D) you should be filing 1040, not 1040A. Capital gain distributions are distributions from mutual funds/ETFs that are attributed to capital gains of the funds (you may not have actually received the distribution, but you still may have gain attributed to you). It is reported on 1099-DIV, and if it is 0 - then you don't have any. If you sold a stock, your broker should have given you 1099-B (which is not the same as 1099-DIV, but may be consolidated by your broker into one large PDF and not provided separately). On 1099-B the sales proceeds are recorded, and if you purchased the stock after 2011 - the cost basis is also recorded. The difference between the proceeds and the cost basis is your gain (or loss, if it is negative). Fees are added to cost basis.",
"title": ""
},
{
"docid": "525337",
"text": "Purchases and sales from the same trade date will both settle on the same settlement date. They don't have to pay for their purchases until later either. Because HFT typically make many offsetting trades -- buying, selling, buying, selling, buying, selling, etc -- when the purchases and sales settle, the amount they pay for their purchases will roughly cancel with the amount they receive for their sales (the difference being their profit or loss). Margin accounts and just having extra cash around can increase their ability to have trades that do not perfectly offset. In practice, the HFT's broker will take a smaller amount of cash (e.g. $1 million) as a deposit of capital, and will then allow the HFT to trade a larger amount of stock value long or short (e.g. $10 million, for 10:1 leverage). That $1 million needs to be enough to cover the net profit/loss when the trades settle, and the broker will monitor this to ensure that deposit will be enough.",
"title": ""
},
{
"docid": "46791",
"text": "\"ECI is relevant to non-resident aliens who are engaged in trade or business in the US. For that, you have to be present in the US, to begin with, or to own a business or property in the US. So the people to whom it is relevant are non-resident aliens in the US or business/property owners, not foreign contractors. From the IRS: The following categories of income are usually considered to be connected with a trade or business in the United States. You are considered to be engaged in a trade or business in the United States if you are temporarily present in the United States as a nonimmigrant on an \"\"F,\"\" \"\"J,\"\" \"\"M,\"\" or \"\"Q\"\" visa. The taxable part of any U.S. source scholarship or fellowship grant received by a nonimmigrant in \"\"F,\"\" \"\"J,\"\" \"\"M,\"\" or \"\"Q\"\" status is treated as effectively connected with a trade or business in the United States. If you are a member of a partnership that at any time during the tax year is engaged in a trade or business in the United States, you are considered to be engaged in a trade or business in the United States. You usually are engaged in a U.S. trade or business when you perform personal services in the United States. If you own and operate a business in the United States selling services, products, or merchandise, you are, with certain exceptions, engaged in a trade or business in the United States. For example, profit from the sale in the United States of inventory property purchased either in this country or in a foreign country is effectively connected trade or business income. Gains and losses from the sale or exchange of U.S. real property interests (whether or not they are capital assets) are taxed as if you are engaged in a trade or business in the United States. You must treat the gain or loss as effectively connected with that trade or business. Income from the rental of real property may be treated as ECI if the taxpayer elects to do so.\"",
"title": ""
}
] |
886
|
One in two surgical randomized controlled trials are discontinued early.
|
[
{
"docid": "6477536",
"text": "OBJECTIVE To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery. DESIGN Cross sectional observational study of registered and published trials. SETTING Randomised controlled trials of interventions in patients undergoing a surgical procedure. DATA SOURCES The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword \"surgery\". Recruitment status was extracted from the ClinicalTrials.gov database. A systematic search for studies published in peer reviewed journals was performed; if they were not found, results posted on the ClinicalTrials.gov results database were sought. Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed. MAIN OUTCOME MEASURES Trial discontinuation before completion and non-publication after completion. Logistic regression was used to determine the effect of funding source on publication status, with adjustment for intervention type and trial size. RESULTS Of 818 registered trials found using the keyword \"surgery\", 395 met the inclusion criteria. Of these, 21% (81/395) were discontinued early, most commonly owing to poor recruitment (44%, 36/81). The remaining 314 (79%) trials proceeded to completion, with a publication rate of 66% (208/314) at a median time of 4.9 (interquartile range 4.0-6.0) years from study completion to publication search. A further 6% (20/314) of studies presented results on ClinicalTrials.gov without a corresponding peer reviewed publication. Industry funding did not affect the rate of discontinuation (adjusted odds ratio 0.91, 95% confidence interval 0.54 to 1.55) but was associated with a lower odds of publication for completed trials (0.43, 0.26 to 0.72). Investigators' email addresses for trials with an uncertain fate were identified for 71.4% (10/14) of discontinued trials and 83% (101/122) of unpublished studies. Only 43% (6/14) and 20% (25/122) replies were received. Email responses for completed trials indicated 11 trials in press, five published studies (four in non-indexed peer reviewed journals), and nine trials remaining unpublished. CONCLUSIONS One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks. To promote future efficiency and transparency, changes are proposed to research governance frameworks to overcome these concerns.",
"title": "Discontinuation and non-publication of surgical randomised controlled trials: observational study"
}
] |
[
{
"docid": "9967265",
"text": "BACKGROUND Patent ductus arteriosus (PDA) with significant left to right shunt in preterm infants increases morbidity and mortality. Early closure of the ductus arteriosus may be achieved pharmacologically using cyclooxygenase inhibitors or by surgery. The efficacy of both treatment modalities is well established. However, the preferred initial treatment of a symptomatic PDA in a preterm infant, surgical ligation or treatment with indomethacin, has not been well established. OBJECTIVES To compare the effect of surgical ligation of PDA vs. medical treatment with cyclooxygenase inhibitors (using indomethacin, ibuprofen, or mefenamic acid), each used as the initial treatment, on neonatal mortality in preterm infants with a symptomatic PDA. SEARCH STRATEGY The standard search strategy of the Cochrane Neonatal Review Group was used. This included search of electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - July 2007), CINAHL (1982 - July 2007), EMBASE (1980 - July 2007); and hand search of abstracts of Pediatric Academic Societies annual meetings published in Pediatric Research (1990 - April 2002) or on line from May 2002 -July 2007. No language restrictions were applied. SELECTION CRITERIA All trials 1) using randomized or quasi-randomized patient allocation, 2) in preterm infants < 37 weeks gestational age or low-birth-weight infants (< 2500 grams) with symptomatic PDA in the neonatal period (< 28 days) and 3) comparing surgical ligation with medical treatment with cyclooxygenase inhibitors, each used as the initial treatment for closure of PDA. DATA COLLECTION AND ANALYSIS Assessment of methodological quality and extraction of data for included trials was undertaken independently by the authors. RevMan 4.1 was used for analysis of the data. MAIN RESULTS Only one study, trial B in the report of Gersony 1983, was found eligible. No additional studies were identified in the literature searches performed in July 2007. The trial compared the effect of surgical ligation of PDA vs. medical treatment with indomethacin, each used as the primary treatment. No trials comparing surgery to other cyclooxygenase inhibitors (ibuprofen, mefenamic acid) were found. Trial B of Gersony 1983 enrolled 154 infants. The study found no statistically significant difference between surgical closure and indomethacin treatment in mortality during hospital stay, chronic lung disease, other bleeding, necrotizing enterocolitis, sepsis, creatinine level, or intraventricular hemorrhage. There was a statistically significant increase in the surgical group in incidence of pneumothorax [RR 2.68 (95% CI 1.45, 4.93); RD 0.25 (95% CI 0.11, 0.38); NNH 4 (95% CI 3, 9)] and retinopathy of prematurity stage III and IV [RR 3.80 (95% CI 1.12, 12.93); RD 0.11 (95% CI 0.02, 0.20), NNH 9 (95% CI 5, 50] compared to the indomethacin group. There was as expected a statistically significant decrease in failure of ductal closure rate in the surgical group as compared to the indomethacin group: [RR 0.04 (95% CI 0.01, 0.27); RD -0.32 (95% CI -0.43, -0.21), NNT 3 (95% CI 2, 4)]. AUTHORS' CONCLUSIONS The data regarding net benefit/harm are insufficient to make a conclusion as to whether surgical ligation or medical treatment with indomethacin is preferred as initial treatment for symptomatic PDA in preterm infants. It should be noted that three recent observational studies indicated an increased risk for one or more of the following outcomes associated with PDA ligation; chronic lung disease, retinopathy of prematurity and neurosensory impairment . It is possible that the duration of the \"waiting-time\" and transport to another facility with surgical capacity to have the PDA ligated could adversely affect outcomes, as could the perioperative care.",
"title": "Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants."
},
{
"docid": "26067999",
"text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l",
"title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement"
},
{
"docid": "9754530",
"text": "Like other branches of surgery, Urology has encountered major challenges in aligning the research processes by which new interventions are assessed with the principles of Evidence-Based Medicine. This article explains the IDEAL framework and recommendations and illustrates how they might affect the evaluation of current controversial urological procedures. From an inside perspective, we provide an overview of the efforts of the IDEAL Working Group to date with special emphasis on the field of Urology. There are clear differences between drugs and interventions in the natural history of innovations. Since the conventional framework for conducting trials of new treatments is largely based on the former, the evaluation of surgical innovations using the same template can encounter significant problems. Difficulties in performing randomized controlled trials of surgical techniques and the persistence of the case series as an important feature of the scientific literature have been the two most controversial aspects of this mismatch between the subject of research and the methodology used. The IDEAL framework provides a description of the process of innovation and development for surgical trials, and the associated recommendations provide a suggested alternative approach to developing study designs, which are appropriate for the specific problems of new techniques. IDEAL provides a new framework for surgical innovation that was developed with broad stakeholder input from the surgical community and is expected to have a transformative impact on the way that urologists perform clinical research.",
"title": "The IDEAL recommendations and urological innovation"
},
{
"docid": "7098463",
"text": "CONTEXT Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes. OBJECTIVE To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. DESIGN, SETTING, AND PARTICIPANTS Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes. INTERVENTIONS Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. MAIN OUTCOME MEASURES Remission of type 2 diabetes (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat. RESULTS Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval, 2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD) of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R2 = 0.46, P < .001) and lower baseline HbA1c levels (combined R2 = 0.52, P < .001). There were no serious complications in either group. CONCLUSIONS Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss. These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed. TRIAL REGISTRATION actr.org Identifier: ACTRN012605000159651.",
"title": "Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial."
},
{
"docid": "8642784",
"text": "OBJECTIVE To assess the efficacy of various controlled ovarian hyperstimulation (COH) regimens in the prior poor-responder patient preparing for assisted reproductive techniques. DESIGN English-language literature review. PATIENT(S) Candidates for assisted reproductive techniques who had been defined as having a prior suboptimal response to standard COH regimens. INTERVENTION(S) A variety of regimes are reviewed, including increased gonadotropin doses, change of gonadotropins, adjunctive growth hormone (GH), luteal phase (long) GnRH agonist (GnRH-a) initiation, early follicular phase (flare) GnRH-a initiation, low-dose luteal phase (ultrashort) GnRH-a initiation, progestin pretreatment, and microdose flare GnRH-a initiation. MAIN OUTCOME MEASURE(S) Maximal serum E(2) levels, follicular development, dose, and duration of gonadotropin therapy, cycle cancellation rates, oocytes retrieved, embryos transferred, and clinical and ongoing pregnancy rates. RESULT(S) A lack of uniformity in definition of the poor responder and of prospective randomized trials make data interpretation somewhat difficult. Of the varied strategies proposed, those that seem to be more uniformly beneficial are microdose GnRH-a flare and late luteal phase initiation of a short course of low-dose GnRH-a discontinued before COH. CONCLUSION(S) No single regimen will benefit all poor responders. General acceptance of uniform definitions and performance of large-scale prospective randomized trials are critical. Development of a reliable precycle screen will allow effective differentiation among normal responders, poor responders, and those who will not conceive with their own oocytes.",
"title": "Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques."
},
{
"docid": "11117498",
"text": "Solitary metastatic brain tumors are the most common intracranial neoplasms encountered by neurosurgeons. Surgical resection of brain metastasis with whole brain radiotherapy (WBR) significantly increases survival in comparison with WBR alone. Stereotactic radiosurgery (SR) seems to provide results that are similar to those of surgical resection. To analyze the economic efficiency of these different treatments, we compared the results of surgical resection and SR as reported in the medical literature between 1974 and 1994. We included studies in which: 1) at least 75% of patients received WBR; 2) study dates were in the computed tomography era (after 1975); 3) operative morbidity, mortality, and median survival were reported; 4) study dates were not included in a more recent update or review; 5) tumor histologies were reported; and 6) the cobalt-60 gamma unit was used for SR. Three surgical resection studies and one SR study met all entry requirements. The WBR baseline was developed from two prospective, randomized trials and used for incremental cost effectiveness analysis. We developed a model of typical resource usage for uncomplicated procedures, reported complications, and subsequent craniotomies (for recurrent tumor or radiation necrosis) for both treatment options. Costs were estimated from the societal viewpoint using the 1992 Medicare Provider Analysis and Review database with average cost:charge ratios for surgery and WBR. A survey of capital and operating costs from five sites was used for radiosurgery. Our analysis revealed that radiosurgery had a lower uncomplicated procedure cost ($20,209 versus $27,587), a lower average complication cost per case ($2,534 versus $2,874), and a lower total cost per procedure ($22,743 versus $30,461), was more cost effective ($24,811 versus $32,149 per life year), and had a better incremental cost effectiveness ($40,648 versus $52,384 per life year) than surgical resection. A sensitivity analysis revealed that large changes in key assumptions would be required to change the analysis outcome. Equalization of the incremental cost effectiveness of the two treatments would require one of the following: 1) a 38.7% reduction in SR annual case volume, 2) a 34.7% increase in SR procedure cost, 3) a 18.8% reduction in surgical resection procedure cost, 4) a 240.5% increase in SR morbidity cost, 5) a 12.7% reduction in SR median survival, 6) a 16.8% increase in surgical resection median survival. Elimination of all surgical resection morbidity cost would still result in superior incremental cost effectiveness for SR.(ABSTRACT TRUNCATED AT 400 WORDS)",
"title": "The cost effectiveness of stereotactic radiosurgery versus surgical resection in the treatment of solitary metastatic brain tumors."
},
{
"docid": "6112053",
"text": "Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. Methods: The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: ‘withdrawal symptoms' OR ‘withdrawal syndrome' OR ‘discontinuation syndrome' OR ‘discontinuation symptoms', AND ‘SSRI' OR ‘serotonin' OR ‘antidepressant' OR ‘paroxetine' OR ‘fluoxetine' OR ‘sertraline' OR ‘fluvoxamine' OR ‘citalopram' OR ‘escitalopram'. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. Results: There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. Conclusions: Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term ‘discontinuation syndrome' that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome'.",
"title": "Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review"
},
{
"docid": "45336190",
"text": "OBJECTIVE To evaluate the safety, tolerability, and amyloid beta (Abeta) response to the gamma-secretase inhibitor LY450139 in Alzheimer disease. DESIGN Multicenter, randomized, double-blind, dose-escalation, placebo-controlled trial. SETTING Community-based clinical research centers. Patients Fifty-one individuals with mild to moderate Alzheimer disease were randomized to receive placebo (n=15) or LY450139 (100 mg [n=22] or 140 mg [n=14]), with 43 completing the treatment phase. Intervention The LY450139 groups received 60 mg/d for 2 weeks, then 100 mg/d for 6 weeks, and then either 100 or 140 mg/d for 6 additional weeks. MAIN OUTCOME MEASURES Primary outcome measures were adverse events, plasma and cerebrospinal fluid Abeta levels, vital signs, electrocardiographic data, and laboratory safety test results. Secondary outcome measures included the Alzheimer's Disease Assessment Scale cognitive subscale and the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale. RESULTS Group differences were seen in skin and subcutaneous tissue concerns (P=.05), including 3 possible drug rashes and 3 reports of hair color change in the treatment groups. There were 3 adverse event-related discontinuations, including 1 transient bowel obstruction. The plasma Abeta(40) concentration was reduced by 58.2% for the 100-mg group and 64.6% for the 140-mg group (P<.001). No significant reduction was seen in cerebrospinal fluid Abeta levels. No group differences were seen in cognitive or functional measures. CONCLUSIONS LY450139 was generally well tolerated at doses of up to 140 mg/d for 14 weeks, with several findings indicating the need for close clinical monitoring in future studies. Decreases in plasma Abeta concentrations were consistent with inhibition of gamma-secretase. Trial Registration clinicaltrials.gov Identifier: NCT00244322.",
"title": "Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease."
},
{
"docid": "7613033",
"text": "Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50% or more reduction in the risk of CRC commencing five years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin's anticancer effect require further investigation.",
"title": "Aspirin in the chemoprevention of colorectal neoplasia: an overview."
},
{
"docid": "18025240",
"text": "OBJECTIVE To summarise the effects of anthelmintic drug treatment on growth and cognitive performance in children. DATA SOURCES Electronic databases: Cochrane Infectious Diseases Group controlled trial register, Cochrane controlled trials register, Embase, and Medline. Citations of all identified trials. Contact with the World Health Organization and field researchers. REVIEW METHODS Systematic review of randomised controlled trials in children aged 1-16 that compared anthelmintic treatment with placebo or no treatment. Assessment of validity and data abstraction conducted independently by two reviewers. MAIN OUTCOME MEASURES Growth and cognitive performance. RESULTS Thirty randomised controlled trials in more than 15 000 children were identified. Effects on mean weight were unremarkable, and heterogeneity was evident in the results. There were some positive effects on mean weight change in the trials reporting this outcome: after a single dose (any anthelmintic) the pooled estimates were 0.24 kg (95% confidence interval 0.15 kg to 0. 32 kg; fixed effects model assumed) and 0.38 kg (0.01 kg to 0.77 kg; random effects model assumed). Results from trials of multiple doses showed mean weight change in up to one year of follow up of 0.10 kg (0.04 kg to 0.17 kg; fixed effects) or 0.15 kg (0.00 to 0.30; random effects). At more than one year of follow up, mean weight change was 0.12 kg (-0.02 kg to 0.26 kg; fixed effects) and 0.43 (-0.61 to 1. 47; random effects). Results from studies of cognitive performance were inconclusive. CONCLUSIONS There is some limited evidence that routine treatment of children in areas where helminths are common has effects on weight gain, but this is not consistent between trials. There is insufficient evidence as to whether this intervention improves cognitive performance.",
"title": "Effects of treatment for intestinal helminth infection on growth and cognitive performance in children: systematic review of randomised trials."
},
{
"docid": "8756719",
"text": "This study represents the first phase III trial of the safety, tolerability, and effectiveness of tafenoquine for malaria prophylaxis. In a randomized (3:1), double-blinded study, Australian soldiers received weekly malaria prophylaxis with 200 mg tafenoquine (492 subjects) or 250 mg mefloquine (162 subjects) for 6 months on a peacekeeping deployment to East Timor. After returning to Australia, tafenoquine-receiving subjects received a placebo and mefloquine-receiving subjects received 30 mg primaquine daily for 14 days. There were no clinically significant differences between hematological and biochemical parameters of the treatment groups. Treatment-related adverse events for the two groups were similar (tafenoquine, 13.4%; mefloquine, 11.7%). Three subjects on tafenoquine (0.6%) and none on mefloquine discontinued prophylaxis because of possible drug-related adverse events. No diagnoses of malaria occurred for either group during deployment, but 4 cases (0.9%) and 1 case (0.7%) of Plasmodium vivax infection occurred among the tafenoquine and mefloquine groups, respectively, up to 20 weeks after discontinuation of medication. In a subset of subjects recruited for detailed safety assessments, treatment-related mild vortex keratopathy was detected in 93% (69 of 74) of tafenoquine subjects but none of the 21 mefloquine subjects. The vortex keratopathy was not associated with any effect on visual acuity and was fully resolved in all subjects by 1 year. Tafenoquine appears to be safe and well tolerated as malaria prophylaxis. Although the volunteers' precise exposure to malaria could not be proven in this study, tafenoquine appears to be a highly efficacious drug for malaria prophylaxis.",
"title": "Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects."
},
{
"docid": "9754833",
"text": "OBJECTIVES To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up. DESIGN Randomised controlled trial. SETTING Nine Dutch hospitals. PARTICIPANTS 283 patients with 6-12 weeks of sciatica. INTERVENTIONS Early surgery or an intended six months of continued conservative treatment, with delayed surgery if needed. MAIN OUTCOME MEASURES Scores from Roland disability questionnaire for sciatica, visual analogue scale for leg pain, and Likert self rating scale of global perceived recovery. RESULTS Of the 141 patients assigned to undergo early surgery, 125 (89%) underwent microdiscectomy. Of the 142 patients assigned to conservative treatment, 62 (44%) eventually required surgery, seven doing so in the second year of follow-up. There was no significant overall difference between treatment arms in disability scores during the first two years (P=0.25). Improvement in leg pain was faster for patients randomised to early surgery, with a significant difference between \"areas under the curves\" over two years (P=0.05). This short term benefit of early surgery was no longer significant by six months and continued to narrow between six months and 24 months. Patient satisfaction decreased slightly between one and two years for both groups. At two years 20% of all patients reported an unsatisfactory outcome. CONCLUSIONS Early surgery achieved more rapid relief of sciatica than conservative care, but outcomes were similar by one year and these did not change during the second year. TRIAL REGISTRY ISRCT No 26872154.",
"title": "Prolonged conservative care versus early surgery in patients with sciatica caused by lumbar disc herniation: two year results of a randomised controlled trial."
},
{
"docid": "44048701",
"text": "IMPORTANCE The need for surgery for the majority of patients with displaced proximal humeral fractures is unclear, but its use is increasing. OBJECTIVE To evaluate the clinical effectiveness of surgical vs nonsurgical treatment for adults with displaced fractures of the proximal humerus involving the surgical neck. DESIGN, SETTING, AND PARTICIPANTS A pragmatic, multicenter, parallel-group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%] were white) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 within 3 weeks after sustaining a displaced fracture of the proximal humerus involving the surgical neck. Patients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data. The data for 231 patients (114 in surgical group and 117 in nonsurgical group) were included in the primary analysis. INTERVENTIONS Fracture fixation or humeral head replacement were performed by surgeons experienced in these techniques. Nonsurgical treatment was sling immobilization. Standardized outpatient and community-based rehabilitation was provided to both groups. MAIN OUTCOMES AND MEASURES Primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months. Sample size was based on a minimal clinically important difference of 5 points for the Oxford Shoulder Score. Secondary outcomes were the Short-Form 12 (SF-12), complications, subsequent therapy, and mortality. RESULTS There was no significant mean treatment group difference in the Oxford Shoulder Score averaged over 2 years (39.07 points for the surgical group vs 38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at individual time points. There were also no significant between-group differences over 2 years in the mean SF-12 physical component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39 points]; P = .18); the mean SF-12 mental component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to surgery or shoulder fracture (30 patients in surgical group vs 23 patients in nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11 patients in both groups), and increased or new shoulder-related therapy (7 patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27). Ten medical complications (2 cardiovascular events, 2 respiratory events, 2 gastrointestinal events, and 4 others) occurred in the surgical group during the postoperative hospital stay. CONCLUSIONS AND RELEVANCE Among patients with displaced proximal humeral fractures involving the surgical neck, there was no significant difference between surgical treatment compared with nonsurgical treatment in patient-reported clinical outcomes over 2 years following fracture occurrence. These results do not support the trend of increased surgery for patients with displaced fractures of the proximal humerus. TRIAL REGISTRATION isrctn.com Identifier: ISRCTN50850043.",
"title": "Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial."
},
{
"docid": "19878070",
"text": "CONTEXT Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis. OBJECTIVE To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998. INTERVENTIONS Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low. MAIN OUTCOME MEASURES Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry. RESULTS The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41 % (95% confidence interval [CI], 18%-58%) over 3 years (11.3 % vs 16.3%; P= .003). A fracture reduction of 65% (95% CI, 38%-81 %) was observed after the first year (2.4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39% (95% CI, 6%-61 %) (5.2 % vs 8.4%; P = .02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1 %), femoral neck (1.6% vs -1.2%), femoral trochanter (3.3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo. CONCLUSIONS These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis.",
"title": "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group."
},
{
"docid": "3770750",
"text": "BACKGROUND The relation between sugar-sweetened beverages (SSBs) and body weight remains controversial. OBJECTIVE We conducted a systematic review and meta-analysis to summarize the evidence in children and adults. DESIGN We searched PubMed, EMBASE, and Cochrane databases through March 2013 for prospective cohort studies and randomized controlled trials (RCTs) that evaluated the SSB-weight relation. Separate meta-analyses were conducted in children and adults and for cohorts and RCTs by using random- and fixed-effects models. RESULTS Thirty-two original articles were included in our meta-analyses: 20 in children (15 cohort studies, n = 25,745; 5 trials, n = 2772) and 12 in adults (7 cohort studies, n = 174,252; 5 trials, n = 292). In cohort studies, one daily serving increment of SSBs was associated with a 0.06 (95% CI: 0.02, 0.10) and 0.05 (95% CI: 0.03, 0.07)-unit increase in BMI in children and 0.22 kg (95% CI: 0.09, 0.34 kg) and 0.12 kg (95% CI: 0.10, 0.14 kg) weight gain in adults over 1 y in random- and fixed-effects models, respectively. RCTs in children showed reductions in BMI gain when SSBs were reduced [random and fixed effects: -0.17 (95% CI: -0.39, 0.05) and -0.12 (95% CI: -0.22, -0.2)], whereas RCTs in adults showed increases in body weight when SSBs were added (random and fixed effects: 0.85 kg; 95% CI: 0.50, 1.20 kg). Sensitivity analyses of RCTs in children showed more pronounced benefits in preventing weight gain in SSB substitution trials (compared with school-based educational programs) and among overweight children (compared with normal-weight children). CONCLUSION Our systematic review and meta-analysis of prospective cohort studies and RCTs provides evidence that SSB consumption promotes weight gain in children and adults.",
"title": "Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis."
},
{
"docid": "20008796",
"text": "OBJECTIVE To report data relating to the informed uptake of screening tests. SEARCH STRATEGY Electronic databases, bibliographies and experts were used to identify relevant published and unpublished studies up until August 2000. INCLUSION CRITERIA RCTs, quasi-RCTs and controlled trials of interventions aimed at increasing the informed uptake of screening. All participants were eligible as defined by the entry criteria of individual programmes. Studies had to report actual uptake and meet three out of four criteria used to define informed uptake. DATA EXTRACTION AND SYNTHESIS Relevant studies were identified, data extracted and their validity assessed by two reviewers independently. Outcome data included screening uptake, knowledge, informed decision-making and attitudes to screening. A random-effects model was used to calculate individual relative risks and 95% confidence intervals. MAIN RESULTS Six controlled trials (five RCTs and one quasi-RCT), focusing on antenatal and prostate specific antigen screening, were included. All reported risks/benefits of screening and assessed knowledge. Two also assessed decision-making. Two reported risks/benefits to all randomized groups and evaluated different ways of presenting information. Neither found that interventions such as videos, information leaflets with decision trees, or touch screen computers conveyed any additional benefits over well-prepared leaflets. CONCLUSIONS There is some evidence to suggest that changing the format of informed choice interventions in screening does not alter knowledge, satisfaction or decisions about screening. It is not clear whether informed choice in screening affects uptake. More well-designed RCTs are required and further research should also be directed towards the development of a valid instrument for measuring all components of informed choice in screening.",
"title": "Increasing informed uptake and non-uptake of screening: evidence from a systematic review."
},
{
"docid": "33417012",
"text": "OBJECTIVE This study compared, in treatment and control groups, the phenomena of coaction, which is the probability that taking effective action on one behavior is related to taking effective action on a second behavior. METHODS Pooled data from three randomized trials of Transtheoretical Model (TTM) tailored interventions (n=9461), completed in the U.S. in 1999, were analyzed to assess coaction in three behavior pairs (diet and sun protection, diet and smoking, and sun protection and smoking). Odds ratios (ORs) compared the likelihood of taking action on a second behavior compared to taking action on only one behavior. RESULTS Across behavior pairs, at 12 and 24 months, the ORs for the treatment group were greater on an absolute basis than for the control group, with two being significant. The combined ORs at 12 and 24 months, respectively, were 1.63 and 1.85 for treatment and 1.20 and 1.10 for control. CONCLUSIONS The results of this study with addictive, energy balance and appearance-related behaviors were consistent with results found in three studies applying TTM tailoring to energy balance behaviors. Across studies, there was more coaction within the treatment group. Future research should identify predictors of coaction in more multiple behavior change interventions.",
"title": "Treated individuals who progress to action or maintenance for one behavior are more likely to make similar progress on another behavior: coaction results of a pooled data analysis of three trials."
},
{
"docid": "19205326",
"text": "BACKGROUND Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years. METHODS The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study. RESULTS Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit. CONCLUSIONS The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.",
"title": "Ten years' experience with alendronate for osteoporosis in postmenopausal women."
},
{
"docid": "24323695",
"text": "RATIONALE Up to 80% of patients with lung cancer have comorbid chronic obstructive pulmonary disease (COPD). Many of them are poor candidates for stage-specific lung cancer treatment due to diminished lung function and poor functional status, and many forego treatment. The negative effect of COPD may be moderated by pulmonologist-guided management. OBJECTIVES This study examined the association between pulmonologist management and the probability of receiving the recommended stage-specific treatment modality and overall survival among patients with non-small cell lung cancer (NSCLC) with preexisting COPD. METHODS Early- and advanced-stage NSCLC cases diagnosed between 2002 and 2005 with a prior COPD diagnosis (3-24 months before NSCLC diagnosis) were identified in Surveillance, Epidemiology, and End Results tumor registry data linked to Medicare claims. Study outcomes included receipt of recommended stage-specific treatment (surgical resection for early-stage NSCLC and chemotherapy for advanced-stage NSCLC [advNSCLC]) and overall survival. Pulmonologist management was considered present if one or more Evaluation and Management visit claims with pulmonologist specialty were observed within 6 months after NSCLC diagnosis. Stage-specific multivariate logistic regression tested association between pulmonologist management and treatment received. Cox proportional hazard models examined the independent association between pulmonologist care and mortality. Two-stage residual inclusion instrumental variable (2SRI-IV) analyses tested and adjusted for potential confounding based on unobserved factors or measurement error. MEASUREMENTS AND MAIN RESULTS The cohorts included 5,488 patients with early-stage NSCLC and 6,426 patients with advNSCLC disease with preexisting COPD. Pulmonologist management was recorded for 54.9% of patients with early stage NSCLC and 35.7% of patients with advNSCLC. Of those patients with pulmonologist involvement, 58.5% of patients with early NSCLC received surgical resection, and 43.6% of patients with advNSCLC received chemotherapy. Pulmonologist management post NSCLC diagnosis was associated with increased surgical resection rates (odds ratio, 1.26; 95% confidence interval, 1.11-1.45) for early NSCLC and increased chemotherapy rates (odds ratio, 1.88; 95% confidence interval, 1.67-2.10) for advNSCLC. Pulmonologist management was also associated with reduced mortality risk for patients with early-stage NSCLC but not AdvNSCLC. CONCLUSIONS Pulmonologist management had a positive association with rates of stage-specific treatment in both groups and overall survival in early-stage NSCLC. These results provide preliminary support for the recently published guidelines emphasizing the role of pulmonologists in lung cancer management.",
"title": "Pulmonologist involvement, stage-specific treatment, and survival in adults with non-small cell lung cancer and chronic obstructive pulmonary disease."
},
{
"docid": "26000593",
"text": "Most osteoporosis treatments have proven efficacy in reducing the risk of vertebral fractures, whereas evidence is less straightforward for prevention of non-vertebral fractures. Conclusions as to the efficacy of a treatment should be based primarily on analyses of the intention to treat (ITT) population rather than on exploratory subgroup analyses; however, non-vertebral anti-fracture efficacy has been largely derived by post-hoc subgroup analyses. This review and meta-analysis was performed to assess non-vertebral anti-fracture efficacy of several osteoporosis therapies, including a more stringent assessment of the ITT populations. Data on non-vertebral anti-fracture efficacy, a defined endpoint of the ITT analyses and confirmed by radiographs, were obtained from randomized, placebo-controlled, phase III clinical trials of at least 3-year duration. Meta-analyses were performed for the two bisphosphonates, alendronate and risedronate. Relative risks (RR), 95% confidence intervals (CI) and statistical significance for active treatment compared with placebo were calculated. Eleven clinical trials met the criteria for review, three of which showed statistically significant ( P ≤0.05) non-vertebral anti-fracture efficacy in the ITT population: two trials with risedronate and one trial with strontium. A meta-analysis showed significant reductions in the relative risk of non-vertebral fracture for both alendronate (RR=0.86; 95% CI: 0.76–0.97, P =0.012) and risedronate (RR=0.81; 95% CI: 0.71–0.92, P =0.001). Risedronate and strontium ranelate were the only treatments to show non-vertebral anti-fracture efficacy in this robust assessment of anti-fracture efficacy of osteoporosis therapy using ITT populations in trials of 3 years or more in duration. Risedronate was the only agent shown to demonstrate efficacy in more than one trial. Meta-analysis showed that both alendronate and risedronate provide non-vertebral anti-fracture efficacy.",
"title": "Effect of osteoporosis treatments on risk of non-vertebral fractures: review and meta-analysis of intention-to-treat studies"
},
{
"docid": "39903312",
"text": "BACKGROUND Experimental studies in animals and observational studies in humans suggest that regular aspirin use may decrease the risk of colorectal adenomas, the precursors to most colorectal cancers. METHODS We conducted a randomized, double-blind trial to determine the effect of aspirin on the incidence of colorectal adenomas. We randomly assigned 635 patients with previous colorectal cancer to receive either 325 mg of aspirin per day or placebo. We determined the proportion of patients with adenomas, the number of recurrent adenomas, and the time to the development of adenoma between randomization and subsequent colonoscopic examinations. Relative risks were adjusted for age, sex, cancer stage, the number of colonoscopic examinations, and the time to a first colonoscopy. The study was terminated early by an independent data and safety monitoring board when statistically significant results were reported during a planned interim analysis. RESULTS A total of 517 randomized patients had at least one colonoscopic examination a median of 12.8 months after randomization. One or more adenomas were found in 17 percent of patients in the aspirin group and 27 percent of patients in the placebo group (P=0.004). The mean (+/-SD) number of adenomas was lower in the aspirin group than the placebo group (0.30+/-0.87 vs. 0.49+/-0.99, P=0.003 by the Wilcoxon test). The adjusted relative risk of any recurrent adenoma in the aspirin group, as compared with the placebo group, was 0.65 (95 percent confidence interval, 0.46 to 0.91). The time to the detection of a first adenoma was longer in the aspirin group than in the placebo group (hazard ratio for the detection of a new polyp, 0.64; 95 percent confidence interval, 0.43 to 0.94; P=0.022). CONCLUSIONS Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer.",
"title": "A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer."
},
{
"docid": "22730024",
"text": "OBJECTIVE To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European). METHODS After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks. RESULTS In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [-2.8 (-4.9, -0.8) mmHg], whereas ramipril did not [+1.5 (-0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]. CONCLUSIONS Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intake.",
"title": "Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies."
},
{
"docid": "5402581",
"text": "CONTEXT Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease and other dementia; however, concerns have arisen about the increased risk for cerebrovascular adverse events, rapid cognitive decline, and mortality with their use. OBJECTIVE To assess the evidence for increased mortality from atypical antipsychotic drug treatment for people with dementia. DATA SOURCES MEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register (2005, Issue 1), meetings presentations (1997-2004), and information from the sponsors were searched using the terms for atypical antipsychotic drugs (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial. STUDY SELECTION Published and unpublished randomized placebo-controlled, parallel-group clinical trials of atypical antipsychotic drugs marketed in the United States to treat patients with Alzheimer disease or dementia were selected by consensus of the authors. DATA EXTRACTION Trials, baseline characteristics, outcomes, all-cause dropouts, and deaths were extracted by one reviewer; treatment exposure was obtained or estimated. Data were checked by a second reviewer. DATA SYNTHESIS Fifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis. CONCLUSIONS Atypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.",
"title": "Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials."
},
{
"docid": "41298619",
"text": "BACKGROUND Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation, yet controversy exists about their impact on kidney function. OBJECTIVES To examine the effects of HES on kidney function compared to other fluid resuscitation therapies in different patient populations. SEARCH STRATEGY We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference lists of articles. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs in which HES was compared to an alternate fluid therapy for the prevention or treatment of effective intravascular volume depletion. Primary outcomes were renal replacement therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as defined by the RIFLE criteria. Secondary outcomes included serum creatinine and creatinine clearance. DATA COLLECTION AND ANALYSIS Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. Authors were contacted when published data were incomplete. Preplanned sensitivity and subgroup analyses were performed after data were analysed with a random effects model. MAIN RESULTS The review included 34 studies (2607 patients). Overall, the RR of author-defined kidney failure was 1.50 (95% CI 1.20 to 1.87; n = 1199) and 1.38 for requiring RRT (95% CI 0.89 to 2.16; n = 1236) in HES treated individuals compared with other fluid therapies. Subgroup analyses suggested increased risk in septic patients compared to non-septic (surgical/trauma) patients. Non-septic patient studies were smaller and had lower event rates, so subgroup differences may have been due to lack of statistical power in these studies. Only limited data was obtained for analysis of kidney outcomes by the RIFLE criteria. Overall, methodological quality of studies was good but subjective outcomes were potentially biased because most studies were unblinded. AUTHORS' CONCLUSIONS Potential for increased risk of AKI should be considered when weighing the risks and benefits of HES for volume resuscitation, particularly in septic patients. Large studies with adequate follow-up are required to evaluate the renal safety of HES products in non-septic patient populations. RIFLE criteria should be applied to evaluate kidney function in future studies of HES and, where data is available, to re-analyse those studies already published. There is inadequate clinical data to address the claim that safety differences exist between different HES products.",
"title": "Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function."
},
{
"docid": "23670644",
"text": "BACKGROUND The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial. METHODS 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915. FINDINGS 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62.0%vs 136.9%, 75% decrease, 95% CI 42.4-107.4%; p<0.0001). 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0.0001), and five children (7%) in the diet group had greater than 90% seizure reduction compared with no controls (p=0.0582). There was no significant difference in the efficacy of the treatment between symptomatic generalised or symptomatic focal syndromes. The most frequent side-effects reported at 3-month review were constipation, vomiting, lack of energy, and hunger. INTERPRETATION The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy. FUNDING HSA Charitable Trust; Smiths Charity; Scientific Hospital Supplies; Milk Development Council.",
"title": "The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial."
},
{
"docid": "32777637",
"text": "BACKGROUND Concurrent use of multiple standing antipsychotics (antipsychotic polypharmacy) is increasingly common among both inpatients and outpatients. Although this has often been cited as a potential quality-of-care problem, reviews of research evidence on antipsychotic polypharmacy have not distinguished between appropriate versus inappropriate use. METHODS A MEDLINE search from 1966 to December 2007 was completed to identify studies comparing changes in symptoms, functioning, and/or side effects between patients treated with multiple antipsychotics and patients treated with a single antipsychotic. The studies were reviewed in two groups on the basis of whether prescribing was concordant with guideline recommendations for multiple-antipsychotic use. RESULTS A review of the literature, including three randomized controlled trials, found no support for the use of antipsychotic polypharmacy in patients without an established history of treatment resistance to multiple trials of monotherapy. In patients with a history of treatment resistance to multiple monotherapy trials, limited data support antipsychotic polypharmacy, but positive outcomes were primarily found in studies of clozapine augmented with a second-generation antipsychotic. DISCUSSION Research evidence is consistent with the goal of avoiding antipsychotic polypharmacy in patients who lack guideline-recommended indications for its use. The Joint Commission is implementing a core measure set for Hospital-Based Inpatient Psychiatric Services. Two of the measures address antipsychotic polypharmacy. The first measure assesses the overall rate. The second measure determines whether clinically appropriate justification has been documented supporting the use of more than one antipsychotic medication.",
"title": "When is antipsychotic polypharmacy supported by research evidence? Implications for QI."
},
{
"docid": "37118634",
"text": "BACKGROUND Umbilical cord infection (omphalitis) is a risk factor for neonatal sepsis and mortality in low-resource settings where home deliveries are common. We aimed to assess the effect of umbilical-cord cleansing with 4% chlorhexidine (CHX) solution, with or without handwashing with antiseptic soap, on the incidence of omphalitis and neonatal mortality. METHODS We did a two-by-two factorial, cluster-randomised trial in Dadu, a rural area of Sindh province, Pakistan. Clusters were defined as the population covered by a functional traditional birth attendant (TBA), and were randomly allocated to one of four groups (groups A to D) with a computer-generated random number sequence. Implementation and data collection teams were masked to allocation. Liveborn infants delivered by participating TBAs who received birth kits were eligible for enrolment in the study. One intervention comprised birth kits containing 4% CHX solution for application to the cord at birth by TBAs and once daily by family members for up to 14 days along with soap and educational messages promoting handwashing. One intervention was CHX solution only and another was handwashing only. Standard dry cord care was promoted in the control group. The primary outcomes were incidence of neonatal omphalitis and neonatal mortality. The trial is registered with ClinicalTrials.gov, number NCT00682006. FINDINGS 187 clusters were randomly allocated to one of the four study groups. Of 9741 newborn babies delivered by participating TBAs, factorial analysis indicated a reduction in risk of omphalitis with CHX application (risk ratio [RR]=0·58, 95% CI 0·41-0·82; p=0·002) but no evidence of an effect of handwashing (RR=0·83, 0·61-1·13; p=0·24). We recorded strong evidence of a reduction in neonatal mortality in neonates who received CHX cleansing (RR=0·62, 95 % CI 0·45-0·85; p=0·003) but no evidence of an effect of handwashing promotion on neonatal mortality (RR=1·08, 0·79-1·48; p=0·62). We recorded no serious adverse events. INTERPRETATION Application of 4% CHX to the umbilical cord was effective in reducing the risk of omphalitis and neonatal mortality in rural Pakistan. Provision of CHX in birth kits might be a useful strategy for the prevention of neonatal mortality in high-mortality settings. FUNDING The United States Agency for International Development.",
"title": "Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of Pakistan: a community-based, cluster-randomised trial."
},
{
"docid": "23349986",
"text": "CONTEXT Dexamethasone is widely used to prevent postoperative nausea and vomiting (PONV) in pediatric tonsillectomy. OBJECTIVE To assess whether dexamethasone dose-dependently reduces the risk of PONV at 24 hours after tonsillectomy. DESIGN, SETTING, AND PATIENTS Randomized placebo-controlled trial conducted among 215 children undergoing elective tonsillectomy at a major public teaching hospital in Switzerland from February 2005 to December 2007. INTERVENTIONS Children were randomly assigned to receive dexamethasone (0.05, 0.15, or 0.5 mg/kg) or placebo intravenously after induction of anesthesia. Acetaminophen-codeine and ibuprofen were given as postoperative analgesia. Follow-up continued until the 10th postoperative day. MAIN OUTCOME MEASURES The primary end point was prevention of PONV at 24 hours; secondary end points were decrease in the need for ibuprofen at 24 hours and evaluation of adverse effects. RESULTS At 24 hours, 24 of 54 participants who received placebo (44%; 95% confidence interval [CI], 31%-59%) had experienced PONV compared with 20 of 53 (38%; 95% CI, 25%-52%), 13 of 54 (24%; 95% CI, 13%-38%), and 6 of 52 (12%; 95% CI, 4%-23%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P<.001 for linear trend). Children who received dexamethasone received significantly less ibuprofen. There were 26 postoperative bleeding episodes in 22 children. Two of 53 (4%; 95% CI, 0.5%-13%) children who received placebo had bleeding compared with 6 of 53 (11%; 95% CI, 4%-23%), 2 of 51 (4%; 95% CI, 0.5%-13%), and 12 of 50 (24%; 95% CI, 13%-38%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P = .003). Dexamethasone, 0.5 mg/kg, was associated with the highest bleeding risk (adjusted relative risk, 6.80; 95% CI, 1.77-16.5). Eight children had to undergo emergency reoperation because of bleeding, all of whom had received dexamethasone. The trial was stopped early for safety reasons. CONCLUSION In this study of children undergoing tonsillectomy, dexamethasone decreased the risk of PONV dose dependently but was associated with an increased risk of postoperative bleeding. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00403806.",
"title": "Dexamethasone and risk of nausea and vomiting and postoperative bleeding after tonsillectomy in children: a randomized trial."
},
{
"docid": "38752049",
"text": "Youths with attention deficit hyperactivity disorder often experience weight loss on stimulants, which may limit optimal dosing and compliance. Cyproheptadine has been shown in medical samples to stimulate weight gain. We conducted a retrospective chart review of 28 consecutive pediatric psychiatry outpatients prescribed cyproheptadine for weight loss or insomnia while on stimulants. Of these, 4 patients never took cyproheptadine consistently, and 3 discontinued it within the first 7 days due to intolerable side effects. Data were analyzed for 21 other patients (age range 4-15 years) who continued with 4-8 mg of cyproheptadine nightly (mean final dose = 4.9 mg/day) for at least 14 days (mean duration = 104.7 days). Most had lost weight on stimulant alone (mean weight loss was 2.1 kg, mean weight velocity was -19.3 g/day). All 21 gained weight taking concomitant cyproheptadine, with a mean gain of 2.2 kg (paired t = 6.87, p < 0.0001) and a mean weight velocity of 32.3 g/day. Eleven of 17 patients who had reported initial insomnia on stimulant alone noted significant improvements in sleep with cyproheptadine added. We conclude that concomitant cyproheptadine may be useful in youths with attention deficit hyperactivity disorder for stimulant-induced weight loss, pending future randomized controlled trials.",
"title": "A chart review of cyproheptadine for stimulant-induced weight loss."
},
{
"docid": "37424881",
"text": "OBJECTIVE Folate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk. DESIGN Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk. SETTING The meta-analysis included fourteen randomized controlled trials, SUBJECTS A total of 39 420 patients. RESULTS Homocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification. CONCLUSIONS Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.",
"title": "The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis."
}
] |
1784
|
What is the lifespan of a series of currency?
|
[
{
"docid": "119853",
"text": "US currency doesn't expire, it is always legal tender. I can see some trouble if you tried to spend a $10,000 bill (you'd be foolish to do so, since they are worth considerably more). Maybe some stores raise eyebrows at old-style $100's (many stores don't take $100 bills at all), but you could swap them for new style at a bank if having trouble with a particular store. Old-series currency can be an issue when trying to exchange US bills in other countries, just because it doesn't expire here, doesn't mean you can't run into issues elsewhere. Other countries have different policies, for example, over the last year the UK phased in a new five pound note, and as of last month (5/5/2017) the old fiver is no longer considered legal tender (can still swap out old fivers at the bank for now at least). Edit: I mistook which currency you took where, and focused on US currency instead of Canadian, but it looks like it's the same story there.",
"title": ""
},
{
"docid": "200136",
"text": "In general, currency has no expiration date. Specifically, in Canada, the Bank of Canada has been issuing banknotes since 1935, and these are still considered legal tender, even though they don't look much like the modern banknotes. Before that, Canadian chartered banks issued currency, and these also still have value. However, there are a few things to note. First of all, with currency of that age, it often has more value as a collector's item than the face value. So spending it at a store would be foolish. Second, store clerks are not experts in old currency, and will not accept a bill that they do not recognize. If you want the face value of your old currency, you may need to exchange it for modern currency at a bank. Having said all that, there are certainly cases where currency does expire. Generally this happens when a country changes currency. For example, when the Euro was introduced, the old currencies were discontinued. After a window of exchange, the old currency in many cases lost its value. So if you have some old French Franc notes, for example, they can no longer be exchanged for Euros. These types of events cannot be predicted in the future, of course, so it is impossible to say when, if ever, the Canadian currency you have today will lose its spending value in Canada.",
"title": ""
},
{
"docid": "494618",
"text": "\"Currency lives no more then 50 years. US currency did not expire in last 100 years, but it was reinstated few times, last one was 2009. Note that currency is not just what you hold in your hand. Currency is system of relations of money supply (currency is not money but we forced to use standard terminology), banking rules and government policy. Currency exists as long as government wants it to. In 2009 for example, US government decided it needs new currency and just printed whole new money supply. So US dollar is now counting as \"\"partially fresh new currency\"\". It was reinstated. Not expired. But today's dollar is totally different from 90s and 00s. Will it be accepted after 200 years? Yes (probably). But most likely at that time there will be totally new US dollars. And new Euros, new Pounds and so on. Currency is method of transfer. You can have that physical coins you have, but as economic agent it will die very quickly. It is not only related to inflation, in fact, inflation is the least of your worries. If you count all currencies in the world which ever existed, most of them 99.99% are completely dead by now (with governments which supported it). Not even single one currency which lived more then 100 years. US dollar was reinstated in 1860, 1907, 1930, 1973, 1987, 2009 and in fact it is not single currency but dozen which were allowed to be used \"\"for compatibility reasons\"\".\"",
"title": ""
}
] |
[
{
"docid": "327369",
"text": "\"The Fed doesn't exactly have a specific schedule when they decide to create a new dollar. Instead, they engage in open market operations, creating and destroying money as is necessary to preserve a certain interest rate for lending and borrowing. It's an ongoing process. When the Fed meets periodically and they see that inflation is getting out of hand, they will raise that rate; when they see that the economy is weak, they will lower it. They change the target rate from time to time, but they seldom tell people exactly what they'll do in advance, aside from them recently saying that rates will remain incredibly low \"\"for an extended period of time\"\". There are people who trade futures contracts based on what they think these rates will be, and the Fed does publish information on what the market thinks the probabilities are. That's probably the closest thing to telling you \"\"how much and when\"\". If you want to know about the size of the money supply, ask the Federal Reserve; you probably want series H.6, Money Stock Measures. For an explanation of what the data series there means, ask Wikipedia: you're probably interested in M2, because that's what actually affects the economy, though M0 is closer to what they actually \"\"print\"\" (currency, bills and coins, and deposits at the central bank). If you're concerned about the actual real value of your dollar dropping, the actual value drop is better understood by looking at either the inflation rate, or an exchange rate against a foreign currency (and depending on what you were hoping to use that dollar for, there are a couple of different inflation rates). The standard inflation rate which measures what happens in your day to day life is the consumer price index, published by the BLS. There are a variety of forecasts of this, but I'm not aware of any official government-agency forecasts.\"",
"title": ""
},
{
"docid": "296870",
"text": "\"Currency Trading For Dummies, no offense. The \"\"For Dummies\"\" series is well known for its expertise in every field one can imagine. That said, what prompts you to want to get into this? The average person is very likely to lose money as the long time experts walk away winners. Do you have an urge to trade commodity futures? I sure don't. While I offer the book as a guide, the real answer is \"\"you shouldn't.\"\"\"",
"title": ""
},
{
"docid": "295294",
"text": "Those are some big aspirations while still in school and certainly are attainable :) Here's a good [article](http://www.mergersandinquisitions.com/proprietary-trading-careers/) that will hopefully outline your expectations of prop trading. Hope this helps! I've been trading currency for going on 4 years and have also been looking into prop trading. I studied finance and econ in college and currently work as a financial advisor for a small firm. I have a series 6 and 63. Currently working on my series 3 to seep my way into the field via a legitimate broker/dealer. If I had plenty of capital, I certainly would rather just be an independent trader.",
"title": ""
},
{
"docid": "203926",
"text": "I haven't read the terms here but the question may not have a good answer. That won't stop me from trying. Call the real rate (interest rate - inflation) and you'll have what is called negative real rates. It's rare for the overnight real rate to be negative. If you check the same sources for historical data you'll find it's usually higher. This is because borrowing money is usually done to gain an economic benefit, ie. make a profit. That is no longer a consideration when borrowing money short term and is IMO a serious problem. This will cause poor investment decisions like you see in housing. Notice I said overnight rate. That is the only rate set by the BoC and the longer rates are set by the market. The central bank has some influence because a longer term is just a series of shorter terms but if you looked up the rate on long Canadian real return bonds, you'd see them with a real rate around 1%. What happens when the central bank raise or lowers rates will depend on the circumstances. The rate in India is so high because they are using it to defend the rupee. If people earn more interest they have a preference to buy that currency rather than others. However these people aren't stupid, they realize it's the real rate that matters. That's why Japan can get away with very low rates and still have demand for the currency - they have, or had, deflation. When that changed, the preference for their currency changed. So if Canada hast forex driven inflation then the BoC will have to raise rates to defend the dollar for the purpose of lowering inflation from imports. Whether it works or not is another story. Note that the Canadian dollar is very dependant on the total dollar value of net oil exports. If Canada has inflation due too an accelerating economy this implies that there are profitable opportunities so businesses and individuals will be more likely to pay a positive real rate of interest. In that scenario the demand for credit money will drive the real rate of return.",
"title": ""
},
{
"docid": "343489",
"text": "\"The prices quoted are for currency pairs traded on the foreign exchange market. For currencies traded on these exchanges, the exchange rates of a given currency pair are determined by the market, so supply and demand, investor confidence, etc. all play a role. EBS and Reuters are the two primary trading platforms in the foreign exchange market, and much of the data on exchange rates comes from them. Websites will usually get their data either from these sources directly or from a data provider that in turn gets it from EBS, Reuters, or another data source like Bloomberg or Haver Analytics. These data sources aren't free, however. In the US, many contracts, transactions, etc. that involve exchange rates use the exchange rate data published by the Federal Reserve. You might see this in contracts that specify to use \"\"the exchange rate published by the Federal Reserve at 12 pm (noon) on date --some date--\"\". You can also look at the Federal Reserve Economic Data, which maintains data series of historical daily, weekly, and monthly exchange rates for major currency pairs. These data are free, although they aren't realtime. Data for each business day is mostly updated the next business day.\"",
"title": ""
},
{
"docid": "397921",
"text": "I've already worked for a major broker dealer. I came to ask this question on Reddit for unbiased advice. I've asked multiple people the same question in industry and they always tell me something different. Since I will be registering in my home state of New York, I looked up what the regulations are and was even further confused. One website says >Licensing Requirements: Series 65, Series 66 and Series 7 combined, or one of the following acceptable professional designations: CFA, CFP, CIC, ChFC, PFS. Whereas another says > If you have taken the Series 65 or both the Series 66 and Series 7 within the last two years, you do not have to do anything. My confusion is the part where the first website says Series 65, Series 66, and Series 7 combined.",
"title": ""
},
{
"docid": "552303",
"text": "There's no magic. Usually these models set out to replace 60-65% of your gross income in retirement. For example, if you: You'll retire with about $850k. That will let you generate an income stream of around 55k for your expected lifespan. Is 15% the right answer for you? No idea -- it depends on what you want, how you invest, and what you can afford.",
"title": ""
},
{
"docid": "490668",
"text": "Because we've gone through a series of bubbles, and have just about completed the second to last bubble, which is fiscal deficits. We are now on the cusp of initiating the last bubble, a currency bubble, which will likely deteriorate quickly. Then we will probably have a large scale war.",
"title": ""
},
{
"docid": "94528",
"text": "\"Your numbers are way off, but the point is still valid regarding diabetes, even at 1/10th or 1/100th of what you claim. The long term health (and lifespan) implications of diabetes (not to mention the larger \"\"obesity\"\" problem) are NOT something to be simply ignored. Likewise with the long term costs/consequence of other health-related problems (STD's, anti-biotic resistant bacteria, etc).\"",
"title": ""
},
{
"docid": "496857",
"text": "\"HSBC, Hang Seng, and other HK banks had a series of special savings account offers when I lived in HK a few years ago. Some could be linked to the performance of your favorite stock or country's stock index. Interest rates were higher back then, around 6% one year. What they were effectively doing is taking the interest you would have earned and used it to place a bet on the stock or index in question. Technically, one way this can be done, for instance, is with call options and zero coupon bonds or notes. But there was nothing to strategize with once the account was set up, so the investor did not need to know how it worked behind the scenes... Looking at the deposit plus offering in particular, this one looks a little more dangerous than what I describe. See, now we are in an economy of low almost zero interest rates. So to boost the offered rate the bank is offering you an account where you guarantee the AUD/HKD rate for the bank in exchange for some extra interest. Effectively they sell AUD options (or want to cover their own AUD exposures) and you get some of that as extra interest. Problem is, if the AUD declines, then you lose money because the savings and interest will be converted to AUD at a contractual rate that you are agreeing to now when you take the deposit plus account. This risk of loss is also mentioned in the fine print. I wouldn't recommend this especially if the risks are not clear. If you read the fine print, you may determine you are better off with a multicurrency account, where you can change your HK$ into any currency you like and earn interest in that currency. None of these were \"\"leveraged\"\" forex accounts where you can bet on tiny fluctuations in currencies. Tiny being like 1% or 2% moves. Generally you should beware anything offering 50:1 or more leverage as a way to possibly lose all of your money quickly. Since you mentioned being a US citizen, you should learn about IRS form TD F 90-22.1 (which must be filed yearly if you have over $10,000 in foreign accounts) and google a little about the \"\"foreign account tax compliance act\"\", which shows a shift of the government towards more strict oversight of foreign accounts.\"",
"title": ""
},
{
"docid": "453318",
"text": "\"**Cycle of poverty** In economics, the cycle of poverty is the \"\"set of factors or events by which poverty, once started, is likely to continue unless there is outside intervention\"\". The cycle of poverty has been defined as a phenomenon where poor families become impoverished for at least three generations, i.e. for enough time that the family includes no surviving ancestors who possess and can transmit the intellectual, social, and cultural capital necessary to stay out of or change their impoverished condition. In calculations of expected generation length and ancestor lifespan, the lower median age of parents in these families is offset by the shorter lifespans in many of these groups. *** ^[ [^PM](https://www.reddit.com/message/compose?to=kittens_from_space) ^| [^Exclude ^me](https://reddit.com/message/compose?to=WikiTextBot&message=Excludeme&subject=Excludeme) ^| [^Exclude ^from ^subreddit](https://np.reddit.com/r/economy/about/banned) ^| [^FAQ ^/ ^Information](https://np.reddit.com/r/WikiTextBot/wiki/index) ^| [^Source](https://github.com/kittenswolf/WikiTextBot) ^] ^Downvote ^to ^remove ^| ^v0.27\"",
"title": ""
},
{
"docid": "305600",
"text": "With trillion dollar plus deficits, it's not like we're running an austerity program here. When you say sacrifice, compared to what? Two trillion dollar deficits? Your observation of constant predictions of imminent doom is valid. The timeline has been extended by a series of bubbles- market, housing, fiscal deficits... The shortcoming of doom prognosticators is that they underestimate the willingness of those in power to do whatever it takes to prolong the status quo, regardless of the long term consequences. The game is perpetuated by ever increasing debt, and government became the borrower of last resort once the rest of the economy was tapped out. The govt's ability to continue along this course in the open market is questionable as the Fed appears to be monetizing a large portion of newly issued debt. The end game is a currency crisis. It's nice to have a timeline accompanying a prediction, and critical for investing, but it is often very difficult to do, and in this case, it has been extremely difficult because the policy decisions have been rational from the perspective of elites maintaining their status, but not optimal from the standpoint of solving the problem. That doesn't mean the predictions are useless though. You could live in a flood zone and not be able to predict with accuracy when the next flood will occur, but that doesn't mean you shouldn't prepare. Given the uncertainty with timing this, it seems to me the best course of action is not to try to time it, especially with respect to investing based on market timing, but to prepare the best you can for what will inevitably eventually occur.",
"title": ""
},
{
"docid": "220284",
"text": "At the heart of this issue is an accounting disagreement that BIS has with current accounting standards. So basically, foreign investors want to invest in lucrative American Dollar investment products but they don't want to have to buy American Dollars in order to do so because of foreign exchange risk (the risk that by the time your investment is realized, any gains are adversely effected by the change in currency values). So instead, they trade in a series of (currency) swaps that allow them to mitigate that foreign exchange risk. In doing so, they are only required by current accounting standards to record such transactions at fair value = 0, thus skipping over the balance sheet and only hitting the footnotes. BIS believes these transactions should be recorded at gross values and on the balance sheet as opposed to the footnotes. The debt is hidden insofar as global dollar debt is calculated using liabilities on balance sheets and not the footnotes. That being said, in no way are these transactions truly hidden as (1) any good analyst values footnotes as much as the financial statements themselves and (2) exposure isn't really the same as debt. TL:DR BIS (as reputable as they are) wants to change currently accepted accounting standards and screaming $14 TRILLION DOLLARS is their way of doing it.",
"title": ""
},
{
"docid": "32282",
"text": "As others have pointed out, the value of Apple's stock and the NASDAQ are most likely highly correlated for a number of reasons, not least among them the fact that Apple is part of the NASDAQ. However, because numerous factors affect the entire market, or at least a significant subset of it, it makes sense to develop a strategy to remove all of these factors without resorting to use of an index. Using an index to remove the effect of these factors might be a good idea, but you run the risk of potentially introducing other factors that affect the index, but not Apple. I don't know what those would be, but it's a valid theoretical concern. In your question, you said you wanted to subtract them from each other, and only see an Apple curve moving around a horizontal line. The basic strategy I plan to use is similar but even simpler. Instead of graphing Apple's stock price, we can plot the difference between its stock price on business day t and business day t-1, which gives us this graph, which is essentially what you're looking for: While this is only the preliminaries, it should give you a basic idea of one procedure that's used extensively to do just what you're asking. I don't know of a website that will automatically give you such a metric, but you could download the price data and use Excel, Stata, etc. to analyze this. The reasoning behind this methodology builds heavily on time series econometrics, which for the sake of simplicity I won't go into in great detail, but I'll provide a brief explanation to satisfy the curious. In simple econometrics, most time series are approximated by a mathematical process comprised of several components: In the simplest case, the equations for a time series containing one or more of the above components are of the form that taking the first difference (the procedure I used above) will leave only the random component. However, if you want to pursue this rigorously, you would first perform a set of tests to determine if these components exist and if differencing is the best procedure to remove those that are present. Once you've reduced the series to its random component, you can use that component to examine how the process underlying the stock price has changed over the years. In my example, I highlighted Steve Jobs' death on the chart because it's one factor that may have led to the increased standard deviation/volatility of Apple's stock price. Although charts are somewhat subjective, it appears that the volatility was already increasing before his death, which could reflect other factors or the increasing expectation that he wouldn't be running the company in the near future, for whatever reason. My discussion of time series decomposition and the definitions of various components relies heavily on Walter Ender's text Applied Econometric Time Series. If you're interested, simple mathematical representations and a few relevant graphs are found on pages 1-3. Another related procedure would be to take the logarithm of the quotient of the current day's price and the previous day's price. In Apple's case, doing so yields this graph: This reduces the overall magnitude of the values and allows you to see potential outliers more clearly. This produces a similar effect to the difference taken above because the log of a quotient is the same as the difference of the logs The significant drop depicted during the year 2000 occurred between September 28th and September 29th, where the stock price dropped from 26.36 to 12.69. Apart from the general environment of the dot-com bubble bursting, I'm not sure why this occurred. Another excellent resource for time series econometrics is James Hamilton's book, Time Series Analysis. It's considered a classic in the field of econometrics, although similar to Enders' book, it's fairly advanced for most investors. I used Stata to generate the graphs above with data from Yahoo! Finance: There are a couple of nuances in this code related to how I defined the time series and the presence of weekends, but they don't affect the overall concept. For a robust analysis, I would make a few quick tweaks that would make the graphs less appealing without more work, but would allow for more accurate econometrics.",
"title": ""
},
{
"docid": "291914",
"text": "Some types of loans allow for reamortization (recasting) - which does exactly what you're talking about (making a big payment and then refiguring the monthly amount rather than the overall lifespan), without requiring any kind of a fee that refinancing does. Not every, or even most, mortgages, allow for recasting. And most that do offer recasting, may limit the recasting to a once-a-loan type of thing. So check beforehand, and make those big payments before you do any recasting. (Most banks and mortgage servicing companies may not advertise or even speak about recasting options unless you specifically ask your loan officer.)",
"title": ""
},
{
"docid": "436020",
"text": "\"TD e-series index funds are great for regular contributions every paycheck since there is no trading commission. The personal finance blog \"\"Canadian Couch Potato\"\" has great examples of what they call \"\"model portfolios\"\" and one consists of entirely TD e-series index funds. Check it out: http://canadiancouchpotato.com/model-portfolios-2/ The e-series portfolio that is described in the Model Portfolios (linked above) made returns of just over 10%. This is very similar to the ETF Model Portolio. One thing to remember is that these funds have a 30 day no sell time frame, otherwise a 2% fee is applied to the funds you withdraw.\"",
"title": ""
},
{
"docid": "391515",
"text": "\"Note that the series you are showing is the historical spot index (what you would pay to be long the index today), not the history of the futures quotes. It's like looking at the current price of a stock or commodity (like oil) versus the futures price. The prompt futures quote will be different that the spot quote. If you graphed the history of the prompt future you might notice the discontinuity more. How do you determine when to roll from one contract to the other? Many data providers will give you a time series for the \"\"prompt\"\" contract history, which will automatically roll to the next expiring contract for you. Some even provide 2nd prompt, etc. time series. If that is not available, you'd have to query multiple futures contracts and interleave them based on the expiry rules, which should be publicly available. Also is there not a price difference from the contract which is expiring and the one that is being rolled forward to? Yes, since the time to delivery is extended by ~30 days when you roll to the next contract. but yet there are no sudden price discontinuities in the charts. Well, there are, but it could be indistinguishable from the normal volatility of the time series.\"",
"title": ""
},
{
"docid": "111281",
"text": "For press releases about economic data, the Bureau of Economic Analysis press release page is helpful. Depending on the series, you could also look at the Bureau of Labor Statistics press release page. For time series of both historical and present data, the St. Louis Federal Reserve maintains a database such data, including numerous measures of GDP, called FRED. They list nearly 15,000 series related to GDP alone. FRED is extremely useful because it allows you to make graphs that indicate areas of recession, like this: On the series' homepage, there's a bold link on the left side to download the data. If you simply need the most recent data, it's listed below the graph on that page. If you're interested in a more in-depth analysis, you can use the Bureau of Economic Analysis as well, specifically the National Income and Product Accounts, which are most of the numbers that feed into the calculation of GDP. FRED also archives some of these data. Both FRED and the BEA compile data on numerous other economic benchmarks as well. Other general sources for a wide range of announcements are the Yahoo, Bloomberg, and the Wall Street Journal economic calendars. These provide the dates of many economic announcements, e.g. existing home sales, durable orders, crude inventories, etc. Yahoo provides links to the raw data where available; Bloomberg and the WSJ provide links to their article where appropriate. This is a great way to learn about various announcements and how they affect the markets; for example, the somewhat disappointing durable orders announcement recently pushed markets down a few points. For Europe, look at Eurostat. On the left side of the page, they list links to common data, including GDP. They list the latest releases on the home page that I previously linked to. For the sake of keeping this question short, I'm lumping the rest of the world into this paragraph. Data for many other countries is maintained by their governments or central banks in a similar fashion. The World Bank's databank also has relevant data like Gross National Income (GNI), which isn't identical to GDP, but it's another (less common) macroeconomic indicator. You can also look at the economic calendar on livecharts.co.uk or xe.com, which list events for the US, Europe, Australasia, and some Latin American countries. If you're only interested in the US, the Bloomberg or Yahoo calendars may have a higher signal-to-noise ratio, but if you're interested in following how global markets like currency markets respond to new information, a global economic calendar is a must. Dailyfx.com also has a global economic calendar that, according to them, is specifically geared towards events that affect the forex market. As I said, governments and central banks compile a lot of this data, so to make searching easier, here are a few links to statistical agencies and central banks for major countries. I compiled this list a while ago on my personal machine, so although I think all the links are accurate, leave a comment if something isn't quite right. Statistics Australia / Brazil / Canada / Canada / China / Eurostat / France / Germany / IMF / Japan / Mexico / OECD / Thailand / UK / US Central banks Australia / Brazil / Canada / Chile / China / ECB / Hungary / India / Indonesia / Israel / Japan / Mexico / Norway / Russia / Sweden / Switzerland / Thailand / UK / US",
"title": ""
},
{
"docid": "117921",
"text": "\"All life insurance is pretty much the same when it comes to cost. You can run the numbers over certain time period and the actual cost of insurance is about the same. A simplified way to explain life insurance and the differences between them below: The 3 characteristics of life insurance: There are 5 popular types of life insurance and they are: Term Whole Life Universal Life Variable Universal Life Indexed Universal Life But first, one must understand the most basic life insurance which is called Annual Renewable Term: This is a policy that covers 1 year and is renewable every year after. The cost of insurance typically increases each year as the insured ages. So for every year of coverage, your premium increases like in the simplified illustration above. This is the building block of all life insurance, term or permanent. There is no cash value; all premium goes to the cost of insurance. This is an ART that spans over a longer time period than 1 year (say 5, 10, 15, 20 or 30 years). All the cost is added together then divided by the number of years of coverage to give a level premium payment for the duration of the policy. The longest coverage offered these days is 30 years. There is no cash value; all premium goes to the cost of insurance. The premium is fixed (level) for the term specified. If the policy comes to an end and the owner wishes to renew it, it will be at higher premium. This can be seen in the simplified illustration above for a 15-year term policy. Because life insurance gets very expensive as you reach old age, life insurance companies came up with a way to make it affordable for the consumer wishing to have coverage for their entire lifespan. They allow you to have interest rate crediting on the cash value account inside the policy. To have cash value in the first place, you must pay premiums that are more than the cost of insurance. The idea is: your cash value grows over time to help pay for the cost of insurance in the later stages of the policy, where the cost of insurance is typically higher. This is illustrated above in an overly simplified way. This is a permanent life insurance policy that is designed to cover the lifespan of the insured. There is cash value that is credited on a fixed interest rate specified by the insurance company (typically 3-5%). The premium is fixed for the life of the policy. It was designed for insuring the entire lifespan of the insured. This is variation of Whole Life. There is cash value; it is credited on a fixed interest rate specified by the insurance company, but it does fluctuate year to year depending on the economy (typically 3-6%). The premium is flexible; you can increase/decrease the premium. This is basically a universal life policy, but the cash value sits in an account that is invested in the market, normally mutual funds. Your interest that is being credited (to your account with your cash value from investments) is subjected to risk in the market, rise/fall with the market depending on the portfolio of your choosing, hence the word \"\"Variable\"\". You take on the risk instead of the insurance company. It can be a very good product if the owner knows how to manage it (just like any other investment products). This is a hybrid of the UL and the VUL. The interest rate depends on the performance of a market index or a set of market indices. The insurance company states a maximum interest rate (or cap) you can earn up to and a guaranteed minimum floor on your cash value interest that will be credited (typically 0% floor and 12% cap). It is purely a method to credit you interest rate. It takes the market risk out of the equation but still retains some of the growth potential of the market. Term policy is designed for temporary coverage. There is no cash value accumulation. Permanent policies such as whole life, universal life, variable universal life and indexed universal life have a cash value accumulation component that was originally designed to help pay for the cost of insurance in the later stages of the policy when the insured is at an advanced age, so it can cover the entire lifespan of the insured. People do take advantage of that cash value component and its tax advantages for retirement income supplement and maximize the premium contribution. Always remember that life insurance is a life insurance product, and not an investment vehicle. There is a cost of insurance that you are paying for. But if you have life insurance needs, you might as well take advantage of the cash value accumulation, deferred tax growth, and tax-free access that these permanent policies offer.\"",
"title": ""
},
{
"docid": "137444",
"text": "\"Why does the value of gold go up when gold itself doesn't produce anything? Why do people invest in gold? Your perception, that the value of gold goes up in the long run, is based on the price of gold measured in your favorite paper currency, for example the US Dollar. An increasing price of gold means that in the visible gold market, market participants are willing to exchange more paper currency units for the same amount of gold. There are many possible reasons for this: While HFT became extremely important for the short term price movements, I will continue with long term effects, excluding HFT. So when - as a simple thought experiment - the amount of available paper currency units (US $ or whatever) doubles, and the amount of goods and services in an economy stay the same, you can expect that the price of everything in this economy will double, including gold. You might perceive that the value of gold doubled. It did not. It stayed the same. The number of printed dollars doubled. The value of gold is still the same, its price doubled. Does the amount of paper currency units grow over time? Yes: https://research.stlouisfed.org/fred2/series/BASE/ In this answer my term \"\"paper currency units\"\" includes dollars that exist only as digits in bank accounts and \"\"printing currency\"\" includes creating those digits in bank accounts out of thin air. So the first answer: gold holds its value while the value of paper currency units shrinks over time. So gold enables you to pass wealth to the next generation (while hiding it from your government). That gold does not produce anything is not entirely true. For those of us mortals who have only a few ounces, it is true. But those who have tons can lease it out and earn interest. (in practice it is leased out multiple times, so multiple that gain. You might call this fraud, and rightfully so. But we are talking about tons of gold. Nobody who controls tons of physical gold goes to jail yet). Let's talk about Fear. You see, the perceived value of gold increases as more paper currency is printed. And markets price in expected future developments. So the value of gold rises, if a sufficient number of wealthy people fear the the government(s) will print too much paper currency. Second Answer: So the price of gold not only reflects the amount of paper currency, it is also a measurement of distrust in government(s). Now you might say something is wrong with my argument. The chart mentioned above shows that we have now (mid 2015) 5 times as much printed currency units than we had 2008. So the price of gold should be 5 times as high as 2008, assuming the amount of distrust in governments stayed the same. There must be more effects (or I might be completely wrong. You decide). But here is one more effect: As the price of gold is a measurement of distrust in governments (and especially the US government since the US Dollar is perceived as the reserve currency), the US government and associated organizations are extremely interested in low gold prices to prove trust. So people familiar with the topic believe that the price of gold (and silver) is massively manipulated to the downside using high frequency trading and shorts in the futures markets by US government and wall street banks to disprove distrust. And wall street banks gain huge amounts of paper currency units by manipulating the price, mostly to the downside. Others say that countries like china and russia are also interested in low gold prices because they want to buy as much physical gold as possible. Knowing of the value that is not reflected by the price at the moment. Is there one more source of distrust in governments? Yes. Since 1971, all paper currencies are debt. They receive their value by the trust that those with debt are willing and able to pay back their debt. If this trust is lost, the downward manipulation (if you think that such a thing exists) of the gold and silver prices in the futures markets might fail some day. If this is the case (some say when this is the case). you might see movements in gold and silver prices that bring them back to equilibrium with the amount of printed paper currencies. In times of the roman empire you got a good toga and a pair of handmade shoes for an ounce of gold. In our days, you get a nice suite and a good pair of shoes for an ounce of gold. In the mean time, the value of each paper currency in the history of each country went to zero and the US $ lost 98% of its initial value. As long as there is not enough distrust, more paper currency is made in equity markets and bond markets on average. (Be aware that you earn that currency only after you were able to sell at this price, not while you hold it) Gerd\"",
"title": ""
},
{
"docid": "470918",
"text": "I'd like to start my own RIA firm. Which licenses do I need to start to get AUM under my belt and charge a 1% fee? Right now I am studying for my Series 7 and after that will be my Series 66. Is this the best path for accomplishing what I want to do?",
"title": ""
},
{
"docid": "598610",
"text": "\"No, they are outselling select models than competitors who have a much broader product range. Each of those sells many times more cars than Tesla and here's a newsflash, they don't make their bread and butter selling the high end cars. Get back to me with total numbers of cars sold and a real market share figure. If the Model 3 outsells the entire range of 3-series cars or A4s, let me know. For the record, BMW sold nearly 150,000 3-series cars last year, and delivered over 2.4 *Million* cars worldwide last year. Tesla, across all models they offer sold less than half of JUST 3-series sales. I don't know if you need a banana for scale or what but Tesla is hardly even a blip on the radar when it comes to market share, period. And no, you cannot compare their Model S to ONE model that anyone else offers, or \"\"COMBINEDZOMG!\"\", that's cherry picking and utterly useless data.\"",
"title": ""
},
{
"docid": "162247",
"text": "There are so many unnoticed issues and concerns that arise on a building’s attic or roof cavities with poor ventilation systems. For this reason, it is important to learn some of the requirements to eliminate mold or mildew problems caused by excess moisture and other causes that will affect the lifespan of a housetop covering.",
"title": ""
},
{
"docid": "171968",
"text": ">-service (many products rely on the company maintaining a server for them to talk to, so you don't know if a product will even work in a few years, which is bad for smart appliances that people expect to use for 10-20 years. This is one of my main gripes with smart home devices. While the functionality can be enhanced with more nuanced and complex control, and also control from basically anywhere in the world, the lifespan of these devices are going to be so short. And we are paying an arm and leg for them. You can get a basic thermostat for what, less than $50 and it will do the main function perfectly well and last you as long as you will live in your home. A smart thermostat will have planned obsolescence. It's functions will start to work more poorly as the software gets automatically updated over a few years. Then you have to pay the same 4x price again.",
"title": ""
},
{
"docid": "192981",
"text": "HVAC refrigerants need frequent servicing to get a prolonged lifespan. Thanks to VacOil HVAC pump oil, the equipment can easily get the durability it needs and function with complete efficiency without the slightest hitch. Trust VacOil to prove to be the best for your HVAC device.",
"title": ""
},
{
"docid": "111867",
"text": "EDIT: After reading one of the comments on the original question, I realized that there is a much more intuitive way to think about this. If you look at it as a standard PV calculation and hold each of the cashflows constant. Really what's happening is that because of inflation the discount rate isn't the full value of the interest rate. Really the discount rate is only the portion of the interest rate above the inflation rate. Hence in the standard perpetuity PV equation PV = A / r r becomes the interest rate less the inflation rate which gives you PV = A / (i - g). That seems like a much better way to get to the answer than all the machinations I was originally trying. Original Answer: I think I finally figured this out. The general term for this type of system in which the payments increase over time is a gradient series annuity. In this specific example since the payment is increasing by a percentage each period (not a constant rate) this would be considered a geometric gradient series. According to this link the formula for the present value of a geometric gradient series of payments is: Where P is the present value of this series of cashflows. A_1 is the initial payment for period 1 (i.e. the amount you want to withdraw adjusted for inflation). g is the gradient or growth rate of the periodic payment (in this case this is the inflation rate) i is the interest rate n is the number of payments This is almost exactly what I was looking for in my original question. The only problem is this is for a fixed amount of time (i.e. n periods). In order to figure out the formula for a perpetuity we need to find the limit of the right side of this equation as the number of periods (n) approaches infinity. Luckily in this equation n is already well isolated to a single term: (1 + g)^n/(1 + i)^-n}. And since we know that the interest rate, i, has to be greater than the inflation rate, g, the limit of that factor is 0. So after replacing that term with 0 our equation simplifies to the following: Note: I don't do this stuff for a living and honestly don't have a fantastic finance IQ. It's been a while since I've done any calculus or even this much algebra so I may have made an error in the math.",
"title": ""
},
{
"docid": "275422",
"text": "\"Not to state the obvious, but whenever an investment is being made, the \"\"nuts and bolts\"\" is your return on investment. Analyzing the rate of return on an investment is the primary factor in any decision. Ideally, once the actual mechanics of investment and side \"\"benefits\"\" are factored out, the goal is to be able to analyze the pure financial return. Usually the biggest problem faced in analyzing various investments is comparing the Present Value of an investment to a series of payments that may be made or received in the future. When considering the purchase of a large equity, for example, you might be looking at what series of payments are required to purchase the asset. You can also reverse this and ask, \"\"What amount of money is equivalent to this series of payments?\"\" Ultimately, the Present Value of an Annuity is the way to make these comparisons equal. Fundamentally, the Present Value of an annuity is an amount of money that should, in theory, be equivalent to a series of payments. There is, for example, technically no difference between $1064.94 today and $100 a month for a year, at an interest rate of 1% per month. Grant you, most people would be happier with the money now, but that is what interest does - it compensates you for waiting on your money. You can fire up a spreadsheet and calculate the Present Value as long as you have the monthly payment, interest rate, and number of periods. Alternatively, you can calculate any one of those missing four variables - and the key is usually to understand what that rate would be in order to compare the investments. Finally, the taxable implication is really just an adjustment to the rate of return. Imagine the following three scenarios: (Obviously the rates are fictional - the goal is to show they are the same). Scenarios 1 & 2 are really just two sides of the same coin. Using the Future Value formula in Excel = FV(0.5%, 12, -100), you get $1233.56. In scenario 1, you would have $1233.56 in your bank account. In scenario 2, your bank would have $1233.56 from you, and you would have $100 less debt per month. They are equivalent transactions. Scenario 3 is really just a variation on scenario 2, localized to the United States. Because the interest is tax deductible, however, the rate of 6% isn't really accurate. Assuming you had a 25% tax bracket, you'd actually be getting back one quarter of your interest. Put another way, 7.5% mortgage interest costs you as much as 6% credit card debt. This is how you compare apples and organges - just turn everything into an annuity or a lump sum, using Present Value calculations. Finally, quick rule of thumb - if you owe taxes in both Canada and the US, your Canadian taxes are probably higher than your American ones. As such, any tax incentives will be concomitantly higher. If you only can only use Canadian tax incentives, then look to those incentives, other things being equal.\"",
"title": ""
},
{
"docid": "147463",
"text": "The steel structures make it impervious to many threats which traditionally constructed buildings are quite vulnerable, such as weathering and termites. However, a little bit of care is mandatory to maintain the metal panels of the building that complete the outer structure of the building, which maximizes the lifespan and keep the steel structure in healthy condition.",
"title": ""
},
{
"docid": "235668",
"text": "Its impact on battery life is an interesting sidenote to this. Having a battery that's capable of 75 kwh, but only ever using 60 kwh, will help extend the battery life. So if you pay for that 75 kwh software upgrade, and you use it, you're also shortening your battery's lifespan.",
"title": ""
},
{
"docid": "93972",
"text": "Checks actually have a limited lifespan before the bank no longer has to honor them, which simplifies this question. After about 6 months you assume that check won't be cashed. If they find it after that, you write them a new check. If they don't, you really should pester them to do so.",
"title": ""
}
] |
PLAIN-723
|
body fat
|
[
{
"docid": "MED-3253",
"text": "OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. METHODS: We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. RESULTS: Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.",
"title": "Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis."
},
{
"docid": "MED-4715",
"text": "The present pilot study analyzed, for the first time, the in vivo effect of Medjool or Hallawi date consumption by healthy subjects on serum glucose, lipids, and oxidative stress. Total phenolics concentration in the Hallawi versus Medjool dates was greater by 20-31%. The major proportion of the soluble phenolics in both date varieties consisted of phenolic acids, mainly ferulic acid and coumaric acid derivatives, and also chlorogenic and caffeic acid derivatives. Unlike the Medjool dates, Hallawi dates contained a significant proportion of catechins as well. In addition, both varieties contained a quercetin derivative. Both date varieties possess antioxidative properties in vitro, but the ferric ion reducing antioxidant power of Hallawi versus Medjool dates was higher by 24%. Ten healthy subjects consumed, for a period of 4 weeks 100 g/day of either Medjool or Hallawi dates. The date consumption did not significantly affect the subjects' body mass index (BMI), their serum total cholesterol, or their cholesterol levels in the VLDL, LDL, or HDL fractions. Most important, fasting serum glucose and triacylglycerol levels were not increased after consumption of either date variety, and serum triacylglycerol levels even significantly (p < 0.05) decreased, by 8 or 15% after Medjool or Hallawi date consumption, respectively. Basal serum oxidative status was significantly (p < 0.01) decreased by 33%, as compared to the levels observed before consumption, after Hallawi (but not Medjool) date consumption. Similarly, the susceptibility of serum to AAPH-induced lipid peroxidation decreased by 12%, but only after Hallawi date consumption. In agreement with the above results, serum activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) significantly increased, by 8%, after Hallawi date consumption. It is concluded that date consumption (and mainly the Hallawi variety) by healthy subjects, despite their high sugar content, demonstrates beneficial effects on serum triacylglycerol and oxidative stress and does not worsen serum glucose and lipid/lipoprotein patterns, and thus can be considered an antiatherogenic nutrient .",
"title": "Effects of date ( Phoenix dactylifera L., Medjool or Hallawi Variety) consumption by healthy subjects on serum glucose and lipid levels and on seru..."
},
{
"docid": "MED-3952",
"text": "Endothelial anti-inflammatory effects of açaí (Ac) and red muscadine grape (Gp) polyphenolics have not been extensively investigated. It was hypothesized that polyphenolics from Ac and Gp exert comparable protective effects in human vascular endothelial cells (HUVEC) upon inflammatory stress. Furthermore, this study investigated whether microRNAs relevant to endothelial function might be regulated by Ac and Gp. Results showed that Ac and Gp (5-20 mg gallic acid equivalent/L) protected HUVEC against glucose-induced oxidative stress and inflammation. Glucose-induced expression of interleukin-6 and -8 was down-regulated by Ac and Gp at mRNA and protein levels. Upon lipopolysaccharide (LPS; 1 μg/L)-induced inflammation, Ac and Gp inhibited gene expression of adhesion molecules and NF-κB activation to similar extents, although Gp was more effective in decreasing PECAM-1 and ICAM-1 protein. Of the screened microRNAs, only microRNA-126 expression was found to be modulated by Ac and Gp as the underlying mechanism to inhibit gene and protein expression of VCAM-1.",
"title": "Polyphenolics from açaí ( Euterpe oleracea Mart.) and red muscadine grape (Vitis rotundifolia ) protect human umbilical vascular Endothelial cell..."
},
{
"docid": "MED-3204",
"text": "Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.",
"title": "Management of grapefruit-drug interactions."
},
{
"docid": "MED-4264",
"text": "Domestic winter indoor temperatures in the USA, UK and other developed countries appear to be following an upwards trend. This review examines evidence of a causal link between thermal exposures and increases in obesity prevalence, focusing on acute and longer-term biological effects of time spent in thermal comfort compared with mild cold. Reduced exposure to seasonal cold may have a dual effect on energy expenditure, both minimizing the need for physiological thermogenesis and reducing thermogenic capacity. Experimental studies show a graded association between acute mild cold and human energy expenditure over the range of temperatures relevant to indoor heating trends. Meanwhile, recent studies of the role of brown adipose tissue (BAT) in human thermogenesis suggest that increased time spent in conditions of thermal comfort can lead to a loss of BAT and reduced thermogenic capacity. Pathways linking cold exposure and adiposity have not been directly tested in humans. Research in naturalistic and experimental settings is needed to establish effects of changes in thermal exposures on weight, which may raise possibilities for novel public health strategies to address obesity. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Could increased time spent in a thermal comfort zone contribute to population increases in obesity?"
},
{
"docid": "MED-2644",
"text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.",
"title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene."
},
{
"docid": "MED-4935",
"text": "Polychlorinated naphthalenes (PCNs) are persistent, bioaccumulative, and toxic contaminants. Prior to this study, the occurrence of PCNs in human adipose tissues from the USA has not been analyzed. Here, we have measured concentrations of PCNs in human adipose tissue samples collected in New York City during 2003-2005. Concentrations of PCNs were in the range of 61-2500pg/g lipid wt. in males and 21-910pg/g lipid wt. in females. PCN congeners 52/60 (1,2,3,5,7/1,2,4,6,7) and 66/67 (1,2,3,4,6,7/1,2,3,5,6,7) were predominant, collectively accounting for 66% of the total PCN concentrations. Concentrations of PCNs in human adipose tissues were 2-3 orders of magnitude lower than the previously reported concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Concentrations of PCNs were not correlated with PCB concentrations. The contribution of PCNs to dioxin-like toxic equivalents (TEQs) in human adipose tissues was estimated to be <1% of the polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F)-TEQs.",
"title": "Polychlorinated naphthalenes in human adipose tissue from New York, USA."
},
{
"docid": "MED-1449",
"text": "Amid soaring health spending, there is growing interest in workplace disease prevention and wellness programs to improve health and lower costs. In a critical meta-analysis of the literature on costs and savings associated with such programs, we found that medical costs fall by about $3.27 for every dollar spent on wellness programs and that absenteeism costs fall by about $2.73 for every dollar spent. Although further exploration of the mechanisms at work and broader applicability of the findings is needed, this return on investment suggests that the wider adoption of such programs could prove beneficial for budgets and productivity as well as health outcomes.",
"title": "Workplace wellness programs can generate savings."
},
{
"docid": "MED-2723",
"text": "Rising prevalence of obesity is a worldwide health concern because excess weight gain within populations forecasts an increased burden from several diseases, most notably cardiovascular diseases, diabetes, and cancers. In this report, we used a simulation model to project the probable health and economic consequences in the next two decades from a continued rise in obesity in two ageing populations--the USA and the UK. These trends project 65 million more obese adults in the USA and 11 million more obese adults in the UK by 2030, consequently accruing an additional 6-8·5 million cases of diabetes, 5·7-7·3 million cases of heart disease and stroke, 492,000-669,000 additional cases of cancer, and 26-55 million quality-adjusted life years forgone for USA and UK combined. The combined medical costs associated with treatment of these preventable diseases are estimated to increase by $48-66 billion/year in the USA and by £1·9-2 billion/year in the UK by 2030. Hence, effective policies to promote healthier weight also have economic benefits. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Health and economic burden of the projected obesity trends in the USA and the UK."
},
{
"docid": "MED-1796",
"text": "Background Several studies have shown that Adenovirus 36 (Ad36) influences the risk of obesity in humans. Clarifying the relationship between Ad36 infection and obesity could lead to more effective approaches for the management of obesity. The objective of this study was to conduct a meta-analysis to confirm the influence of Ad36 infection on obesity and metabolic markers. Methodology/Principal Findings We searched MEDLINE and the Cochrane Library for pertinent articles (including their references) published between 1951 and April 22, 2012. Only English language reports of original observational studies were included in this meta-analysis. Data extraction was performed independently by two reviewers. Weighted mean differences (WMDs) and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using the random effects model. Of 237 potentially relevant studies, 10 cross-sectional studies (n = 2,870) conformed to the selection criteria. Pooled analysis showed that the WMD for BMI of Ad36 infection compared with non-infection was 3.19 (95% CI 1.44–4.93; P<0.001). Sensitivity analysis restricted to studies of adults yielded a similar result of 3.18 (95% CI 0.78–5.57; P = 0.009). The increased risk of obesity associated with Ad36 infection was also significant (OR: 1.9; 95% CI: 1.01–3.56; P = 0.047). No significant differences were found in relation to total cholesterol (P = 0.83), triglycerides (P = 0.64), HDL (P = 0.69), blood glucose (P = 0.08), waist circumstance (P = 0.09), and systolic blood pressure (P = 0.25). Conclusion/Significance Ad36 infection was associated with the risk of obesity and weight gain, but was not associated with abnormal metabolic markers including waist circumstance. It suggests that Ad36 infection is more associated with accumulation of subcutaneous fat than that of visceral fat. The relationship between Ad36 and obesity should be assessed by further studies, including well-designed prospective studies, to gain a better understanding of whether Ad36 plays a role in the etiology of human obesity.",
"title": "Association of Adenovirus 36 Infection with Obesity and Metabolic Markers in Humans: A Meta-Analysis of Observational Studies"
},
{
"docid": "MED-2921",
"text": "Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.",
"title": "Evidence on the Human Health Effects of Low-Level Methylmercury Exposure"
},
{
"docid": "MED-3053",
"text": "BACKGROUND: The hypothalamus is the central homeostatic control region of the brain and, therefore, highly influenced by nutrients such as glucose and fat. Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized. However, studies that used stimulation with fat have mainly investigated immediate perceptional processes. Besides homeostatic processes, the gustatory cortex, including parts of the insular cortex, is crucial for the processing of food items. OBJECTIVE: The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex. DESIGN: Eleven healthy men participated in a single-blinded, functional MRI study of high- and low-fat meals on 2 measurement days. Cerebral blood flow (CBF) was measured before and 30 and 120 min after intake of high- and low-fat yogurts. Hunger was rated and blood samples were taken before each CBF measurement. RESULTS: High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus, and the corresponding CBF change correlated positively with the insulin change. Furthermore, insular activity increased after 120 min in the low-fat condition only. The CBF change in both regions correlated positively in the high-fat condition. CONCLUSIONS: The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis. Therefore, fat might be a modulator of homeostatic and gustatory brain regions and their interaction. This trial was registered at clinicaltrials.gov as NCT01516021.",
"title": "Fat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans."
},
{
"docid": "MED-2652",
"text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.",
"title": "Xeno-estrogenic compounds in precipitation."
},
{
"docid": "MED-4234",
"text": "It has long been appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH). Prospective cohort data originating from recently published randomized trials on the medical treatment of BPH and prevention of prostate cancer have been invaluable. A growing body of evidence suggests that exercise and the intake of specific macronutrients and micronutrients through regular diet play a beneficial role. Most strikingly, the magnitude of these effects is similar to medical therapies using alpha-blockers and 5-alpha-reductase inhibitors. The use of supplements for prostate disease is a multibillion dollar business in the United States, and supplements are more commonly prescribed than medical therapy in many countries. In contrast to consumption of micronutrients through regular diet, supplemental intake of micronutrients and phytotherapies currently lack evidence to support their efficacy.",
"title": "Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia."
},
{
"docid": "MED-5004",
"text": "BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.",
"title": "Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford."
},
{
"docid": "MED-2655",
"text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.",
"title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"
},
{
"docid": "MED-1802",
"text": "Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: -0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.",
"title": "Longitudinal changes in BMI in older adults are associated with meat consumption differentially, by type of meat consumed."
},
{
"docid": "MED-1354",
"text": "Context Antidepressant medications represent the best established treatment for Major Depressive Disorder (MDD), but there is little evidence that they have a specific pharmacological effect relative to pill-placebo for patients with less severe depression. Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. Data Sources Pubmed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. Study Selection Randomized placebo-controlled trials of FDA approved antidepressants in the treatment of Major or Minor Depressive Disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, included a medication vs placebo comparison for at least 6 weeks, did not exclude patients on the basis of a placebo washout period, and utilized the Hamilton Rating Scale for Depression. Data from six studies (718 patients) were included. Data Extraction Individual patient-level data were obtained from study authors. Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with Hamilton scores below 23, Cohen’s d-type effect sizes for the difference between medication and placebo were estimated to be < .20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline Hamilton severity and crossed the NICE threshold for a clinically significant difference at a baseline score of 25. Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms, and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.",
"title": "Antidepressant Drug effects and Depression Severity: A Patient-Level Meta-Analysis"
},
{
"docid": "MED-3820",
"text": "BACKGROUND: A single high-fat meal induces endothelial activation, which is associated with increased serum concentrations of inflammatory cytokines. OBJECTIVE: We compared the effect of 3 different meals on circulating concentrations of interleukin 8 (IL-8), interleukin 18 (IL-18), and adiponectin in healthy subjects and in patients with type 2 diabetes mellitus. DESIGN: Thirty patients with newly diagnosed type 2 diabetes and 30 matched, nondiabetic subjects received the following 3 isoenergetic (780 kcal) meals separated by 1-wk intervals: a high-fat meal; a high-carbohydrate, low-fiber (4.5 g) meal; and a high-carbohydrate, high-fiber meal in which refined-wheat flour was replaced with whole-wheat flour (16.8 g). We analyzed serum glucose and lipid variables and serum IL-8, IL-18, and adiponectin concentrations at baseline and at 2 and 4 h after ingestion of the meals. RESULTS: Compared with nondiabetic subjects, diabetic patients had higher fasting IL-8 (P < 0.05) and IL-18 (P < 0.01) concentrations and lower adiponectin concentrations (P < 0.01) at baseline. In both nondiabetic and diabetic subjects, IL-18 concentrations increased and adiponectin concentrations decreased (P < 0.05) from baseline concentrations after consumption of the high-fat meal. After consumption of the high-carbohydrate, high-fiber meal, serum IL-18 concentrations decreased from baseline concentrations (P < 0.05) in both nondiabetic and diabetic subjects; adiponectin concentrations decreased after the high-carbohydrate, low-fiber meal in diabetic patients. IL-8 concentrations did not change significantly after consumption of any of the 3 meals. CONCLUSIONS: This study provides evidence that circulating IL-18 and adiponectin concentrations are modulated by familiar foodstuffs in humans. Meal modulation of cytokines involved in atherogenesis may represent a safe strategy for ameliorating atherogenetic inflammatory activity in diabetic patients.",
"title": "Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus."
},
{
"docid": "MED-2660",
"text": "BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids.",
"title": "Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men."
},
{
"docid": "MED-1807",
"text": "BACKGROUND: As protein is considered to increase thermogenesis and satiety more than other macronutrients, it may have beneficial effects on prevention of weight gain and weight maintenance. OBJECTIVE: The objective of this study is to assess the association between the amount and type of dietary protein, and subsequent changes in weight and waist circumference (WC). METHODS: 89,432 men and women from five countries participating in European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a mean of 6.5 years. Associations between the intake of protein or subgroups of protein (from animal and plant sources) and changes in weight (g per year) or WC (cm per year) were investigated using gender and centre-specific multiple regression analyses. Adjustments were made for other baseline dietary factors, baseline anthropometrics, demographic and lifestyle factors and follow-up time. We used random effect meta-analyses to obtain pooled estimates across centres. RESULTS: Higher intake of total protein, and protein from animal sources was associated with subsequent weight gain for both genders, strongest among women, and the association was mainly attributable to protein from red and processed meat and poultry rather than from fish and dairy sources. There was no overall association between intake of plant protein and subsequent changes in weight. No clear overall associations between intakes of total protein or any of the subgroups and changes in WC were present. The associations showed some heterogeneity between centres, but pooling of estimates was still considered justified. CONCLUSION: A high intake of protein was not found associated with lower weight or waist gain in this observational study. In contrast, protein from food items of animal origin, especially meat and poultry, seemed to be positively associated with long-term weight gain. There were no clear associations for waist changes.",
"title": "Intake of total, animal and plant protein and subsequent changes in weight or waist circumference in European men and women: the Diogenes project."
},
{
"docid": "MED-2597",
"text": "Since the beginning of the 1990s, increasing evidence supports beneficial effects of nut consumption on health. A new analysis of the Spanish PREDIMED trial, published in BMC Medicine, has expanded our knowledge. The study showed that individuals eating nuts more than three times per week died less often from cardiovascular disease and cancer than non-consumers. The study also adds an important finding that previous epidemiological studies could not provide: a protective effect on premature mortality was only seen in the intervention group in which nut consumption increased during the 4.8 years of follow-up, not in the intervention group with additional olive oil consumption or in the control group. Nut consumption actually decreased during follow-up in the latter two groups. Questions remain to be answered on the quantity of nuts to be consumed for health benefits, on possible mechanisms of action, and on whether some types of nuts should be favored. Please see related research: http://www.biomedcentral.com/1741-7015/11/164.",
"title": "Should we go nuts about nuts?"
},
{
"docid": "MED-3201",
"text": "Background Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction. Methods Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed. Results The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%). Conclusions These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles. Trial registration ClinicalTrials.gov NCT00581074",
"title": "Effects of grapefruit, grapefruit juice and water preloads on energy balance, weight loss, body composition, and cardiometabolic risk in free-living obese adults"
},
{
"docid": "MED-2718",
"text": "This paper describes the interplay among energy intake, energy expenditure and body energy stores and illustrates how an understanding of energy balance can help develop strategies to reduce obesity. First, reducing obesity will require modifying both energy intake and energy expenditure and not simply focusing on either alone. Food restriction alone will not be effective in reducing obesity if human physiology is biased toward achieving energy balance at a high energy flux (i.e. at a high level of energy intake and expenditure). In previous environments a high energy flux was achieved with a high level of physical activity but in today's sedentary environment it is increasingly achieved through weight gain. Matching energy intake to a high level of energy expenditure will likely be more a more feasible strategy for most people to maintain a healthy weight than restricting food intake to meet a low level of energy expenditure. Second, from an energy balance point of view we are likely to be more successful in preventing excessive weight gain than in treating obesity. This is because the energy balance system shows much stronger opposition to weight loss than to weight gain. While large behavior changes are needed to produce and maintain reductions in body weight, small behavior changes may be sufficient to prevent excessive weight gain. In conclusion, the concept of energy balance combined with an understanding of how the body achieves balance may be a useful framework in helping develop strategies to reduce obesity rates.",
"title": "Energy Balance and Obesity"
},
{
"docid": "MED-3353",
"text": "Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.",
"title": "Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health"
},
{
"docid": "MED-3130",
"text": "Although soy phytoestrogens have been postulated to exert a protective effect against breast cancer, the attendant mechanisms, in particular epigenetics underpinnings, have remained elusive. We investigated the putative effects on DNA methylation by two naturally occurring isoflavones, genistein and daidzein, in a study of the BRCA1 and BRCA2 oncosuppressor genes in breast cancer cell lines (MCF-7, MDA-MB 231, and MCF10a). A demethylant agent, the 5-azacytidine, and a methylant, the budesonide, were used as treatment controls. DNA methylation of BRCA1 and BRCA2 was investigated with methylated DNA immunoprecipitation coupled with PCR. In parallel, protein expression was determined by Western blot, immunohistochemistry, and confocal microscopy. Our results suggest that treatment with 18.5 μM Genistein or 78.5 μM Daidzein might reverse DNA hypermethylation and restore the expression of the oncosuppressor genes BRCA1 and BRCA2. 5-Azacitydine also enhanced the reexpression of these genes while budesonide had an opposite effect. To the best of our knowledge, these observations, while requiring replication, provide new evidence on potential epigenetic mechanisms by which genistein and daidzein might contribute to regulation of the BRCA1 and BRCA2. Future studies are warranted on whether the demethylating effect of genistein and daidzein is global or focused on select candidate genes.",
"title": "Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressor genes in breast cancer?"
},
{
"docid": "MED-3202",
"text": "1. The effects of grapefruit juice and naringenin on the activity of the human cytochrome P450 isoform CYP1A2 were evaluated using caffeine as a probe substrate. 2. In vitro naringin was a potent competitive inhibitor of caffeine 3-demethylation by human liver microsomes (Ki = 7-29 microM). 3. In vivo grapefruit juice (1.2 l day-1 containing 0.5 g l-1 naringin, the glycone form of naringenin) decreased the oral clearance of caffeine by 23% (95% CI: 7%-30%) and prolonged its half-life by 31% (95% CI: 20%-44%) (n = 12). 4. We conclude that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2.",
"title": "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man."
},
{
"docid": "MED-3469",
"text": "The purpose of this study was to compare the effects of unsweetened fruit juice and regular, decaffeinated soda on postprandial serum glucose levels in individuals with non-insulin-dependent diabetes mellitus (NIDDM) when these liquids are ingested separately as part of mixed meals. Eighteen individuals with NIDDM consumed three test breakfasts calculated using the diabetic exchange meal-planning system. Foods were identical in each of the breakfasts except for foods in the fruit exchange. Carbohydrate-equivalent amounts of fresh orange slices, unsweetened orange juice, and regular, decaffeinated Coke were consumed in breakfasts 1, 2, and 3, respectively. Serum glucose samples were drawn at fasting and 1, 2, and 3 hours postprandially. No difference was found in the postprandial serum glucose response when Coke versus orange juice was consumed in the breakfast. These findings question the appropriateness of using unsweetened fruit juices in routine meal planning for individuals with NIDDM.",
"title": "Postprandial glycemic response to orange juice and nondiet cola: is there a difference?"
},
{
"docid": "MED-3034",
"text": "In the 1970s several states in the Great Lakes region became concerned about mercury contamination in lakes and rivers and were the first to issue local fish consumption advisories. In 2001, the Food and Drug Administration (FDA) advised pregnant women, nursing mothers, young children, and women who may become pregnant not to consume shark, swordfish, king mackerel, and tilefish and recommended that these women not exceed 12 ounces of other fish per week. In 2004, FDA reissued this advice jointly with the U.S. Environmental Protection Agency (EPA) and modified it slightly to provide information about consumption of canned tuna and more details about consumption of recreationally caught fish. Though several studies have examined consumers' awareness of the joint FDA and EPA advisory as well as different state advisories, few used representative data. We examined the changes in awareness and knowledge of mercury as a problem in fish using the pooled nationally representative 2001 and 2006 Food Safety Surveys (FSS) with sample sizes of 4482 in 2001 and 2275 in 2006. Our results indicated an increase in consumers' awareness of mercury as a problem in fish (69% in 2001 to 80% in 2006, p<.001). In our regression models, we found that in both years, parents having children less than 5 years of age were more aware of mercury in fish and knowledgeable about the information contained in the national advisories about mercury in fish (p<.01) than other adults. In both 2001 and 2006, women of childbearing age (aged 18-45) were less aware and knowledgeable about this information than other women. However, women of all age groups had larger gains in awareness and knowledge than their male counterparts during this time. Participants' race, education, income, region, fish preparation experiences, having a foodborne illness in the past year, and risk perceptions about the safety of food were significant predictors of their awareness and knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Awareness and knowledge of methylmercury in fish in the United States."
},
{
"docid": "MED-3959",
"text": "Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.",
"title": "Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls"
},
{
"docid": "MED-3944",
"text": "Dietary interventions involving antioxidants are of interest for reducing inflammation, improving joint motion, and altering pain perception. We evaluated the effect of oral consumption of a fruit and berry blend on pain and range of motion (ROM). This open-label clinical pilot study involved 14 study participants with limitations in ROM that was associated with pain and affected daily living. Participants included but were not limited to those with age-related osteoarthritis. Study participants consumed 120 mL MonaVie Active® fruit juice, predominantly containing açai pulp (Euterpe oleracea Mart.) and other fruit concentrates, daily for 12 weeks. Study participants were assessed at baseline and 2, 4, 8, and 12 weeks by structured nurse interviews, pain and activities of daily living (ADL) questionnaires, blood samples, and ROM assessment. Pain was scored by using a visual analogue scale. ROM was assessed by using dual digital inclinometry as recommended by American Medical Association guidelines. Consumption of the juice resulted in significant pain reduction, improved ROM measures, and improvement in ADLs. Serum antioxidant status, as monitored by the cell-based antioxidant protection in erythrocytes (CAP-e) assay, was improved within 2 weeks and continued to improve throughout the 12 weeks of study participation (P<.01). The inflammatory marker C-reactive protein was reduced at 12 weeks, but this change did not reach statistical significance. Lipid peroxidation decreased mildly at 12 weeks. The antioxidant status, as measured by the CAP-e bioassay, showed the best correlation with improvements in physical well-being (pain, ROM, and ADL). The significant association among increased antioxidant status, improved ROM, and pain reduction warrants further study.",
"title": "Pain Reduction and Improvement in Range of Motion After Daily Consumption of an Açai (Euterpe oleracea Mart.) Pulp–Fortified Polyphenolic-Rich Fruit and Berry Juice Blend"
},
{
"docid": "MED-3021",
"text": "The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.",
"title": "Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans."
},
{
"docid": "MED-1355",
"text": "Depression and anxiety are the most common psychiatric conditions seen in the general medical setting, affecting millions of individuals in the United States. The treatments for depression and anxiety are multiple and have varying degrees of effectiveness. Physical activity has been shown to be associated with decreased symptoms of depression and anxiety. Physical activity has been consistently shown to be associated with improved physical health, life satisfaction, cognitive functioning, and psychological well-being. Conversely, physical inactivity appears to be associated with the development of psychological disorders. Specific studies support the use of exercise as a treatment for depression. Exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression and has also been shown to improve depressive symptoms when used as an adjunct to medications. While not as extensively studied, exercise has been shown to be an effective and cost-efficient treatment alternative for a variety of anxiety disorders. While effective, exercise has not been shown to reduce anxiety to the level achieved by psychopharmaceuticals.",
"title": "Exercise for the treatment of depression and anxiety."
},
{
"docid": "MED-3371",
"text": "Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.",
"title": "Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults"
},
{
"docid": "MED-2657",
"text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel",
"title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis."
},
{
"docid": "MED-5155",
"text": "Objective: To determine if a supplement of soy protein improves body composition, body fat distribution, and glucose and insulin metabolism in non-diabetic postmenopausal women compared to an isocaloric casein placebo. Design: Randomized, double-blind, placebo-controlled 3-month trial Setting: Clinical Research Center Patients: 15 postmenopausal women Interventions: CT scans at L4/L5, dual energy x-ray absorptiometry (DXA), hyperglycemic clamps Main outcome measures: Total fat, total abdominal fat, visceral fat, subcutaneous abdominal fat, and insulin secretion. Results: Weight by DXA did not change between groups (+1.38 ± 2.02 kg for placebo vs. +0.756 ± 1.32 kg for soy, p=0.48, means ± S.D.). Total and subcutaneous abdominal fat increased more in the placebo compared to the soy group (for differences between groups in total abdominal fat: +38.62 ± 22.84 cm2 for placebo vs. −11.86 ± 31.48 cm2 for soy, p=0.005; subcutaneous abdominal fat: +22.91 ± 28.58 cm2 for placebo vs. −14.73 ± 22.26 cm2 for soy, p=0.013). Insulin secretion, visceral fat, total body fat, and lean mass did not differ between groups. Isoflavone levels increased more in the soy group. Conclusion: A daily supplement of soy protein prevents the increase in subcutaneous and total abdominal fat observed with an isocaloric casein placebo in postmenopausal women.",
"title": "Effect of a Daily Supplement of Soy Protein on Body Composition and Insulin Secretion in Postmenopausal Women"
},
{
"docid": "MED-2906",
"text": "BACKGROUND: Different chemical forms of mercury occur naturally in human milk. The most controversial aspect of early post-natal exposure to organic mercury is ethylmercury (EtHg) in thimerosal-containing vaccines (TCV) still being used in many countries. Thus exclusively breastfed infants can be exposed to both, fish derived methylmercury (MeHg) in maternal diets and to EtHg from TCV. The aim of the study is to evaluate a new analytical method for ethyl and methyl mercury in hair samples of breastfed infants who had received the recommended schedule of TCV. METHODS: The hair of infants (<12 months) that had been exposed to TCV (Hepatitis B and DTaP) was analysed. A method coupling isothermal gas chromatography with cold-vapor atomic fluorescence spectrometry was used for MeHg which can also speciate EtHg in biological matrices. RESULTS: In 20 samples of infants' hair, all but two samples showed variable amounts of MeHg (10.3 to 668 ng/g), while precise and reliable concentrations of EtHg (3.7 to 65.0 ng/g) were found in 15 of the 20 samples. A statistically significant inverse association (r=-05572; p=0.0384) was found between hair-EtHg concentrations and the time elapsed after the last TCV shot. CONCLUSIONS: The analytical method proved sensitive enough to quantify EtHg in babies' hair after acute exposure to thimerosal in vaccine shots. Provided that the mass of hair was above 10mg, organic-mercury exposure during early life can be speciated, and quantified in babies' first hair, thus opening opportunities for clinical and forensic studies. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Speciation of methyl- and ethyl-mercury in hair of breastfed infants acutely exposed to thimerosal-containing vaccines."
},
{
"docid": "MED-1349",
"text": "Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.",
"title": "Antidepressants and the Placebo Effect"
},
{
"docid": "MED-2675",
"text": "Although products of pyrolysis are often cytotoxic and mutagenic, the relationship between the type of material pyrolysed and the toxicity of the resulting pyrolysis products is poorly understood. The objective of this study was to evaluate and compare the cytotoxicity and mutagenicity of several types of common pyrolysis products. The cytotoxicity and mutagenicity of these products were assessed by using neutral red uptake and Ames mutagenicity assays, respectively. The biological activities of four liquid smoke food flavourings (LSF) were compared with two other pyrolysis-derived materials; cigarette smoke condensate (CSC) and a wood smoke condensate (WSC). Results indicated all of the mixtures exhibited a concentration-dependent cytotoxic response. The CSC and WSC were less cytotoxic than three of the LSFs, but more cytotoxic than one of the brands. The CSC was mutagenic in two Salmonella strains; however, none of the LSFs or WSC was mutagenic using TA98, and only three of the LSFs were positive with TA100. The six pyrolysis-derived materials evaluated in this study showed differing patterns and magnitudes of cytotoxicity and mutagenicity. These results indicate that the cytotoxicity and mutagenicity of complex mixtures derived from pyrolysis products are affected by the type of material pyrolysed and/or the method used to prepare the mixture. The cytotoxic potential of some commercial smoke flavourings is greater than cigarette smoke condensate and several of the food flavourings are mutagenic in one Salmonella strain.",
"title": "Comparison of the cytotoxic and mutagenic potential of liquid smoke food flavourings, cigarette smoke condensate and wood smoke condensate."
},
{
"docid": "MED-2905",
"text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.",
"title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study"
},
{
"docid": "MED-2997",
"text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.",
"title": "The Etiological Significance of Related Diseases"
},
{
"docid": "MED-3206",
"text": "To study the effects of grapefruit and grapefruit products on body weight and metabolic syndrome, 91 obese patients were randomized to either placebo capsules and 7 ounces (207 mL) of apple juice, grapefruit capsules with 7 ounces (207 mL) of apple juice, 8 ounces (237 mL) of grapefruit juice with placebo capsule, or half of a fresh grapefruit with a placebo capsule three times a day before each meal. Metabolic syndrome parameters were measured at the beginning and end of 12 weeks. After 12 weeks, the fresh grapefruit group had lost 1.6 kg, the grapefruit juice group had lost 1.5 kg, the grapefruit capsule group had lost 1.1 kg, and the placebo group had lost 0.3 kg. The fresh grapefruit group lost significantly more weight than the placebo group (P < .05). A secondary analysis of those with the metabolic syndrome in the four treatment groups demonstrated a significantly greater weight loss in the grapefruit, grapefruit capsule, and grapefruit juice groups compared with placebo (P < .02). There was also a significant reduction in 2-hour post-glucose insulin level in the grapefruit group compared with placebo. Half of a fresh grapefruit eaten before meals was associated with significant weight loss. In metabolic syndrome patients the effect was also seen with grapefruit products. Insulin resistance was improved with fresh grapefruit. Although the mechanism of this weight loss is unknown it would appear reasonable to include grapefruit in a weight reduction diet.",
"title": "The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome."
},
{
"docid": "MED-4999",
"text": "Curcumin (Cur), a component of turmeric (Curcuma longa), has been reported to exhibit antimetastatic activities, but the mechanisms remain unclear. Other curcuminoids present in turmeric, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) have not been investigated whether they exhibit antimetastatic activity to the same extent as curcumin. The regulation of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) play important role in cancer cell invasion by cleavage of extracellular matrix (ECM). In this line, we comparatively examined the influence of Cur, DMC and BDMC on the expressions of uPA, MMP-2, MMP-9, membrane Type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-2), and in vitro invasiveness of human fibrosarcoma cells. The results indicate that the differential potency for inhibition of cancer cell invasion was BDMC> or =DMC>Cur, whereas the cell migration was not affected. Zymography analysis exhibited that curcumin, DMC and BDMC significantly decreased uPA, active-MMP-2 and MMP-9 but not pro-MMP-2 secretion from the cells in a dose-dependent manner, in which BDMC and DMC show higher potency than curcumin. The suppression of active MMP-2 level correlated with inhibition of MT1-MMP and TIMP-2 protein levels involved in pro-MMP-2 activation. Importantly, BDMC and DMC at 10 microM reduced MT1-MMP and TIMP-2 protein expression, but curcumin slightly reduced only MT1-MMP but not TIMP-2. In addition, three forms of curcuminoids significantly inhibited collagenase, MMP-2, and MMP-9 but not uPA activity. In summary, these data demonstrated that DMC and BDMC show higher antimetastasis potency than curcumin by the differentially down-regulation of ECM degradation enzymes.",
"title": "Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA."
},
{
"docid": "MED-4726",
"text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.",
"title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies."
},
{
"docid": "MED-1718",
"text": "The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin's lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.",
"title": "Obesity as a Major Risk Factor for Cancer"
},
{
"docid": "MED-3209",
"text": "The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.",
"title": "Can grapefruit juice influence ethinylestradiol bioavailability?"
},
{
"docid": "MED-2724",
"text": "Heart rate, rate-pressure product, and VO2 were measured in ten healthy men during four specified sexual activities: coitus with husband on top, coitus with wife on top, noncoital stimulation of husband by wife, and self-stimulation by husband. Foreplay generated slight, but statistically significant, increases above resting baseline in cardiac and metabolic variables. From stimulation through orgasm, average effort was modest for relatively short spans. Maximum exercise values occurred during the brief spans of orgasm, then returned quickly to near baseline levels. The two noncoital activities required lower expenditures than the two coital positions, with man-on-top coitus rating the highest. Large variations among subjects and among activities discourage use of a general equivalent activity for comparison, such as \"two flights of stairs,\" to represent \"sexual activity.\"",
"title": "Heart rate, rate-pressure product, and oxygen uptake during four sexual activities."
},
{
"docid": "MED-4739",
"text": "Contemporary reproductive aged women and their offspring are facing an unprecedented onslaught of toxicant exposures from myriad sources in their day-to-day life. Public health recommendations regarding optimal diet and nutrition in pregnancy must incorporate several considerations including safety of available foodstuffs, cultural practices and lifestyle issues. Gestational consumption of contaminated seafood remains a potential source of toxicant exposure, including mercury, for the developing child. Health care professionals responsible for the care of women and their developing children need to become apprised of: a) risks associated with toxicant bioaccumulation in pregnancy; b) ongoing information emerging in the important field of reproductive toxicology; and c) strategies within the clinical setting to facilitate nutritional sufficiency and precautionary avoidance of adverse exposure among young women.",
"title": "Nowhere to hide: Chemical toxicants and the unborn child."
},
{
"docid": "MED-1347",
"text": "AIMS: To evaluate new generation antidepressants in relation to the placebo response. METHODS: I review meta-analyses in which response to antidepressant medication and response to placebo were calculated. RESULTS: All but one of these meta-analyses included unpublished as well as published trials. Most trials failed to show a significant advantage of SSRIs over inert placebo, and the differences between drug and placebo are not clinically significant for most depressed patients. Documents obtained from the U.S. Food and Drug Administration (FDA) revealed an explicit decision to keep this information from the public and from prescribing physicians. CONCLUSIONS: Because they do not incur drug risks, exercise and psychotherapy, which show at benefits at least equal to those of antidepressants, may be a better treatment choice for depressed individuals.",
"title": "Antidepressants and the placebo response."
},
{
"docid": "MED-1717",
"text": "BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.",
"title": "Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies."
},
{
"docid": "MED-4005",
"text": "The aim of the present study was to examine the effect of a single high-fat meal with different fat quality on circulating inflammatory markers and gene expression in peripheral blood mononuclear cells (PBMC) to elucidate the role of fat quality on postprandial inflammation. A postprandial study with fourteen healthy females consuming three test meals with different fat quality was performed. Test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analysed. The test meal consisted of three cakes enriched with coconut fat (43 % energy as saturated fat and 1 % energy as α-linolenic acid (ALA)), linseed oil (14 % energy as ALA and 30 % energy as saturated fat) and cod liver oil (5 % energy as EPA and DHA and 5 % energy as ALA in addition to 31 % energy as saturated fat). In addition, ex vivo PBMC experiments were performed in eight healthy subjects investigating the effects of EPA and ALA on release and gene expression of inflammatory markers. The IL-8 mRNA level was significantly increased after intake of the cod liver oil cake at 6 h compared with fasting level, which was significantly different from the effect observed after the intake of linseed cake. In contrast, no effect was seen on circulating level of IL-8. In addition, ALA and EPA were shown to elicit different effects on the release and mRNA expression levels of inflammatory markers in PBMC cultured ex vivo, with EPA having the most prominent pro-inflammatory potential.",
"title": "Effect of the fat composition of a single high-fat meal on inflammatory markers in healthy young women."
},
{
"docid": "MED-1804",
"text": "There is increasing evidence that obesity in humans is associated with infection with human adenovirus-36 (Adv36). Infection of experimental animals with Adv36 demonstrates that this virus causes obesity. Human studies have shown a prevalence of Adv36 infection of 30% or greater in obese adult humans, but a correlation with obesity has not always been demonstrated. In contrast, three published studies and one presented study with a total of 559 children all show that there is an increase in prevalence of Adv36 infection in obese children (28%) compared to non-obese children (10%). The explanation for the apparently more robust correlation of Adv36 infection with obesity in children vs. adults is not clear. The data in animals and people suggests that Adv36 has contributed to the worldwide increase in childhood obesity. More research is needed to identify prevalences and consequences of Adv36 infection in people of all age groups and geographic locations.",
"title": "Human adenovirus-36 and childhood obesity."
},
{
"docid": "MED-4937",
"text": "In the late 1960s the first scientific studies on contamination in Antarctica demonstrated the presence of pollutants in Antarctic ecosystems. Many Persistent Organic Pollutants (POPs) are transported globally from the areas in which they are produced and released into the environment in remote areas, including Antarctica. Here we report results obtained concerning the accumulation of polybrominated diphenyl ethers (PBDEs), mono- and non-ortho-polychlorobiphenyls (PCBs), polychlorodibenzodioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in the tissues of two species of Antarctic fish (Chionodraco hamatus and Trematomus bernacchii). The 2,3,7,8-TCDD toxic equivalents (TEQs) were also calculated to evaluate the potential risk of these compounds for the two species. In general, POP levels were higher in the tissues of T. bernacchii than in C. hamatus and the highest concentrations were found in the liver of both species. The PBDE levels varied from 160.5 pg g(-1) wet wt in C. hamatus muscle to 789.9 pg g(-1) wet wt in T. bernacchii liver and were lower than the levels of PCBs. PCBs were the main organochlorine compounds detected and their concentrations ranged from 0.3 ng g(-1) wet wt in C. hamatus muscle to 15.1 ng g(-1) wet wt in T. bernacchii liver. TEQ concentrations resulted higher in C. hamatus than in T. bernacchii and were due mainly to PCDDs. The presence of PBDEs and organochlorine pollutants in the tissues of Antarctic organisms confirms their global transport and distribution.",
"title": "Levels of polybrominated diphenyl ethers (PBDEs) and organochlorine pollutants in two species of Antarctic fish (Chionodraco hamatus and Trematomus..."
},
{
"docid": "MED-5176",
"text": "A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from \"moderate/severe\" to \"mild\" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.",
"title": "Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia."
},
{
"docid": "MED-1448",
"text": "OBJECTIVE: To quantify per capita and aggregate medical expenditures and the value of lost productivity, including absenteeism and presenteeism, because of overweight, and grade I, II, and III obesity among U.S. employees. METHODS: Cross-sectional analysis of the 2006 Medical Expenditure Panel Survey and the 2008 National Health and Wellness Survey. RESULTS: Among men, estimates range from -$322 for overweight to $6087 for grade III obese men. For women, estimates range from $797 for overweight to $6694 for grade III. In aggregate, the annual cost attributable to obesity among full-time employees is $73.1 billion. Individuals with a body mass index >35 represent 37% of the obese population but are responsible for 61% of excess costs. CONCLUSIONS: Successful efforts to reduce the prevalence of obesity, especially among those with a body mass index >35, could result in significant savings to employers.",
"title": "The costs of obesity in the workplace."
},
{
"docid": "MED-2653",
"text": "Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 microg/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 microg/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats.",
"title": "Nonylphenol and octylphenol in human breast milk."
},
{
"docid": "MED-2678",
"text": "Smoked foods including turkey, pork, chicken, beef and fish products were screened for the presence of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons (PAHs). Eighteen commercial liquid smoke flavourings and seasonings were also analysed. Total PAH concentrations in smoked meat products ranged from 2.6 micrograms/kg in a cooked ham sample to 29.8 micrograms/kg in grilled pork chops, while those in fish products ranged from 9.3 micrograms/kg in smoked shrimp to 86.6 micrograms/kg in smoked salmon. Total concentrations of the carcinogenic PAHs (benzo[a]anthracene, benzo[b]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, and indeno[1,2,3-c,d]pyrene) ranged from non-detectable in several meat products to 7.4 micrograms/kg in grilled pork chops, and from 0.2 micrograms/kg in trout to 16.0 micrograms/kg in salmon. In liquid smoke flavourings and seasonings, total PAH concentrations ranged from 6.3 to 43.7 micrograms/kg, with the carcinogenic PAHs ranging from 0.3 to 10.2 micrograms/kg.",
"title": "Polycyclic aromatic hydrocarbons in smoked food products and commercial liquid smoke flavourings."
},
{
"docid": "MED-2679",
"text": "Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.",
"title": "Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice."
},
{
"docid": "MED-3013",
"text": "A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.",
"title": "Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008."
},
{
"docid": "MED-1799",
"text": "Human adenovirus Ad-36 is causatively and correlatively linked with animal and human obesity, respectively. Ad-36 enhances differentiation of rodent preadipocytes, but its effect on adipogenesis in humans is unknown. To indirectly assess the role of Ad-36-induced adipogenesis in human obesity, the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly greater lipid accumulation, suggestive of their commitment to the adipocyte lineage. Even in the absence of adipogenic inducers, Ad-36 significantly increased hASC differentiation, as indicated by a time-dependent expression of genes within the adipogenic cascade—CCAAT/Enhancer binding protein-β, peroxisome proliferator-activated receptor-γ, and fatty acid-binding protein—and consequentially increased lipid accumulation in a time- and viral dose-dependent manner. Induction of hASC to the adipocyte state by Ad-36 was further supported by increased expression of lipoprotein lipase and the accumulation of its extracellular fraction. hASC from subjects harboring Ad-36 DNA in their adipose tissue due to natural infection had significantly greater ability to differentiate compared with Ad-36 DNA-negative counterparts, which offers a proof of concept. Thus, Ad-36 has the potential to induce adipogenesis in hASC, which may contribute to adiposity induced by the virus.",
"title": "Adipogenic Human Adenovirus Ad-36 Induces Commitment, Differentiation, and Lipid Accumulation in Human Adipose-Derived Stem Cells"
},
{
"docid": "MED-2715",
"text": "OBJECTIVE: Obesity results from protracted energy imbalance. Whether this comprises excessive energy intake, lowered physical activity or both, remains disputed. DESIGN: Physical activity energy expenditure, evaluated in three different ways from daily energy expenditure (DEE) measured using doubly labelled water, was examined for trends over time. Data included subjects in Europe (Maastricht, the Netherlands) and North America extending back to the 1980s. These data were compared with measures from the third world, and measures made on wild terrestrial mammals. RESULTS: Physical activity expenditure in Europe (residual of the regression of DEE on basal energy expenditure (BEE)) has slightly but significantly increased since the 1980s. There was no trend over time in physical activity level (PAL=DEE/BEE), or in the residual variance in DEE once mass, sex and age were accounted for. This latter index of physical activity expenditure also significantly increased over time in North America. DEE of individuals in Europe and North America was not significantly different from individuals measured in the third world. In wild terrestrial mammals, DEE mostly depended on body mass and ambient temperature. Predicted DEE for a 78 kg mammal living at 20 degrees C was 9.2 MJ per day (95% CI: 7.9-12.9 MJ per day), not significantly different from the measured DEE of modern humans (around 10.2-12.6 MJ per day). CONCLUSION: As physical activity expenditure has not declined over the same period that obesity rates have increased dramatically, and daily energy expenditure of modern man is in line with energy expenditure in wild mammals, it is unlikely that decreased expenditure has fuelled the obesity epidemic.",
"title": "Physical activity energy expenditure has not declined since the 1980s and matches energy expenditures of wild mammals."
},
{
"docid": "MED-4233",
"text": "OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.",
"title": "Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l..."
},
{
"docid": "MED-3369",
"text": "Background: Strategies are needed to increase children's intake of a variety of vegetables, including vegetables that are not well liked. Objective: We investigated whether incorporating puréed vegetables into entrées to reduce the energy density (ED; in kcal/g) affected vegetable and energy intake over 1 d in preschool children. Design: In this crossover study, 3- to 5-y-old children (n = 40) were served all meals and snacks 1 d/wk for 3 wk. Across conditions, entrées at breakfast, lunch, dinner, and evening snack were reduced in ED by increasing the proportion of puréed vegetables. The conditions were 100% ED (standard), 85% ED (tripled vegetable content), and 75% ED (quadrupled vegetable content). Entrées were served with unmanipulated side dishes and snacks, and children were instructed to eat as much as they liked. Results: The daily vegetable intake increased significantly by 52 g (50%) in the 85% ED condition and by 73 g (73%) in the 75% ED condition compared with that in the standard condition (both P < 0.0001). The consumption of more vegetables in entrées did not affect the consumption of the vegetable side dishes. Children ate similar weights of food across conditions; thus, the daily energy intake decreased by 142 kcal (12%) from the 100% to 75% ED conditions (P < 0.05). Children rated their liking of manipulated foods similarly across ED amounts. Conclusion: The incorporation of substantial amounts of puréed vegetables to reduce the ED of foods is an effective strategy to increase the daily vegetable intake and decrease the energy intake in young children. This trial was registered at clinicaltrials.gov as NCT01252433.",
"title": "Hiding vegetables to reduce energy density: an effective strategy to increase children's vegetable intake and reduce energy intake"
},
{
"docid": "MED-4729",
"text": "In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources.",
"title": "Do Organohalogen Contaminants Contribute to Histopathology in Liver from East Greenland Polar Bears (Ursus maritimus)?"
},
{
"docid": "MED-4267",
"text": "The aim of our studies was to determine the amount of polyphenols reaching the colon after oral intake of apple juice and blueberries. After a polyphenol-free diet healthy ileostomy volunteers consumed a polyphenol-rich cloudy apple juice while others consumed anthocyanin-rich blueberries. Ileostomy effluent was collected and polyphenols were identified using HPLC-DAD as well as HPLC-ESI-MS/MS; quantification was performed with HPLC-DAD. Most of the orally administered apple polyphenols were absorbed from or metabolized in the small intestine. Between 0 and 33% of the oral dose was recovered in the ileostomy bags with a maximum of excretion after 2 h. A higher amount of the blueberry anthocyanins under study (up to 85%, depending on the sugar moiety) were determined in the ileostomy bags and therefore would reach the colon under physiological circumstances. Such structure-related availability has to be considered when polyphenols are used in model systems to study potential preventive effects in colorectal diseases.",
"title": "Studies on apple and blueberry fruit constituents: do the polyphenols reach the colon after ingestion?"
},
{
"docid": "MED-3478",
"text": "Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 μM of HN and 32 μM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line--a comparative study."
},
{
"docid": "MED-3467",
"text": "The effects of antioxidant diet supplements on blood lactate concentration and on the aerobic and anaerobic thresholds and their adaptations to training were analysed. Fifteen amateur male athletes were randomly assigned to either a placebo group or an antioxidant-supplemented group (90 days supplementation with 500 mg x day(-1) of vitamin E and 30 mg x day(-1) of beta-carotene, and the last 15 days also with 1 g x day(-1) of vitamin C). Before and after the antioxidant supplements, the sportsmen performed a maximal exercise test on a cycle ergometer and maximal and submaximal physiological parameters were assessed together with blood lactate concentration. Maximal oxygen uptake (VO(2max)), maximal blood lactate concentration, and the maximal workload attained rose significantly in both groups after the 3 months of training. At the end of the study, maximal blood lactate concentration was lower in the group that took supplements than in the placebo group. The percentage of VO(2max) attained at the anaerobic threshold rose significantly in both groups after 3 months of training, although the final value in the supplemented group was higher than that in the placebo group. Antioxidant diet supplements induced lower increases in blood lactate concentration after a maximal exercise test and could improve the efficiency in which aerobic energy is obtained.",
"title": "Antioxidant diet supplementation enhances aerobic performance in amateur sportsmen."
},
{
"docid": "MED-2662",
"text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.",
"title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)."
},
{
"docid": "MED-1450",
"text": "Background/objectives: To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting. Subjects/methods: Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and/or previous diagnosis of type 2 diabetes were randomized to either follow a low-fat vegan diet, with weekly group support and work cafeteria options available, or make no diet changes for 18 weeks. Dietary intake, body weight, plasma lipid concentrations, blood pressure and glycated hemoglobin (HbA1C) were determined at baseline and 18 weeks. Results: Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups, respectively (P<0.001). Total and low-density lipoprotein (LDL) cholesterol fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group (P<0.01). HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group, respectively (P<0.01). Among study completers, mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups, respectively (P<0.001). Total and LDL cholesterol fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group (P<0.001). HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group, respectively (P<0.01). Conclusions: An 18-week dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight, plasma lipids, and, in individuals with diabetes, glycemic control.",
"title": "A multicenter randomized controlled trial of a plant-based nutrition program to reduce body weight and cardiovascular risk in the corporate setting: the GEICO study"
},
{
"docid": "MED-1801",
"text": "OBJECTIVE: In 1976, the Royal College of Physicians and the British Cardiac Society recommended eating less fatty red meat and more poultry instead because it was lean. However, the situation has changed since that time, with a striking increase in fat content of the standard broiler chicken. The aim of the present study was to report a snapshot of data on fat in chickens now sold to the public. DESIGN: Samples were obtained randomly between 2004 and 2008 from UK supermarkets, farm shops and a football club. The amount of chicken fat was estimated by emulsification and chloroform/methanol extraction. SETTING: Food sold in supermarkets and farms in England. SUBJECTS: Chicken samples. RESULTS: The fat energy exceeded that of protein. There has been a loss of n-3 fatty acids. The n-6:n-3 ratio was found to be as high as 9:1, as opposed to the recommendation of about 2:1. Moreover, the TAG level in the meat and whole bird mostly exceeded the proportion of phospholipids, which should be the higher for muscle function. The n-3 fatty acid docosapentaenoic acid (DPA, 22 : 5n-3) was in excess of DHA (22 : 6n-3). Previous analyses had, as usual for birds, more DHA than DPA. CONCLUSIONS: Traditional poultry and eggs were one of the few land-based sources of long-chain n-3 fatty acids, especially DHA, which is synthesized from its parent precursor in the green food chain. In view of the obesity epidemic, chickens that provide several times the fat energy compared with protein seem illogical. This type of chicken husbandry needs to be reviewed with regard to its implications for animal welfare and human nutrition.",
"title": "Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein."
},
{
"docid": "MED-3351",
"text": "Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "The color red reduces snack food and soft drink intake."
},
{
"docid": "MED-3054",
"text": "The relationship between overeating, substance abuse and (behavioral) addiction is controversial. Medically established forms of addiction so far pertain to substance use disorders only. But the preliminary Diagnostic and Statistical Manual for Mental Disorders V (DSM V) suggests replacing the previous category 'Substance-Related Disorders' with 'Addiction and Related Disorders', thus for the first time allowing the diagnosis of behavioral addictions. In the past psychiatrists and psychologists have been reluctant to systematically delineate and classify the term behavioral addiction. However, there is a broad overlap between chemical and behavioral addiction including phenomenological, therapeutic, genetic, and neurobiological aspects. It is of interest to point out that the hormone leptin in itself has a pronounced effect on the reward system, thus suggesting an indirect link between overeating and 'chemical' addiction. Thus, leptin-deficient individuals could be classified as fulfilling criteria for food addiction. In our overview we first review psychological findings in chemical (substance-based) and subsequently in behavioral addiction to analyze the overlap. We discuss the diagnostic validity of food addiction, which in theory can be chemically and/or behaviorally based. Copyright © 2012 S. Karger GmbH, Freiburg.",
"title": "Does food addiction exist? A phenomenological discussion based on the psychiatric classification of substance-related disorders and addiction."
},
{
"docid": "MED-4257",
"text": "We conducted a systematic review investigating body fat distribution in older adults and its association with morbidity and mortality. Our search yielded 2,702 citations. Following three levels of screening, 25 studies were selected to evaluate the association between body fat distribution and comorbidity, and 17 studies were used in the mortality analysis. Most of the selected studies in our analyses used anthropometric measures, e.g., body mass index (BMI), waist circumference, and waist-hip ratio; relatively few studies used direct measures, such as body fat/lean mass, and percentage body fat. Studies reported inconsistent findings regarding the strongest predictor(s) of morbidity and mortality. However, the majority of studies suggested that BMI per se was not the most appropriate predictor of morbidity and mortality in the elderly because of its inability to discern or detect age-related body fat redistribution. In addition, studies using BMI found that the optimal BMI range for the lowest mortality in the elderly was overweight (25 kg/m2 ≤ BMI < 30 kg/m2) or mildly obese (30 kg/m2 ≤ BMI < 35 kg/m2). Our findings suggest that the current clinical guidelines, recommending that overweight and obesity are major risk factors for increased morbidity and mortality are not applicable to this population. Therefore, the central message of this review is to admonish the government to establish new guidelines specifically for this population, using a combination of body fat distribution measurements, and to certify that these guidelines will not be applied to inappropriate populations.",
"title": "A Systematic Review of Body Fat Distribution and Mortality in Older People"
},
{
"docid": "MED-3028",
"text": "OBJECTIVE The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09–1.26), 0.98 (0.70–1.37), and 0.90 (0.82–0.98). CONCLUSIONS Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged.",
"title": "Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes"
},
{
"docid": "MED-2650",
"text": "Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.",
"title": "Inadvertent exposure to xenoestrogens."
},
{
"docid": "MED-1715",
"text": "Summary Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg −1 of body weight per day to 0.95 g kg −1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL −1 to 152 ng mL −1 . These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.",
"title": "Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans"
},
{
"docid": "MED-3023",
"text": "Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. Mothers and their newborns are divided in two groups according to their hair mercury levels; examined group with high body levels of mercury (≥ 1 μg/g) and control group with low body levels of mercury (<1 μg/g). Neurosonographic examination was conducted to all newborns. Two dimensions of cerebellum in the sagital-medial plane have been measured: maximum height and width starting from the roof of the fourth chamber. Majority of mothers had hair mercury levels lower than 1 μg/g (N = 107). Mean value was 0.88 μg/g (SD 1.24), ranging from 0.02 to 8.71 μg/g. There was no significant difference between the two groups when it comes to the width of cerebellum (Mann-Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 μg/g (Mann-Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn's cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Relationship between the prenatal exposure to low-level of mercury and the size of a newborn's cerebellum."
},
{
"docid": "MED-3900",
"text": "Epidemiological studies examining potential associations between dried fruit consumption, diet quality, and weight status are lacking. The goal of this study was to examine the association of dried fruit consumption with nutrient intake, diet quality, and anthropometric indicators of overweight/obesity. A secondary analysis of dietary and anthropometric data collected from adult (19+ years) participants (n = 13 292) of the 1999-2004 National Health and Nutrition Examination Survey was conducted. Dried fruit consumers were defined as those consuming amounts ⅛ cup-equivalent fruit per day or more and identified using 24-hour recalls. Diet quality was measured using the Healthy Eating Index 2005. Covariate-adjusted means, SEs, prevalence rates, and odds ratios were determined to conduct statistical tests for differences between dried fruit consumers and nonconsumers. Seven percent of the population consumed dried fruit. Mean differences (P < .01) between consumers and nonconsumers in adult shortfall nutrients were dietary fiber (+6.6 g/d); vitamins A (+173 μg retinol activity equivalent per day), E (+1.5 mg α-tocopherol per day), C (+20 mg/d), and K (+20 mg/d); calcium (+103 mg/d); phosphorus (+126 mg/d); magnesium (+72 mg/d); and potassium (+432 mg/d). Dried fruit consumers had improved MyPyramid food intake, including lower solid fats/alcohol/added sugars intake, and a higher solid fats/alcohol/added sugars score (11.1 ± 0.2 vs 8.2 ± 0.1) than nonconsumers. The total Healthy Eating Index 2005 score was significantly higher (P < .01) in consumers (59.3 ± 0.5) than nonconsumers (49.4 ± 0.3). Covariate-adjusted weight (78.2 ± 0.6 vs 80.7 ± 0.3 kg), body mass index (27.1 ± 0.2 vs 28.1 ± 0.2), and waist circumference (94.0 ± 0.5 vs 96.5 ± 0.2 cm) were lower (P < .01) in consumers than nonconsumers, respectively. Dried fruit consumption was associated with improved nutrient intakes, a higher overall diet quality score, and lower body weight/adiposity measures. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Dried fruit consumption is associated with improved diet quality and reduced obesity in US adults: National Health and Nutrition Examination Survey..."
},
{
"docid": "MED-3052",
"text": "Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.",
"title": "Obesity and addiction: neurobiological overlaps."
},
{
"docid": "MED-1353",
"text": "Depression is a potentially life-threatening disorder affecting millions of people across the globe. It is a huge burden to both the individual and society, costing over £9 billion in 2000 alone: the World Health Organisation (WHO) cited it as the third leading cause of global disability in 2004 (first in the developed world), and project it will be the leading cause by 2030. The serendipitous discovery of antidepressants has revolutionized both our understanding and management of depression: however, their efficacy in the treatment of depression has long been debated and recently been brought very much into the public limelight by a controversial publication by Kirsch, in which the role of placebo response in antidepressant efficacy trials is highlighted. Whilst antidepressants offer benefits in both the short and long term, important problems persist such as intolerability, delayed therapeutic onset, limited efficacy in milder depression and the existence of treatment-resistant depression.",
"title": "The drugs don’t work? antidepressants and the current and future pharmacological management of depression"
},
{
"docid": "MED-3354",
"text": "The luminance contrast between facial features and facial skin is greater in women than in men, and women's use of make-up enhances this contrast. In black-and-white photographs, increased luminance contrast enhances femininity and attractiveness in women's faces, but reduces masculinity and attractiveness in men's faces. In Caucasians, much of the contrast between the lips and facial skin is in redness. Red lips have been considered attractive in women in geographically and temporally diverse cultures, possibly because they mimic vasodilation associated with sexual arousal. Here, we investigate the effects of lip luminance and colour contrast on the attractiveness and sex typicality (masculinity/femininity) of human faces. In a Caucasian sample, we allowed participants to manipulate the colour of the lips in colour-calibrated face photographs along CIELab L* (light--dark), a* (red--green), and b* (yellow--blue) axes to enhance apparent attractiveness and sex typicality. Participants increased redness contrast to enhance femininity and attractiveness of female faces, but reduced redness contrast to enhance masculinity of men's faces. Lip blueness was reduced more in female than male faces. Increased lightness contrast enhanced the attractiveness of both sexes, and had little effect on perceptions of sex typicality. The association between lip colour contrast and attractiveness in women's faces may be attributable to its association with oxygenated blood perfusion indicating oestrogen levels, sexual arousal, and cardiac and respiratory health.",
"title": "Lip colour affects perceived sex typicality and attractiveness of human faces."
},
{
"docid": "MED-4753",
"text": "BACKGROUND: Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregnant cows. The purpose of the present study was therefore to examine concentrations of serum and urine sex hormones after the intake of cow milk. METHODS: Subjects were seven men, six prepubertal children, and five women. The men and children drank 600 mL/m(2) of cow milk. Urine samples were collected 1 h before the milk intake and four times every hour after intake. In men the serum samples were obtained before and 15, 30, 45, 60, 90 and 120 min after milk intake. Women drank 500 mL of cow's milk every night for 21 days beginning on the first day of the second menstruation. In three successive menstrual cycles, the day of ovulation was examined using an ovulation checker. RESULTS: After the intake of cow milk, serum estrone (E1) and progesterone concentrations significantly increased, and serum luteinizing hormone, follicle-stimulating hormone and testosterone significantly decreased in men. Urine concentrations of E1, estradiol, estriol and pregnanediol significantly increased in all adults and children. In four out of five women, ovulation occurred during the milk intake, and the timing of ovulation was similar among the three menstrual cycles. CONCLUSIONS: The present data on men and children indicate that estrogens in milk were absorbed, and gonadotropin secretion was suppressed, followed by a decrease in testosterone secretion. Sexual maturation of prepubertal children could be affected by the ordinary intake of cow milk.",
"title": "Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows."
},
{
"docid": "MED-3058",
"text": "Recent research indicates similarities between obesity and addictive disorders on both the phenomenological and neurobiological level. In particular, neuroendocrine and imaging studies suggest a close link between the homeostatic regulation of appetite on the on hand, and motivation and reward expectancy on the other. In addition, findings from neuropsychological studies additionally demonstrate alterations of cognitive function in both obesity and addictive disorders that possibly contribute to a lack of control in resisting consumption. In this review, recent findings on overlapping neurobiological and phenomenological pathways are summarized and the impact with regard to new treatment approaches for obesity is discussed. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.",
"title": "Implications from addiction research towards the understanding and treatment of obesity."
},
{
"docid": "MED-2643",
"text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.",
"title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action"
},
{
"docid": "MED-2654",
"text": "4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated.",
"title": "Endocrine disrupting nonylphenols are ubiquitous in food."
},
{
"docid": "MED-2719",
"text": "Summary Weight loss resulting from an exercise intervention tends to be lower than predicted. Modest weight loss can arise from an increase in energy intake, physiological reductions in resting energy expenditure, an increase in lean tissue or a decrease in non-exercise activity. Lower than expected, weight loss could also arise from weak and invalidated assumptions within predictive models. To investigate these causes, we systematically reviewed studies that monitored compliance to exercise prescriptions and measured exercise-induced change in body composition. Changed body energy stores were calculated to determine the deficit between total daily energy intake and energy expenditures. This information combined with available measurements was used to critically evaluate explanations for low exercise-induced weight loss. We conclude that the small magnitude of weight loss observed from the majority of evaluated exercise interventions is primarily due to low doses of prescribed exercise energy expenditures compounded by a concomitant increase in caloric intake.",
"title": "Why do individuals not lose more weight from an exercise intervention at a defined dose? An energy balance analysis"
},
{
"docid": "MED-1352",
"text": "Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted.",
"title": "Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good"
},
{
"docid": "MED-3035",
"text": "Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986–1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.",
"title": "Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity"
},
{
"docid": "MED-4006",
"text": "BACKGROUND: Dietary fat type is known to modulate the plasma lipid profile, but its effects on plasma homocysteine and inflammatory markers are unclear. OBJECTIVE: We investigated the effects of high-protein Malaysian diets prepared with palm olein, coconut oil (CO), or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease (CVD) in healthy adults. DESIGN: A randomized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects. The 3 test fats, namely palmitic acid (16:0)-rich palm olein (PO), lauric and myristic acid (12:0 + 14:0)-rich CO, and oleic acid (18:1)-rich virgin olive oil (OO), were incorporated at two-thirds of 30% fat calories into high-protein Malaysian diets. RESULTS: No significant differences were observed in the effects of the 3 diets on plasma total homocysteine (tHcy) and the inflammatory markers TNF-α, IL-1β, IL-6, and IL-8, high-sensitivity C-reactive protein, and interferon-γ. Diets prepared with PO and OO had comparable nonhypercholesterolemic effects; the postprandial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower (P < 0.05) than for the CO diet. Unlike the PO and OO diets, the CO diet was shown to decrease postprandial lipoprotein(a). CONCLUSION: Diets that were rich in saturated fatty acids prepared with either PO or CO, and an OO diet that was high in oleic acid, did not alter postprandial or fasting plasma concentrations of tHcy and selected inflammatory markers. This trial was registered at clinicaltrials.gov as NCT00941837.",
"title": "Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homoc..."
},
{
"docid": "MED-3815",
"text": "Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.",
"title": "Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes"
},
{
"docid": "MED-2946",
"text": "OBJECTIVE: Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians. DESIGN: Double-blind, placebo controlled, randomised crossover study. SETTING: Community dwelling vegetarians. PARTICIPANTS: Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. INTERVENTION: Vitamin B-12 (500 µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41). MEASUREMENT: Flow-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound. RESULTS: The mean age of the subjects was 45±9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150 pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09 mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09 mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (β=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028). CONCLUSIONS: Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention.",
"title": "Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status."
},
{
"docid": "MED-3943",
"text": "The health benefits associated with pomegranate juice have led to the development of pomegranate extracts as botanical dietary supplements. Pomegranates contain hydrolyzable tannins in the form of punicalagins and punicalin as well as tannin-based complex oligomers that account for much of the antioxidant activity in juice. The content of ellagic acid has been used to standardize most pomegranate extract dietary supplements marketed. However, supplements can be adulterated with ellagic acid from less expensive plant sources and undercut this method of standardization. To compare the phytochemical contents and antioxidant activities of commercially available pomegranate extract dietary supplements beyond their content of ellagic acid, a total of 27 different supplements in the form of capsules, tablets, and soft gels were studied. Total phenolics were measured using both gallic acid equivalent (GAE) and ellagic acid equivalent (EAE) assays. Punicalagins, punicalin, and ellagic acid contents were determined by HPLC, whereas antioxidant capacity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay. Of the 27 supplements tested, only 5 had the typical pomegranate tannin profile by HPLC, 17 had ellagic acid as the predominant chemical with minor or no detectable pomegranate tannins, and 5 had no detectable tannins or ellagic acid. Therefore, standardization of pomegranate extract supplements based on their ellagic acid content does not guarantee pomegranate supplement authenticity. Future research is needed to assess the health impact of substituting ellagic acid for the complex mix of phytochemicals in a pomegranate extract dietary supplement.",
"title": "Absence of pomegranate ellagitannins in the majority of commercial Pomegranate extracts: implications for standardization and quality control."
},
{
"docid": "MED-3207",
"text": "Summary Grapefruit is a popular, tasty and nutritive fruit enjoyed globally. Biomedical evidence in the last 10 years has, however, shown that consumption of grapefruit or its juice is associated with drug interactions, which, in some cases, have been fatal. Grapefruit-induced drug interactions are unique in that the cytochrome P450 enzyme CYP3A4, which metabolises over 60% of commonly prescribed drugs as well as other drug transporter proteins such as P-glycoprotein and organic cation transporter proteins, which are all expressed in the intestines, are involved. However, the extent to which grapefruit–drug interactions impact on clinical settings has not been fully determined, probably because many cases are not reported. It has recently emerged that grapefruit, by virtue of its rich flavonoid content, is beneficial in the management of degenerative diseases such as diabetes and cardiovascular disorders. This potentially explosive subject is reviewed here.",
"title": "The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives"
},
{
"docid": "MED-3127",
"text": "AIM: Isoflavones in soy foods are part of a larger class of flayonoid compounds that have have been demonstrated to be potent dietary anti-cancer agents, and the effect of soy intake on the survival of ovarian cancer is conflicting. Therefore, we aimed to explore the whether soy intake is related to the risk of death of breast cancer. METHODS: A prospective study was conducted. A total of 256 patients included in this study had breast cancer and were recruited between January 2004 and January 2006. All of them were followed up from since January 2011. A univariate Cox's regression analysis was used to assess the association between soy intake and survival. RESULTS: The education level, menopausal status, ER/PR status and TNM stage were significant difference in the survival of breast cancer. The highest soy isoflavone was associated with a decreased death risk of breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of soy protein also presented a trend decreased breast cancer risk, and the highest consumption significantly reduced the cancer risk compared with the lowest consumption (OR=0.38, 95% CI=0.17-0.86). CONCLUSION: The present study suggests soy intake is associated with a significant reduced death risk of breast cancer in Chinese population. Further large sample studies are warranted to confirm the inverse association of soy consumption and breast cancer survival by menopausal status.",
"title": "Study on soy isoflavone consumption and risk of breast cancer and survival."
},
{
"docid": "MED-2939",
"text": "Background: Vegetarianism is associated with a lower risk of cardiovascular disease. However, studies of arterial function in vegetarians are limited. Methods: This study investigated arterial function in vegetarianism by comparing 49 healthy postmenopausal vegetarians with 41 age-matched omnivores. The arterial function of the common carotid artery was assessed by carotid duplex, while the pulse dynamics method was used to measure brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR). Fasting blood levels of glucose, lipids, lipoprotein (a), high-sensitivity C-reactive protein, homocysteine, and vitamin B12 were also measured. Results: Vegetarians had significantly lower serum cholesterol, high-density and low-density lipoprotein, and glucose compared with omnivores. They also had lower vitamin B12 but higher homocysteine levels. Serum levels of lipoprotein (a) and high-sensitivity C-reactive protein were no different between the two groups. There were no significant differences in carotid beta stiffness index, BAC, and BAD between the two groups even after adjustment for associated covariates. However, BAR was significantly lower in vegetarians than in omnivores. Multiple linear regression analysis revealed that age and pulse pressure were two important determinants of carotid beta stiffness index and BAD. Vegetarianism is not associated with better arterial elasticity. Conclusion: Apparently healthy postmenopausal vegetarians are not significantly better in terms of carotid beta stiffness index, BAC, and BAD, but have significantly decreased BAR than omnivores. Prevention of vitamin B12 deficiency might be beneficial for cardiovascular health in vegetarians.",
"title": "Arterial function of carotid and brachial arteries in postmenopausal vegetarians"
},
{
"docid": "MED-3949",
"text": "In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.",
"title": "Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia."
},
{
"docid": "MED-4262",
"text": "Satiety, which is the inhibition of eating following the end of a meal, is influenced by a number of food characteristics, including compositional and structural factors. An increased understanding of these factors and the mechanisms whereby they exert their effects on satiety may offer a food-based approach to weight management. Water and gas, which are often neglected in nutrition, are major components of many foods and contribute to volume, and to sensory and other characteristics. A review of previous short-term studies that evaluated the effects of water or gas in foods on satiety showed that while satiety was generally increased, effects on subsequent intakes were not always apparent. These studies were diverse in terms of design, timings and food matrices, which precludes definitive conclusions. However, the results indicate that solids may be more effective at increasing satiety than liquids, but gas may be as effective as water. Although increased gastric distension may be the main mechanism underlying these effects, pre-ingestive and ingestive impacts on cognitive, anticipatory and sensory responses also appear to be involved. Furthermore, there is limited evidence that water on its own may be effective at increasing satiety and decreasing intakes when drunk before, but not with, a meal. Longer-term extrapolation suggests that increasing food volumes with water or gas may offer weight-management strategies. However, from a practical viewpoint, the effects of water and gas on satiety may be best exploited by using these non-nutrients to manipulate perceived portion sizes, without increasing energy contents.",
"title": "Satiety: have we neglected dietary non-nutrients?"
},
{
"docid": "MED-2436",
"text": "The content of low density lipoprotein (LDL) receptors in tissue from primary breast cancers was determined and its prognostic information compared with that of variables of established prognostic importance. Frozen tumour specimens were selected, and tissue from 72 patients (32 of whom had died) were studied. The LDL receptor content showed an inverse correlation with the survival time. Analysis by a multivariate statistical method showed that the presence of axillary metastasis, content of receptors for oestrogen and LDL, diameter of the tumour, and DNA pattern were all of prognostic value with regard to patient survival. Improved methods of predicting survival time in patients with breast cancer may be of value in the choice of treatment for individual patients.",
"title": "Content of low density lipoprotein receptors in breast cancer tissue related to survival of patients."
},
{
"docid": "MED-3139",
"text": "Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.",
"title": "Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women"
},
{
"docid": "MED-3129",
"text": "BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50 % tumour cells) in 41 (43 %) cases, reduced (20-50 % tumour cells) in 33 (35 %) cases and absent/markedly reduced (<20 % tumour cells) in 21 (22.1 %) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5 %) and were more often ER-negative (62 versus 39 %) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24 %). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.",
"title": "BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression."
},
{
"docid": "MED-2434",
"text": "The specific role of dietary fat in breast cancer progression is unclear, although a low-fat diet was associated with decreased recurrence of estrogen receptor alpha negative (ER(-)) breast cancer. ER(-) basal-like MDA-MB-231 and MDA-MB-436 breast cancer cell lines contained a greater number of cytoplasmic lipid droplets compared to luminal ER(+) MCF-7 cells. Therefore, we studied lipid storage functions in these cells. Both triacylglycerol and cholesteryl ester (CE) concentrations were higher in the ER(-) cells, but the ability to synthesize CE distinguished the two types of breast cancer cells. Higher baseline, oleic acid- and LDL-stimulated CE concentrations were found in ER(-) compared to ER(+) cells. The differences corresponded to greater mRNA and protein levels of acyl-CoA:cholesterol acyltransferase 1 (ACAT1), higher ACAT activity, higher caveolin-1 protein levels, greater LDL uptake, and lower de novo cholesterol synthesis in ER(-) cells. Human LDL stimulated proliferation of ER(-) MDA-MB-231 cells, but had little effect on proliferation of ER(+) MCF-7 cells. The functional significance of these findings was demonstrated by the observation that the ACAT inhibitor CP-113,818 reduced proliferation of breast cancer cells, and specifically reduced LDL-induced proliferation of ER(-) cells. Taken together, our studies show that a greater ability to take up, store and utilize exogenous cholesterol confers a proliferative advantage to basal-like ER(-) breast cancer cells. Differences in lipid uptake and storage capability may at least partially explain the differential effect of a low-fat diet on human breast cancer recurrence.",
"title": "High ACAT1 expression in estrogen receptor negative basal-like breast cancer cells is associated with LDL-induced proliferation."
},
{
"docid": "MED-1722",
"text": "Overexpression of growth factors and/or their receptors is a common event in malignancy and provides the underlying mechanisms for one of the hallmarks of cancer, uncontrolled proliferation. Mounting evidence suggests that IGF-1 is involved in the pathogenesis and progression of different types of human cancer such as colon, breast, prostate and lung. However, only a few studies have investigated the association between IGF-1 levels and childhood cancer risk. We aimed to compare the IGF-1 serum level in children with de novo malignancies to healthy children, and to assess its relationship with cancer type, stage, metastasis and different disease characteristics. The study was carried out on 100 children; 50 children with de novo malignancies and 50 healthy children of matched age and gender as a control group. The patients were subjected to a routine work-up for their cancers according to our local standards. Estimation of the serum level of IGF-1 was carried out in the two groups using ELISA. Our results showed that children with cancer had significantly higher levels of IGF-1 than healthy controls of the same age and gender. No association was found between IGF-1 and tumor type, stage, metastasis and other disease characteristics. In conclusion, the IGF-1 serum level is an important indicator of risk for the most prevalent forms of childhood cancer. It may be used to identify children at the highest risk for these cancers and aid in determing who may benefit most from preventive strategies. Given the small number of children in our study, studies with larger populations are required to confirm these results.",
"title": "Insulin-like growth factor-1 and childhood cancer risk"
},
{
"docid": "MED-2649",
"text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.",
"title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"
},
{
"docid": "MED-2661",
"text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.",
"title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)."
},
{
"docid": "MED-3817",
"text": "Background: Putrescine, spermidine, and spermine are the polyamines required for human cell growth. The inhibition of ornithine decarboxylase (ODC), which is the rate-limiting enzyme of polyamine biosynthesis, decreases tumor growth and the development of colorectal adenomas. A database was developed to estimate dietary polyamine exposure and relate exposure to health outcomes. Objective: We hypothesized that high polyamine intake would increase risk of colorectal adenoma and that the allelic variation at ODC G>A +316 would modify the association. Design: Polyamine exposure was estimated in subjects pooled (n = 1164) from the control arms of 2 randomized trials for colorectal adenoma prevention [Wheat Bran Fiber low-fiber diet arm (n = 585) and Ursodeoxycholic Acid placebo arm (n = 579)] by using baseline food-frequency questionnaire data. All subjects had to have a diagnosis of colorectal adenoma to be eligible for the trial. Results: A dietary intake of polyamines above the median amount in the study population was associated with 39% increased risk of colorectal adenoma at follow-up (adjusted OR: 1.39; 95% CI: 1.06, 1.83) in the pooled sample. In addition, younger participants (OR: 1.94; 95% CI: 1.23, 3.08), women (OR: 2.43; 95% CI: 1.48, 4.00), and ODC GG genotype carriers (OR: 1.59; 95% CI: 1.00, 2.53) had significantly increased odds of colorectal adenoma if they consumed above-median polyamine amounts. Conclusions: This study showed a role for dietary polyamines in colorectal adenoma risk. Corroboration of these findings would confirm a previously unrecognized, modifiable dietary risk factor for colorectal adenoma.",
"title": "Dietary polyamine intake and risk of colorectal adenomatous polyps"
},
{
"docid": "MED-2646",
"text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.",
"title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..."
},
{
"docid": "MED-4271",
"text": "Dietary fibres are indigestible food ingredients that reach the colon and are then fermented by colonic bacteria, resulting mainly in the formation of short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate. Those SCFA, especially butyrate, are recognised for their potential to act on secondary chemoprevention by slowing growth and activating apoptosis in colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different drug metabolising enzymes. This can reduce the burden of carcinogens and, therefore, decrease the number of mutations, reducing cancer risk. Activation of GSTs by butyrate has been studied on mRNA, protein, and enzyme activity level by real-time RT-PCR, cDNA microarrays, Western blotting, or photometrical approaches, respectively. Butyrate had differential effects in colon cells of different stages of cancer development. In HT29 tumour cells, e.g., mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced. In LT97 adenoma cells, GSTM3, GSTT2, and MGST3 were induced, whereas GSTA2, GSTT2, and catalase (CAT) were elevated in primary colon cells. Colon cells of different stages of carcinogenesis differed in post-transcriptional regulatory mechanisms because butyrate increased protein levels of different GST isoforms and total GST enzyme activity in HT29 cells, whereas in LT97 cells, GST protein levels and activity were slightly reduced. Because butyrate increased histone acetylation and phosphorylation of ERK in HT29 cells, inhibition of histone deacetylases and the influence on MAPK signalling are possible mechanisms of GST activation by butyrate. Functional consequences of this activation include a reduction of DNA damage caused by carcinogens like hydrogen peroxide or 4-hydroxynonenal (HNE) in butyrate-treated colon cells. Treatment of colon cells with the supernatant from an in vitro fermentation of inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells. Additional animal and human studies are needed to define the exact role of dietary fibre and butyrate in inducing GST activity and reducing the risk of colon cancer.",
"title": "Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre."
},
{
"docid": "MED-5005",
"text": "AIM: To evaluate consumption of foods rich in dietary fibre and its relation to the prevalence of constipation in pre-school children. METHODS: In total, 368 children aged 3-5 years were randomly selected from kindergartens in Hong Kong. Constipation was confirmed by Rome-criteria. Children with normal bowel habits served as non-constipated controls. Consumption of vegetables, fruits, whole-grain cereals and fluid were determined using a 3-day food record. RESULTS: A total of 28.8% children were reported to have constipation. Median dietary fibre intake of constipated children was significantly lower than non-constipated children (3.4 g/d (inter-quartile range (IQR): 2.3-4.6 g/d) vs. 3.8 g/d (IQR: 2.7-4.9 g/d); P = 0.044) corresponding to 40% reference dietary fibre intake. Constipated children also had significantly lower intakes of vitamin C (P = 0.041), folate (P = 0.043) and magnesium (P = 0.002). Fruit intake and total plant foods intake were significantly lower in the constipated than non-constipated children: (61 g/d (IQR: 23.8-115 g/d) vs. 78 g/d (IQR: 41.7-144.6 g/d); P = 0.047) and (142.5 g/d (IQR: 73.7-214.7 g/d) vs. 161.1 g/d (IQR: 98.3-233.3 g/d); P = 0.034), respectively. Total fluid intake did not differ between groups but milk intake among the constipated children was marginally higher than the non-constipated children (P = 0.055) CONCLUSION: Insufficient dietary fibre intake is common in Hong Kong pre-school children. Constipated children had significantly lower intakes of dietary fibre and micronutrients including vitamin C, folate and magnesium than non-constipated counterparts which was attributable to under-consumption of plant foods. However, milk intake was marginally higher in the constipated children. More public education is necessary for parents to help develop healthy dietary habit and bowel habit in early life in order to prevent childhood constipation.",
"title": "Increased prevalence of constipation in pre-school children is attributable to under-consumption of plant foods: A community-based study."
},
{
"docid": "MED-5008",
"text": "In view of the increasing prevalence of obesity all over the world, we have seen morbid obesity occurring at earlier ages, and especially in adolescents. The first and main approach has been a conservative one, including change of lifestyle - implying better feeding habits and physical activity. However, our weapons to deal with this 'pandemic of obesity' have not solved a large number of cases, and we have to admit that bariatric surgery should be contemplated in special cases. Many different approaches have been devised by bariatric surgeons and although the complications over the short- and long-term are high and potentially severe, in some cases it is the only approach that has the potential to put the patient back to a more 'normal' metabolic situation with a significant weight loss. We discuss the main surgical approaches for morbid obesity and we comment on the pros and cons of each of them.",
"title": "Bariatric surgery in pediatrics--is it time?"
},
{
"docid": "MED-4933",
"text": "Recently, we reported on the analysis of polychlorinated biphenyls (PCBs) and chlorinated pesticides in farmed Atlantic salmon (Salmo salar) from Maine, eastern Canada, and Norway, and wild Alaskan Chinook salmon (Oncorhynchus tshawytscha). In this paper, we extend the analysis to polybrominated diphenyl ethers (PBDEs) in these samples. Total PBDE concentrations in the farmed salmon (0.4-1.4ng/g, wet weight, ww) were not significantly different from those in the wild Alaskan Chinook samples (0.4-1.2ng/g, ww), nor were significant differences found among regions. However, significant intra-regional variations in concentrations of total PBDEs and tetra-BDE 47 were observed in the salmon from the Canadian farms (p<0.01). Congener profiles were dominated by BDE-47, followed by the penta-BDEs 99 and 100. PBDE concentrations in the Canadian samples were lower than those reported two years earlier. Removal of skin resulted in no overall reduction in PBDE concentrations in our farmed salmon, and in some cases, PBDE concentrations were higher in skin-off samples. PBDEs were correlated with lipids only in the skinned samples, suggesting that there is greater accumulation and retention of PBDEs in muscle lipids than in skin-associated fat. In skin-on samples, modest correlations were observed between concentrations of PBDEs and PCBs (R(2)=0.47) and mono-ortho PCBs (R(2)=0.50), whereas PBDEs were not correlated with non-ortho PCBs.",
"title": "Polybrominated diphenyl ethers (PBDEs) in farmed and wild salmon marketed in the Northeastern United States."
},
{
"docid": "MED-4755",
"text": "OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.",
"title": "Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence."
},
{
"docid": "MED-3051",
"text": "The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI) studies have indicated that glucose consumption has some effect on the neuronal activity levels in the hypothalamus, this matter has not been investigated extensively yet. For instance, dose-dependency of the hypothalamic responses to glucose ingestion has not been addressed. We measured the effects of two different glucose loads on neuronal activity levels in the human hypothalamus using fMRI. After an overnight fast, the hypothalamus of 15 normal weight men was scanned continuously for 37 min. After 7 min, subjects ingested either water or a glucose solution containing 25 or 75 g of glucose. We observed a prolonged decrease of the fMRI signal in the hypothalamus, which started shortly after subjects began drinking the glucose solution and lasted for at least 30 min. Moreover, the observed response was dose-dependent: a larger glucose load resulted in a larger signal decrease. This effect was most pronounced in the upper anterior hypothalamus. In the upper posterior hypothalamus, the signal decrease was similar for both glucose loads. No effect was found in the lower hypothalamus. We suggest a possible relation between the observed hypothalamic response and changes in the blood insulin concentration.",
"title": "Functional MRI of human hypothalamic responses following glucose ingestion."
},
{
"docid": "MED-3046",
"text": "Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.",
"title": "Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study."
},
{
"docid": "MED-1723",
"text": "The lower rates of some cancers in Asian countries than in Western countries may be partly because of diet, although the mechanisms are unknown. The aim of this cross-sectional study was to determine whether a plant-based (vegan) diet is associated with a lower circulating level of insulin-like growth factor I (IGF-I) compared with a meat-eating or lacto-ovo-vegetarian diet among 292 British women, ages 20-70 years. The mean serum IGF-I concentration was 13% lower in 92 vegan women compared with 99 meat-eaters and 101 vegetarians (P = 0.0006). The mean concentrations of both serum IGF-binding protein (IGFBP)-1 and IGFBP-2 were 20-40% higher in vegan women compared with meat-eaters and vegetarians (P = 0.005 and P = 0.0008 for IGFBP-1 and IGFBP-2, respectively). There were no significant differences in IGFBP-3, C-peptide, or sex hormone-binding globulin concentrations between the diet groups. Intake of protein rich in essential amino acids was positively associated with serum IGF-I (Pearson partial correlation coefficient; r = 0.27; P < 0.0001) and explained most of the differences in IGF-I concentration between the diet groups. These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I and higher levels of IGFBP-1 and IGFBP-2.",
"title": "The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans."
},
{
"docid": "MED-3136",
"text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.",
"title": "Influence of frequent and long-term bean consumption on colonic function and fermentation."
},
{
"docid": "MED-3137",
"text": "A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.",
"title": "Americans Do Not Meet Federal Dietary Recommendations"
},
{
"docid": "MED-4007",
"text": "Background Alzheimer's disease (AD) is characterized by early and region-specific declines in cerebral glucose metabolism. Ketone bodies are produced by the body during glucose deprivation and are metabolized by the brain. An oral ketogenic compound, AC-1202, was tested in subjects with probable AD to examine if ketosis could improve cognitive performance. Methods Daily administration of AC-1202 was evaluated in 152 subjects diagnosed with mild to moderate AD in a US-based, 90-day, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were on a normal diet and continued taking approved AD medications. Primary cognitive end points were mean change from Baseline in the AD Assessment Scale-Cognitive subscale (ADAS-Cog), and global scores in the AD Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC). AC-1202 was compared to Placebo in several population groups, including: intention-to-treat (ITT), per protocol, and dosage compliant groups. Results were also stratified by APOE4 carriage status (a predefined analysis based on the epsilon 4 (E4) variant of the apolipoprotein E gene). This trial was registered with ClinicalTrials.gov, registry number NCT00142805, information available at http://clinicaltrials.gov/ct2/show/NCT00142805 Results AC-1202 significantly elevated a serum ketone body (β-hydroxybutyrate) 2 hours after administration when compared to Placebo. In each of the population groups, a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45: 1.9 point difference, p = 0.0235 in ITT; 2.53 point difference, p = 0.0324 in per protocol; 2.6 point difference, p = 0.0215 in dosage compliant. Among participants who did not carry the APOE4 allele (E4(-)), a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45 and Day 90. In the ITT population, E4(-) participants (N = 55) administered AC-1202 had a significant 4.77 point difference in mean change from Baseline in ADAS-Cog scores at Day 45 (p = 0.0005) and a 3.36 point difference at Day 90 (p = 0.0148) compared to Placebo. In the per protocol population, E4(-) participants receiving AC-1202 (N = 37) differed from placebo by 5.73 points at Day 45 (p = 0.0027) and by 4.39 points at Day 90 (p = 0.0143). In the dosage compliant population, E4(-) participants receiving AC-1202 differed from placebo by 6.26 points at Day 45 (p = 0.0011, N = 38) and 5.33 points at Day 90 (p = 0.0063, N = 35). Furthermore, a significant pharmacologic response was observed between serum β-hydroxybutyrate levels and change in ADAS-Cog scores in E4(-) subjects at Day 90 (p = 0.008). Adverse events occurred more frequently in AC-1202 subjects, were primarily restricted to the gastrointestinal system, and were mainly mild to moderate in severity and transient in nature. Conclusion AC-1202 rapidly elevated serum ketone bodies in AD patients and resulted in significant differences in ADAS-Cog scores compared to the Placebo. Effects were most notable in APOE4(-) subjects who were dosage compliant.",
"title": "Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial"
},
{
"docid": "MED-3059",
"text": "AIMS: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling, but no studies have compared the effects of glucose and fructose. We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process. METHODS: Nine healthy, normal weight subjects underwent blood oxygenation level dependent (BOLD) fMRI measurements during either intravenous (IV) glucose (0.3 mg/kg), fructose (0.3 mg/kg) or saline, administered over 2 min in a randomized, double-blind, crossover study. Blood was sampled every 5 min during a baseline period and following infusion for 60 min in total for glucose, fructose, lactate and insulin levels. RESULTS: No significant brain BOLD signal changes were detected in response to IV saline. BOLD signal in the cortical control areas increased during glucose infusion (p = 0.002), corresponding with increased plasma glucose and insulin levels. In contrast, BOLD signal decreased in the cortical control areas during fructose infusion (p = 0.006), corresponding with increases of plasma fructose and lactate. Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus. CONCLUSION: In normal weight humans, cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose. Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake. © 2011 Blackwell Publishing Ltd.",
"title": "Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans."
},
{
"docid": "MED-3947",
"text": "Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.",
"title": "Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells."
},
{
"docid": "MED-4407",
"text": "Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Addition of açaí (Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice."
},
{
"docid": "MED-2940",
"text": "In the past 3 decades, the total number of CT scans performed has grown exponentially. In 2007, > 70 million CT scans were performed in the United States. CT scan studies of the chest comprise a large portion of the CT scans performed today because the technology has transformed the management of common chest diseases, including pulmonary embolism and coronary artery disease. As the number of studies performed yearly increases, a growing fraction of the population is exposed to low-dose ionizing radiation from CT scan. Data extrapolated from atomic bomb survivors and other populations exposed to low-dose ionizing radiation suggest that CT scan-associated radiation may increase an individual's lifetime risk of developing cancer. This finding, however, is not incontrovertible. Because this topic has recently attracted the attention of both the scientific community and the general public, it has become increasingly important for physicians to understand the cancer risk associated with CT scan and be capable of engaging in productive dialogue with patients. This article reviews the current literature on the public health debate surrounding CT scan and cancer risk, quantifies radiation doses associated with specific studies, and describes efforts to reduce population-wide CT scan-associated radiation exposure. CT scan examinations of the chest, including CT scan pulmonary and coronary angiography, high-resolution CT scan, low-dose lung cancer screening, and triple rule-out CT scan, are specifically considered.",
"title": "Radiation and chest CT scan examinations: what do we know?"
},
{
"docid": "MED-3038",
"text": "The effects of 50 mg naltrexone on eating and subjective appetite were assessed in a double-blind placebo-controlled study with 20 male volunteers. Appetite was monitored using a disguised digital balance connected to a micro-computer, which constantly monitored the amount of food remaining, and which automatically interrupted feeding for 30 s after every 50 g consumed to allow appetite ratings to be made. Half the subjects ate pasta with a cheese sauce, and the remainder pasta with a tomato sauce. Subjects ate significantly less of both foods after 50 mg naltrexone than in either the placebo condition or on the initial (familiarisation) day. Naltrexone also reduced the rated pleasantness of both foods, and reduced overall eating rate. When best-fit quadratic functions were used to describe changes in rated hunger in relation to intake within the meal, naltrexone abolished the positive linear component reflecting the initial stimulation of appetite without altering either intercept or the negative quadratic function. Although mood ratings suggested that naltrexone had a mild sedative effect, mood changes alone could not explain the effects of naltrexone on appetite. Overall, these data suggest a specific role for opioids in the stimulation of appetite through palatability.",
"title": "Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect."
},
{
"docid": "MED-4767",
"text": "We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.",
"title": "Association of adenovirus infection with human obesity."
},
{
"docid": "MED-1445",
"text": "PURPOSE: This study investigated the effect of a low-fat, plant-based diet on body weight, metabolism, and insulin sensitivity, while controlling for exercise in free-living individuals. SUBJECTS AND METHODS: In an outpatient setting, 64 overweight, postmenopausal women were randomly assigned to a low-fat, vegan diet or a control diet based on National Cholesterol Education Program guidelines, without energy intake limits, and were asked to maintain exercise unchanged. Dietary intake, body weight and composition, resting metabolic rate, thermic effect of food, and insulin sensitivity were measured at baseline and 14 weeks. RESULTS: Mean +/- standard deviation intervention-group body weight decreased 5.8 +/- 3.2 kg, compared with 3.8 +/- 2.8 kg in the control group (P = .012). In a regression model of predictors of weight change, including diet group and changes in energy intake, thermic effect of food, resting metabolic rate, and reported energy expenditure, significant effects were found for diet group (P < .05), thermic effect of food (P < .05), and resting metabolic rate (P < .001). An index of insulin sensitivity increased from 4.6 +/- 2.9 to 5.7 +/- 3.9 (P = .017) in the intervention group, but the difference between groups was not significant (P = .17). CONCLUSION: Adoption of a low-fat, vegan diet was associated with significant weight loss in overweight postmenopausal women, despite the absence of prescribed limits on portion size or energy intake.",
"title": "The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity."
},
{
"docid": "MED-4004",
"text": "Evidence suggests that monounsaturated and polyunsaturated fats facilitate greater absorption of carotenoids than saturated fats. However, the comparison of consuming a polyunsaturated fat source versus a saturated fat source on tomato carotenoid bioaccumulation has not been examined. The goal of this study was to determine the influence of coconut oil and safflower oil on tomato carotenoid tissue accumulation in Mongolian gerbils ( Meriones unguiculatus ) fed a 20% fat diet. Coconut oil feeding increased carotenoid concentrations among many compartments including total carotenoids in the serum (p = 0.0003), adrenal glandular phytoene (p = 0.04), hepatic phytofluene (p = 0.0001), testicular all-trans-lycopene (p = 0.01), and cis-lycopene (p = 0.006) in the prostate-seminal vesicle complex compared to safflower oil. Safflower oil-fed gerbils had greater splenic lycopene concentrations (p = 0.006) compared to coconut oil-fed gerbils. Coconut oil feeding increased serum cholesterol (p = 0.0001) and decreased hepatic cholesterol (p = 0.0003) compared to safflower oil. In summary, coconut oil enhanced tissue uptake of tomato carotenoids to a greater degree than safflower oil. These results may have been due to the large proportion of medium-chain fatty acids in coconut oil, which might have caused a shift in cholesterol flux to favor extrahepatic carotenoid tissue deposition.",
"title": "Coconut oil enhances tomato carotenoid tissue accumulation compared to safflower oil in the Mongolian gerbil ( Meriones unguiculatus )."
},
{
"docid": "MED-4934",
"text": "Concentrations of polybrominated diphenyl ethers (PBDEs), pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons were measured in 136 fish from 14 remote lakes in 8 western US National Parks/Preserves between 2003 and 2005 and compared to human and wildlife contaminant health thresholds. A sensitive (median detection limit −18 pg/g wet weight), efficient (61% recovery at 8 ng/g), reproducible (4.1 %RSD), and accurate (7 % deviation from SRM) analytical method was developed and validated for these analyses. Concentrations of PCBs, hexachlorobenzene, hexachlorocyclohexanes, DDTs and chlordanes in western US fish were comparable to or lower than mountain fish recently collected from Europe, Canada, and Asia. Dieldrin and PBDE concentrations were higher than recent measurements in mountain fish and Pacific Ocean salmon. Concentrations of most contaminants in western US fish were 1–6 orders of magnitude below calculated recreational fishing contaminant health thresholds. However, contaminant concentrations exceeded subsistence fishing cancer screening values in 8 of 14 lakes. Average contaminant concentrations in fish exceeded wildlife contaminant health thresholds for piscivorous mammals in 5 lakes, and piscivorous birds in all 14 lakes. These results indicate that atmospherically deposited organic contaminants can accumulate in high elevation fish, reaching concentrations relevant to human and wildlife health.",
"title": "Atmospherically Deposited PBDEs, Pesticides, PCBs, and PAHs in Western US National Park Fish: Concentrations and Consumption Guidelines"
},
{
"docid": "MED-2763",
"text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.",
"title": "Facing the facelessness of public health: what's the public got to do with it?"
},
{
"docid": "MED-3199",
"text": "It has been well established that complex mixtures of phytochemicals in fruits and vegetables can be beneficial for human health. Moreover, it is becoming increasingly apparent that phytochemicals can influence the pharmacological activity of drugs by modifying their absorption characteristics through interactions with drug transporters as well as drug-metabolizing enzyme systems. Such effects are more likely to occur in the intestine and liver, where high concentrations of phytochemicals may occur. Alterations in cytochrome P450 and other enzyme activities may influence the fate of drugs subject to extensive first-pass metabolism. Although numerous studies of nutrient-drug interactions have been published and systematic reviews and meta-analyses of these studies are available, no generalizations on the effect of nutrient-drug interactions on drug bioavailability are currently available. Several publications have highlighted the unintended consequences of the combined use of nutrients and drugs. Many phytochemicals have been shown to have pharmacokinetic interactions with drugs. The present review is limited to commonly consumed fruits and vegetables with significant beneficial effects as nutrients and components in folk medicine. Here, we discuss the phytochemistry and pharmacokinetic interactions of the following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry, pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli, cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that our knowledge of the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate potential risks resulting from food-drug interactions should be intensified in order to prevent undesired and harmful clinical consequences. © 2011 Institute of Food Technologists®",
"title": "Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters."
},
{
"docid": "MED-3956",
"text": "Early onset of puberty may confer adverse health consequences. Thus, modifiable factors influencing the timing of puberty are of public health interest. Childhood overweight as a factor in the earlier onset of menarche has been supported by prospective evidence; nonetheless, its overall contribution may have been overemphasized, since secular trends toward a younger age at menarche have not been a universal finding during the recent obesity epidemic. Current observational studies suggest notable associations between dietary intakes and pubertal timing beyond contributions to an energy imbalance: children with the highest intakes of vegetable protein or animal protein experience pubertal onset up to 7 months later or 7 months earlier, respectively. Furthermore, girls with high isoflavone intakes may experience the onset of breast development and peak height velocity approximately 7-8 months later. These effect sizes are on the order of those observed for potentially neuroactive steroid hormones. Thus, dietary patterns characterized by higher intakes of vegetable protein and isoflavones and lower intakes of animal protein may contribute to a lower risk of breast cancer or a lower total mortality. © 2012 International Life Sciences Institute.",
"title": "Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty."
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-4756",
"text": "BACKGROUND/OBJECTIVES: Little is known about nutritional factors that influence circulating concentrations of steroid hormones, which are consistently associated with risk of breast cancer for postmenopausal women. We aimed to investigate the association between consumption of animal products and the plasma concentrations of steroid hormones and sex hormone-binding globulin (SHBG). SUBJECTS/METHODS: Cross-sectional analysis was conducted on plasma from 766 naturally postmenopausal women. We measured plasma concentrations of steroid hormones and SHBG, and estimated dietary intakes using a 121-item food frequency questionnaire. Log-transformed values of hormone concentrations were regressed on quartiles of intake of meat and dairy products among food items, and fats, proteins and cholesterol among nutrient intake. RESULTS: Total red and fresh red meat consumption was negatively associated with SHBG levels (P for trend=0.04 and <0.01, respectively). Mean SHBG concentrations were approximately 8% and 13% lower for women in the highest quartile compared with the lowest quartile of total red and fresh red meat consumption, respectively. Positive associations were observed between dairy product consumption and total and free estradiol concentrations (P for trend=0.02 and 0.03, respectively). Mean concentrations of total and free estradiol were 15 and 14% higher for women in the highest quartile of dairy product consumption than for those in the lowest quartile, respectively. No associations were observed with consumption of processed meat, chicken, fish, eggs, cholesterol, fats or protein. CONCLUSIONS: Our study suggests that greater consumption of total red and fresh red meat and dairy products might influence circulating concentrations of SHBG and estradiol, respectively. Confirmation and further investigation is required.",
"title": "Consumption of animal products, their nutrient components and postmenopausal circulating steroid hormone concentrations."
},
{
"docid": "MED-3906",
"text": "Date palm is one of the oldest trees cultivated by man. In the folk-lore, date fruits have been ascribed to have many medicinal properties when consumed either alone or in combination with other herbs. Although, fruit of the date palm served as the staple food for millions of people around the world for several centuries, studies on the health benefits are inadequate and hardly recognized as a healthy food by the health professionals and the public. In recent years, an explosion of interest in the numerous health benefits of dates had led to many in vitro and animal studies as well as the identification and quantification of various classes of phytochemicals. On the basis of available documentation in the literature on the nutritional and phytochemical composition, it is apparent that the date fruits are highly nutritious and may have several potential health benefits. Although dates are sugar-packed, many date varieties are low GI diet and refutes the dogma that dates are similar to candies and regular consumption would develop chronic diseases. More investigations in these areas would validate its beneficial effects, mechanisms of actions, and fully appreciate as a potential medicinal food for humans all around the world. Therefore, in this review we summarize the phytochemical composition, nutritional significance, and potential health benefits of date fruit consumption and discuss its great potential as a medicinal food for a number of diseases inflicting human beings.",
"title": "Date fruits (Phoenix dactylifera Linn): an emerging medicinal food."
},
{
"docid": "MED-5000",
"text": "BACKGROUND: High oxalate intake resulting from consuming supplemental doses of cinnamon and turmeric may increase risk of hyperoxaluria, a significant risk factor for urolithiasis. OBJECTIVE: This study assessed urinary oxalate excretion from supplemental doses of cinnamon and turmeric as well as changes in fasting plasma glucose, cholesterol, and triacylglycerol concentrations. DESIGN: Eleven healthy subjects, aged 21-38 y, participated in an 8-wk, randomly assigned, crossover study that involved the ingestion of supplemental doses of cinnamon and turmeric for 4-wk periods that provided 55 mg oxalate/d. Oxalate load tests, which entailed the ingestion of a 63-mg dose of oxalate from the test spices, were performed after each 4-wk experimental period and at the study onset with water only (control treatment). Fasting plasma glucose and lipid concentrations were also assessed at these time points. RESULTS: Compared with the cinnamon and control treatments, turmeric ingestion led to a significantly higher urinary oxalate excretion during the oxalate load tests. There were no significant changes in fasting plasma glucose or lipids in conjunction with the 4-wk periods of either cinnamon or turmeric supplementation. CONCLUSIONS: The percentage of oxalate that was water soluble differed markedly between cinnamon (6%) and turmeric (91%), which appeared to be the primary cause of the greater urinary oxalate excretion/oxalate absorption from turmeric. The consumption of supplemental doses of turmeric, but not cinnamon, can significantly increase urinary oxalate levels, thereby increasing risk of kidney stone formation in susceptible individuals.",
"title": "Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects."
},
{
"docid": "MED-4680",
"text": "OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.",
"title": "Diet throughout childhood and age at menarche in a contemporary cohort of British girls."
},
{
"docid": "MED-4230",
"text": "PURPOSE OF REVIEW: Although age, genetics, and sex steroid hormones play prominent roles in the cause of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS), recent epidemiological studies suggest that modifiable lifestyle factors also contribute substantially to the pathogenesis of these conditions. RECENT FINDINGS: Lifestyle and metabolic factors associated with significantly increased risks of benign prostatic hyperplasia and lower urinary tract symptoms include obesity, diabetes, and meat and fat consumption. Factors associated with decreased risks include physical activity, moderate alcohol intake, and vegetable consumption. Factors for which no clear risk patterns have emerged include lipids and smoking. Randomized clinical trials of lifestyle alterations - such as weight loss, exercise, and diet - for the prevention or treatment of benign prostatic hyperplasia and lower urinary tract symptoms have yet to be performed. SUMMARY: Lifestyle factors present a novel opportunity for the prevention and treatment of benign prostatic hyperplasia and lower urinary tract symptoms. Although clinical trials of lifestyle modifications have not yet been undertaken, promotion of healthy lifestyle alternatives within the context of standard benign prostatic hyperplasia and lower urinary tract symptoms treatment algorithms is potentially beneficial.",
"title": "Lifestyle factors, benign prostatic hyperplasia, and lower urinary tract symptoms."
},
{
"docid": "MED-3896",
"text": "BACKGROUND: The frequency of unhealthful snacking has increased dramatically over the last three decades. Fruits and nuts have been shown to have positive health effects. No study has investigated the aggregate effects of various fruits combined with nuts in the form of snack bars on cardiovascular risk factors. The aim of this randomised trial was to investigate the effects of a fruit and nut snack bar on anthropomorphic measures, lipid panel and blood pressure in overweight adults. METHODS: Ninety-four overweight adults (body mass index > 25 kg m(-2)) were randomly assigned to add two fruit and nut bars totalling 1421.9 kJ (340 kcal) to their ad libitum diet (intervention group) or to continue with their ad libitum diet (control group). Subjects underwent assessment for weight (primary outcome measure), as well as waist circumference, lipid panel and blood pressure (secondary outcome measures), before and at the end of the 8-week treatment. RESULTS: Weight did not change from baseline after snack bar addition compared to controls (P = 0.44). Waist circumference (P = 0.69), blood pressure (systolic, P = 0.83; diastolic, P = 0.79) and blood lipid panel (total cholesterol, P = 0.72; high-density lipoprotein, P = 0.11; total cholesterol/high-density lipoprotein, P = 0.37; triglycerides, P = 0.89; low-density lipoprotein, P = 0.81) also did not change from baseline compared to controls. CONCLUSIONS: Two daily fruit and nut bars, totalling 1421.9 kJ (340 kcal), did not cause weight gain. The role of habitual snacking on nutrient dense and satiating foods on both weight over time, and diet quality, warrants further study. Satiating snacks rich in fibre may provide a means to weight stabilisation. © 2011 The Authors. Journal of Human Nutrition and Dietetics © 2011 The British Dietetic Association Ltd.",
"title": "The effect of the addition of daily fruit and nut bars to diet on weight, and cardiac risk profile, in overweight adults."
},
{
"docid": "MED-1714",
"text": "BACKGROUND: Western diets, obesity, and sedentary lifestyles are associated with increased cancer risk. The mechanisms responsible for this increased risk, however, are not clear. OBJECTIVE: We hypothesized that long-term low protein, low calorie intake and endurance exercise are associated with low concentrations of plasma growth factors and hormones that are linked to an increased risk of cancer. DESIGN: Plasma growth factors and hormones were evaluated in 21 sedentary subjects, who had been eating a low-protein, low-calorie diet for 4.4 +/- 2.8 y (x +/- SD age: 53.0 +/- 11 y); 21 endurance runners matched by body mass index (BMI; in kg/m2); and 21 age- and sex-matched sedentary subjects eating Western diets. RESULTS: BMI was lower in the low-protein, low-calorie diet (21.3 +/- 3.1) and runner (21.6 +/- 1.6) groups than in the Western diet (26.5 +/- 2.7; P < 0.005) group. Plasma concentrations of insulin, free sex hormones, leptin, and C-reactive protein were lower and sex hormone-binding globulin was higher in the low-protein, low-calorie diet and runner groups than in the sedentary Western diet group (all P < 0.05). Plasma insulin-like growth factor I (IGF-I) and the concentration ratio of IGF-I to IGF binding protein 3 were lower in the low-protein, low-calorie diet group (139 +/- 37 ng/mL and 0.033 +/- 0.01, respectively) than in the runner (177 +/- 37 ng/mL and 0.044 +/- 0.01, respectively) and sedentary Western (201 +/- 42 ng/mL and 0.046 +/- 0.01, respectively) diet groups (P < 0.005). CONCLUSIONS: Exercise training, decreased adiposity, and long-term consumption of a low-protein, low-calorie diet are associated with low plasma growth factors and hormones that are linked to an increased risk of cancer. Low protein intake may have additional protective effects because it is associated with a decrease in circulating IGF-I independent of body fat mass.",
"title": "Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk."
},
{
"docid": "MED-1345",
"text": "This article explores the reaction when an article challenging received wisdom is published and covered extensively by the media (1). The article in question was a meta-analysis of antidepressant clinical trials indicating that for most patients, difference between drug and placebo was not clinically significant. Reactions ranged from denial that the effects of antidepressants are so small to criticisms of the clinical trials that were analyzed. Each of these reactions is explored and countered.",
"title": "Challenging Received Wisdom: Antidepressants and the Placebo Effect"
},
{
"docid": "MED-1351",
"text": "The relationship between psychiatry and pharmaceutical companies has come under scrutiny during the past decade. Concerns are growing that financial ties of psychiatrists to the pharmaceutical industry may unduly influence professional judgments involving the primary interests of patients. Such conflicts of interest threaten the public trust in psychiatry. The goal of conflict of interest policies is to protect the integrity of professional judgment and to preserve public trust. The disclosure of individual and institutional financial relationships is a critical but limited first step in the process of identifying and responding to conflicts of interest. Conflict of interest policies and procedures can be strengthened by engaged psychiatrists, researchers, institutions, and professional associations in developing policies and consensus standards. Research on conflicts of interest can provide a stronger evidence base for policy design and implementation. Society has traditionally granted the medical profession considerable autonomy and may be willing to continue do so in the case of conflicts of interest. Nevertheless, concern is growing that stronger measures are needed. To avoid undue regulatory burdens, psychiatrists can play a vital role in designing responsible and reasonable conflict of interest policies that reduce the risks of bias and the loss of trust. Psychiatrists and the institutions that carry out research, education, clinical care, and practice guideline development must recognize public concerns about conflicts of interest and take effective measures soon to maintain public trust with a cultural change in the practice of psychiatry, from reactive treatment-seeking for mental illness to proactive advocacy for patients. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.",
"title": "Conflicts of interest in psychiatry: strategies to cultivate literacy in daily practice."
},
{
"docid": "MED-2435",
"text": "Breast cancer is the leading cause of cancer-related deaths in women in the United States and many other countries. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for many cancers, especially for breast cancer. Natural products are being tested with a hope of identifying novel potent molecules as anticancer agents. Phytochemicals and dietary compounds have been used for the treatment of various illnesses throughout history due to their safety, low toxicity, and general availability. Currently, many active phytochemicals are in clinical trials. Preclinical and clinical studies have indicated that daily consumption of dietary phytochemicals reduces the risk of several cancers. Phytochemicals can inhibit, delay, or reverse carcinogenesis by inducing detoxifying and antioxidant enzymes, by regulating inflammatory/proliferative signaling pathways, and by inducing apoptosis. This review article describes some of the potential natural cancer preventive compounds, along with a mechanistic discussion of their interactions with key cellular signal transduction pathways as well as their contribution to the suppression of breast cancer cell growth.",
"title": "Chemoprevention of breast cancer by dietary compounds."
},
{
"docid": "MED-3910",
"text": "Background Figs are a rich source of soluble fiber. We evaluated the effect of consuming dried California Mission figs on serum lipids in hyperlipidemic adults. Methods In a crossover trial men and women aged 30–75 years with elevated low-density lipoprotein cholesterol (100–189 mg/dl) were randomized to add dried California Mission figs (120 g/day) to their usual diet for 5 weeks or eat their usual diet for 5 weeks, then crossed over to the other condition for another 5 weeks. Six 24-hour dietary recalls were obtained. Results Low- and high-density lipoprotein cholesterol and triglyceride concentrations did not differ between usual and figs-added diets (Bonferroni-corrected p > 0.017), while total cholesterol tended to increase with fig consumption (p = 0.02). Total cholesterol increased in participants (n = 41) randomized to usual followed by figs-added diet (p = 0.01), but remained unchanged in subjects (n = 42) who started with figs-added followed by usual diet (p = 0.4). During the figs-added diet, soluble fiber intake was 12.6 ± 3.7 versus 8.2 ± 4.1 g/day in the usual diet (p < 0.0001). Sugar intake increased from 23.4 ± 6.5 to 32.2 ± 6.3% of kcal in the figs-added diet (p < 0.0001). Body weight did not change (p = 0.08). Conclusions Daily consumption of figs did not reduce low-density lipoprotein cholesterol. Triglyceride concentrations were not significantly changed despite an increase in sugar intake.",
"title": "Effect of Consumption of Dried California Mission Figs on Lipid Concentrations"
},
{
"docid": "MED-4290",
"text": "BACKGROUND AND AIMS: Nut intake has been inversely related to body mass index (BMI) in prospective studies. We examined dietary determinants of adiposity in an elderly Mediterranean population with customarily high nut consumption. METHODS AND RESULTS: A cross-sectional study was conducted in 847 subjects (56% women, mean age 67 years, BMI 29.7kg/m(2)) at high cardiovascular risk recruited into the PREDIMED study. Food consumption was evaluated by a validated semi-quantitative questionnaire, energy expenditure in physical activity by the Minnesota Leisure Time Activity questionnaire, and anthropometric variables by standard measurements. Nut intake decreased across quintiles of both BMI and waist circumference (P-trend <0.005; both). Alcohol ingestion was inversely related to BMI (P-trend=0.020) and directly to waist (P-trend=0.011), while meat intake was directly associated with waist circumference (P-trend=0.018). In fully adjusted multivariable models, independent dietary associations of BMI were the intake of nuts inversely (P=0.002) and that of meat and meat products directly (P=0.042). For waist circumference, independent dietary associations were intake of nuts (P=0.002) and vegetables (P=0.040), both inversely, and intake of meat and meat products directly (P=0.009). From the regression coefficients, it was predicted that BMI and waist circumference decreased by 0.78kg/m(2) and 2.1cm, respectively, for each serving of 30g of nuts. Results were similar in men and women. CONCLUSION: Nut consumption was inversely associated with adiposity independently of other lifestyle variables. It remains to be explored whether residual confounding related to a healthier lifestyle of nut eaters might in part explain these results. Copyright © 2009 Elsevier B.V. All rights reserved.",
"title": "Cross-sectional association of nut intake with adiposity in a Mediterranean population."
},
{
"docid": "MED-3254",
"text": "We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.",
"title": "Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study."
},
{
"docid": "MED-2720",
"text": "In this study we examined the effect of physical activity based labels on the calorie content of meals selected from a sample fast food menu. Using a web-based survey, participants were randomly assigned to one of four menus which differed only in their labeling schemes (n=802): (1) a menu with no nutritional information, (2) a menu with calorie information, (3) a menu with calorie information and minutes to walk to burn those calories, or (4) a menu with calorie information and miles to walk to burn those calories. There was a significant difference in the mean number of calories ordered based on menu type (p=0.02), with an average of 1020 calories ordered from a menu with no nutritional information, 927 calories ordered from a menu with only calorie information, 916 calories ordered from a menu with both calorie information and minutes to walk to burn those calories, and 826 calories ordered from the menu with calorie information and the number of miles to walk to burn those calories. The menu with calories and the number of miles to walk to burn those calories appeared the most effective in influencing the selection of lower calorie meals (p=0.0007) when compared to the menu with no nutritional information provided. The majority of participants (82%) reported a preference for physical activity based menu labels over labels with calorie information alone and no nutritional information. Whether these labels are effective in real-life scenarios remains to be tested. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Potential effect of physical activity based menu labels on the calorie content of selected fast food meals."
},
{
"docid": "MED-3000",
"text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.",
"title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer."
},
{
"docid": "MED-1798",
"text": "The most important factors leading to fat accumulation in children are genetic inheritance, endocrine alterations, and behavioural/environmental causes. In addition, experimental animal studies have shown that infections due to various pathogens can lead to overweight and obesity conditions, and studies of humans have found that the incidence of seroconversion against some of these may be significantly more frequent in obese adults and children than in normal subjects. However, the results of these studies are not conclusive and, in some cases, have raised more questions than answers. We reviewed the literature concerning the role of adenovirus 36 (AD-36), the most widely studied infectious agent in animals and humans, because of its potential association with childhood obesity. The available evidence suggests that more studies are needed to evaluate whether or not the association between the presence of AD-36 antibodies and obesity is simply unrelated, and to verify whether there are subjects that have greater tendency to become obese because more easily susceptible to AD-36 infection or with a predisposition to suffer from persistent viral infection more easily leading to the development of obesity. If it is demonstrated that AD-36 does play a role in obesity, it will be important to investigate possible vaccines against the infection itself or antiviral drugs capable of inhibiting disease progression. Copyright © 2012 Elsevier B.V. All rights reserved.",
"title": "Adenovirus 36 infection and obesity."
},
{
"docid": "MED-2439",
"text": "While many factors are involved in the etiology of cancer, it has been clearly established that diet significantly impacts one’s risk for this disease. More recently, specific food components have been identified which are uniquely beneficial in mitigating the risk of specific cancer subtypes. Plant sterols are well known for their effects on blood cholesterol levels, however research into their potential role in mitigating cancer risk remains in its infancy. As outlined in this review, the cholesterol modulating actions of plant sterols may overlap with their anti-cancer actions. Breast cancer is the most common malignancy affecting women and there remains a need for effective adjuvant therapies for this disease, for which plant sterols may play a distinctive role.",
"title": "Plant Sterols as Anticancer Nutrients: Evidence for Their Role in Breast Cancer"
},
{
"docid": "MED-2722",
"text": "Background Obesity and physical inactivity are associated with several chronic conditions, increased medical care costs, and premature death. Methods We used the Behavioral Risk Factor Surveillance System (BRFSS), a state-based random-digit telephone survey that covers the majority of United States counties, and the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US civilian noninstitutionalized population. About 3.7 million adults aged 20 years or older participated in the BRFSS from 2000 to 2011, and 30,000 adults aged 20 or older participated in NHANES from 1999 to 2010. We calculated body mass index (BMI) from self-reported weight and height in the BRFSS and adjusted for self-reporting bias using NHANES. We calculated self-reported physical activity—both any physical activity and physical activity meeting recommended levels—from self-reported data in the BRFSS. We used validated small area estimation methods to generate estimates of obesity and physical activity prevalence for each county annually for 2001 to 2011. Results Our results showed an increase in the prevalence of sufficient physical activity from 2001 to 2009. Levels were generally higher in men than in women, but increases were greater in women than men. Counties in Kentucky, Florida, Georgia, and California reported the largest gains. This increase in level of activity was matched by an increase in obesity in almost all counties during the same time period. There was a low correlation between level of physical activity and obesity in US counties. From 2001 to 2009, controlling for changes in poverty, unemployment, number of doctors per 100,000 population, percent rural, and baseline levels of obesity, for every 1 percentage point increase in physical activity prevalence, obesity prevalence was 0.11 percentage points lower. Conclusions Our study showed that increased physical activity alone has a small impact on obesity prevalence at the county level in the US. Indeed, the rise in physical activity levels will have a positive independent impact on the health of Americans as it will reduce the burden of cardiovascular diseases and diabetes. Other changes such as reduction in caloric intake are likely needed to curb the obesity epidemic and its burden.",
"title": "Prevalence of physical activity and obesity in US counties, 2001–2011: a road map for action"
},
{
"docid": "MED-3210",
"text": "Folklore has suggested that consuming grapefruit may promote weight control. Sparse data exist to support this hypothesis, although there is some evidence of health promotion effects with regard to blood pressure control and modulation of circulating lipids. The aim of this randomized controlled trial was to prospectively evaluate the role of grapefruit in reducing body weight and blood pressure and in promoting improvements in the lipid profile in overweight adults (N = 74). Following a 3-week washout diet low in bioactive-rich fruits and vegetables, participants were randomized to either the control diet (n = 32) or daily grapefruit (n = 42) in the amount of one half of a fresh Rio-Red grapefruit with each meal (3× daily) for 6 weeks. No differences between group in weight, blood pressure, or lipids were demonstrated. Grapefruit consumption was associated with modest weight loss (-0.61 ± 2.23 kg, P = .097), a significant reduction in waist circumference (-2.45 ± 0.60 cm, P = .0002), and a significant reduction in systolic blood pressure (-3.21 ± 10.13 mm Hg, P = .03) compared with baseline values. Improvements were observed in circulating lipids of those consuming grapefruit, with total cholesterol and low-density lipoprotein significantly decreasing by -11.7 mg/dL (P = .002) and -18.7 mg/dL (P < .001), respectively, compared with baseline values. This study suggests that consumption of grapefruit daily for 6 weeks does not significantly decrease body weight, lipids, or blood pressure as compared with the control condition. However, the improvements in blood pressure and lipids demonstrated in the intervention group suggest that grapefruit should be further evaluated in the context of obesity and cardiovascular disease prevention. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults."
},
{
"docid": "MED-2907",
"text": "Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.",
"title": "Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices"
},
{
"docid": "MED-4727",
"text": "The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.",
"title": "Dietary intake of organotin compounds in Finland: a market-basket study."
},
{
"docid": "MED-2721",
"text": "BACKGROUND: The major drivers of the obesity epidemic are much debated and have considerable policy importance for the population-wide prevention of obesity. OBJECTIVE: The objective was to determine the relative contributions of increased energy intake and reduced physical activity to the US obesity epidemic. DESIGN: We predicted the changes in weight from the changes in estimated energy intakes in US children and adults between the 1970s and 2000s. The increased US food energy supply (adjusted for wastage and assumed to be proportional to energy intake) was apportioned to children and adults and inserted into equations that relate energy intake to body weight derived from doubly labeled water studies. The weight increases predicted from the equations were compared with weight increases measured in representative US surveys over the same period. RESULTS: For children, the measured weight gain was 4.0 kg, and the predicted weight gain for the increased energy intake was identical at 4.0 kg. For adults, the measured weight gain was 8.6 kg, whereas the predicted weight gain was somewhat higher (10.8 kg). CONCLUSIONS: Increased energy intake appears to be more than sufficient to explain weight gain in the US population. A reversal of the increase in energy intake of approximately 2000 kJ/d (500 kcal/d) for adults and of 1500 kJ/d (350 kcal/d) for children would be needed for a reversal to the mean body weights of the 1970s. Alternatively, large compensatory increases in physical activity (eg, 110-150 min of walking/d), or a combination of both, would achieve the same outcome. Population approaches to reducing obesity should emphasize a reduction in the drivers of increased energy intake.",
"title": "Increased food energy supply is more than sufficient to explain the US epidemic of obesity."
},
{
"docid": "MED-4757",
"text": "The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.",
"title": "Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women."
},
{
"docid": "MED-1810",
"text": "BACKGROUND: We previously reported that human adenovirus Ad-36 induces adiposity and paradoxically lower levels of serum cholesterol (CHOL) and triglycerides (TG) in animals. OBJECTIVE: To evaluate the transmissibility of Ad-36 and Ad-36 induced adiposity using a chicken model. DESIGN: Experiment 1--four chickens were housed (two per cage) and one from each cage was inoculated with Ad-36. Duration of presence of Ad-36 DNA in the blood of all chickens was monitored. Experiment 2--two groups of chickens were intranasally inoculated with Ad-36 (infected donors, I-D) or media (control donors, C-D). Blood drawn 36 h later from I-D and C-D groups was inoculated into wing veins of recipient chickens (infected receivers, I-R, and control receivers, C-R, respectively). On sacrifice, 5 weeks post-inoculation, blood was drawn, body weight noted and visceral fat was separated and weighed. RESULTS: Experiment 1--Ad-36 DNA appeared in the blood of the inoculated chickens and that of uninoculated chickens (cage mates) within 12 h of inoculation and the viral DNA persisted up to 25 days in the blood. Experiment 2--compared with C-D, visceral and total body fat were significantly greater and CHOL significantly lower for the I-D and I-R. TG were significantly lower for the I-D. Ad-36 was isolated from 12 out of 16 blood samples of the I-D that were used for inoculating I-R chickens. Ad-36 DNA was present in the blood and the adipose tissue of the I-D and I-R but not in the skeletal muscles of animals selected randomly for testing. CONCLUSION: As seen in experiment 1, Ad-36 infection can be transmitted horizontally from an infected chicken to another chicken sharing the cage. Additionally, experiment 2 demonstrated blood-borne transmission of Ad-36-induced adiposity in chickens. Transmissibility of Ad-36-induced adiposity in chicken model raises serious concerns about such a possibility in humans that needs further investigation.",
"title": "Transmissibility of adenovirus-induced adiposity in a chicken model."
},
{
"docid": "MED-3208",
"text": "This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight. Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal), but differed in energy density. We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro, Brazil. Forty-nine women, ages ranging from 30 to 50 years, with body mass index (BMI)>25 kg/m2, were randomly chosen to add three apples (0.63 kcal/g energy density) or three pears (0.64 kcal/g energy density) or three oat cookies (3.7 kcal/g energy density) to their usual diet for 10 weeks. Fiber composition was similar ( approximately 6g). Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures. Results showed a significant decrease in the energy density during the follow-up (-1.23 kcal/g, p<0.04, and -1.29 kcal/g, p<0.05) for apples and pears, respectively, compared to the oat group. The energy intake also decreased significantly (-25.05 and -19.66 kcal/day) for the apple and pear group, respectively, but showed a small increase (+0.93) for the oat group. Apples and pears were also associated (p<0.001) with weight reduction (-0.93 kg for the apple and -0.84 for the pear group), whereas weight was unchanged (+0.21; p=0.35) in the oat group. Results suggest that energy densities of fruits, independent of their fiber amount can reduce energy consumption and body weight over time.",
"title": "A low-energy-dense diet adding fruit reduces weight and energy intake in women."
},
{
"docid": "MED-5003",
"text": "Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.",
"title": "Genistein inhibits differentiation of primary human adipocytes."
},
{
"docid": "MED-2943",
"text": "BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.",
"title": "Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk."
},
{
"docid": "MED-3135",
"text": "Background: Only 5% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known. Methods: CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1. Results: Although the overall frequency of CpG island promoter methylation events increased with age (P < 0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P = 0.051), INK4a/ARF (P = 0.042), HIN-1 (P = 0.044), and PRA (P = 0.032), as well as the overall frequency of methylation events (P = 0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women had ≤4 methylation events), whereas women without a mutation showed a high frequency of promoter methylation events (24 of 25 women had 5-8 methylation events; P < 0.0001). Of women with a BRCA1/2 mutation, none showed methylation of HIN-1 and only 1 of 15 women showed CpG island methylation of RARB M4, INK4a/ARF, or PRB promoters. Conclusions: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer.",
"title": "CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis"
},
{
"docid": "MED-2651",
"text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.",
"title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan."
},
{
"docid": "MED-3255",
"text": "BACKGROUND: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention reduces children's serum total cholesterol concentration, but its effect on vascular endothelial function is unknown. METHODS AND RESULTS: Between 1990 and 1992, we randomized healthy 7-month-old infants (n=1062) to intervention (low-saturated-fat diet) and control (unrestricted diet) groups. At the age of 11 years, endothelium-dependent (flow-mediated) and endothelium-independent (nitrate-mediated) vasodilatory responses of the brachial artery were measured with high-resolution ultrasound in 179 intervention and 190 control children. The effect of intervention on endothelial function was significant in boys (P=0.0034) but not in girls (P=0.69). The maximum endothelium-dependent dilation response (mean+/-SD) was 9.62+/-3.53% and 8.36+/-3.85% in intervention boys and control boys and 8.84+/-4.00% and 8.44+/-3.60% in intervention girls and control girls, respectively. Intervention had no effect on nitrate-mediated dilation. The difference in endothelial function in boys remained significant after adjustment for current serum total or LDL cholesterol but became nonsignificant after adjustment for mean cholesterol measured under 3 years of age (adjusted means: 9.46% [CI 8.68% to 10.24%] versus 8.54% [CI 7.75% to 9.32%], P=0.11). CONCLUSIONS: A low-saturated-fat diet introduced in infancy and maintained during the first decade of life is associated with enhanced endothelial function in boys. The effect is explained in part by the diet-induced reduction in serum cholesterol concentration.",
"title": "Endothelial function in healthy 11-year-old children after dietary intervention with onset in infancy: the Special Turku Coronary Risk Factor Inter..."
},
{
"docid": "MED-3348",
"text": "Fruit and vegetable consumption is inadequate among adults in the United States; this contributes to preventable morbidity and mortality. More effective dietary intervention strategies are needed. Recently, interventions that advertise the consequences of behavior for appearance have been successful in modifying sun-exposure habits and tobacco use. Such an approach might also facilitate dietary improvement. Consumption of carotenoid-rich fruit and vegetables positively affects skin color, which influences perceptions of health and attractiveness, and promoting such an effect may motivate target audiences to increase consumption of this important food group. This approach represents a novel direction for the field and is potentially suitable for cost-effective, population-level dissemination through the visual media.",
"title": "Appealing to Vanity: Could Potential Appearance Improvement Motivate Fruit and Vegetable Consumption?"
},
{
"docid": "MED-3951",
"text": "INTRODUCTION: This case report describes a patient who developed rhabdomyolysis temporally associated with the use of a mislabeled acai berry dietary supplement. METHODS AND RESULTS: The authors describe a 22-year-old man presenting with rhabdomyolysis approximately 2 weeks after starting a weight-loss dietary supplement. His medical history was significant only for hypertension treated with amlodipine. The diagnosis of rhabdomyolysis was confirmed (creatine kinase, 84,000 IU/L, positive urine myoglobin) with other potential causes ruled out. The signs and symptoms of the patient gradually resolved and he was discharged on hospital day 5. Assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 3, indicating a possible relationship between the supplement and rhabdomyolysis. Although the product was labeled and promoted as containing acai berry and additional ingredients, there was no acai berry found on analysis. CONCLUSION: Clinicians should be aware that all dietary supplements may vary in uniformity and contain unknown contaminants.",
"title": "Rhabdomyolysis associated with the use of a mislabeled \"acai berry\" dietary supplement."
},
{
"docid": "MED-2904",
"text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.",
"title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data"
},
{
"docid": "MED-3822",
"text": "Only a limited number of studies on cellulite have been published in the international literature and many of them reach somewhat antithetical conclusions. Consequently, it is not yet possible to reconcile the extreme differences of opinion which have lingered on for years concerning the nature of this disorder, as well as its origin and even the most basic aspects of its histopathological classification. It does not even have a recognized name: in fact, the term 'cellulitis' is used in scientific English to indicate a spreading gangrenous infection of the subcutaneous cellular tissue. The other terms used from time to time [panniculitis, lipodystrophy, edematofibrosclerotic panniculitis (EFP), liposclerosis, lipoedema, etc.] have quite different morphological and pathogenetic connotations in general. Over the last few decades, three major conflicting theories have emerged in relation to the ethiopathogenesis of cellulite. These indicate, respectively, the following causes: 1. Oedema caused by excessive hydrophilia of the intercellular matrix. 2. A homeostatic alteration on a regional microcirculatory level; this pathogenetic theory is summarized in a synthetic and self-explanatory denomination: EFP. 3. A peculiar anatomical conformation of the subcutaneous tissue of women, different from male morphology. These theories must all now be updated in the light of recent advances on the sophisticated and composite physiopathology of the adipose organ - which acts not only as a control device which regulates the systematic equilibrium of energy and modulates the food intake and the metabolism of other tissue substrate through a multiple glandular secretion of hormones and parahormones.",
"title": "Cellulite: nature and aetiopathogenesis."
},
{
"docid": "MED-4768",
"text": "The rapid increase in obesity and the associated health care costs have prompted a search for better approaches for its prevention and management. Such efforts may be facilitated by better understanding the etiology of obesity. Of the several etiological factors, infection, an unusual causative factor, has recently started receiving greater attention. In the last two decades, 10 adipogenic pathogens were reported, including human and nonhuman viruses, scrapie agents, bacteria, and gut microflora. Some of these pathogens are associated with human obesity, but their causative role in human obesity has not been established. This chapter presents information about the natural hosts, signs and symptoms, and pathogenesis of the adipogenic microorganisms. If relevant to humans, \"Infectobesity\" would be a relatively novel, yet extremely significant concept. A new perspective about the infectious etiology of obesity may stimulate additional research to assess the contribution of hitherto unknown pathogens to human obesity and possibly to prevent or treat obesity of infectious origins.",
"title": "Infectobesity: obesity of infectious origin."
},
{
"docid": "MED-3350",
"text": "Normotensive adults on low-sodium, weight-loss, and control diets recorded preferences and perceived saltiness for sodium chloride (NaCl) added to cream soup at intervals over 1 yr. Reduction in sodium intake and excretion accompanied a shift in preference toward less salt: preferred concentrations by ad libitum salting declined from 0.72% at the onset to 0.33% NaCl at week 24; hedonic scores for high concentrations of NaCl decreased significantly while scores for low concentrations increased. After 3 mo of sodium restriction, NaCl preferences readjusted to a lower level: ad libitum additions of NaCl were similar after 13, 24, and 52 wk. Less hedonic variation was observed among controls than among Na-restricted groups. The weight-loss group showed increased liking for mid-range NaCl levels. Mechanisms underlying preference changes, including physiological, behavioral, and context effects, may provide insights into maintenance of low-sodium diets for treatment and prevention of hypertension.",
"title": "Effect of dietary sodium restriction on taste responses to sodium chloride: a longitudinal study."
},
{
"docid": "MED-1806",
"text": "OBJECTIVE Ad36, a human adenovirus, increases adiposity but improves glycemic control in animal models. Similarly, natural Ad36 infection is cross-sectionally associated with greater adiposity and better glycemic control in humans. This study compared longitudinal observations in indices of adiposity (BMI and body fat percentage) and glycemic control (fasting glucose and insulin) in Ad36-infected versus uninfected adults. RESEARCH DESIGN AND METHODS Baseline sera from Hispanic men and women (n = 1,400) were screened post hoc for the presence of Ad36-specific antibodies. Indices of adiposity and glycemic control at baseline and at ∼10 years past the baseline were compared between seropositive and seronegative subjects, with adjustment for age and sex. In addition to age and sex, indices of glycemic control were adjusted for baseline BMI and were analyzed only for nondiabetic subjects. RESULTS Seropositive subjects (14.5%) had greater adiposity at baseline, compared with seronegative subjects. Longitudinally, seropositive subjects showed greater adiposity indices but lower fasting insulin levels. Subgroup analyses revealed that Ad36-seropositivity was associated with better baseline glycemic control and lower fasting insulin levels over time in the normal-weight group (BMI ≤25 kg/m2) and longitudinally, with greater adiposity in the overweight (BMI 25–30 kg/m2) and obese (BMI >30 kg/m2) men. Statistically, the differences between seropositive and seronegative individuals were modest in light of the multiple tests performed. CONCLUSIONS This study strengthens the plausibility that in humans, Ad36 increases adiposity and attenuates deterioration of glycemic control. Panoptically, the study raises the possibility that certain infections may modulate obesity or diabetes risk. A comprehensive understanding of these under-recognized factors is needed to effectively combat such metabolic disorders.",
"title": "Long-Term Changes in Adiposity and Glycemic Control Are Associated With Past Adenovirus Infection"
},
{
"docid": "MED-3908",
"text": "BACKGROUND: Evidence suggests that consumption of apple or its bioactive components modulate lipid metabolism and reduce the production of proinflammatory molecules. However, there is a paucity of such research in human beings. OBJECTIVE: Women experience a lower rate of cardiovascular disease before menopause compared with men. However, after the onset of menopause, the risk of cardiovascular disease increases drastically due to ovarian hormone deficiency. Hence, we conducted a 1-year clinical trial to evaluate the effect of dried apple vs dried plum consumption in reducing cardiovascular disease risk factors in postmenopausal women. DESIGN: One-hundred sixty qualified postmenopausal women were recruited from the greater Tallahassee, FL, area during 2007-2009 and were randomly assigned to one of two groups: dried apple (75 g/day) or dried plum (comparative control). Fasting blood samples were collected at baseline, 3, 6, and 12 months to measure various parameters. Physical activity recall and 7-day dietary recall were also obtained. RESULTS: Neither of the dried fruit regimens significantly affected the participants' reported total energy intake throughout the study period. On the contrary, women who consumed dried apple lost 1.5 kg body weight by the end of the study, albeit not significantly different from the dried plum group. In terms of cholesterol, serum total cholesterol levels were significantly lower in the dried apple group compared with the dried plum group only at 6 months. Although dried plum consumption did not significantly reduce serum total cholesterol and low-density lipoprotein cholesterol levels, it lowered their levels numerically by 3.5% and 8%, respectively, at 12 months compared with baseline. This may explain the lack of significance observed between the groups. However, within the group, women who consumed dried apple had significantly lower serum levels of total cholesterol and low-density lipoprotein cholesterol by 9% and 16%, respectively, at 3 months compared with baseline. These serum values were further decreased to 13% and 24%, respectively, after 6 months but stayed constant thereafter. The within-group analysis also reported that daily apple consumption profoundly improved atherogenic risk ratios, whereas there were no significant changes in lipid profile or atherogenic risk ratios as a result of dried plum consumption. Both dried fruits were able to lower serum levels of lipid hydroperoxide and C-reactive protein. However, serum C-reactive protein levels were significantly lower in the dried plum group compared with the dried apple group at 3 months. CONCLUSIONS: There were no significant differences between the dried apple and dried plum groups in altering serum levels of atherogenic cholesterols except total cholesterol at 6 months. However, when within treatment group comparisons are made, consumption of 75 g dried apple (about two medium-sized apples) can significantly lower atherogenic cholesterol levels as early as 3 months. Furthermore, consumption of dried apple and dried plum are beneficial to human health in terms of anti-inflammatory and antioxidative properties. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.",
"title": "Daily apple versus dried plum: impact on cardiovascular disease risk factors in postmenopausal women."
},
{
"docid": "MED-1720",
"text": "BACKGROUND: Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate cell growth and survival, and are thought to be important in tumour development. Circulating concentrations of IGF-I might be associated with an increased risk of cancer, whereas IGFBP-3 concentrations could be associated with a decreased cancer risk. METHODS: We did a systematic review and meta-regression analysis of case-control studies, including studies nested in cohorts, of the association between concentrations of IGF-I and IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung cancer. Study-specific dose-response slopes were obtained by relating the natural log of odds ratios for different exposure levels to blood concentrations normalised to a percentile scale. FINDINGS: We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137 controls. High concentrations of IGF-I were associated with an increased risk of prostate cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations were larger in assessments of plasma samples than in serum samples, and in standard case-control studies compared with nested studies. INTERPRETATION: Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk of common cancers, but associations are modest and vary between sites. Although laboratory methods need to be standardised, these epidemiological observations could have major implications for assessment of risk and prevention of cancer.",
"title": "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis."
},
{
"docid": "MED-3821",
"text": "Reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is important. Limited information about polyamine content of food is available, especially for diets in the United States. This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). Values for spermine, spermidine, and putrescine were calculated and reported per serving size (nmol/serving). Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine (36,988 nmol/serving). The polyamine database and FFQ were tested with a convenience sample (n=165). Average daily polyamine intakes from the sample were: 159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day spermine. Orange and grapefruit juices contributed the greatest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest amount of spermine (2,186 nmol/day). Development of this database linked to an FFQ provides a means of estimating polyamine intake and contributes to investigations relating polyamines to cancer.",
"title": "Development of a Polyamine Database for Assessing Dietary Intake"
},
{
"docid": "MED-4256",
"text": "This systematic review collated seventy-eight studies exploring waist-to-height ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and CVD, published in English between 1950 and 2008. Twenty-two prospective analyses showed that WHtR and WC were significant predictors of these cardiometabolic outcomes more often than BMI, with similar OR, sometimes being significant predictors after adjustment for BMI. Observations from cross-sectional analyses, forty-four in adults, thirteen in children, supported these predictions. Receiver operator characteristic (ROC) analysis revealed mean area under ROC (AUROC) values of 0·704, 0·693 and 0·671 for WHtR, WC and BMI, respectively. Mean boundary values for WHtR, covering all cardiometabolic outcomes, from studies in fourteen different countries and including Caucasian, Asian and Central American subjects, were 0·50 for men and 0·50 for women. WHtR and WC are therefore similar predictors of diabetes and CVD, both being stronger than, and independent of, BMI. To make firmer statistical comparison, a meta-analysis is required. The AUROC analyses indicate that WHtR may be a more useful global clinical screening tool than WC, with a weighted mean boundary value of 0·5, supporting the simple public health message 'keep your waist circumference to less than half your height'.",
"title": "A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0·5 could be a suitable..."
},
{
"docid": "MED-4002",
"text": "The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences (WC) >88 cm (abdominal obesity) were investigated. The randomised, double-blind, clinical trial involved 40 women aged 20-40 years. Groups received daily dietary supplements comprising 30 mL of either soy bean oil (group S; n = 20) or coconut oil (group C; n = 20) over a 12-week period, during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day. Data were collected 1 week before (T1) and 1 week after (T2) dietary intervention. Energy intake and amount of carbohydrate ingested by both groups diminished over the trial, whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged. At T1 there were no differences in biochemical or anthropometric characteristics between the groups, whereas at T2 group C presented a higher level of HDL (48.7 +/- 2.4 vs. 45.00 +/- 5.6; P = 0.01) and a lower LDL:HDL ratio (2.41 +/- 0.8 vs. 3.1 +/- 0.8; P = 0.04). Reductions in BMI were observed in both groups at T2 (P < 0.05), but only group C exhibited a reduction in WC (P = 0.005). Group S presented an increase (P < 0.05) in total cholesterol, LDL and LDL:HDL ratio, whilst HDL diminished (P = 0.03). Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity.",
"title": "Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity."
},
{
"docid": "MED-2716",
"text": "BACKGROUND Many beliefs about obesity persist in the absence of supporting scientific evidence (presumptions); some persist despite contradicting evidence (myths). The promulgation of unsupported beliefs may yield poorly informed policy decisions, inaccurate clinical and public health recommendations, and an unproductive allocation of research resources and may divert attention away from useful, evidence-based information. METHODS Using Internet searches of popular media and scientific literature, we identified, reviewed, and classified obesity-related myths and presumptions. We also examined facts that are well supported by evidence, with an emphasis on those that have practical implications for public health, policy, or clinical recommendations. RESULTS We identified seven obesity-related myths concerning the effects of small sustained increases in energy intake or expenditure, establishment of realistic goals for weight loss, rapid weight loss, weight-loss readiness, physical-education classes, breast-feeding, and energy expended during sexual activity. We also identified six presumptions about the purported effects of regularly eating breakfast, early childhood experiences, eating fruits and vegetables, weight cycling, snacking, and the built (i.e., human-made) environment. Finally, we identified nine evidence-supported facts that are relevant for the formulation of sound public health, policy, or clinical recommendations. CONCLUSIONS False and scientifically unsupported beliefs about obesity are pervasive in both scientific literature and the popular press. (Funded by the National Institutes of Health.)",
"title": "Myths, Presumptions, and Facts about Obesity"
},
{
"docid": "MED-2717",
"text": "The United States is in the midst of a significant public health problem that relates to obesity and inactivity. This epidemic has far-ranging consequences for our workforce and our children and shows no signs of slowing in the near future. Significant research has been performed on the effects of exercise for the reduction of body weight; results of most studies indicate that exercise alone has a small effect on body-weight reduction independent of caloric restriction. However, when combined with dietary restriction, exercise has a synergistic effect and enhances weight loss beyond the effect of diet alone. In addition, exercise has been shown to have significant beneficial effects on cardiovascular and metabolic risk factors independent of actual weight loss, and losing just a small amount of weight can have a significant beneficial effect on these parameters. Genetic factors related to obesity have been found to be positively modified when persons incorporate physical activity into their lifestyle. Sitting time appears to be an independent risk factor for the development of metabolic risk factors; persons who spend more time sitting and watching television have worse metabolic profiles, even if they achieve the recommended amount of physical activity per week, than do those who move about throughout the day. Exercise also is essential for the prevention of weight gain over a life span, although the amount required to prevent weight gain may be closer to twice the amount of exercise recommended by the current Physical Activity Guidelines for Americans (www.health.gov/paguidelines). In many ways, the physiatrist is the most well prepared of all the specialists to address the complex, multidimensional problems of obesity and inactivity. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.",
"title": "The role of exercise in the treatment of obesity."
},
{
"docid": "MED-3143",
"text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.",
"title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial."
},
{
"docid": "MED-4250",
"text": "The purpose of this study was to test the hypothesis that a preload including dried prunes consumed as a snack before a meal, compared to an isoenergetic and equal weighed bread product preload would: (a) have greater short-term effect on satiety measured by subsequent ad libitum meal intake, (b) induce greater satiety as assessed by visual analogue scales (VAS), and (c) reduce appetite for dessert offered shortly after lunch. Forty-five healthy, normal-weight subjects participated in this randomised within-subject crossover study. Statistical analysis of the results showed that when subjects consumed the preload that included dried prunes, also consumed less amount of dessert and had lower total energy intake at meal. Additionally, subjects' feeling of hunger, desire and motivation to eat, as assessed with the use of VAS, were lower at all time points between snack and meal. Since macronutrients content of both preloads were similar, the satiating power of prunes could be due to their relatively high fiber content. Identifying meal patterns and foods that promote satiety without increasing considerably the overall energy intake is very important. The addition of dried prunes to a snack seems to promote satiety besides providing valuable nutrients. 2010 Elsevier Ltd. All rights reserved.",
"title": "Short-term effects of a snack including dried prunes on energy intake and satiety in normal-weight individuals."
},
{
"docid": "MED-1719",
"text": "OBJECTIVE: Overexpression of IGF-I occurs in tumors diagnosed in childhood (osteosarcoma, Wilms tumor, neuroblastoma, etc.) and in adults (breast, ovaries, colon and prostate cancer). The aim of our study was to establish the prevalence of malignancies in states of congenital IGF-I deficiency. SUBJECTS: We surveyed 222 patients with congenital IGF-I deficiency (Laron syndrome, GH gene deletion, GHRH receptor defects and IGF-I resistance) and 338 first and second-degree relatives. RESULTS: None of the IGF-I deficient patients had cancer, whereas 9-24% of the family members had a history of malignancy. CONCLUSIONS: Congenital IGF-I deficiency acts as a protecting factor for the development of cancer.",
"title": "Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report."
},
{
"docid": "MED-2910",
"text": "Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.",
"title": "Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure"
},
{
"docid": "MED-3030",
"text": "Consumption of marine fish provides both benefits (lean protein, omega-3 fatty acids and essential nutrients) and risks (main source of mercury (Hg) exposure for humans). Mercury is a potent neurotoxin and the source of more fish advisories nationwide than any other toxicant. Despite the widespread nature of Hg, it is unknown whether local Hg contamination reflects national and regional levels often used as bases to inform consumers of potential fish consumption risk. Thus, the objectives of our study were to examine Hg levels of six commonly consumed marine species harvested locally off the North Carolina coast and to compare our results to published regional (Monterey Bay Aquarium's Seafood Watch List) and national (Environmental Protection Agency, EPA, and Food and Drug Administration, FDA) Hg averages, action levels, and guidelines. We found significant differences in Hg concentrations among collected species, and we identified correlations between Hg concentration and fish length and trophic levels. Collected mahi mahi and triggerfish were below the EPA fish tissue action level (0.3ppm). Wahoo and grouper exceeded the EPA action level but were below the FDA action level (1.0ppm). King mackerel had the highest Hg concentration among targeted species, exceeding both EPA and FDA action levels. Further, our local results were not always consistent with calculated averages from EPA and FDA databases for the same species, and although many of our findings were consistent with Monterey Bay Aquarium's Seafood Watch List (southeast region), recommendations based on Hg levels would conflict with recommendations they provide based on sustainability. We find regional and national averages are not always reflective of local Hg contamination and suggest local data may be needed to accurately assess consumer risk.",
"title": "Do national advisories serve local consumers: an assessment of mercury in economically important North Carolina fish."
},
{
"docid": "MED-4261",
"text": "BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management.",
"title": "Meat consumption and prospective weight change in participants of the EPIC-PANACEA study."
},
{
"docid": "MED-1800",
"text": "Background Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals. Principal Findings Using a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 non-diabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from ∼7% in 1992–1998 to 15–20% in 2002–2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08). Conclusion Using a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals.",
"title": "Adenovirus-36 Is Associated with Obesity in Children and Adults in Sweden as Determined by Rapid ELISA"
},
{
"docid": "MED-3001",
"text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").",
"title": "Towards a new system of health: the challenge of Western disease."
},
{
"docid": "MED-1451",
"text": "OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. METHODS: Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. RESULTS: A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. CONCLUSIONS: Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.",
"title": "The link between workforce health and safety and the health of the bottom line: tracking market performance of companies that nurture a \"culture of..."
},
{
"docid": "MED-3473",
"text": "OBJECTIVE: This study investigated how consumption of orange juice associated with aerobic training affected serum lipids and physical characteristics of overweight, middle-aged women. METHODS: The experimental group consisted of 13 women who consumed 500 mL/d of orange juice and did 1h aerobic training 3 times a week for 3 months. The control group consisted of another 13 women who did the same aerobic training program but did not consume orange juice. RESULTS: At the end of the experiment, the control group lost an average of 15% of fat mass (P<0.05) and 2.5% of weight (P<0.05), whereas the experimental group lost 11% of fat mass and 1.2% of weight (P<0.05). Consumption of orange juice by the experimental group was associated with increased dietary intake of vitamin C and folate by 126% and 61% respectively. Serum LDL-C decreased 15% (P<0.05) and HDL-C increased 18% (P<0.05) in the experimental group, but no significant change was observed in the control group. Both groups improved the anaerobic threshold by 20% (P<0.05), but blood lactate concentration decreased 27% in the experimental group compared to the 17% control group, suggesting that experimental group has less muscle fatigue and better response to training. CONCLUSIONS: The consumption of 500 mL/d of orange juice associated with aerobic training in overweight women decreased cardiovascular disease risk by reducing LDL-C levels and increasing HDL-C levels. This association also decreased blood lactate concentration and increased anaerobic threshold, showing some improvement in the physical performance. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.",
"title": "Orange juice improved lipid profile and blood lactate of overweight middle-aged women subjected to aerobic training."
},
{
"docid": "MED-4289",
"text": "BACKGROUND: Few recent epidemiologic studies have assessed the effect that nut consumption (including tree nuts and peanuts) has on health risks, including metabolic syndrome (MetS). OBJECTIVE: This study compared the health risk for cardiovascular disease, type 2 diabetes, and MetS of nut consumers with that of nonconsumers. DESIGN: Adults 19+ years (n = 13,292) participating in the 1999-2004 National Health and Nutrition Examination Survey were used. Intake from 24-hour recalls was used to determine intake. Nut/tree nut consumers consumed ≥¼; ounce per day. Covariate-adjusted means, standard errors, and prevalence rates were determined for the nut consumption groups. RESULTS: The prevalence of nut consumers was 18.6% ± 0.7% and 21.0% ± 0.9% in those 19-50 years and 51 years and older, respectively. Nut consumption was associated with a decreased body mass index (27.7 kg/m(2) ± 0.2 vs 28.1 ± 0.1 kg/m(2), p < 0.05), waist circumference (95.6 ± 0.4 cm vs 96.4 ± 0.3 cm, p < 0.05), and systolic blood pressure (121.9 ± 0.4 mmHg vs 123.20 ± 0.3 mmHg, p < 0.01) compared with nonconsumers. Tree nut consumers also had a lower weight (78.8 ± 0.7 kg vs 80.7 ± 0.3 kg, p < 0.05). Nut consumers had a lower percentage of two risk factors for MetS: hypertension (31.5% ± 1.0% vs 34.2% ± 0.8%, p < 0.05) and low high density lipoprotein-cholesterol (HDL-C) (29.6% ± 1.0% vs 34.8% ± 0.8%, p < 0.01). Tree nut consumers had a lower prevalence of four risk factors for MetS: abdominal obesity (43.6% ± 1.6% vs 49.5% ± 0.8%, p < 0.05), hypertension (31.4% ± 1.2% vs 33.9% ± 0.8%, p < 0.05), low HDL-C (27.9% ± 1.7% vs 34.5% ± 0.8%, p < 0.01), high fasting glucose (11.4% ± 1.4% vs 15.0% ± 0.7%, p < 0.05), and a lower prevalence of MetS (21.2% ± 2.1% vs 26.6% ± 0.7%, p < 0.05). CONCLUSION: Nut/tree nut consumption was associated with a decreased prevalence of selected risk factors for cardiovascular disease, type 2 diabetes, and MetS.",
"title": "Nut consumption is associated with decreased health risk factors for cardiovascular disease and metabolic syndrome in U.S. adults: NHANES 1999-2004."
},
{
"docid": "MED-3203",
"text": "The contents of the bioactive compounds in red and blond grapefruits and their influence on humans suffering from hypertriglyceridemia were studied. It was found that red grapefruit has a higher content of bioactive compounds and a higher antioxidant potential than blond grapefruit, determined by oxygen radical scavenging capacity, 1,1-diphenyl-2-picrylhydrazyl, carotenoid bleaching, and Folin-Ciocalteu assays. Fifty-seven hyperlipidemic patients, ages 39-72 years, after coronary bypass surgery, recruited from the Institute's pool of volunteers, were randomly divided into three equal in number (19) groups: two experimental (red and blond groups) and one control group (CG). During 30 consecutive days of the investigation the diets of the patients of the red and blond dietary groups were daily supplemented with one equal in weight fresh red or blond grapefruit, respectively. Before and after this trial, serum lipid levels of all fractions and serum antioxidant activity were determined. It was found that serum lipid levels in patients of the red and blond groups versus the CG after treatment were decreased: (a) total cholesterol, 6.69 versus 7.92 mmol/L, 15.5%, and 7.32 versus 7.92 mmol/L, 7.6%, respectively; (b) low-density lipoprotein cholesterol, 5.01 versus 6.29 mmol/L, 20.3%, and 5.62 versus 6.29 mmol/L, 10.7%, respectively; (c) triglycerides, 1.69 versus 2.32 mmol/L, 17.2%, and 2.19 versus 2.32 mmol/L, 5.6%, respectively. No changes in the serum lipid levels in patients of the CG were found. In conclusion, fresh red grapefruit contains higher quantities of bioactive compounds and has significantly higher antioxidant potential than blond grapefruit. Diet supplemented with fresh red grapefruit positively influences serum lipid levels of all fractions, especially serum triglycerides and also serum antioxidant activity. The addition of fresh red grapefruit to generally accepted diets could be beneficial for hyperlipidemic, especially hypertriglyceridemic, patients suffering from coronary atherosclerosis.",
"title": "Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans."
},
{
"docid": "MED-4740",
"text": "The US Environmental Protection Agency's 2004 Dioxin Reassessment included a characterization of background exposures to dioxin-like compounds, including an estimate of an average background intake dose and an average background body burden. These quantities were derived from data generated in the mid-1990s. Studies conducted in the 2000s were gathered in an attempt to update the estimates generated by the Reassessment. While these studies suggest declines in the average background dose and body burden, a precise quantification of this decline, much less a conclusion that a decline has indeed occurred, cannot be made because of the inconsistency of study design and data sources, and the treatment of non-detects in the generation of congener average concentrations. The average background intake of the Reassessment was 61.0 pg TEQ/day, and using more current data, the average background intake was 40.6 pg TEQ/day. The average body burden from the surveys in the mid-1990s was 22.9 pg TEQ/g lipid weight (pg/g lwt). More recent blood concentration data, from NHANES 2001/2, suggest an adult average at 21.7 pg/g TEQ lwt. These TEQ values include the 17 dioxin and furan congeners and 3 coplanar PCBs, and were generated substituting ND=(1/2)DL or ND=DL/sq rt (2). Results are provided for ND=0 and analyses conducted to evaluate the impacts of this substitution. A more detailed examination of beef and pork data from similarly designed national statistical surveys show that declines in pork are statistically significant while the beef concentrations appeared to have remained constant between the time periods.",
"title": "Evaluation of background exposures of Americans to dioxin-like compounds in the 1990s and the 2000s."
},
{
"docid": "MED-3027",
"text": "Background Some persistent environmental chemicals are suspected of causing an increased risk of type 2 diabetes mellitus, a disease particularly common after age 70. This concern was examined in a cross-sectional study of elderly subjects in a population with elevated contaminant exposures from seafood species high in the food chain. Methods Clinical examinations of 713 Faroese residents aged 70-74 years (64% of eligible population) included fasting plasma concentrations of glucose and insulin, and glycosylated hemoglobin. Lifetime exposure to persistent environmental chemicals from pilot whale and other traditional food was estimated from a dietary questionnaire and by analysis of blood samples for polychlorinated biphenyls (PCBs) and related food contaminants. Results Septuagenarians with type 2 diabetes or impaired fasting glycemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. In non-diabetic subjects, the fasting insulin concentration decreased by 7% (95% CI= −12% to −2%) for each doubling of the PCB concentration after adjustment for sex and body mass index at age 20. Conversely, the fasting glucose concentration increased by 6% (−1% to 13%) for each doubling in PCB. Similar associations were seen in subjects without impaired fasting glycemia, while further adjustment for current body mass index and lipid metabolism parameters attenuated some of the associations. Conclusions Impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants.",
"title": "Marine Food Pollutants as a Risk Factor for Hypoinsulinemia and Type 2 Diabetes"
},
{
"docid": "MED-3205",
"text": "Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate > or = 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of > or =60 g/day had a HR of 0.93 (95% CI 0.77-1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.",
"title": "Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and ..."
},
{
"docid": "MED-3955",
"text": "BACKGROUND Polybrominated Diphenyl Ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS We analyzed the data from a sample of 271 adolescent girls (age 12–19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003–2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS The median total serum BDE concentration was 44.7 ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of −0.10 (95% CI: −0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.",
"title": "Serum PBDEs and Age at Menarche in Adolescent Girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004"
},
{
"docid": "MED-3819",
"text": "Adiponectin is discussed to regulate energy balance and insulin sensitivity. Several studies indicated an association of fasting adiponectin with parameters of the metabolic syndrome. We investigated postprandial adiponectin release and its relation to traits of the metabolic syndrome. Serum adiponectin concentration after an oral glucose tolerance test and after ingestion of a standardised mixed, fat-containing meal in 110 male non-diabetic subjects was assessed. Fasting and postprandial adiponectin and the decrease of adiponectin were correlated with anthropometric and metabolic parameters. Subjects were genotyped for adiponectin - 11 388 G/A promoter single nucleotide polymorphism. Adiponectin slightly decreased after both test meals. A significant decrease was attained 5 and 6 h after the lipid load and 2 h after the glucose load. Particularly, the mixed meal postprandial adiponectin showed stronger correlations with most traits of the metabolic syndrome than fasting adiponectin: postprandial adiponectin with HDL (r 0.30) v. fasting adiponectin with HDL (r 0.23); with postprandial insulin (area under the curve): r - 0.20 v. r - 0.16; with fasting insulin: r 0.10 v. r 0.14; with BMI: r - 0.23 v. r - 0.20; with waist: r - 0.18 v. - 0.16; with systolic blood pressure: r - 0.14 v. r - 0.12; with diastolic blood pressure: r - 0.18 v. r - 0.15. In multivariate analysis, postprandial TAG were the only independent predictor of adiponectin. There was no significant association of adiponectin, NEFA and TAG with - 11 388 G/A adiponectin promoter polymorphism. Our findings favour the interpretation that postprandial adiponectin has the strongest and independent associations to postprandial TAG metabolism.",
"title": "Postprandial plasma adiponectin decreases after glucose and high fat meal and is independently associated with postprandial triacylglycerols but no..."
},
{
"docid": "MED-4266",
"text": "The relative proportion of Bacteroidetes to Firmicutes is decreased in obese people. This imbalance in gut microbiota generates signals controlling the expression of genes by the epithelial intestinal cells. Both dairy and non-dairy probiotics increase body weight, reportedly through Lactobacillus species growth in the gut. On the other hand, daily intake of some fruits and drinks such as three apples or three pears or grapefruit, or green tea, which all are rich in polyphenols, can significantly reduce body weight in obese people. Metabolism of polyphenols by microbiota involves the cleavage of glycosidic linkages. Glycans, which are the product of glycosidic cleavage, are necessary for survival of the intestinal microbiota as a nutrient foundation. There are two pivotal points: (i) Firmicutes possess a disproportionately smaller number of glycan-degrading enzymes than Bacteroidetes, (ii) Firmicutes are more repressed than the Bacteroidetes by phenolic compounds' antimicrobial properties. The Bacteroidetes community prevails following dietary polyphenol intake and its fermentation to phenolic compounds, due to having more glycan-degrading enzymes, so this may thus be a mechanism by which dietary polyphenols exert their weight lowering effect. I suggest that future studies utilize clone libraries and fingerprinting techniques enabling identification of the composition and community structure of the microbiota, and dot blot hybridization or fluorescent in situ hybridization to analyze abundance of particular taxa in obese and individuals. A supplementation with polyphenols with high bioavailability in obese individuals with higher Firmicutes/Bacteroides community ratio phenotype, when associated to a probiotic restricted diet, is proposed for weight loss; this hypothesis could have relevant implication in planning a successful dietary regimen and/or neutraceutical/pharmaceutical preparations for achieving and maintaining a normal body weight in obese individuals, especially including much more use of polyphenol-rich foodstuffs and/or polyphenol-rich syrups, and including low amounts of probiotic-rich foodstuffs like yogurt, soy yogurt, or as probiotic supplements. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.",
"title": "High polyphenol, low probiotic diet for weight loss because of intestinal microbiota interaction."
},
{
"docid": "MED-4269",
"text": "PURPOSE OF REVIEW: High-fiber diets have been shown to reduce plasma concentrations of inflammation markers. Increased production of fermentation-derived short-chain fatty acids (SCFAs) is one of the factors that could exert these positive effects. This review examines the effects of SCFAs on immune cells and discusses the relevance of their effects on systemic inflammation, as frequently seen in obesity. RECENT FINDINGS: SCFAs have been shown to reduce chemotaxis and cell adhesion; this effect is dependent on type and concentration of SCFA. In spite of conflicting results, especially butyrate seems to have an anti-inflammatory effect, mediated by signaling pathways like nuclear factor-κB and inhibition of histone deacetylase. The discrepancies in the results could be explained by differences in cell types used and their proliferative and differentiation status. SUMMARY: SCFAs show anti-inflammatory effects and seem to have the potency to prevent infiltration of immune cells from the bloodstream in, for example, the adipose tissue. In addition, their ability to inhibit the proliferation and activation of T cells and to prevent adhesion of antigen-presenting cells could be important as it recently has been shown that obesity-associated inflammation might be antigen-dependent. More studies with concentrations in micromolar range are needed to approach more physiological concentrations.",
"title": "Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health?"
},
{
"docid": "MED-4730",
"text": "We successfully optimized an analytical method using gel permeation chromatography followed by direct sample introduction comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry to quantify multiple groups of targeted persistent organic pollutants and halogenated natural products (HNPs) simultaneously in fish oil samples. This new method has a wider analytical scope than the traditional approach to use multiple methods to cover each class of compounds. Our analysis revealed that the relatively more volatile and lighter organic compounds, such as polychlorinated biphenyls (PCBs), organochlorine pesticides, and other smaller organohalogen compounds, were still present in two brands of \"PCB-free\" cod liver oils, albeit at much lower levels than in an untreated commercial sample. Moreover, the less volatile organic compounds, such as polybrominated diphenyl ethers and brominated HNPs, were detected at similar levels in all three cod liver oils. This suggests that the commercial molecular distillation treatment used for removal of organic/inorganic toxic contaminants is only effective for the lighter organic contaminants.",
"title": "Simultaneous quantitation of multiple classes of organohalogen compounds in fish oils with direct sample introduction comprehensive two-dimensional..."
},
{
"docid": "MED-2438",
"text": "Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.",
"title": "The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control st..."
},
{
"docid": "MED-3481",
"text": "The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer approaches for the treatment of obesity have involved inhibition of dietary triglyceride absorption via inhibition of pancreatic lipase (PL) as this is the major source of excess calories. Natural products provide a vast pool of PL inhibitors that can possibly be developed into clinical products. This article reviews various extracts and secondary metabolites from plants and microbial origin with PL inhibitory activity that can be focused for drug development programs.",
"title": "Pancreatic lipase inhibitors from natural sources: unexplored potential."
},
{
"docid": "MED-4732",
"text": "Background Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives In this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis. Methods PCB-77 or 2,2′,4,4,5,5′-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR)−/− mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE−/− mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis. Results Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol–3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor γ, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR−/− mice. ApoE−/− mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. Conclusions Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.",
"title": "Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis"
},
{
"docid": "MED-2999",
"text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.",
"title": "Western diseases and their emergence related to diet."
},
{
"docid": "MED-2648",
"text": "The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.",
"title": "Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals"
},
{
"docid": "MED-2677",
"text": "Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.",
"title": "Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring"
},
{
"docid": "MED-5006",
"text": "We projected future prevalence and BMI distribution based on national survey data (National Health and Nutrition Examination Study) collected between 1970s and 2004. Future obesity-related health-care costs for adults were estimated using projected prevalence, Census population projections, and published national estimates of per capita excess health-care costs of obesity/overweight. The objective was to illustrate potential burden of obesity prevalence and health-care costs of obesity and overweight in the United States that would occur if current trends continue. Overweight and obesity prevalence have increased steadily among all US population groups, but with notable differences between groups in annual increase rates. The increase (percentage points) in obesity and overweight in adults was faster than in children (0.77 vs. 0.46-0.49), and in women than in men (0.91 vs. 0.65). If these trends continue, by 2030, 86.3% adults will be overweight or obese; and 51.1%, obese. Black women (96.9%) and Mexican-American men (91.1%) would be the most affected. By 2048, all American adults would become overweight or obese, while black women will reach that state by 2034. In children, the prevalence of overweight (BMI >/= 95th percentile, 30%) will nearly double by 2030. Total health-care costs attributable to obesity/overweight would double every decade to 860.7-956.9 billion US dollars by 2030, accounting for 16-18% of total US health-care costs. We continue to move away from the Healthy People 2010 objectives. Timely, dramatic, and effective development and implementation of corrective programs/policies are needed to avoid the otherwise inevitable health and societal consequences implied by our projections .",
"title": "Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic."
},
{
"docid": "MED-1343",
"text": "BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients. Copyright 2008 Massachusetts Medical Society.",
"title": "Selective publication of antidepressant trials and its influence on apparent efficacy."
},
{
"docid": "MED-4258",
"text": "The objective of the present study was to assess animal and plant protein intakes in the Belgian population and to examine their relationship with overweight and obesity (OB). The subjects participated in the Belgian National Food Consumption Survey conducted in 2004. Food consumption was assessed by using two non-consecutive 24 h dietary recalls. About 3083 participants ( ≥ 15 years of age; 1546 males, 1537 females) provided completed dietary information. Animal protein intake (47 g/d) contributed more to total protein intakes of 72 g/d than plant protein intake, which accounted for 25 g/d. Meat and meat products were the main contributors to total animal protein intakes (53 %), whereas cereals and cereal products contributed most to plant protein intake (54 %). Males had higher animal and plant protein intakes than females (P < 0·001). Legume and soya protein intakes were low in the whole population (0·101 and 0·174 g/d, respectively). In males, animal protein intake was positively associated with BMI (β = 0·013; P = 0·001) and waist circumference (WC; β = 0·041; P = 0·002). Both in males and females, plant protein intake was inversely associated with BMI (males: β = - 0·036; P < 0·001; females: β = - 0·046; P = 0·001) and WC (male: β = - 0·137; P < 0·001; female: β = - 0·096; P = 0·024). In conclusion, plant protein intakes were lower than animal protein intakes among a representative sample of the Belgian population and decreased with age. Associations with anthropometric data indicated that plant proteins could offer a protective effect in the prevention of overweight and OB in the Belgian population.",
"title": "Plant and animal protein intake and its association with overweight and obesity among the Belgian population."
},
{
"docid": "MED-1808",
"text": "BACKGROUND: Human adenovirus-36 (Ad-36) is thought to induce obesity by a direct effect of the viral E4orf1 gene on lipogenic enzymes in host adipocytes. Ad-36 prevalence is 30% in obese adults, but prevalence has not been reported in childhood obesity. OBJECTIVES: To determine the prevalence of Ad-36 infection in obese Korean children (age 14.8 +/- 1.9; range 8.3-6.3 years); correlation of infection with BMI z-score and other obesity measures. METHODS: Blood was drawn at the annual school physical exam or clinic visit; Ad-36 status was determined by serum neutralization assay; and routine serum chemistry values. RESULTS: A total of 30% of subjects were positive (N = 25) for Ad-36; 70% were negative (N = 59). Significantly higher BMI z-scores (1.92 vs. 1.65, p < 0.01) and waist circumferences (96.3 vs. 90.7 cm, p = 0.05) were found in infected versus uninfected children. Cardiovascular risk factors were not significantly different. CONCLUSIONS: Ad-36 infection is common in obese Korean children and correlates highly with obesity. Ad-36 may have played a role in the obesity and Type 2 diabetes epidemic in children.",
"title": "Human adenovirus-36 antibody status is associated with obesity in children."
},
{
"docid": "MED-4998",
"text": "Curcumin has been reported to have the potential to prevent obesity as well as cancers. The downstream targets regulated by AMP-activated protein kinase (AMPK) for inhibiting adipocyte differentiation or cancer cell proliferation of curcumin were investigated. The activation of AMPK by curcumin was crucial for the inhibition of differentiation or growth in both adipocytes and cancer cells. Stimulation of AMPK by curcumin resulted in the down-regulation of PPAR (peroxisome proliferator-activated receptor)-gamma in 3T3-L1 adipocytes and the decrease in COX-2 in MCF-7 cells. Application of a synthetic AMPK activator also supported the evidence that AMPK acts as an upstream signal of PPAR-gamma in 3T3-L1 adipocytes. In cancer cells, AMPK was found to act as a regulator of ERK1/2, p38, and COX-2. Regulation of AMPK and its downstream targets such as PPAR-gamma, Mapkinases, and COX-2 by curcumin appears to be important in controlling adipocytes and cancerous cells.",
"title": "Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 i..."
},
{
"docid": "MED-2437",
"text": "BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and METHODS: This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. RESULTS: The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. CONCLUSION: Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.",
"title": "Diet and breast cancer: understanding risks and benefits."
},
{
"docid": "MED-2676",
"text": "Smokehouse smoke, which is used for flavouring meat products, was investigated for its mutagenic activity in the Salmonella typhimurium assay. We were chiefly concerned with the fractions free of polycyclic aromatic hydrocarbons but containing phenol compounds, which are responsible for the preservative and aromatizing properties of the smoke. The most abundantly occurring phenol compounds (phenol, cresols, 2,4-dimethylphenol, brenzcatechine, syringol, eugenol, vanilline and guaiacol) gave negative results when they were tested for mutagenicity at five concentrations up to 5000 micrograms/plate, with and without S-9 mix, using five strains of S. typhimurium. Even when phenol was further investigated in a variety of test conditions, no induction of his+ revertants was observed. When smokehouse smoke was condensed and fractionated the majority of the various phenolic fractions also gave negative results when tested at five concentrations using five strains of S. typhimurium. However there was a slight increase in the number of revertants in a few cases. The presence in the phenolic fractions of very small amounts of mutagenic impurities, the nature of which needs further investigation, cannot be excluded. These results support the further development of non-hazardous smoke-aroma preparations, based on the phenolic components of smokehouse smoke.",
"title": "Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates."
},
{
"docid": "MED-1348",
"text": "Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. Editors' Summary Background. Everyone feels miserable occasionally. But for some people—those with depression—these sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless, worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving). For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine. Why Was This Study Done? Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical Excellence (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy. What Did the Researchers Do and Find? The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants. What Do These Findings Mean? These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050045.",
"title": "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration"
},
{
"docid": "MED-3142",
"text": "AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.",
"title": "Positive effects of soy isoflavone food on survival of breast cancer patients in China."
},
{
"docid": "MED-2593",
"text": "Background Prospective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person. Methods We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality. Results During a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend <0.05, all). Compared to non-consumers, subjects consuming nuts >3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66). Conclusions Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165. Trial registration Clinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.",
"title": "Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial"
},
{
"docid": "MED-3012",
"text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment."
},
{
"docid": "MED-3941",
"text": "The effects of açai polyphenolics on the antiproliferation and induction of apoptosis in HL-60 human leukemia cells were investigated. Interactions between anthocyanins and non-anthocyanin-polyphenolics in both their glycosidic and their aglycone forms were also investigated to determine additive or nonadditive responses. Polyphenolic fractions at 0.17-10.7 microM were found to reduce cell proliferation from 56 to 86% likely due to caspase-3 activation (apoptosis). Anthocyanin and polyphenolic fractions were nonadditive in their contribution to the cell antiproliferation activity. At equimolar concentrations, the glycosidic forms of phenolic acids and flavonoids induced a higher magnitude of change in cell parameters (proliferation and apoptosis) than their respective aglycone forms, while the opposite trend was observed for anthocyanin aglycones. This study demonstrated that açai offers a rich source of bioactive polyphenolics and confirmed the importance of investigating whole food systems when evaluating the potential health benefits of individual phytochemical compounds.",
"title": "Açai (Euterpe oleracea Mart.) polyphenolics in their glycoside and aglycone forms induce apoptosis of HL-60 leukemia cells."
},
{
"docid": "MED-1712",
"text": "Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.",
"title": "Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici..."
},
{
"docid": "MED-3359",
"text": "Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.",
"title": "You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes"
},
{
"docid": "MED-2656",
"text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.",
"title": "Effects of intestinal microflora and the environment on the development of asthma and allergy."
},
{
"docid": "MED-2596",
"text": "BACKGROUND Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. METHODS We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses’ Health Study (1980–2010) and 42,498 men in the Health Professionals Follow-up Study (1986–2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. RESULTS During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. CONCLUSIONS In two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death. (Funded by the National Institutes of Health and the International Tree Nut Council Nutrition Research and Education Foundation.)",
"title": "Association of Nut Consumption with Total and Cause-Specific Mortality"
},
{
"docid": "MED-3356",
"text": "OBJECTIVE: This study examined changes in desires to eat high-fat and low-fat foods across an obesity treatment program. The hypotheses under examination were (1) preferences for low-fat foods would increase across time and (2) preferences for high-fat foods would decrease across time. DESIGN: Single-group, prospective examination of desires to eat 48 foods, categorized according to fat content, before and after the 16-week treatment program. SETTING: University clinic, Memphis, Tennessee. PARTICIPANTS: 118 obese (mean weight = 194.4 lbs) women (mean age = 45.24 years) participating in an obesity treatment program. INTERVENTION: A 16-week cognitive-behavioral program for obesity. VARIABLES MEASURED: Desires to eat 48 foods varying in fat content and whether or not participants actually ate these foods. ANALYSIS: Analysis of variance, multiple regression, and paired t tests. RESULTS: The results indicate that during the program, preferences for low-fat foods increased, whereas preferences for high-fat foods decreased. These changes mirrored the changes in consumption of both low-fat and high-fat foods. CONCLUSIONS AND IMPLICATIONS: Within a behavioral economic perspective, the reinforcement value of low-fat foods may increase following a low-fat dietary intervention, whereas the reinforcing properties of high-fat foods may decline. This is desirable as low-fat foods hold many advantages over high-fat foods in terms of weight maintenance.",
"title": "Desire to eat high- and low-fat foods following a low-fat dietary intervention."
},
{
"docid": "MED-1447",
"text": "Background/objectives: To assess the effects on macro- and micronutrient intake of a nutrition intervention program in corporate settings across the United States. Subjects/methods: Two hundred and ninety-two individuals who were overweight or had type 2 diabetes were recruited from 10 sites of a US insurance company. Two hundred and seventy-one participants completed baseline diet recalls, and 183 participants completed dietary recalls at 18 weeks. Sites were randomly assigned to an intervention group (five sites) or to a control group (five sites) for 18 weeks. At intervention sites, participants were asked to follow a low-fat vegan diet and attend weekly group meetings. At control sites, participants continued their usual diets. At baseline and 18 weeks, participants completed 2-day diet recalls. Between-group differences in changes in nutrient intake were assessed using an analysis of covariance. Results: Compared with those in the control group, intervention-group participants significantly reduced the reported intake of total fat (P=0.02), saturated (P=0.006) and monounsaturated fats (P=0.01), cholesterol (P=0.009), protein (P=0.03) and calcium (P=0.02), and increased the intake of carbohydrate (P=0.006), fiber (P=0.002), β-carotene (P=0.01), vitamin C (P=0.003), magnesium (P=0.04) and potassium (P=0.002). Conclusions: An 18-week intervention program in a corporate setting reduces intake of total fat, saturated fat and cholesterol and increases the intake of protective nutrients, particularly fiber, β-carotene, vitamin C, magnesium and potassium. The reduction in calcium intake indicates the need for planning for this nutrient.",
"title": "Nutrient intake in the GEICO multicenter trial: the effects of a multicomponent worksite intervention"
},
{
"docid": "MED-4121",
"text": "The present study investigated the feasibility of a new experimental approach for studying the effect of covert nutritive dilution on the spontaneous food intake of obese individuals. Eight obese subjects were studied as inpatients on a metabolic unit for 15 days during which time they were unaware that their food intake was being monitored. A platter method of food presentation encouraged ad libitum ingestion. Caloric dilution was achieved by replacing sucrose-containing products with aspartame-sweetened analogues in an otherwise normal diet. During the base-line period the subjects spontaneously ate sufficient conventional food to maintain or even slightly increase body weight. Covert substitution of aspartame-sweetened products for their sucrose counterparts resulted in an immediate reduction in spontaneous energy intake of approximately 25%. The aspartame analogues were as well accepted as their conventional counterparts, as indicated by the equal quantity of each consumed. These preliminary results demonstrate that, in a metabolic ward setting, it is possible to maintain the spontaneous food intake of obese individuals at levels sufficient to preserve body weight and arbitrarily to decrease those levels of intake by 25% or more through covert changes in the caloric density of the diet.",
"title": "Effect of covert nutritive dilution on the spontaneous food intake of obese individuals: a pilot study."
},
{
"docid": "MED-2941",
"text": "Several cohort studies have examined the association of carotid intima-media thickness (IMT) with the risk of stroke or myocardial infarction in apparently healthy persons. We investigated the predictive value of IMT of cardiovascular mortality in elderly community-dwelling people, beyond the prediction provided by age and MMSE. assessed by means of a multivariate Cox model. Carotid IMT and plaque were evaluated bilaterally with ultrasonography in 298 people older than 75 years ( 120 men and 178 women, average age: 79.6 years). The LILAC study started on July 25, 2000. Consultations were repeated every year. The follow-up ended on November 30, 2004. During the mean follow-up span of 1152 days, 30 subjects (21 men and nine women) died. Nine deaths were attributable to cardiovascular causes Imyocardial infarction: two men and three women; stroke: two men and two women). The age- and MMSE-adjusted relative risk (RR) and 95% confidence interval (95% CI) of developing all-cause mortality was assessed. A 0.3 mm increase in left IMT was associated with a RR of predicted 1.647 (1.075-2.524), and a similar increase in right IMT with a RR of 3.327 (1.429-7.746). For cardiovascular mortality, the corresponding RR values were 2.351 (1.029-5.372) and 2.890 (1.059-7.891), respectively. Carotid IMT assessed by ultrasonography is positively associated with an increased risk of all-cause and cardiovascular death in elderly community-dwelling people.",
"title": "Common carotid intima-media thickness is predictive of all-cause and cardiovascular mortality in elderly community-dwelling people: Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study"
},
{
"docid": "MED-3050",
"text": "Background: Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. Objective: We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream–based milkshake and examined the influence of adipose tissue and the specificity of this relation. Design: Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. Results: Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. Conclusions: Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity.",
"title": "Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream–based milkshake"
},
{
"docid": "MED-4769",
"text": "Excessive fat accumulation has been observed in the field in chickens infected with adenovirus. In the present study this has been verified under experimental conditions. Chickens inoculated with adenovirus showed lesser weight gain but excessive adiposity compared to normal control chickens. These changes could not be explained by variation in food consumption. Chickens acquiring adenovirus naturally from the inoculated group showed similar adiposity. Serum cholesterol and triglyceride levels of inoculated and naturally infected chickens were significantly lower compared to those of the control group. Such an association between adenovirus infection and adiposity has been shown, probably, for the first time, which might help in further understanding of the complex problem of obesity.",
"title": "Effect of adenovirus infection on adiposity in chicken."
},
{
"docid": "MED-2595",
"text": "Nuts are an integral part of the Mediterranean food patterns, and their incorporation into the regular diets of human beings is believed to provide many health benefits. The recent recognition of nuts as \"heart-healthy\" foods by the U.S. Food and Drug Administration has given a major boost to the positive image of nuts. Nut consumption has been associated with several health benefits, such as antioxidant, hypocholesterolemic, cardioprotective, anticancer, anti-inflammatory, and antidiabetic benefits, among other functional properties. However, although nuts possess these many health benefits, their consumption has been hampered by a lack of adequate information regarding those benefits. In addition, because nuts are energy-dense foods with high-fat content, there is a misconception among consumers that increased consumption may lead to unwanted gain in body weight with the risk of developing overweight/obesity. Nonetheless, available epidemiologic studies and short-term controlled feeding trials have supported the theory that the inclusion of nuts in the typical diet does not induce weight gain, despite an expected increase in total caloric intake. To address the misperception about nuts and body weight gain, the present review focuses mainly on the relation between nut consumption and body weight gain, in the context of the many health benefits of nuts. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Health benefits of nut consumption with special reference to body weight control."
},
{
"docid": "MED-4765",
"text": "BACKGROUND: Previous studies on the association between macronutrient intake and the development of abdominal obesity, which carries an increased health risk, have not shown a consistent pattern, possibly due to mixed effects of other aspects of the food intake. OBJECTIVE: This study investigated the association between intake from 21 food and beverage groups and the subsequent 5-year difference in waist circumference. METHODS: The study population consisted of 22,570 women and 20,126 men, aged 50 to 64 years at baseline, with complete data on baseline and follow-up waist circumference, baseline diet (192 items food frequency questionnaire), body mass index, and selected potential confounders (eg, smoking status, sport activities, and intake of alcoholic beverages). Multiple linear regression analyses were performed. RESULTS: For women, 5-year difference in waist circumference was inversely related to intake from red meat, vegetables, fruit, butter, and high-fat dairy products, whereas intake from potatoes, processed meat, poultry, and snack foods was positively associated. For men, red meat and fruit intakes were inversely associated with 5-year difference in waist circumference, whereas snack foods intake was positively associated. Sex differences occurred for vegetables, high-fat dairy products, and processed meat. CONCLUSIONS: The results suggest that a diet low in fruits and red meat and high in snack foods was associated with larger waist circumference gains in both sexes. Furthermore, in women a diet low in vegetables, butter, and high-fat dairy products, and high in poultry, potatoes, and processed meat were likely determinants of subsequent gain at the waist.",
"title": "Dietary predictors of 5-year changes in waist circumference."
},
{
"docid": "MED-4231",
"text": "OBJECTIVE: To analyze the relationship between onion and garlic intake and benign prostatic hyperplasia (BPH), using data from a multicenter case-control study conducted in Italy. METHODS: A multicenter case-control study of 1369 patients with BPH and 1451 controls, admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, was conducted in Italy between 1991 and 2002. Information was collected by trained interviewers using a validated and reproducible food frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were obtained after allowance for recognized confounding factors and energy intake. RESULTS: Compared with nonusers, the multivariate ORs for the highest category of onion and garlic intake were 0.41 (95% CI 0.24 to 0.72) and 0.72 (95% CI 0.57 to 0.91), respectively. The combined OR for frequent users versus nonusers of both onion and garlic was 0.65 (95% CI 0.49 to 0.86). The inverse relationships were consistent across age strata. CONCLUSIONS: This uniquely large data set from European populations showed an inverse association between allium vegetable consumption and BPH.",
"title": "Onion and garlic intake and the odds of benign prostatic hyperplasia."
},
{
"docid": "MED-1342",
"text": "Background Previous meta-analyses of published and unpublished trials indicate that antidepressants provide modest benefits compared to placebo in the treatment of depression; some have argued that these benefits are not clinically significant. However, these meta-analyses were based only on trials submitted for the initial FDA approval of the medication and were limited to those aimed at treating depression. Here, for the first time, we assess the efficacy of a selective serotonin reuptake inhibitor (SSRI) in the treatment of both anxiety and depression, using a complete data set of all published and unpublished trials sponsored by the manufacturer. Methods and Findings GlaxoSmithKline has been required to post the results for all sponsored clinical trials online, providing an opportunity to assess the efficacy of an SSRI (paroxetine) with a complete data set of all trials conducted. We examined the data from all placebo-controlled, double-blind trials of paroxetine that included change scores on the Hamilton Rating Scale for Anxiety (HRSA) and/or the Hamilton Rating Scale for Depression (HRSD). For the treatment of anxiety (k = 12), the efficacy difference between paroxetine and placebo was modest (d = 0.27), and independent of baseline severity of anxiety. Overall change in placebo-treated individuals replicated 79% of the magnitude of paroxetine response. Efficacy was superior for the treatment of panic disorder (d = 0.36) than for generalized anxiety disorder (d = 0.20). Published trials showed significantly larger drug-placebo differences than unpublished trials (d’s = 0.32 and 0.17, respectively). In depression trials (k = 27), the benefit of paroxetine over placebo was consistent with previous meta-analyses of antidepressant efficacy (d = 0.32). Conclusions The available empirical evidence indicates that paroxetine provides only a modest advantage over placebo in treatment of anxiety and depression. Treatment implications are discussed.",
"title": "The Efficacy of Paroxetine and Placebo in Treating Anxiety and Depression: A Meta-Analysis of Change on the Hamilton Rating Scales"
},
{
"docid": "MED-2659",
"text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.",
"title": "European bans on surfactant trigger transatlantic debate."
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-3200",
"text": "In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.",
"title": "Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study"
},
{
"docid": "MED-4265",
"text": "Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.",
"title": "Microbial ecology: human gut microbes associated with obesity."
},
{
"docid": "MED-4731",
"text": "BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.",
"title": "No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-..."
},
{
"docid": "MED-3132",
"text": "Little is known about dietitians current practice in counselling clients about the use of legumes in a low fat, high fibre diet. An exploratory e-mail questionnaire was sent to members of Dietitians of Canada to assess: dietitian use and preferences for legumes, dietitian practice, opinions about clients attitudes and preferences, and resource needs. Counsellors (n=256) had high personal use of legumes (64% > or = 1 serving/week) and frequently recommended legumes in counselling. The legumes most preferred by respondents and their clients were: peanuts, kidney beans, split peas, chickpeas, and lentils. Respondents often recommended canned bean products (76%) and tofu (61%), but other legume grocery products were less often recommended. The most common client issues identified were: flatulence (87% agreed), lack of familiarity (85%), and knowledge of preparation (82%). Dietitians were not satisfied with current resources to support practice, especially those respondents providing primarily clinical counselling services. The most requested resources were: recipes (90%), pamphlets (82%), food demonstrations (75%) and Internet sites (63%). Client level research is now needed to confirm the importance of the issues identified and to develop and test strategies for legume promotion in counselling.",
"title": "Legume promotion in counselling: an e-mail survey of dietitians."
},
{
"docid": "MED-4741",
"text": "BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.",
"title": "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay."
},
{
"docid": "MED-3950",
"text": "The Açaí (Acai) fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.",
"title": "Polysaccharides Isolated from Açaí Fruit Induce Innate Immune Responses"
},
{
"docid": "MED-1446",
"text": "Literature on the association of protein intake with body weight is inconsistent. Little is known about the relation of long-term protein intake to obesity. This study aimed to determine the association between protein intake and obesity. A cohort of 1,730 employed white men ages 40–55 years from the Chicago Western Electric Study was followed from 1958 to 1966. Diet was assessed twice with Burke’s comprehensive diet history method, at two baseline examinations; height, weight, and other covariates were measured annually by trained interviewers. Generalized estimating equation (GEE) was used to examine the relation of baseline total, animal, and vegetable protein intake to likelihood of being overweight or obese at sequential annual examinations. Dietary animal protein was positively related to overweight and obesity over seven years of follow up. With adjustment for potential confounders (age, education, cigarette smoking, alcohol intake, energy, carbohydrate and saturated fat intake, and history of diabetes or other chronic disease), the odds ratios (95% confidence intervals) for obesity were 4.62 (2.68–7.98, p for trend<0.01) for participants in the highest compared to the lowest quartile of animal protein and 0.58 (0.36, 0.95, p for trend=0.053) for those in the highest quartile of vegetable protein intake. A statistically significant, positive association was seen between animal protein intake and obesity; those in higher quartiles of vegetable protein intake had lower odds of being obese. These results indicate that animal and vegetable protein may relate differently to occurrence of obesity in the long run.",
"title": "Longitudinal association between animal and vegetable protein intake and obesity among adult males in the United States: the Chicago Western Electric Study"
},
{
"docid": "MED-1344",
"text": "Is it ever right to prescribe placebos to patients in clinical practice? The General Medical Council is ambivalent about the issue; the American Medical Association asserts that placebos can be administered only if the patient is (somehow) 'informed'. The potential problem with placebos is that they may involve deception: indeed, if this is the case, an ethical tension arises over the patient's autonomy and the physician's requirement to be open and honest, and the notion that medical care should be the primary concern. This paper examines the case of depression as an entry point for understanding the complexities of the prescription of placebos. Recent important meta-analyses of antidepressants claim that they are not significantly more effective in a clinical setting than placebos. Given that antidepressants have numerous adverse side effects and are hugely expensive, this provocative research has serious potential ethical and practical implications for patients and medical providers. Should placebos be prescribed in place of antidepressants? The case of depression highlights another important issue which medical ethical codes have hitherto overlooked: well-being is not synonymous with being realistic about oneself, one's circumstances and the future. While severely depressed individuals are unduly pessimistic about themselves and the world around them, treatment of depressed individuals can be deemed successful when patients have successfully attained those positive illusions that are indicative of psychological health. This is exactly what successful psychological treatments of depression seem to achieve. It is therefore possible that there may be a limited unavoidable role for deception in medicine.",
"title": "Deception as treatment: the case of depression."
},
{
"docid": "MED-2913",
"text": "The elimination kinetics of polychlorinated biphenyls (PCBs) in humans is difficult to assess in observational studies, because PCB exposure is never completely abolished. In a community with high dietary PCB exposures from whale blubber, we examined two groups of children with increased body burdens from breast-feeding. Follow-up was from ages 4.5 years to 7.5 years (99 subjects) and 7 to 14 years (101 subjects). The calculations were performed by the use of structural equation models, with adjustment for body weight and dietary blubber intake as the main source of postnatal exposure. As a likely result of background exposures, apparent elimination half-lives were unexpectedly long when based on results from all cohort members. Subjects with exposures above the median and in the highest quartile showed half-lives of about 3-4 years for CB-138, and 4.5-5.5 years for CB-105 and CB-118; 6.5-7.5 years for CB-156, CB-170, and CB-187; and 7-9 years for CB-153 and CB-180. The longest half-lives correspond to elimination of the parent PCB solely with a daily fat excretion rate of 1-2 g, while shorter half-lives assume metabolic break-down.",
"title": "Elimination Half-lives of Polychlorinated Biphenyl Congeners in Children"
},
{
"docid": "MED-3818",
"text": "BACKGROUND: Cellulite, which appears as orange peel-type or cottage cheese-like dimpling of the skin on the thighs and buttocks, is a complex, multifactorial, cosmetic disorder of the subcutaneous fat layer and the overlying superficial skin. Adiponectin is an adipocyte-derived hormone mainly produced by subcutaneous fat that shows important protective anti-inflammatory and vasodilatory effects. We hypothesized that adiponectin expressed in the subcutaneous adipose tissue (SAT) might play a role in the pathogenesis of cellulite. We reasoned that a reduction in the expression of adiponectin - a humoral vasodilator - in the SAT of cellulite areas might contribute to the altered microcirculation frequently found in these regions. METHODS: A total of 15 lean (body mass index [BMI] < 25 kg/m(2) ) women with cellulite and 15 age- and BMI-matched women without cellulite participated in this study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess adiponectin gene expression. Plasma adiponectin levels were measured using a commercial enzyme immunoassay kit. RESULTS: Adiponectin mRNA expression in the SAT of the gluteal region was significantly lower in areas with cellulite compared with those without (12.6 ± 3.1 AU versus 16.6 ± 4.1 AU; P=0.006). However, plasma adiponectin levels did not differ between women with (20.3 ± 7.3 μg/ml) and without (19.3 ± 6.1 μg/ml) cellulite (P=0.69). CONCLUSIONS: Adiponectin expression is significantly reduced in the SAT in areas affected by cellulite. Our findings provide novel insights into the nature of cellulite and may give clues to the treatment of this cosmetic issue. © 2011 The International Society of Dermatology.",
"title": "Adiponectin expression in subcutaneous adipose tissue is reduced in women with cellulite."
},
{
"docid": "MED-1716",
"text": "Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.",
"title": "A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors"
},
{
"docid": "MED-5016",
"text": "OBJECTIVE: The aim of this present study was to determine plasma levels of lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in butter, coconut fat and safflower oil. DESIGN: The study consisted of sequential six week periods of diets rich in butter, coconut fat then safflower oil and measurements were made at baseline and at week 4 in each diet period. SUBJECTS: Forty-one healthy Pacific island polynesians living in New Zealand participated in the trial. INTERVENTIONS: Subjects were supplied with some foods rich in the test fats and were given detailed dietary advice which was reinforced regularly. RESULTS: Plasma lathosterol concentration (P < 0.001), the ratio plasma lathosterol/cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol (P<0.001) and apoB (P<0.001) levels were significantly different among the diets and were significantly lower during coconut and safflower oil diets compared with butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also significantly (P< or =0.001) different among the diets and were not significantly different between buffer and coconut diets. CONCLUSIONS: These data suggest that cholesterol synthesis is lower during diets rich in coconut fat and safflower oil compared with diets rich in butter and might be associated with lower production rates of apoB-containing lipoproteins.",
"title": "Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels."
},
{
"docid": "MED-1721",
"text": "Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Main outcome measures Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.",
"title": "Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study"
},
{
"docid": "MED-3025",
"text": "Detailed clinical and neuropathological studies have been made in two fullterm newborn human infants who were exposed to methylmercury in utero as a result of maternal ingestion of methylmercury-contaminated bread in early phases of pregnancy. High levels of mercury were detected in various regions of the brain at autopsy. Study of the brains revealed a disturbance in the development in both cases, consisting essentially of an incomplete or abnormal migration of neurons to the cerebellar and cerebral cortices, and deranged cortical organization of the cerebrum. There were numerous heterotopic neurons, both isolated and in groups, in the white matter of cerebrum and cerebellum and the laminar cortical pattern of the laminar cortical pattern of the cerebrum was disturbed in many regions as was shown by the irregular groupings and the deranged alignment of cortical. Prominent in the white matter of the cerebrum and the cerebellum was diffuse gemistocytic astrocytosis accompanied by an accumulation of mercury grains in their cytoplasm. These findings indicate a high degree of vulnerability of human fetal brain to maternal intoxication by methylmercury. A major effect appears to be related to faulty development and not to destructive focal neuronal damage as has been observed in mercury intoxicaiton in adults and children exposed postnatally.",
"title": "Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: a major effect of..."
},
{
"docid": "MED-3358",
"text": "BACKGROUND & AIMS: Taste sensitivity to fatty acids influences food ingestion and may regulate fat intake and body weight status. Fatty acids are detected via homologous receptors within the mouth and gastrointestinal (GI) tract, where attenuated sensitivity may be associated with greater fat intake and BMI. This study aimed to extend observations surrounding fatty acid taste, specifically the types of foods consumed and dietary behaviours that may be associated with fatty acid taste sensitivity. METHODS: 51 subjects (41 female; BMI, 21.4 ± 0.46 kg/m², age, 20 ± 0.52 yrs, 10 male; BMI, 23.6 ± 1.4 kg/m², age, 22 ± 1 yrs) were screened for oral sensitivity to oleic acid (3.8 mM) using triplicate sensory evaluations, and classified as hypersensitive; (3/3 correct identifications), or hyposensitive, (<3/3). Fat-taste perception (using sensory-matched custards made with 0, 2, 6, 10% oil), recent diet (4-day diet record) and food habits and behaviours (food habits and behaviours questionnaire) were also established. RESULTS: 75% (n = 38) of subjects were classified as hyposensitive to oleic acid and these subjects differed from those who were classified as hypersensitive. Hyposensitive subjects consumed significantly more energy, fat, saturated fat, fatty foods (butter, meat, dairy), had greater BMI and were less perceptive of small changes in the fat content of custard (all P < 0.05), compared to hypersensitive subjects. CONCLUSION: An inability to perceive low concentrations of fatty acids in foods was associated with greater consumption of fatty foods, specifically butter, meat, dairy, and increasing BMI. 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",
"title": "Oral sensitivity to oleic acid is associated with fat intake and body mass index."
},
{
"docid": "MED-1724",
"text": "A considerable amount of evidence is consistent with the proposition that systemic IGF-I activity acts as pacesetter in the aging process. A reduction in IGF-I activity is the common characteristic of rodents whose maximal lifespan has been increased by a wide range of genetic or dietary measures, including caloric restriction. The lifespans of breeds of dogs and strains of rats tend to be inversely proportional to their mature weight and IGF-I levels. The link between IGF-I and aging appears to be evolutionarily conserved; in worms and flies, lifespan is increased by reduction-of-function mutations in signaling intermediates homologous to those which mediate insulin/IGF-I activity in mammals. The fact that an increase in IGF-I activity plays a key role in the induction of sexual maturity, is consistent with a broader role for-IGF-I in aging regulation. If down-regulation of IGF-I activity could indeed slow aging in humans, a range of practical measures for achieving this may be at hand. These include a low-fat, whole-food, vegan diet, exercise training, soluble fiber, insulin sensitizers, appetite suppressants, and agents such as flax lignans, oral estrogen, or tamoxifen that decrease hepatic synthesis of IGF-I. Many of these measures would also be expected to decrease risk for common age-related diseases. Regimens combining several of these approaches might have a sufficient impact on IGF-I activity to achieve a useful retardation of the aging process. However, in light of the fact that IGF-I promotes endothelial production of nitric oxide and may be of especial importance to cerebrovascular health, additional measures for stroke prevention-most notably salt restriction-may be advisable when attempting to down-regulate IGF-I activity as a pro-longevity strategy.",
"title": "A low-fat, whole-food vegan diet, as well as other strategies that down-regulate IGF-I activity, may slow the human aging process."
},
{
"docid": "MED-1803",
"text": "WHO has declared obesity to be a global epidemic. Obesity management strategies mainly target behavioural components of the disorder, but are only marginally effective. A comprehensive understanding of the causative factors of obesity might provide more effective management approaches. Several microbes are causatively and correlatively linked with obesity in animals and human beings. If infections contribute to human obesity, then entirely different prevention and treatment strategies and public health policies could be needed to address this subtype of the disorder. Ethical reasons preclude experimental infection of human beings with candidate microbes to unequivocally determine their contribution to obesity. As an alternative, the available information about the adipogenic human adenovirus Ad36 has been used to create a template that can be used to examine comprehensively the contributions of specific candidate microbes to human obesity. Clinicians should be aware of infectobesity (obesity of infectious origin), and its potential importance in effective obesity management. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A framework for identification of infections that contribute to human obesity."
},
{
"docid": "MED-1711",
"text": "Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.",
"title": "Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer"
},
{
"docid": "MED-2942",
"text": "BACKGROUND: There are no long-term prospective studies assessing the impact of the vegan diet on vitamin B-12 (B-12) status. Many vegans take B-12 supplements irregularly or refuse to adopt them at all, considering them to be \"unnatural\" products. The use of B-12 fortified food may be an alternative. Therefore, we aimed to estimate the long-term effect of a vegan diet on serum B-12 concentrations in healthy omnivore adults, comparing the influence of natural products consumption and B-12 fortified food. MATERIAL AND METHODS: A five year prospective study was carried out comprising 20 omnivore healthy adult subjects, who moved to strict vegan diet for 5 years. Ten volunteers followed vegan diet based entirely on natural products, while the remaining ten subjects consumed food fortified in B-12. In all subjects serum vitamin B-12 concentration was determined before and 6, 12, 24 and 60 months after the implementation of the diet. RESULTS: A significant decrease (p < 0.0002) of serum B-12 concentrations in the whole studied group was noted after 60 months of vegan diet. However, observed changes were in fact limited to the subgroup consuming exclusively natural products (p < 0.0001). CONCLUSIONS: Transition from omnivore to vegan diet is associated with the risk of vitamin B-12 deficiency. B-12 fortified products might constitute a valuable alternative in vegans refusing to take vitamin supplements.",
"title": "The impact of vegan diet on B-12 status in healthy omnivores: five-year prospective study."
},
{
"docid": "MED-3942",
"text": "Background The purpose of this study was to evaluate the effect of açai fruit pulp on risk factors for metabolic disorders in overweight subjects. The açaí palm (Euterpe oleracea Mart.), which is native to South America, produces a small, black-purple fruit which is edible. The fruit has recently become popular as a functional food due to its antioxidant potential. Although several studies have been conducted in vitro and with animals, little is known about the potential health benefits in humans aside from an increase in plasma anti-oxidant capacity. Metabolic syndrome is a condition which is defined by a cluster of risk factors for cardiovascular disease and/or type-2 diabetes. Preliminary studies indicate that a reduction in reactive oxygen species can assist in the normalization of the metabolic pathways involved in this syndrome. Methods This was an open label pilot study conducted with 10 overweight adults (BMI ≥ 25 kg/m2 and ≤ 30 kg/m2) who took 100 g açai pulp twice daily for 1 month. The study endpoints included levels of fasting plasma glucose, insulin, cholesterol, triglycerides, exhaled (breath) nitric oxide metabolites (eNO) and plasma levels of high sensitivity C-reactive protein (hs-CRP). The response of blood glucose, blood pressure and eNO to a standardized meal was determined at baseline and following the 30 day treatment. Results Compared to baseline, there were reductions in fasting glucose and insulin levels following the 30 day treatment (both p < 0.02). There was also a reduction in total cholesterol (p = 0.03), as well as borderline significant reductions in LDL-cholesterol and the ratio of total cholesterol to HDL-cholesterol (both p = 0.051). Compared to baseline, treatment with açai ameliorated the post-prandial increase in plasma glucose following the standardized meal, measured as the area under the curve (p = 0.047). There was no effect on blood pressure, hs-CRP or eNO. Conclusion In this uncontrolled pilot study, consumption of açai fruit pulp reduced levels of selected markers of metabolic disease risk in overweight adults, indicating that further studies are warranted.",
"title": "Effects of Açai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: A pilot study"
},
{
"docid": "MED-3355",
"text": "OBJECTIVE: To evaluate the effects of a high-fat and low-fat diet on taste sensitivity to oleic acid (C18:1) in lean and overweight/obese (OW/OB) subjects. DESIGN: Randomized cross-over dietary intervention involving the consumption of a high-fat (>45% fat) and low-fat (<20% fat) diet, both consumed over a 4-week period. SUBJECTS: A total of 19 lean, mean age 33±13 years, mean body mass index (BMI) 23.2±2.2 kg m(-2) and 12 OW/OB, mean age 39.5±3 years, mean BMI 28±2.6 kg m(-2), subjects participated in the study, which measured taste thresholds for C18:1, fat perception and hedonic ratings for regular (RF) and lowered-fat (LF) foods before, and following consumption of a high- and low-fat diet. RESULTS: Consumption of the low-fat diet increased taste sensitivity to C18:1 among lean and OW/OB subjects (P<0.05) and increased the subjects ability to perceive small differences in the fat content of custard (P=0.05). Consumption of the high-fat diet significantly decreased taste sensitivity to C18:1 among lean subjects (P<0.05), with no change in sensitivity among OW/OB persons (P=0.609). The hedonic ratings for several RF and LF foods differed following the diets. CONCLUSION: Alterations in the fat content of the diet modulated taste sensitivity to C18:1 among lean subjects, which was increased following a 4-week period of fat restriction and attenuated following the high-fat diet. The failure of the high-fat diet to alter fatty acid taste thresholds among OW/OB subjects suggests that these individuals were 'adapted' to high-fat exposure, perhaps because of differences in habitual fat consumption. Taken together, these data suggest that excessive dietary fat attenuates nutrient sensing epithelia response in the oral cavity, which could be associated with changes in diet and weight status.",
"title": "Recent fat intake modulates fat taste sensitivity in lean and overweight subjects."
},
{
"docid": "MED-4000",
"text": "Coconut oil is a common edible oil in many countries, and there is mixed evidence for its effects on lipid profiles and cardiovascular disease risk. Here we examine the association between coconut oil consumption and lipid profiles in a cohort of 1,839 Filipino women (age 35–69 years) participating in the Cebu Longitudinal Health and Nutrition Survey, a community based study in Metropolitan Cebu City. Coconut oil intake was measured as individual coconut oil intake calculated using two 24-hour dietary recalls (9.54 ± 8.92 grams). Cholesterol profiles were measured in plasma samples collected after an overnight fast. Mean lipid values in this sample were total cholesterol (TC) (186.52 ± 38.86 mg/dL), high density lipoprotein cholesterol (HDL-c) (40.85 ± 10.30 mg/dL), low density lipoprotein cholesterol (LDL-c) (119.42 ± 33.21 mg/dL), triglycerides (130.75 ± 85.29 mg/dL) and the TC/HDL ratio (4.80 ± 1.41). Linear regression models were used to estimate the association between coconut oil intake and each plasma lipid outcome after adjusting for total energy intake, age, body mass index (BMI), number of pregnancies, education, menopausal status, household assets and urban residency. Dietary coconut oil intake was positively associated with HDL-c levels.",
"title": "Coconut oil predicts a beneficial lipid profile in pre-menopausal women in the Philippines"
},
{
"docid": "MED-4232",
"text": "OBJECTIVES: To evaluate the role of a wide range of foods on the risk of benign prostatic hyperplasia (BPH), we conducted a case-control study in Italy between 1991 and 2002. Although BPH is an extremely common condition, particularly among older men, its risk factors, including dietary ones, remain largely undefined. METHODS: Included in the study were 1369 patients younger than 75 years old surgically treated for BPH and 1451 controls younger than 75 years of age who had been admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. A validated and reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate section on alcoholic beverages, was used to assess patients' dietary habits 2 years before diagnosis or hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake and other major potential confounding factors. RESULTS: A significant trend of increasing risk with more frequent consumption was found for cereals (OR 1.55 for the greatest versus lowest quintile), bread (OR 1.69), eggs (OR 1.43), and poultry (OR 1.39). Inverse associations were observed for soups (OR 0.74), pulses (OR 0.74), cooked vegetables (OR 0.66), and citrus fruit (OR 0.82). No association was observed for milk and yogurt products, coffee and tea, pasta and rice, fish, cheese, row vegetables, potatoes, fruit, or desserts. CONCLUSIONS: The results of this study suggest a role for dietary habits on the risk of BPH. In particular, a diet rich in cereals and some types of meat and poor in vegetables and pulses may have an unfavorable effect in this Italian population.",
"title": "Food groups and risk of benign prostatic hyperplasia."
},
{
"docid": "MED-2944",
"text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.",
"title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States"
},
{
"docid": "MED-3044",
"text": "OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.",
"title": "Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli."
},
{
"docid": "MED-2647",
"text": "Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.",
"title": "Dietary exposure to xenoestrogens in New Zealand."
},
{
"docid": "MED-3352",
"text": "The popularity of low- and reduced-fat foods has increased as consumers seek to decrease their energy consumption. Fat replacers may be used in fat-reduced products to maintain their sensory properties. However, these ingredients have been largely formulated to replicate nongustatory properties of fats to foods and have only achieved moderate success. There is increasing evidence that fats also activate the taste system and uniquely evoke responses that may influence product acceptance. Work supporting a taste component of fat has prompted questions about whether fat constitutes an additional \"primary\" or \"basic\" taste quality. This review briefly summarizes this evidence, focusing on human studies, when possible. Effective stimuli, possible receptors, and physiological changes due to oral fat exposure are discussed. Some studies suggest that there are fatty acid tasters and nontasters and if verified could have implications for targeted product development. © 2011 Institute of Food Technologists®",
"title": "Are free fatty acids effective taste stimuli in humans? Presented at the symposium \"The Taste for Fat: New Discoveries on the Role of Fat in Sensor..."
},
{
"docid": "MED-4766",
"text": "The aetiology of obesity is multifactorial. An understanding of the contributions of various causal factors is essential for the proper management of obesity. Although it is primarily thought of as a condition brought on by lifestyle choices, recent evidence shows there is a link between obesity and viral infections. Numerous animal models have documented an increased body weight and a number of physiologic changes, including increased insulin sensitivity, increased glucose uptake and decreased leptin secretion that contribute to an increase in body fat in adenovirus-36 infection. Other viral agents associated with increasing obesity in animals included canine distemper virus, rous-associated virus 7, scrapie, Borna disease virus, SMAM-1 and other adenoviruses. This review attempted to determine if viral infection is a possible cause of obesity. Also, this paper discussed mechanisms by which viruses might produce obesity. Based on the evidence presented in this paper, it can be concluded that a link between obesity and viral infections cannot be ruled out. Further epidemiologic studies are needed to establish a causal link between the two, and determine if these results can be used in future management and prevention of obesity.",
"title": "Viral obesity: fact or fiction?"
},
{
"docid": "MED-1350",
"text": "Background Starting in the 1960s, a broad-based patients’ rights movement began to question doctors’ paternalism and to demand disclosure of medical information, informed consent, and active participation by the individual in personal health care. According to scholars, these changes contributed to downplay the biomedical approach in favor of a more patient-oriented perspective. The Swedish non-profit organization Consumer Association for Medicines and Health (KILEN) has offered the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. Methodology In this paper, qualitative content analysis was used to analyze 181 KILEN consumer reports of adverse events from antidepressant medications in order to explore patients’ views of mental ill health symptoms and the doctor-patient interaction. Principal Findings Overall, the KILEN stories contained negative experiences of the patients’ medical encounters. Some reports indicated intense emotional outrage and strong feelings of abuse by the health care system. Many reports suggested that doctors and patients had very different accounts of the nature of the problems for which the patient was seeking help. Although patients sought help for problems like tiredness and sleeplessness (often with a personal crisis of some sort as a described cause), the treating doctor in most cases was exceptionally quick in both diagnosing depression and prescribing antidepressant treatment. When patients felt they were not being listened to, trust in the doctor was compromised. This was evident in the cases when the doctor tried to convince them to take part in medical treatment, sometimes by threatening to withdraw their sick-listing. Conclusions Overall, this study suggests that the dynamics happening in the medical encounter may still be highly affected by a medical dominance, instead of a patient-oriented perspective. This may contribute to a questionable medicalization and/or pharmaceuticalization of depression.",
"title": "A Pill for the Ill? Patients’ Reports of Their Experience of the Medical Encounter in the Treatment of Depression"
},
{
"docid": "MED-3946",
"text": "The fruit of Euterpe oleraceae, commonly known as acai, has been demonstrated to exhibit significantly high antioxidant capacity in vitro, especially for superoxide and peroxyl scavenging, and, therefore, may have possible health benefits. In this study, the antioxidant capacities of freeze-dried acai fruit pulp/skin powder (OptiAcai) were evaluated by different assays with various free radical sources. It was found to have exceptional activity against superoxide in the superoxide scavenging (SOD) assay, the highest of any food reported to date against the peroxyl radical as measured by the oxygen radical absorbance capacity assay with fluorescein as the fluorescent probe (ORACFL), and mild activity against both the peroxynitrite and hydroxyl radical by the peroxynitrite averting capacity (NORAC) and hydroxyl radical averting capacity (HORAC) assays, respectively. The SOD of acai was 1614 units/g, an extremely high scavenging capacity for O2*-, by far the highest of any fruit or vegetable tested to date. Total phenolics were also tested as comparison. In the total antioxidant (TAO) assay, antioxidants in acai were differentiated into \"slow-acting\" and \"fast-acting\" components. An assay measuring inhibition of reactive oxygen species (ROS) formation in freshly purified human neutrophils showed that antioxidants in acai are able to enter human cells in a fully functional form and to perform an oxygen quenching function at very low doses. Furthermore, other bioactivities related to anti-inflammation and immune functions were also investigated. Acai was found to be a potential cyclooxygenase (COX)-1 and COX-2 inhibitor. It also showed a weak effect on lipopolysaccharide (LPS)-induced nitric oxide but no effect on either lymphocyte proliferation and phagocytic capacity.",
"title": "Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai)."
},
{
"docid": "MED-2945",
"text": "BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS: One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.",
"title": "Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men."
},
{
"docid": "MED-3816",
"text": "Most of adult women exhibit cellulite on the hips, buttock and thighs. Although extracellular matrix and lymphatic system disorders can increase its appearance, cellulite basically results from an excessive fat storage in the adipose tissue which exerts considerable pressure on the surrounding skin tissue and creates a dimpled irregular appearance. Caffeine, the most widely used anti-cellulite ingredient, favours fat break-down by inhibiting the phosphodiesterase enzyme and encouraging a high intracellular level of cAMP. A series of studies has shown that spermine and spermidine, two ubiquitous polyamines, encouraged fat storage and slowed fat break-down in the adipose tissue. Besides, it was shown that heparan sulfate glycosaminoglycans had a strong affinity for polyamines. To design a new cosmetic ingredient with anti-cellulite properties, we used molecular modelling to screen several ingredients with a structure similar to that of heparan sulfate glycosaminoglycans. This way, we identified sulfo-carrabiose as a potent molecule for trapping spermine and spermidine. These virtual results were first confirmed in tubo where sulfo-carrabiose was shown to dose-dependently inactivate spermine and spermidine. In vitro, adipocytes cultured with sulfo-carrabiose exhibited a significant reduction of lipogenesis and a significant increase of lipolysis. When sulfo-carrabiose was incorporated in a cosmetic formula, significant improvements were observed in thigh circumference, with better results than those obtained with caffeine after 28 days of use. Furthermore, a combination of caffeine and sulfo-carrabiose led to results significantly better than those obtained with caffeine alone. As measured by fringe projection, thigh volume was also significantly reduced after sulfo-carrabiose treatment. Finally, the appearance of cellulite assessed by clinical evaluation was also significantly reduced within 28 days. © 2010 BASF Beauty Care Solutions. ICS © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie.",
"title": "In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic ingredient with anti-cellulite properties."
},
{
"docid": "MED-4001",
"text": "Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans.",
"title": "An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity"
},
{
"docid": "MED-2592",
"text": "Background Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content. Purpose To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome. Methods Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks. Results Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups. Conclusion Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.",
"title": "Effects of pistachios on body weight in Chinese subjects with metabolic syndrome"
},
{
"docid": "MED-3897",
"text": "Background This study was designed to determine the glycemic indices of five commonly used varieties of dates in healthy subjects and their effects on postprandial glucose excursions in individuals with type 2 diabetes mellitus. Methods Composition analysis was carried out for five types of dates (Tamer stage). The weights of the flesh of the dates equivalent to 50 g of available carbohydrates were calculated. The study subjects were thirteen healthy volunteers with a mean (± SD) age of 40.2 ± 6.7 years and ten participants with type 2 diabetes mellitus (controlled on lifestyle measures and/or metformin) with a mean HbA1c (± SD) of 6.6 ± (0.7%) and a mean age (± SD) of 40.8 ± 5.7 years. Each subject was tested on eight separate days with 50 g of glucose (on 3 occasions) and 50 g equivalent of available carbohydrates from the 5 varieties of date (each on one occasion). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. The glycemic indices were determined as ratios of the incremental areas under the response curves for the dates compared to glucose. Statistical analyses were performed using the Mann-Whitney U test and repeated measures analysis of variance. Results Mean glycemic indices ± SEM of the dates for the healthy individuals were 54.0 ± 6.1, 53.5 ± 8.6, 46.3 ± 7.1, 49.1 ± 3.6 and 55.1 ± 7.7 for Fara'd, Lulu, Bo ma'an, Dabbas and Khalas, respectively. Corresponding values for those with type 2 diabetes were very similar (46.1 ± 6.2, 43.8 ± 7.7, 51.8 ± 6.9, 50.2 ± 3.9 and 53.0 ± 6.0). There were no statistically significant differences in the GIs between the control and the diabetic groups for the five types of dates, nor were there statistically significant differences among the dates' GIs (df = 4, F = 0.365, p = 0.83). Conclusion The results show low glycemic indices for the five types of dates included in the study and that their consumption by diabetic individuals does not result in significant postprandial glucose excursions. These findings point to the potential benefits of dates for diabetic subjects when used in a healthy balanced diet. Trial Registration Number ClinicalTrials.gov NCT01307904",
"title": "Glycemic indices of five varieties of dates in healthy and diabetic subjects"
},
{
"docid": "MED-4276",
"text": "Propionate is produced along with acetate and butyrate as a result of fermentative activity of gut microflora on dietary fiber. It has long been known to exhibit hypophagic effects in ruminants, however, its potential physiological roles in non-ruminants as well as humans remained unnoticed over the years. In view of various studies pointing towards the hypophagic as well as hypocholesterolemic effects of propionate in humans, it may act as an important factor in amelioration of obesity, a lifestyle disease arising due to energy imbalance and growing at a startling rate globally. Short chain fatty acids have recently been ascribed as ligands to G-protein coupled receptors (GPRs) 41 and 43. Thus, propionate along with acetate may also be involved in the regulation of adipogenesis and adipokine release mediated via GPRs. The present review summarizes the evidence which collectively raise the possibility of propionate as a dietary factor to depress appetite and combat the obesity epidemic. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Propionate. Anti-obesity and satiety enhancing factor?"
},
{
"docid": "MED-4728",
"text": "Over the last two decades, the incidence of obesity and associated metabolic syndrome diseases has risen dramatically, becoming a global health crisis. Increased caloric intake and decreased physical activity are believed to represent the root causes of this dramatic rise. However, recent findings highlight the possible involvement of environmental obesogens, xenobiotic chemicals that can disrupt the normal developmental and homeostatic controls over adipogenesis and energy balance. Environmental estrogens, i.e. chemicals with estrogenic potential, have been reported to perturb adipogenic mechanisms using in vitro model systems, but other classes of endocrine-disrupting chemicals are now coming under scrutiny as well. Organotins represent one class of widespread persistent organic pollutants with potent endocrine-disrupting properties in both invertebrates and vertebrates. New data identify tributyltin chloride and triphenyltin chloride as nanomolar agonist ligands for retinoid X receptor (RXR alpha, RXR beta, and RXR gamma) and peroxisome proliferator-activated receptor gamma, nuclear receptors that play pivotal roles in lipid homeostasis and adipogenesis. The environmental obesogen hypothesis predicts that inappropriate receptor activation by organotins will lead directly to adipocyte differentiation and a predisposition to obesity and/or will sensitize exposed individuals to obesity and related metabolic disorders under the influence of the typical high-calorie, high-fat Western diet. The linking of organotin exposure to adipocyte differentiation and obesity opens an important new area of research into potential environmental influences on human health and disease.",
"title": "Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling."
},
{
"docid": "MED-2594",
"text": "BACKGROUND: Epidemiologic studies have shown an inverse association between the frequency of nut consumption and body mass index (BMI) and risk of obesity. However, clinical trials that evaluated nut consumption on adiposity have been scarce and inconclusive. OBJECTIVE: We performed a systematic review and meta-analysis of published, randomized nut-feeding trials to estimate the effect of nut consumption on adiposity measures. DESIGN: MEDLINE and the Cochrane Central Register of Controlled Trials databases were searched for relevant clinical trials of nut intake that provided outcomes of body weight, BMI (in kg/m(2)), or waist-circumference measures and were published before December 2012. There were no language restrictions. Two investigators independently selected and reviewed eligible studies. The weighted mean difference (WMD) between nut or control diets was estimated by using a random-effects meta-analysis with 95% CIs. RESULTS: Thirty-three clinical trials met our inclusion criteria. Pooled results indicated a nonsignificant effect on body weight (WMD: -0.47 kg; 95% CI: -1.17, 0.22 kg; I(2) = 7%), BMI (WMD: -0.40 kg/m(2); 95% CI: -0.97, 0.17 kg/m(2); I(2) = 49%), or waist circumference (WMD: -1.25 cm; 95% CI: -2.82, 0.31 cm; I(2) = 28%) of diets including nuts compared with control diets. These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. CONCLUSION: Compared with control diets, diets enriched with nuts did not increase body weight, body mass index, or waist circumference in controlled clinical trials.",
"title": "Nut intake and adiposity: meta-analysis of clinical trials."
},
{
"docid": "MED-2947",
"text": "PURPOSE: To measure prospectively and directly both organ dose and effective dose (ED) for adult cardiac and pulmonary computed tomographic (CT) angiography by using current clinical protocols for 64-detector CT in an anthropomorphic female phantom and to estimate lifetime attributable risk of breast and lung cancer incidence on the basis of measured ED and organ dose. MATERIALS AND METHODS: Cardiac and pulmonary 64-detector CT angiography was performed by using current clinical protocols to evaluate the pulmonary veins (electrocardiographically [ECG] gated, 64 sections at 0.625-mm collimation, 120 kVp, 300 mA, 0.35-second tube rotation), native coronary arteries (ECG gated; 64 sections at 0.625 mm; 120 kVp; maximum current, 500-750 mA; minimum, 100-350 mA; 0.35-second tube rotation) and pulmonary embolus (64 sections at 1.25 mm, 140 kVp, 645 mA, 0.5-second tube rotation). Absorbed organ doses were measured by using an anthropomorphic female phantom and metal oxide semiconductor field effect transistor detectors. ED was calculated from measured organ doses and the dose-length product. RESULTS: ED for current adult cardiac and pulmonary 64-detector CT angiography protocols were 12.4-31.8 mSv. Overall, skin, breast, and esophagus and heart had the highest recorded absorbed organ doses. Relative risk for breast cancer incidence for girls and women was 1.004-1.042 for a single examination. Relative risk for lung cancer incidence for men and women was 1.005-1.076 from a single examination. CONCLUSION: EDs and organ doses from 64-detector CT are higher than those previously reported for adult cardiac and pulmonary CT angiography protocols. Risk for breast and lung cancer induction from these studies is greatest for the younger patient population. (c) RSNA, 2007.",
"title": "Radiation dose from contemporary cardiothoracic multidetector CT protocols with an anthropomorphic female phantom: implications for cancer induction."
},
{
"docid": "MED-3057",
"text": "The ongoing epidemics of obesity is one main health concern of the present time. Overeating in some obese individuals shares similarities with the loss of control and compulsive behavior observed in drug-addicted subjects, suggesting that obesity may involve food addiction. Here, we review the contributions provided by the use of positron emission tomography to the current understanding of the cerebral control of obesity and food intake in humans. The available studies have shown that multiple areas in the brain are involved with the reward properties of food, such as prefrontal, orbitofrontal, somatosensory cortices, insula, thalamus, hypothalamus, amygdala, and others. This review summarizes the current evidence, supporting the concepts that i) regions involved in the somatosensory response to food sight, taste, and smell are activated by palatable foods and may be hyperresponsive in obese individuals, ii) areas controlling executive drive seem to overreact to the anticipation of pleasure during cue exposure, and iii) those involved in cognitive control and inhibitory behavior may be resistant to the perception of reward after food exposure in obese subjects. All of these features may stimulate, for different reasons, ingestion of highly palatable and energy-rich foods. Though these same regions are similarly involved in drug abusers and game-addicted individuals, any direct resemblance may be an oversimplification, especially as the heterogeneities between studies and the prevalent exclusion of sensitive groups still limit a coherent interpretation of the findings. Further work is required to comprehensively tackle the multifaceted phenotype of obesity and identify the role of food dependency in its pathophysiology. Copyright © 2012 S. Karger GmbH, Freiburg.",
"title": "Brain PET imaging in obesity and food addiction: current evidence and hypothesis."
},
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-3471",
"text": "BACKGROUND: Orange juice-a rich source of vitamin C, folate, and flavonoids such as hesperidin-induces hypocholesterolemic responses in animals. OBJECTIVE: We determined whether orange juice beneficially altered blood lipids in subjects with moderate hypercholesterolemia. DESIGN: The sample consisted of 16 healthy men and 9 healthy women with elevated plasma total and LDL-cholesterol and normal plasma triacylglycerol concentrations. Participants incorporated 1, 2, or 3 cups (250 mL each) of orange juice sequentially into their diets, each dose over a period of 4 wk. This was followed by a 5-wk washout period. Plasma lipid, folate, homocyst(e)ine, and vitamin C (a compliance marker) concentrations were measured at baseline, after each treatment, and after the washout period. RESULTS: Consumption of 750 mL but not of 250 or 500 mL orange juice daily increased HDL-cholesterol concentrations by 21% (P: < 0.001), triacylglycerol concentrations by 30% (from 1.56 +/- 0.72 to 2.03 +/- 0.91 mmol/L; P: < 0.02), and folate concentrations by 18% (P: < 0.01); decreased the LDL-HDL cholesterol ratio by 16% (P: < 0.005); and did not affect homocyst(e)ine concentrations. Plasma vitamin C concentrations increased significantly during each dietary period (2.1, 3.1, and 3.8 times, respectively). CONCLUSIONS: Orange juice (750 mL/d) improved blood lipid profiles in hypercholesterolemic subjects, confirming recommendations to consume >/=5-10 servings of fruit and vegetables daily.",
"title": "HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia."
},
{
"docid": "MED-2674",
"text": "The process of malignant transformation universally entails genetic damage and oncogenic signaling, two stresses that are signaled to p53 through different genetic pathways. Based on this, it is possible to distinguish two jobs for p53: \"guardian of the genome\" that consists in sensing and reacting to DNA damage through the ATM/ATR and Chk1/Chk2 kinases, and \"policeman of the oncogenes\" that, correspondingly, consists in responding to oncogenic signaling through the p53-stabilizing protein ARF. Contrary to expectation, recent genetic evidence in mice indicates that the response of p53 to DNA damage has little or no impact on cancer protection. In contrast, ARF-dependent activation of p53 is critical for p53-mediated tumor suppression. Here, we discuss the mechanistic implications of these observations and their relevance for cancer therapy.",
"title": "p53: guardian of the genome and policeman of the oncogenes."
},
{
"docid": "MED-2917",
"text": "The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted.",
"title": "Nutrients and contaminants in human milk from mothers on macrobiotic and omnivorous diets."
},
{
"docid": "MED-3024",
"text": "This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Dietary lipids modulate methylmercury toxicity in Atlantic salmon."
},
{
"docid": "MED-3140",
"text": "To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \"Food Habits in Later Life \"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.",
"title": "Legumes: the most important dietary predictor of survival in older people of different ethnicities."
},
{
"docid": "MED-3945",
"text": "The pomegranate fruit ( Punica granatum ) has become an international high-value crop for the production of commercial pomegranate juice (PJ). The perceived consumer value of PJ is due in large part to its potential health benefits based on a significant body of medical research conducted with authentic PJ. To establish criteria for authenticating PJ, a new International Multidimensional Authenticity Specifications (IMAS) algorithm was developed through consideration of existing databases and comprehensive chemical characterization of 45 commercial juice samples from 23 different manufacturers in the United States. In addition to analysis of commercial juice samples obtained in the United States, data from other analyses of pomegranate juice and fruits including samples from Iran, Turkey, Azerbaijan, Syria, India, and China were considered in developing this protocol. There is universal agreement that the presence of a highly constant group of six anthocyanins together with punicalagins characterizes polyphenols in PJ. At a total sugar concentration of 16 degrees Brix, PJ contains characteristic sugars including mannitol at >0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.",
"title": "International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration."
},
{
"docid": "MED-3953",
"text": "An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.",
"title": "An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration."
},
{
"docid": "MED-3958",
"text": "Flanders is densely populated with much industry and intensive farming. Sexual maturation of adolescents (aged 14-15 years) was studied in relation to internal exposure to pollutants. Serum levels of pollutants and sex hormones were measured in 1679 participants selected as a random sample of the adolescents residing in the study areas. Data on sexual development were obtained from the medical school examination files. Self-assessment questionnaires provided information on health, use of medication and lifestyle factors. In boys, serum levels of hexachlorobenzene (HCB), p,p'-DDE and polychlorinated biphenyls (sum of marker PCB138, 153 and 180) were significantly and positively associated with pubertal staging (pubic hair and genital development). Higher levels of serum HCB and blood lead were associated with, respectively, a lower and a higher risk of gynecomastia. In girls, significant and negative associations were detected between blood lead and pubic hair development; higher exposure to PCBs was significantly associated with a delay in timing of menarche. Environmental exposures to pollutants at levels actually present in the Flemish population are associated with measurable effects on pubertal development. However, further understanding of toxic mode of action and sensitive windows of exposure is needed to explain the current findings.",
"title": "Internal exposure to pollutants and sexual maturation in Flemish adolescents."
},
{
"docid": "MED-3055",
"text": "Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects-partly mediated by dopamine increases in the limbic system-that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioural inhibition), stress reactivity, and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that shed light on the role of dopamine in drug addiction and in obesity, and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.",
"title": "Food and drug reward: overlapping circuits in human obesity and addiction."
},
{
"docid": "MED-3033",
"text": "Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.",
"title": "Smoking and lung cancer risk in American and Japanese men: an international case-control study."
},
{
"docid": "MED-3056",
"text": "Opioids are important in reward processes leading to addictive behavior such as self-administration of opioids and other drugs of abuse including nicotine and alcohol. Opioids are also involved in a broadly distributed neural network that regulates eating behavior, affecting both homeostatic and hedonic mechanisms. In this sense, opioids are particularly implicated in the modulation of highly palatable foods, and opioid antagonists attenuate both addictive drug taking and appetite for palatable food. Thus, craving for palatable food could be considered as a form of opioid-related addiction. There are three main families of opioid receptors (µ, ĸ, and δ) of which µ-receptors are most strongly implicated in reward. Administration of selective µ-agonists into the NAcc of rodents induces feeding even in satiated animals, while administration of µ-antagonists reduces food intake. Pharmacological studies also suggest a role for ĸ- and δ-opioid receptors. Preliminary data from transgenic knockout models suggest that mice lacking some of these receptors are resistant to high-fat diet-induced obesity. Copyright © 2012 S. Karger GmbH, Freiburg.",
"title": "The opioid system and food intake: homeostatic and hedonic mechanisms."
},
{
"docid": "MED-2440",
"text": "Purpose To further clarify the relationship between total cholesterol and cancer, which remains unclear. Methods We prospectively examined the association between total cholesterol and site-specific and all-cancer incidence among 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent a standardized biennial medical examination in 1992 to 1995 and were observed for 14 years until cancer diagnosis or death. Results Over follow-up, 53,944 men and 24,475 women were diagnosed with a primary cancer. Compared with levels less than 160 mg/dL, high total cholesterol (≥ 240 mg/dL) was positively associated with prostate cancer (hazard ratio [HR], 1.24; 95% CI, 1.07 to 1.44; P trend = .001) and colon cancer (HR, 1.12; 95% CI, 1.00 to 1.25; P trend = .05) in men and breast cancer in women (HR, 1.17; 95% CI, 1.03 to 1.33; P trend = .03). Higher total cholesterol was associated with a lower incidence of liver cancer (men: HR, 0.42; 95% CI, 0.38 to 0.45; P trend < .001; women: HR, 0.32; 95% CI, 0.27 to 0.39; P trend < .001), stomach cancer (men: HR, 0.87; 95% CI, 0.82 to 0.93; P trend ≤ .001; women: HR, 0.86; 95% CI, 0.77 to 0.97; P trend = .06), and, in men, lung cancer (HR, 0.89; 95% CI, 0.82 to 0.96; P trend < .001). Results for liver cancer were slightly attenuated after additional adjustment for liver enzyme levels and hepatitis B surface antigen status (men: HR, 0.60; P trend < .001; women: HR, 0.46; P trend = .003) and exclusion of the first 10 years of follow-up (men: HR, 0.59; P trend < .001; women: HR, 0.44; P trend < .001). Total cholesterol was inversely associated with all-cancer incidence in both men (HR, 0.84; 95% CI, 0.81 to 0.86; P trend < .001) and women (HR, 0.91; 95% CI, 0.87 to 0.95; P trend < .001), but these associations were attenuated after excluding incident liver cancers (men: HR, 0.95; P trend < .001; women: HR, 0.98; P trend = .32). Conclusion In this large prospective study, we found that total cholesterol was associated with the risk of several different cancers, although these relationships differed markedly by cancer site.",
"title": "Total Cholesterol and Cancer Risk in a Large Prospective Study in Korea"
},
{
"docid": "MED-4936",
"text": "Food and nutrition professionals question whether supplement-sourced nutrients appear to be equivalent to those derived from natural food sources. We compared the nutritional availability of docosahexaenoic acid (DHA) from algal-oil capsules to that from assayed cooked salmon in 32 healthy men and women, ages 20 to 65 years, in a randomized, open-label, parallel-group study. In this 2-week study comparing 600 mg DHA/day from algal-oil capsules to that from assayed portions of cooked salmon, mean change from baseline in plasma phospholipids and erythrocyte DHA levels was analyzed and DHA levels were compared by Student's t tests. In post-hoc analyses to determine bioequivalence, least-squares mean ratios of percent change from baseline in plasma phospholipid and erythrocyte DHA levels were compared. DHA levels increased by approximately 80% in plasma phospholipids and by approximately 25% in erythrocytes in both groups. Changes in DHA levels in plasma phospholipids and erythrocytes were similar between groups. As measured by delivery of DHA to both plasma and erythrocytes, fish and algal-oil capsules were equivalent. Both regimens were generally well-tolerated. These results indicate that algal-oil DHA capsules and cooked salmon appear to be bioequivalent in providing DHA to plasma and red blood cells and, accordingly, that algal-oil DHA capsules represent a safe and convenient source of non-fish-derived DHA.",
"title": "Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid."
},
{
"docid": "MED-5001",
"text": "We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system of curcumin into different analogues; the benzyloxime and the isoxazole and pyrazole heterocycles showed remarkable increases in the antitumor potency both in the parental and in the MDR MCF-7 cells. Furthermore, curcumin or, more potently, the isoxazole analogue, produced early reductions in the amounts of relevant gene transcripts that were diverse (i.e., they were relative to Bcl-2 and Bcl-X(L) in MCF-7 and the inhibitory of apoptosis proteins and COX-2 in MCF-7R) in the two cell lines. Thus, the two compounds exhibited the remarkable property of being able to modify their molecular activities according to the distinct characteristics of the parental and MDR cells. We discuss also how curcumin may (1) exert antitumor effects in breast cancer through ER-dependent and ER-independent mechanisms; and (2) act as a drug transporter-mediated MDR reversal agent. Overall, the structure of curcumin may represent the basis for the development of new, effective anticancer agents in hormone-independent MDR breast cancer.",
"title": "Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer."
},
{
"docid": "MED-2938",
"text": "Since the adoption of vegetarian diets as a healthy lifestyle has become popular, the cardiovascular effects of long-term vegetarianism need to be explored. The present study aimed to compare the presence and severity of carotid atherosclerosis (CA), and the blood levels of Vitamin B12, homocysteine (Hcy) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between 57 healthy postmenopausal vegetarians and 61 age-matched omnivores. Carotid atherosclerosis, as measured by ultrasound, was found to be of no significant difference between the two groups. Yet, fasting blood glucose, low-density lipoprotein cholesterol, and Vitamin B12 were significantly lower, while Hcy and sVCAM-1 were higher in the vegetarians as comparing with the omnivores. Multivariate regression analysis showed that the level of Vitamin B12 was negatively associated with the level of Hcy. Vegetarianism itself and Hcy level were significantly associated with sVCAM-1 level in univariate analysis; however, after adjustment for covariates, we identified age but not vegetarianism as the determinant of sVCAM-1 level. Multiple linear regression analysis identified age and systolic blood pressure, but not vegetarianism, as determinants of common carotid artery IMT. In conclusion, there was no significant difference in CA between apparently healthy postmenopausal vegetarians and omnivores. The findings of elevated Hcy in vegetarians indicate the importance of prevention of Vitamin B12 deficiency.",
"title": "Homocysteine, circulating vascular cell adhesion molecule and carotid atherosclerosis in postmenopausal vegetarian women and omnivores."
},
{
"docid": "MED-5007",
"text": "Circulating adiponectin is emerging as an important link between obesity, type 2 diabetes, and cardiovascular disease (CVD). However, the spectrum of lifestyle factors that modulate the adiponectin concentration remains to be elucidated, particularly among women. We conducted a cross-sectional study of 877 female twin pairs from the TwinsUK adult twin registry. Using a co-twin design, we examined dietary and body composition influences on adiponectin by conducting matched, within-pair analyses to eliminate confounding. Following multivariable adjustment within-twin pairs, significant influences on adiponectin (log-transformed, percent change per SD of the dietary/body composition variable) were observed for nonstarch polysaccharides (3.25%; 95% CI: 0.06, 6.54; P < 0.05) and magnesium intake (3.80%; 95%CI: 0.17, 7.57; P < 0.05), with a trend toward an association for fruit and vegetable (F&V) intakes (2.55%; 95% CI: -0.26, 5.45; P = 0.08). These modest positive associations cannot be explained by confounding through other lifestyle factors shared by the twins. A significant relationship between adiponectin and 3 derived dietary patterns (F&V, dieting, traditional English), carbohydrate, protein, trans fat, and alcohol intake was also observed. Strong inverse associations with adiponectin were observed for BMI (-10.72%; 95% CI: -13.78, -7.55), total (-6.89%: 95% CI: -10.34, -3.30; P < 0.05), and central fat mass (-12.50%; 95% CI: -15.82, -9.05; P < 0.05); these relationships were significant both when twins were analyzed as individuals and when characteristics were contrasted within-twin pairs, suggesting a direct effect. We observed modest associations between dietary factors and adiponectin in female twins, independent of adiposity, and report strong inverse associations with body composition. These data reinforce the importance of weight maintenance and increasing consumption of diets rich in plant-based foods to prevent CVD and type 2 diabetes.",
"title": "Plasma adiponectin concentrations are associated with body composition and plant-based dietary factors in female twins."
},
{
"docid": "MED-3123",
"text": "DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.",
"title": "The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption."
},
{
"docid": "MED-2645",
"text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.",
"title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."
},
{
"docid": "MED-3373",
"text": "Objectives. We considered the relationship between an urban adult population's fruit and vegetable consumption and several selected social and psychological processes, beneficial aesthetic experiences, and garden participation. Methods. We conducted a population-based survey representing 436 residents across 58 block groups in Denver, Colorado, from 2006 to 2007. We used multilevel statistical models to evaluate the survey data. Results. Neighborhood aesthetics, social involvement, and community garden participation were significantly associated with fruit and vegetable intake. Community gardeners consumed fruits and vegetables 5.7 times per day, compared with home gardeners (4.6 times per day) and nongardeners (3.9 times per day). Moreover, 56% of community gardeners met national recommendations to consume fruits and vegetables at least 5 times per day, compared with 37% of home gardeners and 25% of nongardeners. Conclusions. Our study results shed light on neighborhood processes that affect food-related behaviors and provides insights about the potential of community gardens to affect these behaviors. The qualities intrinsic to community gardens make them a unique intervention that can narrow the divide between people and the places where food is grown and increase local opportunities to eat better.",
"title": "The Influence of Social Involvement, Neighborhood Aesthetics, and Community Garden Participation on Fruit and Vegetable Consumption"
},
{
"docid": "MED-3954",
"text": "BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex-specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (≥ 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty.",
"title": "Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population?"
},
{
"docid": "MED-1797",
"text": "The selection of meat-type chickens (broilers) for rapid growth has been accompanied by excessive fat deposition. In this study, we analysed 53 candidate genes that are associated with obesity and obesity-related traits in humans, for which we found chicken orthologues by BLAST searches. We have identified single nucleotide polymorphisms (SNPs) with significant differences in allele frequencies between broilers and layers in each of the following six candidate genes: adrenergic, beta-2-, receptor, surface (ADRB2); melanocortin 5 receptor (MC5R); leptin receptor (LEPR), McKusick-Kaufman syndrome (MKKS), milk fat globule-EGF factor 8 protein (MFGE8) and adenylate kinase 1 (AK1). To examine associations with fatness and/or body weight, we used birds of extreme phenotypes in F(2) and backcross populations with varying levels of abdominal fat weight per cent (%AFW) and body weight. We then assessed the level of gene expression by real-time PCR. In two genes, ADRB2 and MFGE8, we found significant association with %AFW. The ADRB2 gene was found to have a significantly higher expression in the liver of lean chickens compared with those of the fat individuals. We believe that this approach can be applied for the identification of other quantitative genes. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.",
"title": "Comparative genome analysis with the human genome reveals chicken genes associated with fatness and body weight."
},
{
"docid": "MED-4124",
"text": "OBJECTIVE: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.g., by the diet. Erythritol, a simple polyol, could be such a compound. It is orally available, well tolerated, and its chemical structure resembles that of mannitol, a well-known hydroxyl radical (HO*) scavenger. METHODS: We studied the antioxidant properties of erythritol in vitro and subsequently determined its antioxidant activity and its vasoprotective effect in the streptozotocin diabetic rat. RESULTS: Erythritol was shown to be an excellent HO* radical scavenger and an inhibitor of 2,2'-azobis-2-amidinopropane dihydrochloride-induced hemolysis but inert toward superoxide radicals. High-performance liquid chromatographic and electron spin resonance spectroscopy studies showed that the reaction of erythritol with hydroxyl radicals resulted in the formation of erythrose and erythrulose by abstraction of a carbon-bound hydrogen atom. In the streptozotocin diabetic rat, erythritol displayed an endothelium-protective effect and, in accordance with the in vitro experiments, erythrose was found in the urine of erythritol-consuming rats. CONCLUSION: Erythritol acts as an antioxidant in vivo and may help protect against hyperglycemia-induced vascular damage. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Erythritol is a sweet antioxidant."
},
{
"docid": "MED-3060",
"text": "Context Research has implicated an addictive process in the development and maintenance of obesity. Although parallels in neural functioning between obesity and substance dependence have been found, no studies have examined the neural correlates of addictive-like eating behavior. Objective To test the hypothesis that elevated “food addiction” scores are associated with similar patterns of neural activation as substance dependence. Design Between-Subjects fMRI study. Participants Forty-eight healthy adolescent females ranging from lean to obese recruited for a healthy weight maintenance trial. Main Outcome Measure The relation between elevated “food addiction” scores and blood oxygen level-dependent fMRI activation in response to receipt and anticipated receipt of palatable food (chocolate milkshake). Results Food addiction scores (N = 39) correlated with greater activation in the anterior cingulate cortex (ACC), medial orbitofrontal cortex (OFC), and amygdala in response to anticipated receipt of food (P <0.05, false-discovery rate (FDR) corrected for multiple comparisons in small volumes). Participants with higher (n=15) versus lower (n=11) food addiction scores showed greater activation in the dorsolateral prefrontal cortex (DLPFC) and the caudate in response to anticipated receipt of food, but less activation in the lateral OFC in response to receipt of food (pFDR <0.05). Conclusions Similar patterns of neural activation are implicated in addictive-like eating behavior and substance dependence; elevated activation in reward circuitry in response to food cues and reduced activation of inhibitory regions in response to food intake.",
"title": "The Neural Correlates of “Food Addiction”"
},
{
"docid": "MED-4551",
"text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S",
"title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."
}
] |
[
{
"docid": "MED-5321",
"text": "Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron emission tomography and computed tomography, we previously reported that BAT decreases with age and thereby accelerates age-related accumulation of body fat in humans. Thus, the recruitment of BAT may be effective for body fat reduction. In this study, we examined the effects of repeated stimulation by cold and capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 weeks resulted in a parallel increase in BAT activity and CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks increased CIT. These results demonstrate that human BAT can be recruited even in individuals with decreased BAT activity, thereby contributing to body fat reduction.",
"title": "Recruited brown adipose tissue as an antiobesity agent in humans"
},
{
"docid": "MED-1873",
"text": "Research finding on the composition of macronutrient intakes on body weight has not been consistent. Furthermore, little research has examined the impact of subcomponents of macronutrients such as saturated fat or plant protein on body weight. The purpose of this report was to examine the impact of saturated fat, animal and plant protein, and other macronutrient intakes at the end of an intensive intervention on subsequent follow-up body weight. This is a secondary, observational data analysis using data from PREMIER, an 18-month randomized clinical trial that enrolled a total of 810 participants. Participants completed group and individual sessions designed to help them improve blood pressure (BP) control by making lifestyle changes. Dietary intakes were assessed by two 24-h diet recalls at baseline, 6, and 18 months. Body weight and physical fitness were monitored regularly. Regression models were used to examine the impact of animal or plant protein and other macronutrient intakes on subsequent body weight. After controlling for potential confounders, none of the calorie-contributing nutrient intakes at baseline was associated with subsequent weight at 6 or 18 months. However, a greater intake of saturated fat at 6 months was associated with higher weight at 18 months (P = 0.002). A greater intake of plant protein at 6 month was marginally associated with lower absolute weight at 18 month (P = 0.069). We conclude that macronutrient intakes before the intervention were not associated with subsequent body weight at 6 or 18 months. However, a lower saturated fat intake achieved after 6-month intervention predicts a lower body weight at 18 months and thus greater weight-loss maintenance.",
"title": "Dietary saturated fat intake is negatively associated with weight maintenance among the PREMIER participants."
},
{
"docid": "MED-829",
"text": "OBJECTIVES: The aims of the present study were to compare the distribution and accumulation of body fat in women with polycystic ovary syndrome (PCOS) and healthy controls matched for age and body mass index (BMI), and to investigate the association between androgen levels, insulin resistance and fat distribution. MATERIALS AND METHODS: Thirty-one PCOS women and 29 age- and BMI-matched healthy control women were evaluated in terms of subcutaneous adipose tissue thickness determined with a skinfold caliper and body composition analyzed by bioelectrical impedance analysis. Blood samples were obtained for determination of follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, 17-hydroxyprogesterone, basal prolactin, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), androstenedione, insulin and glucose levels. Insulin sensitivity was estimated by fasting glucose/insulin ratio and free androgen index (FAI) was calculated as 100 x testosterone/SHBG. Differences between means were analyzed by Student's t test or the Mann-Whitney U test according to distribution of the data. Correlation analysis was performed between the body fat distribution and parameters concerning insulin resistance and androgens. RESULTS: FAI was significantly higher in patients with PCOS compared with the control group (p = 0.001). Fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the PCOS group vs. controls (p = 0.03 and 0.001, respectively). There was significantly less subcutaneous adipose tissue in the controls than the PCOS women at the triceps (p = 0.04) and subscapular region (p = 0.04). Waist-to-hip ratio of PCOS women was significantly higher than that of control subjects (p = 0.04). CONCLUSION: Upper-half type body fat distribution is linked with PCOS, high free testosterone levels and insulin resistance.",
"title": "Body fat composition and distribution in women with polycystic ovary syndrome."
},
{
"docid": "MED-5312",
"text": "PURPOSE OF REVIEW: Capsaicin and its nonpungent analog (capsinoids) are known to be food ingredients that increase energy expenditure and decrease body fat. This article reviews the role of brown adipose tissue (BAT) for the thermogenic effect of these compounds in humans and proposes the possibility of some other antiobesity food ingredients. RECENT FINDINGS: A single oral ingestion of capsinoids increases energy expenditure in human individuals with metabolically active BAT, but not those without it, indicating that capsinoids activate BAT and thereby increase energy expenditure. This finding gave a rational explanation for discrepant results of the effects of capsinoids in the previous studies. Human BAT may be largely composed of inducible 'beige' adipocytes more than typical brown adipocytes because its gene expression patterns are similar to beige cells isolated from murine white fat depots. In fact, preadipocytes isolated from supraclavicular fat deposits - where BAT is often detected - are capable of differentiating into brown-like adipocytes in vitro, providing evidence of inducible brown adipogenesis in adult humans. SUMMARY: As human BAT may be inducible, a prolonged ingestion of capsinoids would recruit active BAT and thereby increase energy expenditure and decrease body fat. In addition to capsinoids, there are numerous food ingredients that are expected to activate BAT and so be useful for the prevention of obesity in daily life.",
"title": "Capsinoids and related food ingredients activating brown fat thermogenesis and reducing body fat in humans."
},
{
"docid": "MED-5113",
"text": "OBJECTIVE: This study investigated the effects of a soy-based low-calorie diet on weight control, body composition, and blood lipid profiles compared with a traditional low-calorie diet. METHODS: Thirty obese adults (mean body mass index 29-30 kg/m(2)) were randomized to two groups. The soy-based low-calorie group consumed soy protein as the only protein source, and the traditional low-calorie group consumed two-thirds animal protein and the rest plant protein in a 1200 kcal/d diet for 8 wk. A diet record was kept everyday throughout the study. Food intake was analyzed before and after the study. Anthropometric data were acquired every week, and biochemical data from before and after the 8-wk experiment were compared. RESULTS: Body weight, body mass index, body fat percentage, and waist circumference significantly decreased in both groups (P < 0.05). The decrease in body fat percentage in the soy group (2.2%, 95% confidence interval 1.6-2.8) was greater than that in the traditional group (1.4%, 95% confidence interval -0.1 to 2.8). Serum total cholesterol concentrations, low-density lipoprotein cholesterol concentrations, and liver function parameters decreased in the soy-based group and were significantly different from measurements in the traditional group (P < 0.05). No significant change in serum triacylglycerol levels, serum high-density lipoprotein cholesterol levels, and fasting glucose levels was found in the soy or traditional group. CONCLUSION: Soy-based low-calorie diets significantly decreased serum total cholesterol and low-density lipoprotein cholesterol concentrations and had a greater effect on reducing body fat percentage than traditional low-calorie diets. Thus, soy-based diets have health benefits in reducing weight and blood lipids.",
"title": "Effectiveness of a soy-based compared with a traditional low-calorie diet on weight loss and lipid levels in overweight adults."
},
{
"docid": "MED-1564",
"text": "Background In 2007 the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) released eight recommendations related to body fatness, physical activity and diet aimed at preventing the most common cancers worldwide. However, limited information exists on the association between meeting these recommendations and risks of specific cancers, including breast cancer. Methods We operationalized six recommendations (related to body fatness, physical activity, foods that promote weight gain, plant foods, red and processed meats, and alcohol) and examined their association with invasive breast cancer incidence over 6.7 years of follow-up in the VITamins And Lifestyle (VITAL) study cohort. Participants included 30,797 post-menopausal women ages 50–76 years at baseline in 2000–2002 with no history of breast cancer. Breast cancers (n=899) were tracked through the Western Washington Surveillance, Epidemiology and End Results (SEER) database. Results Breast cancer risk was reduced by 60% in women who met at least five recommendations compared to those who met none (HR: 0.40; 95% CI: 0.25–0.65; Ptrend<0.001). Further analyses that sequentially removed individual recommendations least associated with reduced risk suggested that this reduction is due to meeting recommendations related to body fatness, plant foods and alcohol (HR for meeting vs. not meeting these three recommendations: 0.38; 95% CI: 0.25–0.58; Ptrend <0.001). Conclusions Meeting the WCRF/AICR cancer prevention recommendations, specifically those related to alcohol, body fatness and plant foods, is associated with reduced post-menopausal breast cancer incidence. Impact Increased adherence to the WCRF/AICR cancer prevention recommendations could substantially reduce post-menopausal breast cancer risk in US women.",
"title": "Adherence to WCRF/AICR cancer prevention recommendations and risk of post-menopausal breast cancer"
},
{
"docid": "MED-1558",
"text": "Dietary fat and its effects on health and disease has attracted interest for research and Public Health. Since the 1980s many bodies and organizations have published recommendations regarding fat intake. In this paper different sets of recommendations are analyzed following a systematic review process to examine dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids. A literature search was conducted in relevant literature databases along a search for suitable grey literature reports. Documents were included if they reported information on either recommended intake levels or dietary reference values or nutritional objectives or dietary guidelines regarding fat and/or fatty acids and/or cholesterol intake or if reported background information on the process followed to produce the recommendations. There is no standard approach for deriving nutrient recommendations. Recommendations vary between countries regarding the levels of intake advised, the process followed to set the recommendations. Recommendations on fat intake share similar figures regarding total fat intake, saturated fats and trans fats. Many sets do not include a recommendation about cholesterol intake. Most recent documents provide advice regarding specific n-3 fatty acids. Despite efforts to develop evidence based nutrient recommendations and dietary guidelines that may contribute to enhance health, there are still many gaps in research. It would be desirable that all bodies concerned remain transparent about the development of dietary recommendations. In order to achieve this, the type of evidence selected to base the recommendations should be specified and ranked. Regular updates of such recommendations should be planned.",
"title": "Recommended dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids: a systematic review."
},
{
"docid": "MED-4894",
"text": "SUMMARY: This cross-sectional study showed that, although vegans had lower dietary calcium and protein intakes than omnivores, veganism did not have adverse effect on bone mineral density and did not alter body composition. INTRODUCTION: Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue. We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women. METHODS: One hundred and five Mahayana Buddhist nuns and 105 omnivorous women (average age = 62, range = 50-85) were randomly sampled from monasteries in Ho Chi Minh City and invited to participate in the study. By religious rule, the nuns do not eat meat or seafood (i.e., vegans). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and whole body (WB) was measured by DXA (Hologic QDR 4500). Lean mass, fat mass, and percent fat mass were also obtained from the DXA whole body scan. Dietary calcium and protein intakes were estimated from a validated food frequency questionnaire. RESULTS: There was no significant difference between vegans and omnivores in LSBMD (0.74 +/- 0.14 vs. 0.77 +/- 0.14 g/cm(2); mean +/- SD; P = 0.18), FNBMD (0.62 +/- 0.11 vs. 0.63 +/- 0.11 g/cm(2); P = 0.35), WBBMD (0.88 +/- 0.11 vs. 0.90 +/- 0.12 g/cm(2); P = 0.31), lean mass (32 +/- 5 vs. 33 +/- 4 kg; P = 0.47), and fat mass (19 +/- 5 vs. 19 +/- 5 kg; P = 0.77) either before or after adjusting for age. The prevalence of osteoporosis (T scores < or = -2.5) at the femoral neck in vegans and omnivores was 17.1% and 14.3% (P = 0.57), respectively. The median intake of dietary calcium was lower in vegans compared to omnivores (330 +/- 205 vs. 682 +/- 417 mg/day, P < 0.001); however, there was no significant correlation between dietary calcium and BMD. Further analysis suggested that whole body BMD, but not lumbar spine or femoral neck BMD, was positively correlated with the ratio of animal protein to vegetable protein. CONCLUSION: These results suggest that, although vegans have much lower intakes of dietary calcium and protein than omnivores, veganism does not have adverse effect on bone mineral density and does not alter body composition.",
"title": "Veganism, bone mineral density, and body composition: a study in Buddhist nuns."
},
{
"docid": "MED-3492",
"text": "AIM: The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. METHODS: A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. RESULTS: At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. CONCLUSION: The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.",
"title": "Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extrac..."
},
{
"docid": "MED-1072",
"text": "The purpose of this study was to examine the relationship of body mass index, abdomen-hip ratio, and dietary intake to fasting and postprandial insulin concentrations among 652 men aged 43-85 y, followed in the Normative Aging Study. Log-transformed fasting insulin was significantly associated with body mass index, abdomen-hip ratio, total fat energy, and saturated fatty acid energy, with correlation coefficients ranging from 0.14 for total fat to 0.45 for body mass index. When multivariate models were used, body mass index, abdomen-hip ratio, and saturated fatty acid intake were statistically significant independent predictors of both fasting and postprandial insulin concentrations, after age, cigarette smoking, and physical activity were adjusted for. If saturated fatty acids as a percentage of total energy were to decrease from 14% to 8%, there would be an 18% decrease in fasting insulin and a 25% decrease in postprandial insulin. These data suggest that overall adiposity, abdominal obesity, and a diet high in saturated fatty acids are independent predictors for both fasting and postprandial insulin concentrations.",
"title": "Relationship of dietary saturated fatty acids and body habitus to serum insulin concentrations: the Normative Aging Study."
},
{
"docid": "MED-5324",
"text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.",
"title": "Effects of a high-fat meal on pulmonary function in healthy subjects."
},
{
"docid": "MED-4748",
"text": "BACKGROUND: Adrenarche is the increase in adrenal androgen (AA) production starting in childhood. Until now, it has been unknown whether or not nutritional factors modulate adrenarche. OBJECTIVE: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes. DESIGN: Androgen and glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3-12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios. RESULTS: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R(2) = 5%). Animal protein intake was also positively associated with AA secretion (P < 0.05), which explained 1% of its variation. FFM (P = 0.1) and total protein intake (P = 0.05) showed positive trends. The difference in daily AA secretion between the lowest and highest quartile of FM was comparable to that between the lowest and highest estimated activity of one of the major steroidogenic enzymes. CONCLUSIONS: Body fat mass may relevantly influence prepubertal adrenarchal androgen status. In addition, animal protein intake may also make a small contribution to AA secretion in children.",
"title": "Body fat and animal protein intakes are associated with adrenal androgen secretion in children."
},
{
"docid": "MED-4246",
"text": "PURPOSE: To determine whether a multicomponent nutrition intervention program at a corporate site reduces body weight and improves other cardiovascular risk factors in overweight individuals. DESIGN: Prospective clinical intervention study. SUBJECTS/SETTING: Employees of the Government Employees Insurance Company (GEICO) (N = 113), aged 21 to 65 years, with a body mass index > or =25 kg/m(2) and/or previous diagnosis of type 2 diabetes. INTERVENTION: A 22-week intervention including a low-fat, vegan diet. MEASURES: Changes in body weight, anthropometric measures, blood pressure, lipid profile, and dietary intake. ANALYSIS: Multivariate analyses of variance were calculated for clinical and nutrient measures, followed by univariate analyses of variance, to determine the significance of differences between groups in changes over time. RESULTS: Intervention-group participants experienced greater weight changes compared with control-group participants (mean, -5.1 [SE, .6] kg vs. + .1 [SE, .6] kg, p < .0001), as well as greater changes in waist circumference (mean, -4.7 [SE, .6] cm vs. + .8 [SE, .6] cm, p < .0001) and waistratiohip ratio (mean, -.006 [SE, .003] vs. + .014 [SE, .005], p = .0007). Weight loss of 5% of body weight was more frequently observed in the intervention group (48.5%) compared with the control group (11.1%) (chi(2)[1, N = 113] = 16.99, p < .0001). CONCLUSIONS: Among individuals volunteering for a 22-week worksite research study, an intervention using a low-fat, vegan diet effectively reduced body weight and waist circumference.",
"title": "A multicomponent intervention reduces body weight and cardiovascular risk at a GEICO corporate site."
},
{
"docid": "MED-3794",
"text": "OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.",
"title": "Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms."
},
{
"docid": "MED-1004",
"text": "Background Exposure of the U.S. population to polybrominated diphenyl ethers (PBDEs) is thought to be via exposure to dust and diet. However, little work has been done to empirically link body burdens of these compounds to either route of exposure. Objectives The primary goal of this research was to evaluate the dietary contribution to PBDE body burdens in the United States by linking serum levels to food intake. Methods We used two dietary instruments—a 24-hr food recall (24FR) and a 1-year food frequency questionnaire (FFQ)—to examine food intake among participants of the 2003–2004 National Health and Nutrition Examination Survey. We regressed serum concentrations of five PBDEs (BDE congeners 28, 47, 99, 100, and 153) and their sum (∑PBDE) against diet variables while adjusting for age, sex, race/ethnicity, income, and body mass index. Results ∑PBDE serum concentrations among vegetarians were 23% (p = 0.006) and 27% (p = 0.009) lower than among omnivores for 24FR and 1-year FFQ, respectively. Serum levels of five PBDE congeners were associated with consumption of poultry fat: Low, medium, and high intake corresponded to geometric mean ∑PBDE concentrations of 40.6, 41.9, and 48.3 ng/g lipid, respectively (p = 0.0005). We observed similar trends for red meat fat, which were statistically significant for BDE-100 and BDE-153. No association was observed between serum PBDEs and consumption of dairy or fish. Results were similar for both dietary instruments but were more robust using 24FR. Conclusions Intake of contaminated poultry and red meat contributes significantly to PBDE body burdens in the United States.",
"title": "Diet Contributes Significantly to the Body Burden of PBDEs in the General U.S. Population"
},
{
"docid": "MED-3489",
"text": "OBJECTIVE: To examine in overweight humans the short-term safety and efficacy for weight loss of an herbal supplement containing Ma Huang, Guarana and other ingredients. DESIGN: An 8 week randomized, double-blind placebo controlled study of a herbal dietary supplement (72 mg/day ephedrine alkaloids and 240 mg/day caffeine). SUBJECTS: Overweight men and women (body mass index, > or =29 and < or =35 kg/m2). MEASUREMENTS: The primary outcome variable was body weight change. Secondary variables included anthropometric, metabolic and cardiovascular changes. RESULTS: Sixty-seven subjects were randomized to either placebo (n=32) or active Ma Huang/Guarana (n=35). Twenty-four subjects in each group completed the study. Active treatment produced significantly (P<0.006) greater loss of weight (X+/-s.d.,-4.0+/-3.4 kg) and fat (-2.1+/-3.0% fat) over the 8-week treatment period than did placebo (-0.8+/-2.4 kg and 0.2+/-2.3% fat). Active treatment also produced greater reductions in hip circumference and serum triglyceride levels. Eight of the 35 actively treated subjects (23%) and none of the 32 placebo-treated control subjects withdrew from the protocol because of potential treatment-related effects. Dry mouth, insomnia and headache were the adverse symptoms reported most frequently by the herbal vs placebo group at the final evaluation visit. CONCLUSIONS: This herbal mixture of Ma Huang and Guarana effectively promoted short-term weight and fat loss. Safety with long-term use requires further investigation.",
"title": "An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial."
},
{
"docid": "MED-1456",
"text": "OBJECTIVE: To test the hypothesis that dietary factors in the vegan diet lead to improved insulin sensitivity and lower intramyocellular lipid (IMCL) storage. DESIGN: Case-control study. SETTING: Imperial College School of Medicine, Hammersmith Hospital Campus, London, UK. SUBJECTS: A total of 24 vegans and 25 omnivores participated in this study; three vegan subjects could not be matched therefore the matched results are shown for 21 vegans and 25 omnivores. The subjects were matched for gender, age and body mass index (BMI). INTERVENTIONS: Full anthropometry, 7-day dietary assessment and physical activity levels were obtained. Insulin sensitivity (%S) and beta-cell function (%B) were determined using the homeostatic model assessment (HOMA). IMCL levels were determined using in vivo proton magnetic resonance spectroscopy; total body fat content was assessed by bioelectrical impedance. RESULTS: There was no difference between the groups in sex, age, BMI, waist measurement, percentage body fat, activity levels and energy intake. Vegans had a significantly lower systolic blood pressure (-11.0 mmHg, CI -20.6 to -1.3, P=0.027) and higher dietary intake of carbohydrate (10.7%, CI 6.8-14.5, P<0.001), nonstarch polysaccharides (20.7 g, CI 15.8-25.6, P<0.001) and polyunsaturated fat (2.8%, CI 1.0-4.6, P=0.003), with a significantly lower glycaemic index (-3.7, CI -6.7 to -0.7, P=0.01). Also, vegans had lower fasting plasma triacylglycerol (-0.7 mmol/l, CI -0.9 to -0.4, P<0.001) and glucose (-0.4 mmol/l, CI -0.7 to -0.09, P=0.05) concentrations. There was no significant difference in HOMA %S but there was with HOMA %B (32.1%, CI 10.3-53.9, P=0.005), while IMCL levels were significantly lower in the soleus muscle (-9.7, CI -16.2 to -3.3, P=0.01). CONCLUSION: Vegans have a food intake and a biochemical profile that will be expected to be cardioprotective, with lower IMCL accumulation and beta-cell protective.",
"title": "Veganism and its relationship with insulin resistance and intramyocellular lipid."
},
{
"docid": "MED-1309",
"text": "Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our recent report suggested that oat, rich in beta-glucan, had a metabolic-regulating and liver-protecting effect in an animal model. In this study, we performed a clinical trial to further confirm the effect of oat. Subjects with BMI ≥27 and aged 18-65, were randomly divided into a control (n=18) and an oat-treated (n=16) group, taking a placebo or beta glucan-containing oat cereal, respectively, for 12 weeks. Our data showed that consumption of oat reduced body weight, BMI, body fat and the waist-to-hip ratio. Profiles of hepatic function, including AST, but especially ALT, were useful resources to help in the evaluation of the liver, since both showed decrements in patients with oat consumption. Nevertheless, anatomic changes were still not observed by ultrasonic image analysis. Ingestion of oat was well tolerated and there was no adverse effect during the trial. In conclusion, consumption of oat reduced obesity, abdominal fat, and improved lipid profiles and liver functions. Taken as a daily supplement, oat could act as an adjuvant therapy for metabolic disorders.",
"title": "Oat prevents obesity and abdominal fat distribution, and improves liver function in humans."
},
{
"docid": "MED-1868",
"text": "Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our previous report suggested that Hibiscus sabdariffa extracts (HSE) had a metabolic-regulating and liver-protecting potential. In this study, we performed a clinical trial to further confirm the effect of HSE. Subjects with a BMI ≧ 27 and aged 18-65, were randomly divided into control (n = 17) and HSE-treated (n = 19) groups, respectively, for 12 weeks. Our data showed that consumption of HSE reduced body weight, BMI, body fat and the waist-to-hip ratio. Serum free fatty acid (FFA) was lowered by HSE. Anatomic changes revealed that HSE improved the illness of liver steatosis. Ingestion of HSE was well tolerated and there was no adverse effect during the trial. No alteration was found for serum α-amylase and lipase. The clinical effect should mainly be attributed to the polyphenols of HSE, since composition analysis showed that branched chain-amino acids, which is associated with obesity, is not obviously high. In conclusion, consumption of HSE reduced obesity, abdominal fat, serum FFA and improved liver steatosis. HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver.",
"title": "Hibiscus sabdariffa extract inhibits obesity and fat accumulation, and improves liver steatosis in humans."
},
{
"docid": "MED-5320",
"text": "Increased (18)F-FDG activity in fatty tissue has previously been reported with PET/CT. We previously named this activity uptake in supraclavicular area fat (\"USA-Fat\"). We and others have speculated that this uptake exists in metabolically active brown adipose tissue (BAT). Such tissue might be expected to have varying metabolic activity depending on the ambient temperature. The purpose of this study was to evaluate the frequency of USA-Fat and its relationship to the outdoor temperature. METHODS: Between July 2001 and June 2002, 1,017 consecutive whole-body scans were obtained with a PET/CT scanner and (18)F-FDG for clinical patients. PET images were reviewed for the presence of USA-Fat. RESULTS: USA-Fat was observed in 68 scans obtained from 62 patients (51 female and 11 male). The incidence of USA-Fat was highest, at 13.7%, in January through March, while outside temperatures were low, and was significantly lower, at 4.1%, during the rest of the year. CONCLUSION: The incidence of USA-Fat is clearly increased during the cooler period of the year. This finding suggests that stimulation by cold temperatures increases the frequency with which USA-Fat occurs, supporting underlying BAT as the etiology for this activity.",
"title": "\"USA-Fat\": prevalence is related to ambient outdoor temperature-evaluation with 18F-FDG PET/CT."
},
{
"docid": "MED-1468",
"text": "Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells (adipocytes) is thought to be most important. Here we show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese individuals, even after marked weight loss, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analysing the integration of 14C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in early onset obesity, suggesting a tight regulation of fat cell number in this condition during adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.",
"title": "Dynamics of fat cell turnover in humans."
},
{
"docid": "MED-1301",
"text": "PURPOSE: There is evidence that dietary habits contribute to the presence and severity of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to explore any associations between consumption of grains and the development and severity of NAFLD. METHODS: Seventy-three consecutive NAFLD patients were enrolled. Additionally, 58 controls matched for age, sex and body mass index with 58 patients were also included. Consumption of grains was estimated through a semi-quantitative food frequency questionnaire. Medical history, anthropometric indices, body composition analysis, physical activity data, biochemical and inflammatory markers were available for all the participants. Liver stiffness measurement by transient elastography was performed in 58 and liver biopsy in 34 patients. RESULTS: In patients, consumption of whole grains was associated with lower abdominal fat level (β = -0.24, p = 0.02) and lower levels of insulin resistance index (β = -0.28, p = 0.009), while it also correlated inversely with interleukin-6 levels (ρ = -0.23, p = 0.05). Consumption of whole grains was associated with lower likelihood of having histological steatohepatitis (OR 0.97, 95% CI 0.94-1.000), after adjusting for sex and energy intake, but the association became weaker after further adjusting for abdominal fat or interleukin-6 levels. In the case-control analysis, consumption of refined grains was associated with higher odds of having NAFLD (OR 1.021, 95% CI 1.001-1.042), after adjusting for age, sex, energy intake, abdominal fat level, HOMA-IR, LDL, adiponectin and TNF-α. CONCLUSIONS: Although refined grain consumption increased the likelihood of having NAFLD, whole-grain consumption favorably affected clinical characteristics of patients with NAFLD and tended to be associated with less severe disease.",
"title": "The impact of cereal grain consumption on the development and severity of non-alcoholic fatty liver disease."
},
{
"docid": "MED-5230",
"text": "CONTEXT: Dietary composition may affect insulin secretion, and high insulin levels, in turn, may increase the risk for cardiovascular disease (CVD). OBJECTIVE: To examine the role of fiber consumption and its association with insulin levels, weight gain, and other CVD risk factors compared with other major dietary components. DESIGN AND SETTING: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter population-based cohort study of the change in CVD risk factors over 10 years (1985-1986 to 1995-1996) in Birmingham, Ala; Chicago, III; Minneapolis, Minn; and Oakland, Calif. PARTICIPANTS: A total of 2909 healthy black and white adults, 18 to 30 years of age at enrollment. MAIN OUTCOME MEASURES: Body weight, insulin levels, and other CVD risk factors at year 10, adjusted for baseline values. RESULTS: After adjustment for potential confounding factors, dietary fiber showed linear associations from lowest to highest quintiles of intake with the following: body weight (whites: 174.8-166.7 lb [78.3-75.0 kg], P<.001; blacks: 185.6-177.6 lb [83.5-79.9 kg], P = .001), waist-to-hip ratio (whites: 0.813-0.801, P = .004; blacks: 0.809-0.799, P = .05), fasting insulin adjusted for body mass index (whites: 77.8-72.2 pmol/L [11.2-10.4 microU/mL], P = .007; blacks: 92.4-82.6 pmol/L [13.3-11.9 microU/mL], P = .01) and 2-hour postglucose insulin adjusted for body mass index (whites: 261.1-234.7 pmol/L [37.6-33.8 microU/mL], P = .03; blacks: 370.2-259.7 pmol/L [53.3-37.4 microU/mL], P<.001). Fiber was also associated with blood pressure and levels of triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fibrinogen; these associations were substantially attenuated by adjustment for fasting insulin level. In comparison with fiber, intake of fat, carbohydrate, and protein had inconsistent or weak associations with all CVD risk factors. CONCLUSIONS: Fiber consumption predicted insulin levels, weight gain, and other CVD risk factors more strongly than did total or saturated fat consumption. High-fiber diets may protect against obesity and CVD by lowering insulin levels.",
"title": "Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults."
},
{
"docid": "MED-4211",
"text": "Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).",
"title": "Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Jap..."
},
{
"docid": "MED-1323",
"text": "Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.",
"title": "Low-carbohydrate diet scores and risk of type 2 diabetes in men"
},
{
"docid": "MED-4823",
"text": "Background Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. Methods We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. Results Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; Ptrend = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; Ptrend < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; Ptrend = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; Ptrend < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). Conclusion In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.",
"title": "Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and Health Study"
},
{
"docid": "MED-1616",
"text": "The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.",
"title": "Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials."
},
{
"docid": "MED-5286",
"text": "Obesity remains a major public health challenge, and its prevalence is dramatically increasing. Diet and exercise are typically recommended to prevent and manage obesity; however, the results are often conflicting. Polyphenols, a class of phytochemicals that have been shown to reduce the risk factors for diabetes type II and cardiovascular diseases, are recently suggested as complementary agents in the management of obesity through several mechanisms such as decreasing fat absorption and/or fat synthesis. Dark chocolate, a high source of polyphenols, and flavanols in particular, has lately received attention for its possible role in modulating obesity because of its potential effect on fat and carbohydrate metabolism, as well as on satiety. This outcome was investigated in animal models of obesity, cell cultures and few human observational and clinical studies. The research undertaken to date has shown promising results, with the possible implication of cocoa/dark chocolate in the modulation of obesity and body weight through several mechanisms including decreasing the expression of genes involved in fatty acid synthesis, reducing the digestion and absorption of fats and carbohydrates and increasing satiety. Copyright © 2013 John Wiley & Sons, Ltd.",
"title": "Dark chocolate: an obesity paradox or a culprit for weight gain?"
},
{
"docid": "MED-5314",
"text": "We here discuss the role of brown adipose tissue on energy homeostasis and assess its potential as a target for body weight management. Because of their high number of mitochondria and the presence of uncoupling protein 1, brown fat adipocytes can be termed as energy inefficient for adenosine-5′-triphosphate (ATP) production but energy efficient for heat production. Thus, the energy inefficiency of ATP production, despite high energy substrate oxidation, allows brown adipose tissue to generate heat for body temperature regulation. Whether such thermogenic property also plays a role in body weight regulation is still debated. The recent (re)discovery of brown adipose tissue in human adults and a better understanding of brown adipose tissue development have encouraged the quest for new alternatives to treat obesity since obese individuals seem to have less brown adipose tissue mass/activity than do their lean counterparts. In this review, we discuss the physiological relevance of brown adipose tissue on thermogenesis and its potential usefulness on body weight control in humans.",
"title": "The Implication of Brown Adipose Tissue for Humans"
},
{
"docid": "MED-4069",
"text": "To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.",
"title": "Meat, fat and risk of breast cancer: a case-control study from Uruguay."
}
] |
PLAIN-2035
|
saffron
|
[
{
"docid": "MED-3670",
"text": "Generalized and persistent anxiety, accompanied by nervousness and other symptoms (Generalised Anxiety Disorder, GAD) is frequent in the general population and leads to benzodiazepine usage. Unfortunately, these substances induce sedation and have a high potential for drug abuse, and there is thus a need for alternatives. As the anxiolytic properties of lavender have already been demonstrated in pharmacological studies and small-scale clinical trials, it was postulated that lavender has a positive effect in GAD. A controlled clinical study was then performed to evaluate the efficacy of silexan, a new oral lavender oil capsule preparation, versus a benzodiazepine. In this study, the efficacy of a 6-week-intake of silexan compared to lorazepam was investigated in adults with GAD. The primary target variable was the change in the Hamilton Anxiety Rating Scale (HAM-A-total score) as an objective measurement of the severity of anxiety between baseline and week 6. The results suggest that silexan effectively ameliorates generalized anxiety comparable to a common benzodiazepine (lorazepam). The mean of the HAM-A-total score decreased clearly and to a similar extent in both groups (by 11.3+/-6.7 points (45%) in the silexan group and by 11.6+/-6.6 points (46%) in the lorazepam group, from 25+/-4 points at baseline in both groups). During the active treatment period, the two HAM-A subscores \"somatic anxiety\" (HAM-A subscore I) and \"psychic anxiety\" (HAM-A subscore II) also decreased clearly and to a similar extent in both groups. The changes in other subscores measured during the study, such as the SAS (Self-rating Anxiety Scale), PSWQ-PW (Penn State Worry Questionnaire), SF 36 Health survey Questionnaire and Clinical Global Impressions of severity of disorder (CGI item 1, CGI item 2, CGI item 3), and the results of the sleep diary demonstrated comparable positive effects of the two compounds. In conclusion, our results demonstrate that silexan is as effective as lorazepam in adults with GAD. The safety of silexan was also demonstrated. Since lavender oil showed no sedative effects in our study and has no potential for drug abuse, silexan appears to be an effective and well tolerated alternative to benzodiazepines for amelioration of generalised anxiety. Copyright 2009 Elsevier GmbH. All rights reserved.",
"title": "A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder."
},
{
"docid": "MED-1501",
"text": "BACKGROUND: Many biological, behavioral, social, and environmental factors may contribute to the delay or prevention of cognitive decline. PURPOSE: To summarize evidence about putative risk and protective factors for cognitive decline in older adults and the effects of interventions for preserving cognition. DATA SOURCES: English-language publications in MEDLINE, HuGEpedia, AlzGene, and the Cochrane Database of Systematic Reviews from 1984 through 27 October 2009. STUDY SELECTION: Observational studies with 300 or more participants and randomized, controlled trials (RCTs) with 50 or more adult participants who were 50 years or older, drawn from general populations, and followed for at least 1 year were included. Relevant, good-quality systematic reviews were also eligible. DATA EXTRACTION: Information on study design, outcomes, and quality were extracted by one researcher and verified by another. An overall rating of the quality of evidence was assigned by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. DATA SYNTHESIS: 127 observational studies, 22 RCTs, and 16 systematic reviews were reviewed in the areas of nutritional factors; medical factors and medications; social, economic, or behavioral factors; toxic environmental exposures; and genetics. Few of the factors had sufficient evidence to support an association with cognitive decline. On the basis of observational studies, evidence that supported the benefits of selected nutritional factors or cognitive, physical, or other leisure activities was limited. Current tobacco use, the apolipoprotein E epsilon4 genotype, and certain medical conditions were associated with increased risk. One RCT found a small, sustained benefit from cognitive training (high quality of evidence) and a small RCT reported that physical exercise helps to maintain cognitive function. LIMITATIONS: The categorization and definition of exposures were heterogeneous. Few studies were designed a priori to assess associations between specific exposures and cognitive decline. The review included only English-language studies, prioritized categorical outcomes, and excluded small studies. CONCLUSION: Few potentially beneficial factors were identified from the evidence on risk or protective factors associated with cognitive decline, but the overall quality of the evidence was low. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and the National Institute on Aging, through the Office of Medical Applications of Research, National Institutes of Health.",
"title": "Systematic review: factors associated with risk for and possible prevention of cognitive decline in later life."
},
{
"docid": "MED-1505",
"text": "The important role of diet in cardiometabolic health is generally well recognised; for mental health, it is not so well understood. However, lifestyle risk factors for poor physical health are the same risk factors for mental illness, including poor diet. This is reflected by the high level of poor physical health in people with mental illness. Mediterranean, whole food diets have been associated with reduced risk for chronic disease, but very little research has investigated their mental health benefits. We provide a model for the pathways by which food components provided by a Mediterranean-style diet can facilitate healthy brain function. We then review evidence for the role of selected nutrients/food components - antioxidants, omega-3 fatty acids and B vitamins - in the brain and, hence, modulation of cognitive function and mental health. Converging evidence indicates multiple pathways by which these nutrients can assist in brain function, drawing from studies investigating them in isolation. There is very little work done on synergistic actions of nutrients and whole diets, highlighting a need for human intervention studies investigating benefits of Mediterranean-style diets for mental, as well as cardiometabolic health. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Nutritional modulation of cognitive function and mental health."
},
{
"docid": "MED-745",
"text": "The double-blind randomized controlled trial (RCT) is accepted by medicine as objective scientific methodology that, when ideally performed, produces knowledge untainted by bias. The validity of the RCT rests not just on theoretical arguments, but also on the discrepancy between the RCT and less rigorous evidence (the difference is sometimes considered an objective measure of bias). A brief overview of historical and recent developments in \"the discrepancy argument\" is presented. The article then examines the possibility that some of this \"deviation from truth\" may be the result of artifacts introduced by the masked RCT itself. Can an \"unbiased\" method produce bias? Among the experiments examined are those that augment the methodological stringency of a normal RCT in order to render the experiment less susceptible to subversion by the mind. This methodology, a hypothetical \"platinum\" standard, can be used to judge the \"gold\" standard. The concealment in a placebo-controlled RCT seems capable of generating a \"masking bias.\" Other potential biases, such as \"investigator self-selection,\" \"preference,\" and \"consent\" are also briefly discussed. Such potential distortions indicate that the double-blind RCT may not be objective in the realist sense, but rather is objective in a \"softer\" disciplinary sense. Some \"facts\" may not exist independent of the apparatus of their production.",
"title": "The double-blind, randomized, placebo-controlled trial: gold standard or golden calf?"
},
{
"docid": "MED-4192",
"text": "AIM: The purpose of this study was to clarify the effects of saffron odor on symptoms unique to women, such as premenstrual syndrome (PMS), dysmenorrhea (menstrual pain) and irregular menstruation. MATERIALS AND METHODS: Thirty-five women with a normal sense of smell were exposed to saffron odor for 20 min. Saliva samples were then collected to measure levels of cortisol (C), testosterone (T) and 17-β estradiol (E) by enzyme immunoassay, and the State-Trait Anxiety Inventory (STAI) was administered as a psychological test. RESULTS: Saffron odor significantly decreased C levels after short-term stimulation (20 min) in both follicular and luteal phases. E level after exposure to saffron odor was increased in both the follicular- and luteal-phase groups. STAI score decreased in the follicular and luteal phases in the saffron group. CONCLUSIONS: The present findings support the existence of physiological and psychological effects of saffron odor in women. Our results indicate that saffron odor exert some effects in the treatment of PMS, dysmenorrhea and irregular menstruation. This is the first report to suggest that saffron odor may be effective in treating menstrual distress. Copyright © 2010 Elsevier GmbH. All rights reserved.",
"title": "Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus)."
},
{
"docid": "MED-746",
"text": "In this study, the effect of Crocus sativus (saffron) was studied on male erectile dysfunction (ED). Twenty male patients with ED were followed for ten days in which each morning they took a tablet containing 200mg of saffron. Patients underwent the nocturnal penile tumescence (NPT) test and the international index of erectile function questionnaire (IIEF-15) at the start of the treatment and at the end of the ten days. After the ten days of taking saffron there was a statistically significant improvement in tip rigidity and tip tumescence as well as base rigidity and base tumescence. ILEF-15 total scores were significantly higher in patients after saffron treatment (before treatment 22.15+/-1.44; after treatment 39.20+/-1.90, p<0.001). Saffron showed a positive effect on sexual function with increased number and duration of erectile events seen in patients with ED even only after taking it for ten days.",
"title": "Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: a pilot study."
},
{
"docid": "MED-3668",
"text": "OBJECTIVE: Investigate the effects of lavender oil on the central nervous system, autonomic nervous system, and mood responses in humans after inhalation. MATERIAL AND METHOD: Twenty healthy volunteers participated in the experiments. The present study assessed autonomic parameters such as blood pressure, heart rate, respiratory rate, and skin temperature to determine the arousal level of the autonomic nervous system. In addition, subjects were asked to estimate their mood responses such as feeling pleasant or unpleasant, uncomfortable, sensuality, relaxation, or refreshing in order to assess subjective behavioral arousal. Finally, electroencephalogram (EEG) was recorded from 31 electrodes on the scalp according to the international 10 to 20 system, and EEG power spectra were calculated by Fast Fourier Transform (FFT). Data was analyzed by comparing the effects of lavender oil on physiological and mood states with sweet almond oil. These assessments were measured before and after using paired t-test statistical procedure. RESULTS: The results revealed that lavender oil caused significant decreases of blood pressure, heart rate, and skin temperature, which indicated a decrease of autonomic arousal. In terms of mood responses, the subjects in the lavender oil group categorized themselves as more active, fresher relaxed than subjects just inhaling base oil. Compared with base oil, lavender oil increased the power of theta (4-8 Hz) and alpha (8-13 Hz) brain activities. The topographic map showed obviously more scattering power in alpha range waves particularly in bilateral temporal and central area. CONCLUSION: The findings provided evidence the relaxing effect of inhaling lavender oil.",
"title": "The effects of lavender oil inhalation on emotional states, autonomic nervous system, and brain electrical activity."
},
{
"docid": "MED-1496",
"text": "Oxidative stress (OS) and damages due to excessive reactive oxygen species (ROS) are common causes of injuries to cells and organisms. The prevalence of neurodegenerative diseases (ND) increases with aging and much of the research involving ROS and OS has emerged from works in this field. This text reviews some recent published articles about the role of OS in ND. Since there are many reviews in this field, the focus was centered in articles published recently. The Scientific Journals Directory supported by the Brazilian Ministry of Education Office for the Coordination of Higher Educational Personnel Improvement (CAPES) was used to search, download, and review articles. The search engine looked for the terms 'oxidative stress AND neurodegenerative diseases AND nutrition' in 10 different scientific collections. Biochemical markers for ND lack sensitivity or specificity for diagnosis or for tracking response to therapy today. OS has an intimate connection with ND, albeit low levels of ROS seem to protect the brain. Deleterious changes in mitochondria, OS, calcium, glucocorticoids, inflammation, trace metals, insulin, cell cycle, protein aggregation, and hundreds to thousands of genes occur in ND. The interaction of genes with their environment, may explain ND. Although OS has received much attention over the years, which increased the number of scientific works on antioxidant interventions, no one knows how to stop or delay ND at present. Interventions in vitro, in vivo, and in humans will continue to contribute for a better understanding of these pathologies.",
"title": "Brain rust: recent discoveries on the role of oxidative stress in neurodegenerative diseases."
},
{
"docid": "MED-1499",
"text": "Nature has gifted mankind with a plethora of flora-bearing fruits, vegetables and nuts. The diverse array of bioactive nutrients present in these natural products plays a pivotal role in prevention and cure of various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and other neuronal dysfunctions. Accumulated evidence suggests that naturally occurring phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive function. Nuts such as walnut have also demonstrated neuroprotective effect against AD. The molecular mechanisms behind the curative effects rely mainly on the action of phytonutrients on distinct signalling pathways associated with protein folding and neuroinflammation. The neuroprotective effects of various naturally occurring compounds in AD is evaluating in this review.",
"title": "Neuroprotective effect of natural products against Alzheimer's disease."
},
{
"docid": "MED-1500",
"text": "BACKGROUND: Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is currently unsupported by a systematic review of the literature. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer's disease or cognitive decline in regard to the frequency of fruit and vegetables consumption. FINDINGS: Nine studies with a total of 44,004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined. CONCLUSION: Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.",
"title": "Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies."
},
{
"docid": "MED-1506",
"text": "Intake of saturated fats and simple carbohydrates, two of the primary components of a modern Western diet, is linked with the development of obesity and Alzheimer's Disease. The present paper summarizes research showing that Western diet intake is associated with cognitive impairment, with a specific emphasis on learning and memory functions that are dependent on the integrity of the hippocampus. The paper then considers evidence that saturated fat and simple carbohydrate intake is correlated with neurobiological changes in the hippocampus that may be related to the ability of these dietary components to impair cognitive function. Finally, a model is described proposing that Western diet consumption contributes to the development of excessive food intake and obesity, in part, by interfering with a type of hippocampal-dependent memory inhibition that is critical in the ability of animals to refrain from responding to environmental cues associated with food, and ultimately from consuming energy intake in excess of that driven solely by caloric need.",
"title": "Western Diet Consumption and Cognitive Impairment: Links to Hippocampal Dysfunction and Obesity"
},
{
"docid": "MED-1503",
"text": "Epidemiologic studies suggest that dietary lutein and zeaxanthin may be of benefit in maintaining cognitive health. Among the carotenoids, lutein and zeaxanthin are the only two that cross the blood-retina barrier to form macular pigment (MP) in the eye. They also preferentially accumulate in the human brain. Lutein and zeaxanthin in macula from nonhuman primates were found to be significantly correlated with their concentrations in matched brain tissue. Therefore, MP can be used as a biomarker of lutein and zeaxanthin in primate brain tissue. This is of interest given that a significant correlation was found between MP density and global cognitive function in healthy older adults. An examination of a relation between cognition and lutein and zeaxanthin concentrations in the brain tissue of decedents from a population-based study in centenarians found that zeaxanthin concentrations in brain tissue were significantly related to antemortem measures of global cognitive function, memory retention, verbal fluency, and dementia severity after adjustment for age, sex, education, hypertension, and diabetes. In univariate analyses, lutein was related to recall and verbal fluency, but the strength of the associations was attenuated with adjustment for covariates. However, lutein concentrations in the brain were significantly lower in individuals with mild cognitive impairment than in those with normal cognitive function. Last, in a 4-mo, double-blinded, placebo-controlled trial in older women that involved lutein supplementation (12 mg/d), alone or in combination with DHA (800 mg/d), verbal fluency scores improved significantly in the DHA, lutein, and combined-treatment groups. Memory scores and rate of learning improved significantly in the combined-treatment group, who also showed a trend toward more efficient learning. When all of these observations are taken into consideration, the idea that lutein and zeaxanthin can influence cognitive function in older adults warrants further study.",
"title": "A possible role for lutein and zeaxanthin in cognitive function in the elderly."
},
{
"docid": "MED-3666",
"text": "Most cases of male prepubertal gynecomastia are classified as idiopathic. We investigated possible causes of gynecomastia in three prepubertal boys who were otherwise healthy and had normal serum concentrations of endogenous steroids. In all three boys, gynecomastia coincided with the topical application of products that contained lavender and tea tree oils. Gynecomastia resolved in each patient shortly after the use of products containing these oils was discontinued. Furthermore, studies in human cell lines indicated that the two oils had estrogenic and antiandrogenic activities. We conclude that repeated topical exposure to lavender and tea tree oils probably caused prepubertal gynecomastia in these boys. 2007 Massachusetts Medical Society",
"title": "Prepubertal gynecomastia linked to lavender and tea tree oils."
},
{
"docid": "MED-4669",
"text": "RATIONALE: There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer's disease (AD). OBJECTIVE: The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group. CONCLUSION: This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer's disease. This trial is registered with the Iranian Clinical Trials Registry (IRCT138711051556N1).",
"title": "A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease."
},
{
"docid": "MED-1497",
"text": "Traumatic brain injury (TBI) constitutes a major global health and socio-economic problem with neurobehavioral sequelae contributing to long-term disability. It causes brain swelling, axonal injury and hypoxia, disrupts blood brain barrier function and increases inflammatory responses, oxidative stress, neurodegeneration and leads to cognitive impairment. Epidemiological studies show that 30% of patients, who die of TBI, have Aβ plaques which are pathological features of Alzheimer's disease (AD). Thus TBI acts as an important epigenetic risk factor for AD. This review focuses on AD related genes which are expressed during TBI and its relevance to progression of the disease. Such understanding will help to diagnose the risk of TBI patients to develop AD and design therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Traumatic brain injury: a risk factor for Alzheimer's disease."
},
{
"docid": "MED-743",
"text": "OBJECTIVE: To evaluate herbal medicines, other than St. John's wort, in the treatment of depression. DATA SOURCES/SEARCH METHODS: A computer-based search of Medline, Cinahl, AMED, ALT Health Watch, Psych Articles, Psych Info, Current Contents databases, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews, was performed. Researchers were contacted, and bibliographies of relevant papers and previous meta-analysis were hand searched for additional references. REVIEW METHODS: Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints. RESULTS: Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located. DISCUSSION: Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo. CONCLUSION: A number of herbal medicines show promise in the management of mild-to-moderate depression.",
"title": "Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review."
},
{
"docid": "MED-744",
"text": "This paper presents a new interpretation of a unique Bronze Age (c. 3000-1100 BCE) Aegean wall painting in the building of Xeste 3 at Akrotiri,Thera. Crocus carturightianus and its active principle, saffron, are the primary subjects at Xeste 3. Several lines of evidence suggest that the meaning of these frescoes concerns saffron and healing: (1) the unusual degree of visual attention given to the crocus, including the variety of methods for display of the stigmas; (2) the painted depiction of the line of saffron production from plucking blooms to the collection of stigmas; and (3) the sheer number (ninety) of medical indications for which saffron has been used from the Bronze Age to the present. The Xeste 3 frescoes appear to portray a divinity of healing associated with her phytotherapy, saffron. Cultural and commercial interconnections between the Therans, the Aegean world, and their neighboring civilizations in the early 2nd millennium BCE indicate a close network of thematic exchange, but there is no evidence that Akrotiri borrowed any of these medicinal (or iconographic) representations. The complex production line, the monumental illustration of a goddess of medicine with her saffron attribute, and this earliest botanically accurate image of an herbal medication are all Theran innovations.",
"title": "Therapy with saffron and the goddess at Thera."
},
{
"docid": "MED-4671",
"text": "WHAT IS KNOWN: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer's disease (AD). OBJECTIVE: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. METHODS: Forty-six patients with probable AD were screened for a 16-week, double-blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating scale-sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16-week study. RESULTS: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS-cog: F=4·12, d.f.=1, P=0·04; CDR: F=4·12, d.f.=1, P=0·04). There were no significant differences in the two groups in terms of observed adverse events. WHAT IS NEW AND CONCLUSION: This double-blind, placebo-controlled study suggests that at least in the short-term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for. Copyright © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.",
"title": "Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial."
},
{
"docid": "MED-1498",
"text": "Many studies have documented the role of risk and protective factors for late life dementing illnesses, particularly Alzheimer's disease. A \"Systematic Review\" from the US Agency for Healthcare Research and Quality and the National Institute on Aging concluded that because the overall quality of evidence was low, recommendations for public health could not be made. In order to gain evidence for the efficacy of lifestyle interventions, we propose a \"Modest Proposal\" to study 10,000 subjects over 40 years randomly assigned to groups of low or high saturated fat in the diet, head injury, and high or low levels of mental activity, physical activity, or inactivity as well as smoking or non-smoking. This proposed study cannot be accomplished. The \"Modest Proposal\" illustrates that the absence of definitive evidence should not restrict physicians from making reasonable recommendations based on the evidence that is available.",
"title": "A modest proposal for a longitudinal study of dementia prevention (with apologies to Jonathan Swift, 1729)."
},
{
"docid": "MED-2215",
"text": "We investigated the relationship between animal product consumption and evidence of dementia in two cohort substudies. The first enrolled 272 California residents matched for age, sex, and zip code (1 vegan, 1 lacto-ovo-vegetarian, and 2 'heavy' meat eaters in each of 68 quartets). This design ensured a wide range of dietary exposure. The second included 2,984 unmatched subjects who resided within the Loma Linda, California area. All subjects were enrolled in the Adventist Health Study. The matched subjects who ate meat (including poultry and fish) were more than twice as likely to become demented as their vegetarian counterparts (relative risk 2.18, p = 0.065) and the discrepancy was further widened (relative risk 2.99, p = 0.048) when past meat consumption was taken into account. There was no significant difference in the incidence of dementia in the vegetarian versus meat-eating unmatched subjects. There was no obvious explanation for the difference between the two substudies, although the power of the unmatched sub-study to detect an effect of 'heavy' meat consumption was unexpectedly limited. There was a trend towards delayed onset of dementia in vegetarians in both substudies.",
"title": "The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study."
},
{
"docid": "MED-4544",
"text": "Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian gooseberry or amla, is arguably the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Various parts of the plant are used to treat a range of diseases, but the most important is the fruit. The fruit is used either alone or in combination with other plants to treat many ailments such as common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive. Preclinical studies have shown that amla possesses antipyretic, analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, antihypercholesterolemia, wound healing, antidiarrheal, antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective properties. In addition, experimental studies have shown that amla and some of its phytochemicals such as gallic acid, ellagic acid, pyrogallol, some norsesquiterpenoids, corilagin, geraniin, elaeocarpusin, and prodelphinidins B1 and B2 also possess antineoplastic effects. Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities, properties that are efficacious in the treatment and prevention of cancer. This review for the first time summarizes the results related to these properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a cancer preventive and therapeutic drug in humans.",
"title": "Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer."
},
{
"docid": "MED-1504",
"text": "BACKGROUND: Numerous studies have investigated risk factors for Alzheimer disease (AD). However, at a recent National Institutes of Health State-of-the-Science Conference, an independent panel found insufficient evidence to support the association of any modifiable factor with risk of cognitive decline or AD. OBJECTIVE: To present key findings for selected factors and AD risk that led the panel to their conclusion. DATA SOURCES: An evidence report was commissioned by the Agency for Healthcare Research and Quality. It included English-language publications in MEDLINE and the Cochrane Database of Systematic Reviews from 1984 through October 27, 2009. Expert presentations and public discussions were considered. STUDY SELECTION: Study inclusion criteria for the evidence report were participants aged 50 years and older from general populations in developed countries; minimum sample sizes of 300 for cohort studies and 50 for randomized controlled trials; at least 2 years between exposure and outcome assessment; and use of well-accepted diagnostic criteria for AD. DATA EXTRACTION: Included studies were evaluated for eligibility and data were abstracted. Quality of overall evidence for each factor was summarized as low, moderate, or high. DATA SYNTHESIS: Diabetes mellitus, hyperlipidemia in midlife, and current tobacco use were associated with increased risk of AD, and Mediterranean-type diet, folic acid intake, low or moderate alcohol intake, cognitive activities, and physical activity were associated with decreased risk. The quality of evidence was low for all of these associations. CONCLUSION: Currently, insufficient evidence exists to draw firm conclusions on the association of any modifiable factors with risk of AD.",
"title": "Risk factors and preventive interventions for Alzheimer disease: state of the science."
},
{
"docid": "MED-3660",
"text": "Lavender essential oil has been used as an anxiolytic drug, a mood stabilizer, a sedative, spasmolytic, antihypertensive, antimicrobial, analgesic agent as well as a wound healing accelerator. We have studied for the first time the efficacy of lavender essential oil inhalation for the treatment of migraine in a placebo-controlled clinical trial. METHODS: Forty-seven patients with definite diagnosis of migraine headache were divided into cases and controls. Cases inhaled lavender essential oil for 15 min, whereas the control group used liquid paraffin for the same time period. Patients were asked to record their headache severity and associated symptoms in 30-min intervals for a total of 2 h. We matched the two groups for key confounding factors. RESULTS: The mean reduction of headache severity in cases was 3.6 ± 2.8 based on Visual Analogue Scale score. The reduction was 1.6 ± 1.6 in controls. This difference between the controls and cases was statistically significant with p < 0.0001. From 129 headache attacks in cases, 92 responded entirely or partially to lavender. In the control group, 32 out of 68 recorded headache attacks responded to placebo. The percentage of responders was significantly higher in the lavender group than the placebo group (p = 0.001). CONCLUSION: The present study suggests that inhalation of lavender essential oil may be an effective and safe treatment modality in acute management of migraine headaches. Copyright © 2012 S. Karger AG, Basel.",
"title": "Lavender essential oil in the treatment of migraine headache: a placebo-controlled clinical trial."
},
{
"docid": "MED-4188",
"text": "Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.",
"title": "Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot tr..."
},
{
"docid": "MED-1502",
"text": "Animal work over the last three decades has generated a convincing body of evidence that a Western diet - one high in saturated fat and refined carbohydrates (HFS diet) - can damage various brain systems. In this review we examine whether there is evidence for this in humans, using converging lines of evidence from neuropsychological, epidemiological and neuroimaging data. Using the animal research as the organizing principal, we examined evidence for dietary induced impairments in frontal, limbic and hippocampal systems, and with their associated functions in learning, memory, cognition and hedonics. Evidence for the role of HFS diet in attention deficit disorder and in neurodegenerative conditions was also examined. While human research data is still at an early stage, there is evidence of an association between HFS diet and impaired cognitive function. Based upon the animal data, and a growing understanding of how HFS diets can disrupt brain function, we further suggest that there is a causal link running from HFS diet to impaired brain function in humans, and that HFS diets also contribute to the development of neurodegenerative conditions. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.",
"title": "The longer-term impacts of Western diet on human cognition and the brain."
},
{
"docid": "MED-4193",
"text": "OBJECTIVE: The aim of this double-blind and placebo-controlled trial was to investigate whether saffron (stigma of Crocus sativus L.) could relieve symptoms of premenstrual syndrome (PMS). DESIGN: Double-blind, randomised and placebo-controlled trial. SETTING: Departments of Gynaecology/Obstetrics and Psychiatry, Tehran and Zanjan University of Medical Sciences. POPULATION: Women aged 20-45 years with regular menstrual cycles and experience of PMS symptoms for at least 6 months were eligible for the study. METHOD: Women were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice a day; morning and evening) (group A) or capsule placebo (twice a day) for a two menstrual cycles (cycles 3 and 4). MAIN OUTCOME MEASURES: The primary outcome measure was the Daily Symptom Report, and secondary outcome measure was the Hamilton Depression Rating Scale. RESULTS: In this trial, saffron was found to be effective in relieving symptoms of PMS. A significant difference was observed in efficacy of saffron in cycles 3 and 4 in the Total Premenstrual Daily Symptoms and Hamilton Depression Rating Scale. CONCLUSION: The results of this study indicate the efficacy of C. sativus L. in the treatment of PMS. However, a tolerable adverse effects profile of saffron may well confirm the application of saffron as an alternative treatment for PMS. These results deserved further investigations.",
"title": "Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial."
},
{
"docid": "MED-3665",
"text": "There is widespread belief that the use of aromatherapy and massage in an intensive care environment offers a means of increasing the quality of sensory input that patients receive, as well as reducing levels of stress and anxiety. Despite a wealth of anecdotal evidence in support of these claims, there have been few objective studies to evaluate the effects of these therapies. In this experimental study 122 patients admitted to a general intensive care unit were randomly allocated to receive either massage, aromatherapy using essential oil of lavender, or a period of rest. Both pre- and post-therapy assessments included physiological stress indicators and patients' evaluation of their anxiety levels, mood and ability to cope with their intensive care experience. Ninety-three patients (77%) were able to complete subjective assessments. There were no statistically significant differences in the physiological stress indicators or observed or reported behaviour of patients' ability to cope following any of the three interventions. However, those patients who received aromatherapy reported significantly greater improvement in their mood and perceived levels of anxiety. They also felt less anxious and more positive immediately following the therapy, although this effect was not sustained or cumulative.",
"title": "Sensing an improvement: an experimental study to evaluate the use of aromatherapy, massage and periods of rest in an intensive care unit."
}
] |
[
{
"docid": "MED-938",
"text": "Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.",
"title": "Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines."
},
{
"docid": "MED-940",
"text": "Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.",
"title": "An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for t..."
},
{
"docid": "MED-937",
"text": "Male factor infertility is a multifactorial disorder that affects a significant percentage of infertile couples; however, many of them remained untreated. In recent years, considerable numbers of infertile men have sought 'herbal remedies' as an effective treatment. Among 'herbal remedies', saffron is recommended for male infertility in our community. The effect of saffron was evaluated compared with placebo for the treatment of idiopathic male factor infertility. The study included 260 infertile men with idiopathic oligoasthenoteratozoospermia (OAT) who were randomized to saffron 60 mg/day (130, group 1) or a similar regimen of placebo (130, group 2) for 26 weeks. The two groups were compared for changes in semen parameters and total seminal plasma antioxidant capacity. Saffron administration did not result in beneficial effects. At the end of the study no statistically significant improvements were observed in either group in any of the studied semen parameters (sperm density, morphology and motility) (all p = 0.1). At the end of the trial, patients in group 1 had a mean motility of 25.7 ± 2.4%, which was not statistically different from the mean of 24.9 ± 2.8% in the placebo group (p = 0.1). Normal sperm morphology was 18.7 ± 4.7% and 18.4 ± 4.3%, in groups 1 and 2, respectively (p = 0.1). Patients treated with saffron and placebo had a mean sperm density of 20.5 ± 4.6% and 21.4 ± 4.6% per mL, respectively (p = 0.1). Saffron administration did not improve total seminal plasma antioxidant capacity, compared with baseline (p = 0.1) and placebo subjects (p = 0.1). Based on Pearson correlations, each semen parameter did not correlate significantly with treatment duration, including sperm density (r = 0.146, p = 0.13), percent of motile sperm (r = 0.145, p = 0.15) and percent of sperm with normal morphology (r = 0.125, p = 0.30). Saffron does not statistically significantly improve semen parameters in infertile men with idiopathic OAT. If medical professionals want to prescribe herbal remedies for male infertility, previous rigorous scientific investigations, documenting their safety and efficacy are required. Copyright © 2010 John Wiley & Sons, Ltd.",
"title": "A prospective double-blind randomized placebo-controlled study of the effect of saffron (Crocus sativus Linn.) on semen parameters and seminal plas..."
},
{
"docid": "MED-939",
"text": "Snacking is an uncontrolled eating behavior, predisposing weight gain and obesity. It primarily affects the female population and is frequently associated with stress. We hypothesized that oral supplementation with Satiereal (Inoreal Ltd, Plerin, France), a novel extract of saffron stigma, may reduce snacking and enhance satiety through its suggested mood-improving effect, and thus contribute to weight loss. Healthy, mildly overweight women (N = 60) participated in this randomized, placebo-controlled, double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period. Snacking frequency, the main secondary variable, was assessed by daily self-recording of episodes by the subjects in a nutrition diary. Twice a day, enrolled subjects consumed 1 capsule of Satiereal (176.5 mg extract per day (n = 31) or a matching placebo (n = 29). Caloric intake was left unrestricted during the study. At baseline, both groups were homogeneous for age, body weight, and snacking frequency. Satiereal caused a significantly greater body weight reduction than placebo after 8 weeks (P < .01). The mean snacking frequency was significantly decreased in the Satiereal group as compared with the placebo group (P < .05). Other anthropometric dimensions and vital signs remained almost unchanged in both groups. No subject withdrawal attributable to a product effect was reported throughout the trial, suggesting a good tolerability to Satiereal. Our results indicate that Satiereal consumption produces a reduction of snacking and creates a satiating effect that could contribute to body weight loss. The combination of an adequate diet with Satiereal supplementation might help subjects engaged in a weight loss program in achieving their objective. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, health..."
},
{
"docid": "MED-1602",
"text": "Background: Nitrate and nitrite are present in many foods and are precursors of N-nitroso compounds, known animal carcinogens and potential human carcinogens. We prospectively investigated the association between nitrate and nitrite intake from dietary sources and risk of renal cell carcinoma (RCC) overall and clear cell and papillary histological subtypes in the NIH-AARP Diet and Health Study. Methods: Nitrate and nitrite intakes were estimated from a 124-item food frequency questionnaire. Over a mean follow-up of 9 years, we identified 1816 RCC cases (n=498, clear cell; n=115, papillary cell) among 491 841 participants. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Individuals in the highest quintile of nitrite intake from animal sources compared with those in the lowest quintile, had an increased risk of total RCC and clear cell subtype (HR=1.28, 95% CI, 1.10–1.49 and HR=1.68, 95% CI, 1.25–2.27, respectively). Nitrite from processed meats and other animal sources were associated with increased clear cell adenocarcinoma risk (HR=1.33, 95% CI, 1.01–1.76 and HR=1.78, 95% CI, 1.34–2.36, respectively). We found no association for nitrite intake from plant sources or nitrate intake overall. Conclusion: Our findings suggest that nitrite from animal sources may increase the risk of RCC, particularly clear cell adenocarcinomas.",
"title": "Dietary intake of nitrate and nitrite and risk of renal cell carcinoma in the NIH-AARP Diet and Health Study"
},
{
"docid": "MED-2763",
"text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.",
"title": "Facing the facelessness of public health: what's the public got to do with it?"
},
{
"docid": "MED-3512",
"text": "BACKGROUND: Abdominal pain, that characterizes irritable bowel syndrome (IBS) together with bloating and disordered defecation, is mainly related to a visceral hypersensitivity due to an increase of TRPV(1) nociceptive nerve fiber activity. AIM: As capsaicin contained in red pepper is able to desensitize the TRPV(1) fibres, we evaluated whether the red pepper oral administration can decrease the symptoms of visceral hypersensitivity in IBS patients. METHODS: The study was performed on 50 patients with IBS diagnosed following Rome II criteria. After a 2-week washout period, 23 patients were planned to receive 4 pills/day, for 6 weeks randomly and in a double blind manner, each containing 150 mg of red pepper powder with a coat that dissolves in the colon, and 27 patients placebo. The patients scored each day in a diary the abdominal pain and bloating intensities following the 5-point Likert scale. The weekly symptom mean scores and the final patient subjective evaluation on treatment effectiveness were statistically compared among groups and intra-groups with appropriate tests. RESULTS: Eight patients dropped from the study: 6 in the red pepper group for abdominal pain and 2 in the placebo group. In 8 patients, the pills were reduced to 2/day, because of the abdominal pain at the onset of treatment. The intra-group comparisons showed that in patients taking red pepper the abdominal pain and bloating mean score values of the last weeks of treatment were significantly improved with respect to pre-treatment values, unlike patients taking placebo. The final patient subjective evaluation on the treatment effectiveness showed that red pepper group scored significantly better than placebo. CONCLUSIONS: The results of this preliminary study indicate that the chronic administration of red pepper powder in IBS patients with enteric-coated pills was significantly more effective than placebo in decreasing the intensity of abdominal pain and bloating and was considered by the patients more effective than placebo.",
"title": "Effect of red pepper on symptoms of irritable bowel syndrome: preliminary study."
},
{
"docid": "MED-4903",
"text": "The antioxidant properties of dietary phenolics are believed to be reduced in vivo because of their affinity for proteins. In this study we assessed the bioavailability of phenolics and the in vivo plasma antioxidant capacity after the consumption of blueberries (Vaccinium corymbosum L.) with and without milk. In a crossover design, 11 healthy human volunteers consumed either (a) 200 g of blueberries plus 200 ml of water or (b) 200 g of blueberries plus 200 ml of whole milk. Venous samples were collected at baseline and at 1, 2, and 5 h postconsumption. Ingestion of blueberries increased plasma levels of reducing and chain-breaking potential (+6.1%, p<0.001; +11.1%, p<0.05) and enhanced plasma concentrations of caffeic and ferulic acid. When blueberries and milk were ingested there was no increase in plasma antioxidant capacity. There was a reduction in the peak plasma concentrations of caffeic and ferulic acid (-49.7%, p<0.001, and -19.8%, p<0.05, respectively) as well as the overall absorption (AUC) of caffeic acid (p<0.001). The ingestion of blueberries in association with milk, thus, impairs the in vivo antioxidant properties of blueberries and reduces the absorption of caffeic acid.",
"title": "Antioxidant activity of blueberry fruit is impaired by association with milk."
},
{
"docid": "MED-2844",
"text": "OBJECTIVE It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic β-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM. RESEARCH DESIGN AND METHODS A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors. RESULTS Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87–1.43), 1.31 (1.03–1.68), 1.51 (1.17–1.93), and 1.58 (1.21–2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10–1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk. CONCLUSIONS These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.",
"title": "A Prospective Study of Prepregnancy Dietary Iron Intake and Risk for Gestational Diabetes Mellitus"
},
{
"docid": "MED-1442",
"text": "We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h2 from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype–phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.",
"title": "Genetic Analysis of Chemosensory Traits in Human Twins"
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-1736",
"text": "Glyphosate is a herbicide widely used to kill weeds both in agricultural and non-agricultural landscapes. Its reproductive toxicity is related to the inhibition of a StAR protein and an aromatase enzyme, which causes an in vitro reduction in testosterone and estradiol synthesis. Studies in vivo about this herbicide effects in prepubertal Wistar rats reproductive development were not performed at this moment. Evaluations included the progression of puberty, body development, the hormonal production of testosterone, estradiol and corticosterone, and the morphology of the testis. Results showed that the herbicide (1) significantly changed the progression of puberty in a dose-dependent manner; (2) reduced the testosterone production, in semineferous tubules' morphology, decreased significantly the epithelium height (P < 0.001; control = 85.8 +/- 2.8 microm; 5 mg/kg = 71.9 +/- 5.3 microm; 50 mg/kg = 69.1 +/- 1.7 microm; 250 mg/kg = 65.2 +/- 1.3 microm) and increased the luminal diameter (P < 0.01; control = 94.0 +/- 5.7 microm; 5 mg/kg = 116.6 +/- 6.6 microm; 50 mg/kg = 114.3 +/- 3.1 microm; 250 mg/kg = 130.3 +/- 4.8 microm); (4) no difference in tubular diameter was observed; and (5) relative to the controls, no differences in serum corticosterone or estradiol levels were detected, but the concentrations of testosterone serum were lower in all treated groups (P < 0.001; control = 154.5 +/- 12.9 ng/dL; 5 mg/kg = 108.6 +/- 19.6 ng/dL; 50 mg/dL = 84.5 +/- 12.2 ng/dL; 250 mg/kg = 76.9 +/- 14.2 ng/dL). These results suggest that commercial formulation of glyphosate is a potent endocrine disruptor in vivo, causing disturbances in the reproductive development of rats when the exposure was performed during the puberty period.",
"title": "Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology."
},
{
"docid": "MED-3960",
"text": "Dietary microparticles are non-biological bacterial-sized particles of the gastrointestinal lumen that occur due to endogenous formation (calcium phosphate) or following oral exposure (exogenous microparticle). In the UK, about 40 mg (1012) of exogenous microparticles are ingested per person per day, through exposure to food additives, pharmaceutical/supplement excipients or toothpaste constituents. Once ingested, exogenous microparticles are unlikely to pass through the gastrointestinal tract without adsorbing to their surfaces some ions and molecules of the intestinal lumen. Both entropy and ionic attraction drive such interactions. Calcium ions are especially well adsorbed by dietary microparticles which then provide a positively charged surface for the attraction (adsorption) of other organic molecules such as lipopolysaccharides, peptidoglycans or protein antigen from the diet or commensal flora. The major (but not only) sites of microparticle entry into intestinal tissue are the M-cell rich lymphoid aggregates (termed Peyer’s patches in the small bowel). Indeed, it is well established that this is an efficient transport route for non-biological microparticles although it is unclear why. We hypothesise that this pathway exists for “endogenous microparticles” of calcium phosphate, with immunological and physiological benefit, and that “exogenous dietary microparticles”, such as titanium dioxide and the silicates, hijack this route. This overview focuses on what is known of these microparticles and outlines their potential role in immune tolerance of the gut (endogenous microparticles) or immune activation (exogenous microparticles) and inflammation of the gut.",
"title": "Dietary microparticles and their impact on tolerance and immune responsiveness of the gastrointestinal tract"
},
{
"docid": "MED-3973",
"text": "Background Fever is one of the most common symptoms among children and is usually caused by respiratory infections. Although Japanese health authorities have long recommended gargling to prevent respiratory infections, its effectiveness among children is not clear. Methods The children in this observational study were enrolled from 145 nursery schools in Fukuoka City, Japan. Children in the exposure group were instructed to gargle at least once a day. The endpoints of this study were incidence of fever during the daytime and incidence of sickness absence. Differences among gargling agents for each endpoint were also analyzed. Results A total of 19 595 children aged 2 to 6 years were observed for 20 days (391 900 person-days). In multivariate logistic regression, the overall odds ratio (OR) for fever onset in the gargling group was significantly lower (OR = 0.68). In age-stratified analysis, ORs were significantly lower at age 2 (OR = 0.67), 4 (OR = 0.46), and 5 (OR = 0.41) years. Regarding sickness absence, the overall OR was 0.92 (not significant) in the gargling group. In age-stratified analysis, ORs were significantly lower at age 4 (OR = 0.68), 5 (OR = 0.59), and 6 (OR = 0.63) years. In subgroup analysis, significantly lower ORs for fever onset were observed for children who gargled with green tea (OR = 0.32), functional water (OR = 0.46), or tap water (OR = 0.70). However, the ORs were not significant for sickness absence. Conclusions Gargling might be effective in preventing febrile diseases in children.",
"title": "Gargling for Oral Hygiene and the Development of Fever in Childhood: A Population Study in Japan"
},
{
"docid": "MED-2665",
"text": "Objective Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women. Methods Beginning in 1980, a semi-quantitative food frequency questionnaire was administered every four years to Nurses’ Health Study participants. In 1995–2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at two-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariable-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes. Results Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (e.g., for a global score averaging all six cognitive tests, for blueberries: p-trend=0.014 and mean difference=0.04 [95% CI=0.01, 0.07] comparing extreme categories of intake; for strawberries: p-trend= 0.022 and mean difference=0.03 [95% CI=0.00, 0.06] comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we find for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends= 0.015 and 0.053, respectively, for the global score). Interpretation Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.",
"title": "Dietary intake of berries and flavonoids in relation to cognitive decline"
},
{
"docid": "MED-1596",
"text": "Recent observed feminization of aquatic animals has raised concerns about estrogenic compounds in water supplies and the potential for these chemicals to reach drinking water. Public perception frequently attributes this feminization to oral contraceptives (OCs) in wastewater and raises concerns that exposure to OCs in drinking water may contribute to the recent rise in human reproductive problems. This paper reviews the literature regarding various sources of estrogens, in surface, source and drinking water, with an emphasis on the active molecule that comes from OCs. It includes discussion of the various agricultural, industrial, and municipal sources and outlines the contributions of estrogenic chemicals to the estrogenicity of waterways and estimates that the risk of exposure to synthetic estrogens in drinking water on human health is negligible. This paper also provides recommendations for strategies to better understand all the potential sources of estrogenic compounds in the environment and possibilities to reduce the levels of estrogenic chemicals in the water supply.",
"title": "Are oral contraceptives a significant contributor to the estrogenicity of drinking water?"
},
{
"docid": "MED-2033",
"text": "BACKGROUND: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this \"new\" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS: We reviewed the international literature through PubMed and Medline, using the search terms \"wheat (hyper)sensitivity,\" \"wheat allergy,\" \"wheat intolerance,\" \"gluten (hyper)sensitivity,\" and \"gluten intolerance,\" and we discuss current knowledge about NCGS. RESULTS: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.",
"title": "Non-celiac gluten sensitivity: literature review."
},
{
"docid": "MED-2928",
"text": "Natural killer (NK) cells were discovered more than 30 years ago. NK cells are large granular lymphocytes that belong to the innate immune system because unlike T or B lymphocytes of the adaptive or antigen-specific immune system, NK cells do not rearrange T-cell receptor or immunoglobulin genes from their germline configuration. During the past 2 decades there has been a substantial gain in our understanding of what and how NK-cells “see,” lending important insights into their functions and purpose in normal immune surveillance. The most recent discoveries in NK-cell receptor biology have fueled translational research that has led to remarkable results in treating human malignancy.",
"title": "ASH 50th Anniversary Review: Human natural killer cells"
},
{
"docid": "MED-2715",
"text": "OBJECTIVE: Obesity results from protracted energy imbalance. Whether this comprises excessive energy intake, lowered physical activity or both, remains disputed. DESIGN: Physical activity energy expenditure, evaluated in three different ways from daily energy expenditure (DEE) measured using doubly labelled water, was examined for trends over time. Data included subjects in Europe (Maastricht, the Netherlands) and North America extending back to the 1980s. These data were compared with measures from the third world, and measures made on wild terrestrial mammals. RESULTS: Physical activity expenditure in Europe (residual of the regression of DEE on basal energy expenditure (BEE)) has slightly but significantly increased since the 1980s. There was no trend over time in physical activity level (PAL=DEE/BEE), or in the residual variance in DEE once mass, sex and age were accounted for. This latter index of physical activity expenditure also significantly increased over time in North America. DEE of individuals in Europe and North America was not significantly different from individuals measured in the third world. In wild terrestrial mammals, DEE mostly depended on body mass and ambient temperature. Predicted DEE for a 78 kg mammal living at 20 degrees C was 9.2 MJ per day (95% CI: 7.9-12.9 MJ per day), not significantly different from the measured DEE of modern humans (around 10.2-12.6 MJ per day). CONCLUSION: As physical activity expenditure has not declined over the same period that obesity rates have increased dramatically, and daily energy expenditure of modern man is in line with energy expenditure in wild mammals, it is unlikely that decreased expenditure has fuelled the obesity epidemic.",
"title": "Physical activity energy expenditure has not declined since the 1980s and matches energy expenditures of wild mammals."
},
{
"docid": "MED-1790",
"text": "The Healthy Hunger-Free Kids Act of 2010 presents an opportunity to change the nutritional quality of foods served in low-income childcare centers, including Head Start centers. Excessive fruit juice consumption is associated with increased risk for obesity. Moreover, there is recent scientific evidence that sucrose consumption without the corresponding fiber, as is commonly present in fruit juice, is associated with the metabolic syndrome, liver injury, and obesity. Given the increasing risk of obesity among preschool children, we recommend that the US Department of Agriculture’s Child and Adult Food Care Program, which manages the meal patterns in childcare centers such as Head Start, promote the elimination of fruit juice in favor of whole fruit for children.",
"title": "Reducing Childhood Obesity by Eliminating 100% Fruit Juice"
},
{
"docid": "MED-724",
"text": "In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.",
"title": "Flatulence--causes, relation to diet and remedies."
},
{
"docid": "MED-5350",
"text": "The short-term effects of rye bran bread intake in prostate cancer were investigated. Ten men with conservatively treated prostate cancer were randomised to a daily supplement of 295 g of rye bran bread and eight men to 275 g of wheat bread (control) with similar fibre content for three weeks. Blood samples, ultrasound-guided core biopsies of the prostate, and urine samples were taken. In the rye group, there was a significant increase in plasma enterolactone, and the apoptotic index increased significantly from 2.1% (SD 1.3) to 5.9% (SD 1.8), P<0.005 as measured by a TUNEL index in four cases in the rye group and seven cases in the control group. Besides a significant decrease in weight in both groups, only small changes were observed in plasma concentrations of prostate specific antigen (PSA), circulating sex hormones, excreted oestrogens, insulin-like growth factor (IGF)-I, and in the endothelial fibrinolytical system. High intake of rye bran bread is suggested to increase apoptosis in prostate tumours.",
"title": "Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer."
},
{
"docid": "MED-4622",
"text": "We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment.",
"title": "A probabilistic characterization of the health benefits of reducing methyl mercury intake in the United States."
},
{
"docid": "MED-3876",
"text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.",
"title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom."
},
{
"docid": "MED-3438",
"text": "Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection satisfactory for sexual performance. Evidence is accumulating to consider ED as a vascular disorder. Common risk factors for atherosclerosis are frequently found in association with ED, and ED is frequently reported in vascular syndromes, such as coronary artery disease (CAD), hypertension, cerebrovascular disease, peripheral arterial disease, and diabetes mellitus. Finally, similar early impairment of endothelium-dependent vasodilatation and late obstructive vascular changes has been reported in both ED and other vascular syndromes. Recently, we proposed a pathophysiologic mechanism to explain the link between ED and CAD called the artery size hypothesis. Given the systemic nature of atherosclerosis, all major vascular beds should be affected to the same extent. However, symptoms rarely become evident at the same time. This difference in rate of occurrence of different symptoms is proposed to be caused by the different size of the arteries supplying different vascular beds that allow a larger vessel to better tolerate the same amount of plaque compared with a smaller one. According to this hypothesis, because penile arteries are smaller in diameter than coronary arteries, patients with ED will seldom have concomitant symptoms of CAD, whereas patients with CAD will frequently complain of ED. Available clinical evidence appears to support this hypothesis.",
"title": "The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease."
},
{
"docid": "MED-2361",
"text": "The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.",
"title": "Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York."
},
{
"docid": "MED-1682",
"text": "Background The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products. Methods We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair. Results Plasma vitamin C increased after supplementation as did resistance towards H2O2-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation. Conclusion Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.",
"title": "Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection"
},
{
"docid": "MED-1182",
"text": "Background Sale of organic foods is one of the fastest growing market segments within the global food industry. People often buy organic food because they believe organic farms produce more nutritious and better tasting food from healthier soils. Here we tested if there are significant differences in fruit and soil quality from 13 pairs of commercial organic and conventional strawberry agroecosystems in California. Methodology/Principal Findings At multiple sampling times for two years, we evaluated three varieties of strawberries for mineral elements, shelf life, phytochemical composition, and organoleptic properties. We also analyzed traditional soil properties and soil DNA using microarray technology. We found that the organic farms had strawberries with longer shelf life, greater dry matter, and higher antioxidant activity and concentrations of ascorbic acid and phenolic compounds, but lower concentrations of phosphorus and potassium. In one variety, sensory panels judged organic strawberries to be sweeter and have better flavor, overall acceptance, and appearance than their conventional counterparts. We also found the organically farmed soils to have more total carbon and nitrogen, greater microbial biomass and activity, and higher concentrations of micronutrients. Organically farmed soils also exhibited greater numbers of endemic genes and greater functional gene abundance and diversity for several biogeochemical processes, such as nitrogen fixation and pesticide degradation. Conclusions/Significance Our findings show that the organic strawberry farms produced higher quality fruit and that their higher quality soils may have greater microbial functional capability and resilience to stress. These findings justify additional investigations aimed at detecting and quantifying such effects and their interactions.",
"title": "Fruit and Soil Quality of Organic and Conventional Strawberry Agroecosystems"
},
{
"docid": "MED-1574",
"text": "Crohn's disease (CD) is associated with intestinal dysbiosis evidenced by an altered microbiome forming thick biofilms on the epithelium. Additionally, adherent-invasive E. coli (AIEC) strains are frequently isolated from ileal lesions of CD patients indicating a potential role for these strains in disease pathogenesis. The composition and characteristics of the host microbiome are influenced by environmental factors, particularly diet. Polysaccharides added to food as emulsifiers, stabilizers or bulking agents have been linked to bacteria-associated intestinal disorders. The escalating consumption of polysaccharides in Western diets parallels an increased incidence of CD during the latter 20th century. In this study, the effect of a polysaccharide panel on adhesiveness of the CD-associated AIEC strain LF82 was analyzed to determine if these food additives promote disease-associated bacterial phenotypes. Maltodextrin (MDX), a polysaccharide derived from starch hydrolysis, markedly enhanced LF82 specific biofilm formation. Biofilm formation of multiple other E. coli strains was also promoted by MDX. MDX-induced E. coli biofilm formation was independent of polysaccharide chain length indicating a requirement for MDX metabolism. MDX exposure induced type I pili expression, which was required for MDX-enhanced biofilm formation. MDX also increased bacterial adhesion to human intestinal epithelial cell monolayers in a mechanism dependent on type 1 pili and independent of the cellular receptor CEACAM6, suggesting a novel mechanism of epithelial cell adhesion. Analysis of mucosa-associated bacteria from individuals with and without CD showed increased prevalence of malX, a gene essential for MDX metabolism, uniquely in the ileum of CD patients. These findings demonstrate that the ubiquitous dietary component MDX enhances E. coli adhesion and suggests a mechanism by which Western diets rich in specific polysaccharides may promote dysbiosis of gut microbes and contribute to disease susceptibility.",
"title": "Crohn's Disease-Associated Adherent-Invasive Escherichia coli Adhesion Is Enhanced by Exposure to the Ubiquitous Dietary Polysaccharide Maltodextrin"
},
{
"docid": "MED-1670",
"text": "The effect of polyphenols, phenolic acids and tannins (PPTs) from strawberry and apple on uptake and apical to basolateral transport of glucose was investigated using Caco-2 intestinal cell monolayers. Substantial inhibition on both uptake and transport was observed by extracts from both strawberry and apple. Using sodium-containing (glucose transporters SGLT1 and GLUT2 both active) and sodium-free (only GLUT2 active) conditions, we show that the inhibition of GLUT2 was greater than that of SGLT1. The extracts were analyzed and some of the constituent PPTs were also tested. Quercetin-3-O-rhamnoside (IC₅₀ =31 μM), phloridzin (IC₅₀=146 μM), and 5-caffeoylquinic acid (IC₅₀=2570 μM) contributed 26, 52 and 12%, respectively, to the inhibitory activity of the apple extract, whereas pelargonidin-3-O-glucoside (IC₅₀=802 μM) contributed 26% to the total inhibition by the strawberry extract. For the strawberry extract, the inhibition of transport was non-competitive based on kinetic analysis, whereas the inhibition of cellular uptake was a mixed-type inhibition, with changes in both V(max) and apparent K(m) . The results in this assay show that some PPTs inhibit glucose transport from the intestinal lumen into cells and also the GLUT2-facilitated exit on the basolateral side. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Polyphenols and phenolic acids from strawberry and apple decrease glucose uptake and transport by human intestinal Caco-2 cells."
}
] |
1312
|
Is being a landlord a good idea? Is there a lot of risk?
|
[
{
"docid": "167896",
"text": "If you are able to buy a 150K home for 50K now that would be a good deal! However, you can't you have to borrow 100K in order to make this deal happen. This dramatically increases the risk of any investment, and I would no longer classify it as passive income. The mortgage on a 150K place would be about 710/month (30 year fixed). Reasonably I would expect no more than 1200/month in rent, or 14,400. A good rule of thumb is to assume that half of rental revenue can be counted as profit before debt service. So in your case 7200, but you would have a mortgage payment of 473/month. Leaving you a profit of 1524 after debt service. This is suspiciously like 2K per year. Things, in the financial world, tend to move toward an equilibrium. The benefit of rental property you can make a lot more than the numbers suggest. For example the home could increase in value, and you can have fewer than expected repairs. So you have two ways to profit: rental revenue and asset appreciation. However, you said that you needed passive income. What happens if you have a vacancy or the tenant does not pay? What happens if you have greater than expected repairs? What happens if you get a fine from the HOA or a special assessment? Not only will you have dip into your pocket to cover the payment, you might also have to dip into your pocket to cover the actual event! In a way this would be no different than if you borrowed 100K to buy dividend paying stocks. If the fund/company does not pay out that month you would still have to make the loan payment. Where does the money come from? Your pocket. At least dividend paying companies don't collect money from their shareholders. Yes you can make more money, but you can also lose more. Leverage is a two edged sword and rental properties can be great if you are financial able to absorb the shocks that are normal with ownership.",
"title": ""
},
{
"docid": "503742",
"text": "\"I have been a landlord in Texas for just over 3 years now. I still feel like a novice, but I will give you the benefit of my experience. If you are relying on rental properties for current income versus a long term return you are going to have to do a good job at shopping for bargains to get monthly cash flow versus equity growth that is locked up in the property until you sell it. If you want to pull a lot of cash out of a property on a regular basis you probably are going to have to get into flipping them, which is decidedly not passive investing. Also, it is easy to underestimate the expenses associated with rental properties. Texas is pretty landlord friendly legally, however it does have higher than usual property taxes, which will eat into your return. Also, you need to factor in maintenance, vacancy, tenant turnover costs, etc. It can add up to a lot more than you would expect. If you are handy and can do a lot of repairs yourself you can increase your return, but that makes it less of a passive investment. The two most common rules I have heard for initially evaluating whether an investment property is likely to be cash flow positive are the 1% and 50% rules. The 1% rule says the expected monthly rent needs to be 1% or greater of the purchase price of the house. So your hypothetical $150K/$10K scenario doesn't pass that test. Some people say this rule is 2% for new landlords, but in my experience you'd have to get lucky in Texas to find a house priced that competitively that didn't need a lot of work to get rents that high. The 50% rule says that the rent needs to be double your mortgage payment to account for expenses. You also have to factor in the hassle of dealing with tenants, the following are not going to happen when you own a mutual fund, but are almost inevitable if you are a landlord long enough: For whatever reason you have to go to court and evict a tenant. A tenant that probably lost their job, or had major medical issues. The nicest tenant you ever met with the cutest kids in the world that you are threatening to make homeless. Every fiber of your being wants to cut them some slack, but you have a mortgage to pay and can't set an expectation that paying the rent on time is a suggestion not a rule. or the tenant, who seemed nice at first, but now considers you \"\"the man\"\" decides to fight the eviction and won't move out. You have to go through a court process, then eventually get the Sheriff to come out and forcibly remove them from the property, which they are treating like crap because they are mad at you. All the while not paying rent or letting you re-let the place. The tenant isn't maintaining the lawn and the HOA is getting on your butt about it. Do you pay someone to mow the grass for them and then try to squeeze the money out of the tenant who \"\"never agreed to pay for that\"\"? You rent to a college kid who has never lived on their own and has adopted you as their new parent figure. \"\"The light in the closet went out, can you come replace the bulb?\"\" Tenants flat out lying to your face. \"\"Of course I don't have any pets that I didn't pay the deposit for!\"\" (Pics all over facebook of their kids playing with a dog in the \"\"pet-free\"\" house)\"",
"title": ""
},
{
"docid": "560195",
"text": "\"Risk is the capital you have staked in pursuit of profit. The danger is that you lose what you have risked. For some bets (risks), you can get insurance to cover for losses. Now the \"\"game\"\" of Landlord and Tenant requires you to play fully by the rules set forth by your legislators. In your case, that is the legislators of the State of Texas. Without knowing those rules, you could be liable (open to civil prosecution) for violating those rules. Tenants could be savvy to those rules or savvy enough to hire someone, a lawyer, who knows those rules. As well, in the game of Landlord and Tenant, you must ascertain the creditworthiness of your would-be tenant. If the tenant fails to pay rent, that tenant can detain the residence. You will incur additional outlays to gain possession of your property (ownership in your rental). Now the game of Landlord vs Landlord is different. You can't pick up houses easily enough and even if you could, likely the expense of doing so could wipe out any would profits from having the house as a rental. So, in Landlord vs Landlord, you get constrained by where your rental sits. Thus you must forecast what will the neighborhood look like in five, ten, fifteen years.\"",
"title": ""
},
{
"docid": "383921",
"text": "Based on what you've said I think buying a rental is risky for you. It looks like you heard that renting a house is profitable and Zillow supported that idea. Vague advice + a website designed for selling + large amounts of money = risky at the very least. That doesn't mean that rental property is super risky it just means that you haven't invested any time into learning the risks and how you can manage them. Once you learn that your risk reduces dramatically. In general though I feel that rental property has a good risk/reward ratio. If you're willing to put in the time and energy to learn the business then I'd encourage you to buy property. If you're not willing to do that then rentals will always be a crap shoot. One thing about investing in rental property is you have the ability to have more impact on your investment than you do dropping money in the stock market which is good and bad.",
"title": ""
},
{
"docid": "422331",
"text": "Buying a property and renting it out can be a good investment if it matches your long term goals. Buying an investment property is a long term investment. A large chunk of your money will be tied up with the property and difficult to access. If you put your money into dividend producing stocks you can always sell the stock and have your money back in a matter of days this is not so with a property. (But you can always do a Home equity line of credit (HELOC)) I would also like to point out landlording is not a passive endeavor as JohnFx stated dealing with a tenant can be a lot of work. This is not work you necessarily have to deal with, it is possible to contract with a property management company that would place tenants and take care of those late night calls. Property management companies often charge 10% of your monthly rent and will eat a large portion of your profits. It could be worth the time and headache of tenant relations. You should build property management into you expenses anyway in case you decide to go that route in the future. There are good things about owning an investment property. It can produce returns in a couple of ways. If you choose this route it can be lucrative but be sure to do your homework. You must know the area you are investing very well. Know the rent, and vacancy rates for Single family homes, look at multifamily homes as a way of mitigating risk(if one unit is vacant the others are still paying).",
"title": ""
},
{
"docid": "528206",
"text": "\"Rather than thinking of becoming a landlord as a passive \"\"investment\"\" (like a bank account or mutual fund), it may be useful to think of it as \"\"starting a small part-time business\"\". While certainly many people can and do start their own businesses, and there are many success stories, there are many cases where things don't work out quite as they hoped. I wouldn't call starting any new business \"\"low risk\"\", even one that isn't expected to be one's main full-time job, though some may be \"\"acceptable risk\"\" for your particular circumstances. But if you're going to start a part-time business, is there any particular reason you'd do so in real estate as opposed to some other activity? It sounds like you'd be completely new to real estate, so perhaps for your first business you're starting you'd want it to be something you're more familiar with. Or, if you do want to enter the real estate world (or any other new business), be sure to do a lot of research, come up with a business plan, and be prepared for the possibility of losing money as with any investment or new business.\"",
"title": ""
}
] |
[
{
"docid": "42329",
"text": "\"The perceived risk depends on the entire situation, but often it is considered more risk, especially if you want to occupy yourself. Things you need to consider: It can be very difficult to show a property with tenants occupying it. There are many reasons for this and most homes show / sell better empty. I have found many tenants make it difficult on the seller. Leaving their areas a mess, being unaccommodating and especially in markets that are flooded with options, a lot of buyers just won't bother with the difficulty of scheduling a showing in occupied properties. I've tried to purchase many properties where the renter insists on being there during a showing, but won't open the door and there's no recourse for the landlord because his lease or laws in the area don't allow you to enter without permission. Also, it can be difficult to look past a lot of clutter and other people's decorating and aroma \"\"preferences\"\" to be kind. :) Is the property currently under lease and what is the period of that lease? It could be that the lease is month to month, or it could be years remaining on the lease period. It is likely a legal requirement in most areas that you honor the existing lease. I would never buy a property that has multiple years remaining. While some amateur landlords will allow 2 or even 5 year leases, this is a very bad idea for many reasons! What are laws like in your area for evicting tenants? You should know this regardless of whether or not you intend to occupy or keep it a rental. It can be a very difficult process evicting tenants and this process is vastly different from country to country and state to state here in the USA. Look into the security deposit - assuming there is one. How much is the deposit? Will it cover damage that may not exist yet? Don't think that just because you plan on evicting them soon, it isn't important. People can trash a place on the way out and an expensive lawsuit could be your only recourse. It is far easier to take a deposit than sue. I would absolutely demand that the deposit transfer to you upon sale. View the current renters with a fresh eye. Especially if you are considering leave it a rental, look into all of the typical requirements: Their monthly income, their credit history, their criminal record, their payment history, their references. Are they likely to be good or terrible renters? If you're interested in the property, consider an offer which requires the current landlord to evict within the time-frame of the buy/sell agreement. This isn't an uncommon requirement. I think the first thing to do is go look at the property and see if you can determine for yourself why it hasn't sold yet. Properties all have different reasons for not selling in a reasonable time to the local market. Having renters alone in most markets shouldn't be that big of a factor. I would suspect bad smells, nasty renters, or an unfavorable lease agreement exists.\"",
"title": ""
},
{
"docid": "496050",
"text": "\"In financial markets, the gains you can expect to make (whether in the form of dividends or capital gains) correspond to the risks you are bearing. There are a variety of REITs but you can expect to make only as much money in them as you bear risk (meaning you can also lose a lot of money in the ones that earn a lot). In that sense they are just like other financial assets like stocks. If you are generically trying to increase your wealth by bearing risk, you can get a better risk/reward ratio in a fully diversified portfolio including stocks and bonds as well and REITs. \"\"Passive income\"\" means making money by bearing risk. REITs alone, without diversifying into other financial assets, do a poor job of generating income for the amount of risk you bear. So why are REITs not very comparable to buying a house and renting it out? Because in the latter case you are being paid not only for bearing the risk of the house depreciating but also you are being compensated for the work you do as a landlord. Moreover, because the house doesn't trade in a liquid market like REITs do, it is possible to actually get a good deal, as opposed to the fair deal you will get on a REIT. TL;DR: The \"\"passive income\"\" generated by REIT investment is more similar to generic equity/bond investment than it is to an investment in a physical home that you rent out. If what you want is to make money without doing anything besides bear risk, you should invest in a fully diversified portfolio of financial assets (equity and bonds being the primary constituents but REITs potentially being a part as well).\"",
"title": ""
},
{
"docid": "449745",
"text": "Unfortunately, in this market environment your goal is not very realistic. At the moment real interest rates are negative (and have been for some time). This means if you invest in something that will pay out for sure, you can expect to earn less than you lose through inflation. In other words, if you save your $50K, when you withdraw it in a few years you will be able to buy less with it then than you can now. You can invest in risky securities like stocks or mutual funds. These assets can easily generate 10% per year, but they can (and do) also generate negative returns. This means you can and likely will lose money after investing in them. There's an even better chance that you will make money, but that varies year by year. If you invest in something that expects to make 10% per year (meaning it makes that much on average), it will be extremely risky and many years it will lose money, perhaps a lot of it. That's the way risk is. Are you comfortable taking on large amounts of risk (good chances of losing a lot of your money)? You could make some kind of real investment. $50K is a little small to buy real estate, but you may be able to find something like real estate that can generate income, especially if you use it as a down payment to borrow from the bank. There is risk in being a landlord as well, of course, and a lot of work. But real investments like that are a reasonable alternative to financial markets for some people. Another possibility is to just keep it in your bank account or something else with no risk and take $5000 out per year. It will only last you 10 years that way, but if you are not too young, that will be a significant portion of your life. If you are young, you can work and add to it. Unfortunately, financial markets don't magically make people rich. If you make a lot of money in the market, it's because you took a risk and got lucky. If you make a comfortable amount with no risk, it means you invested in a market environment very different from what we see today. --------- EDIT ------------ To get an idea of what risk free investments (after inflation) earn per year at various horizons see this table at the treasury. At the time of this writing you would have to invest in a security with maturity almost 10 years in order to break even with inflation. Beating it by 10% or even 3% per year with minimal risk is a pipe dream.",
"title": ""
},
{
"docid": "487094",
"text": "\"The biggest question is do you want to be a landlord? There are a lot of ups and down to managing property from bad tenants to having to fix a water heater or replace a fridge. If you aren't interested in being a landlord, it is definitely a bad idea. If you do want to be a landlord, then the question is how close do you want to be to your tenants? What if they are up late making noise, etc.? What if they watch TV all night and you hear it through the walls? What is your plan? You ask if people have trouble \"\"sharing\"\" a house. If you are the landlord and the other party the tenant, then you aren't \"\"Sharing\"\", you are leasing. It's a different relationship with different strains.\"",
"title": ""
},
{
"docid": "563959",
"text": "It's doable, but there's a fair amount of risk involved. The biggest issue is that your roommates could move out. It's possible that they could have a falling out, get a job in a different city, or just move on. How difficult would it be to find another roommate? How many roommates can you lose and still afford to pay the mortgage, insurance, taxes, and all the rest of your living expenses? Even if you you retain all of your roommates until the mortgage is paid off, there's still some risk involved. If you were to lose your job, could you continue to make mortgage payments? Worst case scenario is that you could become unemployed for a time while home values in your State/City/neighborhood are crashing. Last, the position on landlord has the potential to be lucrative, but also comes with a fair amount of responsibility. It will be a drain on your time to maintain the house and to make sure you always have tenants. I know you said that your roommates are good about paying on time, but are you willing to evict a friend because they won't/can't pay rent? It's easier to ask the landlord for an extension on rent when you're friends. All that being said, I think that this idea is worth considering. My recommendation is that you consider every aspect of it, and proceed cautiously if you choose to do so.",
"title": ""
},
{
"docid": "388575",
"text": "While there is no legal reason to have a minimum number of employees, there can be a practical reason. They want to look like a good solid investment so that investors will give them money, which is what an IPO is, really. Hiring lots of people is part of that. Once the investors are committed, they can cut expenses by firing people again. I have no idea how common this is, but it is a possibility. However, if it were really common, investors wouldn't be fooled anymore. Also, they risk being sued for fraud over this. Even if your friend's worry is probably unfounded, you should be aware that working for a startup is always risky. They very often go bankrupt even if they try their best. They can misjudge their intended market. They can get higher expenses than expected. There can be another company with same idea being launched at the same time. Other things can go wrong. Working for a startup is a risk, but it beats being unemployed, right?",
"title": ""
},
{
"docid": "71424",
"text": "Let me add a few thoughts that have not been mentioned so far in the other answers. Note that for the decision of buying vs. renting a home i.e. for personal use, not for renting out there's a rule of thumb that if the price for buying is more than 20 year's (cold) rents it is considered rather expensive. I don't know how localized this rule of thumb is, but I know it for Germany which is apparently the OP's country, too. There are obviously differences between buying a house/flat for yourself and in order to rent it out. As others have said, maintenance is a major factor for house owners - and here a lot depends on how much of that you do yourself (i.e. do you have the possibility to trade working hours for costs - which is closely related to financial risk exposure, e.g. increasing income by cutting costs as you do maintenance work yourself if you loose your day-time job?). This plays a crucial role for landlords I know (they're all small-scale landlords, and most of them do put in substantial work themselves): I know quite a number of people who rent out flats in the house where they actually live. Some of the houses were built with flats and the owner lives in one of the flats, another rather typical setup is that people built their house in the way that a smaller flat can easily be separated and let once the kids moved out (note also that the legal situation for the landlord is easier in that special case). I also know someone who owns a house several 100 km away from where they live and they say they intentionally ask a rent somewhat below the market price for that (nice) kind of flat so that they have lots of applicants at the same time and tenants don't move out as finding a new tenant is lots of work and costly because of the distance. My personal conclusion from those points is that as an investment (i.e. not for immediate or future personal use) I'd say that the exact circumstances are very important: if you are (stably) based in a region where the buying-to-rental-price ratio is favorable, you have the necessary time and are able to do maintenance work yourself and there is a chance to buy a suitable house closeby then why not. If this is not the case, some other form of investing in real estate may be better. On the other hand, investing in further real estate closeby where you live in your own house means increased lump risk - you miss diversification into regions where the value of real estate may develop very differently. There is one important psychological point that may play a role with the observed relation between being rich and being landlord. First of all, remember that the median wealth (without pensions) for Germany is about 51 k€, and someone owning a morgage-free 150 k€ flat and nothing else is somewhere in the 7th decile of wealth. To put it the other way round: the question whether to invest 150 k€ into becoming a landlord is of practical relevance only for rich (in terms of wealth) people. Also, asking this question is typically only relevant for people who already own the home they live in as buying for personal use will typically have a better return than buying in order to rent. But already people who buy for personal use are on average wealthier (or at least on the track to become more wealthy in case of fresh home owners) than people who rent. This is attributed to personal characteristics and the fact that the downpayment of the mortgage enforces saving behaviour (which is typically kept up once the house is paid, and is anyways found to be more pronounced than for non-house-owners). In contrast, many people who decide never to buy a home fall short of their initial savings/investment plans (e.g. putting the 150 k€ into an ETF for the next 21 years) and in the end spend considerably more money - and this group of people rarely invests into directly becoming a landlord. Assuming that you can read German, here's a relevant newspaper article and a related press release.",
"title": ""
},
{
"docid": "24603",
"text": "\"That wasn't really my point. I was countering the attitudes that 1. Landlords vs slumlords - somehow I doubt if the author lives in a real slum with a landlord that provides substandard housing. Why call a landlord a derogatory name for providing you a place to live>? 2. The idea that the \"\"slumlords\"\" somehow conspired to artificially inflate, then deflate the quiet and lovely neighborhood. Pretty ridiculous notion in my opinion. Not to mention that buying a home in an area with abysmal schools doesn't seem to be a good idea if you have a \"\"gifted daughter\"\", unless you can afford to send her to private schools.\"",
"title": ""
},
{
"docid": "315972",
"text": "You may be in a situation where buying is preferred, especially because you can enter the market in a strong position - with a 20% down payment. If you have the financial ability to assume the risk of owning, you may be better off. I would consider two things. Renting is purchasing a service. You are buying the flexibility to move with minimum hassle and the landlord is assuming the risk of owning the asset (property). They will make money on you, like any service provider. Buying is purchasing an asset. You are buying the underlying asset and assume all the risks associated with it. This is large, unforeseen maintenance, fees, taxes, depreciation, etc... Some of these risks were passed to you as a renter, but some were not. Just like purchasing $400k in stock, if you have to sell when the market is down, you lose big. You win if you can hold. Unlike a stock, real estate will eat your cash in taxes and repairs unless it is rented. If you are willing to be a long-distance landlord, this may work out. Understand that property management fees will eat into your rent income and being long-distance will give more potential for a bad tenant to ruin your property value. These and other factors (e.g. vacancy rate) will increase your risk of loss and should be considered. Some of this will be your preference, since you will spend much more time dealing with buying/selling/property management as opposed to a more clean rental situation. Is this hassle worth the savings? For many, yes; others, no. Finally, I hope this calculator can help clarify some of the financial aspects for you. http://www.nytimes.com/interactive/2014/upshot/buy-rent-calculator.html?_r=0 Good Luck!",
"title": ""
},
{
"docid": "178278",
"text": "\"This might be a good idea, depending on your personality and inclinations. Key points: How close is the building to you? Do not buy any building that is more than 20 minutes travel from where you are. Do you have any real hard experience with doing construction, building maintenance and repair? Do you have tools? Example: do you have a reciprocating saw? do you know what a reciprocating saw is? If your answer to both those questions is \"\"no\"\", think twice about acquiring a property that involves renovation. Renovation costs can be crushing, especially for someone who is not an experienced carpenter and electrician. Take your estimates of costs and quadruple them. Can you still afford it? Do you want to be a landlord? Being a landlord is a job. You will be called in the middle of the night by tenants who want their toilet to get fixed and stuff like that. Is that what you want to spend your time doing, driving 20 minutes to change lightbulbs and fix toilets?\"",
"title": ""
},
{
"docid": "23774",
"text": "With student loans at 2%, I wouldn't pay a dime over minimum on that, and I certainly wouldn't sell an investment property to pay them off, you can get CD's that beat 2% interest. With the rentals, you could sell the one that isn't performing as well and pay no capital gains tax if you lived in it 2 of the last 5 years (counting 5 years back from sale date). That'd be a nice chunk of money for your down-payment. The risk of using proceeds to buy a different rental property is that you may find you don't like being a distance landlord, and then you'd lose money selling or be stuck doing something you don't enjoy for a while until you can sell without a loss. Like you mentioned, the risk of selling either/both rental properties is that if the Arizona housing/rental markets do well you'd have given up your position and missed out. Ultimately, I think it's about your desired timeline, if you are content to wait a while to buy in San Diego, you could have a handsome down payment, will know whether or not you like being a distance landlord, and can sell/keep the rentals accordingly. Alternatively, if you want to get a house in San Diego sooner, then selling one or both rentals gets you there faster. If I was in your position, I'd probably sell the rental that I lived in and put that toward a down-payment on a primary residence, keeping the other rental for now and trying my hand at being a distance landlord.",
"title": ""
},
{
"docid": "51715",
"text": "\"Theory of Levered Investing Borrowing in order to increase investment exposure is a time-honored and legitimate activity. It's the optimal way to increase your exposure, according to finance theory (which assumes you get a good interest rate...more on this later). In your case it may or may not be a good idea. Based on the information in your post, I believe that in your case it is not a good idea. Consider the following concerns. Risk In finance, reward comes with risk and in no other way. Investing borrowed money means there is a good (not small) chance that you will lose enough money that you will need to pull significant wealth from your own savings in order to make up the difference. If you are in a position to do this and OK with that possibility, then proceed to to the next concern. If losing a lot of money means financial calamity for you, then this is a bad idea. You haven't described your financial situation so I don't know in which camp you fall. If the idea of losing, say, $100K means complete financial failure for you, then the strategy you have described simply has too much risk. Make no mistake, just because the market makes money on average does not mean it will make money, or as much money as you expect, over your horizon. It may lose money, perhaps a lot of money. Make sure this idea is very clear in your mind before taking action. Rewards Your post implies that you think you can reliably get 10%-12% on an investment. This is not the case. There are many years in which a reasonable portfolio makes this much or more, but on average you will earn less. No ones knows the true long-term market risk premium, but it is definitely less than 10%. A better guess would be 6.5% plus whatever the risk-free rate is (currently about 0%). Buying \"\"riskier\"\" investments means deviating from the optimal portfolio, meaning you took on more risk than is justified by how much extra money you expect to make. I never encourage people to invest based on optimistic or unrealistic goals. If anything, you should be conservative about how you expect things to go. And remember, these are averages. Any portfolio that earns 10%-12% also has a very good chance of losing 25% or more. People who sell or give advice on investments frequently get you charged up by pointing at times and investments that have done very well. Unfortunately, we never know whether the investments and time period in which we are investing will be a good one, a bad one, or an unexciting one. The reality of investing is...well, more realistic than what you have described. Costs I can't imagine how you could borrow that much money and only have an annual payment of $2000 as you imply--that must be a mistake. No individual borrows at a rate significantly below 1%. It sounds like it's not a collateralized loan of any kind, so unless you are some kind of prime-loan customer, your interest rate will be significant. Subtract whatever rate you actually pay from 6.5% to get a rough idea of how much you will make if things go as well as they do on average. You will pay the interest whether times are good or bad. If your rate is typical of noncollateralized personal loans, there's a good chance you will lose money on average using the strategy you have described. If you are OK with taking risk with a negative expected return, consider a trip to Las Vegas. It's more exciting. Ethics I'm not one to make people feel guilty for doing things that are legal but of questionable morality. If that's the case and you are OK with it, more power to you. I'm not sure under what pretense you expect to obtain the money, but it sounds like you might be crossing legal lines and committing actual crimes (like fraud). Make sure to check on whether what you intend is a white lie or something that can get you thrown in prison. For example, if you are proposing obtaining a subsidized education loan and using it for speculation, I could easily see you spending serious time in prison and permanently ruining your life, even if your plan works out. A judge and 12 of your peers are not going to think welfare fraud is a harmless twist of the truth. Summary I've said a lot of negative things here. This is because I have to guess about your financial situation and it sounds like you may have unrealistic expectations of the safety and generosity of investing. Quite frankly, people for whom borrowing $250K is no big deal don't normally come and ask about it on StackExchange and they definitely don't tend to lie in order to get loans. Also $18K a year doesn't change their quality of life. However, I don't know. If $250K is small relative to your wealth and you need a good way to increase your exposure to the market risk premium, then borrowing and investing may well be a good idea.\"",
"title": ""
},
{
"docid": "76283",
"text": "House as investment is not a good idea. Besides the obvious calculations don't forget the property tax, home maintenance costs and time, insurance costs, etc. There are a lot of hidden drains on the investment value of the house; most especially the time that you have to invest in maintaining it. On the other hand, if you plan on staying in the area, having children, pets or like do home improvements, landscaping, gardening, auto repair, wood/metal shopping then a house might be useful to you. Also consider the housing market where you are. This gets a bit more difficult to calculate but if you have a high-demand rental market then the house might make sense as an investment if you can rent it out for more than your monthly cost (including all of those factors above). But being a landlord is not for everyone. Again more of your time invested into the house, you have to be prepared to go months without renting it, you may have to deal with crazy people that will totally trash your house and threaten you if you complain, and you may need to part with some of the rent to a management company if you need their skills or time. It sounds like you are just not that interested right now. That's fine. Don't rush. Invest your money some other way (i.e.: the stock market). More than likely when you are ready for a house, or to bail your family out of trouble (if that's what you choose to do), you'll have even more assets to do either with.",
"title": ""
},
{
"docid": "293083",
"text": "Your calculations are good as far as they go, but there are lots of other factors and pros and cons to each decision. Yes, you should certainly compare the monthly rent to what your mortgage payments would be, as you have done. Yes, you should consider how long you might live there. If you do move out, how difficult will it be to sell the house, given market conditions in your area? If you try to rent it, how difficult is it to find a tenant, and what rent could you expect to receive? Speaking of moving out and renting the place: Who will manage the property and do maintenance? Would you still be close enough to do this yourself? Would you be willing and able to spend the time? Or would you have to hire someone? Also, what if the tenant does not pay the rent? How difficult is it to evict someone in your area? Speaking from personal experience, I own a rental property in Ohio, and the law says you can evict someone with 3 days notice. But in practice they don't just leave, so then you have to take them to court. It takes months to get a court date and months longer before the police actually show up to order them out of the house. And you have to pay the lawyer and court fees. In that time they're living in your property rent free. In my case one tenant also totally trashed the place and stole everything that wasn't nailed down -- I had to spend $13,000 on repairs to a house worth a fraction of what you're talking about. Being a landlord is NOT just a matter of sitting back and collecting rent checks: there's a fair amount of work and a lot of risk. What do you have to pay the realtor, and what other closing costs would you have to pay? Where I live, realtors typically charge 6 to 7%. You may also have to pay for an appraisal, title search, and bunch of other little fees. Mortgage interest is deductible on your federal income taxes. Rent is not. If you own and something needs to be repaired, you have to pay for it. If you rent, the landlord has to pay for it. If you own, you can do pretty much what you like with the property -- subject to zoning ordinances and building codes and maybe homeowners association rules, but you should have a pretty good amount of leeway. If you want to install ceiling fans or remodel the kitchen or add a deck, it's up to you. If you're renting, it's up to the landlord to decide what you can do to the property. And if he agrees to let you do some upgrade, when you're done, it belongs to him. With a condo, you are not usually responsible for exterior maintenance, like mowing the lawn and trimming the bushes and washing the outer walls. With a house, you are. You might pay someone to do this, which adds to the cost, or you might do it yourself, which takes time. Insurance on a condo or aparment is much less than insurance on a house. In my area, anyway. You should investigate those costs. If you buy, eventually you own the place and don't have to pay a mortgage any more. If you rent, you continue to pay forever. (Even if you don't live in the same house forever, as long as you don't take a terrible loss when you sell you should then have some money left over to apply to the next house, so you are still building equity.) Some of these pros and cons are easily quantifiable. Others are probabilities, like how likely is it that your water heater will fail?, and how long is it likely to take to find a buyer if you want to sell? And others are pretty subjective.",
"title": ""
},
{
"docid": "451849",
"text": "\"The general answer is: \"\"it depends on how long you want to live there\"\". Here is a good calculator to figure it out: http://www.nytimes.com/interactive/business/buy-rent-calculator.html Basically, if you plan to move in a few years, then renting makes more sense. It is a lot easier to move from an apartment when your lease is up versus selling a house, which can be subject to fluctuations in the real-estate market. As an example, during the real estate bubble, a lot of \"\"young professional\"\" types bought condos and town homes instead of renting. Now these people are married with kids, need to move somewhere bigger, but they can't get rid of their old place because they can't sell it for what they still owe. If these people had rented for a few years, they would be in a better position financially. (Many people fell for the mantra \"\"If you are renting, you are throwing your money away\"\", without looking at the long-term implications.) However, your question is a little unique, because you mentioned renting for the rest of your life, and putting the savings into an investment, which is a cool idea. (Thinking outside the box, I like it.) I'm going to assume you mean \"\"rent the same place for many years\"\" versus \"\"moving around the country every few years\"\". If you are staying in one place for a long time, I am going to say that buying a house is probably a better option. Here's why: So what about investing? Let's look at some numbers: So, based on the above, I say that buying a house is the way to go (as long as you plan to live in the same place for several years). However, if you could find a better investment than the Dow, or if mortgage interest rates change drastically, things could tip in another direction. Addendum: CrimsonX brought up a good point about the costs of owning a house (upkeep and property taxes), which I didn't mention above. However, I don't think they change my answer. If you rent, you are still paying those costs. They are just hidden from you. Your landlord pays the contractor or the tax man, and then you pay the landlord as part of your rent.\"",
"title": ""
},
{
"docid": "565356",
"text": "The debt is absolutely real. China loans money to US via buying the US treasury bonds. The bond is essentially a promise to pay back the money with interest, just like a loan. As you point out, the US can print money. If this were to happen, then the USD that the owner of a treasury bond receives when the bond matures are worth less that than the USD used to purchase the bonds. There are lots of reasons why the US doesn't want to print lots of money, so the purchaser of the bond is probably confident it won't happen. If for some reason they think it is possible, then they will want to cover that risk by only purchasing bonds that have a higher interest rate. The higher interest offsets the risk of the USD being worth less. Of course, there are lots more details, e.g., the bonds themselves are bought and sold before maturity, but this is the basic idea.",
"title": ""
},
{
"docid": "334391",
"text": "The idea you present is not uncommon, many have tried it before. It would be a great step to find landlords in your area and talk to them about lessons learned. It might cost you a lunch or cup of coffee but it could be the best investment you make. rent it out for a small profit (hopefully make around 3 - 5k a year in profit) Given the median price of a home is ~220K, and you are investing 44K, you are looking to make between a 6 and 11% profit. I would not classify this as small in the current interest rate environment. One aspect you are overlooking is risk. What happens if a furnace breaks, or someone does not pay their rent? While some may advocate borrowing money to buy rental real estate all reasonable advisers advocate having sufficient reserves to cover emergencies. Keep in mind that 33% of homes in the US do not have a mortgage and some investment experts advocate only buying rentals with cash. Currently owning rental property is a really good deal for the owners for a variety of reasons. Markets are cyclical and I bet things will not be as attractive in 10 years or so. Keep in mind you are borrowing ~220K or whatever you intend to pay. You are on the hook for that. A bank may not lend you the money, and even if they do a couple of false steps could leave you in a deep hole. That should at least give you pause. All that being said, I really like your gumption. I like your desire and perhaps you should set a goal of owning your first rental property for 5 years from now. In the mean time study and become educated in the business. Perhaps get your real estate license. Perhaps go to work for a property management company to learn the ins and outs of their business. I would do this even if I had a better paying full time job.",
"title": ""
},
{
"docid": "112535",
"text": "In addition to what @HartCO and @rocketman wrote, being a successful landlord either takes a lot of either:",
"title": ""
},
{
"docid": "96538",
"text": "\"Have you been rejected from a rental for a specific reason (leading to this question)? Landlords are in the business of exchanging space for regular payments with no drama. Anything they ask in an application should be something to minimize the risk of drama. The \"\"happy path\"\" optimistic goal is that you pay your rent by the due date every month. If your income is not sufficient for this, demonstrating you have assets and would be able to pay for the full term of the lease is part of the decision to enter into the lease with you. In the non-happy-path, say you fall off the face of the earth before ending the lease. The landlord could be owed several months of rent, and could pursue a legal judgment on your assets. With a court order, they can make the bank pay out what is owed; having bank information reduces the landlord's cost and research efforts in the event the story has degenerated to this point (in the jargon of landlording, this means the tenant is \"\"collectable\"\"). While of course you could have zeroed out your accounts or moved money to a bank you didn't tell the landlord in the meantime, if you are not the bad actor in this story, you probably wouldn't have. If you get any kind of \"\"spidey-sense\"\" about a landlord or property at all there is probably a better rental situation in your city. You also want to minimize drama. If the landlord is operating like a business, they're not in this to perform identity theft. If the landlord is sloppy, or has sloppy office workers, that would be different. In the event sharing your asset information truly bothers you, and the money is for rental expense anyway, you could offer to negotiate a 1 year prepaid rental (of course knock another 5%-10% off for time value of money and lower risk to landlord) if you're sure you wouldn't want to leave early.\"",
"title": ""
},
{
"docid": "321361",
"text": "\"As others have said, congratulations on saving up 75K in cash while seemingly not neglecting other areas of personal finance. Considering that only 15% of Americans have more than 10K saved this is quite a feat. source If you sell your old house, and buy the new one you will still be in really good financial shape. No need to comment further. Renting your current home and buying a new home introduces a great amount of risk into your life. The risk in this case is mitigated by cash. As others have pointed out, you will need to save a lot more to remove an acceptable amount of risk. Here is what I see: So without paying off your existing house I would see a minimum savings account balance of about double of what you have now. Once you purchase the new house, the amount would be reduced by the down payment, so you will only have about 50K sitting around. The rental emergency fund may be a little light depending on how friendly your state is to landlords. Water heaters break, renters don't pay, and properties can sit vacant. Also anytime you move into a new business there will be mistakes made that are solved by writing checks. Do you have experience running rentals? You might be better off to sell your existing home, and move into a more expensive home than what you are suggesting. You can continue to win at money without introducing a new factor into your life. Alternatively, if you are \"\"bitten by the real estate bug\"\" you could mitigate a lot risk by buying a property that is of similar value to your current home or even less expensive. You can then choose which home to live in that makes the most financial sense. For example some choose to live in the more dilapidated home so they can do repairs as time permits. To me upgrading the home you live in, and renting an expensivish home for a rental is too much to do in such a short time frame. It is assuming far too much risk far to quickly for a person with your discipline. You will get there.\"",
"title": ""
},
{
"docid": "273187",
"text": "why does it make sense financially to buy property and become a landlord? Because then your investment generates cash instead of just sitting idle. All taxes, fees and repairs aside it would take almost 21 years before I start making profits. No - your profit will be the rents that you collect (minus expenses). You still have an asset that is worth roughly what you paid for it (and might go up in value), so you don't need to recoup the entire cost of the property before making a profit. Compared to investing the same 150k in an ETF portfolio with conservative 4% in annual returns I would have made around 140k € after taxes in the same 21 years i.e. almost doubled the money. If you charge 600 € / month (and never miss a month of rental income), after 21 years you have made 151k € in rents plus you still have a property. That property is most likely going to be worth more than you paid for it, so you should have at least 300k € in assets. Having said all that, it does NOT always make sense to invest in rental property. Being a landlord can be a hard job, and there are many risks involved that are different that risks in financial investments.",
"title": ""
},
{
"docid": "278197",
"text": "Diversity of risk is always a good idea. The cheapest equity-based investment (in terms of management costs) is some form of tracker or indexed fund. They're relatively low risk and worth putting in a fixed amount for long-term investment. I agree with Ngu Soon Hui, you're going to need a lot of cash if you decide to start your own business. You may have to cover a significant amount of time without an income and you don't want all your cash tied up. However, putting all your money into one business is not good risk management. Keep some savings where they can be a lifeline, should you need it.",
"title": ""
},
{
"docid": "390744",
"text": "\"I don't think you've mentioned which State you're in. Here in Ontario, a person who is financially incapable can have their financial responsibility and authority removed, and assigned to a trustee. The trustee might be a responsible next of kin (as her ex, you would appear unsuitable: that being a potential conflict of interest); otherwise, it can be the Public Guardian and Trustee. It that happens, then the trustee handles the money; and handles/makes any contracts on behalf of (in the name of) the incapable person. The incapable person might have income (e.g. spousal support payments) and money (e.g. bank accounts), which the trustee can document in order to demonstrate credit-worthiness (or at least solvency). For the time being, the kids see it as an adventure, but I suspect, it will get old very fast. I hope you have a counsellor to talk with about your personal relationships (I've had or tried several and at least one has been extraordinarily helpful). You're not actually expressing a worry about the children being abused or neglected. :/ Is your motive (for asking) that you want her to have a place, so that the children will like it (being there) better? As long as your kids see it as an adventure, perhaps you can be happy for them. Perhaps (I don't know: depending on the people) too it's a good (or at least a better) thing that they are visiting with friends and relatives; and, a better conversational topic with those people might be how they show your children a good time (instead of your ex's money). One possible way I thought of co-signing is if a portion of child/spousal support goes directly to the landlord. I asked the Child Support Services (who deduct money from my paycheck monthly to pay support to my ex) and they told me that they are not authorized to do this. Perhaps (I don't know) there is some way to do that, if you have your ex's cooperation and a lawyer (and perhaps a judge). You haven't said what portions of your payments are for Child support, versus Spousal support (nor, who has custody, etc). If a large part of the support is for the children, then perhaps the children can rent the place. (/wild idea) Note that, in Ontario, there are two trusteeship decisions to make: 1) financial; and 2) personal care, which includes housing and medical. Someone can retain their own 'self-care' authority even if they're judged financially incapable (or vice versa if there's a personal-care or medical decision which they cannot understand). The technical language is, \"\"Mentally Incapable of Managing Property\"\" This term applies to a person who is unable to understand information that is relevant to making a decision or is unable to appreciate the reasonably foreseeable consequences of a decision or lack of decision about his or her property. Processes for certifying an individual as being mentally incapable of managing property are prescribed in the SDA (Substitute Decisions Act), and in the Mental Health Act.\"\" The Mental Heath Act is for medical emergencies (only); but Ontario has a Substitute Decisions Act as well. An intent of the law is to protect vulnerable people. People may also acquire and/or name their own trustee and/or guardian voluntarily: via a power of attorney, a living will, etc. I don't know: how about offering the landlord a year's rent in advance, or in trust? I guess that 1) a court order can determine/override/guarantee the way in which the child support payments are directed 2) it's easier to get that order/agreement if you and your ex cooperate 3) there are housing specialists in your neighborhood: They can buy housing instead of renting it. Or be given (gifted) housing to live in.\"",
"title": ""
},
{
"docid": "121382",
"text": "I think people are missing the most obvious thing. The yearly rate increases are just part of the landlord schtick and it is good business for them. My grandmother owned several large apartment complexes. She would raise rates for any resident that had been there between 1-5 years by 5-7% a year. Even when she had vacancies and property values didn't go up. For the following reasons: So yes it is not only normal but just part of the business. If there are better apartments for less money I suggest you move there. Soon those other apartments will even out and if they are better they will be much more. So if you see a gap take advantage of it. If you would rather stay, then simply say you will not pay the increase. There is no use arguing about why. The landlord will either be OK with it or say no. Probably the biggest factors include whether you will tell other tenants (or their perception if you would) and how good of a tenant/risk they feel you are.",
"title": ""
},
{
"docid": "279693",
"text": "There is (almost) always money involved somewhere, but it doesn't have to come from you. It can be investors, credit cards, or even seller-financing (I've done all 3). Examples: If you can find partners with the money to make the deals happen, then your job is to put the deal together. Find the properties, negotiate the price, even get the property under contract (all without any obligation or cost on your part... yes it absolutely can be done). Then your partners will fund the deal if it's good enough and their terms are met, etc. In some areas you can put a property on a credit card. If you find a house say for $25,000 that will rent for $300/month, and you can put it on a credit card (especially at zero percent for a year or something similar), then you can generate cashflow as a landlord without putting up any cash of your own on the purchase. Of course there are many risks associated with landlording and i could tell you horror stories... but we're not addressing that here. You can negotiate a sale with an owner who agrees to finance the entire purchase for you. I once purchased 3 properties at once this way from a seller who financed the entire sale, all closing costs, everything, this way. Of course they needed a lot of repair and such so I had to fund that another way, but at least the purchase itself cost me no money out of pocket. So these infomercials/courses are not inherently scams in the sense that what they are teaching is (usually... I'm sure there are exceptions) true. However they generally give you enough information to get into trouble, and not out. But that's what true learning is... it's getting into trouble and finding a way out that doesn't kill you. =) That's called experience, and you can't buy that for any price.",
"title": ""
},
{
"docid": "579763",
"text": "4) Beef up my emergency fund, make sure my 401(k) or IRA was fully funded, put the rest into investments. See many past answers. A house you are living in is not an investment. It is a purchase, just as rental is a purchase. Buying a house to rent out is starting a business. If you want to spend the ongoing time and effort and cash running a business, and if you can buy at the right time in the right place for the righr price, this can be a reasonable investment. If you aren't willing to suffer the pains of being a landlord, it's less attractive; you can hire someone to manage it for you but that cuts the income significantly. Starting a business: Remember that many, perhaps most, small businesses fail. If you really want to run a business it can be a good investment, again assuming you can buy at the right time/price/place and are willing and able to invest the time and effort and money to support the business. Nothing produces quick return with low risk.",
"title": ""
},
{
"docid": "128338",
"text": "\"I was thinking more of a limit on the TOTAL # of patents (something fairly small, like maybe 10,000 total patents are allowed to be valid at any given moment in time), so that patent applications from multiple sources have to be somehow compared with each other to decide which would provide more societal-benefit by being allowed patent status. If you want to take the government (mostly) out of the picture, then maybe use an auction format - when a valid patent \"\"slot\"\" becomes available (due to a previously-granted patent expiring, or being invalidated due to court challenge), then anyone who wants their idea to get patent rights submits their application to an \"\"auction\"\" for that slot. Then the people who want to OWN the patent rights to any of those submitted ideas will bid for them. Whoever pays the top bid will get the patent rights for the concepts in the specific application they were targeting. This will force the people who are doing the bidding to basically do the \"\"due diligence\"\" on each patent application (instead of depending on the patent examiners), since they will not want to pay a lot of money to get the patent rights for an idea, only to have that patent's value be destroyed by being declared invalid in court. If you want to encourage small inventors to throw their hat into the ring, then set things up so that the money from the winning bid goes to the inventor who submitted the original application. This way, you get the best of both worlds - the inventor gets compensated (handsomely in most cases) for their good idea, and the idea being patented gets into the hands of someone with enough resources to exploit the idea in a broad scale.\"",
"title": ""
},
{
"docid": "408865",
"text": "Be radical! (I assume you are not working for a city bank getting paid “city wages” – e.g. you are one of the 99% of people in London or more “normal” income.) House prices and rents in London and anywhere within reasonable commuting distances are now so high that couples in reasonable jobs often have to rent rooms in shared houses (HMOs). This is due to so many people wishing to live/work in London and there not being enough new homes built. If you are looking at buying a property to rent out, you need the rent to be about double the interest payments on the mortgage – otherwise you will not be able to afford repairs, or cope when interest rates increase – (you could also get a tax bill that is more the your profit). Finding such a property is very hard in London, as the prices of homes have gone up a lot more in London then rents have. There are still some flats where the rent will cover the landlord’s costs, but not many. (Any landlord that brought more than a few years ago, is making a very nice profit in London, as the rents have gone up a lot since they brought – but are you willing to bet your life on the rents going up even more?) Moving a short distance out of London, does not help much. So look at somewhere like Manchester or Birmingham",
"title": ""
},
{
"docid": "422579",
"text": "It depends on the terms of the lease, but it's hard to imagine a lease that would allow to do this unilaterally with no strings attached. That means it actually depends not on how much you like your landlady, but on how much she likes you. In general, by signing the lease you assume a contractual obligation to pay the rent every month for the entire term of the lease. In theory, you can be sued if you don't do that. In practice, a lot depends on your relationship with your landlord, as well as the rental market in your area. If the landlord can easily find a replacement tenant, they may be willing to allow you to leave early. If the rental market is slow, they will be more likely to hold you to the agreement. Obviously, if you have a good relationship with the landlord, they may be more inclined to go easy on you. As far as telling your landlady you want to terminate the lease early, unless she's a particularly nasty person, you can just go ahead and tell her you'd like to leave early. What you can't do is actually stop paying rent. If you're on reasonably good terms with your landlady, you could just tell her your situation and say you'd like to move out. She may be willing to work out an arrangement where she lists the apartment while you're still living there, allows prospective tenants to view it while it's occupied, and then has you move out if and when someone else wants to move in (e.g., at the end of the month). Again, exactly how this works will probably depend on the rental market. Assuming you're in the USA, here is a useful page with some info on breaking a lease. As mentioned there, the legal details vary by state.",
"title": ""
},
{
"docid": "99619",
"text": "Slightly abbreviated version of the guidance from NOLO.com California state law limits credit check or application screening fees landlords can charge prospective tenants and specifies what landlords must do when accepting these types of fees. (Cal. Civ. Code § 1950.6.) Here are key provisions: I am not a lawyer, but it would seem you have two options if you catch a landlord violating these rules. An idea to avoid the whole problem in the first place: Get a copy of your credit report yourself and take a copy with you to meet the landlord. If they want an application fee, ask why they need it making it clear you know the above law. If they say for a credit report offer to give them a copy in lieu of the fee.",
"title": ""
}
] |
PLAIN-3213
|
Is Matcha Good for You?
|
[
{
"docid": "MED-706",
"text": "Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H(2)O(2) and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity. Copyright 2009 Elsevier GmbH. All rights reserved.",
"title": "The aqueous extract of Hibiscus sabdariffa calices modulates the production of monocyte chemoattractant protein-1 in humans."
},
{
"docid": "MED-1867",
"text": "OBJECTIVES: There is increasing evidence that intake of sour tea (Hibiscus sabdariffa) has hypoglycemic and hypolipidemic effects and may benefit patients suffering from metabolic disorders such as diabetes. The objective of the present study was to investigate the hypolipidemic effects of sour tea in patients with diabetes and compare them with those of black tea. DESIGN: In this sequential randomized controlled clinical trial, 60 patients with diabetes were recruited and randomly assigned into two groups: sour tea (ST) and black tea (BT). They were instructed to consume sour tea or black tea two times a day for 1 month. OUTCOME MEASURES: Fasting blood samples were taken at the beginning and at the end of the study for evaluation of lipids, lipoproteins, and apoproteins. RESULTS: Fifty-three (53) patients concluded the study. In the ST group, mean of high-density lipoprotein-cholesterol (HDLc) increased significantly (p = 0.002) at the end of the study, whereas changes in apolipoprotein-A1, and lipoprotein (a) were not significant. Also, a significant decrease in the mean of total cholesterol, low density lipoprotein-cholesterol, triglycerides, and Apo-B100 were seen in this group. In the BT group, only HDLc showed significant change (p = 0.002) at the end of the study and changes in the other measures were not statistically significant. CONCLUSIONS: The results of the present study showed that ST has a significant effect on blood lipid profile in patients with diabetes.",
"title": "Effects of sour tea (Hibiscus sabdariffa) on lipid profile and lipoproteins in patients with type II diabetes."
},
{
"docid": "MED-4049",
"text": "More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.",
"title": "Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine"
},
{
"docid": "MED-4332",
"text": "There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce \"artificial\" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as \"scavenging\" the reactive intermediate(s).",
"title": "Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay."
},
{
"docid": "MED-709",
"text": "The sub-chronic effect of Hibiscus sabdariffa (HS) calyx aqueous extract on the rat testes was investigated with a view to evaluate the pharmacological basis for the use of HS calyx extract as an aphrodisiac. Three test groups received different doses of 1.15, 2.30, and 4.60 g/kg based on the LD(50). The extracts were dissolved in the drinking water. The control group was given equivalent volume of water only. The animals were allowed free access to drinking solution during the 12-week period of exposure. At the expiration of the treatment period, animals were sacrificed, testes excised and weighed, and epididymal sperm number recorded. The testes were processed for histological examination. Results did not show any significant (P>0.05) change in the absolute and relative testicular weights. There was, however, a significant (P<0.05) decrease in the epididymal sperm counts in the 4.6 g/kg group, compared to the control. The 1.15 g/kg dose group showed distortion of tubules and a disruption of normal epithelial organization, while the 2.3 g/kg dose showed hyperplasia of testis with thickening of the basement membrane. The 4.6 g/kg dose group, on the other hand, showed disintegration of sperm cells. The results indicate that aqueous HS calyx extract induces testicular toxicity in rats.",
"title": "Testicular effects of sub-chronic administration of Hibiscus sabdariffa calyx aqueous extract in rats."
},
{
"docid": "MED-711",
"text": "Insulin resistance, obesity, hypertension, and dyslipidemia are strongly associated with metabolic syndrome (MeSy), which is considered to be a reversible clinical stage before its evolution to coronary heart disease and diabetes. Currently, the antihypertensive and hypolipidemic properties of aqueous Hibiscus sabdariffa extracts (HSE) have been demonstrated in clinical trials and in vivo experiments. The aim of the present study was to evaluate the effects of a Hibiscus sabdariffa extract powder (HSEP) and a recognized preventive treatment (diet) on the lipid profiles of individuals with and without MeSy according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The protocol was a follow-up study carried out in a factorial, randomized design (T1=preventive treatment comprises Diet, T2=HSEP, T3=HSEP+preventive treatment (Diet) X MeSy, non-MeSy individuals). A total daily dose of 100 mg HSEP was orally administered in capsules for one month. The preventive treatment (diet) was selected according to NCEP-ATP III recommendations and adjusted individually. Total cholesterol, LDL-c, HDL-c, VLDL-c, triglycerides, glucose, urea, creatinine, AST, and ALT levels in the blood were determined in all individuals pre- and post-treatment. The MeSy patients treated with HSEP had significantly reduced glucose and total cholesterol levels, increased HDL-c levels, and an improved TAG/HDL-c ratio, a marker of insulin resistance (t-test p<0.05). Additionally, a triglyceride-lowering effect was observed in MeSy patients treated with HSEP plus diet, and in individuals without MeSy treated with HSEP. Significant differences in total cholesterol, HDL-c, and the TAG/HDL-c ratio were found when the means of absolute differences among treatments were compared (ANOVA p<0.02). Therefore, in addition to the well documented hypotensive effects of Hibiscus sabdariffa, we suggest the use of HSEP in individuals with dyslipidemia associated with MeSy.",
"title": "Effects of Hibiscus sabdariffa extract powder and preventive treatment (diet) on the lipid profiles of patients with metabolic syndrome (MeSy)."
},
{
"docid": "MED-4055",
"text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.",
"title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells."
},
{
"docid": "MED-713",
"text": "The effect of beverages prepared from the dried calyx of the flowers of Hibiscus sabdariffa on the excretion of diclofenac was investigated using a controlled study in healthy human volunteers. A high pressure liquid chromatographic method was used to analyse the 8 h urine samples collected after the administration of diclofenac with 300 mL (equivalent to 8.18 mg anthocyanins) of the beverage administered daily for 3 days. An unpaired two-tailed t-test was used to analyse for significant difference observed in the amount of diclofenac excreted before and after administration of the beverage. There was a reduction in the amount of diclofenac excreted and the wide variability observed in the control with the water beverage of Hibiscus sabdariffa (p < 0.05). There is an increasing need to counsel patients against the use of plant beverages with drugs.",
"title": "Effects of water extract of Hibiscus sabdariffa, Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation."
},
{
"docid": "MED-708",
"text": "Heterocyclic aromatic amines (HAA) are carcinogenic compounds found in the crust of fried meat. The objective was to examine the possibility of inhibiting HAA formation in fried beef patties by using marinades with different concentrations of hibiscus extract (Hibiscus sabdariffa) (0.2, 0.4, 0.6, 0.8 g/100g). After frying, patties were analyzed for 15 different HAA by HPLC-analysis. Four HAA MeIQx (0.3-0.6 ng/g), PhIP (0.02-0.06 ng/g), co-mutagenic norharmane (0.4-0.7 ng/g), and harmane (0.8-1.1 ng/g) were found at low levels. The concentration of MeIQx was reduced by about 50% and 40% by applying marinades containing the highest amount of extract compared to sunflower oil and control marinade, respectively. The antioxidant capacity (TEAC-Assay/Folin-Ciocalteu-Assay) was determined as 0.9, 1.7, 2.6 and 3.5 micromol Trolox antioxidant equivalents and total phenolic compounds were 49, 97, 146 and 195 microg/g marinade. In sensory ranking tests, marinated and fried patties were not significantly different (p>0.05) to control samples. Copyright (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Inhibitory effect of marinades with hibiscus extract on formation of heterocyclic aromatic amines and sensory quality of fried beef patties."
},
{
"docid": "MED-4331",
"text": "There is a belief that caffeinated drinks, such as tea, may adversely affect hydration. This was investigated in a randomised controlled trial. Healthy resting males (n 21) were recruited from the general population. Following 24 h of abstention from caffeine, alcohol and vigorous physical activity, including a 10 h overnight fast, all men underwent four separate test days in a counter-balanced order with a 5 d washout in between. The test beverages, provided at regular intervals, were 4 × 240 ml black (i.e. regular) tea and 6 × 240 ml black tea, providing 168 or 252 mg of caffeine. The controls were identical amounts of boiled water. The tea was prepared in a standardised way from tea bags and included 20 ml of semi-skimmed milk. All food taken during the 12 h intervention period was controlled, and subjects remained at rest. No other beverages were offered. Blood was sampled at 0, 1, 2, 4, 8 and 12 h, and a 24 h urine sample was collected. Outcome variables were whole blood cell count, Na, K, bicarbonate, total protein, urea, creatinine and osmolality for blood; and total volume, colour, Na, K, creatinine and osmolality for urine. Although data for all twenty-one participants were included in the analysis (mean age 36 years and mean BMI 25·8 kg/m(2)), nineteen men completed all conditions. Statistical analysis, using a factorial ANOVA approach within PROC MIXED, revealed no significant differences between tea and water for any of the mean blood or urine measurements. It was concluded that black tea, in the amounts studied, offered similar hydrating properties to water.",
"title": "Black tea is not significantly different from water in the maintenance of normal hydration in human subjects: results from a randomised controlled ..."
},
{
"docid": "MED-712",
"text": "Hibiscus sabdariffa Linne is a traditional Chinese rose tea and has been effectively used in folk medicines for treatment of hypertension, inflammatory conditions. H. sabdariffa aqueous extracts (HSE) were prepared from the dried flowers of H. sabdariffa L., which are rich in phenolic acids, flavonoids and anthocyanins. In this review, we discuss the chemopreventive properties and possible mechanisms of various H. sabdariffa extracts. It has been demonstrated that HSE, H. sabdariffa polyphenol-rich extracts (HPE), H. sabdariffa anthocyanins (HAs), and H. sabdariffa protocatechuic acid (PCA) exert many biologic effects. PCA and HAs protected against oxidative damage induced by tert-butyl droperoxide (t-BHP) in rat primary hepatocytes. In rabbits fed cholesterol and human experimental studies, these studies imply HSE could be pursued as atherosclerosis chemopreventive agents as they inhibit LDL oxidation, foam cell formation, as well as smooth muscle cell migration and proliferation. The extracts also offer hepatoprotection by influencing the levels of lipid peroxidation products and liver marker enzymes in experimental hyperammonemia. PCA has also been shown to inhibit the carcinogenic action of various chemicals in different tissues of the rat. HAs and HPE were demonstrated to cause cancer cell apoptosis, especially in leukemia and gastric cancer. More recent studies investigated the protective effect of HSE and HPE in streptozotocin induced diabetic nephropathy. From all these studies, it is clear that various H. sabdariffa extracts exhibit activities against atherosclerosis, liver disease, cancer, diabetes and other metabolic syndromes. These results indicate that naturally occurring agents such as the bioactive compounds in H. sabdariffa could be developed as potent chemopreventive agents and natural healthy foods.",
"title": "Chemopreventive properties and molecular mechanisms of the bioactive compounds in Hibiscus sabdariffa Linne."
},
{
"docid": "MED-4051",
"text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients."
},
{
"docid": "MED-4050",
"text": "Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.",
"title": "Green tea consumption and breast cancer risk or recurrence: a meta-analysis."
},
{
"docid": "MED-1842",
"text": "Considering the high prevalence of hypertension, its debilitating end organ damage, and the side effects of chemical drugs used for its treatment, we conducted this experimental study to evaluate the effect of sour tea (Hibiscus sabdariffa) on essential hypertension. For this purpose, 31 and 23 patients with moderate essential hypertension were randomly assigned to an experimental and control group, respectively. Patients with secondary hypertension or those consuming more than two drugs were excluded from the study. Systolic and diastolic blood pressures were measured before and 15 days after the intervention. In the experimental group, 45% of the patients were male and 55% were female, and the mean age was 52.6 +/- 7.9 years. In the control group, 30% of the patients were male, 70% were female, and the mean age of the patients was 51.5 +/- 10.1 years. Statistical findings showed an 11.2% lowering of the systolic blood pressure and a 10.7% decrease of diastolic pressure in the experimental group 12 days after beginning the treatment, as compared with the first day. The difference between the systolic blood pressures of the two groups was significant, as was the difference of the diastolic pressures of the two groups. Three days after stopping the treatment, systolic blood pressure was elevated by 7.9%, and diastolic pressure was elevated by 5.6% in the experimental and control groups. This difference between the two groups was also significant. This study proves the public belief and the results of in vitro studies concerning the effects of sour tea on lowering high blood pressure. More extensive studies on this subject are needed.",
"title": "The effect of sour tea (Hibiscus sabdariffa) on essential hypertension."
},
{
"docid": "MED-707",
"text": "AIM OF THE STUDY: The Roselle (Hibiscus sabdariffa) was investigated for its uricosuric effect. MATERIALS AND METHODS: A human model with nine subjects with no history of renal stones (non-renal stone, NS) and nine with a history of renal stones (RS) was used in this study. A cup of tea made from 1.5 g of dry Roselle calyces was provided to subjects twice daily (morning and evening) for 15 days. A clotted blood and two consecutive 24-h urine samples were collected from each subject three times: (1) at baseline (control); (2) on days 14 and 15 during the tea drinking period; and (3) 15 days after the tea drinking was stopped (washout). Serum and 24-h urinary samples were analyzed for uric acid and other chemical compositions related to urinary stone risk factors. RESULTS: All analyzed serum parameters were within normal ranges and similar; between the two groups of subjects and among the three periods. Vis-à-vis the urinary parameters, most of the baseline values for both groups were similar. After taking the tea, the trend was an increase in oxalate and citrate in both groups and uric acid excretion and clearance in the NS group. In the RS group, both uric acid excretion and clearance were significantly increased (p<0.01). When the fractional excretion of uric acid (FEUa) was calculated, the values were clearly increased in both the NS and SF groups after the intake of tea and returned to baseline values in the washout period. These changes were more clearly observed when the data for each subject was presented individually. CONCLUSIONS: Our data demonstrate a uricosuric effect of Roselle calyces. Since the various chemical constituents in Roselle calyces have been identified, the one(s) exerting this uricosuric effect need to be identified.",
"title": "Uricosuric effect of Roselle (Hibiscus sabdariffa) in normal and renal-stone former subjects."
}
] |
[
{
"docid": "MED-2291",
"text": "PURPOSE: This review focuses on the health benefits of viscous versus nonviscous soluble fibers, why symptoms can occur with increased fiber consumption, and how to avoid symptoms to improve adherence with a high-fiber diet. DATA SOURCES: Review of scientific literature as well as evidence-based guidelines and resources. CONCLUSIONS: While it is generally known that \"fiber is good for you,\" it is less well known that specific health benefits are associated with specific fiber characteristics. Many of the health benefits of fiber can be directly correlated with the viscosity of soluble fibers when hydrated (i.e., gel-forming). A reduction in viscosity of a given fiber will attenuate these health benefits, and a nonviscous fiber does not exhibit these health benefits. IMPLICATIONS FOR PRACTICE: Increasing the viscosity of chyme with a viscous soluble fiber has been shown clinically to lower cholesterol for cardiovascular health, improve glycemic control in type 2 diabetes, normalize stool form in both constipation (softens hard stool) and diarrhea (firms loose/liquid stool), and improve the objective clinical measures of metabolic syndrome (glycemic control, lipoprotein profile, body mass index/weight loss, and blood pressure). ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.",
"title": "Viscous versus nonviscous soluble fiber supplements: mechanisms and evidence for fiber-specific health benefits."
},
{
"docid": "MED-3109",
"text": "The aryl hydrocarbon receptor (AhR) is responsible for the toxic effects of environmental pollutants such as dioxin, but little is known about its normal physiological functions. Li et al. (2011) now show that specific dietary compounds present in cruciferous vegetables act through the AhR to promote intestinal immune function, revealing AhR as a critical link between diet and immunity. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "You AhR what you eat: linking diet and immunity."
},
{
"docid": "MED-3359",
"text": "Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.",
"title": "You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes"
},
{
"docid": "MED-3776",
"text": "Little research has examined the effect of water consumption on cognition in children. We examined whether drinking water improves performance from baseline to test in twenty-three 6-7-year-old children. There were significant interactions between time of test and water group (water/no water), with improvements in the water group on thirst and happiness ratings, visual attention and visual search, but not visual memory or visuomotor performance. These results indicate that even under conditions of mild dehydration, not as a result of exercise, intentional water deprivation or heat exposure, children's cognitive performance can be improved by having a drink of water.",
"title": "Does having a drink help you think? 6-7-Year-old children show improvements in cognitive performance from baseline to test after having a drink of ..."
},
{
"docid": "MED-4236",
"text": "PURPOSE: We reviewed recent literature and treatment guidelines regarding the prevalence, pathophysiology, and management of BPO related to BPH; and management of lower urinary tract symptoms secondary to BPH. MATERIALS AND METHODS: Published literature and current treatment concepts were reviewed regarding the diagnosis and treatment options for BPO. RESULTS: BPH is a histological diagnosis that can contribute to medical problems, including enlargement of the prostate and BPO. These conditions should be treated only if the symptoms are troublesome, there is considerable risk of progression, and/or cancer is suspected. Very effective medical and surgical options are available to treat BPO and improve patient quality of life. CONCLUSIONS: BPO is highly treatable, but should be managed in close collaboration with the patient. Pharmacological agents and minimally invasive procedures, when appropriate, are generally preferred to more invasive surgery. Patients with mild or moderate symptoms usually can be treated by a primary care physician; more complicated cases should be referred to a urologist for evaluation and management.",
"title": "Benign prostatic hyperplasia in primary care: what you need to know."
},
{
"docid": "MED-940",
"text": "Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.",
"title": "An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for t..."
},
{
"docid": "MED-4034",
"text": "OBJECTIVES: To determine whether foods that are good to excellent sources of fiber reduce periodontal disease progression in men. DESIGN: Prospective, observational study. SETTING: Greater Boston, Massachusetts, metropolitan area. PARTICIPANTS: Six hundred twenty-five community-dwelling men participating in the Department of Veterans Affairs Dental Longitudinal Study. MEASUREMENTS: Dental and physical examinations were conducted every 3 to 5 years. Diet was assessed using food frequency questionnaires (FFQs). Mean follow-up was 15 years (range: 2-24 years). Periodontal disease progression on each tooth was defined as alveolar bone loss (ABL) advancement of 40% or more, probing pocket depth (PPD) of 2 mm or more, or tooth loss. Good and excellent fiber sources provided 2.5 g or more of fiber per serving. Multivariate proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of periodontal disease progression and tooth loss in relation to fiber sources, stratified according to age younger than 65 versus 65 and older, and controlled for smoking, body mass index, calculus, baseline periodontal disease level, caries, education, exercise, carotene, thiamin and caffeine intake, and tooth brushing. RESULTS: In men aged 65 and older, each serving of good to excellent sources of total fiber was associated with lower risk of ABL progression (HR = 0.76, 95% CI = 0.60-0.95) and tooth loss (HR = 0.72, 95% CI = 0.53-0.97). Of the different food groups, only fruits that were good to excellent sources of fiber were associated with lower risk of progression of ABL (HR = 0.86 per serving, 95% CI = 0.78-0.95), PPD (HR = 0.95, 95% CI = 0.91-0.99), and tooth loss (HR = 0.88, 95% CI = 0.78-0.99). No significant associations were seen in men younger than 65. CONCLUSION: Benefits of higher intake of high-fiber foods, especially fruits, on slowing periodontal disease progression are most evident in men aged 65 and older. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.",
"title": "High-fiber foods reduce periodontal disease progression in men aged 65 and older: the Veterans Affairs normative aging study/Dental Longitudinal St..."
},
{
"docid": "MED-4901",
"text": "The present study was designed to evaluate the possible effect of the consumption of blackberry juices (BJ) prepared with water (BJW) and defatted milk (BJM) on the plasma antioxidant capacity and the enzymatic and nonenzymatic antioxidants. A significant (p < 0.05) increase in the ascorbic acid content in the plasma was observed after intake of both BJs. However, no changes were observed in the plasma urate and alpha-tocopherol levels. An increase on the plasma antioxidant capacity, by ORAC assay, was observed only after consumption of BJW but not statistically significant. Plasma antioxidant capacity had a good positive correlation with ascorbic acid (r = 0.93) and a negative correlation with urate level (r = -0.79). No correlation was observed between antioxidant capacity and total cyanidin or total ellagic acid contents. Further, it was observed that plasma catalase increased following intake of BJ's. No change was observed on the plasma and erythrocyte CAT and glutathione peroxidase activities. A significant decrease (p < 0.05) in the urinary antioxidant capacity between 1 and 4 h after intake of both BJs was observed. A good correlation was observed between total antioxidant capacity and urate and total cyanidin levels. These results suggested association between anthocyanin levels and CAT and a good correlation between antioxidant capacity and ascorbic acid in the human plasma after intake of BJs. Follow-up studies investigating the antioxidant properties and health benefits are necessary to demonstrate the health benefits of polyphenols.",
"title": "Antioxidant status in humans after consumption of blackberry (Rubus fruticosus L.) juices with and without defatted milk."
},
{
"docid": "MED-3108",
"text": "The external surfaces of the body, such as the skin and the gastrointestinal mucosal membrane, are an important line of defence preventing the invasion of microorganisms and their products. Mucosal immune cells, especially intraepithelial lymphocytes, are involved in maintaining the integrity of these epithelial barriers. They contribute towards the tolerance to commensal organisms, which occupy these same sites, and to the immune responses against harmful organisms and their products. The composition of the microbiota is influenced by immune cells as well as external environmental factors, especially the use of antibiotics and diet. There is an increasing appreciation that the microbiota affects systemic immune responses in addition to local immunity. Failure to control the occupancy by microorganisms may result in the disruption of the delicate homeostasis between beneficial and harmful microorganisms and contribute to inflammatory pathologies. This review will discuss some of our current understanding of the impact of immune cells and diet on the microbiota.",
"title": "Epithelial barrier biology: good fences make good neighbours"
},
{
"docid": "MED-1786",
"text": "Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.",
"title": "Good semen quality and life expectancy: a cohort study of 43,277 men."
},
{
"docid": "MED-2009",
"text": "Chickpea (Cicer arietinum L.) is an important pulse crop grown and consumed all over the world, especially in the Afro-Asian countries. It is a good source of carbohydrates and protein, and protein quality is considered to be better than other pulses. Chickpea has significant amounts of all the essential amino acids except sulphur-containing amino acids, which can be complemented by adding cereals to the daily diet. Starch is the major storage carbohydrate followed by dietary fibre, oligosaccharides and simple sugars such as glucose and sucrose. Although lipids are present in low amounts, chickpea is rich in nutritionally important unsaturated fatty acids such as linoleic and oleic acids. β-Sitosterol, campesterol and stigmasterol are important sterols present in chickpea oil. Ca, Mg, P and, especially, K are also present in chickpea seeds. Chickpea is a good source of important vitamins such as riboflavin, niacin, thiamin, folate and the vitamin A precursor β-carotene. As with other pulses, chickpea seeds also contain anti-nutritional factors which can be reduced or eliminated by different cooking techniques. Chickpea has several potential health benefits, and, in combination with other pulses and cereals, it could have beneficial effects on some of the important human diseases such as CVD, type 2 diabetes, digestive diseases and some cancers. Overall, chickpea is an important pulse crop with a diverse array of potential nutritional and health benefits.",
"title": "Nutritional quality and health benefits of chickpea (Cicer arietinum L.): a review."
},
{
"docid": "MED-1352",
"text": "Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted.",
"title": "Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good"
},
{
"docid": "MED-2762",
"text": "BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of s of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.",
"title": "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. ..."
},
{
"docid": "MED-5012",
"text": "This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.",
"title": "The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol."
},
{
"docid": "MED-4529",
"text": "Context Lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be present due to the practice of rasa shastra (combining herbs with metals, minerals, and gems). Whether toxic metals are present in both US- and Indian-manufactured Ayurvedic medicines is unknown. Objectives To determine the prevalence of Ayurvedic medicines available via the Internet containing detectable lead, mercury, or arsenic and to compare the prevalence of toxic metals in US- vs Indian-manufactured medicines and between rasa shastra and non–rasa shastra medicines. Design A search using 5 Internet search engines and the search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda, indicated for oral use, and available for sale. From 673 identified products, 230 Ayurvedic medicines were randomly selected for purchase in August–October 2005. Country of manufacturer/Web site supplier, rasa shastra status, and claims of Good Manufacturing Practices were recorded. Metal concentrations were measured using x-ray fluorescence spectroscopy. Main Outcome Measures Prevalence of medicines with detectable toxic metals in the entire sample and stratified by country of manufacture and rasa shastra status. Results One hundred ninety-three of the 230 requested medicines were received and analyzed. The prevalence of metal-containing products was 20.7% (95% confidence interval [CI], 15.2%–27.1%). The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%–30.4%) compared with 19.5% (95% CI, 11.3%–30.1%) in Indian products (P=.86). Rasa shastra compared with non–rasa shastra medicines had a greater prevalence of metals (40.6% vs 17.1%; P=.007) and higher median concentrations of lead (11.5 μg/g vs 7.0 μg/g; P=.03) and mercury (20 800 μg/g vs 34.5 μg/g; P=.04). Among the metal-containing products, 95% were sold by US Web sites and 75% claimed Good Manufacturing Practices. All metal-containing products exceeded 1 or more standards for acceptable daily intake of toxic metals. Conclusion One-fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain detectable lead, mercury, or arsenic.",
"title": "Lead, Mercury, and Arsenic in US- and Indian-Manufactured Ayurvedic Medicines Sold via the Internet"
},
{
"docid": "MED-4782",
"text": "A survey of a broad range of chocolate- and cocoa-containing products marketed in the United States was conducted to provide a more detailed analysis of flavan-3-ol monomers, oligomers, and polymers, which can be grouped into a class of compounds called procyanidins. Samples consisted of the three or four top-selling products within the following six categories: natural cocoa powder, unsweetened baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and chocolate syrup. Composite samples were characterized for percent fat (% fat), percent nonfat cocoa solids (% NFCS), antioxidant level by ORAC, total polyphenols, epicatechin, catechin, total monomers, and flavan-3-ol oligomers and polymers (procyanidins). On a gram weight basis epicatechin and catechin content of the products follow in decreasing order: cocoa powder > baking chocolate > dark chocolate = baking chips > milk chocolate > chocolate syrup. Analysis of the monomer and oligomer profiles within product categories shows there are two types of profiles: (1) products that have high monomers with decreasing levels of oligomers and (2) products in which the level of dimers is equal to or greater than the monomers. Results show a strong correlation (R(2) = 0.834) of epicatechin to the level of % NFCS and also very good correlations for N = 2-5 oligomers to % NFCS. A weaker correlation was observed for catechin to % NFCS (R(2) = 0.680). Other analyses show a similar high degree of correlation with epicatechin and N = 2-5 oligomers to total polyphenols, with catechin being less well correlated to total polyphenols. A lesser but still good correlation exists between the calculated percent cacao (calcd % cacao) content, a proxy for percent cacao, and these same flavanol measures, with catechin again showing a lesser degree of correlation to calcd % cacao. Principal component analysis (PCA) shows that the products group discretely into five classes: (1) cocoa powder, (2) baking chocolate, (3) dark chocolate and semisweet chips, (4) milk chocolates, and (5) syrup. PCA also shows that most factors group closely together including the antioxidant activity, total polyphenols, and the flavan-3-ol measures with the exception of catechin and % fat in the product, which group separately. Because catechin distribution appears to be different from the other flavan-3-ol measures, an analysis of the epicatechin to catechin ratio was done, indicating there is a >5-fold variation in this measure across the products studied. The cocoa-containing products tested range from cocoa powder with 227.34 +/- 17.23 mg of procyanidins per serving to 25.75 +/- 9.91 mg of procyanidins per serving for chocolate syrup. These results are discussed with respect to other studies on commercial products, the bioavailability of the flavanols, and the possible role of processing on the amount of catechin in products.",
"title": "Survey of commercially available chocolate- and cocoa-containing products in the United States. 2. Comparison of flavan-3-ol content with nonfat co..."
},
{
"docid": "MED-2298",
"text": "Exercise is a fundamental component of good health. The American College of Sports Medicine and \"Exercise is Medicine\" recommend treating exercise as a vital sign, and assessing and prescribing physical activity at every medical visit. Meeting the recommended goals of physical activity results in a significant reduction in all-cause mortality. Physicians can improve health by prescribing exercise. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "A guide to exercise prescription."
},
{
"docid": "MED-4600",
"text": "Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.",
"title": "Essentials of Healthy Eating: A Guide"
},
{
"docid": "MED-1961",
"text": "Dioxins and related compounds are undesirable and unintended contaminants in the food supply, and dietary intake is the major route of exposure. Reducing dietary exposure to dioxins among the most vulnerable segments of the population (i.e., pregnant women, infants, and young girls) is an effective strategy for reducing body burdens in future generations. Exposure to dioxins through foods can be minimized by selecting lower-fat versions of meats, poultry, and dairy products. Consuming all foods, including fatty fish, in recommended amounts is congruent with the goal of reducing dioxin intake exposure and maintaining good health.",
"title": "Reducing exposure to dioxins and related compounds through foods in the next generation."
},
{
"docid": "MED-3386",
"text": "Common complications of thoracic radiotherapy include esophagitis and radiation pneumonitis. However, it is important to be aware of uncommon post-radiotherapy complications such as bronchiolitis obliterans organizing pneumonia (BOOP). We report on two patients with carcinoma of the breast who developed an interstitial lung disease consistent with BOOP. BOOP responds to treatment with corticosteroids and the prognosis is generally good despite of the need for long-term administration of corticosteroids as relapses can occur during tapering of steroids. This report provides guidelines for the evaluation and treatment of patients with pulmonary infiltrates after radiotherapy.",
"title": "Bronchiolitis obliterans organizing pneumonia (BOOP) after thoracic radiotherapy for breast carcinoma"
},
{
"docid": "MED-1173",
"text": "We designed a questionnaire concerned with attitudes and behaviour towards organic foods, environmentally friendly behaviour (EFB), and perceived consequences of organic food choice in terms of human health, the environment and animal welfare. It was mailed in 1998 to a random nation-wide sample of 2000 Swedish citizens, ages 18-65 years, and 1154 (58%) responded. Self-reported purchase of organic foods was most strongly related to perceived benefit for human health. Performance of EFBs such as refraining from car driving was also a good predictor of purchase frequency. The results indicate that egoistic motives are better predictors of the purchase of organic foods than are altruistic motives.",
"title": "Choice of organic foods is related to perceived consequences for human health and to environmentally friendly behaviour."
},
{
"docid": "MED-4226",
"text": "Bone, as well as liver and lung, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers and the consequences are always devastating. Like other metastasis, breast cancer bone metastasis consists of several steps from the escape of primary site to the colonization in target site. This review focuses on several key steps including: 1. Invasion and escape from primary tumor site. 2. Target migration toward bone. 3. Specific adhesion and arrest in bone. 4. Establishment of metastasis in bone. The factors involved in this process will provide good targets for therapy. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.",
"title": "Mechanisms of breast cancer bone metastasis."
},
{
"docid": "MED-1366",
"text": "My concern about diet as a public health problem began in the early 1950s in Naples, where we observed very low incidences of coronary heart disease associated with what we later came to call the \"good Mediterranean diet.\" The heart of this diet is mainly vegetarian, and differs from American and northern European diets in that it is much lower in meat and dairy products and uses fruit for dessert. These observations led to our subsequent research in the Seven Countries Study, in which we demonstrated that saturated fat is the major dietary villain. Today, the healthy Mediterranean diet is changing and coronary heart disease is no longer confined to medical textbooks. Our challenge is to persuade children to tell their parents to eat as Mediterraneans do.",
"title": "Mediterranean diet and public health: personal reflections."
},
{
"docid": "MED-3846",
"text": "A HPLC method was developed for the analysis of secoisolariciresinol diglucoside (SDG) and hydroxycinnamic acid glucosides in milled defatted flaxseed flour. Direct extraction by 1 M NaOH for 1 h at 20 degrees C resulted in a higher yield than that obtained by hydrolysis of alcoholic extracts. An internal standard, o-coumaric acid, was used and the method was found to be easy, fast, and with good repeatability. On dry matter basis, different samples of flaxseeds varied considerably in their content of (+)-SDG (11.9-25.9 mg/g), (-)-SDG (2.2-5.0 mg/g), p-coumaric acid glucoside (1.2-8.5 mg/g), and ferulic acid glucoside (1.6-5.0 mg/g).",
"title": "High-performance liquid chromatographic analysis of secoisolariciresinol diglucoside and hydroxycinnamic acid glucosides in flaxseed by alkaline ex..."
},
{
"docid": "MED-4113",
"text": "Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary for the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus.",
"title": "Good riddance: Thymocyte clonal deletion prevents autoimmunity."
},
{
"docid": "MED-1709",
"text": "In the preceding point narrative, Drs. Bray and Popkin provide their opinion and review data that suggest to them that we need to reconsider the consumption of dietary sugar based on the growing concern of obesity and type 2 diabetes. In the counterpoint narrative below, we argue that there is no clear or convincing evidence that any dietary or added sugar has a unique or detrimental impact relative to any other source of calories on the development of obesity or diabetes. Sugar is purely a highly palatable source of energy; because it has no other property that appears to contribute to our nutritional well-being, it is not an essential food for most of us. For those who wish to reduce energy consumption, ingesting less sugar is a good place to start. However, doing so does not automatically portend any clinical benefit.",
"title": "Dietary sugar and body weight: have we reached a crisis in the epidemic of obesity and diabetes?: we have, but the pox on sugar is overwrought and ..."
},
{
"docid": "MED-2790",
"text": "Vasa (Adhatoda vasica Linn.) is a well known and easily available drug in almost all the seasons. Easy availability of any drug gains popularity among physicians as well as pharmaceuticals and this is the reason why almost every Kalpana of Vasa is found described in the Ayurvedika text. The different dosage forms of Vasa like Kvatha, Avaleha, Sneha, and Sandhana have been used for the treatment of Shwasa Roga. A number of research studies have been performed on different formulations of Vasa and its effect on Shwasa Roga. Therefore, a review study has been carried out on the Vasa extract, Vasa Avaleha (prepared from Svarasa and Kvatha), Vasa Ghrita, Vasarishta, and Vasakasava on Shwasa Roga, to know which formulation is better. It was found in the review that Vasa Ghana, Vasa Ghrita (1), and Vasa Avaleha have shown good results on Tamaka Shwasa.",
"title": "A clinical review of different formulations of Vasa (Adhatoda vasica) on Tamaka Shwasa (asthma)"
},
{
"docid": "MED-3518",
"text": "Compared with other industrialized countries, the lower incidence of chronic-degenerative disorders in Mediterranean populations has been emphasized in recent decades. The health-promoting effects arising from Mediterranean dietary habits have been attributed to the large intake of plant foodstuffs rich in bioactive phytochemicals, such as melatonin. Recently, it has been suggested that melatonin present in edible plants may improve human health, by virtue of its biological activities and its good bioavailability. Plant melatonin, besides contributing to optimize the physiological functions regulated, in humans, by endogenous melatonin, may be involved in nutritional therapy to reduce the risk of cancer, cardiovascular and neurodegenerative diseases in western populations. In this view, the presence of melatonin in some Mediterranean foods and beverages adds a new element to the hypothesis of health benefits associated to Mediterranean dietary patterns, although the available data are still preliminary and incomplete.",
"title": "Melatonin in traditional Mediterranean diets."
},
{
"docid": "MED-3728",
"text": "On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.",
"title": "Strawberry fields forever?"
},
{
"docid": "MED-3768",
"text": "In this paper, the negative and the positive effects of alcohol on health are reviewed. It is first of all established facts that a high alcohol intake implies an increased risk of a large number of health outcomes, such as dementia, breast cancer, colorectal cancer, cirrhosis, upper digestive tract cancer and alcohol dependency. Second, it is justified that alcohol has beneficial effects for some individuals, especially with regard to prevention of thrombosis of the heart. The public health relevance of these results is considered. The sensible drinking limits, used in both the UK and Denmark, of a maximum of 21 drinks per week for men and 14 drinks per week for women seem valid. A broader public health message of the beneficial effects of alcohol does not seem to be of interest in Western societies, where only a very small fraction of the population are non drinkers and may have very good reasons therefore.",
"title": "The positive and negative health effects of alcohol- and the public health implications."
}
] |
5abed3565542993fe9a41d4f
|
Which Actress appears in the News Room And The Chaos Theory
|
[
{
"docid": "36405394",
"text": "\"We Just Decided To\" is the first episode of the first season of the American television series \"The Newsroom\". It first aired on June 24, 2012 in the United States on HBO. \"We Just Decided To\" was written by creator Aaron Sorkin and directed by Greg Mottola. In the aftermath of his public tirade, acclaimed Atlantis Cable News anchor Will McAvoy (Jeff Daniels) returns to his job to find that most of his staff are leaving and his new executive producer is his ex-girlfriend, MacKenzie McHale (Emily Mortimer) and when some breaking news about a potentially disastrous oil spill in the Gulf of Mexico hits the network, the staff faces a new challenge.",
"title": ""
},
{
"docid": "869862",
"text": "Emily Kathleen Anne Mortimer (born 1 December 1971) is an English actress and screenwriter. She began acting in stage productions, and has since appeared in several film and television roles. In 2003, she won an Independent Spirit Award for her performance in \"Lovely and Amazing\". She is also known for playing roles in \"Match Point\" (2005), \"Lars and the Real Girl\" (2007), \"Chaos Theory\" (2008), \"Harry Brown\" (2009), \"Shutter Island\" (2010), \"Hugo\" (2011), and the HBO series \"The Newsroom\".",
"title": ""
}
] |
[
{
"docid": "42290401",
"text": "Chaos Theory: Part 1 is the second studio album from New Zealand hard rock band Like A Storm. Written and recorded while the band was on a nationwide American tour, early pre-sales of the album began in November, 2012. Most recently, \"Chaos Theory: Part 1\" was released in New Zealand, through Warner Music.",
"title": ""
},
{
"docid": "6670070",
"text": "In organizational development, chaos theory is a subset of more general chaos theory that incorporates principles of quantum mechanics and presents them in a complex systems environment. To the observer the systems seem to be in chaos. Organizational Development of a business system is the management of that apparent chaos. The term “Managing Organized Chaos” is used in the book by the same name Managing Organized Chaos – Business Planning 1.0, to describe the daily management of an entity (business) engaged in continual activity.",
"title": ""
},
{
"docid": "7458308",
"text": "Chaos: Making a New Science is a debut non-fiction book by James Gleick that initially introduced the principles and early development of the chaos theory to the public. It was a finalist for the National Book Award and the Pulitzer Prize in 1987, and was shortlisted for the Science Book Prize in 1989. The book was published on October 29, 1987 by Viking Books.",
"title": ""
},
{
"docid": "51838760",
"text": "In mathematics, a chaos machine is a class of algorithms constructed on the base of chaos theory (mainly deterministic chaos) to produce pseudo-random oracle. It represents the idea of creating a universal scheme with modular design and customizable parameters, which can be applied wherever randomness and sensitiveness is needed.",
"title": ""
},
{
"docid": "47930292",
"text": "Tom X. Chao is a comedic playwright, actor, and musician based in New York City whose works have been produced in the United States and Canada. Chao regularly stars in his own work, usually playing an unflattering autobiographical character named \"Tom.\" During the 1990s, Chao was a member of New York City's Art Stars alternative performance scene, and \"The New York Times\" called him \"a dryly funny downtown comedian,\" and \"Time Out New York\" labeled him a \"hilariously angsty writer-performer.\" He is best known for his play \"Cats Can See the Devil\", which appears in \"Plays and Playwrights 2004\".",
"title": ""
},
{
"docid": "254965",
"text": "Rosalind Chia-Ling Chao ( ; ; born () ) is an American actress. Chao's best-known roles have been as a star of CBS's \"AfterMASH\" portraying South Korean refugee Soon-Lee Klinger for both seasons, and the recurring character Keiko O'Brien with twenty-seven appearances on the syndicated science fiction series \"\" and \"\".",
"title": ""
},
{
"docid": "10218184",
"text": "Chaos communications is an application of chaos theory which is aimed to provide security in the transmission of information performed through telecommunications technologies. By secure communications, one has to understand that the contents of the message transmitted are inaccessible to possible eavesdroppers.",
"title": ""
},
{
"docid": "3997866",
"text": "Chaos theory is a scientific theory describing erratic behavior in certain nonlinear dynamical systems.",
"title": ""
},
{
"docid": "313779",
"text": "Quantum chaos is a branch of physics which studies how chaotic classical dynamical systems can be described in terms of quantum theory. The primary question that quantum chaos seeks to answer is: \"What is the relationship between quantum mechanics and classical chaos?\" The correspondence principle states that classical mechanics is the classical limit of quantum mechanics. If this is true, then there must be quantum mechanisms underlying classical chaos (although this may not be a fruitful way of examining classical chaos). If quantum mechanics does not demonstrate an exponential sensitivity to initial conditions, how can exponential sensitivity to initial conditions arise in classical chaos, which must be the correspondence principle limit of quantum mechanics? In seeking to address the basic question of quantum chaos, several approaches have been employed:",
"title": ""
},
{
"docid": "30626354",
"text": "Ariane Labed (born 8 May 1984) is a Greek-born French actress. She made her feature film debut in \"Attenberg\" (2010), for which she won the Volpi Cup for Best Actress. Later, she appeared in \"Alps\" (2011) and \"Before Midnight\" (2013). In 2014, she starred in several short films such as \"High and Dry\" and played the leading role of Alice in the film \"Fidelio, Alice's Odyssey\", for which she was nominated the César Award for Most Promising Actress. In 2015, she appeared in \"The Forbidden Room\" and in \"The Lobster\".",
"title": ""
},
{
"docid": "16288585",
"text": "\"Slave New World\" is Sepultura's fifth official single, and the final of three to be taken from the album \"Chaos A.D.\", released in 1994. The lyrics were co-written by Evan Seinfeld from Sepultura's Roadrunner label-mates Biohazard. Like most of the band's singles, the song is one of the band's best-known songs and remains a concert staple to this day. A music video was filmed for the single which features the band playing on what appears to be a volcano, intercut with footage of severe human conditioning, including branding people with barcodes. This video can be found on the VHS \"Third World Chaos\", which was later released on DVD as part of \"Chaos DVD\". The title of the song is a wordplay of Aldous Huxley's 1932 dystopian novel \"Brave New World.\"",
"title": ""
},
{
"docid": "22168509",
"text": "Does God Play Dice: The New Mathematics of Chaos is a non-fiction book about chaos theory written by British mathematician Ian Stewart. The book was initially published by Blackwell Publishing in 1989.",
"title": ""
},
{
"docid": "33034198",
"text": "Miguel Angel Fernández Sanjuán (Miguel A. F. Sanjuán) is a Spanish Theoretical Physicist from Leon, Spain. He is known for his contributions in nonlinear dynamics, chaos theory, and control of chaos, and has published several scientific papers and popular news articles. He has supervised around 20 PhD students in Nonlinear Dynamics, Chaos and Complex Systems.",
"title": ""
},
{
"docid": "34697887",
"text": "Canonical Theory (also named the \"canonical form\") is a molecular theory developed by Joel E. Keizer and coworkers which claims to explain many physical, chemical, and biological processes in an unified and canonical way. Ronald F. Fox and Keizer showed the application of the canonical theory to chaos.",
"title": ""
},
{
"docid": "4009387",
"text": "Cyndi Lou Williams is a voice actress and script writer. She has mainly appeared in anime series by ADV Films. She was nominated for an Independent Spirit Award for Best Lead Actress for her performance in Kyle Henry's film, \"Room (2005)\", which was nominated for the Cassavetes Award.",
"title": ""
},
{
"docid": "9004262",
"text": "Isabelle Stengers ( ; ] ; born 1949) is a Belgian philosopher, noted for her work in the philosophy of science. She has written books on Chaos Theory with Ilya Prigogine, the Russian-Belgian physical chemist and Nobel Laureate noted for his work on dissipative structures, complex systems, and irreversibility, especially \"Order out of Chaos\" and \"The End of Certainty: Time, Chaos and the New Laws of Nature\". Stengers and Prigogine often draw from the work of Deleuze, treating him as an important philosophical source to think through questions regarding irreversibility and the universe as an open system. Stengers' most recent work has turned to her proposition of Cosmopolitics, a key aspect of which Bruno Latour refers to as the \"progressive composition of a common world\" in which the non-human and the human are intimately entwined, and secondly, her revisiting and pragmatic modulation of the speculative philosophy of Alfred North Whitehead.",
"title": ""
},
{
"docid": "53170049",
"text": "'Chaos Theory is a computer demo by Conspiracy released in August 2006 at Assembly. It has been realised by Gergely Szelei, Barna Buza and Zoltan Szabo.",
"title": ""
},
{
"docid": "2857411",
"text": "Norman Harry Packard (born 1954 in Billings, Montana) is a chaos theory physicist and one of the founders of the Prediction Company and ProtoLife. He is an alumnus of Reed College and the University of California, Santa Cruz . Packard is known for his contributions to both chaos theory and cellular automata. He also coined the phrase \"the edge of chaos\".",
"title": ""
},
{
"docid": "40159314",
"text": "In physics, relativistic chaos is the application of chaos theory to dynamical systems described primarily by general relativity, and also special relativity.",
"title": ""
},
{
"docid": "21590151",
"text": "Lawrence Paul Horwitz (born October 14, 1930) is an American/Israeli physicist and mathematician who has made contributions in particle physics, statistical mechanics, mathematical physics, theory of unstable systems, classical chaos and quantum chaos, relativistic quantum mechanics, quantum field theory, general relativity, representations of quantum theory on hypercomplex Hilbert modules, group theory and functional analysis and stochastic theories of irreversible quantum evolution.",
"title": ""
},
{
"docid": "44165401",
"text": "Marie Denarnaud (born 1978) is a French actress. She has appeared in numerous films including \"Chaos\" (2001), \"Eager Bodies\" (2003), \"The Adopted\" (2011) and \"Une histoire banale\" (2014). She has also participated in the made-for-television film \"Nuit noire, 17 octobre 1961\" (2005) which chronicled the events of the Paris massacre of 1961.",
"title": ""
},
{
"docid": "1589732",
"text": "The Chaos Theory is the debut extended play of American rapper Jumpsteady. It was advertised in the booklet of Tunnel of Love and was originally scheduled for a 1997 release, but was delayed several years. It was eventually released on July 23, 2002, it did not chart.",
"title": ""
},
{
"docid": "6295",
"text": "Chaos theory is a branch of mathematics focused on the behavior of dynamical systems that are highly sensitive to initial conditions. 'Chaos' is an interdisciplinary theory stating that within the apparent randomness of chaotic complex systems, there are underlying patterns, constant feedback loops, repetition, self-similarity, fractals, self-organization, and reliance on programming at the initial point known as \"sensitive dependence on initial conditions\". The butterfly effect describes how a small change in one state of a deterministic nonlinear system can result in large differences in a later state, e.g. a butterfly flapping its wings in Brazil can cause a tornado in Texas.",
"title": ""
},
{
"docid": "11591129",
"text": "Carrie Finlay (born 19 September 1986) is a Canadian actress. She began her professional career as an actress, first appearing as a voice actress in the Canadian-US animated television series The Kids from Room 402 in 2000. She has had several live-action roles, appearing in \"The Worst Witch\", \"Gambling and Addiction\", \"The Gazette\", \"The Reagans\", \"The Score\" and \"Timeline\". She has also appeared onstage in several productions.",
"title": ""
},
{
"docid": "3997782",
"text": "Chaos Theory is a 2008 comedy-drama film starring Ryan Reynolds, Emily Mortimer, and Stuart Townsend. The film was directed by Marcos Siega, written by Daniel Taplitz and Kathy Gori, and was shot in Vancouver, British Columbia, Canada.",
"title": ""
},
{
"docid": "42623157",
"text": "Ying-Cheng Lai is a Chinese theoretical physicist who works in the area of chaos theory. He is one among the pioneers in the nonlinear and complex systems and chaos theory. Currently he works in Arizona State University holding an ISS Chair Professorship.",
"title": ""
},
{
"docid": "228484",
"text": "Chaos magic, also spelled chaos magick, is a contemporary magical practice which emphasizes the pragmatic use of belief systems and the creation of new and unorthodox methods.",
"title": ""
},
{
"docid": "13029212",
"text": "Kaiyuan Za Bao, or Kaiyuan Chao Bao, Bulletin of the Court, was an official publication which first appeared in the 8th century, during the Kaiyuan era. It has been described as the first Chinese newspaper or official gazette, and also as the world's first magazine. Its main subscribers were imperial officials. Every day the political news and domestic news were collected by the editors, and the writers transcribed it to send to the provinces. It was hand printed on silk, and appeared between 713 and 734.",
"title": ""
},
{
"docid": "3977589",
"text": "In chaos theory, the correlation sum is the estimator of the correlation integral, which reflects the mean probability that the states at two different times are close:",
"title": ""
},
{
"docid": "40721426",
"text": "Celso Grebogi (born 1947) is a Brazilian theoretical physicist who works in the area of chaos theory. He is one among the pioneers in the nonlinear and complex systems and chaos theory. Currently he works at the University of Aberdeen as the \"Sixth Century Chair in Nonlinear and Complex Systems\". He has done extensive research in the field of plasma physics before his work on the theory of dynamical systems. He and his colleagues (Edward Ott and James A. Yorke) have shown with a numerical example that one can convert a chaotic attractor to any one of a large number of possible attracting time-periodic motions by making only small time-dependent perturbations of an available system parameter. This article is considered as one among the classic works in the control theory of chaos and their control method is known as the famous O.G.Y. method.",
"title": ""
}
] |
7542
|
How can OTC scams affect you?
|
[
{
"docid": "68187",
"text": "\"Am I being absurd? No. Should I be worrying? Yes. If I sell in the morning, I've only lost a couple hundred dollars, and learned a valuable lesson. Is there any reason to believe it won't be that simple? If you're lucky, you'll be able to dump your stocks to someone like you who'll be punching himself in the face tomorrow night. If not - you're stuck. You may end up selling them to your broker as worthless. You might have become a victim of a \"\"pump and dump\"\" fraud. Those are hard to identify in real-time, but after been burned like that myself (for much lesser amounts than you though), I avoid any \"\"penny\"\" stocks that go up for no apparent (and verifiable) reason. In fact, I avoid them altogether.\"",
"title": ""
}
] |
[
{
"docid": "416941",
"text": "Merrill charges $500 flat fee to (I assume purchase) my untraded or worthless security. In my case, it's an OTC stock whose management used for a microcap scam, which resulted in a class action lawsuit, etc. but the company is still listed on OTC and I'm stuck with 1000s of shares. (No idea about the court decision)",
"title": ""
},
{
"docid": "271116",
"text": "Absolute scam. Any time anyone asks you to open a bank account so they can send you money and then you have to send some portion of it back to them, it's a guarantee that it's a scam. What happens is that your dad will deposit the check and transfer it to this woman, then the check will bounce (or turn out to be fake altogether) and your dad will be on the hook for the money to the bank. These schemes are dependent on the fact that people want hope and believe in quick, easy money, and it works as long as the con artists are able to get the 'mark' (the person who deposits the check and sends them the money) to send the money before the check (always drawn on some obscure foreign bank) has a chance to clear. This is another variation of a long-running type of bank scam, and if you get involved, you'll regret it. I hope you can keep your dad from getting involved, because it will create a financial mess and affect his credit as well. The basic premise of this scam is this: In the interests of providing good customer service, most banks will make some or all of a deposit available right away, even though the check hasn't cleared. The scammer has you withdraw the money (either a cashier's check, have you send a wire transfer, etc) immediately and send it to them. Eventually the check is returned because it is The bank charges the check back against your account, often imposing pretty substantial penalties and fees, so you as the account holder are left without the money you sent the scammer and all of the fees. This is the easy version of events. You could end up in legal trouble, depending on the nature of the scam and what they determine your involvement to be. It will certainly badly affect your banking history (ChexSystems tracks how we all treat bank accounts, much like the credit agencies do with our credit), so you may have trouble opening bank accounts. So there are many consequences to this to think about, and it's why you JUST SAY NO!! Don't walk away from this -- RUN!!!",
"title": ""
},
{
"docid": "390779",
"text": "\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \"\"Get Rich on Penny Stock\"\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\"",
"title": ""
},
{
"docid": "421688",
"text": "It's not enough just to check if your order doesn't exceed 10% of the 20 day average volume. I'll quote from my last answer about NSCC illiquid charges: You may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. The NSCC issues a charge to the clearing firm if in aggregate, their orders exceed the limits, and the clearing firm usually passes these charges on to the broker(s) that placed the orders. Your broker may or may not pass the charges through to you; they may simply charge you significantly higher commissions for trading OTC securities and use those to cover the charges. Since checking how the volume of your orders compares to the average past volume, ask your broker about their policies on trading OTC stocks. They may tell you that you won't face illiquid charges because the higher cost of commissions covers these, or they may give you specifics on how to verify that your orders won't incur such charges. Only your broker can answer this with certainty.",
"title": ""
},
{
"docid": "346407",
"text": "\"This is colloquially referred to as a \"\"pump and dump\"\" scheme. You basically buy up some stock, and then try to pump up the demand through false and misleading positive statements and market activity. You then close your position once market interest is sufficiently high. If your firm has access to high frequency trading mechanisms, you may even be able to front run other market participants attracted by your buying activities. >I am wondering what is the best route to go down. Definitely micro-cap stocks. Things listed on the OTC markets, especially penny stocks, have this tendency to attract retail buyers just begging to be scammed. Emerging biotech firms also have a lot of potential due to investors' hopes of successful clinical trials. I should warn you though, this is very illegal and falls under market manipulation [according to the SEC](https://www.sec.gov/fast-answers/answerspumpdumphtm.html) and can lead to up to 25 years in prison. So make sure you stay small enough to avoid the regulatory radar. (But seriously, this belongs in r/personalfinance or elsewhere, r/finance isn't the sub you want).\"",
"title": ""
},
{
"docid": "528576",
"text": "I am in complete agreement with you. The place i have found with the sort of charts you are looking for is stockcharts.com. To compare the percentage increase of several stocks over a period of 2 market-open days or more, which is quite useful to follow the changes in various stocks… etc., an example: Here the tickers are AA to EEEEE (OTC) and $GOLD / $SILVER for the spot gold / silver price (that isn't really a ticker). It is set to show the last 6 market days (one week+)...the '6' in '6&O'. You can change it in the URL above or change it on the site for the stocks you want... up to 25 in one chart but it gets really hard to tell them apart! By moving the slider just left of the ‘6’ at the bottom right corner of the chart, you can look at 2 days or more. For a specific time period in days, highlight the ‘6’ and type any number of market-open days you want (21 days = about one month, etc.). By setting a time period in days, and moving the entire slider, you can see how your stocks did in the last bull/bear run, as an example. The site has a full how-to, for this and the other types of charts they offer. The only problem is that many OTC stocks are not charted. Save the comparison charts you use regularly in a folder in your browser bookmarks. Blessings. I see the entire needed link isn't in blue... but you need it all.",
"title": ""
},
{
"docid": "63848",
"text": "The only way for a mutual fund to default is if it inflated the NAV. I.e.: it reports that its investments worth more than they really are. Then, in case of a run on the fund, it may end up defaulting since it won't have the money to redeem shares at the NAV it published. When does it happen? When the fund is mismanaged or is a scam. This happened, for example, to the fund Madoff was managing. This is generally a sign of a Ponzi scheme or embezzlement. How can you ensure the funds you invest in are not affected by this? You'll have to read the fund reports, check the independent auditors' reports and check for clues. Generally, this is the job of the SEC - that's what they do as regulators. But for smaller funds, and private (i.e.: not public) investment companies, SEC may not be posing too much regulations.",
"title": ""
},
{
"docid": "545752",
"text": "If your concern is scams, we should be talking about counterparties, not bitcoin itself. Unless you think the protocol itself is a scam, which imo it most certainly is not. You're conflating the trustworthiness of counterparties with the trustworthiness of the underlying protocol, which imo is not a very good model to operate by. You'll understand the situation better of you look at them independently. Bitcoin isn't trying to be a credit agency or the better business bureau, it's just trying to be digital money. Don't expect it to protect you from scams any more than cash will. That's not its job, and does not affect its trustworthiness as money.",
"title": ""
},
{
"docid": "545789",
"text": "\"How can I say this more clearly? SCAM, SCAM, SCAM! This is another one of the oldest scams out there, where you've won a prize or an inheritance has come in, and all you have to do is pay the taxes on it to claim it. Don't be a sucker! Ask yourself why the government couldn't (and wouldn't) just take the taxes due out of the funds they have and give the rest to the person they belong to? Wouldn't that be the smartest and easiest thing to do? As an example, let's say that you have $1,000 that belongs to me, and I owe you $100. Would you tell me to pay you the $100 and then you'll give me the $1,000 or would you take the $100 I owe you out of the $1,000 and give me the remaining $900? The fact this is someone you know from the internet and they want your \"\"help\"\" to claim their money should tell you how much of a scam this is. Stop talking to this person, and don't tell them anything personal about you. They are scam artists, and whatever you tell them could be used to steal your identity or take your money. Be careful, my friend!\"",
"title": ""
},
{
"docid": "42347",
"text": "Something to consider is that in the case of the company you chose, on the OTC market, that stock is thinly traded and with such low volume, it can be easy for it to fluctuate greatly to have trades occur. This is why volume can matter for some people when it comes to buying shares. Some OTC stocks may have really low volume and thus may have bigger swings than other stocks that have higher volume.",
"title": ""
},
{
"docid": "339268",
"text": "\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \"\"T\"\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \"\"ANET\"\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \"\"P\"\" to the end for \"\"preferreds\"\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\"",
"title": ""
},
{
"docid": "597519",
"text": "it looks like using an ADR is the way to go here. michelin has an ADR listed OTC as MGDDY. since it is an ADR it is technically a US company that just happens to be a shell company holding only shares of michelin. as such, there should not be any odd tax or currency implications. while it is an OTC stock, it should settle in the US just like any other US OTC. obviously, you are exposing yourself to exchange rate fluctuations, but since michelin derives much of it's income from the US, it should perform similarly to other multinational companies. notes on brokers: most US brokers should be able to sell you OTC stocks using their regular rates (e.g. etrade, tradeking). however, it looks like robinhood.com does not offer this option (yet). in particular, i confirmed directly from tradeking that the 75$ foreign settlement fee does not apply to MGDDY because it is an ADR, and not a (non-ADR) foreign security.",
"title": ""
},
{
"docid": "225030",
"text": "\"It's a scam. The cashier's check will be forged. Craigslist has a warning about it here (item #3). What kind of payment do you think is not fakable? Or at least not likely to be used in scams? When on craigslist - deal only locally and in person. You can ask to see the person's ID if you're being paid by check When being paid by check, how can seeing his/her ID help? In case the check isn't cashable, I can find that person by keeping record of his/her ID? If you're paid by check, the payers details should be printed on the check. By checking the ID you can verify that the details match (name/address), so you can find the payer later. Of course the ID can be faked too, but there's so much you can do to protect yourself. You'll get better protection (including verified escrow service) by selling on eBay. Is being paid by cash the safest way currently, although cash can be faked too, but it is the least common thing that is faked currently? Do you recommend to first deposit the cash into a bank (so that let the bank verify if the cash is faked), before delivering the good? For Craigslist, use cash and meet locally. That rules out most scams as a seller. What payment methods do you think are relatively safe currently? Then getting checks must be the least favorite way of being paid. Do you think cash is better than money order or cashier order? You should only accept cash. If it is a large transaction, you can meet them at your bank, have them get cash, and you receive the cash from the bank. Back to the quoted scam, how will they later manipulate me? Are they interested in my stuffs on moving sale, or in my money? They will probably \"\"accidentally\"\" overpay you and ask for a refund of some portion of the overpayment. In that case you will be out the entire amount that you send back to them and possibly some fees from your bank for cashing a bad check.\"",
"title": ""
},
{
"docid": "346669",
"text": "The OTC market is a marketplace, the location it definitely relied on the purchaser marketplace. The OTC market is mostly used to exchange bonds among the two occasions and all this technique are executed by way of manner of the third celebration. They are able to also be used to alternate equity, such because of the OTC QX and purple marketplaces within the USA. The minamargroup is the Florida, USA situated agency, who elements their purchase investor relation with to present organization into to make new ones. OTC way it's far a protection traded in some context other, changing between parties or groups inclusive of New York Stock trade.",
"title": ""
},
{
"docid": "343518",
"text": "\"This is clearly a scam, and you should stay away from it. Anyone reading this knew that from the title alone - and it seems that you know it too. Don't \"\"test\"\" whether something is a scam by putting your own money in it. That is exactly how these scammers make money, and how you lose it. How their scam works is irrelevant. The simple fact is that there is no way you can safely earn 20% return over the course of a year, let alone in 1 day*. You know this is true. Don't bother trying to figure out what makes it true in this case. There is no free lunch. Best case scenario, this is a hyper-risky investment strategy [on the level of putting your money down at a roulette wheel]. Worst case scenario, they simply steal your money. Either way, you won't come out ahead. Although I agree with others that this is likely a Ponzi scheme, that doesn't really matter. What matters is, there is no way they can guarantee those returns. Just go to a casino and throw your money away yourself, if you want that level of risk. *For reference, if you invested $100 for a year, earning 20% returns every day, you would have 6 million trillion trillion dollars by the end of the year. that's $6,637,026,647,624,450,000,000,000,000,000. that number doesn't even make sense. It's more money than exists on earth. So why would they need your $100?\"",
"title": ""
},
{
"docid": "263659",
"text": "There are several red flags here. can they get my bank account info in any way from me transferring money to them? Probably yes. Almost all bank transactions are auditable, and intentionally cause a money track. This track can be followed from both sides. If they can use your bank account as if they were you, that is a bit deeper than what you are asking, but yes they (and the polish cops) can find you through that transfer. I did look up the company and didn't find any scam or complaints concerning them. Not finding scams or complains is good, but what did you find? Did you find good reviews, the company website, its register, etc, etc? How far back does the website goes (try the wayback machine) Making a cardboard front company is very easy, and if they are into identity theft the company is under some guy in guam that never heard of poland or paypal. As @Andrew said above, it is probably a scam. I'd add that this scam leverages on the how easier is to get a PayPal refund compared to a regular bank transfer. It is almost impossible to get the money back on an international transaction. Usually reverting a bank transfer requires the agreement in writing of the receiver and of both banks. As for paypal, just a dispute from the other user: You are responsible for all Reversals, Chargebacks, fees, fines, penalties and other liability incurred by PayPal, a PayPal User, or a third party caused by your use of the Services and/or arising from your breach of this Agreement. You agree to reimburse PayPal, a User, or a third party for any and all such liability. (source) Also, you might be violating the TOS: Allow your use of the Service to present to PayPal a risk of non-compliance with PayPal’s anti-money laundering, counter terrorist financing and similar regulatory obligations (including, without limitation, where we cannot verify your identity or you fail to complete the steps to lift your sending, receiving or withdrawal limit in accordance with sections 3.3, 4.1 and 6.3 or where you expose PayPal to the risk of any regulatory fines by European, US or other authorities for processing your transactions); (emphasis mine, source) So even if the PayPal transfer is not disputed, how can you be sure you are not laundering money? Are you being paid well enough to assume that risk?",
"title": ""
},
{
"docid": "282196",
"text": "\"In general I don’t think you can blame the news stories. You can blame everyone’s preconceived notion that any sort of LBO or leveraged restructuring is the devil’s work. Every American is of course well-versed in the subject. From the Sealy example, you clearly have a journalist who has no idea what they are talking about. All you have is a cherry-picked summary of what took place. As such, the “finance scholars” jump in and explain how it’s all a giant scam. Bain LBO’d Sealy in 1997. As a part of that, it was saddled with ~$700m in debt. That of course is fodder for the \"\"finance scholars\"\" because they don't understand the benefits of debt and more generally how LBOs work, none of which are noted in the article. The article then notes that Sealy has recently encountered trouble. To the \"\"geniuses\"\" this is of course because of Romney's work and the ~$700m in debt. No one notices the fact that Bain unloaded this in 2004 for double what it paid for it. For those that did, the unloading was a textbook Bain scam. Bain unloaded this to KKR, perhaps the sharpest and most successful PE firm in history. Would KKR put $1.5b into this if it were a scam? According to the \"\"geniuses\"\", of course they would. How could Mitt Romney actually improve a business? No one looks at the fact that revenues were up considerably, margins had expanded tremendously, growth prospects were higher, and FCF yields were fantastic. This is why KKR bought the company, and this is what an LBO is supposed to be. I haven't done a ton of work on this case, it was before my time, but I would be very surprised if the growth wasn't accompanied by employee expansion as well. You also get the “I wish I had a way to just walk away from my debt” comment. I don’t even know where to begin explaining how asinine that is. Equity is subordinated to debt. That’s the definition of equity. The article also notes the one-sided-mattress idea, which is construed as Romney's giant scam to screw the average American while flipping this company and making his millions. The article of course didn't note that this one-sided mattress idea was a mere fraction of revenue. This was designed as an economy mattress, with an advertised shorter shelf life. Plus how can this be a scam? Would you go into the mattress store and pay the same amount for a mattress with only one side? If you would you deserve to get half of a mattress. So the crux of it is, this is in actuality an example of what an LBO should be. At least for Bain’s part. Bain took a business that was ripe for an LBO (reasonable steady FCF, low leverage), did the LBO, improved the business, and came out on top. What KKR did with it afterwords I have no idea. I would imagine it has more to do with deteriorating business conditions than the debt on its balance sheet. I work with restructurings over 100 hours a week. I of course don’t come up with the plans (I’m a lowly analyst building models and associated bitchwork) but I see just how brilliant these ideas are. In a lot of cases restructurings prevent the tripping of covenants and associated bankruptcy and allow for strategy to play out and for companies to grow. I can of course give a more detailed rant on the article, but I figured no one will read this anyway.\"",
"title": ""
},
{
"docid": "593644",
"text": "NSCC illiquid charges are charges that apply to the trading of low-priced over-the counter (OTC) securities with low volumes. Open net buy quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net buy quantity must be less than 5,000,000 shares per stock for your entire firm Basically, you can't hold a long position of more than 5 million shares in an illiquid OTC stock without facing a fee. You'll still be assessed this fee if you accumulate a long position of this size by breaking your purchase up into multiple transactions. Open net sell quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net sell quantity must be less than 10% percent of the 20-day average volume If you attempt to sell a number of shares greater than 10% of the stock's average volume over the last 20 days, you'll also be assessed a fee. The first link I included above is just an example, but it makes the important point: you may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. Technically, these fees are assessed to the clearing firm, not the individual investor, but usually the clearing firm will pass the fees along to the broker (and possibly add other charges as well), and the broker will charge a fee to the individual account(s) that triggered the restriction. Also, remember that when buying OTC/pink sheet stocks, your ability to buy or sell is also contingent on finding someone else to buy from/sell to. If you purchase 10,000 shares one day and attempt to sell them sometime in the future, but there aren't enough buyers to buy all 10,000 from you, you might not be able to complete your order at the desired price, or even at all.",
"title": ""
},
{
"docid": "467352",
"text": "Depends on how you measure liquidity. There's papers out there that approach this very question. Measured in order book spreads for a consolidated $100m trade, I'd say the second biggest market is FX swaps, followed or par'd by the money market (government bonds). If you disallow OTC venues, it's most definitely exchange listed government bonds. If, however, you happen to think in terms of sheer volume per time, the most liquid market phase could be considered the NYSE closing auction, as you can move billions in a matter of minutes, or expressed in speed terms: several m$/s (million dollars per second). You should pick a definition and we can provide you with a more accurate list of candidates and actual data.",
"title": ""
},
{
"docid": "123511",
"text": "\"What can I do to help him out, but at the same time protect myself from any potential scams? Find out why he can't do this himself. Whether your relative is being sincere or not, if he owns both accounts then he should be able to transfer money between them by himself. If you can find a way to solve that issue without involving your bank account, so much the better. Don't settle for \"\"something about authorized payees and expired cards.\"\" Get details, write them down. If possible, get documents. Then go to a bank or financial adviser you can trust and run those details by them to see what they have to say. Even if there's no scam, if what he's trying to do is illegal (even if he doesn't realize it himself) then you want to know before you get involved. You say you're willing to deal with \"\"other issues\"\" separately, but keep in mind that, even if there's no external scam here, those \"\"other issues\"\" could include hefty fees, censures on your own account, or jail time. Ask yourself: Does it make sense that this relative has an account overseas? I don't have any overseas accounts, because I don't do business in other countries. Is your relative a dual-citizen? Does he travel a lot? What country is the overseas account in? How long has he had this account? What bank is it with? Where the money is going is just as important as how it gets there (ie: through your account.) Arguably more so. Keep in mind that many scammers tell their marks not to share what's going on with anyone else. (Because doing so increases the odds of someone telling them to snap out of it.) It's entirely possible he's being scammed himself and just not telling you the whole story because the 419er is telling him to keep it quiet. (Check out that link for more details on common scams that your relative may be unwittingly part of, btw.) Get as many details as possible about what he's doing and why. If he's communicating with anyone else regarding this transfer, find out who. If there are emails, ask his permission to read them and watch for anything suspicious (ie: people who can't spell their own name consistently, constant pressure to act quickly, etc.)\"",
"title": ""
},
{
"docid": "432727",
"text": "\"Shares sold to private investors are sold using private contracts and do not adhere to the same level of strict regulations as publicly traded shares. You may have different classes of shares in the company with different strings attached to them, depending on the deals made with the investors at the time. Since public cannot negotiate, the IPO prospectus is in fact the investment contract between the company and the public, and the requirements to what the company can put there are much stricter than private sales. Bob may not be able to sell his \"\"special\"\" stocks on the public exchange, as the IPO specifies which class of stock is being listed for trading, and Bob's is not the same class. He can sell it on the OTC market, which is less regulated, and then the buyer has to do his due diligence. Yes, OTC-sold stocks may have strings attached to them (for example a buy back option at a preset time and price).\"",
"title": ""
},
{
"docid": "249643",
"text": "In a perfect the world, the most ideal solution would be to find a way to pay back all of your debt so that your credit will not be affected any further. Unfortunately, it does not work this way most of the time. Debt settlement is where you work with a creditor to settle your a credit card debt for less than the full amount owed. This could be a very viable solution for you instead of filing for bankruptcy. However, there are many scams out there when it applies to debt settlement so you must tread carefully. Debt settlement can only occur when you're behind on your payments. If you are currently paying off your payments successfully, the creditor has no obligation to settle when they think you should be able to pay it fully back.",
"title": ""
},
{
"docid": "517573",
"text": "\"Affinity fraud. You see, Madoff really didn't have to sell himself, people recommended him to their friends. In a similar way, it's easy once a scammer reels in one sucker to keep him on the hook long enough to get 10 friends to invest as well. I've written about Mortgage Acceleration scams, and the common thread is that they are first sold to friends, relatives, neighbors. People tell their fellow church goer about it and pretty soon people's belief just takes over as they want it to work. Edit - the scam I referenced above was the \"\"Money Merge Account\"\" and its reincarnated \"\"Wealth Unlimited.\"\" It claimed to use sophisticated software to enable one to pay their mortgage in less than half the time while not changing their budget. The sellers of the product weren't able to explain how it was supposed to work, since it was nonsense anyway. You were supposed to be able to borrow against a HELOC at a rate higher than your mortgage, yet come out ahead, enough to cut the time in half or less. The link I posted above leads to a spreadsheet I wrote in a weekend, which was better at the math than their software and free. It also linked to 66 pages of accumulated writing I did over a number of months starting in 2008. In the end, I never saw any prosecution over this scam, I suppose people were too embarrassed once they realized they wasted $3500. How can I get scammed buying S&P ETFs through Schwab? Easy, I can't.\"",
"title": ""
},
{
"docid": "319599",
"text": "Well I'm not going to advise whether it's a good idea to invest in this company (though often OTC is pretty scary), but it DOES have a product (vivio, an ad blocker), it did post financials and it's trading on the OTC-QB (which is better than the pink sheets), so you need to look these over and study up on the product to decide if it is overpriced or not. What might have occurred (viz the Patriot Berry Farm becoming Cyberfort) is that the latter bought up the stock of the former (this is, I believe, called using a shell, which is not necessarily a bad thing) and is using this as a way to be registered, i.e. sell to non-accredited investors via the OTC market. So I'm really just answering your third question: yes, you have to do a lot of due diligence to see if buying this stock is a good deal or not. It might be the next big thing. Or it might not. It certainly is the case that low trading volume allows a relatively small trade to really change the stock price, so the penny stocks do tend to be easier to 'inflate'. Side comment: the bid/ask spreads are pretty big, with a best bid of 0.35 and best ask of 0.44.",
"title": ""
},
{
"docid": "29571",
"text": "how are the ways he could scam me? There are hundreds of different ways the scam can progress ... broadly;",
"title": ""
},
{
"docid": "214518",
"text": "\"It is likely a scam. In fact the whole mystery shopping \"\"job\"\" may be a scam. There is a Snopes page about cashier's check scams, as well as a US government page which specifically mentions mystery shopping as a scam angle. As for how the scam works, from the occ.gov site I just linked: However, cashier’s checks lately have become an attractive vehicle for fraud when used for payments to consumers. Although, the amount of a cashier’s check quickly becomes \"\"available\"\" for withdrawal by the consumer after the consumer deposits the check, these funds do not belong to the consumer if the check proves to be fraudulent. It may take weeks to discover that a cashier’s check is fraudulent. In the meantime, the consumer may have irrevocably wired the funds to a scam artist or otherwise used the funds—only to find out later, when the fraud is detected—that the consumer owes the bank the full amount of the cashier’s check that had been deposited. It is somewhat unusual in that, from what you say, there has been no attempt thus far to get money back. However, your sister-in-law may have received that info separately, or received it as part of her mystery shopping job but didn't mention it to you with regard to this check. Typically the scam involves telling the recipient to transfer money to a third party (e.g., by buying goods as a mystery shopper, or via wire transfer to \"\"reimburse\"\" someone associated with a sham operation). By the time the cashier's check is revealed as fraudulent, the victim has already transferred away his/her own real money. It's probably worth taking the check to your or her bank and asking them about it. They may have more info. Also, banks usually want to know about scams like this because, in the long run, they accumulate data on them and share that with law enforcement and can eventually catch some of the scammers. Edit: Just to help anyone who may be reading this later. The letter you added confirms it is absolutely a scam. My boss was once contacted via a scam operation very similar to this. The huge red flag (in addition to others already mentioned) is that you are being \"\"given\"\" a check for over $2000, of which only $25 is purportedly for actual mystery shopping and $285 is payment for you, the mystery shopper. The whole rest of the $2000+ amount is for you to wire to \"\"another Mystery/Secret Shopper in order for them to complete their assignment\"\". They are giving you $2000 to give to someone else who is supposedly another one of their own employees/contractors. Ask yourself what sane business would conduct their operations in this way. If you work at a law office, or a hamburger stand, or a school, or anything you like, does your boss ever say \"\"Here is your paycheck for $5000. I know you only earned $1000, but I'm just going to give you the whole $5000, and you're supposed to use $4000 of it to pay your coworker Joe his wages.\"\" No. There is no reason to do that except that the \"\"other mystery shopper\"\" is actually the scammer.\"",
"title": ""
},
{
"docid": "526073",
"text": "Publicly traded companies perform dilution via an FPO (Follow-up Public Offer). It is a process similar to IPO, with announcements, prospectus, etc. You will know ahead of time when that happen. Stocks traded OTC are not required to file a lot of regulatory documents that publicly traded stocks are required to file, and may not disclose dilutions or additional issues. By buying OTC you agree to these terms. You will probably get a notice and a chance to vote on that in your proxy statement, but that happens when you already own the stock.",
"title": ""
},
{
"docid": "208507",
"text": "$15 being how much it costs to drive a car about 10 miles, and does not account for a driver's time. Hilarious shit, from the biggest payday loan scam the planet has ever seen. Because Uber is nothing but a scam where you work your ass off, to steal money from your future self, and give 25% of it to Uber! But if you think 6 cents a mile is a decent wage for a cab driver (which is what you can make, if you are lucky), then by all means, please sign up!",
"title": ""
},
{
"docid": "510163",
"text": "\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \"\"IPO Date\"\" is wrong on this one. However, there are several companies that appear to do an \"\"IPO\"\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \"\"IPO\"\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \"\"IPO\"\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \"\"IPO\"\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \"\"Initial\"\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\"",
"title": ""
},
{
"docid": "496370",
"text": "\"Yeah, I'll take the challenge...:) How trustworthy these are and what are their sources of income? These are in fact two separate questions, but the answers are related. How trustworthy? As trustworthy as they're clear about their own sources of income. If you cannot find any clue as to why, what for and how they're paying you - you probably should walk away. What's too good to be true usually is indeed too good to be true. For those of the sites that I know of their sources of income, it is usually advertisements and surveys. To get paid, you have to watch advertisements and/or answer surveys. I know of some sites who are legit, and pay people (not money, but gift cards, airline miles, etc) for participating in surveys. My own HMO (Kaiser in California) in fact pays (small amounts) to members who participate in enough surveys, so its legit. Are these sites worthwhile to consider for extra income? Not something you could live off, but definitely can get you enough gift cards for your weekly trip to Starbucks. What do I need to consider tax wise? Usually the amounts are very low, and are not paid in cash. While it is income, I doubt the IRS will chase you if you don't report the $20 Amazon gift card you got from there. It should, strictly speaking, be reported (probably as hobby income) on your tax return. Most people don't bother dealing with such small amounts though. In some cases (like the HMO I mentioned), its basically a rebate of the money paid (you pay your copays, deductibles etc. Since the surveys are only for members, you basically get your money back, not additional income). This is in fact similar to credit card rebates. Is there a best practice for handling the income? If we're talking about significant amounts (more than $20-30 a year), then you need to keep track of the income and related expenses, and report it as any other business income on your taxes, Schedule C. Is there a good test to determine what is and isn't a scam? As I said - if it looks too good to be true - it most likely is. If you're required to provide your personal/financial information without any explanation as to why, what it will be used for, and why and what for you're going to be paid - I'd walk away. Otherwise, you can also check Internet reviews, BBB ratings, FTC information and the relevant state agencies and consumer watchdogs (for example: http://www.scamadviser.com) whether they've heard of that particular site, and what is the information they have on it. A very good sign for a scam is contact information. Do they have a phone number to call to? Is it in your own country? If its not in your own country - definitely go away (for example the original link that was in the question pointed to a service whose phone number is in the UK, but listed address is in Los Angeles, CA. A clear sign of a scam). If they do have a phone number - try it, talk to them, call several times and see how many different people you're going to talk to. If its always the same person - run and hide. Do they have an address? If not - walk away. If they do - look it up. Is it a PMB/POB? A \"\"virtual\"\" office? Or do they have a proper office set up, which you can see on the map and in the listings as their office? And of course your guts. If your guts tell you its a scam - it very likely is.\"",
"title": ""
}
] |
3574
|
Credit report - Not able to establish identity
|
[
{
"docid": "36833",
"text": "The suggestion may be very delayed, have you personally gone to the Experian Office with all the documentation (in xerox copy and in original)? If not, please do so, there is always a difference between dealing with govt/semi-govt institutions over electronic channels and in person.",
"title": ""
},
{
"docid": "105199",
"text": "I suggest you begin by double checking what kinds of credit products you have and to which credit bureaus your bank reports. Not all financial institutions report to all bureaus. For example, if your bank only reports your one and only line of credit to Experian, TransUnion still won't have a file on you. Also, some lines of credit such as being an authorized user on a credit card aren't tracked by all of the bureaus. The other thing to consider is the amount of time that your lines of credit have been open. You said it's been less than one year but if it's been less than six months you might try waiting six months to try requesting your reports. If none of the above solves your problem, I would respond to their letter exactly as they instruct you to. Send everything certified with return receipt, and get into the habit of saving all of these records. When you send your reply be sure to include all of the requested information, a brief summary of your issue, and a reference to their previous letter to you. If they don't respond to your letter or they aren't able to help you, try calling the credit bureaus directly to inquire about the problem. Usually the consumer phone lines are automated, so try the corporate or business contacts they list on their website. On a final note, never submit your information on any of the bureaus websites. By doing so you agree to binding arbitration agreements which limit your right to sue. Only communicate with the bureaus by mail or on rare occasions phone.",
"title": ""
},
{
"docid": "260623",
"text": "It looks like from their response, they would like you to send a copy of your social security card. Your drivers license or passport will not help verify your social security number. Another option you could try is to get your credit report from one of the other credit bureaus. You should be able to choose from Experian, Trans Union, and Equifax all on annualcreditreport.gov",
"title": ""
}
] |
[
{
"docid": "587778",
"text": "Freezing your credit should be the default configuration. EDIT: More info on Why. Basically you're adding a password to your credit report access. https://www.privacyrights.org/consumer-guides/identity-theft-monitoring-services 4. Is there a low-cost alternative to monitoring services? The best low-cost alternative to credit monitoring services is a security freeze. A security freeze locks your credit files at the three credit reporting agencies (Equifax, Experian, and TransUnion) until you unlock your file with a password or PIN. The freeze stops new accounts from being established by imposters because potential creditors are not able to check your credit report or credit score, the standard procedure when financial accounts are opened. Any potential creditors’ requests for access to your credit files will be denied. However, a security freeze cannot stop misuse of your existing bank or credit accounts. You still must check the monthly statements on your current accounts for any erroneous charges or debits. Generally, you will pay no more than $30 for a lifetime of security freeze protection. In some circumstances (identity theft victims and senior citizens in some states), this protection may be free. With a security freeze, your credit reports cannot be seen by prospective creditors, insurance companies, landlords, utilities, or for employment screening. However, you may lift the freeze when necessary to allow a company to check your credit report. This is easily done by means of a password. It is important to realize that a security freeze does not prevent existing creditors from seeing your credit report. While a security freeze may be the best available deterrent to new account fraud, it may not be the best solution for everyone. It can be cumbersome for individuals who frequently apply for credit, are contemplating a new mortgage, or who plan to change jobs. On the other hand, a security freeze is particularly well-suited for seniors who are no longer in the market for new credit. And a freeze provides protection for individuals affected by data breaches involving Social Security numbers, as well as victims of identity theft or mail theft. For a more complete discussion of the pros and cons of security freezes, read this report in Consumer Reports. Brian Krebs' post How I Learned to Stop Worrying and Embrace the Security Freeze is a primer on what you can do to avoid becoming a victim of identity theft. Fees, supporting documentation, and procedures for placing a security freeze vary from state to state and among the three credit reporting agencies. The web sites of each of the credit reporting agencies provide state-specific instructions for placing a security freeze. The websites of each of the credit reporting agencies provide state-specific instructions for placing a security freeze. Equifax Experian TransUnion",
"title": ""
},
{
"docid": "90632",
"text": "What can I do to make sure it won't happen? Who is the right person to report this to? (apparently, the police can't make sure that it won't be used for identity theft) You want to contact any one of the credit bureaus and put a fraud alert on your account. Once you contact one, they automatically contact the other bureaus for you. As part of this, they should send you a credit report. Review it carefully and note any items that are not yours. You'll then need to dispute any items that are a result of this identity theft. You may be required to file a police report regarding the stolen identity, but if you filed one for your stolen wallet, that may be sufficient. If the person who stole your wallet wants to steal your identity, it may be months before it shows up on your credit report. Make it a practice to regularly check your credit reports. How do I check at any given time whether my identity was stolen? Unfortunately, there is no easy way to check if your identity was stolen. The most common way is to check your credit report, but that only checks things that are reported to the credit reporting bureaus. If they use your information to start an account with a utility company at a rental house that typically won't go on your credit report until they are substantially delinquent. If they use your information to check into a hospital, that information typically won't show up on your credit report until the hospital sends the bill to collections. I've had a case where the identity theft happened at Chase, but was never reported on my credit. So my credit report was clear, but Chase disallowed me from banking with them because the identity thief had delinquent accounts with Chase that for whatever reason were not reported to the bureaus. How likely is it that it will be used in any form of identity theft? My gut feeling is that someone who snatches a wallet and immediately runs up the credit cards isn't looking to steal identities, but rather for a quick score. I don't know if there are statistics that back up my hunch.",
"title": ""
},
{
"docid": "581889",
"text": "First thing to do when you notice a credit card fraud is to call the respective banks who issues the credit card and most banks immediately (as far as my experience goes - twice) they will cancel the credit card and issue a new card with different number. Your credit card account will remain the same, no effect on credit score as the account is still active, its just the credit card number is changed. If you are more concerned about Identity Theft, there are two further options you can pursue. Place a Fraud Alert : Ask 1 of the 3 credit reporting companies to put a fraud alert on your credit report. They must tell the other 2 companies. An initial fraud alert can make it harder for an identity thief to open more accounts in your name. The alert lasts 90 days but you can renew it. - as per Federal Trade Commission Credit Freeze : If you’re concerned about identity theft, those reported mega-data breaches, or someone gaining access to your credit report without your permission, you might consider placing a credit freeze on your report. - as per Federal Trade Commission",
"title": ""
},
{
"docid": "531137",
"text": "\"I was I a similar position as you, and sometimes credit bureaus might be difficult to deal with, especially when high amounts of money are involved. To make the long story short, someone opened a store credit card under my name and made a charge of around 3k. After reporting this to the bureaus, they did not want to remove the account from my credit report citing that the claim was \"\"frivolous\"\". After filing a police report, the police officer gave me the phone number for the fraud department of this store credit card, and after they investigated, they removed the account from my credit. I would suggest to do the following: Communicating with Creditors and Debt Collectors You have the right to: Stop creditors and debt collectors from reporting fraudulent accounts. After you give them a copy of a valid identity theft report, they may not report fraudulent accounts to the credit reporting companies. Get copies of documents related to the theft of your identity, like transaction records or applications for new accounts. Write to the company that has the documents, and include a copy of your identity theft report. You also can tell the company to give the documents to a specific law enforcement agency. Stop a debt collector from contacting you. In most cases, debt collectors must stop contacting you after you send them a letter telling them to stop. Get written information from a debt collector about a debt, including the name of the creditor and the amount you supposedly owe. If a debt collector contacts you about a debt, request this information in writing. I know that you said that the main problem was that your credit account was combined with another. But there might be a chance that identity theft was involved. If this is the case, and you can prove it, then you might have access to more tools to help you. For example, you can file a report with the FTC, and along with a police report, this can be a powerful tool in stopping these charges. Feel free to go to the identitytheft.gov website for more information.\"",
"title": ""
},
{
"docid": "304179",
"text": "You signed a contract to pay the loan. You owe the money. Stories of people being arrested over defaulted student loans are usually based in contempt of court warrants when the person failed to appear in court when the collection agency filed suit against them. Explore student loan forgiveness program. Research collections and bankruptcy and how to deal with collection agencies. There are pitfalls in communicating with them which restart the clock on bad debt aging off the credit report, and which can be used to say that you agreed to pay a debt. For instance, if you make any sort of payment on any debt, a case can be made that you have assumed the debt. Once you are aware of the pitfalls, contact the collection agency (in writing) and dispute the debt. Force them to prove that it is your debt. Force them to prove that they have the right to collect it. Force them to prove the amount. Dispute the fairness of the amount. Doubling your principal in 6 years is a bit flagrant. So, work with the collectors, establish that the debt is valid and negotiate a settlement. Or let it stay in default. Your credit report in the US is shot. It will be a long time before the default ages off your report. This is important if you try to open a bank account, rent an apartment, or get a job in the US. These activities do not always require a credit report, but they often do. You will not be able to borrow money or establish a credit card in the US. Here's a decent informational site regarding what they can do to collect the loan. Pay special attention to Administrative Wage Garnishment. They can likely hit you with that one. You might be unreachable for a court summons, but AWG only requires that the collectors be able to confirm that you work for a company that is subject to US laws. Update: I am informed that federally funded student loans are not available to international students. AWG is only possible for debts to the federal government. Private companies must go through the courts to force settlement of debt. OP is safe from AWG.",
"title": ""
},
{
"docid": "171510",
"text": "While everything can be fixed in the end, and you can usually get all your money back, recovering from identity theft can take months or years. In the meantime, these are some of the things which you might not be able to do: In addition, you could face the following events: For all that, checking your credit report / score once or twice a year is probably enough. If you're planning on a major purchase, though, you should get a copy of your full credit report from all three major bureaus (Equifax, Transunion and Experian) a few months ahead of time. Even if everything on them is kosher, having that information on hand will give you a leg up when you go for financing.",
"title": ""
},
{
"docid": "115712",
"text": "fine because the application was declined anyway. No it isn't fine. Credit card applications generally need a hard pull, so get it rectified. Firstly check if an application was really made on your behalf. Some companies use this ploy to pull you into a scheme of making you apply for a credit card. Secondly call up the credit card company and ask them about the details of who had made the application as you haven't done so and inform them that it was a fraudulent application. It might be somebody is using your personal details to do a identity theft in your name. Thirdly get in touch with the credit rating firms and see if a check has been made on your credit report. Dispute it if you see a check in your record and have it removed from your report. If you subscribe to credit agency, get the identity theft protection, helps you in such cases. And finally keep a diligent eye on your credit records from now on. Once bitten, twice shy.",
"title": ""
},
{
"docid": "29813",
"text": "If they have your account numbers (which are necessary for direct deposits) they could possibly initiate ACH withdrawals from your accounts too (requires some setup but they may have accomplices). Note that even if you didn't have money there, depending on the local bank rules you may be still on the hook for overdrafts they create, at least by default. You may be able to prove later that this was fraud but the burden of proof will be on you, and in the meantime they might be gone with the money. They could use your documents to either establish other accounts in your name (identity theft) or take over your accounts (e.g. by contacting customer service of the bank and claiming to be you, and presenting the documents you sent as a proof), request credits under your identity (possibly using the money on the account as a collateral since the bank may not know where the money is from), etc. This is even easier given you will give them all the documents and information needed for a loan, your signature, etc. And the fact that they ask you to send documents to a specific address doesn't mean they could be found at that address when the problems start - it may be rented short-term, belong to either knowing or unknowing accomplice, be a forwarding service, etc. Could be money laundering of course too. That's just what comes to mind after a short while thinking about it.",
"title": ""
},
{
"docid": "185656",
"text": "I have never been requested to send a voter registration card. What on earth for? It sounds as if you don't have a credit report available on your SSN, so they're having trouble verifying your identity. But the most I have ever been requested to send to an online bank (ING Direct in my case, and I too didn't have a credit report yet when I opened an account there) was the Social Security card and a driver's license. Once you have a proper credit report information (a couple of loans and a couple of address changes), they can compile the data into a set of verification questions, which would be used to verify your identity. If you do send stuff - make sure to fax it to their 800 fax number, do not send via email. It may also be that their user database is compromised and someone is phishing you. Make sure they're the ones asking for info (and getting it) by calling their phone number (take the number from their web-site, not the emails).",
"title": ""
},
{
"docid": "459695",
"text": "These kinds of credit card offers are incredibly common. More often you will get a certain reward if you spend $X within Y days of getting the card. In many cases you can take advantage of them with very little downside. However, are you responsible enough to have a credit card and be able to pay off the balance every month? If not the interest charges could quickly wipe out the $50 bonus you get. And hard inquiries and new accounts could potentially affect your credit score, particularly if you don't have a well-established credit history. There's also the chance you get denied in which case you add a hard inquiry to your credit report for no gain.",
"title": ""
},
{
"docid": "423809",
"text": "Since we seem to be discussing credit score and credit history interchangeably, if I can add credit report as the third part of the puzzle, I have another point. Your credit score and credit report can be effective tools to notice identity theft or fraud in your name. Keeping track of your report will allow you to not only protect your good name (which is apparently in dispute here) but also those businesses who ultimately end up paying for the stolen goods or services.",
"title": ""
},
{
"docid": "360491",
"text": "Well, it is a negative point of view, but nobody in the history of money has ever loaned money because they like you. I suppose you could paint it as an honest point of view. All money lending is for profit. If you have a high score, you are very likely to repay your loan because you are lower risk. We always hear lower risk... but the risk is that they won't make money off of you. I think that just like we buy previously owned vehicles cars instead of used cars, and we banks call them service fees instead of junk fees, our credit score discusses our credit worthiness instead of profitability But none of that means you can't benefit from it. It isn't a fear tactic, it is a way to judge each other. You probably pay interest and fees to keep it high, but that is price of lending. I think the questioner has a negative view of credit (which I suppose is fine and is their right, I will defend their right to an opinion) but the way we do and judge credit is neither evil or benevolent. I could certainly agree that more transparency would be good, but only for honest folks. If the credit bureaus made it public how they judged us, there would be a new industry for people who want to game the system. Update Since it always will cost to use credit, and using credit is the only way to prove your a low credit risk, it will therefore always cost money to raise your credit score. However the return on investment is exemplified in this question: a person with no credit was able to get a loan, but at serious out of pocket cost. Later, after establishing credit at a price of real money, he was able to secure a nearly identical loan for considerably less cost (in terms of interest paid) because he had proven himself worthy. When I say proven, I mean paid interest. There is nothing wrong with questioning the system, change only occurs when people question the status quo. And for sure our current system is not perfect, but like many employed systems while it is terrible but there is nothing better.",
"title": ""
},
{
"docid": "538217",
"text": "I would keep the letter in a file for follow-up, and I would do what you are already planning to do and wait to see what shows up on the credit report. If this does reflect an identity theft attempt, chances are that others will follow, so vigilance is key here. If there is a hard credit check, then you can dispute that on your credit report. If there is not a hard credit check, there is nothing further this credit card company can do to help you anyway.",
"title": ""
},
{
"docid": "280140",
"text": "The first thing you need to know is that getting a new social security number will not erase your credit history. In fact, using a name change or a social security number change to get out of debt is considered fraud in most jurisdictions and you can be arrested for it. As soon as you are issued a new social security number, your old number and new number are linked in the government and credit bureau files. Everything that was on your old credit report will appear on your new credit report. The second big thing to know is if you suspect that your social security number has been used fraudulently in regards to credit, stop reading this right now, immediately call one of the three major credit bureaus (Experian, TransUnion, or Equifax), and place what's called an initial fraud alert. You only need to call one of the three. The one you call will notify the other two. This places a flag on your credit file at all three bureaus which says that your identity may have been stolen and any financial institution which is processing an application for credit should immediately contact you at the phone number you provide. The alert is good for 90 days and you can renew it as many times as you wish. I suggest using TransUnion as your one call because I've called them when my identity was stolen, and they're automated system is very well designed. Now that that is out of the way... you said that they have your email address, but it is very unusual for people to be contacted by email for a debt. In fact, I would automatically disregard any emails about debts. Every legitimate financial institution I've ever come across will either call you or send mail to your last known address. Regarding what's being reported on your credit report, you need to type a letter to each credit bureau which is reporting the information telling them who you are and that you are disputing this information on your report. Mail it to the bureaus by certified mail with return receipt. Under United States law they are required to verify the information on your report, if you dispute it, and remove the information if they are unable to verify it. In many cases, it's too much of a hassle and the bureaus just remove the information. The other thing I'll leave you with is that you said you've only had credit in the past six months. Six months is not enough time to build an adequate credit profile. You really need to be strategic about your credit score. Every time you apply for credit, it drags the score just a little bit lower. Your question wasn't really about building credit, so I'll spare you the novel on that, but I would encourage you to seek out one of the many resources which are readily available online. I am not an attorney. This is not legal advice. You should consult with an attorney who is licensed to practice law in your particular jurisdiction.",
"title": ""
},
{
"docid": "556219",
"text": "While I agree with keshlam@ that the gym had no reason (or right) to ask for your SSN, giving false SSN to obtain credit or services (including gym membership) may be considered a crime. While courts disagree on whether you can be charged with identity theft in this scenario, you may very well be charged with fraud, and if State lines are crossed (which in case of store cards is likely the case) - it would be a Federal felony charge. Other than criminal persecution, obviously not paying your debt will affect your credit report. Since you provided false identity information, the negative report may not be matched to you right away, but it may eventually. In the case the lender discovers later that you materially misrepresented information on your mortgage application - they may call on your loan and either demand repayment in full at once or foreclose on you. Also, material misrepresentation of facts on loan application is also a criminal fraud. Again, if State lines are crossed (which in most cases, with mortgages they are), it becomes a Federal wire fraud case. On mortgage application you're required to disclose your debts, and that includes lines of credits (store cards and credit cards are the same thing) and unpaid debts (like your gym membership, if its in collection).",
"title": ""
},
{
"docid": "205196",
"text": "My son who is now 21 has never needed me to cosign on a loan for him and I did not need to establish any sort of credit rating for him to establish his own credit. One thing I would suggest is ditch the bank and use a credit union. I have used one for many years and opened an account there for my son as soon as he got his first job. He was able to get a debit card to start which doesn't build credit score but establishes his account work the credit union. He was able to get his first credit card through the same credit union without falling work the bureaucratic BS that comes with dealing with a large bank. His interest rate may be a bit higher due to his lack of credit score initially but because we taught him about finance it isn't really relevant because he doesn't carry a balance. He has also been able to get a student loan without needing a cosigner so he can attend college. The idea that one needs to have a credit score established before being an adult is a fallacy. Like my son, I started my credit on my own and have never needed a cosigner whether it was my first credit card at 17 (the credit union probably shouldn't have done that since i wasn't old enough to be legally bound), my first car at 18 or my first home at 22. For both my son and I, knowing how to use credit responsibly was far more valuable than having a credit score early. Before your children are 18 opening credit accounts with them as the primary account holder can be problematic because they aren't old enough to be legally liable for the debt. Using them as a cosigner is even more problematic for the same reason. Each financial institution will have their own rules and I certainly don't know them all. For what you are proposing I would suggest a small line of credit with a credit union. Being small and locally controlled you will probably find that you have the best luck there.",
"title": ""
},
{
"docid": "526106",
"text": "\"It is called \"\"Credit card installments\"\" or \"\"Equal pay installments\"\", and I am not aware of them being widely used in the USA. While in other countries they are supported by banks directly (right?), in US you may find this option only in some big stores like home improvement stores, car dealerships, cell phone operators (so that you can buy a new phone) etc. Some stores allow 0% financing for, say, 12 months which is not exactly the same as installments but close, if you have discipline to pay $250 each month and not wait for 12 months to end. Splitting the big payment in parts means that the seller gets money in parts as well, and it adds risks of customer default, introduces debt collection possibility etc. That's why it's usually up to the merchants to support it - bank does not care in this case, from the bank point of view the store just charges the same card another $250 every month. In other countries banks support this option directly, I think, taking over or dividing the risk with the merchants. This has not happened in US. There is a company SplitIt which automates installments if stores want to support it but again, it means stores need to agree to it. Here is a simple article describing how credit cards work: https://www.usbank.com/credit-cards/how-credit-cards-work.html In general, if you move to US, you are unlikely to be able to get a regular credit card because you will not have any \"\"credit history\"\" which is a system designed to track each customer ability to get & pay off debt. The easiest way to build the history - request \"\"secured credit card\"\", which means you have to give the bank money up front and then they will give you a credit card with a credit limit equal to that amount. It's like a \"\"practice credit card\"\". You use it for 6-12 months and the bank will report your usage to credit bureaus, establishing your \"\"credit score\"\". After that you should be able to get your money back and convert your secured card into a regular credit card. Credit history can be also built by paying rent and utilities but that requires companies who collect money to report the payments to credit bureaus and very few do that. As anything else in US, there are some businesses which help to solve this problem for extra money.\"",
"title": ""
},
{
"docid": "535555",
"text": "\"The Wells Fargo scandal was and still is a big deal because Wells Fargo opened over 1.5 million unauthorized bank and credit card accounts. The credit card accounts were opened without authorization, which means people's credit scores and reports were pulled without permission. That is considered fraud and identity theft. Other than the legal side of it, by opening more bank accounts without authorization, it was showing \"\"synthetic growth\"\", which resulted in an inflated number when quarterly and annual performance numbers were reported. This caused people to invest more in Wells Fargo stock, not knowing that the growth in stock was not organic. After the scandal was uncovered, stocks decreased. However, the root cause of this can be traced to the culture at Wells Fargo, where customer service reps (i.e. bank tellers, and store operations employees) were faced with the challenges of meeting quotas that could be considered a stretch. As a result, faced with pressure from upper management, they opened unauthorized accounts. In addition, these unauthorized accounts cost consumers money either because credit cards had balances, or bank accounts did not meet a minimum balance. It is not about ending \"\"up with 8 rows in their database instead of just 1 row\"\" as OP wrote. It is about stealing consumer money and committing fraud and stealing the consumer's identity. *Suggestions and constructive criticism are welcomed in improving my answer.\"",
"title": ""
},
{
"docid": "500755",
"text": "Set up a meeting with the bank that handles your business checking account. Go there in person and bring your business statements: profit and loss, balance sheet, and a spreadsheet showing your historical cash flow. The goal is to get your banker to understand your business and your needs and also for you to be on a first-name basis with your banker for an ongoing business relationship. Tell them you want to establish credit and you want a credit card account with $x as the limit. Your banker might be able to help push your application through even with your credit history. Even if you can't get the limit you want, you'll be on your way and can meet again with your banker in 6 or 12 months. Once your credit is re-established you'll be able to shop around and apply for other rewards cards. One day you might want a line of credit or a business loan. Establishing a relationship with your banker ahead of time will make that process easier if and when the time comes. Continue to meet with him or her at least annually, and bring updated financial statements each time. If nothing else, this process will help you analyze your business, so the process itself is useful even if nothing comes of it immediately.",
"title": ""
},
{
"docid": "212883",
"text": "The negative effects of multiple hard inquiries in a short span of time don't stack, they're treated as a single inquiry (and inquiries aren't *that* bad anyway, the only ding you by a few points). The bigger problem here is the **other** reason your bank gave you - Too many overdrawn accounts. If you don't believe you currently have any overdrawn accounts, you need to pull your credit report *now* and make sure it's accurate. Maybe there's a mistake on your credit, maybe you're a victim of identity theft. That said, 1.5 years isn't really very long in credit terms for managing to keep your record clean, so maybe your credit just needs a few more years to heal. But *definitely* pull your credit report to rule out the worst possibilities.",
"title": ""
},
{
"docid": "519644",
"text": "Wrong sub. You're looking for /r/personalfinance >will freezing just that credit report hurt them in any way? No, but it will help prevent an identity thief from wrecking your credit. >Can I still get a loan with only one of the three frozen? Depends, but yes. You should freeze your credit at all 5 credit bureaus for personal financial protections.",
"title": ""
},
{
"docid": "536497",
"text": "\"Banks are businesses, and as such should have the right to refuse service, so they should probably be able to choose one customer over another at will. [I say \"\"should\"\" because business owners protecting themselves against litigation related to discrimination could restrict their freedom as business owners.] However, banks are businesses and if the customers are identical, both will be approved (or not) according to credit records. Does not make sense to approve one person with a given credit record and refuse someone with a similar record. Unless they barely qualify. Since no two credit histories are identical, there are surely edge cases. Finally, if a customer is a long term customer with large deposits and/or significant amounts of business with the bank, the bankers will likely be inclined to do more business.\"",
"title": ""
},
{
"docid": "214358",
"text": "Here is a quote from the IRS website on this topic: You may be able to deduct premiums paid for medical and dental insurance and qualified long-term care insurance for yourself, your spouse, and your dependents. The insurance can also cover your child who was under age 27 at the end of 2011, even if the child was not your dependent. A child includes your son, daughter, stepchild, adopted child, or foster child. A foster child is any child placed with you by an authorized placement agency or by judgment, decree, or other order of any court of competent jurisdiction. One of the following statements must be true. You were self-employed and had a net profit for the year reported on Schedule C (Form 1040), Profit or Loss From Business; Schedule C-EZ (Form 1040), Net Profit From Business; or Schedule F (Form 1040), Profit or Loss From Farming. You were a partner with net earnings from self-employment for the year reported on Schedule K-1 (Form 1065), Partner's Share of Income, Deductions, Credits, etc., box 14, code A. You used one of the optional methods to figure your net earnings from self-employment on Schedule SE. You received wages in 2011 from an S corporation in which you were a more-than-2% shareholder. Health insurance premiums paid or reimbursed by the S corporation are shown as wages on Form W-2, Wage and Tax Statement. The insurance plan must be established, or considered to be established as discussed in the following bullets, under your business. For self-employed individuals filing a Schedule C, C-EZ, or F, a policy can be either in the name of the business or in the name of the individual. For partners, a policy can be either in the name of the partnership or in the name of the partner. You can either pay the premiums yourself or your partnership can pay them and report the premium amounts on Schedule K-1 (Form 1065) as guaranteed payments to be included in your gross income. However, if the policy is in your name and you pay the premiums yourself, the partnership must reimburse you and report the premium amounts on Schedule K-1 (Form 1065) as guaranteed payments to be included in your gross income. Otherwise, the insurance plan will not be considered to be established under your business. For more-than-2% shareholders, a policy can be either in the name of the S corporation or in the name of the shareholder. You can either pay the premiums yourself or your S corporation can pay them and report the premium amounts on Form W-2 as wages to be included in your gross income. However, if the policy is in your name and you pay the premiums yourself, the S corporation must reimburse you and report the premium amounts on Form W-2 as wages to be included in your gross income. Otherwise, the insurance plan will not be considered to be established under your business. Medicare premiums you voluntarily pay to obtain insurance in your name that is similar to qualifying private health insurance can be used to figure the deduction. If you previously filed returns without using Medicare premiums to figure the deduction, you can file timely amended returns to refigure the deduction. For more information, see Form 1040X, Amended U.S. Individual Income Tax Return. Amounts paid for health insurance coverage from retirement plan distributions that were nontaxable because you are a retired public safety officer cannot be used to figure the deduction. Take the deduction on Form 1040, line 29.",
"title": ""
},
{
"docid": "571430",
"text": "It also depends on where you work. If you move your home and your job then the date you establish residency in the new state is the key date. All income before that date is considered income for state 1, and all income on or after that date is income for state 2. If there is a big difference in income you will want to clearly establish residency because it impacts your wallet. If they had the same rates moving wouldn't impact your wallet, but it would impact each state. So make sure when going from high tax state to low tax state that you register your vehicles, register to vote, get a new drivers license... It becomes more complex if you move your home but not your job. In that case where you work might be the deciding factor. Same states have agreed that where you live is the deciding factor; in other cases it is not. For Virginia, Maryland, and DC you pay based on where you live if the two states involved are DC, MD, VA. But if you Live in Delaware and work in Virginia Virginia wants a cut of your income tax. So before you move you need to research reciprocity for the two states. From Massachusetts information for Nonresident and Part-Year Resident Income, Exemptions, Deductions and Credits Massachusetts gross income includes items of income derived from sources within Massachusetts. This includes income: a few questions later: Massachusetts residents and part-year residents are allowed a credit for taxes due to any other jurisdiction. The credit is available only on income reported and taxed on a Massachusetts return. Nonresidents may not claim the taxes paid to other jurisdiction credit on their Massachusetts Form 1-NR/PY. The credit is allowed for income taxes paid to: The credit is not allowed for: taxes paid to the U.S. government or a foreign country other than Canada; city or local tax; and interest and penalty paid to another jurisdiction. The computation is based on comparing the Massachusetts income tax on income reported to the other jurisdiction to the actual tax paid to the other jurisdiction; the credit is limited to the smaller of these two numbers. The other jurisdiction credit is a line item on the tax form but you must calculate it on the worksheet in the instruction booklet and also enter the credit information on the Schedule OJC. So if you move your house to New Hampshire, but continue to work in Massachusetts you will owe income tax to Massachusetts for that income even after you move and establish residency in New Hampshire.",
"title": ""
},
{
"docid": "164262",
"text": "\"Assuming you live in the US, it is quite normal when you are applying for a loan that the application will ask you to confirm your identity. One of these methods is to ask you which of the following addresses you have lived at, with some of them being very similar (i.e. same city, or maybe even the same street). Sometimes they will ask questions and your answer would be \"\"None of the above.\"\" This is done to prevent fraudsters from applying for a loan under your identity. If you see no signs of unauthorized accounts or activities on your credit reports, and you initiated the car loan application, then you should be fine.\"",
"title": ""
},
{
"docid": "504989",
"text": "\"First I would like to say, do not pay credit card companies in an attempt to improve your credit rating. In my opinion it's not worth the cash and not fair for the consumer. There are many great resources online that give advice on how to improve your credit score. You can even simulate what would happen to your score if you did \"\"this\"\". Credit Karma - will give you your TransUnion credit score for free and offers a simulation calculator. If you only have one credit card, I would start off by applying for another simply because $700 is such a small limit and to pay a $30 annual fee seems outrageous. Try applying with the bank where you hold your savings or checking account they are more likely to approve your application since they have a working relationship with you. All in all I would not go out of my way and spend money I would not have spent otherwise just to increase my credit score, to me this practice is counter intuitive. You are allowed a free credit report from each bureau, once annually, you can get this from www.annualcreditreport.com, this won't include your credit score but it will let you see what banks see when they run your credit report. In addition you should check it over for any errors or possible identity theft. If there are errors you need to file a claim with the credit agency IMMEDIATELY. (edit from JoeT - with 3 agencies to choose from, you can alternate during the year to pull a different report every 4 months. A couple, every 2.) Here are some resources you can read up on: Improve your FICO Credit Score Top 5 Credit Misconceptions 9 fast fixes for your credit scores\"",
"title": ""
},
{
"docid": "499090",
"text": "I agree. I pulled my free reports (by going to ftc.gov first to get link to the truly free reports). The Equifax data was out of date. Didn't bother trying to correct it. As I don't need any new credit lines, I just put a security freeze on my records at all four bureaus. Makes my data virtually worthless to any potential identity their, and (best of all) nearly worthless to the bureaus.",
"title": ""
},
{
"docid": "504293",
"text": "This is a good idea, but it will barely affect your credit score at all. Credit cards, while a good tool to use for giving a minor boost to your credit score and for purchasing things while also building up rewards with those purchases, aren't very good for building credit. This is because when banks calculate your credit report, they look at your long-term credit history, and weigh larger, longer-term debt much higher than short-term debt that you pay off right away. While having your credit card is better than nothing, it's a relatively small drop in the pond when it comes to credit. I would still recommend getting a credit card though - it will, if you haven't already started paying off a debt like a student or car loan, give you a credit identity and rewards depending on the credit card you choose. But if you do, do not ever let yourself fall into delinquency. Failing to pay off loans will damage your credit score. So if you do plan to get a credit card, it is much better to do as you've said and pay it all off as soon as possible. Edit: In addition to the above, using a credit card has the added benefit of having greater security over Debit cards, and ensures that your own money won't be stolen (though you will still have to report a fraudulent charge).",
"title": ""
},
{
"docid": "49321",
"text": "Request verification in writing of the debt. They are required to provide this by law. Keep this for your records. Send them a notice by certified mail stating that this is not your debt and not to contact you again. Indicate that you will take legal action if they continue to try and collect. Keep a log of if/when they continue to call or harass you. Contact counsel about your rights under the fair debt collection laws, but if they keep harassing you after being provided proof of your identity, they are liable. You could win a judgement in court if you have proof of bad behavior. If your identity is stolen, you are not legally responsible for the charges. However it is a mess to clean up, so pull your credit reports and review your accounts to be sure.",
"title": ""
},
{
"docid": "478230",
"text": "Sorry to hear about your difficult circumstances. Secured Credit Card You may want to suggest a secured credit card. These are credit cards that are backed by a deposit that she would place with the credit issuer. The card issuer provides a line of credit backed by the deposit, with a credit limit not greater than the deposit. In this way, the card issuer is not putting any of their own money at risk. These cards are often used by students or high-risk borrowers to establish credit, and function like a normal credit card. This may be a good option for her to establish a history of handling credit responsibly. Given all of the activity you described, it's very likely the process of rehabilitating her credit will take a number of years. I would strongly recommend that you not assist her in placing the deposit for a secured credit card. If she can't put aside enough money for a deposit (often $500 or less), it's unlikely she'll be able to set aside the money to pay her card statements each month. Best of luck - I hope things work out well.",
"title": ""
}
] |
2671
|
What to do when paying for an empty office space?
|
[
{
"docid": "98372",
"text": "Generally speaking, yes, you're obliged to pay rent for the remainder of the lease term. But the landlord is obliged to mitigate damages, so if you can find a suitable tenant the landlord has to let you out of the lease.",
"title": ""
},
{
"docid": "237895",
"text": "This sounds obvious, but: If the landlord is easygoing, you could ask him if he's okay with you subletting the space, and then you could sublet it. Of course you may have to do some work yourself to find an appropriate tenant and make sure you're doing everything legally, but if it works, it's better than paying rent for nothing.",
"title": ""
}
] |
[
{
"docid": "13071",
"text": "Agreed that the CEO is lame and only in it for himself in the meantime. But regardless what Lampert does, he has lost billions on Sears already just over time and his recent actions will just recoup a small fraction of it. There is no way he's going to make back his investment. What I don't see how in this economy that most of those locations would be rentable to boutiques that pay more when all it's doing is throwing more retail space onto a market deluged with retail space. Some locations maybe, but many are old and away from the action in the meantime. For instance, many of the closed Kmarts, part of Sears, at least five near me are either still empty after 3-5 years or occupied by something that definitely doesn't pay the same rent, like indoor storage units or indoor paintball arenas and whatnot.",
"title": ""
},
{
"docid": "156070",
"text": "I worked in two open office space environments. It is hard to focus when people are eavesdropping in and commenting on your desk conversations and phone calls, and you'd just like privacy to do your work without scrutiny by prying colleagues. When you are in a coffee shop or coworking space, people have completely different companies or projects to focus on. I'd rather a quiet working space, but I'd also rather coffee shop/coworking over an open office space any day.",
"title": ""
},
{
"docid": "403726",
"text": "I am quite sure you can set up an office in your basement for a lot less than $15,000. Don't build any walls, install any flooring, or upgrade the ceiling. Just install more lights and plugs. Set up your desks, bookshelves and what not in whatever corner is furthest from noises like the laundry room or the furnace. The kids and the nanny get the main floor - just let the whole living room be a giant playroom, for example. This gives you the separation you need to work at home, but you can hear if something really needs your attention. When the kids go off to school, you can refinish the basement into a playroom for kids who don't always need supervision, using the money you are no longer spending on the nanny to install carpeting, real walls, a drop ceiling and so on. Your office stuff can move up to the main floor or to a spare room upstairs if you had one but it wasn't usable during the baby years when upstairs generally has to be quiet. As the kids get older the basement can get tailored to what preteens and teens like. This is essentially what we did, and our square footages and child counts match yours almost precisely. We did eventually convert our garage to carpeted and finished space, and it spent time as an office with staff coming in each day, then some time as a teen playroom (think video games and loud music) after the business rented office space outside the house, but if you don't intend to hire staff for your business you don't need to do this part. We did the majority of the basement wiring ourselves and got an electrician to hook it into the panel and check our work. The budget would probably be less than 10% of the guess from your real estate agent.",
"title": ""
},
{
"docid": "338439",
"text": "Bartering is a tricky discussion. Yes, it definitely applies when you are self-employed and do a job that you would charge anyone else for, but what if you are helping a friend in your spare time? If you receive something in exchange, the value of the item you received would be your income, but what if you don't receive anything in exchange? If the company bought a computer that they loan to you to do occasional work for them, there's no reason you couldn't take the computer home and have that company retain ownership of the property. They could still expense the depreciation of the computer without giving it to you. If it were a car though, you would have to count mileage for personal use as income. What if you exchange occasional tech support for the use of an empty desk and Internet connection? As long as they aren't renting desks for money to others, there's probably no additional marginal cost to them if they allow you to use the space, so the fair market value question breaks down.",
"title": ""
},
{
"docid": "443879",
"text": "Many business owners simply cannot afford to procure office space. An obvious solution to this problem may be what is referred to as a virtual office. A virtual office offers many of the benefits of an actual office without an expensive lease. A virtual office can be especially appealing to small startup businesses which simply haven't grown large enough yet to start looking for commercial office space.",
"title": ""
},
{
"docid": "150721",
"text": "I'm guessing it depends on how much you'd be paying for membership. If you save more than the membership costs you and you actually use the products you buy and they don't get thrown away, then it's worth it. I'm not a member of a warehouse club but I do have a membership for another wholesale outlet, so I know a little bit about buying in bulk. You need to take the same approach to buying goods wholesale as you would in an ordinary outlet, and do a few more things besides. Things like writing a list and sticking to it, making that list logically, so that you minimise the amount of time you spend walking around the shop. The less you see, the less you are likely to buy. Don't be taken in by offers, it's only a bargain if it's something you would have bought anyway. Don't shop on an empty stomach or with you children. And with bulk buying, you have to stick to things with long dates, unless your family gets through something at a phenomenal rate. Things like pet food are good, sugar too if you do a lot of home baking, that kind of thing. Toilet paper and kitchen roll are great to buy in bulk if you have the storage space and toothbrushes are good too. You'll always need them, always need to replace them, they don't take up much space and don't have a use by. The rules differ from family to family. Look at what your family uses and how much time it takes to get through something. That's the best place to start.",
"title": ""
},
{
"docid": "456389",
"text": "\"Scenario 1: Assume that you plan to keep the parking space for the rest of your life and collect the income from the rental. You say these spaces rent for $250 per month and there are fees of $1400 per year. Are there any other costs? Like would you be responsible for the cost of repaving at some point? But assuming that's covered in the $1400, the net profit is 250 x 12 - 1400 = $1600 per year. So now the question becomes, what other things could you invest your money in, and what sort of returns do those give? If, say, you have investments in the stock market that are generating a 10% annual return and you expect that rate of return to continue indefinitely, than if you pay a price that gives you a return of less than 10%, i.e. if you pay more than $16,000, then you would be better off to put the money in the stock market. That is, you should calculate the fair price \"\"backwards\"\": What return on investment is acceptable, and then what price would I have to pay to get that ROI? Oh, you should also consider what the \"\"occupancy rate\"\" on such parking spaces is. Is there enough demand that you can realistically expect to have it rented out 100% of the time? When one renter leaves, how long does it take to find another? And do you have any information on how often renters fail to pay the rent? I own a house that I rent out and I had two tenants in a row who failed to pay the rent, and the legal process to get them evicted takes months. I don't know what it takes to \"\"evict\"\" someone from a parking space. Scenario 2: You expect to collect rent on this space for some period of time, and then someday sell it. In that case, there's an additional piece of information you need: How much can you expect to get for this property when you sell it? This is almost surely highly speculative. But you could certainly look at past pricing trends. If you see that the value of a parking space in your area has been going up by, whatever, say 4% per year for the past 20 years, it's reasonable to plan on the assumption that this trend will continue. If it's been up and down and all over the place, you could be taking a real gamble. If you pay $30,000 for it today and when the time comes to sell the best you can get is $15,000, that's not so good. But if there is some reasonable consistent average rate of growth in value, you can add this to the expected rents. Like if you can expect it to grow in value by $1000 per year, then the return on your investment is the $1600 in rent plus $1000 in capital growth equals $2600. Then again do an ROI calculation based on potential returns from other investments.\"",
"title": ""
},
{
"docid": "500836",
"text": "Call 09910006454 for Fully Furnished Office Space for Rent in Noida. Fully furnished office space for rent in noida is the smart choice for every corporate as it always reduces the Fixed investment cost of the Organization. If you take a fully furnished office space then in maximum cases the owner will furnish your office space as per your approved layout.",
"title": ""
},
{
"docid": "427837",
"text": "Propworld Realty offers luxurious Office Space for Rent in Noida at very economical rentals. As we all know good office space influence your business. In today scenario office space is now being seen as a significant factor in recruiting, maintaining and maximising talent. Hence,if you are looking supreme quality Office Space for Rent in Noida then call us 09810000375.",
"title": ""
},
{
"docid": "169723",
"text": "I agree with mhoran_psprep's answer, but would like to add a few additional points to consider. TurboTax and the professional it will send to represent you in case of a tax audit have no more information about your tax return than what you entered into the program. Now, there are three (or four) different kinds of audits. The correspondence audit is the most common kind where IRS sends a letter requesting copies of documents supporting a deduction or tax credit that you have claimed. Representation is hardly necessary in this case. The office audit is more serious where you have to make an appointment and go to the local IRS office with paperwork that the examining agent needs to see physically, and to answer questions, etc. It would be better to be accompanied by a representative at these meetings. But, office audits are not as common as correspondence audits, and, because they are expensive for the IRS, usually occur when the IRS is fairly sure of recovering a substantial sum of money. If you have been cutting corners and pushing the envelope in taking large enough deductions to make it worthwhile for the IRS to go after you, you probably should not have been using TurboTax to file your income tax return but should have been using an accountant or tax preparer, who would be representing you in case of an audit. If the reason that you used TurboTax is that no accountant was willing to prepare a tax return with the deductions that you wished to claim, I doubt that having TurboTax's representative with you when you go to the IRS office will help you all that much. An example of a field audit is when the IRS agent comes to your home to see if you actually have a space set aside to use exclusively as your home office as you claimed you did etc. A Taxpayer Compliance Measurement Program (TCMP) audit is where the IRS randomly chooses returns for statistical checks that taxpayers are complying with the regulations. The taxpayer has to prove every line of the return. You claim to be filing as Married Filing Jointly? Bring in your marriage certificate. Submit birth certificates and Social Security cards of your dependent children. And so on. Yes, having TurboTax represent you for only $49.95 will help, but not if you are not married and cannot provide the IRS with a marriage certificate etc. So, pay the fee for peace of mind if you like, and as insurance as littleadv suggests. But be sure you understand what you might be getting for the money. Most tax returns selected for audit are selected for what the IRS believes are good reasons, not at random. If what you said If my tax return is randomly selected for audit they will represent me. is interpreted literally, TurboTax will represent you only if your return is selected for examination under the TCMP program, not if it is selected for audit because the IRS believes that something is fishy about your return. And as always, you get what you pay for.",
"title": ""
},
{
"docid": "272940",
"text": "\"You are pushing your luck, but not because you're not in the US, because it is likely that you're not qualified. From what you said, I doubt you can take it (I'm not a professional though, get a professional opinion). You say \"\"dedicated space\"\". It has to be an exclusive room. You cannot deduct 10 sq. ft. from your living room because your computer that is used wholly for your business is there. It has to be a room that is used exclusively for your business, and for your business only. I.e.: nothing not related to the business is there, and when you're there the only thing you do is working on your business. Your office doesn't have to be in the US necessarily, to the best of my knowledge. Your office must be in your home. If you take primary residence exclusion as part of your FEI, then I doubt you can deduct as well.\"",
"title": ""
},
{
"docid": "416062",
"text": "\"In May 2011, a report to the board by Promontory Financial Group, a Washington consultant hired as part of the CFTC Dooley settlement, concluded that the firm had vastly improved\"\" its systems and risk controls, and praised management for setting \"\"a tone at the top\"\" supporting \"\"best practices.\"\" I actually did some technology work for Promontory Financial Group for a short period. What a bunch of tools. They had a nice office in a newer office building in the business district of Washington DC, not far from the Treasury. Their \"\"server room\"\" was actually a closet. The number of servers they had produced a lot of heat. It had minimal ventiliation. Their solution? Bring in a portable A/C unit. Great, but due to the humidity and the amount of heat/energy transfer, it produced a lot of condensation runoff. There was no drain. The solution? Think of the largest Rubbermaid outdoor garbage can that you can buy, and put it under the unit to collect the condensation output. It was probably 50 gallons. It filled up in about three or four days, an indication of the output. Part of the nightly cleaning crew's responsibility was to bail (literally) the water out of the can, and put it in a mop bucket, and wheel it down to the cleaning closet that did have a sink and empty it. The can had wheels, but who would want to risk rolling 400 pounds of water on tinkery casters down a lavish passageway? Problem? On long weekends/holidays, there was no cleaning crew. So they purchased a \"\"Mister Sensaphone\"\" (yes there really was such a device), so that when the can started to overflow, the moisture detector would trigger, it would page the system administrator, and they would drive into the office and bail it out. All of that because they did not want to pay $30,000 to install additional ac capacity on the roof and ventilate their server room. I think they were actually proud of this setup, like it was a demonstration of some \"\"out of the box\"\" creativity.\"",
"title": ""
},
{
"docid": "515207",
"text": "\"In \"\"steady state\"\", the refrigerator only has to pump out the heat that has leaked in from outside. The amount of heat leaked is related to the difference between interior and exterior temperatures, and the overall insulation quality. Thus, a refrigerator full of cold food uses the same amount of energy as a refrigerator full of cold air. In practice, people open the door, take cold food out, put \"\"warm\"\" food in, and the unit may also make ice, dispense cold water, and defrost itself. Aside from tweaking those uses, (e.g. minimizing time with the door open), a useful trick is to use empty milk cartons or similar containers to fill up unused space. This helps by reducing the amount of cold air that escapes when the door is opened, and the air in the cartons has low thermal mass, so it cools down rapidly. When you need the space, you can remove the cartons and set them aside. Similarly, water-filled cartons may be used as a sort of thermal ballast--leveling out the temperature fluctuations within the refrigerator, particularly if the electric utilities are erratic. However, they increase the cost of refrigeration when cooling the water in the first place, and when you eventually dump out the water, the expense of cooling it goes down the drain.\"",
"title": ""
},
{
"docid": "489420",
"text": ">Correct. So you feel the proper response is to pepperspray people? Perhaps you can watch the long version of what happened in [this video](http://www.youtube.com/watch?v=hhPdH3wE0_Y&feature=colike). Feel free to skip around if you want. The point is, the police made arrests, the children were blocking them and the children were warned. They were warned so many times it's their own stupidity that got them pepper sprayed. Empty threats are empty. Beats a night stick to the head. I am worried about the bloodbath that might occur when we have to fight off the black bloc idiots that want more free stuff. >what prevents a race to the bottom with wages and benefits if people don't collectively bargain What prevents public sector employees from outpacing wages and benefits of the private sector due to collective coercion? They're already doing it. We cannot pay our debts by creating government jobs. We cannot continue to afford COLAs in a down economy, let alone the lifetime benefits some of them get. What happens when they collapse the system out of their own stupid greed? That seems to be the goal of many on the left. edit: Not sure if OSHA is actually getting cuts, but EEOC is expanding and NLRB is really screwing things up.",
"title": ""
},
{
"docid": "460591",
"text": "With set targets and work analysis of each team member, there's no room for ambiguity or assumptions. Work needs to be regularly submitted for review and excuses won't work if you have already placed a clear picture in team meetings. Ignoring problems (both personal and professional) will only intensify them so find the root cause and move ahead. As a team leader remain motivated and set an inspiring example for the rest of the team to follow suit. Find commercial office space for rent, meeting room space for rent , conference rooms on rent. Many options available for training spaces, co-working spaces and shared office spaces in Mumbai, Hyderabad, Pune, Bengaluru, Gurgaon, Noida & Chennai",
"title": ""
},
{
"docid": "314872",
"text": "If you help find a suitable next tenant and help smooth out the transition, most landlord generally don't have an issue to terminate the lease early, and move the contract to the new tenant. Remember that the biggest concerns for landlords is that they don't want the place to be empty (leaving an apartment empty costs them money due to tax, strata, bills, etc as well as putting in jeopardy whatever future plans they might have made under the assumption of a stable income from the rent). You could also offer to pay for the listing agent and other switching fees (e.g. putting bills under the new tenant's name, etc). If you don't have an early termination clause the rental agreement, or sometimes even when you do, these things are often negotiable. If you can guarantee that your leave won't leave them with an empty apartment with no-one paying rentals, most reasonable landlords wouldn't have issue with terminating early. Many rental agreements also have terms regarding early terminations. This usually involves paying a fee which amounts to a month or two of rent. This may vary.",
"title": ""
},
{
"docid": "324417",
"text": "\"**Reposted so you don't have to look at silly GIFs for 50% of the article.** Sophie is a physical penetration tester and information security consultant. She specializes in social engineering security assessments including physical, voice (vishing) and text (phishing). She consults in remediation and prevention of security incidents through creation of policy and procedures, as well as customized training for your individual office culture. Prior to working in infosec, Sophie was a journalist, photographer, and a mom. Hello! My name is Sophie and I break into buildings. I get paid to think like a criminal. Organizations hire me to evaluate their security, which I do by seeing if I can bypass it. During tests I get to do some lockpicking, climb over walls or hop barbed wire fences. I get to go dumpster diving and play with all sorts of cool gadgets that Q would be proud of. But usually, I use what is called social engineering to convince the employees to let me in. Sometimes I use email or phone calls to pretend to be someone I am not. Most often I get to approach people in-person and give them the confidence to let me in. My frequently asked questions include: What break-in are you most proud of? What have you done for a test that you were the most ashamed of? What follows is the answer to both of these questions. A few months ago, a client had hired me to test two of their facilities. A manufacturing plant, plus data center and office building nearby. First step: open source intelligence, or OSINT. I look at maps, satellite images, study what I can of their delivery and supply schedules, and so on. The manufacturing facility looked like a prison. No windows, heavy iron gates, no landscaping. Generally a monstrosity of architecture. This facility had armed guards, badge readers, biometric security controls and turnstiles at every entrance. I remember thinking, \"\"It's got to be hell to work in there. I wonder if I can use that…\"\" One thing was for sure… The chances of tailgating (following behind an employee with valid credentials) into this building were next to non-existent. I was going to have to get down and dirty with my social engineering. First stop: LinkedIn. Your LinkedIn is my best friend. The more information you have on your LinkedIn, the more options I have. I have several fake LinkedIn profiles that you are probably connected to. I scour profiles of employees who work at these facilities, and cross-reference them to other social media sites. And I find a lovely young woman who I'm going to call Mary. Mary was a brand-new hire working as an assistant at the manufacturing facility. Mary had a public Facebook account too. On Mary's public Facebook account, she documented all of her family's adventures. Side note: Now I know where Mary went to high school, her mother's maiden name, the names of her pets, etc. Answers to those \"\"security questions\"\" you use to reset your passwords are very easy to find if you aren't careful with that information. Not to mention that now I know where Mary works, where her kids go to school, where they vacation…I could go on. Scary stuff. This is not an advanced investigation. I'm not a private investigator and I don't have the resources of the NSA. But I can do a lot of damage with simple methods. Most notably to me, there were photos Mary posted of her time volunteering with a certain maternity support center. Her passion for children and caring new moms was very plain. So of course, I took advantage of it. For this assessment I played two roles. For the first, I spoofed my phone number to make it look like it was coming from the company's headquarters. I called the front desk of the manufacturing facility and was transferred to Mary. \"\"Hi Mary!\"\" I said, \"\"My name is Barbara.\"\" \"\"I am a project coordinator with facilities management. We are renovating a few of our facilities. We are sending an interior designer out to you tomorrow so she can put together proposals to update your space!\"\" Mary replied, \"\"Well that's great! But why the short notice?\"\" I could feel her getting suspicious, so I pulled out my trump card… *Sigh* \"\"Well Mary… You really should have heard from me sooner. I've just been so overloaded at work…I feel like I can't catch up, and to top it off the baby is due in 6 weeks. If my boss finds out I messed this up he's going to flip.\"\" I was really getting into this, voice shaking. (Yes, I know, I'm a terrible human being.) She cut me off, \"\"Oh hunny, hunny it's ok. We will work this out! Tell me about the baby! Is it your first? Boy or girl?!\"\" Our Mary was committed at this point. Not because she is stupid, but because she is a good person. She wanted to help me. We talked babies and birth plans for a while (never pick a pretext you can't speak about at length.) Mary took down the name of the \"\"designer\"\" who was coming by the next day and we said our goodbyes. Mary could have saved her company a lot of heartache by simply verifying that I was who I claimed to be. (Just to be clear here, I would never give out Mary's real identity. I'm not totally heartless. This could have happened to anyone. She has not been fired.) I showed up the next day as \"\"Claire\"\" with a fictional architecture firm that I had made business cards and a website for. My alter-ego Barb had done most of the leg work for me. When I arrived, Mary and her boss were waiting for me with smiles. I shook hands all around and handed them the business card I printed out the night before. I was given a visitor badge and the red carpet was rolled out. I gained rapport with the staff there by asking them to tell me what they wanted in an office space. They were so excited. I might have claimed to be on the team that put together the Google offices…(Yes, I am HORRIBLE. This is my inner demon child.) \"\"You want a standing desk? New chairs over here?! Ergonomic keyboards for everyone! Let's look at swatches!\"\" We became best buds. I was given complete and unaccompanied access to the facility where I stayed for several hours. I gained network access and stole several thousands of dollars in physical primitives by picking my way through cheap locks (credit to Deviant Ollam for the rad lockpicking animations.) This client had been pretty confident that I wouldn't get into either facility, much less be able to hit both in a short time span. So the timeline was left to my discretion, but it was assumed that I would need to fly to the area twice. I didn't see the need in burdening them with two round-trip expenses. I went back to Mary's office and said, \"\"Well I think I have what I need from here. How do I get to the office center?\"\" She looked at her watch and said, \"\"It's almost lunch time. I'll take you there!\"\" A whole group of us piled into the parking lot, and they took me to a nearby taco shop. That's right. My Marks took me to get tacos… I love my job. After lunch they drove me to the offices and a few of them came in with me to show me around. I took FOREVER looking around this office space, and eventually they said their goodbyes because they had to go back to work. They had a strict policy of escorting visitors. But I had been seen walking around with trusted insiders so no one questioned me. I was free to take my time. I made myself at home. My main objective at this site was to weasel my way into private corner offices. When I accomplished my goals, I tracked down my point of contact's office. This is the man who hired me in the first place. This is the best part of every job. Steve was there, hard at work when I disturbed his groove by knocking on the door. He glanced up, \"\"Hi there, can I help you?\"\" I smiled. \"\"Hi Steve! I'm Sophie from Sincerely Security. It's nice to meet you in-person!\"\" I will never forget the look on his face… Pure gold. \"\"Who?.... Wait, what? How? How did you get in here?!\"\" We stayed in his office and talked for a long time. I went over exactly the steps that could have prevented my success. First of all, the desire to help others is human and natural. We don't want to discourage that. Second, I'm sure they did have some sort of policy that required visitors to check in showing government issued identification, but they weren't following it. We also need to post by every computer, phone and door: \"\"TRUST, BUT VERIFY.\"\" An employee who does their homework can ruin my day. Third, if it seems too good to be true, it probably is. Is your company going to hire the team who designed Google's offices? Magic 8 ball says no. Lastly, the team who took me to the second location should have found someone else to escort me through the building. I've been doing this job for a couple years now, and almost every job is a variant of this story. Very rarely do I go through an entire assessment without some sort of social engineering. There are ways to protect yourself and your company from attacks like this. I think it starts by sharing stories like these, and educating and empowering each other to be vigilant.\"",
"title": ""
},
{
"docid": "529428",
"text": "Having functional storage spaces in your office, including lockers, are a must, especially when you are working with many employees. Here at Prodigy Office Furniture, we have the highest quality bookcases, filing cabinets, storage cupboards and lockers Melbourne has to offer.",
"title": ""
},
{
"docid": "520386",
"text": "Your best approach is to assess rent levels in your local area for offices of a similar size. You need to take into account all the usuals - amenities, parking, etc, just as if your home-office was provided by a third-party. Get your $/sq ft and work out the monthly amount. With this figure, you need to then work out what % of it you can charge. If the space is used exclusively for the business, charge 100%. If it's used about half the time, charge 50%, etc. I would strongly advise you to do two things - 1. make sure your accountant and your attorney help you get this squared away. 2. document everything about how you arrived at the cost. Nothing fancy, but dates, realtors, addresses, $/sq foot. A simple table will do. By doing these two things, if the IRS should come around to chat, you should be covered.",
"title": ""
},
{
"docid": "268383",
"text": "There is no distribution limit, only a contribution limit. You can empty your HSA completely without tax or penalty, as long as the expenses are used for eligible medical expenses. In addition, you can reimburse yourself in the future for expenses that you have now, as long as you have an HSA account in place. For example, you said that your dental bill was $3500, and you only had $3300 in your HSA, so you emptied your HSA and paid the rest from your checking account. When you do get more money in the HSA, even if it isn't until next year, you can reimburse yourself for the $200 that you had to pay out of pocket on your dental bill. And if you don't have enough money in your HSA this year to cover all of your birth expenses (congrats, by the way), you can reimburse yourself in a future year. Just make sure you keep good records on what the distributions were used for, in case you get audited.",
"title": ""
},
{
"docid": "126743",
"text": "\"Most answers have concentrated on this being a scam, however, it is possible this is an innocent mistake. Australian bank account numbers do not have redundant digits to be used to validate an account number; all of the numbers are data and uniquely identify a bank and branch (the BSB number) and an account (the Account number). Computer check digits are not part of bank account numbers because bank account numbers pre-date computers. It is entirely possible that someone entering an incorrect number can, by chance, hit upon an existing account. As the bank clearance system in Australia is entirely automatic there is no cross-checking of account numbers with account names. Internet banking in Australia is not a wire-transfer as is common in places like the USA (although these can be done): here you are effectively accessing your bank's \"\"back office\"\". Nor is it like the BPay service which is used primarily by B to C businesses as a way for their customers to pay their bills; when using this service the biller code will show you who you are paying and the customer number does have check digit validation. I run a business in Australia and it has happened to us on several occasions than an employee or supplier has given us incorrect numbers. Usually, it is not a real account and after a week or so the money makes its way back to us with a message like NO ACCOUNT or A/C CLOSED. Very occasionally, however, the wrong number hits a live account: when that happens the person who f*&ked up needs to contact their bank and try and get the transaction reversed. If there is money in the destination account this usually happens with little fuss, however, if the destination account has been closed or emptied things get problematic. Of course, taking money that isn't yours is stealing even if it happens to be sitting in your bank account. However, unless the sum involved is significant the police are usually not interested in diverting their attention away from \"\"serious\"\" crimes like homicide, armed robbery and terrorism so the aggrieved party is usually on their own. That said, this is probably a scam because they called you rather than your bank doing so. They cannot get your phone number from your account number: they have to know who you are and what your account number is. This is not as hard to do as it sounds since both your name and account number are prominently printed on your cheques and deposit books (possibly your phone number as well which saves them looking it up in the White Pages).\"",
"title": ""
},
{
"docid": "177074",
"text": "\"If you use \"\"a room or other separately identifiable space\"\" within your apartment exclusively for your business, then you might be able to recoup a fraction of your rent for that. Check the rules for home office at the IRS and adopt a consistent and well-documented approach. (I would pay your full rent out of your personal account, and then do an \"\"expense report\"\" for the portion that's legitimately business related, but that's not a unique approach.) Other than that, I agree with the answer by litteadv - You cannot reduce your tax by the full amount of your rent just by having the S Corp pay, and trying to do so is probably playing with fire. Generally speaking, don't comingle business and personal expenses like that.\"",
"title": ""
},
{
"docid": "179839",
"text": "I believe the worst part about Surface is running Windows 8. It's terrible. Horrible! And yes, most of the terrible experience for users is that everything is all different now, for little reason, just like shifting to the continual interface revamp of *every* version of Office since 2007. Change for change's sake? Users are saying no thanks. I know not *all* of it is change for change's sake, and I know about the requirement for a new OS to handle a touch-based interface--I get that. But users have too much interface-change fatigue and are getting tired of paying more and getting less, all the while having to relearn whole systems of interface design that doesn't truly add to their productivity--especially because the next interface change will occur in only 12 - 24 months. The ribbon interface is a wonderful waste of space, just when every device now made has a much smaller vertical resolution than horizontal (widescreen formats). So take up much more vertical space so now the user cannot see what they're working on. Simply brilliant! Or, they could have put the toolbars off to the side where they would be out of the way--maybe that's the next scheduled interface change? Put a touch-based Windows 7 OS on Surface and I believe you'd see an instant jump in sales. Part of my business is fixing/building computers for people. Many of them have simply purchased the latest laptop/computer/whatever they could find in stores and when they attempt to *use* their nifty new speed machine, they face continual frustration with the bizarre, confusing, and seemingly disconnected double-interface with Windows 8. The bugs have them utterly baffled, and using skype is a disaster, since they can no longer figure out how to quickly tell skype to use the in-system microphone and webcam for the 13th time this month when receiving a call (like they used to be able to do--never mind that skype continually forgets these settings, as usual). They also have to create some pointless Microsoft account to use the software/hardware they just purchased. Why? People aren't interested in being a card-carrying member of the Mickey Mouse Club anymore--so why *require* it of them? They generally need to get something productive done, and all this bullshit stands in their way. Three separated versions of email--that aren't connected at all behind the scenes--is a recipe for confusion. Another part of my business is industrial design, and with that, the creation of productive, comfortable interfaces. Here's my secret--good interface design really isn't that difficult--you just need to listen to what the users want. Bam! Now even Microsoft can turn things around.",
"title": ""
},
{
"docid": "451782",
"text": "Investing in mutual funds, ETF, etc. won't build a large pool of money. Be an active investor if your nature aligns. For e.g. Invest in buying out a commercial space (on bank finance) like a office space and then rent it out. That would give you better return than a savings account. In few years time, you may be able to pay back your financing and then the total return is your net return. Look for options like this for a multiple growth in your worth.",
"title": ""
},
{
"docid": "237784",
"text": "Yes, automatic rate increases are typical in my experience (and I think it's very greedy, when it's based on nothing except that your lease is up for renewal, which is the situation you are describing). Yes, you should negotiate. I've had success going to the apartment manager and having this conversation: Make these points: Conclude: I am not open to a rate increase, though I will sign a renewal at the same rate I am paying now. This conversation makes me very uncomfortable, but I try not to show it. I was able to negotiate a lease renewal at the same rate this way (in a large complex in Sacramento, CA). If you are talking to a manager and not an owner, they will probably have to delay responding until they can check with the owner. The key really is that they want to keep units rented, especially when units are staying empty. Empty units are lost income for the owner. It is the other empty units that are staying empty that are the huge point in your favor.",
"title": ""
},
{
"docid": "476812",
"text": "I'll give you a stark example of China's debt-driven construction growth: Since '09 China has constructed enough physical office space buildings to give every Chinese man, woman, and child their own cubicle - 3 times over! Given that these buildings were largely financed by debt, its hard to see how those creditors get all their money back given that there simply are not enough Chinese people to occupy and pay/rent that space in order for break-even to occur.",
"title": ""
},
{
"docid": "241147",
"text": "As we know location and connectivity plays a very important role in deciding the place you want to work from. Demand of ready to move office spaces in Noida is increasing day by day. The Metro rail extension or emergence in Noida has a huge impact on increasing the demand of ready to move office space in Noida.",
"title": ""
},
{
"docid": "240865",
"text": "\">A lot of countries with harsher rules and higher taxes have lots of big companies that makes massive profits. Often with price protection mandates. Did you know in Germany the same Jeans they sell in Wal-mart for $18/pair sell for $80-100/pair? Do you know why? The government set's MSRP price controls and no one can sell below that amount. The same is true for all sorts of products. Do we really want to go down that path? >I have no sympathy for this man. Compete or die. That's a bit unfair when you don't know the intimate details of the accounting/liabilities any changes would cost. But surely we could use a few hundred more \"\"for lease\"\" warehouse space and a few thousand more empty storefronts, right? >Obama wont change much that he already hasn't. How much do you think it costs employers to keep 26 year old adult children on their parents healthcare + them living at home? That's ONE example. Obama is also looking at mandating higher employer medical insurance costs in general (employers having to pay a higher percentage of the costs). If somebody can avoid that by cutting payrolls or becoming \"\"more efficent\"\" with the number of employees they will do it. This is true for ANY company. >This is just a guy that in the past has bragged about his ability to affect the florida vote trying to affect it again. And? People brag all the time, about all sorts of things. Personally I think this is less \"\"slimey\"\" than Obama gloating about killing Osama Bin laden as if death is cheap because an individual is an outsider or another religion. >Slimy bastard. Again, you don't know all the details or the guy personally. But it's nice to know you're reserved and mature about somebody you don't even know. From your name should I assume you like Croc shoes? Which are lame and thus making you a loser? Superficial assumptions and judgements help nobody and in many cases are not even true.\"",
"title": ""
},
{
"docid": "232011",
"text": "\"We just got in an argument in another thread, and I don't necessarily want to continue it, but was browsing your comments and saw this. I can say from personal experience (I have several high net worth clients) that this isn't true. The rich do the opposite of leave their money laying around. They invest it to make more money. They buy office buildings, fund new companies, buy up stocks, and drive investment in general. Someone has to do these things. Office buildings can't just be owned by \"\"the people\"\". Someone with a ton of money has to come along and fund them. For example, one of my friends knows Elon Musk (founder of Pay-Pal, Tesla Motors, Solar City, and Space X). He is *worth* $2 billion, but was living on other people's couches (including my friend's) after he sold Pay-Pal because he had just poured all of his cash into starting Tesla Motors. He was a billionaire without a penny to his name (well I'm sure he had a little cash lying around, but was essentially asset rich, cash broke). THAT is what most ultra rich people are like. They invest their money, they don't just horde it away in a savings account. The things people like Musk do create jobs and sometimes entire industries (or three entire industries in his case). I'm by no means arguing that this is right or wrong, but to say rich people just have money lying around is absurd. You don't get rich by saving money in the bank, you get rich by spending it. I'm in my early 20's, but already own multiple apartment buildings. I'm not rich yet and am in the same boat as Musk was. I have tons of assets, but almost no cash I can spend. However, you bet my efforts are creating jobs. I'm employing people to renovate and people to repair and maintain these buildings. I'm helping stop the bleeding in the real estate market, but, according to the narrative, I'm evil because my \"\"income\"\" is six figures.\"",
"title": ""
},
{
"docid": "306742",
"text": "Office space for rent in noida sector 62 is the best option in Noida as it lies near NH 24, East Delhi & Indirapuram, Ghaziabad. Sector 62 Noida is among those sectors of noida which are typically designed for IT & IT enable services usage along with institutional properties. We have all type of office spaces at very economical rentals.",
"title": ""
}
] |
4939
|
How can I find a list of all North American ETF's including symbols?
|
[
{
"docid": "103987",
"text": "You can use www.etfdb.com and search on geography.",
"title": ""
}
] |
[
{
"docid": "29642",
"text": "Some of the ETFs you have specified have been delisted and are no longer trading. If you want to invest in those specific ETFs, you need to find a broker that will let you buy European equities such as those ETFs. Since you mentioned Merrill Edge, a discount broking platform, you could also consider Interactive Brokers since they do offer trading on the London Stock Exchange. There are plenty more though. Beware that you are now introducing a foreign exchange risk into your investment too and that taxation of capital returns/dividends may be quite different from a standard US-listed ETF. In the US, there are no Islamic or Shariah focussed ETFs or ETNs listed. There was an ETF (JVS) that traded from 2009-2010 but this had such little volume and interest, the fees probably didn't cover the listing expenses. It's just not a popular theme for North American listings.",
"title": ""
},
{
"docid": "332924",
"text": "\"I recommend avoiding trading directly in commodities futures and options. If you're not prepared to learn a lot about how futures markets and trading works, it will be an experience fraught with pitfalls and lost money – and I am speaking from experience. Looking at stock-exchange listed products is a reasonable approach for an individual investor desiring added diversification for their portfolio. Still, exercise caution and know what you're buying. It's easy to access many commodity-based exchange-traded funds (ETFs) on North American stock exchanges. If you already have low-cost access to U.S. markets, consider this option – but be mindful of currency conversion costs, etc. Yet, there is also a European-based company, ETF Securities, headquartered in Jersey, Channel Islands, which offers many exchange-traded funds on European exchanges such as London and Frankfurt. ETF Securities started in 2003 by first offering a gold commodity exchange-traded fund. I also found the following: London Stock Exchange: Frequently Asked Questions about ETCs. The LSE ETC FAQ specifically mentions \"\"ETF Securities\"\" by name, and addresses questions such as how/where they are regulated, what happens to investments if \"\"ETF Securities\"\" were to go bankrupt, etc. I hope this helps, but please, do your own due diligence.\"",
"title": ""
},
{
"docid": "472663",
"text": "\"An Exchange-Traded Fund (ETF) is a special type of mutual fund that is traded on the stock exchange like a stock. To invest, you buy it through a stock broker, just as you would if you were buying an individual stock. When looking at a mutual fund based in the U.S., the easiest way to tell whether or not it is an ETF is by looking at the ticker symbol. Traditional mutual funds have ticker symbols that end in \"\"X\"\", and ETFs have ticker symbols that do not end in \"\"X\"\". The JPMorgan Emerging Markets Equity Fund, with ticker symbol JFAMX, is a traditional mutual fund, not an ETF. JPMorgan does have ETFs; the JPMorgan Diversified Return Emerging Markets Equity ETF, with ticker symbol JPEM, is an example. This ETF invests in similar stocks as JFAMX; however, because it is an index-based fund instead of an actively managed fund, it has lower fees. If you aren't sure about the ticker symbol, the advertising/prospectus of any ETF should clearly state that it is an ETF. (In the example of JPEM above, they put \"\"ETF\"\" right in the fund name.) If you don't see ETF mentioned, it is most likely a traditional mutual fund. Another way to tell is by looking at the \"\"investment minimums\"\" of the fund. JFAMX has a minimum initial investment of $1000. ETFs, however, do not have an investment minimum listed; because it is traded like a stock, you simply buy whole shares at whatever the current share price is. So if you look at the \"\"Fees and Investment Minimums\"\" section of the JPEM page, you'll see the fees listed, but not any investment minimums.\"",
"title": ""
},
{
"docid": "112208",
"text": "You can check the website for the company that manages the fund. For example, take the iShares Nasdaq Biotechnology ETF (IBB). iShares publishes the complete list of the fund's holdings on their website. This information isn't always easy to find or available, but it's a place to start. For some index funds, you should just be able to look up the index the fund is trying to match. This won't be perfect (take Vanguard's S&P 500 ETF (VOO); the fund holds 503 stocks, while the S&P 500 index is comprised of exactly 500), but once again, it's a place to start. A few more points to keep in mind. Remember that many ETF's, including equity ETF's, will hold a small portion of their assets in cash or cash-equivalent instruments to assist with rebalancing. For index funds, this may not be reflected in the index itself, and it may not show up in the list of holdings. VOO is an example of this. However, that information is usually available in the fund's prospectus or the fund's site. Also, I doubt that many stock ETF's, at least index funds, change their asset allocations all that frequently. The amounts may change slightly, but depending on the size of their holdings in a given stock, it's unlikely that the fund's manager would drop it entirely.",
"title": ""
},
{
"docid": "271646",
"text": "You have to be kidding. The derivatives market alone is in the hundreds of trillions and that's just a low ball guess. The Zero Interest Money Machine has been running full throttle for 8 years now. You know it's bad when they list the Billionaires and there are all these guys from South America who haven't figured out how to hide their money or care more about the status while all the North American and European Billionaires are disappearing or appear to be losing money (they just figured out how to hide more of it).",
"title": ""
},
{
"docid": "360716",
"text": "\"What you seem to want is a dividend reinvestment plan (DRIP). That's typically offered by the broker, not by the ETF itself. Essentially this is a discounted purchase of new shares when you're dividend comes out. As noted in the answer by JoeTaxpayer, you'll still need to pay tax on the dividend, but that probably won't be a big problem unless you've got a lot of dividends. You'll pay that out of some other funds when it's due. All DRIPs (not just for ETFs) have potential to complicate computation of your tax basis for eventual sale, so be aware of that. It doesn't have to be a show-stopper for you, but it's something to consider before you start. It's probably less of a problem now than it used to be since brokers now have to report your basis on the 1099-B in the year of sale, reducing your administrative burden (if you trust them to get it right). Here's a list of brokerages that were offering this from a top-of-the-search-list article that I found online: Some brokerages, including TD Ameritrade, Vanguard, Scottrade, Schwab and, to a lesser extent, Etrade, offer ETF DRIPs—no-cost dividend reinvestment programs. This is very helpful for busy clients. Other brokerages, such as Fidelity, leave ETF dividend reinvestment to their clients. Source: http://www.etf.com/sections/blog/23595-your-etf-has-drip-drag.html?nopaging=1 Presumably the list is not constant. I almost didn't included but I thought the wide availability (at least as of the time of the article's posting) was more interesting than any specific broker on it. You'll want to do some research before you choose a broker to do this. Compare fees for sure, but also take into account other factors like how soon after the dividend they do the purchase (is it the ex-date, the pay date, or something else?). A quick search online should net you several decent articles with more information. I just searched on \"\"ETF DRIP\"\" to check it out.\"",
"title": ""
},
{
"docid": "276983",
"text": "You haven't looked very far if you didn't find index tracking exchange-traded funds (ETFs) on the Toronto Stock Exchange. There are at least a half dozen major exchange-traded fund families that I'm aware of, including Canadian-listed offerings from some of the larger ETF providers from the U.S. The Toronto Stock Exchange (TSX) maintains a list of ETF providers that have products listed on the TSX.",
"title": ""
},
{
"docid": "61575",
"text": "\"Thanks for the info, things are starting to make more sense now. For some reason I've always neglected learning about investments, now that Im in a position to invest (and am still fairly young) I'm motivated to start learning. As for help with TD Ameritrade, I was looking into Index Funds (as another commenter mentioned that I should) on their site and am a little overwhelmed with the options. First, I'm looking at Mutual Funds, going to symbol lookup and using type = \"\"indeces\"\". I'm assuming that's the same thing as an \"\"Index Fund\"\" but since the language is slightly different I'm not 100% sure. However, at that point I need some kind of search for a symbol in order to see any results (makes sense, but I dont know where to start looking for \"\"good\"\" index funds). So my first question is: If I FIND a good mutual fund, is it correct to simply go to \"\"Buy Mutual Funds\"\" and find it from there? and if so, my second question is: How do I find a good mutual fund? My goal is to have my money in something that will likely grow faster than a savings account. I don't mind a little volatility, I can afford to lose my investment, I'd plan on leaving my money in the fund for a several years at least. My last question is: When investing in these types of funds (or please point me in another direction if you think Index Funds aren't the place for me to start) should I be reinvesting in the funds, or having them pay out dividends? I would assume that reinvesting is the smart choice, but I can imagine situations that might change that in order to mitigate risk...and as I've said a few times in this thread including the title, I'm a complete amateur so my assumptions aren't necessarily worth that much. Thanks for the help, I really appreciate all the info so far.\"",
"title": ""
},
{
"docid": "117049",
"text": "\"It's easy for me to look at an IRA, no deposits or withdrawal in a year, and compare the return to some index. Once you start adding transactions, not so easy. Here's a method that answers your goal as closely as I can offer: SPY goes back to 1993. It's the most quoted EFT that replicates the S&P 500, and you specifically asked to compare how the investment would have gone if you were in such a fund. This is an important distinction, as I don't have to adjust for its .09% expense, as you would have been subject to it in this fund. Simply go to Yahoo, and start with the historical prices. Easy to do this on a spreadsheet. I'll assume you can find all your purchases inc dates & dollars invested. Look these up and treat those dollars as purchases of SPY. Once the list is done, go back and look up the dividends, issues quarterly, and on the dividend date, add the shares it would purchase based on that day's price. Of course, any withdrawals get accounted for the same way, take out the number of SPY shares it would have bought. Remember to include the commission on SPY, whatever your broker charges. If I've missed something, I'm sure we'll see someone point that out, I'd be happy to edit that in, to make this wiki-worthy. Edit - due to the nature of comments and the inability to edit, I'm adding this here. Perhaps I'm reading the question too pedantically, perhaps not. I'm reading it as \"\"if instead of doing whatever I did, I invested in an S&P index fund, how would I have performed?\"\" To measure one's return against a benchmark, the mechanics of the benchmarks calculation are not needed. In a comment I offer an example - if there were an ETF based on some type of black-box investing for which the investments were not disclosed at all, only day's end pricing, my answer above still applies exactly. The validity of such comparisons is a different question, but the fact that the formulation of the EFT doesn't come into play remains. In my comment below which I removed I hypothesized an ETF name, not intending it to come off as sarcastic. For the record, if one wishes to start JoesETF, I'm ok with it.\"",
"title": ""
},
{
"docid": "113786",
"text": "\"There are two umbrellas in investing: active management and passive management. Passive management is based on the idea \"\"you can't beat the market.\"\" Passive investors believe in the efficient markets hypothesis: \"\"the market interprets all information about an asset, so price is equal to underlying value\"\". Another idea in this field is that there's a minimum risk associated with any given return. You can't increase your expected return without assuming more risk. To see it graphically: As expected return goes up, so does risk. If we stat with a portfolio of 100 bonds, then remove 30 bonds and add 30 stocks, we'll have a portfolio that's 70% bonds/30% stocks. Turns out that this makes expected return increase and lower risk because of diversification. Markowitz showed that you could reduce the overall portfolio risk by adding a riskier, but uncorrelated, asset! Basically, if your entire portfolio is US stocks, then you'll lose money whenever US stocks fall. But, if you have half US stocks, quarter US bonds, and quarter European stocks, then even if the US market tanks, half your portfolio will be unaffected (theoretically). Adding different types of uncorrelated assets can reduce risk and increase returns. Let's tie this all together. We should get a variety of stocks to reduce our risk, and we can't beat the market by security selection. Ideally, we ought to buy nearly every stock in the market so that So what's our solution? Why, the exchange traded fund (ETF) of course! An ETF is basically a bunch of stocks that trade as a single ticker symbol. For example, consider the SPDR S&P 500 (SPY). You can purchase a unit of \"\"SPY\"\" and it will move up/down proportional to the S&P 500. This gives us diversification among stocks, to prevent any significant downside while limiting our upside. How do we diversify across asset classes? Luckily, we can purchase ETF's for almost anything: Gold ETF's (commodities), US bond ETF's (domestic bonds), International stock ETFs, Intl. bonds ETFs, etc. So, we can buy ETF's to give us exposure to various asset classes, thus diversifying among asset classes and within each asset class. Determining what % of our portfolio to put in any given asset class is known as asset allocation and some people say up to 90% of portfolio returns can be determined by asset allocation. That pretty much sums up passive management. The idea is to buy ETFs across asset classes and just leave them. You can readjust your portfolio holdings periodically, but otherwise there is no rapid trading. Now the other umbrella is active management. The unifying idea is that you can generate superior returns by stock selection. Active investors reject the idea of efficient markets. A classic and time proven strategy is value investing. After the collapse of 07/08, bank stocks greatly fell, but all the other stocks fell with them. Some stocks worth $100 were selling for $50. Value investors quickly snapped up these stocks because they had a margin of safety. Even if the stock didn't go back to 100, it could go up to $80 or $90 eventually, and investors profit. The main ideas in value investing are: have a big margin of safety, look at a company's fundamentals (earnings, book value, etc), and see if it promises adequate return. Coke has tremendous earnings and it's a great company, but it's so large that you're never going to make 20% profits on it annually, because it just can't grow that fast. Another field of active investing is technical analysis. As opposed to the \"\"fundamental analysis\"\" of value investing, technical analysis involves looking at charts for patterns, and looking at stock history to determine future paths. Things like resistance points and trend lines also play a role. Technical analysts believe that stocks are just ticker symbols and that you can use guidelines to predict where they're headed. Another type of active investing is day trading. This basically involves buying and selling stocks every hour or every minute or just at a rapid pace. Day traders don't hold onto investments for very long, and are always trying to predict the market in the short term and take advantage of it. Many individual investors are also day traders. The other question is, how do you choose a strategy? The short answer is: pick whatever works for you. The long answer is: Day trading and technical analysis is a lot of luck. If there are consistent systems for trading , then people are keeping them secret, because there is no book that you can read and become a consistent trader. High frequency trading (HFT) is an area where people basically mint money, but it s more technology and less actual investing, and would not be categorized as day trading. Benjamin Graham once said: In the short run, the market is a voting machine but in the long run it is a weighing machine. Value investing will work because there's evidence for it throughout history, but you need a certain temperament for it and most people don't have that. Furthermore, it takes a lot of time to adequately study stocks, and people with day jobs can't devote that kind of time. So there you have it. This is my opinion and by no means definitive, but I hope you have a starting point to continue your study. I included the theory in the beginning because there are too many monkeys on CNBC and the news who just don't understand fundamental economics and finance, and there's no sense in applying a theory until you can understand why it works and when it doesn't.\"",
"title": ""
},
{
"docid": "466255",
"text": "You'd have to buy that information. Quoting from this page, Commercial Historical Data Higher resolution and more complete datasets are generally not available for free. Below is a list of vendors which have passed our quality screening (in total, we screened over a dozen vendors). To qualify, the vendor must aggregate data from all US national/regional exchanges as only complete datasets are suitable for research use. The last point is especially important as there are many vendors who just get data from a couple sources and is missing important information such as dark pool trades. They offer some alternatives for free data: Daily Resolution Data 1) Yahoo! Finance– Daily resolution data, with split/dividend adjustments can be downloaded from here. The download procedure can be automated using this tool. Note, Yahoo quite frequently has errors in its database and does not contain data for delisted symbols. 2) QuantQuote Free Data– QuantQuote offers free daily resolution data for the S&P500 at this web page under the Free Data tab. The data accounts for symbol changes, splits, and dividends, and is largely free of the errors found in the Yahoo data. Note, only 500 symbols are available unlike Yahoo which provides all listed symbols. And they list recommendations about who to buy the data from.",
"title": ""
},
{
"docid": "401447",
"text": "SPX options are cash settled European style. You cannot exercise European style options before the expiration date. Assuming it is the day of expiration and you own 2,000 strike puts and the index settlement value is 1,950 - you would exercise and receive cash for the in the money amount times the contract multiplier. If instead you owned put options on the S&P 500 SPDR ETF (symbol SPY) those are American style, physically settled options. You can exercise a long American style option anytime between when your purchase it and when it expires. If you exercised SPY puts without owning shares of SPY you would end up short stock at the strike price.",
"title": ""
},
{
"docid": "405996",
"text": "I have always assumed that there is a regulation that either prohibits, or makes noncompetitive, internet bank business accounts. All of the 1%+ savings accounts offered at the banks listed are internet only. If you broaden the search to include other internet only banks like Capital One 360, American Express Savings, Goldman Sachs Savings, Discover Savings, you'll find they all also only offer accounts to individuals (some may allow a trust to own the account) not businesses.",
"title": ""
},
{
"docid": "71732",
"text": "\"The change is generally known as the Options Symbology Initiative (or \"\"OSI\"\") and there is a highly comprehensive guide to what occurred here. The basic gist of what occurred was a shift FROM: A coded system in which a shorter (3 to 5 letter symbol) could be used, but the symbols required a data source to determine what they meant. MSQ AD used to be a MSFT Jan 20 option, but you had to look up MSQ in a table to know that. TO: A system in which much longer symbols are needed, but they contain all the information required to identify a unique option: DELL 4.000 C 5/16/2010 isn't easy to type, but once you know how to read it, it's easy to see that it's an option on DELL, expiring on May 16th 2010, is a call (rather than a put,) and has a strike price of 4. As to why they did it, there are a number of benefits, but most important reason is this one: they were running out of symbols. The number of permutations of 3-5 letter symbols had been exceeded by the number of options that had been listed, resulting in the need to \"\"recycle\"\" symbols. This meant that a current option symbol would be the same as an old one, in some cases on a different stock, which was wreaking havoc on historical data.\"",
"title": ""
},
{
"docid": "53993",
"text": "\"A company whose stock is available for sale to the public is called a publicly-held or publicly-traded company. A public company's stock is sold on a stock exchange, and anyone with money can buy shares through a stock broker. This contrasts with a privately-held company, in which the shares are not traded on a stock exchange. In order to invest in a private company, you would need to talk directly to the current owners of the company. Finding out if a company is public or private is fairly easy. One way to check this is to look at the Wikipedia page for the company. For example, if you take a look at the Apple page, on the right sidebar you'll see \"\"Type: Public\"\", followed by the stock exchange ticker symbol \"\"AAPL\"\". Compare this to the page for Mars, Inc.; on that page, you'll see \"\"Type: Private\"\", and no stock ticker symbol listed. Another way to tell: If you can find a quote for a share price on a financial site (such as Google Finance or Yahoo Finance), you can buy the stock. You won't find a stock price for Mars, Inc. anywhere, because the stock is not publicly traded.\"",
"title": ""
},
{
"docid": "141585",
"text": "A quick update for people finding this thread through Google. With the help of a few awesome Bogleheads, I compiled all the relevant research done into two Wiki articles: This includes comparing US to Irish domiciled ETFs, how to calculate tax withholding leakage and estate tax concerns. Hope you find this useful.",
"title": ""
},
{
"docid": "498645",
"text": "\"Bonds might not be simple, but in general there are only a few variables that need to be understood: bid, coupon (interest) rate, maturity, and yield. Bond tables clearly lay those out, and if you're talking about government bonds a lot of things (like convertibles) don't apply (although default is still a concern). This might be overly simplistic, but I view ETF's primarily as an easy way to bring somewhat esoteric instruments (like grain futures) into the easily available markets of Nasdaq and the NYSE. That they got \"\"enhanced\"\" with leveraged funds and the such is interesting, but perhaps not the original intent of the instrument. Complicating your situation a bit more is the fee that gets tacked onto the ETF. Even Vanguard government bond funds hang out north of 0.1%. That's not huge, but it's not particularly appealing either considering that (unlike rounding up live cattle futures), it's not that much work to buy US government bonds, so the expense might not seem worth it to someone who's comfortable purchasing the securities directly. I'd be interested to see someone else's view on this, but in general I'd say that if you know what you want and know how to buy it, the government bond ETF becomes a lot less relevant as the liquidity offered (including the actual \"\"ease of transacting\"\") seem to to be the biggest factors in favor. From Investopedia's description: The bond ETF is an exciting new addition to the bond market, offering an excellent alternative to self-directed investors who, looking for ease of trading and increased price transparency, want to practice indexing or active bond trading. However, bond ETFs are suitable for particular strategies. If, for instance, you are looking to create a specific income stream, bond ETFs may not be for you. Be sure to compare your alternatives before investing.\"",
"title": ""
},
{
"docid": "84800",
"text": "\"Your broker, Ameritrade, offers a variety of Exchange Traded Funds (ETFs) that you can buy and sell with zero commission. An ETF is like a mutual fund, but you buy and sell shares the same way you buy and sell shares of stocks. From your point of view, the relevance of this is that you can buy and sell as many or as few shares as you like, even down to a single share. Note that to get the commission-free trades on the available ETFs you have to sign up for it in your account profile. Be sure to do that before you enter any buy orders. You'll want to start by looking at the Ameritrade's list of commission-free ETFs. Notice that they are divided into different categories: stocks, bonds, international, and commodities. Which categories you pick from will depend on your personal investing goals, time horizon, risk tolerance, and so on. There are lots of questions and answers on this site that talk about asset allocation. You should read them, as it is the most important decision you will make with your portfolio. The other thing you want to be aware of is the expense ratio for each fund. These expenses reduce the fund's return (they are included in the calculation of the net asset value of the shares), so lower is definitely better. Personally, I wouldn't even consider paying more than about 0.10% (commonly read \"\"10 basis points\"\" or \"\"10 bp\"\") for a broad-based domestic stock fund. For a sectoral fund you might put up with as much as 20 bp in expenses. Bond funds tend to be a little more expensive, so maybe allow as much as 25 bp, and likewise for international funds. I've never invested in commodity funds, so I'll let someone else opine on appropriate expense ratios for those. Once you've decided what funds you want (and have signed up for commission-free trades), all you have to do is enter the trade orders. The website where you manage your account has tutorials on how to do that. After that you should be all set. Good luck with your investing!\"",
"title": ""
},
{
"docid": "276354",
"text": "\"I'll second what littleadv says about the \"\"entertainment\"\" expenses; they do seem high relative to your income. The numbers for electricity and vehicle insurance seem high to me as well, but that depends on where you live and how you heat your house, etc., so they may be normal for your situation. You've got almost $500/month going to debt payments (vehicle, window replacement, and student loan). You didn't list the credit card payments on there, so that will add to the debt payment amount. Finding a way to get those debts paid off as quickly as possible would free up a lot of cash flow. You could consider trying to find extra income (second job, your wife getting a job or finding a way to make some money from home, sell some things, etc.) I'm wondering about the things I don't see here: food (including restaurants), clothing, fuel, maintenance and repairs (both car and house), etc, etc. With the numbers you list above, you have money left over every month, but when you add in the things I just mentioned, that may not be the case. I suggest that you keep track of all of your expenses for the next month to see what you're really spending (including the things not listed here). Then, using that information, make a plan for the following month (and every month thereafter) about how you're going to live on what you bring home. Just tracking your expenses will likely show you some areas where you could easily cut back on spending. Also, I recommend that you start working on a plan to increase your income, both temporarily as I suggest above, and longer term by focusing on your career direction. You are above the poverty level (assuming you live in the US), but below average in income.\"",
"title": ""
},
{
"docid": "153660",
"text": "\"For a non-ETF mutual fund, you can only buy shares of the mutual fund from the mutual fund itself (at a price that the mutual fund will reveal only at the end of the day) and can only shares back to the mutual fund (again at a price that the mutual fund will reveal only at the end of the day). There is no open market in the sense that you cannot put in a bid to buy, say, 100 shares of VFINX at $217 per share through a brokerage, and if there is a seller willing to sell 100 shares of VFINX to you at $217, then the sale is consummated and you are now the proud owner of 100 shares of VFINX. The only buyer or seller of VFINX is the mutual find itself, and you tell it that you \"\"want to buy 100 shares of VFINX and please take the money out of my checking account\"\". If this order is entered before the markets close at 4 pm, the mutual fund determines its share price as of the end of the day, opens a new account for you and puts 100 shares of VFINX in it (or adds 100 shares of VFINX to your already existing pile of shares) and takes the purchase price out of your checking account via an ACH transfer. Similarly for redeeming/selling shares of VFINX that you own (and these are held in an account at the mutual fund itself, not by your brokerage): you tell the mutual fund to that you \"\"wish to redeem 100 shares and please send the proceeds to my bank account\"\" and the mutual fund does this at the end of the day, and the money appears in your bank account via ACH transfer two or three days later. Generally, these transactions do not need to be for round lots of multiples of 100 shares for efficiency; most mutual fund will gladly sell you fractional shares down to a thousandth of a share. In contrast, shares of an exchange-traded fund (ETF) are just like stock shares in that they can be bought and sold on the open market and your broker will charge you fees for buying and selling them. Selling fractional shares on the open market is generally not possible, and trading in round lots is less expensive. Also, trades occur at all times of the stock exchange day, not just at the end of the day as with non-ETF funds, and the price can fluctuate during the day too. Many non-ETF mutual funds have an ETF equivalent: VOO is the symbol for Vanguard's S&P 500 Index ETF while VFINX is the non-ETF version of the same index fund. Read more about the differences between ETFs and mutual funds, for example, here.\"",
"title": ""
},
{
"docid": "138383",
"text": "Bond ETFs are just another way to buy a bond mutual fund. An ETF lets you trade mutual fund shares the way you trade stocks, in small share-size increments. The content of this answer applies equally to both stock and bond funds. If you are intending to buy and hold these securities, your main concerns should be purchase fees and expense ratios. Different brokerages will charge you different amounts to purchase these securities. Some brokerages have their own mutual funds for which they charge no trading fees, but they charge trading fees for ETFs. Brokerage A will let you buy Brokerage A's mutual funds for no trading fee but will charge a fee if you purchase Brokerage B's mutual fund in your Brokerage A account. Some brokerages have multiple classes of the same mutual fund. For example, Vanguard for many of its mutual funds has an Investor class (minimum $3,000 initial investment), Admiral class (minimum $10,000 initial investment), and an ETF (share price as initial investment). Investor class has the highest expense ratio (ER). Admiral class and the ETF generally have much lower ER, usually the same number. For example, Vanguard's Total Bond Market Index mutual fund has Investor class (symbol VBMFX) with 0.16% ER, Admiral (symbol VBTLX) with 0.06% ER, and ETF (symbol BND) with 0.06% ER (same as Admiral). See Vanguard ETF/mutual fund comparison page. Note that you can initially buy Investor class shares with Vanguard and Vanguard will automatically convert them to the lower-ER Admiral class shares when your investment has grown to the Admiral threshold. Choosing your broker and your funds may end up being more important than choosing the form of mutual fund versus ETF. Some brokers charge very high purchase/redemption fees for mutual funds. Many brokers have no ETFs that they will trade for free. Between funds, index funds are passively managed and are just designed to track a certain index; they have lower ERs. Actively managed funds are run by managers who try to beat the market; they have higher ERs and tend to actually fall below the performance of index funds, a double whammy. See also Vanguard's explanation of mutual funds vs. ETFs at Vanguard. See also Investopedia's explanation of mutual funds vs. ETFs in general.",
"title": ""
},
{
"docid": "253135",
"text": "\"Where can I download all stock symbols of all companies \"\"currently listed\"\" and \"\"delisted\"\" as of today? That's incredibly similar . You can also do it with a Bloomberg terminal but there's no need to pay to do this because he data changes so slowly.\"",
"title": ""
},
{
"docid": "66119",
"text": "How can I calculate my currency risk exposure? You own securities that are priced in dollars, so your currency risk is the amount (all else being equal) that your portfolio drops if the dollar depreciates relative to the Euro between now and the time that you plan to cash out your investments. Not all stocks, though, have a high correlation relative to the dollar. Many US companies (e.g. Apple) do a lot of business in foreign countries and do not necessarily move in line with the Dollar. Calculate the correlation (using Excel or other statistical programs) between the returns of your portfolio and the change in FX rate between the Dollar and Euro to see how well your portfolio correlated with that FX rate. That would tell you how much risk you need to mitigate. how can I hedge against it? There are various Currency ETFs that will track the USD/EUR exchange rate, so one option could be to buy some of those to offset your currency risk calculated above. Note that ETFs do have fees associated with them, although they should be fairly small (one I looked at had a 0.4% fee, which isn't terrible but isn't nothing). Also note that there are ETFs that employ currency risk mitigation internally - including one on the Nasdaq 100 . Note that this is NOT a recommendation for this ETF - just letting you know about alternative products that MIGHT meet your needs.",
"title": ""
},
{
"docid": "198394",
"text": "\"I find this very hard to believe Believe it. The bottom quarter of American households have negative net worth, and the bottom three quarters have no more than a tiny amount saved up. https://en.wikipedia.org/wiki/Wealth_in_the_United_States#/media/File:MeanNetWorth2007.png In an emergency, 63% of Americans would not be able to come up with $500 without going into debt. http://www.forbes.com/sites/maggiemcgrath/2016/01/06/63-of-americans-dont-have-enough-savings-to-cover-a-500-emergency/ Nobody can retire with 5k in the U.S. The money will be gone within a year. Is it possible? Now you begin to see why the long-term stability of Social Security and Medicare are at present hot topics in American political life. Without them, a great many more Americans would die in poverty. What is the actual figure? The $5000 figure is accurate but irrelevant; that median includes people who are thirty years from retirement and people who are two days from retirement. The more relevant statistics are those restricted to people at or close to retirement age, and they can be found lower down in the article you cite, or in numerous other studies. Here's one from the GAO for example: http://www.gao.gov/products/GAO-15-419 The figures here are, unfortunately, no less terrifying: Now $104K is a lot better than $5K, but it's still not much to retire on. Why we believe that it is reasonable to throw out all the zeros before taking the median, I do not know. That seems like bad math to me. UPDATE: There is some discussion of this point in the comments; all I'm saying here is that this is a clumsy and possibly misleading way to characterize the situation. The linked report has the actual data, but let's try to summarize it here in a more meaningful way. Let's suppose that we make buckets for how dependent on SS is a retirement-age household to avoid starving to death, being homeless, and so on? Maybe these buckets are not ideal, and we could move them around a bit. The takeaways here are that the ratios of nothing:inadequate:barely adequate:comfortable is about 40:30:20:10. That only the top decile of retirement-age households can fund a comfortable retirement without help illustrates just how dependent on SS American households are. how do 50% of old Americans survive in their old age? Social Security and Medicare. As the cited GAO report indicates: \"\"Social Security provides most of the income for about half of households age 65 and older.\"\" Do most old Americans rely on their children for financial support? One day I met a woman at a party and we were making small talk about her kids. She had a couple already and one more was on the way. \"\"I want to have lots of children to support me in my old age\"\", she said. \"\"Do you support your parents?\"\" I asked, which frankly seemed like an entirely reasonable question. \"\"Of course not! I can't afford it. I've got a baby on the way and two more kids at home!\"\" I left her to draw her own conclusions as to the viability of her retirement plan.\"",
"title": ""
},
{
"docid": "256542",
"text": "They are wrong. If they offer an FSA, they must abide by the rules regarding FSA eligible expenses, plain and simple. They can offer a lower limit than the general maximum ($5K/yr?) and they can allow a grace period on expenses, or not. But, they must allow reimbursements for reimbursable items. Medical Insurance premiums are included. See this comprehensive list. On the IRS web site, Pub 969 discusses FSAs at a higher level and indicates that Publication 502 has the detailed list of reimbursable expenses. Medical insurance is listed. I offer this chain so one can find the data directly from the IRS and not claim that Wikipedia might not be accurate. At this point you need to decide how far you want to go with your benefits department on this. Do they offer a copy of what they claim is the accepted list of reimbursables?",
"title": ""
},
{
"docid": "466176",
"text": "I don't know answers that would be specific to Canada but one of the main ETF funds that tracks gold prices is GLD (SPDR Gold Trust) another is IAU (iShares Gold Trust). Also, there are several ETF's that combine different precious metals together and can be traded. You can find a fairly decent list here on the Stock Encylopedia site.",
"title": ""
},
{
"docid": "254910",
"text": "Note, the main trade off here is the costs of holding cash rather than being invested for a few months vs trading costs from trading every month. Let's start by understanding investing every month vs every three months. First compare holding cash for two months (at ~0% for most Canadians right now) and then investing on the third month vs being invested in a single stock etf (~5% annually?). At those rates she is forgoing equity returns of around These costs and the $10 for one big trade give total costs of $16+$8+$10=$34 dollars. If you were to trade every month instead there would be no cost for not being invested and the trading costs over three months would just be 3*$10=$30. So in this case it would be better to trade monthly instead of every three months. However, I'm guessing you don't trade all $2000 into a single etf. The more etfs you trade the more trading more infrequently would be an advantage. You can redo the above calculations spliting the amount across more etfs and including the added trading costs to get a feel for what is best. You can also rotate as @Jason suggests but that can leave you unbalanced temporarily if not done carefully. A second option would be to find a discount broker that allows you to trade the etfs you are interested in for free. This is not always possible but often will be for those investing in index funds. For instance I trade every month and have no brokerage costs. Dollar cost averaging and value averaging are for people investing a single large amount instead of regular monthly amounts. Unless the initial amount is much much larger than the monthly amounts this is probably not worth considering. Edit: Hopefully the above edits will clarify that I was comparing the costs (including the forgone returns) of trading every 3 months vs trading every month.",
"title": ""
},
{
"docid": "369266",
"text": "A stock, bond or ETF is basically a commodity. Where you bought it does not really matter, and it has a value in USD only inasmuch as there is a current market price quoted at an American exchange. But nothing prevents you from turning around and selling it on a European exchange where it is also listed for an equivalent amount of EUR (arbitrage activities of investment banks ensure that the price will be equivalent in regard to the current exchange rate). In fact, this can be used as a cheap form of currency conversion. For blue chips at least this is trivial; exotic securities might not be listed in Europe. All you need is a broker who allows you to trade on European exchanges and hold an account denominated in EUR. If necessary, transfer your securities to a broker who does, which should not cost more than a nominal fee. Mutual funds are a different beast though; it might be possible to sell shares on an exchange anyway, or sell them back to the issuer for EUR. It depends. In any case, however, transferring 7 figure sums internationally can trigger all kinds of tax events and money laundering investigations. You really need to hire a financial advisor who has international investment experience for this kind of thing, not ask a web forum!",
"title": ""
},
{
"docid": "449043",
"text": "Have a look at: Diversify Portfolio. The site provides various tools all focused on correlation, diversification and portfolio construction. You can scan through every stock and ETF listed on the NASDAQ and NYSE to find any kind of correlation you're looking for. You can also create a portfolio and then analyze all the correlations within it, or search for specific stocks that can be added to the portfolio based on correlation and various other factors.",
"title": ""
},
{
"docid": "144005",
"text": "As I write this, the NASDAQ Composite is at 2790.00, down 6.14 points from yesterday. To calculate the percentage, you take 6.14 and divide by yesterday's close of 2796.14 to yield 0.22%. In your example, if SPY drops from 133.68 to 133.32, you use the difference of -0.36 and divide by the original, i.e. -0.36/133.68 = -0.27%. SPY is an ETF which you can invest in that tracks the S&P 500 index. Ideally, the index would have dropped the same percentage as SPY, but the points would be different (~10x higher). To answer your question about how one qualifies a point, it completely depends on the index being discussed. For example, the S&P 500 is a market-capitalization weighted index of the common stock of 500 large-cap US public companies. It is as if you owned every share of each of the 500 companies, then divide by some large constant to create a number that's easily understood mentally (i.e. 1330). The NASDAQ Composite used the same methodology but includes practically all stocks listed on the NASDAQ. Meanwhile, the Dow Jones Industrial Average is a price-weighted index of 30 large-cap companies. It's final value is modified using a divisor known as the Dow Divisor, which accounts for stock splits and similar events that have occurred since a stock has joined the index. Thus, points when referring to an index do not typically represent dollars. Rather, they serve as a quantitative measure of how the market is doing based on the performance of the index constituents. ETFs like SPY add a layer of abstraction by creating an investible vehicle that ideally tracks the value of the underlying index directly. Finally, neither price nor index value is related to volume. Volume is a raw measurement of the total number of shares traded for a given stock or the aggregate for a given exchange. Hope this helps!",
"title": ""
}
] |
5a8efaf75542995085b374c0
|
What U.S. Army division, referred to as is the focus of Bravo Company, a 1998 Vietnam War memoir by Robert Hemphill, the commander of this division?
|
[
{
"docid": "444948",
"text": "The 25th Infantry Division (nicknamed \"Tropic Lightning\" and the \"Electric Strawberry\" is a U.S. Army division based in Hawaii. The division, which was activated on 1 October 1941 in Hawaii, conducts military operations in the Asia-Pacific region. Its present deployment is composed of Stryker, light infantry, airborne, and aviation units.",
"title": ""
},
{
"docid": "6194798",
"text": "Platoon: Bravo Company (1998) is a Vietnam War memoir by Robert Hemphill (with foreword by Joe Galloway), who commanded B (Bravo) Company, 3rd Battalion, 22nd Infantry of the 25th Infantry Division (U.S. Army) in Vietnam from 1 October 1967 to 18 February 1968.",
"title": ""
}
] |
[
{
"docid": "11109739",
"text": "Robert C. Mason (born March 20, 1942) is a Vietnam War veteran and author of several books, including his first, best-selling memoir: \"Chickenhawk\" (1983). Mason piloted Huey \"Slicks\" in the United States Army as a Warrant Officer 1. He sailed to Vietnam with the 1st Cavalry Division (Airmobile) and served a one-year tour, nine months with the \"First Cav\", the last three months with the 48th Aviation Company.",
"title": ""
},
{
"docid": "12174014",
"text": "Platoon Leader is a memoir by James R. McDonough. It is narrated by McDonough in first person view and tells of his story in the Vietnam War as a lieutenant in command of 2nd Platoon, Bravo Company, 4th Battalion, 503rd Infantry(Airborne).",
"title": ""
},
{
"docid": "36827941",
"text": "William Robertson Desobry (September 11, 1918 – January 12, 1996) was a senior U.S. Army field commander in Germany during the Cold War, and a Lieutenant General in the United States Army. General Desobry was a decorated hero from World War II, and played a significant role as an advisor to the Republic of Vietnam Army and on the Army Staff during the Vietnam War. In addition to commanding a division and corps, he was the Commanding General of the Armor Center and was the President of the XM-1 Tank Task Force.",
"title": ""
},
{
"docid": "40225233",
"text": "Colonel John Joseph “Jay” McNulty, III was Chief of the House Liaison Division of the Office of the Chief Legislative Liaison (United States Army) U.S. Secretary of the Army at The Pentagon. Prior to closing his 29 years of service in the U.S. Army by serving, finally, in this sensitive position, Col. Jay McNulty was both an Army Vietnam War mechanized cavalry combat commander serving first with the 11th Armored Cavalry Division (Black Horse Regiment) and, later, with the 1st Cavalry Regiment (United States) (1st U.S. Dragoons) (Blackhawks), and, also, in peacetime, an Army commander of the 1st Squadron, 3rd Armored Cavalry Regiment, Ft. Bliss, Texas. McNulty was a 1981 centennial class graduate of the United States Army Command and General Staff College.",
"title": ""
},
{
"docid": "209827",
"text": "The 23rd Infantry Division, more commonly known as the Americal Division, of the United States Army was activated 27 May 1942 on the island of New Caledonia. In the immediate emergency following Pearl Harbor, the United States had hurriedly sent three individual regiments to defend New Caledonia against a feared Japanese attack. This division was the only division formed outside of United States territory during World War II (a distinction it would repeat when reformed during the Vietnam War). At the suggestion of a subordinate, the division's commander, Major General Alexander Patch, requested that the new unit be known as the \"Americal Division\"—the name being a contraction of \"American, New Caledonian Division\". This was unusual, as most U.S. divisions are known by a number. After World War II the Americal Division was officially re-designated as the 23rd Infantry Division. However, it was rarely referred to as such, even on official orders.",
"title": ""
},
{
"docid": "330002",
"text": "The 1st Cavalry Division (\"First Team\") is a combined arms division and is one of the most decorated combat divisions of the United States Army, as well as the other four branches of the U.S. military. It is based at Fort Hood, Texas. It was formed in 1921 and served during World War II, the Korean War, the Vietnam War, the Persian Gulf War, with the Stabilization Force in Bosnia-Herzegovina, in the Iraq War, in the War in Afghanistan and in Operation Freedom’s Sentinel. As of 2017, the 1st Cavalry Division is subordinate to III Corps and is commanded by Major General John C. Thomson III.",
"title": ""
},
{
"docid": "44031726",
"text": "Task Force Barker was a United States Army task force under the command of Lieutenant Colonel Frank A. Barker during the Vietnam War. While a part of Task Force Barker, U.S. Army soldiers from Company C of the 1st Battalion, 20th Infantry Regiment, 11th Brigade of the 23rd (Americal) Infantry Division committed the My Lai Massacre in 1968.",
"title": ""
},
{
"docid": "907691",
"text": "The 81st Infantry Division (\"Wildcat\") was an infantry division of the United States Regular Army that was mobilized for service in both World War I and World War II. The division was inactivated in 1965 and reactivated as the 81st Army Reserve Command (ARCOM) 1967. During that time, the 81st ARCOM was responsible for deploying US Army Reserve units to Vietnam, Southwest Asia, and the Balkans. The 81st was redesignated in 1996 as the 81st Regional Support Command (RSC) and is responsible for all Army Reserve units in the southeast United States and Puerto Rico.",
"title": ""
},
{
"docid": "54340857",
"text": "Death Traps: The Survival of an American Armored Division in World War II is a 1998 memoir by Belton Y. Cooper. The book relates Cooper's experiences during World War II and puts forth an argument against the U.S. Army's use of the M4 Sherman tank during the war.",
"title": ""
},
{
"docid": "31519226",
"text": "Thomas Leonard Harrold (June 21, 1902June 16, 1973) was a United States Army Lieutenant General. He was commander of the 9th Armored Division, U.S. Army Armor School, 1st Cavalry Division, 8th Infantry Division, 10th Mountain Division, III Corps, and U.S. Army Caribbean. From 1958 to 1961 he served as commandant of the National War College.",
"title": ""
},
{
"docid": "29688707",
"text": "Major General Sir Robert Fanshawe KCB, DSO (5 November 1863 – 24 August 1946) was a British Army general, who, during World War I, commanded the 48th (South Midland) Division from 1915 to 1918. He was the youngest of three brothers (Edward, Hew, and Robert) who all rose to command divisions or corps during the war.",
"title": ""
},
{
"docid": "1360493",
"text": "Charles P. Stone (June 17, 1915 – February 6, 2012), also known as Charlie Stone, was a career United States Army officer during the middle of the 20th century. After serving in World War II, in 1968 Major General Stone commanded the U.S. Army's 4th Infantry Division in Vietnam, leading his division to success during the Tet offensive.",
"title": ""
},
{
"docid": "11349050",
"text": "The 18th Division was an infantry division in the III Corps of the Army of the Republic of Vietnam (ARVN). The U.S. Military Assistance Command Vietnam considered the 18th as undisciplined and was well known throughout the ARVN for its \"cowboy\" reputation. In 1975 the 18th was made famous for its tenacious defense of Xuân Lộc, the last major battle before the Fall of Saigon.",
"title": ""
},
{
"docid": "31237825",
"text": "James Benjamin Vaught (November 3, 1926 – September 20, 2013) was a United States Army General who fought during three wars: World War II, the Korean War, and the Vietnam War. In Korea he served as a company commander in the 24th Infantry Division and in 1967, in the Republic of Vietnam, on his first tour he served as the commanding officer of the 5th Battalion, 7th Cavalry. He has also played a major role in numerous United States Special Forces operations.",
"title": ""
},
{
"docid": "43915394",
"text": "Henry J. Muller, Jr. (born 1917) is a retired American soldier who served during World War II in the United States Army with the 11th Airborne Division between 1944 and 1945. During the Vietnam War, he served as assistant division commander of the 101st Airborne Division and as deputy senior adviser to the Vietnamese I Corps commander, Lieutenant General Lam. Muller served as the assistant division commander of the 101st until September 12, 1969.",
"title": ""
},
{
"docid": "28883826",
"text": "The Maywand District killings were the murders of at least three Afghan civilians perpetrated by a group of U.S. Army soldiers in 2010, during the War in Afghanistan. The soldiers, who referred to themselves as the \"Kill Team\", were members of the 3rd Platoon, Bravo Company, 2nd Battalion, 1st Infantry Regiment and 5th Brigade, 2nd Infantry Division. They were based at FOB Ramrod in Maiwand, from Kandahar Province of Afghanistan.",
"title": ""
},
{
"docid": "446647",
"text": "The 5th Infantry Division (Mechanized)—nicknamed the \"Red Diamond\", the \"Red Devils\", or \"die Roten Teufel\"—was an infantry division of the United States Army that served in World War I, World War II and the Vietnam War, and with NATO and the U.S. Army III Corps. It was disbanded and deactivated on 24 November 1992.",
"title": ""
},
{
"docid": "12338597",
"text": "Loren Douglas Hagen (February 25, 1946 – August 7, 1971) was a United States Army Special Forces officer and a recipient of the United States military's highest decoration—the Medal of Honor—for his actions during the Vietnam War as Recon Team (RT) leader of a small special reconnaissance unit \"RT Kansas\", manned by USASF Green Berets and highly trained Montagnard commandos from Task Force One Advisory Element aka Command & Control North, a division of Studies and Observations Group in the Vietnam War. Hagen was the last member of the U.S. Army to earn a Medal of Honor in the Vietnam War.",
"title": ""
},
{
"docid": "12091734",
"text": "A. P. Hill's Light Division was an infantry division in General Robert E. Lee's Confederate Army of Northern Virginia during the American Civil War. Originally including six brigades, the Division's first commander starting May 27, 1862 was then Major General A. P. Hill. Major Generals William Dorsey Pender and Cadmus M. Wilcox commanded a reorganized Light Division in the Army of Northern Virginia after Hill's promotion to corps command and Pender's death at the Battle of Gettysburg, respectively.",
"title": ""
},
{
"docid": "3592971",
"text": "Lieutenant General Robert Frederick Sink (April 3, 1905 – December 13, 1965) was a senior United States Army officer who fought during World War II, the Korean War, and early parts of the Vietnam War, though he was most famous for his command of the 506th Parachute Infantry Regiment, part of the 101st Airborne Division, throughout most of World War II, in France, Holland and Belgium. Sink was portrayed in the television miniseries \"Band of Brothers\" by Captain Dale Dye.",
"title": ""
},
{
"docid": "7261034",
"text": "Robert \"Bobbie\" Evan Brown Jr. (September 2, 1903 – November 8, 1971) was a recipient of the Medal of Honor for his actions at the Battle of Crucifix Hill, near Aachen, Germany, on October 8, 1944. He left home and joined the army in 1918, lying about his age. At the start of World War II, he was the first sergeant of the Headquarters Company of the 2nd Armored Division. He received a battlefield commission to second lieutenant and was transferred to the 1st Infantry Division in 1943. Following the death of his company commander on D-Day he assumed command of his company, Company C. Brown left the army with the rank of captain in 1952.",
"title": ""
},
{
"docid": "7459929",
"text": "Major General Raymond Oscar \"Tubby\" Barton (August 22, 1889 – February 27, 1963) was a career officer in the United States Army and combat commander in World War I and World War II. As commander of the 4th Infantry Division during World War II, Barton is one of only eleven U.S. Army general officers who commanded their divisions for the duration of their combat service.",
"title": ""
},
{
"docid": "55320612",
"text": "The Franklin Guards were a unit of the Florida Army National Guard, stationed in Apalachicola, Florida. The company was founded in 1861 as Company B \"Beauregard Rifles\", Fourth Florida Infantry during the Civil War. After the war, the company reorgaznized as Franklin Guards, a local militia company, under the command of its previous commander, Captain Robert Knickmeyer. The Guards served as an infantry unit for most of its existence, including in the Civil War and World War I. The Guards had reorganized into an engineer company after World War I and deployed as such to the Pacific Theatre with the 31st Infantry Division in World War II.",
"title": ""
},
{
"docid": "26513811",
"text": "The 324th Division (named as 324th-B Division during Vietnam War) is an infantry division of the 4th Military Region (Vietnam People's Army).",
"title": ""
},
{
"docid": "52751467",
"text": "Brigadier General Albin F. Irzyk (born January 2, 1917) is an oldest living veteran of the 3rd Cavalry Regiment. Joining the army in 1940, he was the Commander of the 8th Tank Battalion of the 4th Armored Division of the US Army during World War II, the Commander of the 14th Armored Cavalry Regiment during the Berlin Crisis of 1961, and assistant Commander of the 4th Infantry Division in South Vietnam during his career.",
"title": ""
},
{
"docid": "4520617",
"text": "United States Army Republic of Vietnam (USARV) was an corps-level support command of the United States Army in the Vietnam War. USARV was created on 20 July 1965 out of the U.S. Army Support Command, Vietnam.",
"title": ""
},
{
"docid": "45329510",
"text": "Brigadier General Alfred Judson Force Moody (4 March 1918 – 19 March 1967) was a United States Army officer who served with SHAEF during World War II, and as the Assistant Division Commander of the 1st Cavalry Division during the Vietnam War.",
"title": ""
},
{
"docid": "5400122",
"text": "Von Lewinski was born in Münster in the Province of Westphalia. He served in the 1864 Danish-Prussian War as a captain of the 1st Guard fortress company. In the 1866 German war he was assigned as a staff officer to the First Army division. In 1867 Lewinski was promoted to major on the general staff. He later served in the Franco-Prussian War of 1870, first on the staff of the First Army division and later commanding the quartermaster corps of the South Army. In 1871 he became commander of the general staff of the 9th Army corps. In 1872 he was promoted to lieutenant colonel and assumed command of the South Army's 24th artillery regiment.",
"title": ""
},
{
"docid": "12636669",
"text": "The 1st Landwehr Division (\"1. Landwehr-Division\") was an infantry division of the Imperial German Army during World War I. It was formed on the mobilization of the German Army in August 1914 under the \"Higher \"Landwehr\" Commander 1\" (\"Höherer Landwehr-Kommandeur 1\") and, initially, also referred to as the \"Landwehr-Division Goltz\" after its commander. The Landwehr was the third category of the German Army, after the regular Army and the reserves. Thus Landwehr divisions were made up of older soldiers who had passed from the reserves, and were intended primarily for occupation and security duties rather than heavy combat.",
"title": ""
},
{
"docid": "38390357",
"text": "Julian Ewell (November 5, 1915 – July 27, 2009) was a career United States Army officer who served in World War II, the Korean War and the Vietnam War. He commanded the 9th Infantry Division and II Field Force in Vietnam, and attained the rank of Lieutenant General.",
"title": ""
}
] |
3035
|
How come the government can value a home more than was paid for the house?
|
[
{
"docid": "218622",
"text": "\"When a house is sold at a foreclosure auction, the selling bank usually does not provide the guarantees that a normal house seller provides. Furthermore, the previous owner may have neglected the property, and/or spitefully damaged the property. Bank-owned properties are often neglected and/or vandalized. Banks are usually too short-sighted to properly market the real estate they own, and do a poor job of making it easy to buy the property. Thus, foreclosure sales usually happen at a price that is significantly below the \"\"fair market value\"\" of sales between competent households. It is common for a house that is worth $ 125,000 (even in a depressed market) to sell for only $ 100,000 in a short sale or foreclosure. It is possible that this property sold for an even larger discount. It is also possible that the tax assessor is (inadvertently) comparing a run-down property with well-maintained properties that have extra expensive features, without fully adjusting for the properties' conditions and features. In the latter scenario, the property owner can ask the tax assessor to re-consider the assessment. Usually this request is called an \"\"appeal\"\".\"",
"title": ""
},
{
"docid": "129439",
"text": "Keep in mind, there are times that house is in such bad shape that it's going to need 6 months of renovations, in which case you might ask the town if they are willing to reappraise a lower value until the work is completed. Keep in mind, you'll get a new appraisal when permitted (I mean pulling a permit from the town) work is done. I finished my basement and the town was eager to send the appraiser over even before work was fully complete.",
"title": ""
},
{
"docid": "372834",
"text": "\"The real answer why the government is \"\"allowed\"\" to do something is because they are the government and they make the rules. There are lots of laws that I think make no sense. I ran into a similar situation to yours. I bought a house during a time when the market in my area was way down. The previous owner had paid $140,000 but I got it for only $80,000. The government appraised it for, I forget the exact number, but over $100,000. I appealed, and the argument I made to the appeal board was that the law says it is supposed to be appraised for \"\"fair market value\"\". The definition of \"\"fair market value\"\" is the amount that a willing buyer would pay to a willing seller, absent special conditions like a sweetheart sale to a relative. The house had been advertised for a higher price and the seller had to drop the price several times before getting an offer, and finally accepting mine. This is pretty much the definition of \"\"fair market value\"\". The appeals board replied that it was not FMV because the market was bad at this particular time and so I got a good deal. I said that that's the definition of market value: it goes up and down as market conditions change. If the market happened to be up when someone bought a house and they had to pay a high price, would the government assess the house at a lower value because that was an unusually high price? I doubt it. They ended up reducing the assessed value, but not to what I actually paid. All that said, arguably a foreclosure sale might be considered special conditions. Prices at a foreclosure sale tend to be lower than \"\"ordinary\"\" sales. In a foreclosure, the bank is usually trying to get rid of the property quickly because they don't want to be in the property-management business, they want to be in the money lending and management business. Of course you could say that sort of thing about conditions surrounding many sales. Maybe the price is low because the seller needed cash now to start a business. Maybe the price is high because the buyer was too lazy to shop around. Maybe the price is low because the buyer is a very skilled negotiator. Etc etc. My watch just broke and while I was shopping for a new one I found two listings for the exact same watch, I mean exact same manufacturer and model number, identical picture, on the same web site, one giving the price as $24 and the other as $99. What is the market value of that watch? I presume anyone who saw both listings would pick the $24 one, but I presume some number of people pay the higher price because they never see the lower price. In real life there isn't really one, exact, fair market value. That's an abstraction.\"",
"title": ""
},
{
"docid": "122074",
"text": "\"The property tax valuation and the fair market price are NOT one and the same. They track each other, correlate to each other, but are almost NEVER the same number. In some parts of the USA, a municipality has to re-assess property tax values every ten years. In these places, the tax value of a property is on something like a 10-year moving average, NOT on the volatile daily market price. EDIT: It is easy to fall into the \"\"trap\"\" of thinking that property tax valuation is intended to represent fair market value. It's INTENT is to provide an accurate (or, as accurate as possible) RELATIVE VALUATION of your property compared to the other properties in the municipality. The sum of all the property values is the tax base of the municipality. When the town budget (which is paid in part via property taxes) is set, the town simply divides the tax base into the budget total to arrive at the ratio of tax-to-collect, to the tax base, also called the \"\"tax rate per thousand dollars of valuation.\"\" i.e. if the town tax base is US$10,000,000, and the town budget is US$500,000, then the ratio is 0.05, or $50 per thousand dollars of valuation. If your property is assessed at US$100,000, then you would pay 100 x $50, or $5000 in property taxes that year. Since this is the goal of the property tax valuation, NOT deciding what your house is worth on the open market, then we are left with the question of \"\"why use the market value of a house for property assessment?\"\" and the answer is that of all the various schemes and algorithms you can try, \"\"fair market value\"\" is the easiest and most accurate...IF TIME FLUCUTATIONS ARE TAKEN OUT. For example, if I buy a house in a development for $250,000 today, and next summer the housing market crashes, and you buy the identical house next door to me for $150,000, it does NOT stand to reason that you should pay less taxes than me, because your house is \"\"worth\"\" $100,000 less. In fact, BOTH our houses are worth $100,000 less. What matters most in property tax valuation isn't the actual number, but rather, is YOUR valuation the same as other essentially similar properties in your tax base? Getting the RELATIVE ratio of value between you and your neighbors correct is the goal of property tax valuation.\"",
"title": ""
},
{
"docid": "577605",
"text": "From my perspective I suspect that if the government use the paid price, people will start to buy at very low nominal prices in order to pay less taxes, and will repay the seller by other means.",
"title": ""
}
] |
[
{
"docid": "275410",
"text": "\"TARP was ~$475 billion of loans to institutions. Loans that are to be paid back, with interest (albeit very low interest). A significant percentage of the TARP loans have been (or will be) paid back. So, the final price tag of the TARP was only a few $billion (pretty low considering the scale of the program). There is ~$10 trillion in mortgage debt outstanding. That's a much higher price tag than TARP. Secondly, paying off the mortgages = no repayment to the government as there was with TARP. The initial price tag of your plan would be ~$10 trillion, instead of a few $billion. Furthermore how does a government with >$15 trillion in debt already come up with an extra ~$10 trillion to pay off people's mortgages? Should the government go deeper into debt? Print more money and trigger inflation? (Note: Some people like to talk about a \"\"secret bailout\"\" by the Fed, implying that the true cost of TARP was much higher than claimed by the government. The \"\"secret bailout\"\" was a series of short-term low/no interest loans to banks. Because they were loans, which were paid back, my point still stands.) Some other issues to consider: Remember that the principal balance of your mortgage is only a small portion of your payments to the bank. Over 30 years, you pay a lot of $$$ in interest to the bank (that's how banks make a profit). Banks are expecting that revenue, and it is factored into their financial projections. If those revenue streams suddenly disappeared, I expect it would majorly screw the up the financial industry. Many people bought houses during the real estate boom, when housing prices were inflated far beyond the \"\"real\"\" value of the house. Is it right to overpay for these houses? This rewards the banks for accepting the inflated value during the appraisal process. (Loan modification forces banks to accept the \"\"real\"\" value of the house.) The financial crisis was triggered by people buying houses they could not afford. Should they be rewarded with a free house for making poor financial decisions?\"",
"title": ""
},
{
"docid": "559745",
"text": "\"@fredsbend, Hope this helps! \"\"I understand that a reverse mortgage can be paid out in two ways: A lump sum and monthly payments. I figure that if you take the lump sum, eventually, the bank wants you to start paying it back.\"\" Answer: Actually, there are 3 payout options, or 4 if you consider a combination payout as another one. There's a lump sum, a line of credit, or the monthly payout, or a combination. \"\"I figure that if you take the monthly payments, eventually, the bank stops paying out and wants you to pay it back. In both situations, interest accrues and this is how the bank makes money off of the deal\"\". Answer: The only time the monthly payments would stop would be if the borrower defaults on the lenders' terms or they no longer live at home. You are right though, and interest does accrue on whichever payment is decided on. I'm not sure how the lender makes money, probably by the interest, but I know borrowers are protected against high rates and owing more than your house. Here's an article I found that goes over the protections more in detail: https://www.americanadvisorsgroup.com/news/6-consumer-protections-reverse-mortgage-loan-borrowers. \"\"But what determines when you have to begin paying back the reverse mortgage? Some sources online seem to say that it's based only on if you die or would like to sell/move. That can't be right in all situations, because you could end up with a massive debt on a property more than its value.\"\" Answer: There are a lot of protections or regulations in place to protect anyone who takes out a reverse mortgage. One being, you can't owe MORE than your house is valued at during the time of repayment, a reverse mortgage is a non-recourse loan. In the instance that your house is less than you owe, you either sell the home and the proceeds are used to pay the loan and you keep the rest OR if you owe more than the house proceeds of the home go to the lender. Either way, you're not left paying for a \"\"mortgage\"\" without the house. In the case the parent, grandparent passes, then the heirs would have a choice of either paying back the reverse mortgage in payments, OR they can sell the house, heirs are protected during this as well to make sure they're not left with major debt in case of anything. Is there a formula to figure out when the bank stops the monthly payments and then wants it back? **Answer:**The amount becomes due if loan terms are not met, but the lender will discuss the options if it comes to that. Is there a different formula for when the lump sum would have to be paid back?\"\" Answer: Each payout option has the same terms and the same pay back terms. As long as terms are met, the lender can't ask for early repayment.\"",
"title": ""
},
{
"docid": "163997",
"text": "The problem comes when the borrower cannot afford his home. If a borrower buys more home than they can afford, as long as he can sell the house for more than he owes, he's not in a disastrous situation. He can sell the house, pay off the mortgage, and choose more affordable housing instead. If he is upside-down on his home, he doesn't have that option. He's stuck in his home. If he sells it, he will have to come up with extra money to pay off the mortgage (which he doesn't have, because he is in a home he can't afford). It used to be commonplace for banks to issue mortgages for 100% of the value of the home. As long as the home keeps appreciating, everybody is happy. But if the house drops in value and the homeowner finds himself unable to make house payments, both the homeowner and the bank are at risk. Recent regulations in the U.S. have made no-down-payment mortgages less common.",
"title": ""
},
{
"docid": "566945",
"text": "I think Energy and Mike point out the some serious issues but the prospects for the futures also need to be considered. If the banks no longer have those loans then they need to rebuild their income base that is wiped out by the payoff of their loans. They would be incentivised to make a large number of loans so that they could quickly reestablish their base so they can maintain profitability. This is likely to lead to more poor lending practices that lead to this location in the first place. The high earning heavily leveraged would benefit far more from this than the poor. A function of income is that as it increases the ability to leverage increases in a non lineal fashion. So single person making 250k a year(the benchmark set by the current administration) with a 2 million dollar mortgage(probably underwater currently) on a home would benefit much more than a family of 4 making 50k a year with a 100k mortgage. Assuming that government does pay off all mortages now people can sell of their now fully paid homes for less than their value, as its basically free money, leverage that money to move into a better home, so home values actually crash, in some areas as people sell them off cheap, people try to gamble on cheap houses(like we just saw), etc. It takes a market that is on the verge of recovery and stabilization and shakes it up. How long before it stabilizes again would be a matter of debate but I would not expect to see it in less than a decade. Business and the Economy thrives on stability and retreats from instability. So while this would appear to be an injection to the economy the chaos it creates would likely actually severely retard future economic growth.",
"title": ""
},
{
"docid": "95033",
"text": "It really is a stupid term. What comes to mind with the term underwater? drowning, sunk boats, cars and other property and flooding. All really stressful and damaging. Underwater in mortgages, means you owe more than your house is worth, .... ER your home's value dropped below the value of your mortgage. It does suck but it doesnt mean they are behind on their mortgage and doesnt suck as much as people who are behind. it isnt really something to worry about except for the future when you resell. For a lot of people it is just something they can ignore. In theory, they should get a lower tax bill. Underwater just seems like an odd term for something like your home value dropping below the price your paid for it. If you buy a new car, you can pretty much claim to be underwater as you drive it off the lot, because your car simply isnt worth what you paid for it the second it becomes used. not saying it isnt an interesting stat, or that it is of no concern, it's just an odd term. To me it is more fitting for people behind in their payments than for people whose property lost value. (and yeah i get it is more dire for investors and somewhat for landlords but not always)",
"title": ""
},
{
"docid": "100683",
"text": "\"For the vast majority, \"\"buying\"\" a house via a mortgage is not an investment. I use quotes around buying because from a technical perspective you don't own anything until you've paid it off; this is often an important point that people forget. It's highly unlikely you'll make more on it than the amount you put into it (interest, repairs, etc). Even with relatively low interest rates. The people who successfully invest in homes are those that use actual cash (not borrowed) to buy a home at well below market value. They then clean it up and make enough repairs to make it marketable and sell it shortly there after. Sometimes these people get hosed if the housing market tumbles to the point that the home is now worth less than the amount they put into it. This is especially problematic if they used bank loans to get the process going. They were actually the hardest hit when the housing bubble popped several years ago. Well, them and the people who bought on interest only loans or had balloon payments. Whereas the people who use a mortgage are essentially treating it like a bank account with a negative interest rate. For example, $180k loan on a 30 yr fixed at 4% will mean a total payout of around $310k, excluding normal repairs like roofs, carpet, etc. Due to how mortgage's work, most of the interest is collected during the first half of the loan period. So selling it within 2 to 5 years is usually problematic unless the local housing market has really skyrocketed. Housing markets move up and down all the time due to a hundred different things completely out of your control. It might be a regional depression, weather events, failed large businesses, failed city/local governments, etc. It could go up because businesses moved in, a new highway is built, state/local taxes decline, etc. My point is, homes are not long term investments. They can be short term ones, but only in limited circumstances and there is a high degree of risk involved. So don't let that be a driving point of your decision. Instead you need to focus on other factors. Such as: what is really going on with the house you are currently in? Why would they lose it? Can you help out, and, should you help out? If things are precarious, it might make more sense to sell that home now and everyone move into separate locations, possibly different rentals or apartments. If they are foreclosed on then they will be in a world of financial hurt for a long time. If we ignore your parents situation, then one piece of advice I would give you is this: Rent the cheapest apartment you can find that is still a \"\"safe\"\" place to live in. Put every dollar you can into some type of savings/investment that will actually grow. Stay there for 5+ years, then go pay cash for a nice home. Making $75k a year while single means that you don't need much to live on. In other words, live extremely cheap now so you can enjoy a fantastic living experience later that is free from financial fear. You should be able to put $30k+ per year aside going this route. edit: A bit of support data for those that somehow think buying a home on a mortgage is somehow a good investment: Robert Shiller, who won a Nobel prize in economics and who predicted the bursting of the housing bubble, has shown that a house is not a good investment. Why? First, home prices (adjusted for inflation) have been virtually unchanged for the past 100 years. (link 1, link 2) Second, after you add in the costs of maintenance alone then those costs plus what you've paid for the home will exceed what you get out of it. Adding in the cost of a mortgage could easily double or even triple the price you paid which makes things even worse. Maintenance costs include things like a new roof, carpet/flooring, water heater, appliances, etc. Yes, a home might cost you $100k and you might sell it for $200k after 15 years. However during that time you'll likely replace the roof ($10k to $20k), replace appliances ($2k to $5k), water heater ($1k), carpet/flooring ($5k to $20k), paint ($3k to $6k), and mortgage related costs (~$60k - assuming 30 yr fixed @4%). So your \"\"costs\"\" are between $180k and $200k just on those items. There are many more that could easily escalate the costs further. Like a fence ($5k+), air conditioner ($5k+), windows, etc. The above is assuming the home actually appreciates in value faster than inflation: which they historically haven't over the long term. So you have to consider all of the costs ultimately paid to purchase and maintain the home vs the costs of renting during the same time period. Point is: do your research and be realistic about it. Buying a home is a huge financial risk.\"",
"title": ""
},
{
"docid": "64456",
"text": "1) How does owning a home fit into my financial portfolio? Most seem to agree that at best it is a hedge against rent or dollar inflation, and at worst it should be viewed as a liability, and has no place alongside other real investments. Periods of high inflation are generally accompanied with high(er) interest rates. Any home is a liability, as has been pointed out in other answers; it costs money to live in, it costs money to keep in good shape, and it offers you no return unless you sell it for more than you have paid for it in total (in fact, as long as you have an outstanding mortgage, it actually costs you money to own, even when not considering things like property taxes, utilities etc.). The only way to make a home an investment is to rent it out for more than it costs you in total to own, but then you can't live in it instead. 2) How should one view payments on a home mortgage? How are they similar or different to investing in low-risk low-reward investments? Like JoeTaxpayer said in a comment, paying off your mortgage should be considered the same as putting money into a certificate of deposit with a term and return equivalent to your mortgage interest cost (adjusting for tax effects). What is important to remember about paying off a mortgage, besides the simple and not so unimportant fact that it lowers your financial risk over time, is that over time it improves your cash flow. If interest rates don't change (unlikely), then as long as you keep paying the interest vigilantly but don't pay down the principal (assuming that the bank is happy with such an arrangement), your monthly cost remains the same and will do so in perpetuity. You currently have a cash flow that enables you to pay down the principal on the loan, and are putting some fairly significant amount of money towards that end. Now, suppose that you were to lose your job, which means a significant cut in the household income. If this cut means that you can't afford paying down the mortgage at the same rate as before, you can always call the bank and tell them to stop the extra payments until you get your ducks back in the proverbial row. It's also possible, with a long history of paying on time and a loan significantly smaller than what the house would bring in in a sale, that you could renegotiate the loan with an extended term, which depending on the exact terms may lower your monthly cost further. If the size of the loan is largely the same as or perhaps even exceeds the market value of the house, the bank would be a lot more unlikely to cooperate in such a scenario. It's also a good idea to at the very least aim to be free of debt by the time you retire. Even if one assumes that the pension systems will be the same by then as they are now (some don't, but that's a completely different question), you are likely to see a significant cut in cash flow on retirement day. Any fixed expenses which cannot easily be cut if needed are going to become a lot more of a liability when you are actually at least in part living off your savings rather than contributing to them. The earlier you get the mortgage paid off, the earlier you will have the freedom to put into other forms of savings the money which is now going not just to principal but to interest as well. What is important to consider is that paying off a mortgage is a very illiquid form of savings; on the other hand, money in stocks, bonds, various mutual funds, and savings accounts, tends to be highly liquid. It is always a good idea to have some savings in easily accessible form, some of it in very low-risk investments such as a simple interest-bearing savings account or government bonds (despite their low rate of return) before you start to aggressively pay down loans, because (particularly when you own a home) you never know when something might come up that ends up costing a fair chunk of money.",
"title": ""
},
{
"docid": "546187",
"text": "\"If I have a house that its market value went from $100k to $140k can I get HELOC $40K? Maybe - the amount that you can borrow depends on the market value of the house, so if you already have $100k borrowed against it, it will be tough to borrow another $40k without paying a higher interest rate, since there is a real risk that the value will decrease and you will be underwater. Can I again ask for HELOC after I finish the renovation in order to do more renovation and maybe try to end up renovating the house so its value raises up to $500k? I doubt you can just \"\"renovate\"\" a house and increase its market value from $140k to $500K. Much of a house's value is determined by its location, and you can quickly outgrow a neighborhood. If you put $360k in improvements in a neighborhood where other homes are selling for $140k you will not realize nearly that amount in actual market value. People that buy $500k houses generally want to be in an area where other homes are worth around the same amount. If you want to to a major renovation (such as an addition) I would instead shop around for a Home Improvement Loan. The main difference is that you can use the expected value of the house after improvements to determine the loan balance, instead of using the current value. Once the renovations are complete, you roll it and the existing mortgage into a new mortgage, which will likely be cheaper than a mortgage + HELOC. The problem is that the cost of the improvements is generally more than the increase in market value. It also helps you make a wise decision, versus taking out a $40k HELOC and spending it all on renovations, only to find out that the increase in market value is only $10k and you're now underwater. So in your case, talk to a contractor to plan out what you want to do, which will tell you how much it will cost. Then talk to a realtor to determine what the market value with those improvements will be, which will tell you how much you can borrow. It's highly likely that you will need to pay some out-of-pocket to make up the difference, but it depends on what the improvements are and what comparable homes sell for.\"",
"title": ""
},
{
"docid": "106145",
"text": "If you're looking for some formula, I don't think one exists. People talk about this all the time and give conflicting advice. If there was a proven-accurate formula, they wouldn't be debating it. There are basically 3 reasons to do a home improvement project: (a) Correct a problem so that you prevent on-going damage to your home. For example, have a leaking roof patched or replaced, or exterminate termites. Such a job is worthwhile if the cost of fixing the problem is less than the cost of future damage. In the case of my termite and leaking roof examples, this is almost always worth doing. Lesser maintenance problems might be more debatable. Similarly, some improvements may reduce expenses. Like replacing an old furnace with a newer model may cut your heating bills. Here the question is: how long does it take to repay the investment, compared to other things you might invest your money in. Just to make up numbers: Suppose you find that a new furnace will save you $500 per year. If the new furnace costs $2000, then it will take 4 years to pay for itself. I'd consider that a good investment. If that same $2000 furnace will only cut your heating bills by $100 per year, then it will take 20 years to pay for itself. You'd probably be better off putting the $2000 into the stock market and using the gains to help pay your heating bill. (b) Increase the resale value of your home. If you are paying someone else to do the work, the harsh reality here is: Almost no job will increase the resale value by more than the cost of getting the job done. I've seen many articles over the years citing studies on this. I think most conclude that kitchen remodeling comes closet to paying for itself, and bathrooms come next. New windows are also up there. I don't have studies to prove this, but my guesses would be: Replacing something that is basically nice with a different style will rarely pay for itself. Like, replacing oak cabinets with cherry cabinets. Replacing something that is in terrible shape with something decent is more likely to pay back than replacing something decent with something beautiful. Like if you have an old iron bathtub that's rusting and falling apart, replacing it may pay off. If you have a 5-year-old bathtub that's in good shape but is not premium, top of the line, replacing it with a premium bathtub will probably do very little for resale value. If you can do a lot of the work yourself, the story changes. Many home improvement jobs don't require a lot of materials, but do require a lot of work. If you do the labor, you can often get the job done very cheaply, and it's likely that the increase in resale value will be more than what you spend. For example, most of my house has hardwood floors. Lots of people like pretty hardwood floors. I just restained the floors in two rooms. It cost me, I don't know, maybe $20 or $30 for stain and some brushes. I'm sure if I tried to sell the house tomorrow I'd get my twenty bucks back in higher sale value. Realtors often advise sellers to paint. Again, if you do it yourself, the cost of paint may be a hundred dollars, and it can increase the sale price of the house by thousands. Of course if you do the work yourself, you have to consider the value of your time. (c) To make your home more pleasant to live in. This is totally subjective. You have to make the decision on the same basis that you decide whether anything that is not essential to survival is worth buying. To some people, a bottle of fancy imported wine is worth thousands, even millions, of dollars. Others can't tell the difference between a $10,000 wine and a $15 wine. The thing to ask yourself is, How important is this home improvement to me, compared to other things I could do with the money? Like, suppose you're considering spending $20,000 remodeling your kitchen. What else could you do with $20,000? You could buy a car, go on an elaborate vacation, eat out several times a week for years, retire a little earlier, etc. No one can tell you how much something is worth to you. Any given home improvement may involve a combination of these factors. Like say you're considering that $20,000 kitchen remodeling. Say you somehow find out that this will increase the resale value by $15,000. If the only reason you were considering it was to increase resale value, then it's not worth it -- you'd lose $5,000. But if you also want the nicer kitchen, then it is fair to say, Okay, it will cost me $20,000, but ultimately I'll get $15,000 of that back. So in the long run it will only cost me $5,000. Is having a nicer kitchen worth $5,000 to me? Note, by the way, that resale value only matters if and when you sell the house. If you expect to stay in this house for 20 years, any improvements done are VERY long-term investments. If you live in it until you die, the resale value may matter to your heirs.",
"title": ""
},
{
"docid": "299591",
"text": "The home owner does not start foreclosure, the bank decides when to foreclose. Therefore you cannot really decide a time to foreclose if you are trying to time the decision. The process You miss payments, and the banks will send you a late notice for the missing payments. Expect many notices. The bank will call you at home, on your cell phone and at work. They will mail you letters regarding the missing payments. If you continue to miss payments, the bank will probably demand the loan be paid in full. You will owe the bank the full balance of the principle, all past due interest, all past due late charges and junk fees. The bank won't even take a normal monthly payment from you should you try to pay your regular payment again. Some law enforcement will notify you on the bank's intent to foreclose. The bank has begun legal proceedings. Legal notices are published in the local newspaper. Soon the notices and the legal waiting period will expire. Court proceedings happen. The court will then allow the bank to foreclose. Notices to into the paper again about the updated status of the foreclosure. The house is sold at auction. Money from the auction is used to pay taxes owned, then mortgages, then other liens or creditors who file. Further debt for the home owner Taxes When sold, if the mortgage debt exceeds the home's fair market value, US Federal Tax rules say the selling price as the fair market value. The fair market value can still be higher than the tax basis (which I think is the value of the house at the time of original purchase plus improvements.). If the fair market value is higher, you will own taxes on sale. However tax rules in the US say if you have owned the home more than two years and make less than $250,000 in the transaction ($500,000 if married) you will not owe any tax. State taxes can be different. Additionally, if the mortgage lender forgives the debt and doesn't create a deficiency, that income is taxable as well. This is more an more common these days. There are exceptions if the home is your primary residence. This whole process an take several months to occur, but depends on where you live. If you continue to live in the home after the auction, the new owner must evict you from the property which is another set of legal proceedings. Your credit and ability to buy are home will be damaged for the next several years. I am not so sure on how PMI works for the banks, but I know they are getting some money back.",
"title": ""
},
{
"docid": "496752",
"text": "As mentioned, the main advantage of a 15-year loan compared to a 30-year loan is that the 15-year loan should come at a discounted rate. All things equal, the main advantage of the 30-year loan is that the payment is lower. A completely different argument from what you are hearing is that if you can get a low interest rate, you should get the longest loan possible. It seem unlikely that interest rates are going to get much lower than they are and it's far more likely that they will get higher. In 15 years, if interest rates are back up around 6% or more (where they were when I bought my first home) and you are 15 years into a 30 year mortgage, you'll being enjoying an interest rate that no one can get. You need to keep in mind that as the loan is paid off, you will earn exactly 0% on the principal you've paid. If for some reason the value of the home drops, you lose that portion of the principal. The only way you can get access to that capital is to sell the house. You (generally) can't sell part of the house to send a kid to college. You can take out another mortgage but it is going to be at the current going rate which is likely higher than current rates. Another thing to consider that over the course of 30 years, inflation is going to make a fixed payment cheaper over time. Let's say you make $60K and you have a monthly payment of $1000 or 20% of your annual income. In 15 years at a 1% annualized wage growth rate, it will be 17% of your income. If you get a few raises or inflation jumps up, it will be a lot more than that. For example, at a 2% annualized growth rate, it's only 15% of your income after 15 years. In places where long-term fixed rates are not available, shorter mortgages are common because of the risk of higher rates later. It's also more common to pay them off early for the same reason. Taking on a higher payment to pay off the loan early only really only helps you if you can get through the entire payment and 15 years is still a long way off. Then if you lose your job then, you only have to worry about taxes and upkeep but that means you can still lose the home. If you instead take the extra money and keep a rainy day fund, you'll have access to that money if you hit a rough patch. If you put all of your extra cash in the house, you'll be forced to sell if you need that capital and it may not be at the best time. You might not even be able to pay off the loan at the current market value. My father took out a 30 year loan and followed the advice of an older coworker to 'buy as much house as possible because inflation will pay for it'. By the end of the loan, he was paying something like $250 a month and the house was worth upwards of $200K. That is, his mortgage payment was less than the payment on a cheap car. It was an insignificant cost compared to his income and he had been able to invest enough to retire in comfort. Of course when he bought it, inflation was above 10% so it's bit different today but the same concepts still apply, just different numbers. I personally would not take anything less than a 30 year loan at current rates unless I planned to retire in 15 years.",
"title": ""
},
{
"docid": "149215",
"text": "Both of my primary home purchases were either at, or close to asking price. My first house was during the local seller's market in 2001-2002. There were waiting lines for open houses. In hindsight we bought more home than we needed at the time but that had nothing to do with offering asking price. It was the market for the type of property (location and features) at that time. My second house was a little after the peak in 2008. The value had come down quite a bit and the property was priced on the low side versus the comps. To this day my second house still appraises higher than what we paid for it even though it was at asking price. As a third example, my brother-in-law got into a bidding war on his first home purchase and ended up buying it for above asking price. This was normal for the houses in the area he was looking at. With real estate, like other people have said, it really is important to either know the area you are looking at or to get an agent you trust and have them explain their reasons for their offer strategy through the comps. Yes agents need to make money but the good ones have been in the business a while and also live off of repeat business when you sell your house or refer friends and family to them. Agents do a lot less work when it comes to selling by the way so they would love for you to come back to them when it's time to sell. If I'm not happy with the way things are going with my agent I would have a heart to heart with them and give them a chance to correct the relationship. I've spoken to a realtor friend in the past about getting out of buyer's contracts and he told me it's a lot easier as a buyer than a seller. The buyer has most of the power during the process. The seller just has what the buyer wants.",
"title": ""
},
{
"docid": "582340",
"text": "\"I had the same thing happen to my house. I bought it in 2011 for 137,000, which was the same as the FHA appraised value (because FHA won't guarantee a loan for more than their appraiser thinks its worth). January of last year, I get the letter from the tax office and see that my house has been assessed at only 122,000. I was shocked too, until I read a similar document that Phil told you to read. The short of it is, no matter what the tax assessor calls their calculation, it is an assessment. It was mass-produced along with everyone else's in your neighborhood by looking at its specs on paper (acreage, house square footage, age, beds/baths) and by driving by your home to see its general condition. The fact that your lawn may be less well-kept than the last time they drove by could have affected the decision a little. It's very unlikely to have been a major determinant of the assessment. The assessment value affects taxes, and taxes only. It is, in most states, a matter of public record, and so it could be used by a potential buyer to negotiate a lower price. However, everyone in the housing business knows that the assessed value is not the market value, and the buyer's agent will be encouraging their client to make a more realistic bid. This \"\"assessed value\"\" is not an \"\"appraisal value\"\". An appraisal is done by someone actually walking into and through your home, inspecting the general condition inside and out, to try to make a fair evaluation of what the home is actually worth. That number is almost always going to be more than the assessment value, because it takes into account all the amenities of the home; the current fixtures, the well-kept (or recently-replaced) flooring, the energy-efficient HVAC and hot water system, etc etc. It also takes into account recent comparables; what have other houses, with the same general statistics, the same amenities, relatively close in location, sold for recently? That will still generally be different from the true market value of the home. That value is nothing more or less than what a potential buyer will pay to have it at the time you decide to sell it, and that in turn depends 100% on your potential buyers' myriad situations. Someone may lowball even the assessed value because they're looking for a deal and hoping you're desperate; you just reject the offer. Someone may be looking at comparables indicating the house is maybe overpriced by $10k. You can counter and try to come to an agreement. Or, your potential buyer could work five minutes from your house, and be willing to pay at or above your asking price because the next best possibility is another 10 miles away. Since you aren't looking to sell the home, none of this matters, except to determine any escrow payments you might be making towards property taxes. Just keep making your mortgage payment, and don't worry about it. If you really wanted to, you could petition the state for a second opinion, but you think the value should be higher; if they agree with you, they'll raise the assessed value and you'll pay more in taxes. Why in the world would you want to do that?\"",
"title": ""
},
{
"docid": "145404",
"text": "\"Someone has to hand out cash to the seller. Even if no physical money changes hands (and I've bought a house; I can tell you a LOT of money changes hands at closing in at least the form of a personal check), and regardless of exactly how the bank accounts for the actual disbursement of the loan, the net result is that the buyer has cash that they give the seller, and are now in debt to the bank for least that amount (but, they now have a house). Now, the bank probably didn't have that money just sitting in its vault. Money sitting in a vault is money that is not making more money for the bank; therefore most banks keep only fractionally more than the percentage of deposit balances that they are required to keep by the Feds. There are also restrictions on what depositors' money can be spent on, and loans are not one of them; the model of taking in money in savings accounts and then loaning it out is what caused the savings and loan collapse in the 80s. So, to get the money, it turns to investors; the bank sells bonds, putting itself in debt to bond holders, then takes that money and loans it out at a higher rate, covering the interest on the bond and making itself a tidy profit for its own shareholders. Banks lose money on defaults in two ways. First, they lose all future interest payments that would have been made on the loan. Technically, this isn't \"\"revenue\"\" until the interest is calculated for each month and \"\"accrues\"\" on the loan; therefore, it doesn't show on the balance sheet one way or the other. However, the holders of those bonds will expect a return, and the banks no longer have the mortgage payment to cover the coupon payments that they themselves have to pay bondholders, creating cash flow problems. The second, and far more real and damaging, way that banks lose money on a foreclosure is the loss of collateral value. A bank virtually never offers an unsecured \"\"signature loan\"\" for a house (certainly not at the advertised 3-4% interest rates). They want something to back up the loan, so if you disappear off the face of the earth they have a clear claim to something that can help them recover their money. Usually, that's the house itself; if you default, they get the house from you and sell it to recover their money. Now, a major cause of foreclosure is economic downturn, like the one we had in 2009 and are still recovering from. When the economy goes in the crapper, a lot of things we generally consider \"\"stores of value\"\" lose that value, because the value of the whatzit (any whatzit, really) is based on what someone else would pay to have it. When fewer people are looking to buy that whatzit, demand drops, bringing prices with it. Homes and real estate are one of the real big-ticket items subject to this loss of value; when the average Joe doesn't know whether he'll have a job tomorrow, he doesn't go house-hunting. This average Joe may even be looking to sell an extra parcel of land or an income property for cash, increasing supply, further decreasing prices. Economic downturn can often increase crime and decrease local government spending on upkeep of public lands (as well as homeowners' upkeep of their own property). By the \"\"broken window\"\" effect, this makes the neighborhood even less desirable in a vicious cycle. What made this current recession a double-whammy for mortgage lenders is that it was caused, in large part, by a housing bubble; cheap money for houses made housing prices balloon rapidly, and then when the money became more expensive (such as in sub-prime ARMs), a lot of those loans, which should never have been signed off on by either side, went belly-up. Between the loss of home value (a lot of which will likely turn out to be permanent; that's the problem with a bubble, things never recover to their peak) and the adjustment of interest rates on mortgages to terms that will actually pay off the loan, many homeowners found themselves so far underwater (and sinking fast) that the best financial move for them was to walk away from the whole thing and try again in seven years. Now the bank's in a quandary. They have this loan they'll never see repaid in cash, and they have this home that's worth maybe 75% of the mortgage's outstanding balance (if they're lucky; some homes in extremely \"\"distressed\"\" areas like Detroit are currently trading for 30-40% of what they sold for just before the bubble burst). Multiply that by, say, 100,000 distressed homes with similar declines in value, and you're talking about tens of billions of dollars in losses. On top of that, the guarantor (basically the bank's insurance company against these types of losses) is now in financial trouble themselves, because they took on so many contracts for debt that turned out to be bad (AIG, Fannie/Freddie); they may very well declare bankruptcy and leave the bank holding the bag. Even if the guarantor remains solvent (as they did thanks to generous taxpayer bailouts), the bank's swap contract with the guarantor usually requires them to sell the house, thus realizing the loss between what they paid and what they finally got back, before the guarantor will pay out. But nobody's buying houses anymore, because prices are on their way down; the only people who'd buy a house now versus a year from now (or two or three years) are the people who have no choice, and if you have no choice you're probably in a financial situation that would mean you'd never be approved for the loan anyway. In order to get rid of them, the bank has to sell them at auction for pennies on the dollar. That further increases the supply of cheap homes and further drives down prices, making even the nicer homes the bank's willing to keep on the books worth less (there's a reason these distresed homes were called \"\"toxic assets\"\"; they're poisonous to the banks whether they keep or sell them). Meanwhile, all this price depression is now affecting the people who did everything right; even people who bought their homes years before the bubble even formed are watching years of equity-building go down the crapper. That's to say nothing of the people with prime credit who bought at just the wrong time, when the bubble was at its peak. Even without an adjusting ARM to contend with, these guys are still facing the fact that they paid top dollar for a house that likely will not be worth its purchase price again in their lifetime. Even with a fixed mortgage rate, they'll be underwater, effectively losing their entire payment to the bank as if it were rent, for much longer than it would take to have this entire mess completely behind them if they just walked away from the whole thing, moved back into an apartment and waited it out. So, these guys decide on a \"\"strategic default\"\"; give the bank the house (which doesn't cover the outstanding balance of course) and if they sue, file bankruptcy. That really makes the banks nervous; if people who did everything right are considering the hell of foreclosure and bankruptcy to be preferable to their current state of affairs, the bank's main threat keeping people in their homes is hollow. That makes them very reluctant to sign new mortgages, because the risk of default is now much less certain. Now people who do want houses in this market can't buy them, further reducing demand, further decreasing prices... You get the idea. That's the housing collapse in a nutshell, and what banks and our free market have been working through for the past five years, with only the glimmer of a turnaround picking up home sales.\"",
"title": ""
},
{
"docid": "59147",
"text": "Answers to this your question break down along a few lines regarding opportunity costs of tying up a significant chunk of your salary and assets in one piece of property, as opposed to other things you'd like to do with your life. The 30 year standard mortgage was invented in the 30's as part of FDR's new deal to make housing affordable to more people, while relieving the strain on the market of foreclosed homes from ~10 year interest only balloon mortgages (sound familiar?). The 30 year term tends to follow the career of the average American of that era, allowing them to pay the house off and live out the remainder of their lives there at a lower cost. Houses are depreciating assets because they wear out over time. Their greatest investment value is a place to live. The appreciation on a home comes from the real estate it sits on and the community the property is located in. Value is determined by desirability of the house and community in their current state, and the supply of property in the area. This value can only be extracted when you sell the home. This partially answers your last question noting that you shouldn't buy a really expensive building for investment value. We've learned in recent years that there are no long term guarantees of property value either, because land and communities can decrease in value due to unemployment, over supply, crime, pollution, etc. Only buy as much home as you will need in the next decade or so, in a place that you will like living over that time period, and don't consider it much of an investment. I will tell you to get a fifteen year fixed rate mortgage since it's readily available at lower rates and has a significantly lower total purchase price than the standard 30 years. The monthly payment difference isn't that great, and anyone who looks at the monthly payment as opposed to the total costs, your priorities and the opportunity costs shouldn't be trusted for financial advice. I don't like debt. There are psychological benefits to being free from the bondage and drain of a long term mortgage on your finances. The biggest argument for paying off your home quickly is freedom to pursue other desires with all of your salary and the assets you have available to you. Some financial advisers will tell you to keep your mortgage costs under 25% of your income, so that you can actually live off the money you make. I would also recommend paying at least enough into your 401k to get the company match and fully funding your Roth IRA. I'd also have an emergency fund to cover at least 6 months of expenses, including this mortgage in case you lose your job. A 15 or 20 year mortgage will give you breathing room to take care of these other priorities, and you can overpay on almost any mortgage to decrease the principal and finish in a shorter time period (make sure to get a mortgage that allows prepayment) . More financially savvy people may tell you to take the 30 year mortgage and invest the difference. Especially with mortgage rates around 4%, this is a very cheap way to increase your purchasing power and total assets. Most people lack the investment prowess and self discipline to make this plan pay off. There are even fewer guarantees regarding markets and investments than property. This also is a way of diversifying your total assets to protect against loss of value in your home. This approach has backfired for thousands of people who are underwater on their homes. This problem is often compounded by job loss forcing you to move, or increasing your commute, making your home less desirable for you. Some people will tell you to maintain the mortgage for the tax credit. This fails a basic math test since you only get about a quarter of the money (depending on your tax rate) that you are paying in interest back from the government. The rest of the money goes to bank at no gain to you. This approach is basically a taxpayer subsidized decrease of your 4% interest payment to a 3% interest payment (assuming you have ~ $5000 in other deductions), and only pays off if you can successfully invest the money at a rate somewhat greater than 3%.",
"title": ""
},
{
"docid": "105345",
"text": "An amortization schedule is often used to produce identical payments for the term (repayment period) of a loan, resulting in the principal being paid off and the debt retired at the end of the loan. This is in contrast to an interest only, or balloon loan. These loans require little or no payment against the balance of the loan, requiring the loan to be paid indefinitely if there is no term, or requiring the loan to be entirely paid off from cash or a new loan at the end of the term. A basic amortization formula can be derived from the compound interest formula: This formula comes from the Wikipedia article on amortization. The basics of the formula are the periodic payment amount, A (your monthly payment), can be determined by the principal loan, P, the rate, r, and the number of payments, n. Lenders lend money to make a profit on the interest. They'd like to get back all the money they lent out. Amortization schedules are popular because the fixed low payments make it easier for borrowers to pay the loan off eventually. They also tend to be very profitable for lenders, especially at the start of the term, because they make a lot of profit on interest, just like the start of your mortgage. The principal of a mortgage has more meaning than the principal of a revolving debt credit card. The mortgage principal is fixed at the start, and represents the value of the collateral property that is your home. You could consider the amount of principal paid to be the percentage of your home that you actually own (as part of your net worth calculation). A credit card has a new balance each month depending on how much you charge and how much you pay off. Principal has less meaning in this case, because there is no collateral to compare against, and the balance will change monthly. In this case, the meaning of the amortization schedule on your credit card is how long it will take you to pay off the balance if you stop charging and pay at the proscribed payment level over the term described. Given the high interest rate on credit cards, you may end up paying twice as much for goods in the long run if you follow your lenders schedule. Amortizing loans are common for consumer loans, unless a borrower is seeking out the lowest possible monthly payment. Lenders recognize that people will eventually die, and want to be paid off before that happens. Balloon and interest only bonds and loans are more commonly issued by businesses and governments who are (hopefully) investing in capital improvements that will pay off in the long run. Thousands of people and businesses have gone bankrupt in this financial crisis because their interest only loans reached term, and no one was willing to lend them money anymore to replace their existing loan.",
"title": ""
},
{
"docid": "494950",
"text": "What a joke. The world economy would have collapsed without Goldman Sachs and Citibank? That is blatant propaganda and you're deluded if you believe it. Government intervention caused the housing bubble, and government intervention is what those huge banks relied on when they made 30:1 securities swaps wagers. Those bankers acted like criminals and the government cheered them on and made it easier. There is absolutely zero incentive for either the bankers or the politicians to be fiscally responsible, that is the problem. Printing money has not caused harm? Are you mental? Printing money is outright theft from every working man. It is the epitome of corruption and the hallmark of a failing government slipping into fascism and plutocracy. They won't even tell us how much money is on the books anymore. It is an arbitrary amount which changes at their discretion. There is more debt in the system than actual value, and the debt gains interest faster than the value appreciates. The entire currency system is designed to transfer money to the wealthy and carry a debt which can never be paid off. Those dollars that you and I work for every day are just a means to control us.",
"title": ""
},
{
"docid": "486751",
"text": "\"@Alex B already answered the first question. I want to respond to the second and third: I have heard the term \"\"The equity on your home is like a bank\"\". What does that mean? I suppose I could borrow using the equity in my home as collateral? Yes, you can borrow against the equity in your home. What you should keep in mind is that you can only borrow against the amount that you've paid on your house. For example, if you've paid $100,000 against your house, you can then borrow $100,000 (assuming the value hasn't changed). The argument that this is a good deal misses the obvious alternative: If you didn't spend that $100,000 on a house, then you'd still have it and wouldn't need to take out a loan at all. Of course, equity still has value, and you should consider it when doing the cost/benefit analysis, but make sure to compare your equity to savings you could have from renting. Are there any other general benefits that would drive me from paying $800 in rent, to owning a house? Economically: As you'll notice from my parenthetical remarks, this is extremely situational. It might be good to come up with a spreadsheet for your situation, taking all of the costs into account, and see if you end up better or worse. Also, there's nothing wrong with buying a house for non-economic reasons if that's what you want. Just make sure you're aware of the real cost before you do it.\"",
"title": ""
},
{
"docid": "413169",
"text": "My question is, how do you rebuild a home, without the money to rebuild the home? I ignorantly thought that was why we paid for insurance. The reason that you have insurance is so as to keep the mortgage lender from losing money. That's why you buy the insurance through the mortgage lender and they get paid. Without the insurance, you'd have no home but still have a mortgage. You'd either have to pay off a mortgage with no house or have to declare bankruptcy to shed the mortgage. You essentially have two paths. If you (or the builder/suppliers) can afford to float the cost, you can rebuild the original house. You'll eventually get the $161,000 and can pay off the builder and suppliers. This may involve taking out a construction mortgage to refinance the original mortgage. Presumably the construction mortgage would be with a different lender. The other path is that you can sell the existing property as is, and use the insurance and proceeds to pay off the existing mortgage. Then you'd have no house and no mortgage. You start over and buy a house with a mortgage. It's possible that your insurance payoff isn't enough to pursue either path. Then your option is to get the insurer to make a bigger payoff. This may involve suing them. Note that you may be able to talk the government into suing the insurer for you. They do have regulators who can review things. If you can't get government action, there are lawyers who will do the suing and take their fees out of their winnings.",
"title": ""
},
{
"docid": "257980",
"text": "\"Here are some important things to think about. Alan and Denise Fields discuss them in more detail in Your New House. Permanent work. Where do you want to live? Are there suitable jobs nearby? How much do they pay? Emergency fund. Banks care that you have \"\"reserves\"\" (and/or an unsecured line of credit) in case you have a run of bad luck. This also helps with float the large expenses when closing a loan. Personal line of credit. Who are you building for? If you are not married, then you should consider whether building a home makes that easier, or harder. If you hope to have kids, you should consider whether your home will make it easier to have kids, or harder. If you are married (or seriously considering it), make sure that your spouse helps with the shopping, and is in agreement on the priorities and choices. If you are not married, then what will you do if/when you get married? Will you sell? expand? build another house on the same lot? rent the home out? Total budget. How much can the lot, utilities, permits, taxes, financing charges, building costs, and contingency allowance come to? Talk with a banker about how much you can afford. Talk with a build-on-your-lot builder about how much house you can get for that budget. Consider a new mobile or manufactured home. But if you do choose one, ask your banker how that affects what you can borrow, and how it affects your rates and terms. Talk with a good real estate agent about how much the resale value might be. Finished lot budget. How much can you budget for the lot, utilities, permits required to get zoning approval, fees, interest, and taxes before you start construction? Down payment. It sounds like you have a plan for this. Loan underwriting. Talk with a good bank loan officer about what their expectations are. Ask about the \"\"front-end\"\" and \"\"back-end\"\" Debt-To-Income ratios. In Oregon, I recommend Washington Federal for lot loans and construction loans. They keep all of their loans, and service the loans themselves. They use appraisers who are specially trained in evaluating new home construction. Their appraisers tend to appraise a bit low, but not ridiculously low like the incompetent appraisers used by some other banks in the area. (I know two banks with lots of Oregon branches that use an appraiser who ignores 40% of the finished, heated area of some to-be-built homes.) Avoid any institution (including USAA and NavyFed) that outsources their lending to PHH. Lot loan. In Oregon, Washington Federal offers lot loans with 30% down payments, 20-year amortization, and one point, on approved credit. The interest rate can be a fixed rate, but is typically a few percentage points per year higher than for a mortgage secured by a permanent house. If you have the financial wherewithal to start building within two years, Washington Federal also offers short-term lot loans. Ask about the costs of appraisals, points, and recording fees. Rent. How much will it cost to rent a place to live, between when you move back to Oregon, and when your new home is ready to move into? Commute. How much time will it take to get from your new home to work? How much will it cost? (E.g., car ownership, depreciation, maintenance, insurance, taxes, fuel? If public transportation is an option, how much will it cost?) Lot availability. How many are there to choose from? Can you talk a farmer into selling off a chunk of land? Can you homestead government land? How much does a lot cost? Is it worth getting a double lot (or an extra large lot)? Utilities. Do you want to live off the grid? Are you willing to make the choices needed to do that? (E.g., well, generator, septic system, satellite TV and telephony, fuel storage) If not, how much will it cost to connect to such systems? (For practical purposes, subtract twice the value of these installation costs from the cost of a finished lot, when comparing lot deals.) Easements. These provide access to your property, access for others through your property, and affect your rights. Utility companies often ask for far more rights than they need. Until you sign on the dotted line, you can negotiate them down to just what they need. Talk to a good real estate attorney. Zoning. How much will you be allowed to build? (In terms of home square footage, garage square footage, roof area, and impermeable surfaces.) How can the home be used? (As a business, as a farm, how many unrelated people can live there, etc.) What setbacks are required? How tall can the building(s) be? Are there setbacks from streams, swamps, ponds, wetlands, or steep slopes? Choosing a builder. For construction loans, banks want builders who will build what is agreed upon, in a timely fashion. If you want to build your own house, talk to your loan officer about what the bank expects in a builder. Plansets and permits. The construction loan process. If you hire a general contractor, and if you have difficulties with the contractor, you might be forced to refuse to accept some work as being complete. A good bank will back you up. Ask about points, appraisal charges, and inspection fees. Insurance during construction. Some companies have good plans -- if the construction takes 12 months or less. Some (but not all) auto insurance companies also offer good homeowners' insurance for homes under construction. Choose your auto insurance company accordingly. Property taxes. Don't forget to include them in your post-construction budget. Homeowners' insurance. Avoid properties that need flood insurance. Apply a sanity check to flood maps -- some of them are unrealistic. Strongly consider earthquake insurance. Don't forget to include these costs in your post-construction budget. Energy costs. Some jurisdictions require you to calculate how large a heating system you need. Do not trust their design temperatures -- they may not allow for enough heating during a cold snap, especially if you have a heat pump. (Some heat pumps work at -10°F -- but most lose their effectiveness between 10°F and 25°F.) You can use these calculations, in combination with the number of \"\"heating degree days\"\" and \"\"cooling degree days\"\" at your site, to accurately estimate your energy bills. If you choose a mobile or manufactured home, calculate how much extra its energy bills will be. Home design. Here are some good sources of ideas: A Pattern Language, by Christopher Alexander. Alexander emphasizes building homes and neighborhoods that can grow, and that have niches within niches within niches. The Not-So-Big House, by Sarah Susanka. This book applies many Alexander's design patterns to medium and large new houses. Before the Architect. The late Ralph Pressel emphasized the importance of plywood sheathing, flashing, pocket doors, wide hallways, wide stairways, attic trusses, and open-truss or I-joist floor systems. Lots of outlets and incandescent lighting are good too. (It is possible to have too much detail in a house plan, and too much room in a house. For examples, see any of his plans.) Tim Garrison, \"\"the builder's engineer\"\". Since Oregon is in earthquake country -- and the building codes do not fully reflect that risk -- emphasize that you want a building that would meet San Jose, California's earthquake code.\"",
"title": ""
},
{
"docid": "323932",
"text": "I will just explain the time value of money in general, descriptive terms and save the math for someone else. Imagine: You have half a million dollars. I'd like to borrow it all from you. I'll pay it all back, every penny, but no more. And I'll pay it back in about, oh, thirty years or so. (Imagine also that you can be 100% sure that I'll pay it back.) Does this sound like a good deal? Not really. Why not? Well, you could do something with that sort of money. With that sort of money, you could do a lot of things for 30 years. You could buy a nice house and live in it for 30 years and save yourself from spending a lot of money on rent during that time (or save money on interest by paying off a mortgage early) even if the price of the house goes nowhere. If you already had a house, you could do some home improvement, like insulate the place better (to save on heating bills) or even just on something that you're going to enjoy for part of those 30 years (a patio in the back yard). If you were feeling entrepreneurial, you could take that money and start a business. Or you could invest that money in the stock market, and get a lot more back.... and if that's too risky for you, just start a savings account and earn interest. And finally, in 30 years, the value of the dollar will be lower because of inflation, so it won't buy as much now as it will then. That's the time value of money. It's the opportunity cost of the best of the things that you could have done with that money during the time it was gone. When you take out a loan, your interest payments will depend in part on the time value of the money you're borrowing: the people making the loan could be investing that money somewhere else, like government bonds. (It will also depend on factors like the risk of default on the loan - this is why credit card debt is more expensive than debt like a mortgage that's backed by a big fat asset like a house which can be seized and sold if you happen to default.) This is how the Federal Reserve can affect interest rates across the economy by just buying or selling government bonds.",
"title": ""
},
{
"docid": "315168",
"text": "Your house is not an asset, it is a liability. Assets feed you. Liabilites eat you. Robert Kiyosaki From a cash flow perspective your primary residence (ie your house) is an investment but it is not an asset. If you add up all the income your primary residence generates and subtract all the expenses it incurs, you will see why investment gurus claim this. Perform the same calculations for a rental property and you're more likely to find it has a positive cash flow. If it has a negative cash flow, it's not an asset either; it's a liability. A rental property with a negative cash flow is still an investment, but cash flow gurus will tell you it's a bad investment. While it is possible that your house may increase in value and you may be able to sell it for more than you paid, will you be able to sell it for more than all of the expenses incurred while living there? If so, you have an asset. Some people will purchase a home in need of repair, live in it and upgrade it, sell it for profit exceeding all expenses, and repeat. These people are flipping houses and generating capital gains based on their own hard work. In this instance a person's primary residence can be an asset. How much of an asset is calculated when the renovated house is sold.",
"title": ""
},
{
"docid": "108399",
"text": "Some highly pessimistic things worth noting to go alongside all the stability and tax break upside that homes generally provide: Negative equity is no joke and basically the only thing that bankrupts the middle classes consistently en masse. The UK is at the end of a huge housing bull run where rents are extremely cheap relative to buying (often in the 1% range within the M25), Brexit is looming and interest rates could well sky rocket with inflation. Borrowing ~500k to buy a highly illiquid asset you might have to fire sale in case of emergency/job loss etc for 300k in a few years when lots of (relatively) cheap rental housing is available to rent risk free, could be argued to be a highly lopsided and dangerous bet vs the alternatives. Locking in 'preferential' mortgage rates can be a huge trap: low interest rates generally increase asset values. If/when they rise, assets fall in value as the demand shrinks, making you highly exposed to huge losses if you need to sell before it is paid off. In the case of housing this can be exceptionally vicious as the liquidity dramatically dries up during falls, meaning fire sales become much more severe than they are for more liquid assets like stock. Weirdly and unlike most products, people tend to buy the very best house they can get leverage for, rather than work out what they need/want and finding the best value equivalent. If a bank will lend you £20 a day to buy lunch, and you can just afford to pay it, do you hunt out the very best £20 lunch you can every day, or do you make some solid compromises so you can save money for other things etc? You seem to be hunting very close to the absolute peak amount you can spend on these numbers. Related to above, at that level of mortgage/salary you have very little margin for error if either of you lose jobs etc. Houses are much more expensive to maintain/trade than most people think. You spend ~2-5% every time you buy and sell, and you can easily spend 2-20k+ a year depending what happens just keeping the thing watertight, paid for, liveable and staying up. You need to factor this in and be pessimistic when you do. Most people don't factor in these costs to the apparent 'index' rise in house values and what they expect to sell for in x years. In reality no buy and hold investor can ever realise even close to the quoted house price returns as they are basically stocks you have to pay 5% each time you buy or sell and then 1-20% percent a year to own - they have to rise dramatically over time for you to even break even after all the costs. In general you should buy homes to make memories, not money, and to buy them at prices that don't cause you sleepless nights in case of disasters.",
"title": ""
},
{
"docid": "420496",
"text": "\"Neither you nor others have mentioned the costs of being a homeowner. First, there are monetary costs. If you own a house, you have to pay taxes. They will vary by jurisdiction, but are usually not zero. You also need insurance, which again comes with monthly rates. Then, once in a while, you'll be hit with unpleasant lump sum payments. In 30 years, the mortgage is over and you own the house - but by that time, it will probably need a new roof. That's in the price range of a new car. And over that time, you'll rack up several other repairs which your landlord covers when you rent. Another thing which feels less like an expense emotionally but ends up thinning your wallet is the cosmetic changes you make just because it's your own home. You wouldn't put marble floors in the bathroom if you rent, but you might be tempted to if you live in the house. It might be even worth it from a life satisfaction point of view, but we are talking finance right now, and that's a minus. And then there are the opportunity costs. A house binds you geographically. You may pass up on a nice job offer because your house is too far away, for example. Or you might experience liquidity problems, because a house is difficult to turn into money in a hurry. If you are able to do so, it is usually a much larger sum than you need, and you are paying the costs inherent in that large transaction. These are just examples, you can probably come up with more costs. Then, it is not sure how much money you can get of the house if you change your mind. Say you take this job at the other end of the country, or you become a parent of four and need more space. At the time you decide to sell, the market may have gone down due to the overall state of the economy, or to the house location's popularity, or your own house may have turned undesirable (what if you get a mold infestation which would only go away if you strip it to the concrete and rebuild?) You could let it to renters, but that's a hassle of its own. It takes time to find renters, it may be expensive (income tax, regulations like Energieausweis in Germany), it is risky (if they don't pay, you might not see money even if you sue them). Then there is the problem that prices reflect not some kind of \"\"true\"\" value, but the intersection of supply and demand. And the home market is not as efficient as in a first semester microeconomics textbook. The buyers of private homes deal in small volumes, have little knowledge in the market, pay intermediaries' cuts, and are emotionally attached to the idea of \"\"owning my own house\"\". This drives demand up and creates higher prices than if you had perfectly rational actors on both sides. People pay money for the feeling of being home owners, so those who forego spending on that feeling have more money to invest in something else. Owning something always causes expenses. You have to calculate the savings of having the house vs. the expenses of having it, before you can decide if it is a good deal or not. If you only calculate one side of the equation, you'll be badly mistaken.\"",
"title": ""
},
{
"docid": "321877",
"text": "Having someone else paying you rent is always going to be the better deal financially. The question is, what does $450k buy in the neighborhood in which you want to live, vs $800k? I'm going to assume you can afford either option (buying a $450k home and not selling, or an $800k home and selling your current one) whether someone's paying you rent or not. Let's make up some numbers here; a $450k home, financed 80/20 (360k principal) at 4% for 30 years will cost you about $1720 in P&I payments per year (plus escrows such as RE taxes, PMI, and homeowners insurance where applicable). An $800k home financed 80/20 (640k principal) at 4% for 30yr will give you payments of about $3,055/mo before taxes and insurance. So, the worst case overall is that you buy a 450k home in the new neighborhood and are not, at any given time, collecting rent on the old property. That would (assuming the mortgage terms on both home loans were comparable) cost you $3440/mo and you'd be living in a $450k home in a neighborhood where 450k may not buy a home as nice as the one you moved out of. The question as I stated above is this; assuming you had a reliable tenant in your home for the entire remaining life of the loan on your current home, which is more acceptable to you: buying $450k of home (which might be a downgrade in sqft or amenities) and paying $2020 in P&I, or paying about a grand more ($3055/mo) for a much nicer home in the new location? Strictly from a money perspective, the renter is going to be the best option, IF you get reliable tenancy for the entire life of the mortgage on that house; you'll be paying $2020/mo for 30 years, which is $727,200, to end up with $950k of total home value (plus adjustments for actual home value appreciation/depreciation). That's the only way you'll come out ahead on any mortgage; have someone else pay most of it for you. If you don't rent, the $800k home will cost you $1,099,800, while two $450k homes will cost you $1,454,400. The percentage of home value over total payments for the 800k home would be 72% (you will have paid 137% of the value of the home), while you will have paid 153% of the value of two 450k homes.",
"title": ""
},
{
"docid": "546528",
"text": "\"Based on what you asked and your various comments on other answers, this is the first time that you will be making an offer to buy a house, and it seems that the seller is not using a real-estate agent to sell the house, that is, it is what is called a FSBO (for sale by owner) property (and you can learn a lot of about the seller's perspective by visiting fsbo.com). On the other hand, you are a FTB (first-time buyer) and I strongly recommend that you find out about the purchase process by Googling for \"\"first-time home buyer\"\" and reading some of the articles there. But most important, I urge you DO NOT make a written offer to purchase the property until you understand a lot more than you currently do, and a lot more than all the answers here are telling you about making an offer to buy this property. Even when you feel absolutely confident that you understand everything, hire a real-estate lawyer or a real-estate agent to write the actual offer itself (the agent might well use a standard purchase offer form that his company uses, or the State mandates, and just fill in the blanks). Yes, you will need to pay a fee to these people but it is very important for your own protection, and so don't just wing it when making an offer to purchase. As to how much you should offer, it depends on how much you can afford to pay. I will ignore the possibility that you are rich enough that you can pay cash for the purchase and assume that you will, like most people, be needing to get a mortgage loan to buy the house. Most banks prefer not to lend more than 80% of the appraised value of the house, with the balance of the purchase price coming from your personal funds. They will in some cases, loan more than 80% but will usually charge higher interest rate on the loan, require you to pay mortgage insurance, etc. Now, the appraised value is not determined until the bank sends its own appraiser to look at the property, and this does not happen until your bid has been accepted by the seller. What if your bid (say $500K) is much larger than the appraised value $400K on which the bank is willing to lend you only $320K ? Well, you can still proceed with the deal if you have $180K available to make the pay the rest. Or, you can let the deal fall apart if you have made a properly written offer that contains the usual contingency clause that you will be applying for a mortgage of $400K at rate not to exceed x% and that if you can't get a mortgage commitment within y days, the deal is off. Absent such a clause, you will lose the earnest money that you put into escrow for failure to follow through with the contract to purchase for $500K. Making an offer in the same ballpark as the market value lessens the chances of having the deal fall through. Note also that even if the appraised value is $500K, the bank might refuse to lend you $400K if your loan application and credit report suggest that you will have difficulty making the payments on a $400K mortgage. It is a good idea to get a pre-approval from a lender saying that based on the financial information that you have provided, you will likely be approved for a mortgage of $Z (that is, the bank thinks that you can afford the payments on a mortgage of as much as $Z). That way, you have some feel for how much house you can afford, and that should affect what kinds of property you should be bidding on.\"",
"title": ""
},
{
"docid": "578906",
"text": "I would tell the former owner that you will sell him the house for you current loan balance. He wants the home, he may be willing to pay what you owe. You can't really do a short sale unless you are behind on your payments. Banks only agree to a short sale when they think they are going to have to foreclose on the property. Not to mention a short sale is almost as bad as a foreclosure and will wreck your credit. If the former buying is not willing to buy the house for what you owe your only real option is to come up with the difference. If he offers you say $50K less than you owe, you will have to give the mortgage holder the remaining balance $50K in this example for them to release the property. Another problem you will face, if the former owner is willing to pay more than what the house is worth, and he is going to finance it, he will have to have enough cash to put down so that the loan amount is not more than the property is worth. Finally if none of that works you can just hold on to the property until the value comes up or you mortgage is payed down enough to make the balance of the mortgage less than the value of the house. Then offer the property to the former owner again.",
"title": ""
},
{
"docid": "348415",
"text": "\"The number one reason to borrow is quite simple; when you have no other choice. The primary reason to do this is when renovations or additions must be made in a timeframe that precludes you being able to save enough money to pay cash. Harmanjd's example of a kid on the way with no space to put him is a very good hypothetical. Disaster recovery is another; insurance doesn't cover everything and can sometimes be slow to pay out, and even if the payoff will rebuild the house exactly the way it was, these situations are deceptively good opportunities to improve on what you had. Since you already have to call in the contractors to demo and rebuild, the cost to do that is sunk, and the incremental cost of improvements or even additional square footage is relatively minor. Other acceptable reasons to borrow are: When cost of capital is very cheap. A typical amortized HELOC is pretty expensive when paid on-schedule, but if you can pay it off very early (i.e. when you sell the home next month) or you get a good deal on the interest rate (a subsidized disaster recovery loan, perhaps; you have to be careful with these as they're not intended to turn a burnt-down hovel into a McMansion) the cost of borrowing can be acceptable even if you had cash savings for the project. You have other uses for the cash that can offset cost of borrowing. This generally requires the first point to be true as well, as it's a general rule that borrowing $10,000 costs you more than you would gain by investing $10,000, but there are situations in which the reverse can be true (if you have $10k in oil or major tech stocks right now, it would probably be a bad move to liquidate them for home improvements if you can get a HELOC at less than 6%). You can realize a net gain in home value from the reno. These situations are rare in cases of an already livable home; \"\"flippers\"\", which make their living on renovating homes for a profit, generally choose homes with obvious but easy-to-fix problems that depress home value because they look worse than they are. If you bought your home without any such problems, you probably paid something close to market value at the time, and so you're probably behind the curve. However, if you (or your family in the case of an estate transfer) have owned the home for a long time, long enough for things to fall WAY out of date, then you can catch up a lot of market value with one renovation, where if the home had had two or three renovations along the way a reno now wouldn't gain you as much value.\"",
"title": ""
},
{
"docid": "317552",
"text": "\"So I'm in Australia and we have our very own housing price/credit bubble right now (which is finally deflating) and I'll try explain it as I understand. I welcome anyone to chime in and correct me. The problem we faced (still face to a large degree) is the idea of rising asset prices and how this fuels a feedback loop into increasing personal debt, all based on the false assumption that house prices always go up. Now before I continue, house prices *do* always go up in the long run, but so does the cost of everything and we call that inflation, adjusting for this effect usually reveals that house prices are cyclical in the long term and never really 'grow'. So that aside we in Australia recently saw a long period of increasing house prices (as did the USA and Europe, and more recently China), the thing about house price is it is your 'equity', I'll try and explain: (all figures are made up to provide a simple example) if you borrow $200,000 to buy a house that costs $250,000 you owe the bank 80% of the equity (what your home is 'worth', and notionally this is value that you own) in your home and the bank will be happy, remembering that they make money on your interest payments, not your principal repayments. If your house then increases in value to $300,000 but you still owe $200,000 then you now owe only 66% of your equity. The bank sees you as a lower risk and encourages you to borrow more to get back up to that sweet spot they had before of 80% - this is a nice tradeoff between risk and reward for the bank. You, the consumer, have just been mailed a new credit card with a 50k limit (hypothetical) and theres a new iMac being released next week, and you really did want to trade in your 5yr old car (see where this is going yet?). Not only is this type of spending given a mighty boost but consumers feel like this house thing has done them very well and suddenly they have the ability to borrow lots more money, why not get a second house and do it all over again? The added demand for investment housing drives prices, throw in some generous government incentives (here and in the USA) and demand is pushed hard, prices grow more and the whole thing feeds back into itself. People feel richer, spend more from their credit cards, buy another house, etc. But what happens if your house 'value' then drops to $240k? The bank now sees you as a high risk, so do the bank's investors, you have negative equity, the bank demands the difference paid back to it or it might take your home. Somehow, nobody believed this would happen. Hopefully you start to see the picture? In Australia we are now facing a slow melt in housing prices which has not yet hurt en masse but it has dried up the credit cards, retails spending has collapsed and everyone is worried about the future. Now to realise where the USA got to you have to also understand that banks were not merely asking for a maximum of 80% owed on the asset, many of them let this figure go to 100%, since hey prices always go up, right? They then in some cases went further and neglected to look into your income and confirm you could even *repay* your loan. Sounds dodgey? This is just the setup. Remember I mentioned the bank's investors? Well banks/smart people basically figured out a clever way of 'dealing with' the risk of a few outliers with bad financial situations by collecting large numbers of home loans into a single entity and selling it on. Loans were graded according to risk and I believe they were even cut up into smaller pieces (10% of your high risk loan assigned to 10 different 'debt objects' with different risk profiles). These 'collateralised debt obligations' were traded from one bank/investment firm to another with everyone happily accepting the risk profiles until eventually nobody knew what risk was where. Think about it like \"\"I'll throw 10 high risk loans, 50 medium risk loans and 40 low risk loans into a pot, stir it up and sell the soup as 'pretty safe' \"\". This all seemed like a very good idea until it gradually became clear just how much of these loans were in the 'extremely stupid high risk' category. This is probably extremely confusing by now, but thats the point, investors could no longer judge how risky an investment in a bank or financial institute was, the market did not correct for any of this until it was all too late. The moral of the story is when people tell you an investment is guaranteed to make you money, you stay away from that investment. And to specifically answer your question you can't solely blame government incentives as you might be able to see, but they play a part in a giant orchestra, there are many factors that drive this sort of stupidity, stupidity being the primary one.\"",
"title": ""
},
{
"docid": "574616",
"text": "\"There are a few factors at work here, supply and demand being the main one. The Office for National Statistics has some good information: http://visual.ons.gov.uk/uk-perspectives-housing-and-home-ownership-in-the-uk/ Supply has historically struggled to compete with demand in the UK and this situation has been exacerpated since the 1980s when Margaret Thatcher was Prime Minister. She set up a variety of schemes to encourage people to own their own home, such as tax relief (MIRAS) and since then home ownership in the UK has increased dramatically. The then conservative government also set up the \"\"right to buy\"\" scheme (in 1980) that allowed council tenants to purchase their council houses at a discounted rate. The effect of this was to increase the number of home owners whilst reducing the amount of housing available for councils to rent to new tenants. Anecdotal evidence (I can't find a documented source to back this up) suggests that councils did not build sufficient new homes to replace those purchased by their ex-tenants. The population of the UK has also increased, by around 10 million since 1980 (around 20%) and this has pushed up demand for housing. House building in the UK has not kept pace with these factors that has led to a shortage of supply that has pushed up prices. http://www.ons.gov.uk/ons/rel/pop-estimate/population-estimates-for-uk--england-and-wales--scotland-and-northern-ireland/2013/sty-population-changes.html There's another factor at play here as well. If you go back to the 1970s around 53% of women would go out to work but in 2013 this figure increased to 67% as it became more common for households to have double incomes. This extra supply of cash also pushed up house prices. http://www.ons.gov.uk/ons/dcp171776_328352.pdf Your question regards a debt based monetary system is not entirely clear, but there are limitations put onto how much money people can borrow that are potentially limiting how much house prices can rise by. Today most lenders are more conservative in how much they will lend but this wasn't the case in the mid 2000s when house prices rose very quickly. Lenders are more cautious today after the crash of the late 2000s, but things are begining to relax again and they are starting to lend more which could in turn lead to further house price rises in line with what was seen in the 2000s. Recessions have coincided with house prices falling back or at least being stable. In the 1980s house prices trebled from 1980 to 1988 but then fell back a little as the recession hit, before starting to rise again in 1997. This rise was sustained until 2008 during which time prices trebled again. Based on this you could assume prices will treble again as we come out of the recession, as long as this is sustained for 8 years or so. However, as the potential for more households to become double income is reduced (high female employment already) and wages are unlikely to raise that quickly, this may not be realistic, unless the mortgage lenders become extremely lax, to the point of reckless! To answer your other question, about the affordability of housing, this will be based on the level of wages in the UK and how strict or lax the lenders are, also taking into effect the availability of housing for purchase. If wages rise, house prices will rise, if lenders are willing to lend more money, house prices will rise and if demand continues to outrstip supply, prices will rise. None of the major UK political parties are likely to solve the problems of population growth and not enough houses being built so it is likely prices will rise but you could argue that they are not far off a peak based on current wages and lenders attitudes. If the UK economy continues to recover from the recession, it is possible they will fuel another housing boom by lending ever increasing salary multiples as happened in the 2000s, unless there is government intervention, ie regulation of the lenders.\"",
"title": ""
}
] |
6738
|
Austrailian tax resident earning salary in the UK - how much tax do I pay on foreign income?
|
[
{
"docid": "144844",
"text": "This page and this page on the ATO website provide some information on tax rates. They're rather lengthy and there's a few exceptions, but essentially, your entire foreign income, even if held overseas, is taxable. Australians are taxed worldwide.",
"title": ""
}
] |
[
{
"docid": "326559",
"text": "The link provided by DumbCoder (below) is only relevant to UK resident investors and does not apply if you live in Malaysia. I noticed that in a much older question you asked a similar question about taxes on US stocks, so I'll try and answer both situations here. The answer is almost the same for any country you decide to invest in. As a foreign investor, the country from which you purchase stock cannot charge you tax on either income or capital gains. Taxation is based on residency, so even when you purchase foreign stock its the tax laws of Malaysia (as your country of residence) that matter. At the time of writing, Malaysia does not levy any capital gains tax and there is no income tax charged on dividends so you won't have to declare or pay any tax on your stocks regardless of where you buy them from. The only exception to this is Dividend Withholding Tax, which is a special tax taken by the government of the country you bought the stock from before it is paid to your account. You do not need to declare this tax as it his already been taken by the time you receive your dividend. The rate of DWT that will be withheld is unique to each country. The UK does not have any withholding tax so you will always receive the full dividend on UK stocks. The withholding tax rate for the US is 30%. Other countries vary. For most countries that do charge a withholding tax, it is possible to have this reduced to 15% if there is a double taxation treaty in place between the two countries and all of the following are true: Note: Although the taxation rules of both countries are similar, I am a resident of Singapore not Malaysia so I can't speak from first hand experience, but current Malaysia tax rates are easy to find online. The rest of this information is common to any non-US/UK resident investor (as long as you're not a US person).",
"title": ""
},
{
"docid": "299752",
"text": "\"Yes. You do have to pay taxes in the UK as well but it depends on how much you have already been taxed in the US. http://taxaid.org.uk/situations/migrant-workernew-to-the-uk/income-from-abroad-arising-basis-vs-remittance-basis Say, you have to pay 20% tax in the UK for your earnings here. You ARE required to pay the same percentage on your foreign income as well. Now, if your \"\"home\"\" country already taxed you at 10% (for the sake of example), then you only need to pay the \"\"remaining\"\" 10% in the UK. However, the tax law in the UK does allow you to choose between \"\"arising\"\" basis and \"\"remittance\"\" basis on your income from the country you are domiciled in. What I have explained above is based on when income \"\"arises.\"\" But the laws are complicated, and you are almost always better off by paying it on \"\"arising\"\" basis.\"",
"title": ""
},
{
"docid": "196321",
"text": "\"What theyre fishing for is whether the money was earned in the U.S. It's essentially an interest shelter, and/or avoiding double taxation. They're saying if you keep income you make outside the US in a bank inside the US, the US thanks you for storing your foreign money here and doesn't tax the interest (but the nation where you earned that income might). There is no question that the AirBNB income is \"\"connected with a US trade or business\"\". So your next question is whether the fraction of interest earned from that income can be broken out, or whether IRS requires you to declare all the interest from that account. Honestly given the amount of tax at stake, it may not be worth your time researching. Now since you seem to be a resident nonresident alien, it seems apparent that whatever economic value you are creating to earn your salary, is being performed in the United States. If this is for an American company and wages paid in USD, no question, that's a US trade or business. But what if it's for a Swedish company running on Swedish servers, serving Swedes and paid in Kroner to a Swedish bank which you then transfer to your US bank? Does it matter if your boots are on sovereign US soil? This is a complex question, and some countries (UK) say \"\"if your boots are in our nation, it is trade/income in our nation\"\"... Others (CA) do not. This is probably a separate question to search or ask. To be clear, the fact that your days as a teacher or trainee do not count toward residency, is a separate question from whether your salary as same counts as US income.\"",
"title": ""
},
{
"docid": "597865",
"text": "By earning money, I assume you are being paid a salary [and not allowance] in UK. For the Financial Year 2013-2014: You are still a tax resident in India. India taxes Global income. Hence your salary from 4th Feb to 31st March, needs to be declared as Income. The tax will be at your total tax brackets. India does have a Double Tax Avoidance Treaty [DTAA] with UK, so you can deduct any taxes you paid on this income and pay balance in India. Please note that it is not relevant whether you transfer money to India or keep in UK, it does not change the taxability. For the financial Year 2014-2015: Depending on the exact date, you may or may not be a NRI [away for more than 182 days] for tax purposes. If you are an NRI there no tax, else as above para.",
"title": ""
},
{
"docid": "235266",
"text": "In the general case if you have income coming in from a foreign source you need to declare it on your Canadian tax form, and nominally pay tax on it. However Canada has a tax agreement with the UK to ensure that you are not taxed twice. You also declare how much tax you have paid to the UK, and that is deducted from your Canadian tax bill. You may need to consult a tax professional, or maybe just read the Revenue Canada website to get the details. If you are holding this money for a friend, then you may find that this does not count as income to you. If you are getting it transferred to you in Canada, and then immediately passed on to your friend, it probably doesn't count as income (though again a tax professional will probably be helpful). This would mean you don't have to pay Canadian tax. But it's also a bummer because you've paid UK tax, which you might also have avoided, and you can't get that back without a lot of form filling. If this is going to be an ongoing situation, and the amount is significant, then you might look at getting your friend's money (and any you have in a UK account yourself) transferred to an offshore account, where UK tax is not automatically deducted. Most UK banks will do this for non-UK residents.",
"title": ""
},
{
"docid": "382623",
"text": "It makes no difference (to the UK) what country a bank account is in. What matters is whether you are resident in the UK or not while employed locally in a foreign country. You're taxed on where you are tax resident (which could be either country, both, or neither), not where the money is earned or banked. You can assume, with modern exchange of information agreements, that all money you put in bank accounts anywhere in the world will eventually be known to the UK authorities. The rules for when you are a UK tax resident changed recently, there is now a statutory test for residence (pdf). The rules are complex, but in general if you are outside the UK for less than one full tax year you're still resident, and in many cases where you're gone longer than that you may still be, depending on the length of your trips back to the UK and the ties you have there. So a 6-month winter job in Thailand teaching English as a foreign language will be subject to UK tax if you come back after, even if you leave all the money there or in a third country. If you pay local tax as well there are agreements between countries to avoid double taxation, but these do vary. What you do about National Insurance payments while gone for a short time is another complex area.",
"title": ""
},
{
"docid": "583635",
"text": "Good question - I know you can keep the ISA in the UK and it won't lose its tax free status but you're not able to contribute it while you're not a UK resident. Not that its tax free status buys you that much if you're a non-resident as you could apply to receive tax gross on pretty much any savings account anyway. Given that the idea of tax-free saving outside a retirement account doesn't really exist here in the US I would assume that you will have to declare the interest as income and, if you don't pay any other taxes in the UK that would cover the amount you'd have to pay on your ISA under the foreign tax credit, you'd end up giving the IRS their pound of flesh. As I mentioned in an answer to a previous question, you really need to talk to an US accountant/CPA, preferably one that is familiar with UK taxation law as well.",
"title": ""
},
{
"docid": "385221",
"text": "As the name says, its for income earned in a Foreign country. If you have been paying US income tax on this while living in the US, nothing is going to change here. You should be informing yourself on how to avoid double taxation in your new country of residence. Passive income earned abroad (dividends, interest) also do not fall under this exemption. The purpose of the Foreign Earned Income Exclusion is to make it easy for expats who work abroad to avoid double income taxation without going through the complicated process of applying for tax credits. The US is the only industrial country that taxes its residents regardless of where they reside. That is also why it only goes to about $100,000 a year. If you are a high earner, they want to make it more difficult. Also as a side note, since you are going to be abroad for a year. I will point out that if you have more than $10,000 in foreign accounts at any point in the year you need to declare this in an FBAR form. This is not advertised as well as it should be and carries ridiculous penalties for non-compliance. I can't count the number of times I have heard a US expat say that they were unaware of this.",
"title": ""
},
{
"docid": "256395",
"text": "With a question like this you should talk to a tax professional who knows about international tax and knows about both the UK and the country you will be working in. They will give you up to date advice on what can be an extremely complex question. However to get you started I'll tell you what I was told when I did this nearly twenty years ago. It's all about whether you are resident in the UK for tax purposes or not. If you are, you will pay UK tax. If not, you wont (assuming you are being paid outside the UK - check with your professional exactly what is involved). In those days you could be counted as 'non resident' if you spent a complete period of twelve months outside the UK. You can make occasional visits to the UK without invalidating that. Again, check exactly how much you are allowed to return while still being not resident. Usually you will have to pay tax in the country where you are resident, but check the rules there. With some skilful timing you may be able to be considered non-resident in bouth countries, at least for some of the time. Again, your tax professional will know. The bank account question - again get a professional. I don't think it's a problem, but you may have to establish that you are being paid in the foreign country. In general you are going to need an account in the country where you work, so if its a problem get paid there and transfer any money you need in the UK.",
"title": ""
},
{
"docid": "479093",
"text": "\"If a country had a genuine completely flat income tax system, then it wouldn't matter who paid the tax since it doesn't depend on the employee's other income. Since not many countries run this, it doesn't really make sense for the employee to \"\"take the burden\"\" of the tax, as opposed to merely doing the administration and paying the (probable) amount of tax at payroll, leaving the employee to use their personal tax calculation to correct the payment if necessary. Your prospective employer is probably saying that your tax calculation in Singapore is so simple they can do it for you. They may or may not need to know a lot of information about you in order to do this calculation, depending what the Singapore tax authorities say. If you're not a Singapore national, they may or may not be relying on bilateral tax agreements with your country to assert that you won't have to pay any further tax on the income in your own country. It's possible they're merely asserting that you won't owe anything else in Singapore, and in fact you will have taxes to report (even if it's just reporting to your home tax authority that you've already paid the tax). Still, for a foreign worker a guarantee you won't have to deal with the local tax authority is a good thing to have even if that's all it is. Since there doesn't appear to be any specific allowance for \"\"tax free money\"\" in the Singapore tax system, it looks like what you have here is \"\"just\"\" the employer agreeing to do something that will normally result in the correct tax being paid in your behalf. This isn't uncommon, but it's also not exactly what you asked for. And in particular if you have two jobs in Singapore then they can't both be doing this, since tax is not flat. The example calculation includes varying tax rates for the first X amount of income that (I assume without checking) are per person, not per employment. Joe's answer has the link. In practice in the UK (for example), there are plenty of UK nationals working in the UK who don't need to do a full tax return and whose tax is collected entirely at source (between PAYE and deductions on bank interest and suchlike). In this sense the employer is required by law to take the responsibility for doing the admin and making the tax payments to HMRC. Note that a UK employer doesn't need to know your circumstances in detail to make the correct payroll deductions: all they need is a so-called \"\"tax code\"\", which is calculated by HMRC and communicated to the employer, and which basically encodes how much they can pay you at zero rate before the various tax rate tiers kick in. That's all the employer needs to know here for the typical employee: they don't need to know precisely what credits and liabilities resulted in the figure. However, these employers still don't offer empoyees a net salary (that is, they don't take on the tax burden), because different employees will have different tax codes, which the employer would in effect be cancelling out by offering to pay two people the same net salary regardless of their individual circumstances. The indications seem to be that the same applies in Singapore: this offer is really a net salary subject to certain assumptions (the main one being that you have no other tax liabilities in Singapore). If you're a Singapore millionaire taking that job for fun, you might find that the employer doesn't/can't take on your non-standard tax liability on this marginal income.\"",
"title": ""
},
{
"docid": "552138",
"text": "\"The country from which you purchase stock cannot charge you tax on either income or capital gains. Taxation is based on residency, so even when you purchase foreign stock its the tax laws of Malaysia (as your country of residence) that matter. At the time of writing, Malaysia does not levy any capital gains tax and there is no income tax charged on dividends so you won't have to declare or pay any tax on your stocks regardless of where you buy them from. The only exception to this is Dividend Withholding Tax, which is a special tax taken by the government of the country you bought the stock from before it is paid to your account. You do not need to declare this tax as it his already been taken by the time you receive your dividend. The US withholding tax rate on dividends is 30%, although this can be reduced to 15% if there as a tax treaty in place between the US and your country of residence. Malaysia does have a double taxation agreement with the US (see here: http://www.mida.gov.my/env3/index.php?page=double-taxation-agreement) but it is flagged as a \"\"limited\"\" agreement. You'd need to find the full text of the agreement to see whether a reduced rate of dividend withholding tax would be available in the Malaysia/US treaty. See my other answer for more details on withholding taxes and how to partially reclaim under a double tax treaty: What is the dividend tax rate for UK stock Note: Although the taxation rules of both countries are similar, I am a resident of Singapore not Malaysia so I can't speak from first hand experience, but current Malaysia tax rates are easy to find online. The rest of this information is common to any non-US/UK resident investor (as long as you're not a US person).\"",
"title": ""
},
{
"docid": "531423",
"text": "The broker that is issuing the moneys after vesting is more than likely deducting a notional amount of tax and NI based on UK income tax laws. If you are not a UK resident, then you should pay income tax on those stock options based on your own tax residency. Best thing to do is speak directly with the broker to explain the situation, ask them to not deduct anything from your stock options - but keep in mind that you will need to declare these earnings yourself and pay the correct rate of tax. From my own personal experience, the UK employer more than likely receives the net value (after the notional tax and NI have been deducted) and in usual circumstances create a tax liability on your payslip (if you were working and had earnings). If of course this deduction is being made by the employer, then you can simply ask them to correct this (most UK payroll software will automatically deduct tax and NI for payments after leaving unless manually intervened, so they probably aren't aware if it is them doing so).",
"title": ""
},
{
"docid": "417208",
"text": "\"I'll add a bit to Paul's excellent write up. Foreign Earned Income Exclusion (form 2555): notice the earned there. It doesn't exclude capital gains, interest, dividends, and basically everything that is not salary. You pay US taxes on it from the first cent. Foreign tax credit - foreign tax credit (form 1116) doesn't reduce your US tax dollar for dollar (even though it may appear that it does from the generic explanations). By using this form you may end up accumulating unused credit while still paying double taxes at the same time. Happened to me. Thank Congress for the logical and reasonable US tax laws. New FATCA form 8938: as opposed to FBAR (that goes to the FinCEN in the Treasury), this one goes to the IRS. it contains very similar info, but the threshold requirements are different. You may have to file FBAR, but not these, or you may have to file both. Being an American citizen, some European banks will refuse to provide services to you. Again, thank Congress for FATCA. It requires foreign banks to enforce US tax regulations on US citizens, and banks that won't will get penalized in the US. Many banks refuse to provide services to Americans because of that because what IRS requires is illegal in most countries. Some countries (like UK and some other EU countries) have signed treaties with the US to resolve this, but many haven't. Currency conversion - as I commented to Paul, you convert the amounts when you receive them, which may have your fixed EUR salary be converted to different dollar amounts every time. You need to make sure you do it right. Pensions, savings, investments - if you're doing these in non-US instruments prepare to be penalized. US taxes foreign investments much more aggressively than domestic. If you're investing in indexes/mutual funds, or you're a principle in a corporation, or you create a pension account - you'll get hit by additional reporting requirements and tax. Tax treaties - the US has tax treaties with many EU countries, and equalization treaties with some. The tax treaties affect the standard tax treatment by the US and some of the \"\"generic\"\" info you got here may not apply because of a tax treaty, and some other rules may apply. Equalization treaties work similarly with regards to the Social Security. Bottom line, and I know Paul disagrees with me on this - talk with a US-licensed adviser in the country you're going to. It is very important for your tax adviser to know the relevant treaty (and not read it the first time when you call him), and to understand each and every financial instrument in your country. Missing piece of paper in your tax return can cost you thousands of dollars in penalties (not exaggerating, not filing form 3520 triggers a $10000 penalty, even if there's no tax) and additional taxes.\"",
"title": ""
},
{
"docid": "193367",
"text": "\"Be careful here: If ACME were in California, I would pay taxes on USD 17,000 because I had revenue of 20,000 and expenses of 3,000. To CALIFORNIA. And California taxes S-Corps. And, in addition, you'd pay $800 for the right of doing business in the State. All that in addition to the regular Federal and State taxes to the State where you're resident. Suppose that ACME is in Britain (or anywhere else for that matter). My revenue and expenses are the same, but now my money has been earned and my expenses incurred in a foreign country. Same thing exactly. Except that you'll have to pay taxes to the UK. There may be some provision in the tax treaty to help you though, so you may end up paying less taxes when working in the UK than in California. Check with a licensed tax adviser (EA/CPA licensed in your State) who won't run away from you after you say the words \"\"Tax Treaty\"\". Does it even make sense to use my S-Corporation to do business in a foreign country? That should be a business decision, don't let the tax considerations drive your business.\"",
"title": ""
},
{
"docid": "159952",
"text": "\"As others have stated, CEO's often make more than 200K, and when they do, they're compensated with stock options and other lucrative bonuses and deals that allow them to build wealth above and beyond the face value of their salary. However, remember that having wealth makes it easier to build further wealth. As Victor pointed out, having wealth allows you to increase your wealth in different kinds of investments. Also, it gives you access to more human capital, e.g. wealth management services at firms like Northern Trust, a greater ability to diversify into investments like hedge funds, more abilities to invest abroad through foreign trusts, etc. Also, you have to realize that wealthier people often pay a lower percentage in taxes than people who earn a salary. In the US, long-term capital gains are taxed at a much lower rate than income, so wealthy individuals who earn much of their money from long-term investments won't pay nearly as high a rate. In my case, my current salary places me at the top of the 25% tax bracket (in the US), but if I earned all of my income through long-term capital gains instead of salary, I would only pay around 15-20% in taxes. Plus, I could afford numerous tax accounting firms to help me find ways to pay fewer taxes. It's not altruism that causes CEOs like Steve Jobs and Mark Zuckerberg to take a $1 salary. This isn't directly related to CEOs, and I'm not leveling accusations of corruption against high net worth individuals, but I remember spending a few months in a small town in a country known for its corruption. The mayor had recently purchased a home worth the equivalent of several million dollars, on his annual civil servant salary of approximately $20K. One of the students asked him how he managed to afford such a sizable property, and he replied \"\"I live very frugally.\"\" This is probably a relatively rare case (I'm sure it depends on the country), but nevertheless, it illustrates another way that some people build wealth.\"",
"title": ""
},
{
"docid": "528908",
"text": "Interest earned over my saving only As you are Tax resident in UK, UK taxes Global income. So the interest earned in India is taxable. Further this is taxable when the interest was paid to you in India and it is not relevant whether you kept the funds in India or repatriated to UK. It is not clear in your question as to when the interest was credited to your Indian account. If its been for few years, you are in breach of the UK tax regulation. Consult a tax advisor how this can be corrected. If it is for this year, pay taxes as per normal tax brackets.",
"title": ""
},
{
"docid": "247760",
"text": "In a simple case as the sole UK resident director/shareholder of a company, with that company as your only income, you are usually best paying yourself a salary of the maximum tax free amount allowed under your tax code (~£11k for most people at present). On this you will have to pay some employer and employee National Insurance (NI) contributions (totalling around £1000). Your salary/employer NI counts as an expense, so that is taken off the company profits. You then pay corporation tax on the remainder (20%). The first £5k you take as dividends is tax free, the remainder at a lower tax rate than the equivalent combined income tax/NI (starting at 7.5% instead of 20% tax plus employee plus employer NI), giving a significant saving compared to salaried income even after corporation tax. To declare and pay the tax, you would need to complete a self-assessment tax return. Your company will also need to file a return. The Contractor UK website, although aimed at IT contractors, has some very useful information on operating Ltd companies. That said, finances are rarely that simple so I would concur with the recommendation you engage an accountant, which is a tax-deductible expense.",
"title": ""
},
{
"docid": "325113",
"text": "In the UK you have an allowance of £40,000 per annum for tax relief into a pension. This amount includes both your and your employer's contributions. If you earn more than £150,000 per annum this allowance starts to reduce and if you earn less than the allowance, your allowance is limited to what you earn. You can also carry over unused allowance from up to 3 years previously. If you stick within this allowance you won't pay tax on your pension contributions, if you go over the excess will be subject to tax. Salary exchange normally lets you avoid the National Insurance value of your contribution being taxed. If you paid your own money into your pension (without going through salary exchange), your contributions would have the 20% basic rate of tax credited to them and if you're a higher rate taxpayer you could reclaim the difference between the basic rate of tax and the higher rate of tax you pay but the National Insurance you've paid on your own money would not be reclaimable. You can't get the money back you've paid into your pension till you are are 58 (given that you are 27 now), the minimum age has risen from its historic 55 for your age group. That's the pension trade off, you forgo tax now in the expectation that, once retired, you will be paying tax at a lower rate (because your income will be lower and you are much less likely to be subject to higher rate taxation) in return for locking in your money till you're older. Your pension income will be subject to tax when you eventually take it. There are other options such as ISAs which have lower annual limits (£20,000 currently) and on which your contributions do not attract tax relief, but which are not taxed as income when you eventually spend them. ISAs and pensions are not mutually exclusive so if you have the money, you can do both. It's up to you to determine what mix of savings will be appropriate to generate income for your eventual retirement. If you are living in some other country when you retire your pension will be paid net of UK tax. You might then be able to claim (or pay) any difference between that and your local tax rate depending on what agreement exists between the UK government and the other country's government.",
"title": ""
},
{
"docid": "478408",
"text": "\"My employer decided to pay my salary in India after I submit a form W-8BEN. This means that the wages / salary is deemed accrued for work from India. Hence your employer need not withhold and pay taxes on this wage in US. Is this payment taxable in the States since I am staying outside of States? Should I declare this income to IRS in case if I go back to the States later this year? No tax is due as the work is done outside on US. If you go back this would be similar to as you had gone first. Depending on your \"\"tax residency status\"\" you would have to declare all assets. If my US employer wires my US salary to my NRE account is that taxable in India? This is still taxable in India. It is advised that you have the funds transferred into a regular savings account. Please note you have to pay taxes in advance as per prescribed due dates in Sept, Dec, March. how does the Indian tax man identify if it is a taxable income and not just the regular remittance. This question is off topic here. Whether income taxes finds out about this is irrelevant. By law one is required to pay taxes on income earned in India.\"",
"title": ""
},
{
"docid": "459953",
"text": "As far as I read in many articles, all earnings (capital gains and dividends) from Canadian stocks will be always tax-free. Right? There's no withholding tax, ie. a $100 dividend means you get $100. There's no withholding for capital gains in shares for anybody. You will still have to pay taxes on the amounts, but that's only due at tax time and it could be very minor (or even a refund) for eligible Canadian dividends. That's because the company has already paid tax on those dividends. In contrast, holding U.S. or any foreign stock that yields dividends in a TFSA will pay 15% withholding tax and it is not recoverable. Correct, but the 15% is a special rate for regular shares and you need to fill out a W8-BEN. Your broker will probably make sure you have every few years. But if you hold the same stock in a non-registered account, this 15% withholding tax can be used as a foreign tax credit? Is this true or not or what are the considerations? That's true but reduces your Canadian tax payable, it's not refundable, so you have to have some tax to subtract it from. Another consideration is foreign dividends are included 100% in income no mater what the character is. That means you pay tax at your highest rate always if not held in a tax sheltered account. Canadian dividends that are in a non-registered account will pay taxes, I presume and I don't know how much, but the amount can be used also as a tax credit or are unrecoverable? What happens in order to take into account taxes paid by the company is, I read also that if you don't want to pay withholding taxes from foreign > dividends you can hold your stock in a RRSP or RRIF? You don't have any withholding taxes from US entities to what they consider Canadian retirement accounts. So TFSAs and RESPs aren't covered. Note that it has to be a US fund like SPY or VTI that trades in the US, and the account has to be RRSP/RRIF. You can't buy a Canadian listed ETF that holds US stocks and get the same treatment. This is also only for the US, not foreign like Europe or Asia. Also something like VT (total world) in the US will have withholding taxes from foreign (Europe & Asia mostly) before the money gets to the US. You can't get that back. Just an honourable mention for the UK, there's no withholding taxes for anybody, and I hear it's on sale. But at some point, if I withdraw the money, who do I need to pay taxes, > U.S. or Canada? Canada.",
"title": ""
},
{
"docid": "442853",
"text": "\"As I understand it the usual rule is that the country you are \"\"resident\"\" in taxes you on your worldwide income but gives you credit for foreign tax paid. The country you are not normally resident in taxes you only on income from that one country. Note that residence for tax purposes can have different rules from residence for immigration purposes. At least in the UK being resident in the country for more than half the tax year normally makes you tax resident and there are some other cases too. I expect other countries are similar but the details of the rules and the start/end of the tax years may vary. I don't know the exact rules for finland and belgium but I expect your Belgian taxes will be based on your Belgian income only and your Finnish taxes will be based on your worldwide income but with a credit for your Belgian taxes. Engaging accountants from both countries to confirm the exact rules and what exactly you should put on the forms is almost certainly a good idea.\"",
"title": ""
},
{
"docid": "548299",
"text": "\"Can I use the foreign earned income exclusion in my situation? Only partially, since the days you spent in the US should be excluded. You'll have to prorate your exclusion limit, and only apply it to the income earned while not in the US. If not, how should I go about this to avoid being doubly taxed for 2014? The amounts you cannot exclude are taxable in the US, and you can use a portion of your Norwegian tax to offset the US tax liability. Use form 1116 for that. Form 1116 with form 2555 on the same return will require some arithmetic exercises, but there are worksheets for that in the instructions. In addition, US-Norwegian treaty may come into play, so check that out. It may help you reduce the tax liability in the US or claim credit on the US taxes in Norway. It seems that Norway has a bilateral tax treaty with the US, that, if I'm reading it correctly, seems to indicate that \"\"visiting researchers to universities\"\" (which really seems like I would qualify as) should not be taxed by either country for the duration of their stay. The relevant portion of the treaty is Article 16. Article 16(2)(b) allows you $5000 exemption for up to a year stay in the US for your salary from the Norwegian school. You will still be taxed in Norway. To claim the treaty benefit you need to attach form 8833 to your tax return, and deduct the appropriate amount on line 21 of your form 1040. However, since you're a US citizen, that article doesn't apply to you (See the \"\"savings clause\"\" in the Article 22). I didn't even give a thought to state taxes; those should only apply to income sourced from the state I lived in, right (AKA $0)? I don't know what State you were in, so hard to say, but yes - the State you were in is the one to tax you. Note that the tax treaty between Norway and the US is between Norway and the Federal government, and doesn't apply to States. So the income you earned while in the US will be taxable by the State you were at, and you'll need to file a \"\"non-resident\"\" return there (if that State has income taxes - not all do).\"",
"title": ""
},
{
"docid": "499189",
"text": "In theory the integration of taxes make the tax implications of paying salary or dividends equal. This is what happens when you calculate the taxes using a generic tax calculator, however, the theory breaks down in certain cases. If you are earning less than $100k there is very little difference and paying out a salary is usually the better option. In a large stable company the most efficient option is almost always a mix of both. If you are earning more than $100k a year it depends on a number of factors: 1) Are your companies annual earnings over $500,000? In Canada, private companies that earn more than $500,000 annually are taxed at a higher rate than those earning less than $500,000. If the earnings are above $500,000 generally you should reduce the earning to under $500,000 by paying a salary. However, this depends on the province, the other income of the owners are and how much more than $500,000 your company earns. 2) Are you eligible for deductions or benefits only available on earned income? Earned income is income that you have worked for, which does not include dividends. RRSP contribution room, child care expense deductions, CPP, and many other benefits under the CRA rules are only available to people who have an earned income. It is worth taking advantage of these deductions when they are available. 3) Is your company eligible for any tax deductions? The same as with your personal tax deductions and your personal benefits of earning income, having a corporate income is also a benefit. There are a number of tax credits and tax deductions that corporations can take advantage of and when available these should be taken advantage of before paying everything out in salary. Once all these questions are answered the calculation is based on your marginal tax rate and the tax rate of the Corporation. One other reason to have at least a portion of you salary as a dividend is that if you incur capital loss in your corporation you can pass them to your personal taxes. If you were payed 100% in salary this does not work. Other strategies to be more tax efficient: Income splitting (Pay a salary/dividend to yourself, your wife, your children your parents, or anyone you support). Rolling-over property with taxable gains into your private corporation. Buying insurance policies that gives a return of premium or increase your Capital Dividend Account (CDA).",
"title": ""
},
{
"docid": "284805",
"text": "\"Others have given a lot of advice about how to invest, but as a former expat I wanted to throw this in: US citizens living and investing overseas can VERY easily run afoul of the IRS. Laws and regulations designed to prevent offshore tax havens can also make it very difficult for expats to do effective investing and estate planning. Among other things, watch out for: US citizens owe US income tax on world income regardless of where they live or earn money FBAR reporting requirements affect foreign accounts valued over $10k The IRS penalizes (often heavily) certain types of financial accounts. Tax-sheltered accounts (for education, retirement, etc.) are in the crosshairs, and anything the IRS deems a \"\"foreign-controlled trust\"\" is especially bad. Heavy taxes on investment not purchased from a US stock exchange Some US states will demand income taxes from former residents (including expats) who cannot prove residency in a different US state. I believe California is neutral in that regard, at least. I am neither a lawyer nor an accountant nor a financial advisor, so please take the above only as a starting point so you know what sorts of questions to ask the relevant experts.\"",
"title": ""
},
{
"docid": "440506",
"text": "I have researched this question extensively in previous years as we have notoriously high taxes in California, while neighboring a state that has zero corporate income tax and personal income tax. Many have attempted pull a fast one on the California taxation authorities, the Franchise Tax Board, by incorporating in Nevada or attempting to declare full-year residence in the Silver State. This is basically just asking for an audit, however. California religiously examines taxpayers with any evidence of having presence in California. If they deem you to be a resident in California, and they likely will based on the fact that you live in California (physical presence), you will be subject to taxation on your worldwide income. You could incorporate in Nevada or Bangladesh, and California will still levy its taxation on any business income (Single Member LLCs are disregarded as separate corporate entities, but still taxed at ordinary income rates on the personal income tax basis). To make things worse, if California examines your Single Member LLC and finds that it is doing business in California, based on the fact that its sole owner is based in California all year long, you could feasibly end up with additional penalties for having neglected to file your LLC in California (California LLCs are considered domestic, and only file in California unless they wish to do business in other states; Nevada LLCs are considered foreign to California, requiring the owner to file a domestic LLC organization in Nevada and then a foreign LLC organization in California, which still gets hit with the minimum $800 franchise fee because it is a foreign LLC doing business in California). Evading any filing responsibility in California is not advisable. FTB consistently researches LLCs, S-Corporations and the like to determine whether they've been organized out-of-state but still principally operated in California, thus having a tax nexus with California and the subsequent requirement to be filed in California and taxed by California. No one likes paying taxes, and no one wants to get hit with franchise fees, especially when one is starting a new venture and that minimum $800 assessment seems excessive (in other words, you could have a company that earns nothing, zero, zip, nada, and still has to pay the $800 minimum fee), but the consequences of shirking tax laws and filing requirements will make the franchise fee seem trivial in comparison. If you're committed to living in California and desire to organize an LLC or S-Corp, you must file with the state of California, either as a domestic corporation/LLC or foreign corporation/LLC doing business in California. The only alternatives are being a sole proprietor (unincorporated), or leaving the state of California altogether. Not what you wanted to hear I'm sure, but that's the law.",
"title": ""
},
{
"docid": "438038",
"text": "\"You don't want to do that. DON'T LIE TO THE IRS!!! We live overseas as well and have researched this extensively. You cannot make $50k overseas and then say you only made $45k to put $5k into retirement. I have heard from some accountants and tax attorneys who interpret the law as saying that the IRS considers Foreign Earned Income as NOT being compensation when computing IRA contribution limits, regardless of whether or not you exclude it. Publication 590-A What is Compensation (scroll down a little to the \"\"What Is Not Compensation\"\" section). Those professionals say that any amounts you CAN exclude, not just ones you actually do exclude. Then there are others that say the 'can' is not implied. So be careful trying to use any foreign-earned income to qualify for retirement contributions. I haven't ran across anyone yet who has gotten caught doing it and paid the price, but that doesn't mean they aren't out there. AN ALTERNATIVE IN CERTAIN CASES: There are two things you can do that we have found to have some sort of taxable income that is preferably not foreign so that you can contribute to a retirement account. We do this by using capital gains from investments as income. Since our AGI is always zero, we pay no short or long term capital gains taxes (as long as we keep short term capital gains lower than $45k) Another way to contribute to a Roth IRA when you have no income is to do an IRA Rollover. Of course, you need money in a tax-deferred account to do this, but this is how it works: I always recommend those who have tax-deferred IRA's and no AGI due to the FEIE to roll over as much as they can every year to a Roth IRA. That really is tax free money. The only tax you'll pay on that money is sales tax when you SPEND IT!! =)\"",
"title": ""
},
{
"docid": "290452",
"text": "In principle, when you are the sole owner of a limited company, and also the sole employee, then it is much easier to assume that someone else is the employee. Let's say your twin brother John Adler. John Adler receives a salary from David Adler's company. Of course John has to pay income tax on his salary. Absolutely in the UK, and in Estonia as well if they have any sensible tax laws at all (which I assume but don't know for sure). Then there is the company. It's profit equals revenue, minus cost. You said £4000 revenue, and John Adler's salary, plus anything the company has to pay on top of the salary, is cost, which is subtracted from the revenue to calculate profit. In the UK, the company pays 20% corporation tax on those profits, and the rest stays in its bank account (or may be in goods that the company purchased). Where does David Adler come in? He owns the company, but doesn't work for it and gets no salary. He owns the company, but he does not own the company's money. He can't just help himself to the money. He can get a loan from the company, and is personally responsible for repaying that loan. If it's not repaid, HMRC will be very angry which will hurt. Or he can pay himself a dividend, and pays dividend tax on it. Or of course he can leave the money in the company. That's exactly how it works in the UK, and I would assume Estonia to be similar. And of course if it's not the twin brother who is the employee, but the OP himself, then the situation is exactly the same.",
"title": ""
},
{
"docid": "352307",
"text": "> They deprive the US of valuable income which has been earned through infrastructure, defense, education, etc It doesn't. The main reason it exists is that the US double dips on taxes. The whole point of these inversions is to deal with how the US treats foreign income. Company still pays US taxes on business done in the US: ie., using US infrastructure. That doesn't change. If the company is head quartered in the US then the US expects the company to also pay taxes on foreign income -- ie., income that can't be referenced back to US infrastructure/education/etc. The company has already paid taxes in the foreign country, but the US feels the need to double dip. This double dipping is very much a US thing. It just makes moral, fiscal, and logical sense for them to do the inversion. The US government should have no rights to overseas money. The reason the move to Canada is simply that Canada, like pretty much all capitalist countries, doesn't tax foreign revenue. You Americans really really need to look at your tax system. Speaking as a Canadian business owner who deals with US clients, it's just insane. It's easier to deal with the Chinese tax system in my experience.",
"title": ""
},
{
"docid": "386869",
"text": "It doesn't make much difference in the end. Imagine you have $100 of revenue in your company. You can either pay it to yourself as salary, meaning that you don't pay corporate tax on it, or you can keep it in the company, pay corporate tax on it, then pay yourself a dividend of what is left. While that dividend will be treated better than salary, remember that the company already paid tax on it. You paying less on what's left doesn't equate to paying less overall. Go ahead and run the numbers using your actual corporate tax rate and your personal income tax rate. Try doing your whole salary as dividends - not dollar for dollar, but as how much the company would have as profit to give you a dividend if it didn't spend (and deduct) salary money on you. You are unlikely to see any difference at all. The net final money in your pocket, and the amount that went to the government, will probably be the same. If paying dividends keeps your earned income low, you may find that you can't use RRSP or childcare deductions. You are also not getting CPP credit. That's an argument for salary, or at least a certain minimum amount of salary. You have to deduct taxes at source on salary and send it along to the government, which is an argument for dividends if you feel you could invest that money and use it well before the taxes get around to being due. Possibly you may discover an edge case where you move a few thousand from one marginal tax rate to another and clear a few hundred extra as a result. I don't discourage you from doing the math, I just point out that the various percentages (tax rates, grossups, deductions etc) have all been carefully chosen so that it pretty much works out the same, or gives a small preference to salary. We give excess money to ourselves as bonus rather than dividend having run the numbers a few times. There's no secret trick here.",
"title": ""
},
{
"docid": "160313",
"text": "First, the SSN isn't an issue. She will need to apply for an ITIN together with tax filing, in order to file taxes as Married Filing Jointly anyway. I think you (or both of you in the joint case) probably qualify for the Foreign Earned Income Exclusion, if you've been outside the US for almost the whole year, in which cases both of you should have all of your income excluded anyway, so I'm not sure why you're getting that one is better. As for Self-Employment Tax, I suspect that she doesn't have to pay it in either case, because there is a sentence in your linked page for Nonresident Spouse Treated as a Resident that says However, you may still be treated as a nonresident alien for the purpose of withholding Social Security and Medicare tax. and since Self-Employment Tax is just Social Security and Medicare tax in another form, she shouldn't have to pay it if treated as resident, if she didn't have to pay it as nonresident. From the law, I believe Nonresident Spouse Treated as a Resident is described in IRC 6013(g), which says the person is treated as a resident for the purposes of chapters 1 and 24, but self-employment tax is from chapter 2, so I don't think self-employment tax is affected by this election.",
"title": ""
}
] |
992
|
Pyridostatin deregulates G2/M progression.
|
[
{
"docid": "16472469",
"text": "G-quadruplex (G4)-forming genomic sequences, including telomeres, represent natural replication fork barriers. Stalled replication forks can be stabilized and restarted by homologous recombination (HR), which also repairs DNA double-strand breaks (DSBs) arising at collapsed forks. We have previously shown that HR facilitates telomere replication. Here, we demonstrate that the replication efficiency of guanine-rich (G-rich) telomeric repeats is decreased significantly in cells lacking HR. Treatment with the G4-stabilizing compound pyridostatin (PDS) increases telomere fragility in BRCA2-deficient cells, suggesting that G4 formation drives telomere instability. Remarkably, PDS reduces proliferation of HR-defective cells by inducing DSB accumulation, checkpoint activation, and deregulated G2/M progression and by enhancing the replication defect intrinsic to HR deficiency. PDS toxicity extends to HR-defective cells that have acquired olaparib resistance through loss of 53BP1 or REV7. Altogether, these results highlight the therapeutic potential of G4-stabilizing drugs to selectively eliminate HR-compromised cells and tumors, including those resistant to PARP inhibition.",
"title": "Targeting BRCA1 and BRCA2 Deficiencies with G-Quadruplex-Interacting Compounds"
}
] |
[
{
"docid": "38131471",
"text": "DNA damage is a relatively common event in the life of a cell and may lead to mutation, cancer, and cellular or organismic death. Damage to DNA induces several cellular responses that enable the cell either to eliminate or cope with the damage or to activate a programmed cell death process, presumably to eliminate cells with potentially catastrophic mutations. These DNA damage response reactions include: (a) removal of DNA damage and restoration of the continuity of the DNA duplex; (b) activation of a DNA damage checkpoint, which arrests cell cycle progression so as to allow for repair and prevention of the transmission of damaged or incompletely replicated chromosomes; (c) transcriptional response, which causes changes in the transcription profile that may be beneficial to the cell; and (d) apoptosis, which eliminates heavily damaged or seriously deregulated cells. DNA repair mechanisms include direct repair, base excision repair, nucleotide excision repair, double-strand break repair, and cross-link repair. The DNA damage checkpoints employ damage sensor proteins, such as ATM, ATR, the Rad17-RFC complex, and the 9-1-1 complex, to detect DNA damage and to initiate signal transduction cascades that employ Chk1 and Chk2 Ser/Thr kinases and Cdc25 phosphatases. The signal transducers activate p53 and inactivate cyclin-dependent kinases to inhibit cell cycle progression from G1 to S (the G1/S checkpoint), DNA replication (the intra-S checkpoint), or G2 to mitosis (the G2/M checkpoint). In this review the molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed.",
"title": "Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints."
},
{
"docid": "14145440",
"text": "BACKGROUND DNA replication and mitosis are triggered by activation of kinase complexes, each made up of a cyclin and a cyclin-dependent kinase (Cdk). It had seemed possible that the association of Cdks with different classes of cyclins specifies whether S phase (replication) or M phase (mitosis) will occur. The recent finding that individual B-type cyclins (encoded by the genes CLB1-CLB6) can have functions in both processes in the budding yeast Saccharomyces cerevisiae casts doubt on this notion. RESULTS S. cerevisiae strains lacking C1b1-C1b4 undergo DNA replication once but fail to enter mitosis. We have isolated mutations in two genes, SIM1 and SIM2 (SIM2 is identical to SEC72), which allow such cells to undergo an extra round of DNA replication without mitosis. The Clb5 kinase, which promotes S phase, remains active during the G2-phase arrest of cells of the parental strain, but its activity declines rapidly in sim mutants. Increased expression of the CLB5 gene prevents re-replication. Thus, a cyclin B-kinase that promotes DNA replication in G1-phase cells can prevent re-replication in G2-phase cells. Inactivation of C1b kinases by expression of the specific C1b-Cdk1 inhibitor p40SIC1 is sufficient to induce a prereplicative state at origins of replication in cells blocked in G2/M phase by nocodazole. Re-activation of C1b-Cdk1 kinases induces a second round of DNA replication. CONCLUSIONS We propose that S-phase-promoting cyclin B--Cdk complexes prevent re-replication during S, G2 and M phases by inhibiting the transition of replication origins to a pre-replicative state. This model can explain both why origins 'fire' only once per S phase and why S phase is dependent on completion of the preceding M phase.",
"title": "S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state"
},
{
"docid": "5273056",
"text": "Eukaryotes have numerous checkpoint pathways to protect genome fidelity during normal cell division and in response to DNA damage. Through a screen for G2/M checkpoint regulators in zebrafish, we identified ticrr (for TopBP1-interacting, checkpoint, and replication regulator), a previously uncharacterized gene that is required to prevent mitotic entry after treatment with ionizing radiation. Ticrr deficiency is embryonic-lethal in the absence of exogenous DNA damage because it is essential for normal cell cycle progression. Specifically, the loss of ticrr impairs DNA replication and disrupts the S/M checkpoint, leading to premature mitotic entry and mitotic catastrophe. We show that the human TICRR ortholog associates with TopBP1, a known checkpoint protein and a core component of the DNA replication preinitiation complex (pre-IC), and that the TICRR-TopBP1 interaction is stable without chromatin and requires BRCT motifs essential for TopBP1's replication and checkpoint functions. Most importantly, we find that ticrr deficiency disrupts chromatin binding of pre-IC, but not prereplication complex, components. Taken together, our data show that TICRR acts in association with TopBP1 and plays an essential role in pre-IC formation. It remains to be determined whether Ticrr represents the vertebrate ortholog of the yeast pre-IC component Sld3, or a hitherto unknown metazoan replication and checkpoint regulator.",
"title": "A vertebrate gene, ticrr, is an essential checkpoint and replication regulator."
},
{
"docid": "32852283",
"text": "BACKGROUND Although zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, has been identified as an attractive therapeutic agent against breast cancer, prostate cancer, multiple myeloma as well as small-cell lung cancer (SCLC), as best as we are aware, the anti-tumor effect of ZOL upon non-small-cell lung cancer (NSCLC) remains to be effectively investigated. This study examined the effects of ZOL upon the line-1 tumor cell, using a murine lung adenocarcinoma cell line similar to the behavior of human lung adenocarcinoma. METHODS We investigated the anti-tumor effects of ZOL (3-100 microM) on line-1 tumor cells in vitro, including cellular proliferation, by means of an MTT assay, cell-cycle analysis by flow cytometry and by assessing the level of apoptosis by annexin V/propidium iodide (PI) and 4'-6-diamidino-2-phenylindole (DAPI) staining. Further, we evaluated the growth and survival of line-1 tumor cells following ZOL treatment (1 microg/kg/week) using an animal model. We also examined the in vivo cell-cycle pattern using lacZ-expressing line-1 cells (line-1/lacZ). RESULTS ZOL significantly slowed the line-1 tumor growth in a dose-dependent manner in vitro. The treated line-1 tumor cells typically arrested at the S/G2/M-phase of the cell-cycle following ZOL exposure, but no apoptotic cells could be detected by either annexin V/PI or DAPI staining. When the ZOL was washed out, the drug-inhibited cells continued to proliferate again and the cell-cycle prolongation elicited earlier by the drug, then disappeared. Within 72-96 h following drug removal, the cell-cycle of the treated cells revealed a similar distribution to that of the untreated controls. In vivo studies demonstrated that ZOL significantly slowed the line-1 tumor growth. Indeed, mice lived significantly longer when they had been ZOL-treated than was the case for untreated mice (p<0.05). Using line-1/lacZ cells, the in vivo cell-cycle distribution of line-1 tumor cells subsequent to ZOL exposure revealed S/G2/M-phase arrest that was identical to the in vitro culture. CONCLUSIONS ZOL maintains the potential to reduce tumor burden and prolong survival for murine pulmonary adenocarcinoma. The flow cytometrical analysis of cell-cycle demonstrated that ZOL induces no apoptosis but is able to arrest line-1 tumor cells at the S/G2/M-phase. Although the clinical relevance of these results warrants verification for human lung cancer patients, ZOL combined with chemotherapy and/or radiotherapy appears to be a new therapeutic strategy for the effective treatment of NSCLC.",
"title": "Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers."
},
{
"docid": "6812319",
"text": "Chromosomal instability (CIN) is a hallmark of tumour initiation and progression. Some genomic regions are particularly unstable under replication stress, notably common fragile sites (CFSs) whose rearrangements in tumour cells contribute to cancer development. Recent work has shown that the Fanconi anaemia (FANC) pathway plays a role in preventing defective chromosome segregation and CIN under conditions of replication stress. Strikingly, FANCD2 is recruited to regions hosting CFSs on metaphase chromosomes. To decipher the mechanisms protecting CFSs in G2/M, we searched for proteins that co-localize with FANCD2 on mitotic chromosomes, and identified XPF–ERCC1 and MUS81–EME1, two structure-specific endonucleases. We show that depletion of either ERCC1 or MUS81–EME1 affects accurate processing of replication intermediates or under-replicated DNA that persist at CFSs until mitosis. Depletion of these endonucleases also leads to an increase in the frequency of chromosome bridges during anaphase that, in turn, favours accumulation of DNA damage in the following G1 phase.",
"title": "ERCC1 and MUS81–EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis"
},
{
"docid": "7622767",
"text": "We have used microinjection and time-lapse video microscopy to study the role of cyclin A in mitosis. We have injected purified, active cyclin A/cyclin-dependent kinase 2 (CDK2) into synchronized cells at specific points in the cell cycle and assayed its effect on cell division. We find that cyclin A/CDK2 will drive G2 phase cells into mitosis within 30 min of microinjection, up to 4 h before control cells enter mitosis. Often this premature mitosis is abnormal; the chromosomes do not completely condense and daughter cells fuse. Remarkably, microinjecting cyclin A/CDK2 into S phase cells has no effect on progress through the following G2 phase or mitosis. In complementary experiments we have microinjected the amino terminus of p21Cip1/Waf1/Sdi1 (p21N) into cells to inhibit cyclin A/CDK2 activity. We find that p21N will prevent S phase or G2 phase cells from entering mitosis, and will cause early prophase cells to return to interphase. These results suggest that cyclin A/CDK2 is a rate-limiting component required for entry into mitosis, and for progress through mitosis until late prophase. They also suggest that cyclin A/CDK2 may be the target of the recently described prophase checkpoint.",
"title": "Human Cyclin a Is Required for Mitosis until Mid Prophase"
},
{
"docid": "7165938",
"text": "PURPOSE The circadian clock gene Bmal1 is involved in cancer cell proliferation and DNA damage sensitivity. The aim of this study was to explore the effect of Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in colorectal cancer. EXPERIMENTAL DESIGN Three colorectal cancer cell lines, HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal cancer cell proliferation was tested in vitro and in vivo. MTT and colony formation assays were performed to determine the sensitivity of colorectal cancer cells to oxaliplatin. Flow cytometry was used to examine changes in the cell-cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1 upon its overexpression were determined by Western blotting. Immunohistochemistry was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from patients treated with oxaliplatin-based regimens. RESULTS Bmal1 overexpression inhibited colorectal cancer cell proliferation and increased colorectal cancer sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells model in vivo. Furthermore, the overall survival of patients with colorectal cancer with high Bmal1 levels in their primary tumors was significantly longer than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The progression-free survival of patients with high Bmal1 expression was also significantly longer than that of patients with low Bmal1 expression (11 vs. 5 months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its ability to regulate G2-M arrest by activating the ATM pathway. CONCLUSION Bmal1 shows the potential as a novel prognostic biomarker and may represent a new therapeutic target in colorectal cancer.",
"title": "Overexpression of the circadian clock gene Bmal1 increases sensitivity to oxaliplatin in colorectal cancer."
},
{
"docid": "7736860",
"text": "Store-operated Ca(2+) entry (SOCE) is the principal Ca(2+) entry mechanism in nonexcitable cells. Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca(2+) sensor that triggers SOCE activation. However, the role of STIM1 in regulating cancer progression remains controversial and its clinical relevance is unclear. Here we show that STIM1-dependent signaling is important for cervical cancer cell proliferation, migration, and angiogenesis. STIM1 overexpression in tumor tissue is noted in 71% cases of early-stage cervical cancer. In tumor tissues, the level of STIM1 expression is significantly associated with the risk of metastasis and survival. EGF-stimulated cancer cell migration requires STIM1 expression and EGF increases the interaction between STIM1 and Orai1 in juxta-membrane areas, and thus induces Ca(2+) influx. STIM1 involves the activation of Ca(2+)-regulated protease calpain, as well as Ca(2+)-regulated cytoplasmic kinase Pyk2, which regulate the focal-adhesion dynamics of migratory cervical cancer cells. Because of an increase of p21 protein levels and a decrease of Cdc25C protein levels, STIM1-silencing in cervical cancer cells significantly inhibits cell proliferation by arresting the cell cycle at the S and G2/M phases. STIM1 also regulates the production of VEGF in cervical cancer cells. Interference with STIM1 expression or blockade of SOCE activity inhibits tumor angiogenesis and growth in animal models, confirming the crucial role of STIM1-mediated Ca(2+) influx in aggravating tumor development in vivo. These results make STIM1-dependent signaling an attractive target for therapeutic intervention.",
"title": "Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis."
},
{
"docid": "23356816",
"text": "The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1) and cyclin A2 (encoded by Ccna2). Cyclin A2 promotes both G1/S and G2/M transitions, and targeted deletion of Ccna2 in mouse is embryonic lethal. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and is expressed in humans at highest levels in the testis and certain myeloid leukaemia cells. To investigate the role of cyclin A1 and possible redundancy among the cyclins in vivo, we generated mice bearing a null mutation of Ccna1. Ccna1-/- males were sterile due to a block of spermatogenesis before the first meiotic division, whereas females were normal. Meiosis arrest in Ccna1–/– males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.",
"title": "Cyclin A1 is required for meiosis in the male mouse"
},
{
"docid": "24498673",
"text": "Holliday junctions (HJs) are four-way DNA intermediates that form during homologous recombination, and their efficient resolution is essential for chromosome segregation. Here, we show that three structure-selective endonucleases, namely SLX1-SLX4, MUS81-EME1, and GEN1, define two pathways of HJ resolution in human cells. One pathway is mediated by GEN1, whereas SLX1-SLX4 and MUS81-EME1 provide a second and genetically distinct pathway (SLX-MUS). Cells depleted for SLX-MUS or GEN1 pathway proteins exhibit severe defects in chromosome segregation and reduced survival. In response to CDK-mediated phosphorylation, SLX1-SLX4 and MUS81-EME1 associate at the G2/M transition to form a stable SLX-MUS holoenzyme, which can be reconstituted in vitro. Biochemical studies show that SLX-MUS is a HJ resolvase that coordinates the active sites of two distinct endonucleases during HJ resolution. This cleavage reaction is more efficient and orchestrated than that mediated by SLX1-SLX4 alone, which exhibits a potent nickase activity that acts promiscuously upon DNA secondary structures.",
"title": "Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells."
},
{
"docid": "18374364",
"text": "A rare set of hematopoietic stem cells (HSC) must undergo a massive expansion to produce mature blood cells. The phenotypic isolation of HSC from mice offers the opportunity to determine directly their proliferation kinetics. We analyzed the proliferation and cell cycle kinetics of long-term self-renewing HSC (LT-HSC) in normal adult mice. At any one time, approximately 5% of LT-HSC were in S/G2/M phases of the cell cycle and another 20% were in G1 phase. BrdUrd incorporation was used to determine the rate at which different cohorts of HSC entered the cell cycle over time. About 50% of LT-HSC incorporated BrdUrd by 6 days and >90% incorporated BrdUrd by 30 days. By 6 months, 99% of LT-HSC had incorporated BrdUrd. We calculated that approximately 8% of LT-HSC asynchronously entered the cell cycle per day. Nested reverse transcription-PCR analysis revealed cyclin D2 expression in a high proportion of LT-HSC. Although approximately 75% of LT-HSC are quiescent in G0 at any one time, all HSC are recruited into cycle regularly such that 99% of LT-HSC divide on average every 57 days.",
"title": "In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells."
},
{
"docid": "8774475",
"text": "Loss of cell polarity proteins such as Scribble induces neoplasia in Drosophila by promoting uncontrolled proliferation. In mammals, the role that polarity proteins play during tumorigenesis is not well understood. Here, we demonstrate that depletion of Scribble in mammary epithelia disrupts cell polarity, blocks three-dimensional morphogenesis, inhibits apoptosis, and induces dysplasia in vivo that progress to tumors after long latency. Loss of Scribble cooperates with oncogenes such as c-myc to transform epithelial cells and induce tumors in vivo by blocking activation of an apoptosis pathway. Like depletion, mislocalization of Scribble from cell-cell junction was sufficient to promote cell transformation. Interestingly, spontaneous mammary tumors in mice and humans possess both downregulated and mislocalized Scribble. Thus, we demonstrate that scribble inhibits breast cancer formation and that deregulation of polarity pathways promotes dysplastic and neoplastic growth in mammals by disrupting morphogenesis and inhibiting cell death.",
"title": "Deregulation of Scribble Promotes Mammary Tumorigenesis and Reveals a Role for Cell Polarity in Carcinoma"
},
{
"docid": "12909503",
"text": "DNA damage encountered by DNA replication forks poses risks of genome destabilization, a precursor to carcinogenesis. Damage checkpoint systems cause cell cycle arrest, promote repair and induce programed cell death when damage is severe. Checkpoints are critical parts of the DNA damage response network that act to suppress cancer. DNA damage and perturbation of replication machinery causes replication stress, characterized by accumulation of single-stranded DNA bound by replication protein A (RPA), which triggers activation of ataxia telangiectasia and Rad3 related (ATR) and phosphorylation of the RPA32, subunit of RPA, leading to Chk1 activation and arrest. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) [a kinase related to ataxia telangiectasia mutated (ATM) and ATR] has well characterized roles in DNA double-strand break repair, but poorly understood roles in replication stress-induced RPA phosphorylation. We show that DNA-PKcs mutant cells fail to arrest replication following stress, and mutations in RPA32 phosphorylation sites targeted by DNA-PKcs increase the proportion of cells in mitosis, impair ATR signaling to Chk1 and confer a G2/M arrest defect. Inhibition of ATR and DNA-PK (but not ATM), mimic the defects observed in cells expressing mutant RPA32. Cells expressing mutant RPA32 or DNA-PKcs show sustained H2AX phosphorylation in response to replication stress that persists in cells entering mitosis, indicating inappropriate mitotic entry with unrepaired damage.",
"title": "Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress"
},
{
"docid": "9038803",
"text": "Many human tumours show centrosome aberrations, indicating an underlying deregulation of centrosome structure, duplication or segregation. Centrosomes organize microtubule arrays throughout the cell cycle, thereby influencing both tissue architecture and the accuracy of chromosome segregation. But what are the origins of centrosomal abnormalities in tumours, and what impact do they have on the generation of invasive, genetically unbalanced cells during cancer progression?",
"title": "Centrosome aberrations: cause or consequence of cancer progression?"
},
{
"docid": "27247460",
"text": "Many physiological, biochemical and behavioral processes operate under the circadian rhythm, which is generated by an internal time-keeping mechanism commonly referred to as the biological clock, in almost all organisms from bacteria to mammals. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop, in which CLOCK and BMAL1 are positive regulators. A cell has two mechanisms, \"cell cycle\" and \"cell rhythm\", the relationship between which remains controversial. Therefore, the aim of this study was to explore the effect of Clock and Bmal1 on cell cycle, especially on the G1 phase, using vectors with the tetracycline operator-repressor system. The present study revealed that simultaneous induction of Bmal1 and Clock had an influential effect on the cell cycle in SW480/T-REx/Clock/Bmal1 cells, in which both Clock and Bmal1 could be induced by tetracycline. The observation that induction of both Clock and Bmal1 inhibited cell growth and the significant increase of the G1 phase proportion of in SW480/T-REx/Clock/Bmal1 cells indicated that entry from the G1 to S phase was inhibited by the induction of Clock and Bmal1. Furthermore, overexpression of Clock and Bmal1 prevented the cells from entering into the G2/M phase induced by Paclitaxel, and made the cells more resistant to the agent. In conclusion, we found that overexpression of both Clock and Bmal1 suppressed cell growth. In addition, the present study raised the possibility that Clock and Bmal1 may in part play a role in preventing the cells from entering G1 to S phase of cell cycle via suppression of CyclinD1 expression, and thus acquiring resistance to Paclitaxel.",
"title": "OVEREXPRESSION OF BOTH CLOCK AND BMAL1 INHIBITS ENTRY TO S PHASE IN HUMAN COLON CANCER CELLS."
},
{
"docid": "23634484",
"text": "A predominantly nuclear RNA-binding protein, HuR translocates to the cytoplasm in response to stress and proliferative signals, where it stabilizes or modulates the translation of target mRNAs. Here, we present evidence that HuR phosphorylation at S202 by the G2-phase kinase Cdk1 influences its subcellular distribution. HuR was specifically phosphorylated in synchronous G2-phase cultures; its cytoplasmic levels increased by Cdk1-inhibitory interventions and declined in response to Cdk1-activating interventions. In keeping with the prominently cytoplasmic location of the nonphosphorylatable point mutant HuR(S202A), phospho-HuR(S202) was shown to be predominantly nuclear using a novel anti-phospho-HuR(S202) antibody. The enhanced cytoplasmic presence of unphosphorylated HuR was linked to its decreased association with 14-3-3 and to its heightened binding to target mRNAs. Our findings suggest that Cdk1 phosphorylates HuR during G2, thereby helping to retain it in the nucleus in association with 14-3-3 and hindering its post-transcriptional function and anti-apoptotic influence.",
"title": "Nuclear HuR accumulation through phosphorylation by Cdk1."
},
{
"docid": "25837950",
"text": "Obesity is associated with higher mortality in the general population, but this association is reversed in patients on dialysis. The nature of the relationship of obesity with adverse clinical outcomes in nondialysis-dependent CKD and the putative interaction of the severity of disease with this association are unclear. We analyzed data from a nationally representative cohort of 453,946 United States veterans with eGFR<60 ml/min per 1.73 m(2). The associations of body mass index categories (<20, 20 to <25, 25 to <30, 30 to <35, 35 to <40, 40 to <45, 45 to <50, and ≥50 kg/m(2)) with all-cause mortality and disease progression (using multiple definitions, including incidence of ESRD, doubling of serum creatinine, and the slopes of eGFR) were examined in Cox proportional hazards models and logistic regression models. Multivariable adjustments were made for age, race, comorbidities and medications, and baseline eGFR. Body mass index showed a relatively consistent U-shaped association with clinical outcomes, with the best outcomes observed in overweight and mildly obese patients. Body mass index levels <25 kg/m(2) were associated with worse outcomes in all patients, independent of severity of CKD. Body mass index levels ≥35 kg/m(2) were associated with worse outcomes in patients with earlier stages of CKD, but this association was attenuated in those patients with eGFR<30 ml/min per 1.73 m(2). Thus, until clinical trials establish the ideal body mass index, a cautious approach to weight management is warranted in this patient population.",
"title": "Association of body mass index with outcomes in patients with CKD."
},
{
"docid": "33638477",
"text": "Several components of the Wnt signaling cascade have been shown to function either as tumor suppressor proteins or as oncogenes in multiple human cancers, underscoring the relevance of this pathway in oncogenesis and the need for further investigation of Wnt signaling components as potential targets for cancer therapy. Here, using expression profiling analysis as well as in vitro and in vivo functional studies, we show that the Wnt pathway component BCL9 is a novel oncogene that is aberrantly expressed in human multiple myeloma as well as colon carcinoma. We show that BCL9 enhances beta-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases cell proliferation, migration, invasion, and the metastatic potential of tumor cells by promoting loss of epithelial and gain of mesenchymal-like phenotype. Most importantly, BCL9 knockdown significantly increased the survival of xenograft mouse models of cancer by reducing tumor load, metastasis, and host angiogenesis through down-regulation of c-Myc, cyclin D1, CD44, and vascular endothelial growth factor expression by tumor cells. Together, these findings suggest that deregulation of BCL9 is an important contributing factor to tumor progression. The pleiotropic roles of BCL9 reported in this study underscore its value as a drug target for therapeutic intervention in several malignancies associated with aberrant Wnt signaling.",
"title": "BCL9 promotes tumor progression by conferring enhanced proliferative, metastatic, and angiogenic properties to cancer cells."
},
{
"docid": "4418878",
"text": "The development of an oncogenic state is a complex process involving the accumulation of multiple independent mutations that lead to deregulation of cell signalling pathways central to the control of cell growth and cell fate. The ability to define cancer subtypes, recurrence of disease and response to specific therapies using DNA microarray-based gene expression signatures has been demonstrated in multiple studies. Various studies have also demonstrated the potential for using gene expression profiles for the analysis of oncogenic pathways. Here we show that gene expression signatures can be identified that reflect the activation status of several oncogenic pathways. When evaluated in several large collections of human cancers, these gene expression signatures identify patterns of pathway deregulation in tumours and clinically relevant associations with disease outcomes. Combining signature-based predictions across several pathways identifies coordinated patterns of pathway deregulation that distinguish between specific cancers and tumour subtypes. Clustering tumours based on pathway signatures further defines prognosis in respective patient subsets, demonstrating that patterns of oncogenic pathway deregulation underlie the development of the oncogenic phenotype and reflect the biology and outcome of specific cancers. Predictions of pathway deregulation in cancer cell lines are also shown to predict the sensitivity to therapeutic agents that target components of the pathway. Linking pathway deregulation with sensitivity to therapeutics that target components of the pathway provides an opportunity to make use of these oncogenic pathway signatures to guide the use of targeted therapeutics.",
"title": "Oncogenic pathway signatures in human cancers as a guide to targeted therapies"
},
{
"docid": "25523969",
"text": "Small non-coding microRNAs (miRNAs) contribute to cancer development and progression, and are differentially expressed in normal tissues and cancers. However, the specific role of miRNAs in the metastatic process is still unknown. To seek a specific miRNA expression signature characterizing the metastatic phenotype of solid tumours, we performed a miRNA microarray analysis on 43 paired primary tumours (ten colon, ten bladder, 13 breast, and ten lung cancers) and one of their related metastatic lymph nodes. We identified a metastatic cancer miRNA signature comprising 15 overexpressed and 17 underexpressed miRNAs. Our results were confirmed by qRT-PCR analysis. Among the miRNAs identified, some have a well-characterized association with cancer progression, eg miR-10b, miR-21, miR-30a, miR-30e, miR-125b, miR-141, miR-200b, miR-200c, and miR-205. To further support our data, we performed an immunohistochemical analysis for three well-defined miRNA gene targets (PDCD4, DHFR, and HOXD10 genes) on a small series of paired colon, breast, and bladder cancers, and one of their metastatic lymph nodes. We found that the immunohistochemical expression of these targets significantly follows the corresponding miRNA deregulation. Our results suggest that specific miRNAs may be directly involved in cancer metastasis and that they may represent a novel diagnostic tool in the characterization of metastatic cancer gene targets.",
"title": "MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets."
},
{
"docid": "5271210",
"text": "MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs involved in the regulation of gene expression and protein translation. Many studies have shown that they play a crucial role in driving organ and tissue differentiation during embryogenesis and in the fine-tuning of fundamental biological processes, such as proliferation and apoptosis. Growing evidence indicates that their deregulation plays an important role in cancer onset and progression as well, where they act as oncogenes or oncosuppressors. In this review, we highlight the most recent findings regarding the role of miRNAs in hepatocellular carcinoma (HCC) by analyzing the possible mechanisms by which they contribute to this neoplasm. Moreover, we discuss the possible role of circulating miRNAs as biomarkers, a field that needs urgent improvement in the clinical surveillance of HCC, and the fascinating possibility of using them as therapeutic targets or drugs themselves.",
"title": "MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma?"
},
{
"docid": "195689316",
"text": "BACKGROUND The main associations of body-mass index (BMI) with overall and cause-specific mortality can best be assessed by long-term prospective follow-up of large numbers of people. The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies. METHODS Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with 894 576 participants, mostly in western Europe and North America (61% [n=541 452] male, mean recruitment age 46 [SD 11] years, median recruitment year 1979 [IQR 1975-85], mean BMI 25 [SD 4] kg/m(2)). The analyses were adjusted for age, sex, smoking status, and study. To limit reverse causality, the first 5 years of follow-up were excluded, leaving 66 552 deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): 30 416 vascular; 2070 diabetic, renal or hepatic; 22 592 neoplastic; 3770 respiratory; 7704 other. FINDINGS In both sexes, mortality was lowest at about 22.5-25 kg/m(2). Above this range, positive associations were recorded for several specific causes and inverse associations for none, the absolute excess risks for higher BMI and smoking were roughly additive, and each 5 kg/m(2) higher BMI was on average associated with about 30% higher overall mortality (hazard ratio per 5 kg/m(2) [HR] 1.29 [95% CI 1.27-1.32]): 40% for vascular mortality (HR 1.41 [1.37-1.45]); 60-120% for diabetic, renal, and hepatic mortality (HRs 2.16 [1.89-2.46], 1.59 [1.27-1.99], and 1.82 [1.59-2.09], respectively); 10% for neoplastic mortality (HR 1.10 [1.06-1.15]); and 20% for respiratory and for all other mortality (HRs 1.20 [1.07-1.34] and 1.20 [1.16-1.25], respectively). Below the range 22.5-25 kg/m(2), BMI was associated inversely with overall mortality, mainly because of strong inverse associations with respiratory disease and lung cancer. These inverse associations were much stronger for smokers than for non-smokers, despite cigarette consumption per smoker varying little with BMI. INTERPRETATION Although other anthropometric measures (eg, waist circumference, waist-to-hip ratio) could well add extra information to BMI, and BMI to them, BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22.5-25 kg/m(2). The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal. At 30-35 kg/m(2), median survival is reduced by 2-4 years; at 40-45 kg/m(2), it is reduced by 8-10 years (which is comparable with the effects of smoking). The definite excess mortality below 22.5 kg/m(2) is due mainly to smoking-related diseases, and is not fully explained.",
"title": "Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies."
},
{
"docid": "3230557",
"text": "Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.",
"title": "The Hallmarks of Aging"
},
{
"docid": "30492966",
"text": "Amyotrophic Lateral Sclerosis (ALS) is a progressive degenerative disease of the motor neurons and the cause is unknown. Diverse factors such as genetic defects, nutritional deficiencies, head trauma, environmental toxin, autoimmune responses and viral and bacterial infections are involved. Mycoplasmas have been implicated as causal agents of different illnesses in human. The purpose of this study was to investigate the presence of mycoplasmas in the bloodstream of patients with ALS. Patients with ALS and healthy individuals were included in the study. A blood sample was taken in tubes with or without anticoagulant. Mycoplasmas were detected by culture or direct PCR, and the presence of antibodies IgM and IgG against LAMPs of these microorganisms by Western blot. Cultures for aerobic facultative bacteria were also done. Blood samples from 13 patients and 44 healthy individuals were screened. All blood cultures for non-fermentative mycoplasmas and aerobic facultative bacteria were negative. Cultures for fermentative mycoplasmas were considered positive after identification of mycoplasmal DNA by PCR. Mycoplasma sp. was detected by culture or direct PCR in 6/13 (46%) patients and in 4/44 (9%) of healthy individuals. M. fermentans was detected by PCR using specific primers in six patients and in two healthy individuals. IgM against LAMPs of M. fermentans were detected in 6/13 (46%) blood samples from patients and in 13/44 (30%) from healthy individuals, while. IgG was detected in 4/13 (31%) patients and in 3/44 (7%) healthy individuals. The results of this study show that mycoplasmas cause a systemic infection and could play a role in the origin or progression of the ALS.",
"title": "Detection of Mycoplasmas in Patients with Amyotrophic Lateral Sclerosis"
},
{
"docid": "4346731",
"text": "The development and maintenance of an epithelium requires finely balanced rates of growth and cell death. However, the mechanical and biochemical mechanisms that ensure proper feedback control of tissue growth, which when deregulated contribute to tumorigenesis, are poorly understood. Here we use the fly notum as a model system to identify a novel process of crowding-induced cell delamination that balances growth to ensure the development of well-ordered cell packing. In crowded regions of the tissue, a proportion of cells undergo a serial loss of cell–cell junctions and a progressive loss of apical area, before being squeezed out by their neighbours. This path of delamination is recapitulated by a simple computational model of epithelial mechanics, in which stochastic cell loss relieves overcrowding as the system tends towards equilibrium. We show that this process of delamination is mechanistically distinct from apoptosis-mediated cell extrusion and precedes the first signs of cell death. Overall, this analysis reveals a simple mechanism that buffers epithelia against variations in growth. Because live-cell delamination constitutes a mechanistic link between epithelial hyperplasia and cell invasion, this is likely to have important implications for our understanding of the early stages of cancer development.",
"title": "Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding"
},
{
"docid": "15926408",
"text": "A major challenge each human cell-division cycle is to ensure that DNA replication origins do not initiate more than once, a phenomenon known as re-replication. Acute deregulation of replication control ultimately causes extensive DNA damage, cell-cycle checkpoint activation and cell death whereas moderate deregulation promotes genome instability and tumorigenesis. In the absence of detectable increases in cellular DNA content however, it has been difficult to directly demonstrate re-replication or to determine if the ability to re-replicate is restricted to a particular cell-cycle phase. Using an adaptation of DNA fiber spreading we report the direct detection of re-replication on single DNA molecules from human chromosomes. Using this method we demonstrate substantial re-replication within 1 h of S phase entry in cells overproducing the replication factor, Cdt1. Moreover, a comparison of the HeLa cancer cell line to untransformed fibroblasts suggests that HeLa cells produce replication signals consistent with low-level re-replication in otherwise unperturbed cell cycles. Re-replication after depletion of the Cdt1 inhibitor, geminin, in an untransformed fibroblast cell line is undetectable by standard assays but readily quantifiable by DNA fiber spreading analysis. Direct evaluation of re-replicated DNA molecules will promote increased understanding of events that promote or perturb genome stability.",
"title": "Analysis of re-replication from deregulated origin licensing by DNA fiber spreading"
},
{
"docid": "23269537",
"text": "Cyclin D1 expression is deregulated by chromosome translocation in mantle cell lymphoma and a subset of multiple myeloma. The molecular mechanisms involved in long-distance gene deregulation remain obscure, although changes in acetylated histones and methylated CpG dinucleotides may be important. The patterns of DNA methylation and histone acetylation were determined at the cyclin D1 locus on chromosome 11q13 in B-cell malignancies. The cyclin D1 promoter was hypomethylated and hyperacetylated in expressing cell lines and patient samples, and methylated and hypoacetylated in nonexpressing cell lines. Domains of hyperacetylated histones and hypomethylated DNA extended over 120 kb upstream of the cyclin D1 gene. Interestingly, hypomethylated DNA and hyperacetylated histones were also located at the cyclin D1 promoter but not the upstream major translocation cluster region in cyclin D1-nonexpressing, nontumorigenic B and T cells. RNA polymerase II binding was demonstrated both at the cyclin D1 promoter and 3' immunoglobulin heavy-chain regulatory regions only in malignant B-cell lines with deregulated cyclin D1 expression. Our results suggest a model where RNA polymerase II bound at IgH regulatory sequences can activate the cyclin D1 promoter by either long-range polymerase transfer or tracking.",
"title": "Cyclin D1 activation in B-cell malignancy: association with changes in histone acetylation, DNA methylation, and RNA polymerase II binding to both promoter and distal sequences."
},
{
"docid": "34189936",
"text": "Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm arising from the mesothelial cells lining the parietal pleura and it exhibits poor prognosis. Although there has been significant progress in MPM treatment, development of more efficient therapeutic approaches is needed. BMAL1 is a core component of the circadian clock machinery and its constitutive overexpression in MPM has been reported. Here, we demonstrate that BMAL1 may serve as a molecular target for MPM. The majority of MPM cell lines and a subset of MPM clinical specimens expressed higher levels of BMAL1 compared to a nontumorigenic mesothelial cell line (MeT-5A) and normal parietal pleural specimens, respectively. A serum shock induced a rhythmical BMAL1 expression change in MeT-5A but not in ACC-MESO-1, suggesting that the circadian rhythm pathway is deregulated in MPM cells. BMAL1 knockdown suppressed proliferation and anchorage-dependent and independent clonal growth in two MPM cell lines (ACC-MESO-1 and H290) but not in MeT-5A. Notably, BMAL1 depletion resulted in cell cycle disruption with a substantial increase in apoptotic and polyploidy cell population in association with downregulation of Wee1, cyclin B and p21(WAF1/CIP1) and upregulation of cyclin E expression. BMAL1 knockdown induced mitotic catastrophe as denoted by disruption of cell cycle regulators and induction of drastic morphological changes including micronucleation and multiple nuclei in ACC-MESO-1 cells that expressed the highest level of BMAL1. Taken together, these findings indicate that BMAL1 has a critical role in MPM and could serve as an attractive therapeutic target for MPM.",
"title": "The circadian clock gene BMAL1 is a novel therapeutic target for malignant pleural mesothelioma."
},
{
"docid": "4767806",
"text": "Maintenance and accurate propagation of the genetic material are key features for physiological development and wellbeing. The replication licensing machinery is crucial for replication precision as it ensures that replication takes place once per cell cycle. Thus, the expression status of the components comprising the replication licensing apparatus is tightly regulated to avoid re-replication; a form of replication stress that leads to genomic instability, a hallmark of cancer. In the present review we discuss the mechanistic basis of replication licensing deregulation, which leads to systemic effects, exemplified by its role in carcinogenesis and a variety of genetic syndromes. In addition, new insights demonstrate that above a particular threshold, the replication licensing factor Cdc6 acts as global transcriptional regulator, outlining new lines of exploration. The role of the putative replication licensing factor ChlR1/DDX11, mutated in the Warsaw Breakage Syndrome, in cancer is also considered. Finally, future perspectives focused on the potential therapeutic advantage by targeting replication licensing factors, and particularly Cdc6, are discussed.",
"title": "Exploring and exploiting the systemic effects of deregulated replication licensing."
},
{
"docid": "40790033",
"text": "BACKGROUND The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease. METHODS ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950. FINDINGS The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group. INTERPRETATION Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent. FUNDING Novartis.",
"title": "Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial."
}
] |
5548
|
Can value from labor provided to oneself be taxed?
|
[
{
"docid": "551934",
"text": "The basis of the home is the cost of land and material. That's it. Your time isn't added to basis. No different than if you spend 1000 hours in a soup kitchen. You deduct miles for your car and expenses you can document but you can't deduct your time. Over 2 years, you could have a gain up to $500K per married couple and pay no tax.",
"title": ""
},
{
"docid": "235298",
"text": "I've heard of handyman type people making a living this way untaxed. They move into a fixer-upper, fix it up while living there, stay over two years and sell. They can pocket $125k/yr tax free this way assuming they produce that much value in their fixing-up. (Beware, though, that this will bite you in low social security payments in retirement!)",
"title": ""
},
{
"docid": "291949",
"text": "This is called imputed income, which is generally not taxed in the US.",
"title": ""
}
] |
[
{
"docid": "73950",
"text": "\"A non-trading stock or non-marketable security or unlisted security is one that does not trade continually on an exchange. For tax purposes, this can mean a whole new ball of wax which I would prefer the experts address with an edit to this answer or a new answer. For financial accounting purposes, this is when, say, one owns shares in an unlisted corporation and should be treated very carefully less one delude oneself. For trading stock, the value can be known immediately by checking any valid data provider's price and marking to market. For non-trading stock, the value has to be \"\"marked to model\"\". This can get one into Enron sized trouble. In this case, it's best to either leave the value of the stock at the purchase price and recognize gains upon sale, use a price from another honest transaction by third parties which are most likely difficult to attain, or to use some shorthand measure like applying the market P/E. Be wary of strangely high figures for value from the purchase price by using a market average, and don't throw away the shares just yet if a strangely low one arises. This method can lead to strange results.\"",
"title": ""
},
{
"docid": "158614",
"text": "\"Theres some major logic missing from this report, it didnt mention how technology is disrupting how everything is being distributed. As businesses become more efficient with technological advances and less dependent on human capital, then so must humans become more efficient and less dependent upon an expected level of income. Whats the demand to keep a human alive and well versus the demand for needing a well paid human laborer? If you are easily replacable, then your value to the company is simply cheap labor. Best example is Walmart, the wealthiest family, the largest employer whose many employees require gov assistance to live due to low wages. The only way this business could even exist is with assitance from the goverment to support its workers. So where do these tax subsidies come from? The article responded with a great point \"\"There will never be “piles and piles of valuable goods” laying around with no one to enjoy them.\"\" Whoever said that has never been to Walmart with no money. I suppose there will always be \"\"someone around to enjoy them\"\" but will there also be less and less people who can afford to enjoy such things? Walmart has already shown what happens. This article points out the old ways of doing things economically but ignores the fact technology creates abundance, not scarcity. Were not currently using that abundance to directly improve humanity on a large scale level but rather the opposite to control supply or scarcity aka profits. When the demand to maintain & control financial power overpowers the desire to care & provide for your neighbor, then the rise of inequality and narcissistic options appear. This buying power is the component of influence to being able to survive very well or simply even remain alive. If my daily wage doesnt provide for my daily needs, then how can I use technology to stay alive? How efficient can we all become before we start to share in the abundance of life together?\"",
"title": ""
},
{
"docid": "297694",
"text": "Value is one area where economic theories tend to diverge and the (very) basic schools of thought both have excellent points in their favor. You've identified both here; one being that economic value can always be determined by net labor* or at least cost of inputs and the other being that economic value does not exist in and of itself and that only a market can determine value. In some ways it is just a question of world-view as much as anything but the concepts of natural prices or innate worth are difficult to argue against. At the same time, without exchange the concept of value has little meaning. So, as usual, it is some sophistry mixed with some sense. Both have elements of truth and both are considerably more complex than they seem at first. Interestingly though, neither seems to work very well as predictive models despite providing the basis for some incredibly complex and interesting mathematical workups. * Note that net labor is the sum of ALL labor involved and is incredibly difficult to quantify accurately.",
"title": ""
},
{
"docid": "593197",
"text": "\"Can the companies from USA give job to me (I am from New Zealand)? Job as being employee - may be tricky. This depends on the labor laws in New Zealand, but most likely will trigger \"\"nexus\"\" clause and will force the employer to register in the country, which most won't want to do. Instead you can be hired as a contractor (i.e.: being self-employed, from NZ legal perspective). If so, what are the legal documents i have to provide to the USA for any taxes? If you're employed as a contractor, you'll need to provide form W8-BEN to your US employer on which you'll have to certify your tax status. Unless you're a US citizen/green card holder, you're probably a non-US person for tax purposes, and as such will not be paying any tax in the US as long as you work in New Zealand. If you travel to the US for work, things may become tricky, and tax treaties may be needed. Will I have to pay tax to New Zealand Government? Most likely, as a self-employed. Check how this works locally. As for recommendations, since these are highly subjective opinions that may change over time, they're considered off-topic here. Check on Yelp, Google, or any local NZ professional review site.\"",
"title": ""
},
{
"docid": "373481",
"text": "The short answer is yes, losses get passed through to members. Limits/percentages do apply, primarily based on your share in the business. Check out the final post in this thread: http://community2.business.gov/t5/Other-Business-Issues/Paying-oneself-in-a-LLC/td-p/16060 It's not a bad little summary of the profit/loss pass-through. Regarding your 60K/60K example: the amount of money you earn in your day job will impact how much loss you can claim. Unfortunately I can't find anything more recent at the IRS or business.gov, but see this from 2004 - 40K was the limit before the amount you could claim against started to be mitigated: http://en.allexperts.com/q/Tax-Law-Questions-932/tax-loss-pass.htm HTH",
"title": ""
},
{
"docid": "133020",
"text": "Here is what I was able to find: Yes, but there are special instructions for minors: Working hours: New York State labor laws are slightly more strict than the federal: https://www.labor.state.ny.us/workerprotection/laborstandards/workprot/nyvsfed.shtm Minimum wage: The Dept of Labor's Youth & Labor page states: Occupations such as babysitting are not subject to the minimum wage law. No supporting documentation is given. Another page describes the Youth Minimum Wage Program: A minimum wage of not less than $4.25 may be paid to employees under the age of 20 for their first 90 consecutive calendar days However, I can't find any such exception in New York State minimum wage law. According to Publication 926, Household Employer's Tax Guide: Federal income tax withholding No, I am not required to withhold federal income taxes from a household employee. If we both want them to be withheld, a W-4 should be submitted to me. State income tax withholding No, according to NYS Pub 27: Withholding income tax (federal or New York State) from wages paid to household employees is voluntary on your part and your employee Social security and medicare No, I am not required to withhold FICA taxes because when calculated wages, I should not include: An employee who is under the age of 18 at any time during the year. Exception: Count these wages if providing household services is the employee's principal occupation. If the employee is a student, providing household services is not considered to be his or her principal occupation. Unemployment insurance No, I don't think I have to pay federal unemployment tax. I think the exception for FICA applies to FUTA. For New York (according to Household Employers Guide for Unemployment Insurance), there is an exception for paying state unemployment insurance: Daytime students who attend elementary or high school (However, you must pay UI taxes on wages you pay these students if you are liable under FUTA.) I can't find any specific requirements, but aside from numbers of hours times rate of pay, you might want to consider the information required by the Wage Theft Prevention Act: Also, consider this requirements from the NY Minimum Wage Act Every employer shall keep true and accurate records of hours worked by each employee covered by an hourly minimum wage rate, the wages paid to all employees, and such other information as the commissioner deems material and necessary, and shall, on demand, furnish to the commissioner or his duly authorized representative a sworn statement of the same.",
"title": ""
},
{
"docid": "273998",
"text": "\"Companies often provide cafeteria, or catering services, to employees tax-free at subsidized rates. I'll use \"\"cafeteria\"\" as an illustration. The IRS says that in order to avoid lunch being taxed as income, the employees must pay the \"\"direct costs\"\" of the lunch, food and labor. In addition to those costs, cafeterias add two more items to come up with the total tab; \"\"overhead,\"\" (the cost of renting the space), and of course, profit. The company can waive the last two, and charge employees only materials and labor. That's why subsidized cafeteria food can cost as little as half of what it would cost elsewhere.\"",
"title": ""
},
{
"docid": "175199",
"text": "Typically labor is a company's largest expense. So, when a company receives tax cuts that doesn't translate to more hiring. Long term, if the company expands it might, but it could also choose to invest in a better or different products, maybe more efficient business processes, or invest in overseas operations. Additionally, labor has a diminishing value... just because we could hire more people to make more things doesn't mean we should. Side note: In many states, the largest employers are the state/local governments (schools, public services, etc), and healthcare providers. This tax cut is great for people that are already invested, or high income earners because it lowers the overall tax brackets and aligns capital gains to those. So say I had a million dollars invested and earned a yearly 10% dividend return, I'd earn 100k in dividends and pay 25% as income tax. Source: https://www.forbes.com/sites/anthonynitti/2017/07/13/what-will-the-trump-tax-cuts-mean-for-your-wallet/ However, something like 50% of all Americans are invested in the stock market. Only the top 10% average investments close to a million in investments (example above)... and 38% of all investments are owned by the 1%... Source: http://www.npr.org/2017/03/01/517975766/while-trump-touts-stock-market-many-americans-left-out-of-the-conversation Tax cuts, while popular, wouldn't ever help stimulate consumer spending, esp. considering the amount of consumer debt that exists (~1 Trillion?). What these tax cuts would do create more debt for tax payers.",
"title": ""
},
{
"docid": "300510",
"text": "\"These government mandates of minimum wage will cause more problems than they will solve. I don't know how many of you own a small business but I can give you a real world example here in the City of Chicago. On July 1st, 2017 the minimum wage will increase to $11.00 while at the same time they're introducing a .01 per oz \"\"Sugar Tax.\"\" The amount of additional work needed to keep track of sugar consumption will be burdensome for small businesses who will have to raise prices to accommodate the new labor costs and tax. Customers are price sensitive so they will usually go for the cheaper option which can be provided only by corporate/big business who have the ability to automate certain positions in the labor supply chain which is currently happening. I wouldn't be surprised if the timeline for kiosks/self-service robot implementation is on par with the $15.00 minimum wage deadline in 2019. To sum up, big business wins and labor loses but I guess results don't matter when your intentions are \"\"good.\"\"\"",
"title": ""
},
{
"docid": "347914",
"text": "The 19th century called, they want your socialism back. >I bet neither the military, NASA, FDA or your local police station/firefighters aren't providing any usefullness... Let's see... * Military? - not sure what good I'm getting of some fucker in Afghanistan being killed * NASA - yes, I get value from that * FDA - ditto, but not that much * police - I'd rather get them reduced in size * firefighters - we need a lot of audits on the effectiveness of those When I buy a product from a private corporation, there are a lot of rosources that I can consult on the value they provide. I can choose between the different providers. When the government taxes me, I don't have a choice. I must pay the taxes no matter what. It'a a totally different situation.",
"title": ""
},
{
"docid": "327288",
"text": "This is going to be a list of some things that will likely be of value immediately after some apocalyptic event. However, note that I am not answering your question of what you should invest in now to take advantage of such an event. That is a pretty ridiculous notion. Preparing oneself for such a possibility is certainly a good idea. That said, there are some realistic limitations to how you could take advantage of such a situation. Namely, the very real requirement of physical security. Unless you have a huge posse -- armed to the teeth -- to defend your cache, someone will come along with a bigger and better armed group to take it. (Not to mention that I am the type of person that would -- at least -- consider organizing such a group to take you down; if only as a matter of principle.) Guns & ammo (Also, knives; ideally ones that can be used as weapons and for food preparation/hunting.) Alcohol. Especially liquor. It's concentrated and easier to store than beer or wine. Beside for getting inebriated, it is useful as a sedative and antiseptic. Non-perishable foods. Canned goods are obvious. Though, grains and cereals can be stored with relative ease under some circumstances. (Obviously, not so easily done in an urban area.) Methods of starting a fire. Preferably rugged ones, such as flint and steel. (Lighters would only be of limited use. Matches are bulky and require water-tight storage.) Salt and/or salt-licks. (Possibly, other forms of non-perishable bait.) As bstpierre puts it, hunting will be about survival not sport. Hand-tools. Textiles, fabrics, thread and needles. Medicines of all sorts, though especially antibiotics, antiseptics and painkillers. Books of a practical nature. Topics such as: wilderness survival, cooking, carpentry, etc. The list is mostly ordered in terms of value & practicality. Ultimately, I doubt there is much that will provide a practical investment idea for such a scenario. The physical security issue is a big limiting factor. In a post-apocalyptic scenario it goes back to who is bigger, stronger and better armed. One thing does come to mind: knowledge. Prepare yourself with the skills and knowledge you need to survive in such a scenario and you will be invaluable. Also, as bstpierre notes in the comments, connections will likely also be important. (Probably local or nearby connections.) No one person can do it all alone. It will come down to cooperation.",
"title": ""
},
{
"docid": "575834",
"text": "\"Suppose you have a bar of gold and are hungry. I buy the gold from you for cash, which you then use to buy food, clothes and generally support yourself. Would it be fair to say that I paid for your food, clothes etc? I don't think so - I think *you* paid for them, in gold. I facilitated the exchange of gold into money, and without me or someone like me around to provide liquidity for your gold, you'd still be hungry. But fundamentally, it was the gold that was valuable. Now, suppose there is a lack of liquidity in gold - there's a shortage of gold buyers. I take advantage of this distortion to offer to buy your gold for half its free market value. You don't want to accept this deal, but since your only alternative is starvation, you accept. I say this is wrong, not because of socialism, but because of capitalism. The efficiency of capitalism arises from the price system of value. Goods and services command a fair market price, and buyers and sellers have access to both liquidity and good information about the relative value of things. When distortions are allowed to interfere with free market pricing - as inevitably happens under lassiez-faire capitalism - this efficiency is lost. Good government regulation is necessary to keep markets free and efficient, and this is good for everyone. So what does this have to do with David Siegel? First, nothing in my example above changes when you substitute \"\"labor\"\" for \"\"gold.\"\" If I am hungry but I have a skill, and I sell you some of my labor for cash, then use the cash to buy food, *you did not give me the food*. You did not \"\"pay for my food,\"\" you did not \"\"make it possible for me to get food,\"\" or anything of the sort. *I paid for it myself*, by trading labor for cash in exactly the same way that you could trade gold for cash. Second, the price system of value allows you to earn a \"\"normal profit,\"\" which means sufficient profit for resources to remain within an industry. But \"\"excess profit\"\" harms market efficiency and thus the price system. This is pure capitalist theory, straight from Adam Smith; it is nothing to do with socialism or communism. It is quite clear that David Siegel is taking excess profit. This is no different from the sort of profiteering I described when there's only one gold dealer in town. It is parasitic behavior according to *capitalist* theory. And finally, David Siegel is the guy who invented high-pressure selling of timeshares by inviting familes to a \"\"free\"\" vacation, trapping them in a room, and basically holding them hostage until they sign on the dotted line. His business is near-criminal. You can argue that drug kingpins also create thousands of jobs - that doesn't make them good people, or their actions beneficial to society. I already thought David Siegel was a parasite on society before I ever heard of his opinion on Obama. And quite frankly, I'm shocked and appalled that people are actually defending him.\"",
"title": ""
},
{
"docid": "326329",
"text": "In the US we have social security taxes, where for a full time employee the company pays half and the employee pays half. When you work as a business, what we call 1099 for the form that the wages are reported on, then the contractor pays the full amount of social security tax. There are times when a contractor can negotiate a higher rate because the company does not have to pay that tax. However, most of the time the company just prefers to negotiate the rate based on your value. If you are a 60K year guy, then that is what they will pay you. From the company's perspective it does not matter what your tax rate is, only the value you can bring to the company. If you can add about 180K to the bottom line, then they will be happy to pay you 60K, and you should be happy to get it. Here in the US a contractor can expect to make about 7.5% more of an equivalent employee because of the social security tax savings to the company. However, not all companies are willing to provide that in compensation. Some companies see the legal and administrative costs of employees as normal, and the same costs with contractors as extra so they don't perceive a cost savings. There are other things that would preclude employers from giving the bump although it is logical to do so. First you will really have to feel out your employer for the attitude on the subject. Then I would make a logical case if they are open to providing extra compensation in return for tax savings. If I am an employee at 60K, you would also have to pay the government 18K. How about you pay me 75K as a contractor instead? That would be a great deal for all in the US.",
"title": ""
},
{
"docid": "471755",
"text": "\"You can pontificate about how life is so hard for her because shit costs money and you're right, she can't support herself and kids. However, that doesn't change the basic economic reality that working full time at Popeyes simply DOES NOT provide enough value to her employer and there are two many people with her very low skill set that she cannot command a higher wage. No amount of government programs will change that. Robbing the tax payers through welfare, killing businesses and destroying jobs by imposing a wage that simply is infeasible is counter productive, unsustainable, and simply misguided. Don't believe me? Ask the University of Washington who have the numbers on Seattle's ever escalating minimum wage and the effect on [jobs.] (http://www.zerohedge.com/news/2017-06-26/shocking-study-finds-seattle-min-wage-hikes-has-cost-works-14mm-hours-year-6700-jobs) This is, of course, assuming you care that people are being put out of work so a few can be paid a \"\"living wage\"\". Welfare is an endless tap of free money, [right?] (http://www.usdebtclock.org) The irony of your oh so well cited comment is that you didn't apply it to your own proposed solution of a minimum wage increase. [Here's](http://www.heritage.org/jobs-and-labor/report/higher-fast-food-wages-higher-fast-food-prices) a great analysis of effect of this change on consumer prices, how it affects the capital side of the equation of whether to operate a restaurant at all, and how a higher minimum wage impairs the creation of entry level jobs. Succinctly, minimum wage jobs were never meant to be able to support a family of three, no matter how much you wish it could. By creating artificially higher wages you'll get higher unemployment, more substitution of labor with more capital intensive solutions (ordering kiosks, etc), and higher taxes and consumer prices. Edit: Link B.S. Edit 2: **trigger warning** Also, it's a lot easier to raise kids with two working parents, that's just math for you. Talk about a bad personal choice that no one has touched on. Poor kids :(\"",
"title": ""
},
{
"docid": "390170",
"text": "We can support people incapable of or unwilling to support themselves without tampering with the labor market by setting an artificial wage floor. The real minimum wage is always 0. Any floor you set above that simply guarantees that someone not providing X dollars of value per hour to their employer will be unemployed.",
"title": ""
},
{
"docid": "81897",
"text": "\"I have to disagree with you. **Money is a store of value with which you can redeem your accumulated work for a good or service you need, at any time.** Therefore, you don't have to wait until your crop has perished to trade it for what you need. Any store of value that is not purely useful in terms of \"\"I can consume this\"\" or \"\"I can turn this into value directly through labor\"\" is essentially an IOU. It would be more accurate to say, in the context you provide, that for every asset (your apples) there exists an equivalent combination of liability (what you had to borrow to produce the apples) and equity (what you put in of your own in order to get the apples). Since gold in this very simple hypothetical system has absolutely no use other than a **store of value**, it *is* debt. It is the promise that you will at some point in your process of transactions acquire the utility that you require. You can't fertilize with gold, but you can buy fertilizer. **Until you buy that fertilizer, you've only traded your harvest for a promise that you *can* buy your fertilizer.** Something otherwiseyep didn't elaborate on very much, though he mentioned it and it is integral to his story, is the time value of money. That is, if I can borrow 10 gold pieces today for my future work accumulated, I'll pay you back 12 when it's done. This has an effect greater than just injecting value into the economy. It ensures that the negative value experienced by *not* having those 10 gold pieces will be compensated. Credit provides an opportunity for planning for the cyclical nature of markets. It provides an opportunity to make your transaction now - that you don't have to wait until harvest to trade your deer skins for apples. >Economists like Paul Krugman seem to believe that everything can be fixed by increasing demand, but they totally ignore the costs of production. There exists plenty of demand in the US economy right now, but the cooper has died, the barrels must be brought from China. I also disagree with this. Krugman emphasizes the *importance* of demand-side measures, not their exclusivity. Any policy must account for cost curves, and that economic profit for any firm is maximized when marginal revenue (the revenue increase or decrease of a single unit added to production) is equal to marginal cost. The U.S may have some demand right now, but if the cost of production were truly the issue, then these firms would be adjusting their capacity, and not sitting on trillions of dollars of currency that ought to be liquid. If demand was really that high, companies wouldn't be stuffing their mattresses right now to keep the money injected into the economy by QE *out* of circulation. The real problem is that while in the last few decades consumption has been climbing steadily, real wages have flat-lined, and now we have high unemployment. We can't raise wages, we can't hire more workers, and we still want our cars and houses and corn syrup and lead-filled toys. This, I think we can agree, is where credit goes wrong: the gap between consumption and wages was filled with credit. The housing bubble manifested itself thus: not as simply a boom in quantity and a lowering in price, but a lowering in price as a result of faulty (dishonest and misleading) risk assessment - (by the same folks who downgraded US debt), and an implosion as a result of that debt systematically dissolving through defaults and foreclosures (to put it very, very, very, simply). Instead of an increase in consumer credit, we need greater investment by the companies who currently sit on trillions of dollars of frozen cash. Those investments could be better managed, with transparent risk assessment and greater restrictions on lending policy. Or, ideally, that money could be used to hire workers, expand plants and lower marginal costs. To tie it back to your concluding paragraph, credit makes it possible to satisfy the demand for those barrels of apples by buying them at a fair market value from China. If it weren't for China's ability to provide the apples at a \"\"fair\"\" price (you can, for our purposes here, consider this price to be fair market value if you make a transaction - the selling price equals the buying price), there would be an apple shortage, and the price of apples would climb ridiculously high.\"",
"title": ""
},
{
"docid": "545735",
"text": "This is a super contentious topic but we have to have a floor wage because we don't have a free labor market. In order for the labor market to come up with a fair wage the market must be as close to de-regulated as possible. But we've already seen what happens in an unregulated (or low regulation) market - safety problems, child labor, abysmal wages. Just ready a history book to see how the US clamped down on sweat shops, child labor and the rise of the Unions. No one wants to work like that so we put regulations in place to fix those things. This is why we have safety laws and rules to prevent our employers from stealing wages due to filing a report late or other stupid excuse. So we make the work places safer, and put protections in to make sure people get paid. But now we created a wage floor. Businesses are literally designed to make profit and you make profit by trimming all your expenses as much as necessary. Skilled employees have an easier time negotiating wages and they can band together in unions. But low skilled and unskilled workers don't have this ability so they work for minimum wage. Now regardless of a company's ability to pay their workers $15/hr or not, if you create a wage floor than don't account for yearly COLA/inflation workers get left behind. Why does this matter? There is a strong relationship between crime and poverty. So we decide to create social programs to keep crime down. But as the wage floor is not increased, min wage workers require more government subsidy. Either companies pay their employees enough where full time workers don't qualify for government subsidy or the government/tax payer ends up picking up the tab on behalf of these companies. You can't actually quantify the relationship between min wage and labor because it's not just a labor issue. It impacts crime, health (who has the ability to pay a $30 co pay if you're chronically ill on min wage?), and government social welfare on local,state and federal levels. We can't just demand that unskilled labors get skills so they get more money because that will end up devaluing skilled positions. Right now people argue that skilled positions are devalued when min wage increases. And that's true only if your employer fails to provide a like increase.",
"title": ""
},
{
"docid": "1873",
"text": "\"I expect the company wanted to pay you for a product (on a purchase order) rather than as a contract laborer. Whatever. Would they be willing to re-issue the check to you as a sole proprietor of a business named ABC Consulting (or anything like that)? You can register your sole proprietor business with the state using a \"\"Doing Business As\"\" (DBA, or fictitious name), and then open the bank account for your business using the check provided by the customer as the first deposit. (There is likely a smaller registration fee for the DBA.) If they won't re-issue the check and you have to go the LLC route... Scrounge up $125 doing odd jobs or borrowing from a friend or parents. Seriously, anyone can earn that amount of money in a week or two. Besides the filing fee for the LLC, your bank may require you to provide an Operating Agreement (which is not required by the State). The Operating Agreement can be simple, or more complex if you have a partner (even if it's a spouse). If you do have a partner, it is essential to have such an agreement because it would specify the responsibilities and benefits allocated to each partner, particularly in the event of equity distributions (taking money out of the business, or liquidating and ending the LLC). There are websites that will provide you a boilerplate form for Operating Agreements. But if your business is anything more than just single member LLC, you should pay an attorney to draw one up for you so the wording is right. It's a safeguard against potential future lawsuits. And, while we're at it, don't forget to obtain a EIN (equivalent to a SSN) from the IRS for your LLC. There's no cost, but you'll have to have it to file taxes as a business for every year the LLC exists and has income. Good luck!\"",
"title": ""
},
{
"docid": "568771",
"text": "Not as you suggest. Since you are sole prop, you are taxed on a cash basis. Within reason, you can prepay vendors - so temp to hire through an agency might appear more attractive than direct hire. But there needs to be a justification other than avoidance of taxes. So pre-paying 100k on 12/25 would look fishy as fuck. Plus your quality of candidate will suffer if you need anything other than low skill labor. Look at your other fully deductible expenses - anything you can prepay-prepay. For example, I set my liability insurance renewal January 15 to provide optionality. But it just shifts one year into another .. Means fuckall if you are in the same marginal bracket next year. The IRS has also relaxed depreciation on office technology. Computers are now fully deductible rather than being capitalized. @ 500k revenue you should have a CPA and legal counsel. Simply incorporating isn't tax magic. The purpose is to limit yourersonal liability, not a tax shelter - but shitty things happen once you have employees, don't create the potential for a disgruntled employee lawsuit put your shelter at risk of court judgment. That said, assuming you aren't dumping a hypothetical on the Internet, congrats - for all the headaches, having employees is the ultimate leverage .. it's like a xerox machine for your labor (including loss of fidelity with each copy) ..",
"title": ""
},
{
"docid": "440522",
"text": "Understandably, it appears as if one must construct the flows oneself because of the work involved to include every loan variation. First, it would be best to distinguish between cash and accrued, otherwise known as the economic, costs. The cash cost is, as you've identified, the payment. This is a reality for cash management, and it's wise that you wish to track it. However, by accruals, the only economic cost involved in the payment is the interest. The reason is because the rest of the payment flows from one form of asset to another, so if out of a $1,000 payment, $100 is principal repayment, you have merely traded $100 of cash for $100 of house. The cash costs will be accounted for on the cash flow statement while the accrued or economic costs will be accounted on the income statement. It appears as if you've accounted for this properly. However, for the resolution that you desire, the accounts must first flow through the income statement followed next instead of directly from assets to liabilities. This is where you can get a sense of the true costs of the home. To get better accrual resolution, credit cash and debit mortgage interest expense & principal repayment. Book the mortgage interest expense on the income statement and then cancel the principal repayment account with the loan account. The principal repayment should not be treated as an expense; however, the cash payment that pays down the mortgage balance should be booked so that it will appear on the cash flow statement. Because you weren't doing this before, and you were debiting the entire payment off of the loan, you should probably notice your booked loan account diverging from the actual. This proper booking will resolve that. When you are comfortable with booking the payments, you can book unrealized gains and losses by marking the house to market in this statement to get a better understanding of your financial position. The cash flow statement with proper bookings should show how the cash has flowed, so if it is according to standards, household operations should show a positive flow from labor/investments less the amount of interest expense while financing will show a negative flow from principal repayment. Investing due to the home should show no change due to mortgage payments because the house has already been acquired, thus there was a large outflow when cash was paid to acquire the home. The program should give some way to classify accounts so that they are either operational, investing, or financing. All income & expenses are operational. All investments such as equities, credit assets, and the home are investing. All liabilities are financing. To book the installment payment $X which consists of $Y in interest and $Z in principal: To resolve the reduction in principal: As long as the accounts are properly classified, GnuCash probably does the rest for you, but if not, to resolve the expense: Finally, net income is resolved: My guess is that GnuCash derives the cash flow statement indirectly, but you can do the entry by simply: In this case, it happily resembles the first accrued entry, but with cash, that's all that is necessary by the direct method.",
"title": ""
},
{
"docid": "366284",
"text": "\"I'll concede that you're probably speaking in good faith- I genuinely believe that you're original statement was one that meant to point out that the ruling class seek to squeeze all the value they can out of being the ruling class, which includes maximizing the size of the rest of the population to drive down wages and get the most labor out of payrolls as possible to maximize profit. I can concede that completely and never suspected that you felt otherwise. That said, \"\"reasonable\"\" people are often unequipped to deal with extreme or academic scenarios using reason alone. My entire point of digression came from the use of the term \"\"commodity,\"\" as it refers to things of value who's value arises from their ability to be traded at a profit. Your statement regarding people fitting this definition was true in the time of feudalism- pushing that definition back to the idea that the labor of people was tradable (but people owned themselves) was a major improvement in human rights (happening for different people at different points in history). I drew a point of contention because it's an *important* and *historical* point of contention that should never slip backwards ever, without being pointed out.\"",
"title": ""
},
{
"docid": "391353",
"text": "\"> they find that it is in-line with the 91.8% increase of unemployment rate vs. working age adults. I have another problem with this number. It comes from this statement: \"\"Between October 2008 and July 2014 the working age population grew by 13.4 million persons, but the US labor force grew by only 1.1 million\"\" You can get the labor force by adding two series, LNU01074597 (Civilian Labor Force - With a disability, 16 years and over) and LNU01074593 (Civilian Labor Force - With no disability, 16 years and over). In Oct 2008, the numbers are 6,284 and 148,728, for a total of 155,012. (all values are in thousands) In July 2104, they are 5,648 and 151,924, for a total of 157,572. That's an increase of 2,560. So the labor force grew by 2.56 million, not 1.1. I think they are computing a meaningless number but they're not even using the right numbers as input.\"",
"title": ""
},
{
"docid": "35856",
"text": "\"What do you think the problem is? I notice you edited your post after I read it. >The \"\"value\"\" of HUMAN labor is determined by supply and demand, right? I hire people right now because they are the cheapest supercomputers with arms available for me right now. No, you hire people because they have skills to do tasks with their labor. We will *always* think of new ways to be useful, new things to do, that people will want done, will value being done, and will purchase labor to get done. When we stopped using horses & buggies, all the people in those industries didn't just throw up their hands and walk away from work. *They figured out new ways to create value with their labor*, and the world went on.\"",
"title": ""
},
{
"docid": "265253",
"text": ">The labor theories of value (LTV) are heterodox economic theories of value which argue that the value of a commodity is related to the labor needed to produce or obtain that commodity. (Wikipedia) Note that it does not say that value is always _directly proportional_ to the labor needed, only that the labor needed is _related_ to the value. Ergo: labor does not _create_ value automatically, but value (when existing) is determined by labor, because someone will demand more for something that takes a lot of effort and/or time to create.",
"title": ""
},
{
"docid": "24494",
"text": "I think your right that these people don't have zero bargaining power, but even with everything you've listed, they still don't have much. The difficult thing we have to deal with as a society is that some portion of our population isn't capable of or willing to provide enough value in the labor market to support themselves sufficiently. Personally I think the solution to that is more MGI or UBI. Tampering with the market price for labor just creates an artificial floor that leaves the least skilled earning the real minimum wage, which is always zero.",
"title": ""
},
{
"docid": "282987",
"text": "I think playing certain kinds of lottery is as economically sound as buying certain kinds of insurance. A lottery is an inverted insurance. Let me elaborate. We buy insurance for at least two reasons. The first one is clear: We pay a fee to protect ourselves from a risk which we don't want to (or cannot) bear. Although on average buying insurance is a loss, because we pay all the insurance's office buildings and employee's salaries, it still is a reasonable thing to do. (But it should also be clear that it is unreasonable to buy insurance for risks one could easily bear oneself.) The second reason to buy insurance is that it puts us at ease. We don't have to be afraid of theft or of a mistake we make which would make us liable or of water damage to our house. In that sense we buy freedom of sorrow for a fee, even if the damage wouldn't in fact ruin us. That's totally legitimate. Now I want to make the argument that buying a lottery ticket follows the same logic and is therefore not economically unreasonable at all. While buying a lottery ticket is on average a loss, it provides us with a chance to obtain an amount of money we would normally never get. (Eric Lippert made this argument already.) The lottery fee buys us a small chance of something very valuable, much as the insurance frees us from a small risk of something very bad. If we don't buy the ticket, we may have 0% chance of becoming (extremely) rich. If we buy one, we clearly have a chance > 0%, which can be considered an improvement. (Imagine you'd have a 0.0000001% chance to save the life of a loved one with a ticket who'd be 100% doomed otherwise. You'd bite.) Even the second argument, that an insurance puts us at ease, can be mirrored for lotteries. The chance to win something may provide entertainment in our otherwise dull everyday life. Considering that playing the lottery only makes sense for the chance to obtain more money than otherwise possible, one should avoid lotteries which have lots of smaller prizes because we are not really interested in those. (It would be more economical to save the money for smaller amounts.) We ideally only want lotteries which lean on the big money prizes.",
"title": ""
},
{
"docid": "265747",
"text": "\"These services and other employee perks are referred to as fringe benefits. An employee \"\"fringe benefit\"\" is a form of pay other than money for the performance of services by employees. Any fringe benefit provided to an employee is taxable income for that person unless the tax law specifically excludes it from taxation. One example of taxable fringe benefit is award/prize money (to prevent someone from \"\"winning\"\" most of their salary tax-free.) Cash awards are taxable unless given to charity. Non-cash awards are taxable unless nominal in value or given to charity. A less intuitive example is clothing. Clothing given to employees that is suitable for street wear is a taxable fringe benefit. Your example possibly fits under de minims (low-cost) fringe benefits such as low-value birthday or holiday gifts, event tickets, traditional awards (such as a retirement gift), other special occasion gifts, and coffee and soft drinks working condition fringe benefits--that is, property and services provided to an employee so that the employee can perform his or her job. Note that \"\"cafeteria plans\"\" in the source don't refer to cafeteria but allow employee choice between benefit options available.\"",
"title": ""
},
{
"docid": "526823",
"text": "\"Stocks, as an asset, represent the sum of the current market value of all of your holdings. If your portfolio is showing unrealized gains and losses, then that net amount is inherently reflected in the current market value of your holdings. That's not to say cost basis is not important. Any closed trades, realized gains or losses, will of course have an impact on your taxable income. So, it couldn't hurt to keep track of your cost basis from a tax standpoint, but understand that the term \"\"asset\"\" refers to the current market values and does not consider base amounts. Taxes do. Perhaps consider making separate cells for cost basis, but also bear in mind that most if not all of the major online discount brokers will provide transferring of cost basis information electronically to the major online tax service providers.\"",
"title": ""
},
{
"docid": "11557",
"text": "Where are you operating your business and how is it structured? DBA, LLC? How do you plan on taxing the business? You can purchase whatever hardware you want and resale at whatever price you want. You may be able to contact a vendor and open a dealer account. This means they'll will give you a price break if you purchase X amount of volume but this may require more upfront capital. Warranty will probably be best to be done under your name. Most manufacture warranties require proof of purchase from an approved vendor. If you're buying and reselling at a higher cost then the original receipt will show your profits. Likewise, you can sale the hardware at cost and make all your money on labor. This would allow you to pass the warranty responsibility to the customer. Depending on the customer’s site you may have to mount your routers, repeaters and access points in hard to reach places. The customer might prefer to call you and have you take care of it from there. The way I would do it structure the installations by square footage and predicted users. The greater the square footage the more hardware you’ll need. Offer a remote support plan at a reasonable rate. For 20/month you will provide tear 1 support which can include troubleshooting dead access points remotely, changing network names, and providing up to X amount of network reports. ( Ubiquiti offers network monitoring for free in their suite. You would just be interpreting this information) For issues that require you to come to site you can charge X amount of dollars per visit plus parts and labor. I would offer on the spot replacement for hardware under warranty for a very small fee and then you can ship off the defective hardware and have it replaced. If you do purchase with amazon I know they offer extended plans on a lot of their electronics. It would be worth considering these plans and adding the cost to the hardware you’re reselling. Most of these plans simply write you a check for defective hardware after you ship them in. I would highly suggest going with a business structure that protects your personal assets such as an LLC. I recommend this because you will be proving a service to other people and you may be blamed for damages. If you are found to be at fault they company takes the hit, not you. edit: Also, you can take advantage of amazon's two day shipping. When a customer contracts you for a job simply ask for 50% deposit and a 4 day notice. When you receive the deposit place the order on amazon for the hardware. This will mean less money out of your pocket.",
"title": ""
},
{
"docid": "290862",
"text": "My basic rule of thumb is that if the the bill come from a government office of taxation, and that if you fail to pay the amount they can put a tax lien on the property it is a tax. for you the complication is in Pub530: Assessments for local benefits. You cannot deduct amounts you pay for local benefits that tend to increase the value of your property. Local benefits include the construction of streets, sidewalks, or water and sewer systems. You must add these amounts to the basis of your property. You can, however, deduct assessments (or taxes) for local benefits if they are for maintenance, repair, or interest charges related to those benefits. An example is a charge to repair an existing sidewalk and any interest included in that charge. If only a part of the assessment is for maintenance, repair, or interest charges, you must be able to show the amount of that part to claim the deduction. If you cannot show what part of the assessment is for maintenance, repair, or interest charges, you cannot deduct any of it. An assessment for a local benefit may be listed as an item in your real estate tax bill. If so, use the rules in this section to find how much of it, if any, you can deduct. I have never seen a tax bill that said this amount is for new streets, and the rest i for things the IRS says you can deduct. The issue is that if the Center City tax bill is a separate line or a separate bill then does it count. I would go back to the first line of the quote from Pub 530: You cannot deduct amounts you pay for local benefits that tend to increase the value of your property. Then I would look at the quote from the CCD web site: The Center City District (CCD) is a business improvement district. Our mission is to keep Philadelphia's downtown, called Center City, clean, safe, beautiful and fun. We provide security, cleaning and promotional services that supplement, but do not replace, basic services provided by the City of Philadelphia and the fundamental responsibilities of property owners. CCD also makes physical improvements to the downtown, installing and maintaining lighting, > signs, banners, trees and landscape elements. and later on the same page: CCD directly bills and collects mandatory payments from properties in the district. CCD also receives voluntary contributions from the owners of tax-exempt properties that benefit from our services. The issues is that it is a business improvement district (BID), and you aren't a business: I did find this document from the city of Philadelphia explain how to establish a BID: If the nature of the BID is such that organizers wish to include residential properties within the district and make these properties subject to the assessment, it may make sense to assess these properties at a lower level than a commercial property, both because BID services and benefits are business-focused, and because owner-occupants often cannot treat NID assessments as tax-deductible business expenses, like commercial owners do. Care must be taken to ensure that the difference in commercial and residential assessment rates is equitable, and complies with the requirements of the CEIA. from the same document: Funds for BID programs and services are generated from a special assessment paid by the benefited property owners directly to the organization that manages the BID’s activities. (Note: many leases have a clause that allows property owners to pass the BID assessment on to their tenants.) Because they are authorized by the City of Philadelphia, the assessment levied by the BID becomes a legal obligation of the property owner and failure to pay can result in the filing of a lien. I have seen discussion that some BIDS can accept tax deductible donations. This means if a person itemizes they can deduct the donation. I would then feel comfortable deducting the tax because: If you can't deduct it that would mean the only people who can't deduct it are home owners. So deduct it. (keep in mind I am not a tax professional)",
"title": ""
}
] |
10406
|
Can you use external money to pay trading commissions in tax-free and tax-deferred accounts?
|
[
{
"docid": "569953",
"text": "According to Publication 590, broker's commissions for stock transactions within an IRA cannot be paid in addition to the IRA contribution(s), but they are deductible as part of the contribution, or add to the basis if you are making a nondeductible contribution to a Traditional IRA. (Top of Page 10, and Page 12, column 1, in the 2012 edition of Pub 590). On the other hand, trustees' administrative fees can be paid from outside the IRA if they are billed separately, and are even deductible as a Miscellaneous Deduction on Schedule A of your income tax return (subject to the 2% of AGI threshold). A long time ago, when my IRA account balances were much smaller, I used to get a bill from my IRA custodian for a $20 annual administrative fee which I paid separately (but never got to deduct due to the 2% threshold). My custodian also allowed the option of doing nothing in which case the $20 would be collected from (and thus reduce) the amount of money in my IRA. Note that this does not apply to the expenses charged by the mutual funds that you might have in your IRA; these expenses are treated the same as brokerage commissions and must be paid from within the IRA.",
"title": ""
},
{
"docid": "361639",
"text": "Nice idea. When I started my IRAs, I considered this as well, and the answer from the broker was that this was not permitted. And, aside from transfers from other IRAs or retirement accounts, you can't 'deposit' shares to the IRA, only cash.",
"title": ""
}
] |
[
{
"docid": "308150",
"text": "\"If I understand correctly, the Traditional IRA, if you have 401k with an employer already, has the following features: Actually, #1 and #2 are characteristics of Roth IRAs, not Traditional IRAs. Only #3 is a characteristic of a Traditional IRA. Whether you have a 401(k) with your employer or not makes absolutely no difference in how your IRAs are taxed for the vast majority of people. (The rules for IRAs are different if you have a very high income, though). You're allowed to have and contribute to both kinds of accounts. (In fact, I personally have both). Traditional IRAs are tax deferred (not tax-free as people sometimes mistakenly call them - they're very different), meaning that you don't have to pay taxes on the contributions or profits you make inside the account (e.g. from dividends, interest, profits from stock you sell, etc.). Rather, you pay taxes on any money you withdraw. For Roth IRAs, the contributions are taxed, but you never have to pay taxes on the money inside the account again. That means that any money you get over and above the contributions (e.g. through interest, trading profits, dividends, etc.) are genuinely tax-free. Also, if you leave any of the money to people, they don't have to pay any taxes, either. Important point: There are no tax-free retirement accounts in the U.S. The distinction between different kinds of IRAs basically boils down to \"\"pay now or pay later.\"\" Many people make expensive mistakes in their retirement strategy by not understanding that point. Please note that this applies equally to Traditional and Roth 401(k)s as well. You can have Roth 401(k)s and Traditional 401(k)s just like you can have Roth IRAs and Traditional IRAs. The same terminology and logic applies to both kinds of accounts. As far as I know, there aren't major differences tax-wise between them, with two exceptions - you're allowed to contribute more money to a 401(k) per year, and you're allowed to have a 401(k) even if you have a high income. (By way of contrast, people with very high incomes generally aren't allowed to open IRAs). A primary advantage of a Traditional IRA is that you can (in theory, at least) afford to contribute more money to it due to the tax break you're getting. Also, you can defer taxes on any profits you make (e.g. through dividends or selling stock at a profit), so you can grow your money faster.\"",
"title": ""
},
{
"docid": "350082",
"text": "I know of no way to answer your question without 'spamming' a particular investment. First off, if you are a USA citizen, max out your 401-K. Whatever your employer matches will be an immediate boost to your investment. Secondly, you want your our gains to be tax deferred. A 401-K is tax deferred as well as a traditional IRA. Thirdly, you probably want the safety of diversification. You achieve this by buying an ETF (or mutual fund) that then buys individual stocks. Now for the recommendation that may be called spamming by others : As REITs pass the tax liability on to you, and as an IRA is tax deferred, you can get stellar returns by buying a mREIT ETF. To get you started here are five: mREITs Lastly, avoid commissions by having your dividends automatically reinvested by using that feature at Scottrade. You will have to pay commissions on new purchases but your purchases from your dividend Reinvestment will be commission free. Edit: Taking my own advice I just entered orders to liquidate some positions so I would have the $ on hand to buy into MORL and get some of that sweet 29% dividend return.",
"title": ""
},
{
"docid": "51086",
"text": "\"The primary tax-sheltered investing vehicles in Canada include: The RRSP. You can contribute up to 18% of your prior year's earned income, up to a limit ($24,930 in 2015, plus past unused contribution allowance) and receive an income tax deduction for your contributions. In an RRSP, investments grow on a tax-deferred basis. No tax is due until you begin withdrawals. When you withdraw funds, the withdrawn amount will be taxed at marginal income tax rates in effect at that time. The RRSP is similar to the U.S. \"\"traditional\"\" IRA, being an individual account with pre-tax contributions, tax-deferred growth, and ordinary tax rates applied to withdrawals. Yet, RRSPs have contribution limits higher than IRAs; higher, even, than U.S. 401(k) employee contribution limits. But, the RRSP is dissimilar to the IRA and 401(k) since an individual's annual contribution allowance isn't use-it-or-lose-it—unused allowance accumulates. The TFSA. Once you turn 18, you can put in up to $5,500 each year, irrespective of earned income. Like the RRSP, contribution room accumulates. If you were 18 in 2009 (when TFSAs were introduced) you'd be able to contribute $36,500 if you'd never contributed to one before. Unlike the RRSP, contributions to a TFSA are made on an after-tax basis and you pay no tax when you withdraw money. The post-tax nature of the TFSA and completely tax-free withdrawals makes them comparable to Roth-type accounts in the U.S.; i.e. while you won't get a tax deduction for contributing, you won't pay tax on earnings when withdrawn. Yet, unlike U.S. Roth-type accounts, you are not required to use the TFSA strictly for retirement savings—there is no penalty for pre-retirement withdrawal of TFSA funds. There are also employer-sponsored defined benefit (DB) and defined contribution (DC) retirement pension plans. Generally, employees who participate in these kinds of plans have their annual RRSP contribution limits reduced. I won't comment on these kinds of plans other than to say they exist and if your employer has one, check it out—many employees lose out on free money by not participating. The under-appreciated RESP. Typically used for education savings. A lifetime $50,000 contribution limit per beneficiary, and you can put that all in at once if you're not concerned about maximizing grants (see below). No tax deduction for contributions, but investments grow on a tax-deferred basis. Original contributions can be withdrawn tax-free. Qualified educational withdrawals of earnings are taxed as regular income in the hands of the beneficiary. An RESP beneficiary is typically a child, and in a child's case the Canadian federal government provides matching grant money (called CESG) of 20% on the first $2500 contributed each year, up to age 18, to a lifetime maximum of $7200 per beneficiary. Grant money is subject to additional conditions for withdrawal. While RESPs are typically used to save for a child's future education, there's nothing stopping an adult from opening an RESP for himself. If you've never had one, you can deposit $50,000 of after-tax money to grow on a tax-deferred basis for up to 36 years ... as far as I understand. An adult RESP will not qualify for CESG. Moreover, if you use the RESP strictly as a tax shelter and don't make qualified educational withdrawals when the time comes, your original contributions still come out free of tax but you'll pay ordinary income tax plus 20% additional tax on the earnings portion. That's the \"\"catch\"\"*. *However, if at that time you have accumulated sufficient RRSP contribution room, you may move up to $50,000 of your RESP earnings into your RRSP without any tax consequences (i.e. also avoiding the 20% additional tax) at time of transfer. Perhaps there's something above you haven't considered. Still, be sure to do your own due diligence and to consult a qualified, experienced, and conflict-free financial advisor for advice particular to your own situation.\"",
"title": ""
},
{
"docid": "109540",
"text": "Guaranteed 8.2% annual return sounds too good to be true. Am I right? Are there likely high fees, etc.? You're right. Guaranteed annual return is impossible, especially when you're talking about investments for such a long period of time. Ponzi (and Madoff) schemed their investors using promises of guaranteed return (see this note in Wikipedia: In some cases returns were allegedly determined before the account was even opened.[72]). Her financial advisor doesn't charge by the hour--he takes a commission. So there's obviously some incentive to sell her things, even if she may not need them. Definitely not a good sign, if the advisor gets a commission from the sale then he's obviously not an advisor but a sales person. The problem with this kind of investment is that it is very complex, and it is very hard to track. The commission to the broker makes it hard to evaluate returns (you pay 10% upfront, and it takes awhile to just get that money back, before even getting any profits), and since you're only able to withdraw in 20 years or so - there's no real way to know if something wrong, until you get there and discover that oops- no money! Also, many annuity funds (if not all) limit withdrawals to a long period, i.e.: you cannot touch money for like 10 years from investment (regardless of the tax issues, the tax deferred investment can be rolled over to another tax deferred account, but in this case - you can't). I suggest you getting your own financial advisor (that will work for you) to look over the details, and talk to your mother if it is really a scam.",
"title": ""
},
{
"docid": "11998",
"text": "\"I have a couple other important considerations regarding external HSA accounts vs employer sponsored HSA accounts. Depending on your personal financial situation and goals; some people like to use HSA accounts as an extra retirement account (since the money can be withdrawn penalty free in retirement for non-medical expenses, and completely tax & penalty free at any time for medical expenses). If your intended use for the HSA account is an investment vehicle for retirement, then you may find more use/benefit out of an external provider that may provide more or better investment options than your employers HSA investment options. There can be a lot of additional value in those extra investment options over greater periods of time. Another VERY important consideration for FICA taxes (FICA includes Social Security & Medicare) that I don't believe was mentioned before - for those earners who are under the maximum social security wage limit, you are paying 6.2% of each paycheck into social security taxes. As others have mentioned you can \"\"save\"\" this tax through your employer’s plan if you set up the account to be funded pre-tax from your paychecks. However, in doing so, you are lowering your overall contributions into social security, which may lower your social security benefits in your retirement years! If this is ultimately going to lower your SSA benefits in retirement then that is a big future cost that may steer you against the pre-tax employer contributions. Think of social security as part of your retirement plan, not as a tax but instead as an additional check you put away for yourself for retirement every month. Of course, this is only an important consideration if SSA is still going to be around when you retire, but let's assume that it will be. This is not an issue for higher earners, earning well above the max SSA taxable wages. There is no wage limit on the 1.45% Medicare tax withholding's, and there is certainly no harm in saving Medicare taxes because it will not affect future Medicare benefits. So for taxpayers earning well over the max SSA wages, they will just save the 1.45% Medicare taxes without affecting their SSA contributions and resulting retirement benefits. So again, it all comes down to personal situations. Depending on your earnings and goals, employer plan may or may not be the way to go. Personally, for my lower earning clients, friends and family, I tend to recommend that they do whatever they can to maximize their social security benefits in retirement. So I would advise them to either use the external provider account, or the employer plan but with post-tax contributions so you don't lower the SSA withholding's but can still claim the income tax deduction on your tax return. YMMV -Dan\"",
"title": ""
},
{
"docid": "359515",
"text": "A 401-K is something you get through an employer. I recommend getting a self-directed IRA. You can open an IRA with Scottrade with $500 The money you put into an IRA is tax deferred, meaning that you do not have to pay taxes on profits. It may also lower your tax liability. Scottrade has a feature to automatically reinvest any dividends from the securities you own. This feature allows you to avoid commissions on those automatic purchases. Don't try to time the market. Pick a good ETF (exchange traded fund) that pays dividends. It will give you diversification. Avoid the urge to buy and sell constantly. This only gives commissions to the broker.",
"title": ""
},
{
"docid": "587768",
"text": "4.7 is a pretty low rate, especially if you are deducting that from your taxes. If you reduce the number by your marginal tax rate to get the real cost of the money you end up with a number that isn't far off from inflation, and also represents a pretty low 'yield' in terms of paying off the loan early. (e.g. if your marginal tax rate is 28%, then the net you are paying in interest after the tax deduction is 4.7 * .72 = 3.384) While I'm all for paying off loans with higher rates (since it's in effect the same as making that much risk free on the money) it doesn't make a lot of sense when you are down at 3.4 unless there is a strong 'security factor' (which really makes a difference to some folks) to be had that really helps you sleep at night. (to be realistic, for some folks close to retirement, there can be a lot to be said for the security of not having to worry about house payments, although you don't seem to be in that situation yet) As others have said, first make sure you have enough liquid 'emergency money' in something like a money market account, or a ladder of short term CD's If you are sure that the sprouts will be going to college, then there's a lot to be said for kicking a decent amount into a 529, Coverdell ESA (Educational Savings Account), uniform gift to minors account, or some combination of those. I'm not sure if any of those plans can be used for a kid that has not been born yet however. I'd recommend http://www.savingforcollege.com as a good starting point to get more information on your various options. As with retirement savings, money put in earlier has a lot more 'power' over the final balance due to compounding interest, so there's a lot to be said for starting early, although depending on what it takes to qualify for the plans there could be such a thing as too early ;-) ). There's nothing wrong with Managed mutual funds as long as the fund objective and investing style is in alignment with your objectives and risk tolerance; The fund is giving you a good return relative to the market as a whole; You are not paying high fees or load charges; You are not losing a lot to taxes. I would always look at the return after expenses when comparing to other options, and if the money is not in a tax deferred account, also look at what sort of tax burden you will be faced with. A fund that trades a lot will generate more short term gains which means more taxes than compared to a more passive fund. Anything lost to taxes is money lost to you so needs to come out of the total return when you calculate that. Sometimes such funds are better off as a choice inside an IRA or 401K, and you can instead use more tax efficient vehicles for money where you have to pay the taxes every year on the gains. The reason a lot of folks like index funds better is that: Given your described age, it's not appropriate now, but in the long run as you get closer to retirement, you may want to start looking at building up some investments that are geared more towards generating income, such as bonds, or depending on taxes where you live, Municipal bonds. In any case, the more money you can set aside for retirement now, both inside and outside of tax deferred accounts, the sooner you will get to the point of the 'critical mass' you need to retire, at that point you can work because you want to, not because you have to.",
"title": ""
},
{
"docid": "318338",
"text": "\"Assuming that the will that bequeathed the money to your son did not stipulate any restrictions or set up a trust to hold the money until your son turns 25, or something like that, I don't think you have much choice except to put the money in a UTMA account (which of course can be invested in whatever the trustee (which could be you, or you and your wife jointly) decides. Note: not a UGMA account since the money is not a gift. You also don't have any option except to turn the account over to your son when he turns eighteen. The point is, the investment can be in anything as long as the account is registered as a UTMA account. But do remember also that your son is entitled to sue you for breach of fiduciary duty if you don't take good care of the money, so that blowing it all in risky investments is also not a good idea. If you are worried about taxes and your son's income being taxed at your rate, one way of deferring the issue is to buy US Savings Bonds. The interest can be deferred from taxation until the bonds are redeemed. Edit added in response to JoeTaxpayer's comments: But a better strategy is to declare the accrued interest each year as unearned income of the child on the kiddie tax form that is part of your tax return, and pay the tax, if any, that results To ease your mind or conscience, think of the tax that you pay on your child's behalf as a gift to your child! In any case, there will likely not be much tax due since the first $950 of unearned income of a child is tax-free and the next $950 taxed at 10%. Then, when the bonds are cashed in, the interest that accrued (and was \"\"taxed\"\") in earlier years can be deducted from the interest (cash in price minus purchase price) that you (or your son) will be told is the interest that the bonds earned. Of course, if kiddie tax is not a concern (and it shouldn't be, given the amount available for investment), an even better strategy is to set up the UTMA account(s) in long-term investments in low-cost index funds or ETFs (as JoeTaxpayer suggests) and pay the tax, if any, as it comes due.\"",
"title": ""
},
{
"docid": "264023",
"text": "\"when you contribute to a 401k, you get to invest pre-tax money. that means part of it (e.g. 25%) is money you would otherwise have to pay in taxes (deferred money) and the rest (e.g. 75%) is money you could otherwise invest (base money). growth in the 401k is essentially tax free because the taxes on the growth of the base money are paid for by the growth in the deferred portion. that is of course assuming the same marginal tax rate both now and when you withdraw the money. if your marginal tax rate is lower in retirement than it is now, you would save even more money using a traditional 401k or ira. an alternative is to invest in a roth account (401k or ira). in which case the money goes in after tax and the growth is untaxed. this would be advantageous if you expect to have a higher marginal tax rate during retirement. moreover, it reduces tax risk, which could give you peace of mind considering u.s. marginal tax rates were over 90% in the 1940's. a roth could also be advantageous if you hit the contribution limits since the contributions are after-tax and therefore more valuable. lastly, contributions to a roth account can be withdrawn at any time tax and penalty free. however, the growth in a roth account is basically stuck there until you turn 60. unlike a traditional ira/401k where you can take early retirement with a SEPP plan. another alternative is to invest the money in a normal taxed account. the advantage of this approach is that the money is available to you whenever you need it rather than waiting until you retire. also, investment losses can be deducted from earned income (e.g. 15-25%), while gains can be taxed at the long term capital gains rate (e.g. 0-15%). the upshot being that even if you make money over the course of several years, you can actually realize negative taxes by taking gains and losses in different tax years. finally, when you decide to retire you might end up paying 0% taxes on your long term capital gains if your income is low enough (currently ~50k$/yr for a single person). the biggest limitation of this strategy is that losses are limited to 3k$ per year. also, this strategy works best when you invest in individual stocks rather than mutual funds, increasing volatility (aka risk). lastly, this makes filing your taxes more complicated since you need to report every purchase and sale and watch out for the \"\"wash sale\"\" rules. side note: you should contribute enough to get all the 401k matching your employer offers. even if you cash out the whole account when you want the money, the matching (typically 50%-200%) should exceed the 10% early withdrawal penalty.\"",
"title": ""
},
{
"docid": "388145",
"text": "Yes, absolutely. The HSA, when used for medical expenses, allows you to essentially pay for your medical expenses tax free. Even if you don't have extra room in your budget, you can fund the HSA as you incur medical expenses, then withdraw money to pay the expenses, and you'll see an immediate tax benefit at tax time. However, let's say that you have plenty of room in your budget and you don't have a lot of medical expenses. You already contribute the maximum to your 401(k) or IRA, and you want to do more. The HSA acts like a retirement account in this case, allowing you to contribute before-tax money and let it grow untaxed. The HSA does have a huge benefit that no other retirement account has. If you choose not to reimburse yourself for medical expenses, but you keep track of the unreimbursed expenses you incur, then you can reimburse yourself for these expenses at any point in the future completely tax free. Essentially, your contributions are treated like a traditional IRA, but your withdrawals are treated like a Roth IRA, and can be done at any age. If you don't acquire enough medical expenses, you can still withdraw whatever is left at age 65 and those withdrawals will be taxed like a traditional IRA. The HSA provides for tax-free contributions and growth if used for medical expenses, and tax-deferred growth if withdrawn after age 65 without medical expenses.",
"title": ""
},
{
"docid": "329596",
"text": "\"tl;dr Roth earnings are not necessarily \"\"tax deferred\"\", but they might be. This is a great question because IMHO, the use of the wording \"\"tax deferred\"\" is slightly misleading when talking about a Roth IRA (and Roth 401k too). The phrase \"\"tax deferred\"\" actually means you save tax now and you pay tax later, i.e. you \"\"defer\"\" the tax. As you pointed out, this is the normal terminology used for describing a Traditional IRA/401k. Earnings on a Roth IRA are tax free (not deferred), but only if your distributions are qualified. For the most part distributions are considered qualified if you wait until you are 59.5 years old before taking the money out, but there are some exceptions. If you choose to distribute more than your contributions, meaning you are now taking out earnings, the earnings are tax free only if your distribution is qualified. For example, if you take out the earnings before you are 59.5 (and no other exceptions apply), then you would pay tax on the earnings and also a 10% penalty. So, perhaps a better way to say it is that earnings in a Roth IRA are \"\"conditionally tax deferred\"\".\"",
"title": ""
},
{
"docid": "206442",
"text": "\"It is important to remember that the stock price in principle reflects the value of the company, so the market cap should drop upon issuance of the the dividend. However, the above reasoning neglects to consider taxes, which make the question a bit more interesting. The key fact is that different investors are going to get taxed on the dividend to varying degrees, ranging from 20% for qualified dividends in the USA for a high-income individual in a taxable account (and even worse for non-qualified dividends) to 0% for tax-exempt nonprofits, retirement accounts, and low-income individuals. The high-tax investors are going to be a bit averse to paying tax on that dividend, whereas the tax-free investors are not. Hence in a tax-rational market the tax-free investors are going to be the ones buying right before a dividend and the tax-paying investors will be buying right afterwards. Tax-exempt investors could in principle make some amount of money buying dividends to keep them off the tax-paying investors' books. (Of course, the strategy could backfire if too many people did it all at once.) That said, the tax-payers have the tax disincentive to prevent them from fully exploiting the opposite strategy of selling just before a dividend. In particular, they are subject to capital gains tax when they sell at a profit (unless they have enough compensating capital losses), and it is to their after-tax profit to defer taxation by not trading. That said, the stock market has well-known irrationality when it comes to considering tax consequences, so logic based on assumed rationality of the market does not always apply to the extent one would expect. The foremost example of tax-irrationality is the so-called \"\"dividend paradox\"\", which basically states that corporations should favor stock buybacks (or perhaps loan repayment) to the complete exclusion of dividends because capital gains are taxed less harshly than dividends in a variety of ways, some of which are subtle: 1) Historically (although not currently in the USA for qualified dividends) the tax rate was higher for dividends. (In Canada, for example, dividends are taxed at twice the rate of capital gains.) 2) If you die holding appreciated stock then you (meaning your heirs) completely escape US the capital gains tax on the accrual during your lifetime. 3) Capital gains tax can be deferred by simply not selling. In comparison to dividends, this is roughly equivalent to getting a tax-free loan from the government which is invested for profit and paid at a later date after inflation has eaten away at the real value of the loan. For example, if all your stock investments increase by 10%/year but you sell every year, in a high-tax bracket situation you're total after-tax return will be only 8% per year. In contrast, if you hold the same investments for many many years and then sell, your total return will be nearly 10% per year, because you only pay 20% once (at the end). 4) A capital gain can often be neutralized by a capital loss in another stock, so that no tax results. If you loose money on a stock that is paying dividends, you're still going to have to pay tax on that dividend. There are companies that borrow money to pay out that taxable-dividend each quarter, which seems like gross tax malpractice on the part of the CFO. (If the dividend paradox doesn't make sense, first consider the case that you owned ALL the shares of a company. It wouldn't matter to you at all on a pre-tax basis whether you got a $1000 company buyback or a $1000 dividend, because after the buyback/dividend you'd still own the entire company and $1000. The number of shares would be reduced, but objecting that you owned fewer shares after the buyback would be like saying you have become shorter if your height is measured in inches rather than centimeters.) [Of course, in the case of many shareholders you can get burned by failing to sell into the buyback when the share price is too high, but that is another matter.]\"",
"title": ""
},
{
"docid": "438038",
"text": "\"You don't want to do that. DON'T LIE TO THE IRS!!! We live overseas as well and have researched this extensively. You cannot make $50k overseas and then say you only made $45k to put $5k into retirement. I have heard from some accountants and tax attorneys who interpret the law as saying that the IRS considers Foreign Earned Income as NOT being compensation when computing IRA contribution limits, regardless of whether or not you exclude it. Publication 590-A What is Compensation (scroll down a little to the \"\"What Is Not Compensation\"\" section). Those professionals say that any amounts you CAN exclude, not just ones you actually do exclude. Then there are others that say the 'can' is not implied. So be careful trying to use any foreign-earned income to qualify for retirement contributions. I haven't ran across anyone yet who has gotten caught doing it and paid the price, but that doesn't mean they aren't out there. AN ALTERNATIVE IN CERTAIN CASES: There are two things you can do that we have found to have some sort of taxable income that is preferably not foreign so that you can contribute to a retirement account. We do this by using capital gains from investments as income. Since our AGI is always zero, we pay no short or long term capital gains taxes (as long as we keep short term capital gains lower than $45k) Another way to contribute to a Roth IRA when you have no income is to do an IRA Rollover. Of course, you need money in a tax-deferred account to do this, but this is how it works: I always recommend those who have tax-deferred IRA's and no AGI due to the FEIE to roll over as much as they can every year to a Roth IRA. That really is tax free money. The only tax you'll pay on that money is sales tax when you SPEND IT!! =)\"",
"title": ""
},
{
"docid": "535340",
"text": "\"As user quid states in his answer, all you need to do is open an account with a stock broker in order to gain access to the world's stock markets. If you are currently banking with one of the six big bank, then they will offer stockbroking services. You can shop around for the best commission rates. If you wish to manage your own investments, then you will open a \"\"self-directed\"\" account. You can shelter your investments from all taxation by opening a TFSA account with your stock broker. Currently, you can add $5,500 per year to your TFSA. Unused allowances from previous years can still be used. Thus, if you have not yet made any TFSA contributions, you can add upto $46,500 to your TFSA and enjoy the benefits of tax free investing. Investing in what you are calling \"\"unmanaged index funds\"\" means investing in ETFs (Exchange Traded Funds). Once you have opened your account you can invest in any ETFs traded on the stock markets accessible through your stock broker. Buying shares on foreign markets may carry higher commission rates, but for the US markets commissions are generally the same as they are for Canadian markets. However, in the case of buying foreign shares you will carry the extra cost and risk of selling Canadian dollars and buying foreign currency. There are also issues to do with foreign withholding taxes when you trade foreign shares directly. In the case of the US, you will also need to register with the US tax authorities. Foreign withholding taxes payable are generally treated as a tax credit with respect to Canadian taxation, so you will not be double taxed. In today's market, for most investors there is generally no need to invest directly in foreign market indices since you can do so indirectly on the Toronto stock market. The large Canadian ETF providers offer a wide range of US, European, Asian, and Global ETFs as well as Canadian ETFs. For example, you can track all of the major US indices by trading in Toronto in Canadian dollars. The S&P500, the Dow Jones, and the NASDAQ100 are offered in both \"\"currency hedged\"\" and \"\"unhedged\"\" forms. In addition, there are ETFs on the total US Market, US Small Caps, US sectors such as banks, and more exotic ETFs such as those offering \"\"covered call\"\" strategies and \"\"put write\"\" strategies. Here is a link to the BMO ETF website. Here is a link to the iShares (Canada) ETF website.\"",
"title": ""
},
{
"docid": "8861",
"text": "\"Sure. For starters, you can put it in a savings account. Don't laugh, they used to pay noticeable interest. You know, back in the olden days. You could buy an I-bond from Treasury Direct. They're a government savings bond that pays a specified amount of interest (currently 0%, I believe), plus the amount of the inflation rate (something like 3.5% currently, I believe). You don't get paid the money -- the I-bond grows in value till you sell it. You can open a discount brokerage account, and buy 1 or more shares of stock in a company you like. Discount brokerages generally have a minimum of $500 or so, but will waive that if you set the account up as an IRA. Scot Trade, for instance. (An IRA, in case you didn't know, is a type of account that's tax free but you can't touch it till you turn 59 1/2. It's meant to help you save for retirement.) Incidentally, watch out of \"\"small account\"\" fees that some brokerages might charge you. Generally they're annual or monthly charges they'd charge you to cover their costs on your account -- since they're certainly not going to make it in commissions. That IRA at Scot Trade is no-fee. Speaking of commissions, those will be a big chunk of that $100. It'll be like $7-$10 to buy that stock -- a pretty big bite. However, many of these discount brokerages also offer some mutual funds for no commission. Those mutual funds, in turn, have minimums too, but once again if your account's an IRA many will waive the minimum or set it low -- like $100.\"",
"title": ""
},
{
"docid": "473658",
"text": "ETFs offer the flexibility of stocks while retaining many of the benefits of mutual funds. Since an ETF is an actual fund, it has the diversification of its potentially many underlying securities. You can find ETFs with stocks at various market caps and style categories. You can have bond or mixed ETFs. You can even get ETFs with equal or fundamental weighting. In short, all the variety benefits of mutual funds. ETFs are typically much less expensive than mutual funds both in terms of management fees (expense ratio) and taxable gains. Most of them are not actively managed; instead they follow an index and therefore have a low turnover. A mutual fund may actively trade and, if not balanced with a loss, will generate capital gains that you pay taxes on. An ETF will produce gains only when shifting to keep inline with the index or you yourself sell. As a reminder: while expense ratio always matters, capital gains and dividends don't matter if the ETF or mutual fund is in a tax-advantaged account. ETFs have no load fees. Instead, because you trade it like a stock, you will pay a commission. Commissions are straight, up-front and perfectly clear. Much easier to understand than the various ways funds might charge you. There are no account minimums to entry with ETFs, but you will need to buy complete shares. Only a few places allow partial shares. It is generally harder to dollar-cost average into an ETF with regular automated investments. Also, like trading stocks, you can do those fancy things like selling short, buying on margin, options, etc. And you can pay attention to the price fluctuations throughout the day if you really want to. Things to make you pause: if you buy (no-load) mutual funds through the parent company, you'll get them at no commission. Many brokerages have No Transaction Fee (NTF) agreements with companies so that you can buy many funds for free. Still look out for that expense ratio though (which is probably paying for that NTF advantage). As sort of a middle ground: index funds can have very low expense ratios, track the same index as an ETF, can be tax-efficient or tax-managed, free to purchase, easy to dollar-cost average and easier to automate/understand. Further reading:",
"title": ""
},
{
"docid": "10089",
"text": "Congratulations on deciding to save for retirement. Since you cite Dave Ramsey as the source of your 15% number, what does he have to say about where to invest the money? If you want to have instantaneous penalty-free access to your retirement money, all you need to do is set up one or more ordinary accounts that you think of as your retirement money. Just be careful not to put the money into CDs since Federal law requires a penalty of three months interest if you cash in the CD before its maturity date (penalty!) or put the money into those pesky mutual funds that charge a redemption fee (penalty!) if you take the money out within x months of investing it where x can be anywhere from 3 to 24 or more. In Federal tax law (and in most state tax laws as well) a retirement account has special privileges accorded to it in that the interest, dividends, capital gains, etc earned on the money in your retirement account are not taxed in the year earned (as they would be in a non-retirement account), but the tax is either deferred till you withdraw money from the account (Traditional IRAs, 401ks etc) or is waived completely (Roth IRAs, Roth 401ks etc). In return for this special treatment, penalties are imposed (in addition to tax) if you withdraw money from your retirement account before age 59.5 which presumably is on the distant horizon for you. (There are some exceptions (including first-time home buying and extraordinary medical expenses) to this rule that I won't bother going into). But You are not required to invest your retirement money into such a specially privileged retirement account. It is perfectly legal to keep your retirement money in an ordinary savings account if you wish, and pay taxes on the interest each year. You can invest your retirement money into municipal bonds whose interest is free of Federal tax (and usually free of state tax as well if the municipality is located in your state of residence) if you like. You can keep your retirement money in a sock under your mattress if you like, or buy a collectible item (e.g. a painting) with it (this is not permitted in an IRA), etc. In short, if you are concerned about the penalties imposed by retirement accounts on early withdrawals, forgo the benefits of these accounts and put your retirement money elsewhere where there is no penalty for instant access. If you use a money management program such as Mint or Quicken, all you need to do is name one or more accounts or a portfolio as MyRetirementMoney and voila, it is done. But those accounts/portfolios don't have to be retirement accounts in the sense of tax law; they can be anything at all.",
"title": ""
},
{
"docid": "475397",
"text": "There is no advantage to using one type of account or the other if you are in the same tax bracket at retirement that you are in during your working years. However, for tax planning reasons, it is good to have some money in both a Roth and a traditional IRA plan. JoeTaxpayer has often advocated a good rule of thumb to use a Roth when your tax bracket is 15% or lower, and use a traditional account when in the 25% bracket or above. The reason for this rule of thumb is that you are less likely to be in the higher tax bracket when you are living off retirement savings unless you put away an awful lot of money between now and then. If you are making enough money to be paying a 25% marginal rate on some of the money you would be putting away for retirement, then by all means, put all of that money in a traditional 401k. If after contributing that portion of your savings taxed at the higher rate, you still have money to put away for retirement, put the rest in a Roth and pay the 15% taxes on it. When you are younger, it is likely that you are making less than you will a few years hence, and it is also likely that a larger portion of your income will be paying tax deductible interest on a mortgage. If those are true for you, then by all means, use the Roth. That was true of me when I was single and just getting started. When you do finally retire, it is possible that the tax brackets will be increased to match inflation, and if so, then there is no benefit to having tax free money at retirement vs. paying taxes on deferred accounts, but there is also usually more flexibility in when to spend money. You may find that you have a year where you have to spend a lot, so it is good to be able to pull money out without it increasing your marginal rate for that year, and other years where you spend relatively smaller amounts, and you can withdraw taxable money and pay a lower rate on that money. No one knows what the tax code will look like in 40 years, but having some money in each type of account will give you flexibility to minimize your tax bill at retirement.",
"title": ""
},
{
"docid": "173088",
"text": "\"What is a stock? A share of stock represents ownership of a portion of a corporation. In olden times, you would get a physical stock certificate (looking something like this) with your name and the number of shares on it. That certificate was the document demonstrating your ownership. Today, physical stock certificates are quite uncommon (to the point that a number of companies don't issue them anymore). While a one-share certificate can be a neat memento, certificates are a pain for investors, as they have to be stored safely and you'd have to go through a whole annoying process to redeem them when you wanted to sell your investment. Now, you'll usually hold stock through a brokerage account, and your holdings will just be records in a database somewhere. You'll pick a broker (more on that in the next question), instruct them to buy something, and they'll keep track of it in your account. Where do I get a stock? You'll generally choose a broker and open an account. You can read reviews to compare different brokerages in your country, as they'll have different fees and pricing. You can also make sure the brokerage firm you choose is in good standing with the financial regulators in your country, though one from a major national bank won't be unsafe. You will be required to provide personal information, as you are opening a financial account. The information should be similar to that required to open a bank account. You'll also need to get your money in and out of the account, so you'll likely set up a bank transfer. It may be possible to request a paper stock certificate, but don't be surprised if you're told this is unavailable. If you do get a paper certificate, you'll have to deal with considerably more hassle and delay if you want to sell later. Brokers charge a commission, which is a fee per trade. Let's say the commission is $10/trade. If you buy 5 shares of Google at $739/share, you'd pay $739 * 5 + $10 = $3705 and wind up with $3695 worth of stock in your account. You'd pay the same commission when you sell the stock. Can anyone buy/own/use a stock? Pretty much. A brokerage is going to require that you be a legal adult to maintain an account with them. There are generally ways in which a parent can open an account on behalf of an underage child though. There can be different types of restrictions when it comes to investing in companies that are not publicly held, but that's not something you need to worry about. Stocks available on the public stock market are available to, well, the public. How are stocks taxed? Taxes differ from country to country, but as a general rule, you do have to provide the tax authorities with sufficient information to determine what you owe. This means figuring out how much you purchased the stock for and comparing that with how much you sold it for to determine your gain or loss. In the US (and I suspect in many other countries), your brokerage will produce an annual report with at least some of this information and send it to the tax authorities and you. You or someone you hire to do your taxes will use that report to compute the amount of tax owed. Your brokerage will generally keep track of your \"\"cost basis\"\" (how much you bought it for) for you, though it's a good idea to keep records. If you refuse to tell the government your cost basis, they can always assume it's $0, and then you'll pay more tax than you owe. Finding the cost basis for old investments can be difficult many years later if the records are lost. If you can determine when the stock was purchased, even approximately, it's possible to look back at historical price data to determine the cost. If your stock pays a dividend (a certain amount of money per-share that a company may pay out of its profits to its investors), you'll generally need to pay tax on that income. In the US, the tax rate on dividends may be the same or less than the tax rate on normal wage income depending on how long you've held the investment and other rules.\"",
"title": ""
},
{
"docid": "69841",
"text": "A UTMA may or may not fit your situation. The main drawbacks to a UTMA account is that it will count against your child for financial aid (it counts as the child's asset). The second thing to consider is that taxes aren't deferred like in a 529 plan. The last problem of course is that when he turns 18 he gets control of the account and can spend the money on random junk (which may or may not be important to you). A 529 plan has a few advantages over a UTMA account. The grandparents can open the account with your son as the beneficiary and the money doesn't show up on financial aid for college (under current law which could change of course). Earnings grow tax free which will net you more total growth. You can also contribute substantially more without triggering the gift tax ~$60k. Also many states provide a state tax break for contributing to the state sponsored 529 plan. The account owner would be the grandparents so junior can't spend the money on teenage junk. The big downside to the 529 is the 10% penalty if the money isn't used for higher education. The flip side is that if the money is left for 20 years you will also have additional growth from the 20 years of tax free growth which may be a wash depending on your tax bracket and the tax rates in effect over those 20 years.",
"title": ""
},
{
"docid": "432902",
"text": "\"Your question is based on incorrect assumptions. Generally, there's no \"\"penalty\"\", per se, to make a withdrawal from your RRSP, even if you make a withdrawal earlier than retirement, however you define it. A precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant.* Our U.S. neighbours have a 10% penalty on non-hardship early withdrawals (before age 59 ½) from retirement accounts like the 401k and IRA. It's an additional measure designed to discourage early withdrawals, and raise more tax. Yet, in Canada, there is no similar penalty. Individual investments inside your RRSP may have associated penalties, such as the dreaded \"\"deferred sales charge\"\" (DSC) of some back-end loaded mutual funds, or such as LSVCC funds that generated additional special tax credits that could get clawed back. Yet, these early withdrawal penalties are distinct from the RRSP nature of your account. Choose your investments carefully to avoid these kinds of surprises. Rather, an RRSP is a tax-deferred account, and it works like this: The government allows you to claim a nice juicy tax deduction, which can reduce your income tax at your marginal rate in the year you make a contribution, or later if you should choose to defer the deduction. The resulting pre-tax money accumulated in your RRSP benefits from further tax deferral: assets can grow without attracting annual income tax on earned interest, dividends, or capital gains. You don't need to declare on your income tax return any of the income earned inside your RRSP, unlike a regular investment account. Here's the rub: Once you decide to withdraw money from your RRSP, the entire amount withdrawn is considered regular income in the year in which you make the withdrawal. Thus, your withdrawals are subject to income tax, and yes, at your marginal rate. This is always the case, whether before or after retirement. You mentioned two special programs: The Home Buyers' Plan (HBP), and the Lifelong Learning Plan (LLP). Neither the HBP nor the LLP permit tax-free withdrawals. Rather, each of these programs are special kinds of loans that you can borrow from your own RRSP. HBP and LLP loan money isn't taxed when you get it because you are required to pay it back, and you pay it back into your own RRSP: You always pay income tax at your marginal rate on your RRSP withdrawals.** * Above, I said a precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant. Yet, there are ages that matter: By the end of the year in which you turn 71, you are required to convert your RRSP to a RRIF. It's similar, but you can no longer contribute, and you must withdraw a minimum amount each year. Other circumstances related to age may qualify for minor tax relief intended for retirees, such as the Age Amount or the Pension Income Credit. Generally, such measures don't significantly change the fact that you pay income tax on RRSP withdrawals at your marginal rate – these measures raise the minimum you can take out without attracting tax, but most do nothing at the margin.** ** Exception: One might split eligible pension income with a spouse or common-law partner, which may reduce tax at the margin.\"",
"title": ""
},
{
"docid": "417388",
"text": "The 401(k) contribution is Federal tax free, when you make the contribution, and most likely State too. I believe that is true for California, specifically. There was a court case some years ago about people making 401(k) or IRA contributions in New York, avoiding the New York state income tax. Then they moved to Florida (no income tax), and took the money out. New York sued, saying they had to pay the New York income tax that had been deferred, but the court said no. So you should be able to avoid California state income tax, and then later if you were to move to, for example, Texas (no income tax), have no state income tax liability. At the Federal level, you will have different problems. You won't have the money; it will be held by the 401(k) trustee. When you try to access the money (cash the account out), you will have to pay the deferred taxes. Effectively, when you remove the money it becomes income in the year it is removed. You can take the money out at any time, but if you are less than 59 1/2 at the time that you take it, there is a 10% penalty. The agreement is that the Feds let you defer paying the tax because it is going to finance your retirement, and they will tax it later. If you take it out before 59 1/2, they figure you are not retired yet, and are breaking your part of the agreement. Of course you can generally leave the money in the 401(k) plan with your old employer and let it grow until you are 59.5, or roll it over into another 401(k) with a new employer (if they let you), or into an IRA. But if you have returned to your own country, having an account in the U.S. would introduce both investment risk and currency risk. If you are in another country when you want the money, the question would be where your U.S. residence would be. If you live in California, then go to, say France, your U.S. residence would still be California, and you would still owe California income tax. If you move from California to Texas and then to France, your U.S. residence would be Texas. This is pretty vague, as you might have heard in the Rahm Emanual case -- was he a resident of Chicago or Washington, D.C.? Same problem with Howard Hughes who was born in Texas, but then spent most his life in California, then to Nevada, then to Nicaragua, and the Bahamas. When he died Texas, California and Nevada all claimed him as a resident, for estate taxes. The important thing is to be able to make a reasonable case that you are a resident of where ever you want to be -- driver's license, mailing address, living quarters, and so on.",
"title": ""
},
{
"docid": "170717",
"text": "In the US, the key to understanding the benefits of retirement accounts is to understand capital gains taxes and how they work. Retirement accounts are designed for making investments throughout your career, then after several decades of contributions, withdrawing that money to pay for your needs when your full-time employment has concluded. Normally when you invest money in a brokerage account, if the value of your investment increases, and you sell in less than a year, those investments are considered short-term gains and taxed as ordinary income. If you hold that same investment for over a year, the same investment is taxed at a lower capital gains rate (depending on which tax bracket you are in during that year, the amount due could be up to 20%, but much lower than your regular income tax rate). When you place your money in a retirement account, you are choosing to either pay the tax due on the income when you put it in the account, or put the money in tax free and pay the tax when you withdraw (these are called tax-deferred accounts). When you have money invested several decades, the raw dollar amount increases greatly, but inflation is also reducing the value of those dollars. Imagine you bought some bonds that payed 4% over 40 years, but inflation was 2% during those same years. When you sell those bonds 40 years later, you will owe capital gains on the entire gain even though half of the gain came from inflation. Retirement accounts allow you to buy and sell according to your investment needs and goals without any consideration about whether the gains are short-term or long-term, and they also allow you to pay taxes just once, either when you put it in, or when you take it out, with no worries about whether you're paying taxes on inflated gains.",
"title": ""
},
{
"docid": "299690",
"text": "\"As other people have indicated, traditional IRAs are tax deductable for a particular year. Please note, though, that traditional IRAs are tax deferred (not tax-free) accounts, meaning that you'll have to pay taxes on any money you take out later regardless of why you're making the withdrawal. (A lot of people mistakenly call them tax free, which they're not). There is no such thing as a \"\"tax-free\"\" retirement account. Really, in terms of Roth vs. Traditional IRAs, it's \"\"pay now or pay later.\"\" With the exception of special circumstances like this, I recommend investing exclusively in Roth IRAs for money that you expect to grow much (or that you expect to produce substantial income over time). Just to add a few thoughts on what to actually invest in once you open your IRA, I strongly agree with the advice that you invest mostly in low-cost mutual funds or index funds. The advantage of an open-ended mutual fund is that it's easier to purchase them in odd increments and you may be able to avoid at least some purchase fees, whereas with an ETF you have to buy in multiples of that day's asking price. For example, if you were investing $500 and the ETF costs $200 per share, you could only purchase 2 shares, leaving $100 uninvested (minus whatever fee your broker charged for the purchase). The advantage of an ETF is that it's easy to buy or sell quickly. Usually, when you add money to a mutual fund, it'll take a few days for it to hit your account, and when you want to sell it'll similarly take a few days for you to get your money; when I buy an ETF the transaction can occur almost instantly. The fees can also be lower (if the ETF is just a passive index fund). Also, there's a risk with open-ended mutual funds that if too many people pull money out at once the managers could be forced to sell stocks at an unfavorable price.\"",
"title": ""
},
{
"docid": "38585",
"text": "This is something better asking a licensed professional (EA/CPA licensed in the US) who's also familiar with your home country tax law and the tax treaty your home country has with the US. Assuming no tax treaty and adverse tax consequences at home, you can have this scenario: The last step is critical - unless there's a tax treaty, not every country allows foreign tax credit (tax treaties usually have a provision to avoid double taxation), and you may end up paying both the US tax and local tax on the same money. If there's a tax treaty - step #4 is most likely guaranteed. Step #4 may not work in some places that would not consider the penalty as tax. Again - check it with an accountant proficient with the local law. Step #3 depends on your country. Some countries ignore foreign deferred compensation rules and consider the 401k amounts income to you when it was deposited (the US treats foreign tax deferred accounts this way, I believe that is also the case in India). So you should check locally. In this case you have probably paid taxes (or were exempt) on this amount when you earned it and will not pay taxes again. But then you might also not be able to claim the 10% back as credit. Leaving it is an option, although with such an amount is hardly worth it. You'll have to check how your country deals with foreign accounts of its citizens (the US, for example, puts an enormous reporting and tax burden on these, some countries forbid them altogether). This also applies to step #1.",
"title": ""
},
{
"docid": "335857",
"text": "\"You probably want to think about pools of money separately if they have separate time horizons or are otherwise not interchangeable. A classic example is your emergency fund (which has a potentially-immediate time horizon) vs. your retirement savings. The emergency fund would be all in cash or very short-term bonds, and would not count in your retirement asset allocation. Since the emergency fund usually has a capped value (a certain amount of money you want to have for emergencies) rather than a percentage of net worth value, this especially makes sense; you have to treat the emergency fund separately or you'd have to keep changing your asset allocation percentages as your net worth rises (hopefully) with respect to the capped emergency amount. Similarly, say you are saving for a car in 3 years; you'd probably invest that money very conservatively. Also, it could not go in tax-deferred retirement accounts, and when you buy the car the account will go to zero. So probably worth treating this separately. On the other hand, say you have some savings in tax-deferred retirement accounts and some in taxable accounts, but in both cases you're expecting to use the money for retirement. In that case, you have the same time horizon and goals, and it can pay to think about the taxable and nontaxable accounts as a whole. In particular you can use \"\"asset location\"\" (put less-tax-efficient assets in tax-deferred accounts). In this case maybe you would end up with mostly bonds in the tax-deferred accounts and mostly equities in the taxable accounts, for tax reasons; the asset allocation would only make sense considering all the accounts, since the taxable account would be too equity-heavy and the tax-deferred one too bond-heavy. There can be practical reasons to treat each account separately, too, though. For example if your broker has a convenient automatic rebalancing tool on their website, it probably only works within an account. Treating each account by itself would let you use the automatic rebalancing feature on the website, while a more complicated asset location strategy where you rebalance across multiple accounts might be too hard and in practice you wouldn't get around to it. Getting around to rebalancing could be more important than tax-motivated asset location. You could also take a keep-it-simple attitude: as long as your asset allocation is pretty balanced (say 40% bonds) and includes a cash allocation that would cover emergencies, you could just put all your money in one big portfolio, and think of it as a whole. If you have an emergency, withdraw from the cash allocation and then rebuild it over time; if you have a major purchase, you could redeem some bonds and then rebuild the bond portion over time. (When I say \"\"over time\"\" I'm thinking you might start putting new contributions into the now-underallocated assets, or you might dollar-cost-average back into them by selling bits of the now-overallocated assets.) Anyway there's no absolute rule, it depends on what's simple enough to be manageable for you in practice, and what separate shorter-horizon investing goals you have in addition to retirement. You can always make things complex but remember that a simple plan that happens in real life is better than a complex plan you don't keep up with in practice (or a complex plan that takes away from activities you'd enjoy more).\"",
"title": ""
},
{
"docid": "106501",
"text": "The $50k is subject to the appropriate income taxes, which may include FICA taxes including the employer share if you are self employed. The after tax money can then be invested with the amount invested being the cost basis (I.e., if you invest $40k you will have a cost basis of $40k). In future years you will have taxes due if any of those investments pay dividends (or capital gain distributions). Once you sell you will have a capital gain or loss that you will pay taxes on (or take a deduction if a loss). Now you can improve this picture if you are able to put some of your money into a retirement account (either a tax deductible or a ROTH). With retirement accounts you do not pay tax on the capital gains or dividends. If you use a tax deferred account your tax is higher but that is because you were also investing Uncle Sam's portion of your pay check.",
"title": ""
},
{
"docid": "396792",
"text": "\"Paypal linked with my bank account. 1.Can I use my Saving bank account to receive payments from my clients? Or is it necessary to open a current account? Yes you can get funds into your savings account. However it is advisable to keep a seperate account as it would help with your IT Returns. 2.I will be paying a certain % as commission on every sales to a couple of sales guys (who are not my employees but only working on commission). Can I show this as an expense in my IT returns? As you are earning as freelancer, you are eligible for certain deductions like Phone calls, Laptop, other hardware, payments to partners. It is important that you maintain a book of records. An accountant for a small fee of Rs 5 K should be able to help you. In the Returns you have to show Net income after all these deductions, there is no place to enter expenses. 3.Since I will be receiving all the payments in Euros so am I falling under a category of \"\"Exporter of services\"\"? The work you are doing can be Free Lancing. 4.Do I need an Import Export Code (IEC) for smoothly running this small business? You can run this without one as Free lancing. IEC would be when you grow big and are looking for various benefits under tax and pay different taxes and are incorporated as a company.\"",
"title": ""
},
{
"docid": "236732",
"text": "\"The 529 plan does outline your scenarios. There are stipulations for providing the funds should the child get the scholarship. If the child decides not to go into further education (vocational and community schools count), the money can be withdrawn with a 10% penalty and taxes paid on interest earnings. Taxes wouldn't have to be paid for contributions as taxes were already paid on that money by the gift giver. The 529 could also be transferred to another child in the family (including grandchildren). Here's an excerpt from www.savingforcollege.com: You'll never lose all of your savings. A 529 plan offers tax-free earnings and tax-free withdrawals as long as the money is used to pay for college. If you end up taking a non-qualified withdrawal, you'll incur income tax as well as a 10% penalty - but only on the earnings portion of the withdrawal. Since your contributions were made with after-tax money, they will never be taxed or penalized. You can avoid the penalty if you get a scholarship. There are a few special exceptions to the 10% penalty rule, including when the beneficiary becomes incapacitated, attends a U.S. Military Academy or gets a scholarship. In the case of a scholarship, non-qualified withdrawals up to the amount of the tax-free scholarship can be taken out penalty-free, but you'll have to pay income tax on the earnings. As Savingforcollege.com founder Joe Hurley likes to say, \"\"the scholarships have turned your tax-free 529 investment into a tax-deferred 529 investment\"\". Note, a 529 is ideal for the sum of money you are looking at. A proper trust, set up by a lawyer, will cost as much as $2000 to set up, and would require an annual tax return, both unnecessary burdens. To make matters worse, the trust counts as the child's asset where financial aid is concerned. The 529 counts, but to a much lesser extent.\"",
"title": ""
},
{
"docid": "114912",
"text": "The simplest explanation is that a traditional IRA is a method of deferring taxes. That is, normally you pay taxes on money you earn at the ordinary rate then invest the rest and only pay the capital gains rate. However, with a traditional IRA you don't pay taxes on the money when you earn it, you defer the payment of those taxes until you retire. So in the end it ends up being treated the same. That said, if you are strategic about it you can wind up paying less taxes with this type of account.",
"title": ""
}
] |
5aba5855554299232ef4a297
|
Maugrim is a captain of the secret police for the witch who froze Narnia in what event?
|
[
{
"docid": "723624",
"text": "Jadis is the main antagonist of \"The Magician's Nephew\" and of \"The Lion, the Witch and the Wardrobe\" in C. S. Lewis's series, \"The Chronicles of Narnia\". She is commonly referred to as the White Witch in \"The Lion, the Witch and the Wardrobe\", as she is the Witch who froze Narnia in the Hundred Years Winter.",
"title": ""
},
{
"docid": "30862911",
"text": "Maugrim is a fictional character in the novel \"The Lion, the Witch and the Wardrobe\" by C. S. Lewis. A Narnian wolf, he is Captain of the White Witch's Secret Police. In early American editions of the book, Lewis changed the name to Fenris Ulf (a wolf from Norse mythology), but when HarperCollins took over the books they took out Lewis' revisions, and the name \"Maugrim\" has been used in all editions since 1994.",
"title": ""
}
] |
[
{
"docid": "1880660",
"text": "The Chronicles of Narnia: The Lion, the Witch and the Wardrobe",
"title": ""
},
{
"docid": "11521092",
"text": "Journey into Narnia: Creating The Lion, the Witch, and the Wardrobe",
"title": ""
},
{
"docid": "3354767",
"text": "The Chronicles of Narnia: The Lion, the Witch and the Wardrobe (soundtrack)",
"title": ""
},
{
"docid": "3227990",
"text": "Music Inspired by The Chronicles of Narnia: The Lion, the Witch and the Wardrobe",
"title": ""
},
{
"docid": "5630116",
"text": "The Chronicles of Narnia: The Lion, the Witch and the Wardrobe (video game)",
"title": ""
},
{
"docid": "739362",
"text": "Lucy Pevensie is a fictional character in C. S. Lewis's \"The Chronicles of Narnia\" series. She is the youngest of the four Pevensie children, and the first to find the Wardrobe entrance to Narnia in \"The Lion, the Witch and the Wardrobe\". Of all the Pevensie children, Lucy is the closest to Aslan. Also, of all the humans who have visited Narnia, Lucy is perhaps the one that believes in Narnia the most. She is ultimately crowned Queen Lucy the Valiant, co-ruler of Narnia along with her two brothers and her sister. Lucy is the central character of the four siblings in the novels. Lucy is a principal character in three of the seven books (\"The Lion, the Witch and the Wardrobe\", \"Prince Caspian\", and \"The Voyage of the Dawn Treader\"), and a minor character in two others (\"The Horse and His Boy\" and \"The Last Battle\").",
"title": ""
},
{
"docid": "7609098",
"text": "The Hundred-Year Winter is a time period in the fictional Narnia universe created by C.S. Lewis. It takes place from 900–1000 Narnia time. The White Witch Jadis cast a spell to make it Winter all year round, but never reaches Christmas. But throughout the story, Aslan is entering Narnia and his presence weakens The White Witch, Jadis, causing Spring and Father Christmas to slowly appear. Aslan also brings Peter, Lucy, Susan, and Edmund to Narnia to fulfill the Prophecy of The Four Thrones (\"When two daughters of Eve and two sons of Adam sit together in throne at the Cair Paravel, the reign of the White Witch will be over and done.) This would put an end to White Witch's plan and her reign and the endless winter would come to an end. (The final days of the Hundred Year Winter occur during \"The Lion, the Witch, and the Wardrobe\".)",
"title": ""
},
{
"docid": "596442",
"text": "Tumnus is a fictional character in C. S. Lewis' series \"The Chronicles of Narnia\". He is featured prominently in \"The Lion, the Witch and the Wardrobe\" and also appears in \"The Horse and His Boy\" and \"The Last Battle\". He is close friends with Lucy Pevensie and is the first creature she meets in Narnia, as well as the first Narnian to be introduced in the series. Lewis said that the first Narnia story, \"The Lion, the Witch and the Wardrobe\", all came to him from a single picture he had in his head of a faun carrying an umbrella and parcels through a snowy wood. In that way, Tumnus was the initial inspiration for the entire Narnia series.",
"title": ""
},
{
"docid": "3719331",
"text": "The Chronicles of Narnia is a BBC-produced television serial that was aired from 13 November 1988 to 23 December 1990 and is based on four books of C. S. Lewis's \"The Chronicles of Narnia\" series. The first series aired was \"The Lion, the Witch and the Wardrobe\" in 1988, the second series aired was \"Prince Caspian\" and \"The Voyage of the Dawn Treader\" in 1989 and the third series aired was \"The Silver Chair\" in 1990. This television serial was produced by Paul Stone and teleplayed by Alan Seymour. \"The Lion, the Witch, and the Wardrobe\" was directed by Marilyn Fox, while \"Prince Caspian, The Voyage of the Dawn Treader\" and \"The Silver Chair\" were directed by Alex Kirby.",
"title": ""
},
{
"docid": "3610683",
"text": "The First Battle of Beruna is a fictional battle in C. S. Lewis' fantasy series \"The Chronicles of Narnia\". It is fought in Narnia at the edges of the Great River near the Fords of Beruna, in the year 1000 according to Lewis' Narnian timeline. It is the climactic battle of \"The Lion, The Witch and The Wardrobe\" and one of several battles in the Chronicles of Narnia.",
"title": ""
},
{
"docid": "626876",
"text": "Charn is a fictional city appearing in the 1955 book \"The Magician's Nephew\", book six in C. S. Lewis's Chronicles of Narnia, written as a prequel to \"The Lion, the Witch, and the Wardrobe\". Charn, and the world of which it is the capital city, are the birthplace of Jadis, the evil White Witch who later takes over Narnia. When visited briefly by Digory and Polly, the protagonists of the novel, the city is totally deserted, lifeless and crumbling, under a dying sun. Rivers have dried up, and neither weeds nor insects live. All life on the world of Charn had been destroyed by Jadis through an evil magic spell. In the novel the city stands as an example of the dead end that can result if a civilization succumbs to evil.",
"title": ""
},
{
"docid": "50516736",
"text": "Blair Witch is a 2016 American found footage supernatural horror film directed by Adam Wingard and written by Simon Barrett. It is the third official film in the \"Blair Witch\" series and a direct sequel to the 1999 film \"The Blair Witch Project\", ignoring the events of its 2000 follow-up film \"\", given the events of that film being a film within a film. \"Blair Witch\" stars James Allen McCune, Callie Hernandez, Brandon Scott, Corbin Reid, Wes Robinson, and Valorie Curry. The film, shot in a found footage style, follows a group of college students and their local guides who venture into the Black Hills Forest in Maryland to uncover the mysteries surrounding the disappearance years ago of Heather Donahue, the sister of one of the characters. Initially, the film's connection to the \"Blair Witch\" franchise was kept secret, with the film having been shot under the fake title, \"The Woods\".",
"title": ""
},
{
"docid": "38447269",
"text": "Jadis is the White Witch in C. S. Lewis's \"Narnia Chronicles\"",
"title": ""
},
{
"docid": "43894036",
"text": "The Lion, the Witch and the Wardrobe is an American dramatization of \"The Lion, the Witch and the Wardrobe\" by C.S. Lewis, the British children's novel that inaugurated \"The Chronicles of Narnia\" in 1950. The one-act play for two actors was written by Le Clanché du Rand and published in 1989 by Dramatic Publishing of Woodstock, Illinois. It is licensed by Dramatic to theaters worldwide. One production opened in 2011 Off-Broadway in New York City.",
"title": ""
},
{
"docid": "3327002",
"text": "Lantern Waste is a fictional place in \"The Chronicles of Narnia\" series by C. S. Lewis. It is a wood and is notable as the place where Lucy Pevensie and Mr. Tumnus meet, which is the first scene of Narnia described in the books. The lamppost in the wood is an iconic image of Narnia, and the question of its origin is what convinced Lewis to write more than one book on Narnia. One of King Edmund's titles is \"Duke of Lantern Waste\".",
"title": ""
},
{
"docid": "21478972",
"text": "Aslan ( or ) is the main character in C. S. Lewis's \"The Chronicles of Narnia\" series. He is \"the Great Lion\" of \"The Lion, the Witch and the Wardrobe\" and his role in Narnia is developed throughout the remaining books. He is also the only character to appear in all seven books of the series. \"Aslan\" is Turkish for \"lion\". Lewis often capitalises the word \"lion\" in reference to Aslan, since he represents Jesus Christ.",
"title": ""
},
{
"docid": "1882179",
"text": "The Chronicles of Narnia: Prince Caspian is a 2008 high fantasy film based on \"Prince Caspian\", the second published, fourth chronological novel in C. S. Lewis's epic fantasy series, \"The Chronicles of Narnia\". It is the second in \"The Chronicles of Narnia\" film series from Walden Media, following \"\" (2005). The four Pevensie children (William Moseley, Anna Popplewell, Skandar Keynes, and Georgie Henley) return to Narnia to aid Prince Caspian (Ben Barnes) in his struggle with the \"secret\" help of Aslan (Liam Neeson) for the throne against his corrupt uncle, King Miraz (Sergio Castellitto). The film was released on May 16, 2008 in the United States and on June 26, 2008 in the United Kingdom.",
"title": ""
},
{
"docid": "53588406",
"text": "\"Secret Empire\" is a 2017 Marvel Comics storyline. This limited series event addresses the aftermath of the crossover event \"\" and the ongoing series \"Captain America: Steve Rogers\", in which Captain America has been transformed into a sleeper agent loyal to Hydra and has been covertly setting the stage to establish Hydra as the main world-power.",
"title": ""
},
{
"docid": "1220301",
"text": "Stasiland by Anna Funder is a polyvocal text about individuals who resisted the East German regime, and others who worked for its secret police, the Stasi. It tells the story of what it was like to work for the Stasi, and describes how those who did so now come to terms, or do not, with their pasts.",
"title": ""
},
{
"docid": "22423835",
"text": "Speed Gibson of the International Secret Police was a radio adventure series written by Virginia Cooke. It was centered on the adventures of Speed Gibson, a fifteen-year-old pilot who, through his uncle Clint Barlow, becomes a member of the International Secret Police. Speed was described as “a typical American boy: interested in short wave radio, aviation and most of all - The International Secret Police.”",
"title": ""
},
{
"docid": "16128208",
"text": "Witch Baby (1991) is the second book in the Dangerous Angels series of novels written by Francesca Lia Block. It follows the adventures of Witch Baby, a young purple eyed girl who lives with Weetzie Bat, My-Secret-Agent-Lover-Man, and the rest of their crazy clan.",
"title": ""
},
{
"docid": "10426218",
"text": "Sophie Elizabeth Wilcox (born 2 January 1975 in Croydon, London) is an English actress who is most notable for appearing in the BBC miniseries adaptation of \"The Chronicles of Narnia\" as Lucy Pevensie when she was 13 years old. She appeared in \"The Lion, the Witch and the Wardrobe\" in 1988, as well as its sequel \"Prince Caspian and the Voyage of the Dawn Treader\" in 1989.",
"title": ""
},
{
"docid": "1061021",
"text": "This is a list of current secret police organizations. Fictional secret police organizations and historical secret police organizations are listed on their own respective pages.",
"title": ""
},
{
"docid": "19712795",
"text": "The Secrets of Harry Bright is the seventh novel written by former Los Angeles Police Department detective Joseph Wambaugh. Published in 1985, the book continues a pattern of Wambaugh crime fiction beginning with \"The Choirboys\" that uses black humor to explore the psychological effects of prolonged stress on veteran police officers. As with all his novels, \"The Secrets of Harry Bright\", set in November 1984, is contemporaneous with the time frame in which it was written and includes numerous allusions and references to events and personalities of the time.",
"title": ""
},
{
"docid": "37185247",
"text": "Sabrina: Secrets of a Teenage Witch is a 3-D computer-animated American television series on Hub Network based on the Archie Comics character Sabrina the Teenage Witch. The series was developed by Pamela Hickey and Dennys McCoy and was acquired by Hub Network on October 1, 2012. The series was originally intended for a summer 2013 release but was delayed to fall 2013.",
"title": ""
},
{
"docid": "1069269",
"text": "Mr. and Mrs. Beaver are fictional characters in C. S. Lewis's The Chronicles of Narnia. In \"The Lion, the Witch and the Wardrobe\" they are instrumental in conveying the Pevensie children to Aslan, and they appear briefly in the final novel \"The Last Battle\".",
"title": ""
},
{
"docid": "3283865",
"text": "The Lady of the Green Kirtle, also called Queen of Underland and Queen of the Deep Realm, is the main antagonist in \"The Silver Chair\" by C. S. Lewis. She is sometimes called briefly the \"Green Lady\" (on analogy with Jadis, the \"White Lady\"), and she is known also as the \"Emerald Witch\"; neither name, however, appears in Lewis's text. She enslaved Prince Rilian of Narnia and a horde of gnomes by her witchcraft, and planned to use them to take over Narnia. She is foiled by three friends of Aslan: Eustace Scrubb, Jill Pole, and Puddleglum.",
"title": ""
},
{
"docid": "12244692",
"text": "Secrets of the Witching Hour is the second album of the British indie band, The Crimea, released on 30 April 2007 as a free download on the band's website. The song \"Loop A Loop\" appeared in an advertisement for Trident Gum.",
"title": ""
},
{
"docid": "881855",
"text": "Professor Digory Kirke(1888-1949) is a fictional character from C. S. Lewis' fantasy series \"The Chronicles of Narnia.\" He appears in three of the seven books: \"The Lion, the Witch and the Wardrobe\", \"The Magician's Nephew\", and \"The Last Battle.\"",
"title": ""
},
{
"docid": "47565567",
"text": "The Water Witch is a 1830 novel by James Fenimore Cooper. Set in 17th century New York and the surrounding sea, the novel depicts the abduction of a woman, Alida de Barbérie, by the pirate captain of the brigantine \"Water Witch\", and the subsequent pursuit of that elusive ship by her suitor, Captain Ludlow.",
"title": ""
}
] |
9437
|
How does a stake sale affect a company's stock price?
|
[
{
"docid": "400841",
"text": "Is it normal for such transactions to create new outstanding shares? Yes a company can create new shares or a Majority share holder can sell some of his stake or it can be a mix of both. how will this news affect the short-term and long-term price of the company's stock? This is opinion based and not apt for this site. It can be positive or negative depending on how the market reacts to the news.",
"title": ""
}
] |
[
{
"docid": "275392",
"text": "Theoretically, when a company issues more shares, it does not affect the value of your shares. The reason is that when a company issues and sells more shares, the proceeds from the sale of those shares goes back into the company. Using your example, you have 10 out of 100 shares of the company, for a 10% stake. Let's say that the shares are valued at $1,000 each, meaning that the market value of the company is $100,000, and your stake is worth $10,000. Now the company issues 100 more shares at $1,000 each. The company receives $100,000 from new investors, and now the company is worth $200,000. Your stake is now only 5% of the company, but it is still worth $10,000. The authorized share capital is the amount of shares that a company has already planned on selling. When you buy stock in a company, you can look up how many shares exist, so you know what your percent stake in the company is. When a company wants to sell more shares, this is called an increase of authorized share capital. In order to do this, the company generally needs the approval of a majority of the existing shareholders.",
"title": ""
},
{
"docid": "548673",
"text": "\"I have heard that investing more money into an investment which has gone down is generally a bad idea*. \"\"Throwing good money after bad\"\" so to speak. Is investing more money into a stock, you already have a stake in, which has gone up in price; a good idea? Other things being equal, deciding whether to buy more stocks or shares in a company you're already invested in should be made in the same way you would evaluate any investment decision and -- broadly speaking -- should not be influenced by whether an existing holding has gone up or down in value. For instance, given the current price of the stock, prevailing market conditions, and knowledge about the company, if you think there is a reasonable chance that the price will rise in the time-period you are interested in, then you may want to buy (more) stock. If you think there is a reasonable chance the price will fall, then you probably won't want to buy (more) stock. Note: it may be that the past performance of a company is factored into your decision to buy (e.g was a recent downturn merely a \"\"blip\"\", and long-term prospects remain good; or have recent steady rises exhausted the potential for growth for the time being). And while this past performance will have played a part in whether any existing holding went up or down in value, it should only be the past performance -- not whether or not you've gained or lost money -- that affects the new decision. For instance: let us suppose (for reasons that seemed valid at the time) you bought your original holding at £10/share, the price has dropped to £2/share, but you (now) believe both prices were/are \"\"wrong\"\" and that the \"\"true price\"\" should be around £5/share. If you feel there is a good chance of this being achieved then buying shares at £2, anticipating they'll rally to £5, may be sound. But you should be doing this because you think the price will rise to £5, and not because it will offset the loses in your original holding. (You may also want to take stock and evaluate why you thought it a good idea to buy at £10... if you were overly optimistic then, you should probably be asking yourself whether your current decisions (in this or any share) are \"\"sound\"\"). There is one area where an existing holding does come into play: as both jamesqf and Victor rightly point out, keeping a \"\"balanced\"\" portfolio -- without putting \"\"all your eggs in one basket\"\" -- is generally sound advice. So when considering the purchase of additional stock in a company you are already invested in, remember to look at the combined total (old and new) when evaluating how the (potential) purchase will affect your overall portfolio.\"",
"title": ""
},
{
"docid": "121622",
"text": "\"BigCo is selling new shares and receives the money from Venturo. If Venturo is offering $250k for 25% of the company, then the valuation that they are agreeing on is a value of $1m for the company after the new investment is made. If Jack is the sole owner of one million shares before the new investment, then BigCo sells 333,333 shares to Venturo for $250k. The new total number of shares of BigCo is 1,333,333; Venturo holds 25%, and Jack holds 75%. The amount that Jack originally invested in the company is irrelevant. At the moment of the sale, the Venturo and Jack agree that Jack's stake is worth $750k. The value of Jack's stake may have gone up, but he owes no capital gains tax, because he hasn't realized any of his gains yet. Jack hasn't sold any of his stake. You might think that he has, because he used to hold 100% and now he holds 75%. However, the difference is that the company is worth more than was before the sale. So the value of his stake was unchanged immediately before and after the sale. Jack agrees to this because the company needs this additional capital in order to meet its potential. (See \"\"Why is stock dilution legal?\"\") For further explanation and another example of this, see the question \"\"If a startup receives investment money, does the startup founder/owner actually gain anything?\"\" Your other scenario, where Venturo purchases existing shares directly from Jack, is not practical in this situation. If Jack sells his existing shares, you are correct that the company does not gain any additional capital. An investor would not want to invest in the company this way, because the company is struggling and needs new capital.\"",
"title": ""
},
{
"docid": "2205",
"text": "If the check is written as a check to BigCo, it is less clear how Jack can compensate himself for the equity sale. It is as if the equity was owned by the corporation, not by Jack. This is correct. If the check is written to BigCo, then it is BigCo issuing new shares. Jack doesn't compensate himself for the equity sale, as he didn't sell anything. The company traded shares for money which it uses for expansion. In the long term, the capital gain from expansion may exceed the value of a $200,000 no-interest loan to the company. If the value of the company before investing $250,000 is $1 million, then the value after investing is $1.25 million. So $250,000 is 20% of the value of the company. BigCo should not give the buyer 25% of BigCo but only 20% in that example. If it does give 25%, the buyer is getting a $312,500 stake for only $250,000. With the other example, Jack sells 25% of the company for $250,000 from his personal shares. This doesn't change the assessed value of the company, just Jack's stake. Jack then loans the company $200,000. This also doesn't change the assessed value of the company (at least in theory). It gains $200,000 but has an offsetting debt of $200,000. In net, that's no change. Assets and liabilities balance the same. So if you know that the assessed value of the company is $1 million and that the buyer is paying $250,000 for a 25% stake at that same valuation, then you know that the check is being written to Jack. If the check is written to BigCo, then one or more of those numbers is incorrect. The buyer could be getting a 20% stake. The new value of the company after the investment is $1.25 million. Or paying $333,333.33. The new value of the company after the investment is $1,333,333.33. Or BigCo could only be worth $750,000 before the investment. The new value of the company after the investment is $1 million. Or Jack is getting screwed, selling $312,500 in stock (25%) for only $250,000. Jack's shares drop from being worth $1 million to only $937,500. The value of the company is $1.25 million. Or some combination of smaller changes that balances.",
"title": ""
},
{
"docid": "337736",
"text": "In general, how does a large open market stock sale affect prices? A very general answer, all other things being equal, the price will move down. However there is nothing general. It depends on total number of shares in market and total turn over for that specific shares. The order book for the day etc. What is the maximum percentage of a company you could sell per day before the trading freezes, and what factors matter? Every stock exchange has rules that would determine when a particular stock would be suspended from trading, generally a 10-20% swing [either ways]. Generally highly liquid stock or stock during initial listing are exempt from such limits as they are left to arrive the market price ... A large sell order may or may not swing the price for it to get suspended. At times even a small order may do ... again it is specific to a particular stock.",
"title": ""
},
{
"docid": "334162",
"text": "Here is an example for you. We have a fictional company. It's called MoneyCorp. Its job is to own money, and that's all. Right now it owns $10,000. It doesn't do anything special with that $10,000 - it stores it in a bank account, and whenever it earns interest gives it to the shareholders as a dividend. Also, it doesn't have any expenses at all, and doesn't pay taxes, and is otherwise magic so that it doesn't have to worry about distractions from its mathematical perfection. There are 10,000 shares of MoneyCorp, each worth exactly $1. However, they may trade for more or less than $1 on the stock market, because it's a free market and people trading stock on the stock market can trade at whatever price two people agree on. Scenario 1. MoneyCorp wants to expand. They sell 90,000 shares for $1 each. The money goes in the same bank account at the same interest rate. Do the original shareholders see a change? No. 100,000 shares, $100,000, still $1/share. No problem. This is the ideal situation. Scenario 2: MoneyCorp sells 90,000 shares for less than the current price, $0.50 each. Do the original shareholders lose out? YES. It now has something like $55,000 and 100,000 shares. Each share is now worth $0.55. The company has given away valuable equity to new shareholders. That's bad. Why didn't they get more money from those guys? Scenario 3: MoneyCorp sells 90,000 shares for more than the current price, $2 each, because there's a lot of hype about its business. MoneyCorp now owns $190,000 in 100,000 shares and each share is worth $1.90. Existing shareholders win big! This is why a company would like to make its share offering at the highest price possible (think, Facebook IPO). Of course, the new shareholders may be disappointed. MoneyCorp is actually a lot like a real business! Actually, if you want to get down to it, MoneyCorp works very much like a money-market fund. The main difference between MoneyCorp and a random company on the stock market is that we know exactly how much money MoneyCorp is worth. You don't know that with a real business: sales may grow, sales may drop, input prices may rise and fall, and there's room for disagreement - that's why stock markets are as unpredictable as they are, so there's room for doubt when a company sells their stock at a price existing shareholders think is too cheap (or buys it at a price that is too expensive). Most companies raising capital will end up doing something close to scenario 1, the fair-prices-for-everyone scenario. Legally, if you own part of a company and they do something a Scenario-2 on you... you may be out of luck. Consider also: the other owners are probably hurt as much as you are. Only the new shareholders win. And unless the management approving the deal is somehow giving themselves a sweetheart deal, it'll be hard to demonstrate any malfeasance. As an individual, you probably won't file a lawsuit either, unless you own a very large stake in the company. Lawsuits are expensive. A big institutional investor or activist investor of some sort may file a suit if millions of dollars are at stake, but it'll be ugly at best. If there's nothing evil going on with the management, this is just one way that a company loses money from bad management. It's probably not the most important one to worry about.",
"title": ""
},
{
"docid": "54257",
"text": "\"If you own 1% of a company, you are technically entitled to 1% of the current value and future profits of that company. However, you cannot, as you seem to imply, just decide at some point to take your ball and go home. You cannot call up the company and ask for 1% of their assets to be liquidated and given to you in cash. What the 1% stake in the company actually entitles you to is: 1% of total shareholder voting rights. Your \"\"aye\"\" or \"\"nay\"\" carries the weight of 1% of the total shareholder voting block. Doesn't sound like much, but when the average little guy has on the order of ten-millionths of a percentage point ownership of any big corporation, your one vote carries more weight than those of millions of single-share investors. 1% of future dividend payments made to shareholders. For every dollar the corporation makes in profits, and doesn't retain for future growth, you get a penny. Again, doesn't sound like much, but consider that the Simon property group, ranked #497 on the Fortune 500 list of the world's biggest companies by revenue, made $1.4 billion in profits last year. 1% of that, if the company divvied it all up, is $14 million. If you bought your 1% stake in March of 2009, you would have paid a paltry $83 million, and be earning roughly 16% on your initial investment annually just in dividends (to say nothing of the roughly 450% increase in stock price since that time, making the value of your holdings roughly $460 million; that does reduce your actual dividend yield to about 3% of holdings value). If this doesn't sound appealing, and you want out, you would sell your 1% stake. The price you would get for this total stake may or may not be 1% of the company's book value. This is for many reasons: Now, to answer your hypothetical: If Apple's stock, tomorrow, went from $420b market cap to zero, that would mean that the market unanimously thought, when they woke up tomorrow morning, that the company was all of a sudden absolutely worthless. In order to have this unanimous consent, the market must be thoroughly convinced, by looking at SEC filings of assets, liabilities and profits, listening to executive statements, etc that an investor wouldn't see even one penny returned of any cash investment made in this company's stock. That's impossible; the price of a share is based on what someone will pay to have it (or accept to be rid of it). Nobody ever just gives stock away for free on the trading floor, so even if they're selling 10 shares for a penny, they're selling it, and so the stock has a value ($0.001/share). We can say, however, that a fall to \"\"effectively zero\"\" is possible, because they've happened. Enron, for instance, lost half its share value in just one week in mid-October as the scope of the accounting scandal started becoming evident. That was just the steepest part of an 18-month fall from $90/share in August '00, to just $0.12/share as of its bankruptcy filing in Dec '01; a 99.87% loss of value. Now, this is an extreme example, but it illustrates what would be necessary to get a stock to go all the way to zero (if indeed it ever really could). Enron's stock wasn't delisted until a month and a half after Enron's bankruptcy filing, it was done based on NYSE listing rules (the stock had been trading at less than a dollar for 30 days), and was still traded \"\"over the counter\"\" on the Pink Sheets after that point. Enron didn't divest all its assets until 2006, and the company still exists (though its mission is now to sue other companies that had a hand in the fraud, get the money and turn it around to Enron creditors). I don't know when it stopped becoming a publicly-traded company (if indeed it ever did), but as I said, there is always someone willing to buy a bunch of really cheap shares to try and game the market (buying shares reduces the number available for sale, reducing supply, increasing price, making the investor a lot of money assuming he can offload them quickly enough).\"",
"title": ""
},
{
"docid": "584901",
"text": "News about a company is not the only thing that affects its stock's price. There is also supply and demand. That, of course, is influenced by news, but it is not the only actor. An insider, with a large position in their company's stock, may want to diversify his overall portfolio and thus need to sell a large amount of stock. That may be significant enough to increase supply and likely reduce the stock's price somewhat. That brings me to another influence on stock price: perception. Executives, and other insiders with large positions in their company's stock, have to be careful about how and when they sell some of that stock as to not worry the markets. Many investors watch insider selling to gauge the health of the company. Which brings me to another important point. There are many things that may be considered news which is material to a certain company and its stock. It is not just quarterly filings, earnings reports and such. There is also news related to competitors, news about the economy or a certain sector, news about some weather event that affects a major supplier, news about a major earthquake that will impact the economy of a nation which can then have knock-on effects to other economies, etc... There are also a lot of investors with varying needs which will influence supply and demand. An institutional investor, needing to diversify, may reduce their position in a stock and thus increase supply enough that it impacts the stock's price. Meanwhile, individual investors will make their transactions at varying times during the day. In the aggregate, that may have significant impacts on supply and demand. The overall point being that there are a lot of inputs and a lot of actors in a complicated system. Even if you focus just on news, there are many things that fall into that category. News does not come out at regular intervals and it does not necessarily spread evenly. That alone could make for a highly variable environment.",
"title": ""
},
{
"docid": "449500",
"text": "Its pretty much always a positive to have large institutional investors. Here's a few cases where I can see an argument against large institutional investors: In recent years, we've seen corporate raiders and institutional investors that tend to influence management in ways that are focused on short term gain. They'll often go for board seats and disrupt the existing management team. It can serve as a distraction and really hurt morale. Institutional investors also have rules in their prospectus that they are required to abide by. For example, some institutional investors will not hold on to stock below $5. This really affected major banking stocks, some of which ended up doing reverse stock splits to keep their share price high. Institutional investors will also setup specific funds that require a stock to be listed as part of an index (i.e. the SPY, DJIA etc.,). When a stock is removed from an index, big investors leave quickly and the share price suffers. In recent months, companies like Apple have made their share price more affordable to attract retail investors. It gives an opportunity for retail to feel even more connected to the company. I'm not sure how much this affects overall sales... Generally, a good stock should be able to attract both retail and institutional investors. If there's not a good mix, then its usually a sign that somethings amiss.",
"title": ""
},
{
"docid": "200054",
"text": "When you sell the stock your income is from the difference of prices between when you bought the stock and when you sold it. There's no interest there. The interest is in two places: the underlying company assets (which you own, whether you want it or not), and in the distribution of the income to the owners (the dividends). You can calculate which portion of the interest income constitutes your dividend by allocating the portions of your dividend in the proportions of the company income. That would (very roughly and unreliably, of course) give you an estimate what portion of your dividend income derives from the interest. Underlying assets include all the profits of the company that haven't been distributed through dividends, but rather reinvested back into the business. These may or may not be reflected in the market price of the company. Bottom line is that there's no direct correlation between the income from the sale of the stake of ownership and the company income from interest, if any correlation at all exists. Why would you care about interest income of Salesforce? Its not a bank or a lender, they may have some interest income, but that's definitely not the main income source of the company. If you want to know how much interest income exactly the company had, you'll have to dig deep inside the quarterly and annual reports, and even then I'm not sure if you'll find it as a separate item for a company that's not in the lending business.",
"title": ""
},
{
"docid": "8643",
"text": "Large-scale price range of a stock isn't directly meaningful; that reflects how many shares exist, not just how desirable they are. A stock split, for example, doubles the number of shares everyone holds while cutting the value of each share in half; that's meaningless except that it makes the shares a bit easier to trade in. Change in price is more interesting. In the case of energy companies, that often reflects major changes in energy supply, distribution, use, or how well positioned people feel the company is for the next change in these. Fracking's surge and the questions raised against it, whether a major pipeline will or won't be built, international energy price trends, breakthroughs in renewables... if it might affect energy price, it might affect the company's strength, both absolute and relative to others. In other words, the same kinds of things that affect any stock.",
"title": ""
},
{
"docid": "157597",
"text": "Look at Price/book value and there are more than a few stocks that may have a P/B under 1 so this does happen. There are at least a couple of other factors you aren't considering here: Current liabilities - How much money is the company losing each quarter that may cause it to sell repeatedly. If the company is burning through $100 million/quarter that asset is only going to keep the lights on for another 2.5 years so consider what assumptions you make about the company's cash flow here. The asset itself - Is the price really fixed or could it be flexible? Could the asset seen as being worth $1 billion today be worth much less in another year or two? As an example, suppose the asset was a building and then real estate values drop by 40% in that area. Now, what was worth $1 billion may now be worth only $600 million. As something of a final note, you don't state where the $100 million went that the company received as if that was burned for operations, now the company's position on the asset is $900 million as it only holds a 90% stake though I'd argue my 2 previous points are really worth noting. The Following 6 Stocks Are Trading At or Below 0.5 x Book Value–Sep 2013 has a half dozen examples of how this is possible. If the $100 million was used to pay off debt, then the company doesn't have that cash and thus its assets are reduced by the cash that is gone. Depending on what the plant is producing the value may or may not stay where it is. If you want an example to consider, how would you price automobile plants these days? If the company experiences a reduction in demand, the plant may have to be sold off at a reduced price for a cynic's view here.",
"title": ""
},
{
"docid": "336018",
"text": "\"Learn something new every day... I found this interesting and thought I'd throw my 2c in. Good description (I hope) from Short Selling: What is Short Selling First, let's describe what short selling means when you purchase shares of stock. In purchasing stocks, you buy a piece of ownership in the company. You buy/sell stock to gain/sell ownership of a company. When an investor goes long on an investment, it means that he or she has bought a stock believing its price will rise in the future. Conversely, when an investor goes short, he or she is anticipating a decrease in share price. Short selling is the selling of a stock that the seller doesn't own. More specifically, a short sale is the sale of a security that isn't owned by the seller, but that is promised to be delivered. Still with us? Here's the skinny: when you short sell a stock, your broker will lend it to you. The stock will come from the brokerage's own inventory, from another one of the firm's customers, or from another brokerage firm. The shares are sold and the proceeds are credited to your account. Sooner or later, you must \"\"close\"\" the short by buying back the same number of shares (called covering) and returning them to your broker. If the price drops, you can buy back the stock at the lower price and make a profit on the difference. If the price of the stock rises, you have to buy it back at the higher price, and you lose money. So what happened? The Plan The Reality Lesson I never understood what \"\"Shorting a stock\"\" meant until today. Seems a bit risky for my blood, but I would assume this is an extreme example of what can go wrong. This guy literally chose the wrong time to short a stock that was, in all visible aspects, on the decline. How often does a Large Company or Individual buy stock on the decline... and send that stock soaring? How often does a stock go up 100% in 24 hours? 600%? Another example is recently when Oprah bought 10% of Weight Watchers and caused the stock to soar %105 in 24 hours. You would have rued the day you shorted that stock - on that particular day - if you believed enough to \"\"gamble\"\" on it going down in price.\"",
"title": ""
},
{
"docid": "262925",
"text": "\"It is important to first understand that true causation of share price may not relate to historical correlation. Just like with scientific experiments, correlation does not imply causation. But we use stock price correlation to attempt to infer causation, where it is reasonable to do so. And to do that you need to understand that prices change for many reasons; some company specific, some industry specific, some market specific. Companies in the same industry may correlate when that industry goes up or down; companies with the same market may correlate when that market goes up or down. In general, in most industries, it is reasonable to assume that competitor companies have stocks which strongly correlate (positively) with each-other to the extent that they do the same thing. For a simple example, consider three resource companies: \"\"Oil Ltd.\"\" [100% of its assets relate to Oil]; \"\"Oil and Iron Inc.\"\" [50% of its value relates to Oil, 50% to Iron]; and \"\"Iron and Copper Ltd.\"\" [50% of its value relates to Iron, 50% to Copper]. For each of these companies, there are many things which affect value, but one could naively simplify things by saying \"\"value of a resource company is defined by the expected future volume of goods mined/drilled * the expected resource price, less all fixed and variable costs\"\". So, one major thing that impacts resource companies is simply the current & projected price of those resources. This means that if the price of Oil goes up or down, it will partially affect the value of the two Oil companies above - but how much it affects each company will depend on the volume of Oil it drills, and the timeline that it expects to get that Oil. For example, maybe Oil and Iron Ltd. has no currently producing Oil rigs, but it has just made massive investments which expect to drill Oil in 2 years - and the market expects Oil prices to return to a high value in 2 years. In that case, a drop in Oil would impact Oil Inc. severely, but perhaps it wouldn't impact Oil and Iron Ltd. as much. In this case, for the particular share price movement related to the price of Oil, the two companies would not be correlated. Iron and Copper Ltd. would be unaffected by the price of Oil [this is a simplification; Oil prices impact many areas of the economy], and therefore there would be no correlation at all between this company's shares. It is also likely that competitors face similar markets. If consumer spending goes down, then perhaps the stock of most consumer product companies would go down as well. There would be outliers, because specific companies may still succeed in a falling market, but in generally, there would be a lot of correlation between two companies with the same market. In the case that you list, Sony vs Samsung, there would be some factors that correlate positively, and some that correlate negatively. A clean example would be Blackberry stock vs Apple stock - because Apple's success had specifically negative ramifications for Blackberry. And yet, other tech company competitors also succeeded in the same time period, meaning they did not correlate negatively with Apple.\"",
"title": ""
},
{
"docid": "586984",
"text": "Similar premise, yes. It's an investment so you're definitely hoping it grows so you can sell it for a profit/gain. Public (stock market) vs. private (shark tank) are a little different though in terms of how much money you get and the form of income. With stocks, if you buy X number of shares at a certain price, you definitely want to sell them when they are worth more. However, you don't get, say 0.001% (or whatever percentage you own, it would be trivial) of the profits. They just pay a dividend to you based on a pre-determined amount and multiply it by the number of shares you own and that would be your income. Unless you're like Warren Buffet and Berkshire who can buy significant stakes of companies through the stock market, then they can likely put the investment on the balance sheet of his company, but that's a different discussion. It would also be expensive as hell to do that. With shark tank investors, the main benefit they get is significant ownership of a company for a cheap price, however the risk can be greater too as these companies don't have a strong foundation of sales and are just beginning. Investing in Apple vs. a small business is pretty significant difference haha. These companies are so small and in such a weak financial position which is why they're seeking money to grow, so they have almost no leverage. Mark Cuban could swoop in and offer $50k for 25% and that's almost worth it relative to what $50k in Apple shares would get him. It's all about the return. Apple and other big public companies are mature and most of the growth has already happened so there is little upside. With these startups, if they ever take off then and you own 25% of the company, it can be worth billions.",
"title": ""
},
{
"docid": "87349",
"text": "\"It means that the company earned 15 cents per share in the most recently reported quarter. Share price may or not be affected, depending on how buyers and sellers value the company. Just because profits \"\"jumped,\"\" does not mean the shares will follow suit. An increase in profits may have already been priced into the stock, or the market expected the increase in profit to be even higher. As the shareholder, you don't actually get any of these profits into your hands, unless the company pays out a portion of these profits as a dividend.\"",
"title": ""
},
{
"docid": "529459",
"text": "(community wiki) Ontario special HST sales tax transition rebate cheques: When and how much? What will happen to quarterly GST cheques when HST starts in Ontario? Ontario HST rebate: When would I qualify? Ontario gas prices & HST: What will happen to prices at the pump on July 1, 2010? How will Ontario’s HST apply to books / textbooks, which were PST exempt before? How can I minimize the impact of the HST? How does the HST affect a condominium purchase? Will I need to pay HST on condo maintenance fees? My Ontario small business collects only PST (beneath GST threshold). How will HST affect me?",
"title": ""
},
{
"docid": "220772",
"text": "\"The following is only an overview and does not contain all of the in-depth reasons why you should look more deeply. When you look at a stock's financials in depth you are looking for warning signs. These may warn of many things but one important thing to look for is ratio and growth rate manipulation. Using several different accounting methods it is possible to make a final report reflect a PE ratio (or any other ratio) that is inconsistent with the realities of the company's position. Earnings manipulation (in the way that Enron in particular manipulated them) is more widespread than you might think as \"\"earnings smoothing\"\" is a common way of keeping earnings in line (or smooth) in a recession or a boom. The reason that PE ratio looks so good could well be because professional investors have avoided the stock as there appear to be \"\"interesting\"\" (but legal) accounting decisions that are of concern. Another issue that you don't consider is growth. earnings may look good in the current reporting period but may have been stagnant or falling when considered over multiple periods. The low price may indicate falling revenues, earnings and market share that you would not be aware of when taking only your criteria into account. Understanding a firm will also give you an insight into how future news might affect the company. If the company has a lot of debt and market interest rates rise or fall how will that effect their debt, if another company brings out a competing product next week how will it effect the company? How will it effect their bottom line? How much do they rely on a single product line? How likely is it that their flagship product will become obsolete? How would that effect the company? Looking deeply into a company's financial statements will allow you to see any issues in their accounting practices and give you a feel for how they are preforming over time, it will also let you look into their cost of capital and investment decisions. Looking deeply into their products, company structure and how news will effect them will give you an understanding of potential issues that could threaten your investment before they occur. When looking for value you shouldn't just look at part of the value of the company; you wouldn't just look at sales of a single T-shirt range at Wallmart when deciding whether to invest in them. It is exactly the same argument for why you should look at the whole of the company's state when choosing to invest rather than a few small metrics.\"",
"title": ""
},
{
"docid": "477951",
"text": "\"If I held stock in these companies yesterday, would I have profited by these gains? No. For DZSI, your 5 shares at $1.10 would now be 1 share at $5.50, so you would have the same total amount. For SGY, they closed at $6.95, and opened at $32.80, so your five shares at $6.95 would now be one share at $32.80, so you would have actually lost money (not purely because of the split, but because the \"\"new\"\" shares are trading lower then the expected 1:5 split price). A split in general does not affect market cap (how much your total shares are worth) but there may be residual effects that cause the market value to fluctuate after a split that affect the price.\"",
"title": ""
},
{
"docid": "112461",
"text": "Say a stock is listed in Nasdaq, and the same company has a stock listed in Tsx. Does the Nasdaq price affect the Tsx price as trading commences? Not directly. Basically, an exchange is a market, and the price is defined only by supply and demand in that market. However, any substantial price differential for a commodity traded in multiple market creates an arbitrage opportunity, and there are many traders whose job it is exactly to find and use such opportunities. Their activity in turn has the effect of reducing the price differentials to the point where transaction costs make them unprofitable. With high-frequency traders around, the time for a price differential to disappear is nowadays measured in milliseconds. If a trader buys from one exchange, will it affect the price of the other? Only through the mechanism mentioned above. Are there any benefits to being listed in two exchanges? It increases the liquidity of a stock.",
"title": ""
},
{
"docid": "499344",
"text": "\"The correlation I heard most about in economics/finance was that stock prices and bond yields were negatively correlated; as the stock market does better, bond yields fall (company's doing well as evidenced by stocks, so it's a good credit risk, so YTM of its bonds on the market goes down). The correlation, if any, between the stock and futures market should be visible in the actual price histories. Index prices may be useful, but what's more likely is that various future prices have correlation with various companies' stocks. Where the future reflects the price of a raw material that is a significant cost of goods sold for a company, you'll see these two move inversely to each other in the short term. I think that if there is a causative relationship here, its that futures prices influence stock prices, not the other way around. The futures market generally represents the cost side of a consumer goods producer's bottom line. The stock market represents its profits. As futures go up, profit expectations go down, putting pressure on stock prices. Industries that deal in services, or in other types of goods, can still be affected because a rise in the cost of something consumers need will cause them to spend less on other things which affects margins in those other areas. So, in the short and medium term, when the futures market goes up the stock market sees a dip, and vice versa. However, companies adapt; they can put upward pressure on prices for their goods to restore their desired margins, usually by slowly increasing them to prevent sticker shock (though elasticity of demand plays a part; the more we need something no matter what it costs, the faster prices can increase). To maintain costs, they can make things cheaper using less expensive materials (more plastic, less steel). They can restructure production processes (translated: move factories offshore, or at least to \"\"right-to-work\"\" states with less union strength) to save costs elsewhere. All of these reduce costs and thus increase profits, but take time to implement. Many of these things reduce direct costs, reducing demand for the commodity and causing the futures prices to go back down. So, over the long term, these differences even out, and it's down to the things that affect the entire market (inflation, consumer/investor confidence, monetary policy).\"",
"title": ""
},
{
"docid": "91363",
"text": "As said previously, most of the time volume does not affect stock prices, except with penny stocks. These stocks typically have a small volume in the 3 or 4 figure range and because of this they typically experience very sharp rises and drops in stock prices, contrasting normal stocks that go up and down constantly every minute. Volume is not one thing you should be looking at when analyzing a stock in most cases, since it is simply the number of people of trades made in a day. That has no effect on the value of the company, whereas looking at P/E ratios, dividend growth, etc all can be analyzed to see if a company is growing and is doing well in its field. If I buy an iPhone, it doesn't matter if 100 other people or 100,000 other people have bought it as well, since they won't really affect my experience with the product. Whereas the type of iPhone I buy will.",
"title": ""
},
{
"docid": "411617",
"text": "The same applies if you were looking for a business to buy: would you pay more for a business that is doing well making increasing profits year after year, or for a business that is not doing so well and is losing money. A share in a company is basically a small part of a company which a shareholder can own. So would you rather own a part of a company that is increasing profits year after year or one that is continuously losing money? Someone would buy shares in a company in order to make a better return than they could make elsewhere. They can make a profit through two ways: first, a share of the company's profits through dividends, and second capital gains from the price of the shares going up. Why does the price of the shares go up over the long term when a company does well and increases profits? Because when a company increases profits they are making more and more money which increases the net worth of the company. More investors would prefer to buy shares in a company that makes increasing profits because this will increase the net worth of the company, and in turn will drive the share price higher over the long term. A company's increase in profits creates higher demand for the company's shares. Think about it, if interest rates are so low like they are now, where it is hard to get a return higher than inflation, why wouldn't investors then search for higher returns in good performing companies in the stock market? More investors' and traders' wanting some of the pie, creates higher demand for good performing stocks driving the share price higher. The demand for these companies is there primarily because the companies are increasing their profits and net worth, so over the long term the share price will increase in-line with the net worth. Over the short to medium term other factors can also affect the share price, sometime opposite to how the company is actually performing; however this is a whole different answer to a whole different question.",
"title": ""
},
{
"docid": "372360",
"text": "Yes, but only if they're looking for investors. You would need to contact them directly. Unless you're looking to invest a significant sum, they may not be interested in speaking with you. (Think at least 6 figures, maybe 7 depending on their size and needs). This is otherwise known as being a Venture Capitalist. Some companies don't want additional investors because the capital isn't yet needed and they don't want to give up shares in the profit/control. Alternatively, you could try and figure out which investment groups already have a stake in the company you're interested in. If those companies are publicly traded, you could buy stocks for their company with the expectation that their stock price will increase if the company you know of does well in the long run.",
"title": ""
},
{
"docid": "575554",
"text": "Selling stock means selling a portion of ownership in your company. Any time you issue stock, you give up some control, unless you're issuing non-voting stock, and even non-voting stock owns a portion of the company. Thus, issuing (voting) shares means either the current shareholders reduce their proportion of owernship, or the company reissues stock it held back from a previous offering (in which case it no longer has that stock available to issue and thus has less ability to raise funds in the future). From Investopedia, for exmaple: Secondary offerings in which new shares are underwritten and sold dilute the ownership position of stockholders who own shares that were issued in the IPO. Of course, sometimes a secondary offering is more akin to Mark Zuckerberg selling some shares of Facebook to allow him to diversify his holdings - the original owner(s) sell a portion of their holdings off. That does not dilute the ownership stake of others, but does reduce their share of course. You also give up some rights to dividends etc., even if you issue non-voting stock; of course that is factored into the price presumably (either the actual dividend or the prospect of eventually getting a dividend). And hopefully more growth leads to more dividends, though that's only true if the company can actually make good use of the incoming funds. That last part is somewhat important. A company that has a good use for new funds should raise more funds, because it will turn those $100 to $150 or $200 for everyone, including the current owners. But a company that doesn't have a particular use for more money would be wasting those funds, and probably not earning back that full value for everyone. The impact on stock price of course is also a major factor and not one to discount; even a company issuing non-voting stock has a fiduciary responsibility to act in the interest of those non-voting shareholders, and so should not excessively dilute their value.",
"title": ""
},
{
"docid": "42625",
"text": "\"This question drives at what value a shareholder actually provides to a corporation, and by extent, to the economy. If you subscribe for new shares (like in an Initial Public Offering), it is very straightforward to say \"\"I have provided capital to the corporation, which it is using to advance its business.\"\" If you buy shares that already exist (like in a typical share purchase on a public exchange), your money doesn't go to the company. Instead, it goes to someone who paid someone who paid someone who paid someone (etc.) who originally contributed money to the corporation. In theory, the value of a share price does not directly impact the operation of the company itself, apart from what @DanielCarson aptly noted (employee stock options are affected by share price, impacting morale, etc.). This is because in theory, the true value of a company (and thus, the value of a share) is the present value of all future cashflows (dividends + final liquidation). This means that in a technical sense, a company's share price should result from the company's value. The company's true value does not result from the share price. But what you are doing as a shareholder is impacting the liquidity available to other potential investors (also as mentioned by @DanielCarson, in reference to the desirability for future financing). The more people who invest their money in the stock market, the more liquid those stocks become. This is the true value you add to the economy by investing in stocks - you add liquidity to the market, decreasing the risk of capital investment generally. The fewer people there are who are willing to invest in a particular company, the harder it is for an investor to buy or sell shares at will. If it is difficult to sell shares in a company, the risk of holding shares in that company is higher, because you can't \"\"cash out\"\" as easily. This increased risk then does change the value of the shares - because even though the corporation's internal value is the same, the projected cashflows of the shares themselves now has a question mark around the ability to sell when desired. Whether this actually has an impact on anything depends on how many people join you in your declaration of ethical investing. Like many other forms of social activism, success relies on joint effort. This goes beyond the direct and indirect impacts mentioned above; if 'ethical investing' becomes more pronounced, it may begin to stigmatize the target companies (fewer people wanting to work for 'blacklist' corporations, fewer people buying their products, etc.).\"",
"title": ""
},
{
"docid": "363421",
"text": "\"Feel free to educate man. Everything I can find says the same thing. [Investopedia](http://www.investopedia.com/ask/answers/100314/what-are-key-factors-cause-market-go-and-down.asp) >If there are a greater number of buyers than sellers (more demand), the buyers bid up the prices of the stocks to entice sellers to get rid of them. Conversely, a larger number of sellers bids down the price of stocks hoping to entice buyers to purchase. Yes, if a company is performing well, you might find that more people want to buy then sale. That would cause it to go up. But if no one wants to buy, it doesn't matter how well the company is doing. I mean really, how would that work? Someone in the company notices they had more sales today then yesterday, email someone on wallstreet and they just mouse wheel the stock price up to something higher? Say the stock is $1.00 right now. But the lowest buy order is $.90. and the highest sale order is $1.10. (I guess there is some math there making is $1.) As soon as someone says, yeah. I'll sale at 90 cents, it'll go down. If someone says yeah, I'll buy at $1.10 it'll go up. I'm sure there is more to it than that. But everything I can find. It 100% has to have people more people wanting to buy then sale for it to go up. If more want to sale then buy, it'll go down. But hey, if this is way off base. Go ahead and fill me in. I'm open to CMV. This was all found after a short amount of time researching [\"\"What makes stock prices go up?\"\"](https://www.google.com/search?q=What+makes+stock+prices+go+up%3F&oq=What+makes+stock+prices+go+up%3F&gs_l=psy-ab.3..0i71k1l4.43421.43421.0.43882.0.0.0.0.0.0.0.0..0.0....0...1.1.64.psy-ab..0.0.0....0.6Crfejzb3XY)\"",
"title": ""
},
{
"docid": "261975",
"text": "\"I used to be in research department for big financial data company. Tell your son that there are three factors: Most people think that net sales vs. expectations is the only factor. It might not even be the biggest. It is simply how much money did company make. Note that this is not how many units they sold. For most companies they will have adjustable pricing and incentives in their sector. For example let's talk about a new company selling Superman Kid's Bikes (with a cape the flips out when you hit a certain speed). The company has it in Walmart at one price, Target at another, Toys R' Us even cheaper, Amazon (making more profit there), and other stores. They are doing \"\"OK\"\" come Dec. 1 but holiday season being half way over they slash price from $100 to $80 because they have tons of inventory. What are looking at her is how much money did they make. Note that marketing, advertising, legal (setting up contracts) are a bit fixed. In my opinion consumer sentiment is the #1 thing for a company that sells a product. Incredible consumer sentiment is like millions of dollars in free advertising. So let's say Dec. 15th comes and the reviews on the Superman Bike are through the roof. Every loves it, no major defects. Company can't even supply the retailers now because after slashing the price it became a great buy. A common investor might be pissed that some dummy at the company slashed the prices so they could have had a much better profit margin, but at the same time it wouldn't have led to an onslaught of sales and consumer sentiment. And the last area is product sell-off. This doesn't apply to all product but most. Some products will only have a technology shelf life, some will actually go bad or out of fashion, and even selling Superman bikes you want to get those to the store because the product is so big. So ignoring making a profit can a company sell off inventory at or around cost. If they can't, even if they made a profit, their risk factor goes up. So let's get back to Superman Bikes. This is the only product company ABC has. They had expected holiday sales at 100 million and profits at 40 million. They ended up at 120 million and 44 million. Let's say their stock was $20 before any information was gathered by the public (remember for most companies info is gathered daily now so this is rather simplistic). So you might expect that the stock would rise to maybe $24 - to which if you were an investor is a great profit. However this company has a cult consumer following who are waiting for the Captain America Bike (shoots discs) and the Hulk Bike (turns green when you go fast). Let's say consumer sentiment and projections base off that put next holiday sales at $250 million. So maybe the company is worth $40 a share now. But consumer sentiment is funny because not only does it effect future projections but it also effects perceived present value of company - which may have the stock trading at $60 a share (think earnings and companies like Google). Having a company people feel proud owning or thinking is cool is also a indicator or share worth. I gave you a really good example of a very successful company selling Superman Bikes... There are just as many companies that have the opposite happening. Imagine missing sales goals by a few million with bad consumer feedback and all of a sudden your company goes from $20 to $5 a share.\"",
"title": ""
},
{
"docid": "566205",
"text": "\"I'm not a financial expert, but saying that paying a $1 dividend will reduce the value of the stock by $1 sounds like awfully simple-minded reasoning to me. It appears to be based on the assumption that the price of a stock is equal to the value of the assets of a company divided by the total number of shares. But that simply isn't true. You don't even need to do any in-depth analysis to prove it. Just look at share prices over a few days. You should easily be able to find stocks whose price varied wildly. If, say, a company becomes the target of a federal investigation, the share price will plummet the day the announcement is made. Did the company's assets really disappear that day? No. What's happened is that the company's long term prospects are now in doubt. Or a company announces a promising new product. The share price shoots up. They may not have sold a single unit of the new product yet, they haven't made a dollar. But their future prospects now look improved. Many factors go into determining a stock price. Sure, total assets is a factor. But more important is anticipated future earning. I think a very simple case could be made that if a stock never paid any dividends, and if everyone knew it would never pay any dividends, that stock is worthless. The stock will never produce any profit to the owner. So why should you be willing to pay anything for it? One could say, The value could go up and you could sell at a profit. But on what basis would the value go up? Why would investors be willing to pay larger and larger amounts of money for an asset that produces zero income? Update I think I understand the source of the confusion now, so let me add to my answer. Suppose that a company's stock is selling for, say, $10. And to simplify the discussion let's suppose that there is absolutely nothing affecting the value of that stock except an expected dividend. The company plans to pay a dividend on a specific date of $1 per share. This dividend is announced well in advance. Everyone knows that it will be paid, and everyone is extremely confidant that in fact the company really will pay it -- they won't run out of money or any such. Then in a pure market, we would expect that as the date of that dividend approaches, the price of the stock would rise until the day before the dividend is paid, it is $11. Then the day after the dividend is paid the price would fall back to $10. Why? Because the person who owns the stock on the \"\"dividend day\"\" will get that $1. So if you bought the stock the day before the dividend, the next day you would immediately receive $1. If without the dividend the stock is worth $10, then the day before the dividend the stock is worth $11 because you know that the next day you will get a $1 \"\"refund\"\". If you buy the stock the day after the dividend is paid, you will not get the $1 -- it will go to the person who had the stock yesterday -- so the value of the stock falls back to the \"\"normal\"\" $10. So if you look at the value of a stock immediately after a dividend is paid, yes, it will be less than it was the day before by an amount equal to the dividend. (Plus or minus all the other things that affect the value of a stock, which in many cases would totally mask this effect.) But this does not mean that the dividend is worthless. Just the opposite. The reason the stock price fell was precisely because the dividend has value. BUT IT ONLY HAS VALUE TO THE PERSON WHO GETS IT. It does me no good that YOU get a $1 dividend. I want ME to get the money. So if I buy the stock after the dividend was paid, I missed my chance. So sure, in the very short term, a stock loses value after paying a dividend. But this does not mean that dividends in general reduce the value of a stock. Just the opposite. The price fell because it had gone up in anticipation of the dividend and is now returning to the \"\"normal\"\" level. Without the dividend, the price would never have gone up in the first place. Imagine you had a company with negligible assets. For example, an accounting firm that rents office space so it doesn't own a building, its only tangible assets are some office supplies and the like. So if the company liquidates, it would be worth pretty much zero. Everybody knows that if liquidated, the company would be worth zero. Further suppose that everyone somehow knows that this company will never, ever again pay a dividend. (Maybe federal regulators are shutting the company down because it's products were declared unacceptably hazardous, or the company was built around one genius who just died, etc.) What is the stock worth? Zero. It is an investment that you KNOW has a zero return. Why would anyone be willing to pay anything for it? It's no answer to say that you might buy the stock in the hope that the price of the stock will go up and you can sell at a profit even with no dividends. Why would anyone else pay anything for this stock? Well, unless their stock certificates are pretty and people like to collect them or something like that. Otherwise you're supposing that people would knowingly buy into a pyramid scheme. (Of course in real life there are usually uncertainties. If a company is dying, some people may believe, rightly or wrongly, that there is still hope of reviving it. Etc.) Don't confuse the value of the assets of a company with the value of its stock. They are related, of course -- all else being equal, a company with a billion dollars in assets will have a higher market capitalization than a company with ten dollars in assets. But you can't calculate the price of a company's stock by adding up the value of all its assets, subtracting liabilities, and dividing by the number of shares. That's just not how it works. Long term, the value of any stock is not the value of the assets but the net present value of the total future expected dividends. Subject to all sorts of complexities in real life.\"",
"title": ""
},
{
"docid": "415684",
"text": "\"Well, they don't \"\"make\"\" money in the sense of income, but they receive money in exchange for shares of stock (more of the company is owned by the public). The Warrant entitles the holder to purchase stock directly from the company at a fixed price. It is very much like an open-market call option, but instead of the option holder buying stock from a third party (which does not affect the company at all), the holder buys it directly from the company, increasing the number of shares outstanding, and the proceeds go directly to the company. If the holders do not exercise the warrants, the company does not receive any cash, but they also don't issue any new shares.\"",
"title": ""
}
] |
954
|
Pioglitazone use is significantly associated with an increased risk of prostate cancer.
|
[
{
"docid": "3355397",
"text": "IMPORTANCE Studies suggest pioglitazone use may increase risk of cancers. OBJECTIVE To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. DESIGN, SETTING, AND PARTICIPANTS Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed 193,099 persons aged 40 years or older in 1997-2002 until December 2012; 464 case patients and 464 matched controls were surveyed about additional confounders. A cohort analysis of 10 additional cancers included 236,507 persons aged 40 years or older in 1997-2005 and followed until June 2012. Cohorts were from Kaiser Permanente Northern California. EXPOSURES Ever use, duration, cumulative dose, and time since initiation of pioglitazone as time dependent. MAIN OUTCOMES AND MEASURES Incident cancer, including bladder, prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma. RESULTS Among 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration, 2.8 years; range, 0.2-13.2 years) and 1261 had incident bladder cancer. Crude incidences of bladder cancer in pioglitazone users and nonusers were 89.8 and 75.9 per 100,000 person-years, respectively. Ever use of pioglitazone was not associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95% CI, 0.89-1.26). Results were similar in case-control analyses (pioglitazone use: 19.6% among case patients and 17.5% among controls; adjusted odds ratio, 1.18; 95% CI, 0.78-1.80). In adjusted analyses, there was no association with 8 of the 10 additional cancers; ever use of pioglitazone was associated with increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02-1.26) and pancreatic cancer (HR, 1.41; 95% CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100,000 person-years, respectively. No clear patterns of risk for any cancer were observed for time since initiation, duration, or dose. CONCLUSIONS AND RELEVANCE Pioglitazone use was not associated with a statistically significant increased risk of bladder cancer, although an increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether they are causal or are due to chance, residual confounding, or reverse causality.",
"title": "Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes."
}
] |
[
{
"docid": "31229233",
"text": "BACKGROUND Patients with type 2 diabetes have a 40% increased risk of bladder cancer. Thiazolidinediones, especially pioglitazone, may increase the risk. We conducted a systematic review and meta-analysis to evaluate the risk of bladder cancer among adults with type 2 diabetes taking thiazolidinediones. METHODS We searched key biomedical databases (including MEDLINE, Embase and Scopus) and sources of grey literature from inception through March 2012 for published and unpublished studies, without language restrictions. We included randomized controlled trials (RCTs), cohort studies and case-control studies that reported incident bladder cancer among people with type 2 diabetes who ever (v. never) were exposed to pioglitazone (main outcome), rosiglitazone or any thiazolidinedione. RESULTS Of the 1787 studies identified, we selected 4 RCTs, 5 cohort studies and 1 case-control study. The total number of patients was 2,657,365, of whom 3643 had newly diagnosed bladder cancer, for an overall incidence of 53.1 per 100,000 person-years. The one RCT that reported on pioglitazone use found no significant association with bladder cancer (risk ratio [RR] 2.36, 95% confidence interval [CI] 0.91-6.13). The cohort studies of thiazolidinediones (pooled RR 1.15, 95% CI 1.04-1.26; I(2) = 0%) and of pioglitazone specifically (pooled RR 1.22, 95% CI 1.07-1.39; I(2) = 0%) showed significant associations with bladder cancer. No significant association with bladder cancer was observed in the two RCTs that evaluated rosiglitazone use (pooled RR 0.87, 95% CI 0.34-2.23; I(2) = 0%). INTERPRETATION The limited evidence available supports the hypothesis that thiazolidinediones, particularly pioglitazone, are associated with an increased risk of bladder cancer among adults with type 2 diabetes.",
"title": "Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis."
},
{
"docid": "24581365",
"text": "CONTEXT The appropriate therapy for men with clinically localized prostate cancer is uncertain. A recent study suggested an increasing prostate cancer mortality rate for men who are alive more than 15 years following diagnosis. OBJECTIVE To estimate 20-year survival based on a competing risk analysis of men who were diagnosed with clinically localized prostate cancer and treated with observation or androgen withdrawal therapy alone, stratified by age at diagnosis and histological findings. DESIGN, SETTING, AND PATIENTS A retrospective population-based cohort study using Connecticut Tumor Registry data supplemented by hospital record and histology review of 767 men aged 55 to 74 years with clinically localized prostate cancer diagnosed between January 1, 1971, and December 31, 1984. Patients were treated with either observation or immediate or delayed androgen withdrawal therapy, with a median observation of 24 years. MAIN OUTCOME MEASURES Probability of mortality from prostate cancer or other competing medical conditions, given a patient's age at diagnosis and tumor grade. RESULTS The prostate cancer mortality rate was 33 per 1000 person-years during the first 15 years of follow-up (95% confidence interval [CI], 28-38) and 18 per 1000 person-years after 15 years of follow-up (95% CI, 10-29). The mortality rates for these 2 follow-up periods were not statistically different, after adjusting for differences in tumor histology (rate ratio, 1.1; 95% CI, 0.6-1.9). Men with low-grade prostate cancers have a minimal risk of dying from prostate cancer during 20 years of follow-up (Gleason score of 2-4, 6 deaths per 1000 person-years; 95% CI, 2-11). Men with high-grade prostate cancers have a high probability of dying from prostate cancer within 10 years of diagnosis (Gleason score of 8-10, 121 deaths per 1000 person-years; 95% CI, 90-156). Men with Gleason score of 5 or 6 tumors have an intermediate risk of prostate cancer death. CONCLUSION The annual mortality rate from prostate cancer appears to remain stable after 15 years from diagnosis, which does not support aggressive treatment for localized low-grade prostate cancer.",
"title": "20-year outcomes following conservative management of clinically localized prostate cancer."
},
{
"docid": "4828631",
"text": "BACKGROUND High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING National Institute for Health Research, Wellcome Trust, and Medical Research Council.",
"title": "Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults"
},
{
"docid": "10024681",
"text": "Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.",
"title": "Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer"
},
{
"docid": "10430148",
"text": "CONTEXT No antidiabetic regimen has demonstrated the ability to reduce progression of coronary atherosclerosis. Commonly used oral glucose-lowering agents include sulfonylureas, which are insulin secretagogues, and thiazolidinediones, which are insulin sensitizers. OBJECTIVE To compare the effects of an insulin sensitizer, pioglitazone, with an insulin secretagogue, glimepiride, on the progression of coronary atherosclerosis in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, multicenter trial at 97 academic and community hospitals in North and South America (enrollment August 2003-March 2006) in 543 patients with coronary disease and type 2 diabetes. INTERVENTIONS A total of 543 patients underwent coronary intravascular ultrasonography and were randomized to receive glimepiride, 1 to 4 mg, or pioglitazone, 15 to 45 mg, for 18 months with titration to maximum dosage, if tolerated. Atherosclerosis progression was measured by repeat intravascular ultrasonography examination in 360 patients at study completion. MAIN OUTCOME MEASURE Change in percent atheroma volume (PAV) from baseline to study completion. RESULTS Least squares mean PAV increased 0.73% (95% CI, 0.33% to 1.12%) with glimepiride and decreased 0.16% (95% CI, -0.57% to 0.25%) with pioglitazone(P = .002). An alternative analysis imputing values for noncompleters based on baseline characteristics showed an increase in PAV of 0.64% (95% CI, 0.23% to 1.05%) for glimepiride and a decrease of 0.06% (-0.47% to 0.35%) for pioglitazone (between-group P = .02). Mean (SD) baseline HbA(1c) levels were 7.4% (1.0%) in both groups and declined during treatment an average 0.55% (95% CI, -0.68% to -0.42%) with pioglitazone and 0.36% (95% CI, -0.48% to -0.24%) with glimepiride (between-group P = .03). In the pioglitazone group, compared with glimepiride, high-density lipoprotein levels increased 5.7 mg/dL (95% CI, 4.4 to 7.0 mg/dL; 16.0%) vs 0.9 mg/dL (95% CI, -0.3 to 2.1 mg/dL; 4.1%), and median triglyceride levels decreased 16.3 mg/dL (95% CI, -27.7 to -11.0 mg/dL; 15.3%) vs an increase of 3.3 mg/dL (95% CI, -10.7 to 11.7 mg/dL; 0.6%) (P < .001 for both comparisons). Median fasting insulin levels decreased with pioglitazone and increased with glimepiride (P < .001). Hypoglycemia was more common in the glimepiride group and edema, fractures, and decreased hemoglobin levels occurred more frequently in the pioglitazone group. CONCLUSION In patients with type 2 diabetes and coronary artery disease, treatment with pioglitazone resulted in a significantly lower rate of progression of coronary atherosclerosis compared with glimepiride. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00225277.",
"title": "Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial."
},
{
"docid": "12009265",
"text": "CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer. OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men. DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled. INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. MAIN OUTCOME MEASURES Prostate and total cancer. RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk. CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.",
"title": "Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial."
},
{
"docid": "8512633",
"text": "Long noncoding RNAs (IncRNAs) are increasingly implicated in cancer biology, contributing to essential cancer cell functions such as proliferation, invasion, and metastasis. In prostate cancer, several lncRNAs have been nominated as critical actors in disease pathogenesis. Among these, expression of PCGEM1 and PRNCR1 has been identified as a possible component in disease progression through the coordination of androgen receptor (AR) signaling (Yang et al., Nature 2013, see ref. [1]). However, concerns regarding the robustness of these findings have been suggested. Here, we sought to evaluate whether PCGEM1 and PRNCR1 are associated with prostate cancer. Through a comprehensive analysis of RNA-sequencing data (RNA-seq), we find evidence that PCGEM1 but not PRNCR1 is associated with prostate cancer. We employ a large cohort of >230 high-risk prostate cancer patients with long-term outcomes data to show that, in contrast to prior reports, neither gene is associated with poor patient outcomes. We further observe no evidence that PCGEM1 nor PRNCR1 interact with AR, and neither gene is a component of AR signaling. Thus, we conclusively demonstrate that PCGEM1 and PRNCR1 are not prognostic lncRNAs in prostate cancer and we refute suggestions that these lncRNAs interact in AR signaling.",
"title": "The lncRNAs PCGEM1 and PRNCR1 are not implicated in castration resistant prostate cancer"
},
{
"docid": "6790197",
"text": "PURPOSE To accurately identify gene expression alterations that differentiate neoplastic from normal prostate epithelium using an approach that avoids contamination by unwanted cellular components and is not compromised by acute gene expression changes associated with tumor devascularization and resulting ischemia. EXPERIMENTAL DESIGN Approximately 3,000 neoplastic and benign prostate epithelial cells were isolated using laser capture microdissection from snap-frozen prostate biopsy specimens provided by 31 patients who subsequently participated in a clinical trial of preoperative chemotherapy. cDNA synthesized from amplified total RNA was hybridized to custom-made microarrays composed of 6,200 clones derived from the Prostate Expression Database. Expression differences for selected genes were verified using quantitative reverse transcription-PCR. RESULTS Comparative analyses identified 954 transcript alterations associated with cancer (q < 0.01%), including 149 differentially expressed genes with no known functional roles. Gene expression changes associated with ischemia and surgical removal of the prostate gland were absent. Genes up-regulated in prostate cancer were statistically enriched in categories related to cellular metabolism, energy use, signal transduction, and molecular transport. Genes down-regulated in prostate cancers were enriched in categories related to immune response, cellular responses to pathogens, and apoptosis. A heterogeneous pattern of androgen receptor expression changes was noted. In exploratory analyses, androgen receptor down-regulation was associated with a lower probability of cancer relapse after neoadjuvant chemotherapy followed by radical prostatectomy. CONCLUSIONS Assessments of tumor phenotypes based on gene expression for treatment stratification and drug targeting of oncogenic alterations may best be ascertained using biopsy-based analyses where the effects of ischemia do not complicate interpretation.",
"title": "Prostate cancer-associated gene expression alterations determined from needle biopsies."
},
{
"docid": "8037453",
"text": "PURPOSE Three large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy. PATIENTS AND METHODS Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This exploratory cohort analysis grouped patients by baseline and most recent levels of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol creatinine), or high (> or = 100 nmol/mmol creatinine), and BAP as low (< 146 U/L) or high (> or = 146 U/L). The relative risks for negative clinical outcomes were estimated for each group using multiple-event and Cox regression models with time-varying covariates. RESULTS Patients with high and moderate Ntx levels had 2-fold increases in their risk of skeletal complications and disease progression compared with patients with low Ntx levels (P < .001 for all). High Ntx levels in each solid tumor category were associated with a 4- to 6-fold increased risk of death on study, and moderate Ntx levels a 2- to 4-fold increased risk compared with low Ntx levels (P < .001 for all). Bone alkaline phosphatase also showed some correlation with risk of negative clinical outcomes. CONCLUSION The bone resorption marker Ntx provides valuable prognostic information in patients with bone metastases receiving bisphosphonates.",
"title": "Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid."
},
{
"docid": "10699587",
"text": "PURPOSE Gleason score (GS), T stage, and pathologic lymph node status have been described as major independent predictors of death due to prostate cancer in men treated with external beam radiotherapy (XRT). In this analysis we combine these three factors to define prognostic subgroups that correlate with disease-specific survival (DSS) death from prostate cancer. METHODS AND MATERIALS Men entered on one of four Radiation Therapy Oncology Group (RTOG) Phase III randomized trials between 1975 and 1992, for clinically localized prostate cancer (CAP) (n = 1557), were selected for this analysis. Patients were included if: 1) they were evaluable, and eligible for the trial; 2) they received no hormonal therapy with their initial treatment; and 3) follow-up was available. For this study a DSS event was declared if: 1) death was certified as due to CAP; 2) death was due to complications of treatment; or 3) death was from unknown causes with active malignancy. The median follow-up for patients treated on early and late RTOG studies exceeded 11 and 6 years respectively. Subgroups were identified based on their pretreatment GS, T-stage, and lymph node such that patients with similar risk of dying from prostate cancer were combined. RESULTS By combining patients with similar DSS, four subgroups were identified. Risk Group 1 patients had a GS = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The 5-, 10-, and 15-year DSS was 96%, 86%, and 72%; 94%, 75%, and 61%; 83%, 62%, and 39%; and 64%, 34%, and 27% for Groups 1 through 4, respectively. CONCLUSIONS Recognition of these four risk groups provides a basis for estimating the long-term DSS for men treated with XRT alone and should facilitate the design of future prospective randomized trials.",
"title": "Four prognostic groups predict long-term survival from prostate cancer following radiotherapy alone on Radiation Therapy Oncology Group clinical trials."
},
{
"docid": "6327940",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "24450344",
"text": "PURPOSE We evaluated the long-term outcome of radical prostatectomy for pathological Gleason score 8 or greater prostate cancer and characterized the prognostic significance of other pathological variables. MATERIALS AND METHODS A total of 6,419 patients underwent radical prostatectomy between 1987 and 1996. There were 407 patients classified as having pathological Gleason 8 or greater, including 8 in 48%, 9 in 49% and 10 in 3%. Adjuvant treatment was used in 45% of patients and adjuvant hormonal therapy was administered to 155 (38%). Progression-free, including local or systemic, and/or prostate specific antigen (PSA) 0.4 ng./ml. or greater, and cancer specific survival were determined by the Kaplan-Meier method. The effect of pathological grade and stage, preoperative PSA, DNA ploidy, margin status, tumor dimension, seminal vesicle invasion, and adjuvant treatment was assessed with the univariate and multivariate analyses. RESULTS Pathological stage distribution was pT2 in 26% of patients, pT3 48% and pTxN+ 27%. Overall and progression-free survival at 10 years was 67% and 36%, respectively, compared to cancer specific survival 85%. Adjuvant treatment, pathological stage, preoperative PSA and pathological grade were significant (less than 0.05) univariate predictors of progression-free survival. Pathological stage, margin status and ploidy were univariately associated with cancer specific survival. Progression-free survival at 10 years of those patients who did and did not receive adjuvant treatment was 52% and 23%, respectively. In the multivariate analysis pathological grade (p=0.02), preoperative PSA (p <0.0001), adjuvant therapy (p <0.0001) and pathological stage (p=0.036) were significant independent predictors of progression-free survival. CONCLUSIONS High grade prostate cancer can be controlled with radical prostatectomy in some patients with disease confined pathologically, and 10-year cause specific survival is 96%. Predictors of outcome in patients with Gleason 8 disease or greater are similar to established predictors derived by using all grades. Although adjuvant hormonal therapy appears to improve disease progression rates after radical prostatectomy on the basis of this nonrandomized study, it may not affect prostate cancer death rates within 10 years in patients with high grade cancer.",
"title": "Radical prostatectomy for pathological Gleason 8 or greater prostate cancer: influence of concomitant pathological variables."
},
{
"docid": "4500832",
"text": "gamma-tocopherol is the major form of vitamin E in many plant seeds and in the US diet, but has drawn little attention compared with alpha-tocopherol, the predominant form of vitamin E in tissues and the primary form in supplements. However, recent studies indicate that gamma-tocopherol may be important to human health and that it possesses unique features that distinguish it from alpha-tocopherol. gamma-Tocopherol appears to be a more effective trap for lipophilic electrophiles than is alpha-tocopherol. gamma-Tocopherol is well absorbed and accumulates to a significant degree in some human tissues; it is metabolized, however, largely to 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), which is mainly excreted in the urine. gamma-CEHC, but not the corresponding metabolite derived from alpha-tocopherol, has natriuretic activity that may be of physiologic importance. Both gamma-tocopherol and gamma-CEHC, but not alpha-tocopherol, inhibit cyclooxygenase activity and, thus, possess antiinflammatory properties. Some human and animal studies indicate that plasma concentrations of gamma-tocopherol are inversely associated with the incidence of cardiovascular disease and prostate cancer. These distinguishing features of gamma-tocopherol and its metabolite suggest that gamma-tocopherol may contribute significantly to human health in ways not recognized previously. This possibility should be further evaluated, especially considering that high doses of alpha-tocopherol deplete plasma and tissue gamma-tocopherol, in contrast with supplementation with gamma-tocopherol, which increases both. We review current information on the bioavailability, metabolism, chemistry, and nonantioxidant activities of gamma-tocopherol and epidemiologic data concerning the relation between gamma-tocopherol and cardiovascular disease and cancer.",
"title": "gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention."
},
{
"docid": "25589047",
"text": "CONTEXT Fatal adverse events (FAEs) have been reported in cancer patients treated with the widely used angiogenesis inhibitor bevacizumab in combination with chemotherapy. Currently, the role of bevacizumab in treatment-related mortality is not clear. OBJECTIVE To perform a systematic review and meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of FAEs associated with bevacizumab. DATA SOURCES PubMed, EMBASE, and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences from January 1966 to October 2010 were searched to identify relevant studies. STUDY SELECTION AND DATA EXTRACTION Eligible studies included prospective RCTs in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. DATA SYNTHESIS A total of 10,217 patients with a variety of advanced solid tumors from 16 RCTs were included in the analysis. The overall incidence of FAEs with bevacizumab was 2.5% (95% CI, 1.7%-3.9%). Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs, with an RR of 1.46 (95% CI, 1.09-1.94; P = .01; incidence, 2.5% vs 1.7%). This association varied significantly with chemotherapeutic agents (P = .045) but not with tumor types (P = .13) or bevacizumab doses (P = .16). Bevacizumab was associated with an increased risk of FAEs in patients receiving taxanes or platinum agents (RR, 3.49; 95% CI, 1.82-6.66; incidence, 3.3% vs 1.0%) but was not associated with increased risk of FAEs when used in conjunction with other agents (RR, 0.85; 95% CI, 0.25-2.88; incidence, 0.8% vs 0.9%). The most common causes of FAEs were hemorrhage (23.5%), neutropenia (12.2%), and gastrointestinal tract perforation (7.1%). CONCLUSION In a meta-analysis of RCTs, bevacizumab in combination with chemotherapy or biological therapy, compared with chemotherapy alone, was associated with increased treatment-related mortality.",
"title": "Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis."
},
{
"docid": "6334188",
"text": "BACKGROUND Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. DESIGN We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. RESULTS A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. CONCLUSIONS These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.",
"title": "History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis."
},
{
"docid": "26058927",
"text": "Thiazolidinediones (TZDs) improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). There is growing evidence from in vivo and in vitro studies that TZDs improve pancreatic beta-cell function. The aim of this study was to determine whether TZD-induced improvement in glycemic control is associated with improved beta-cell function. We studied 11 normal glucose-tolerant and 53 T2DM subjects [age 53+/-2 yr; BMI 29.4+/-0.8 kg/m2; fasting plasma glucose (FPG) 10.3+/-0.4 mM; Hb A1c 8.2+/-0.3%]. Diabetic patients were randomized to receive placebo or TZD for 4 mo. Subjects received 1) 2-h OGTT with determination of plasma glucose, insulin, and C-peptide concentrations and 2) two-step euglycemic insulin (40 and 160 mU.m-2.min-1) clamp with [3-(3)H]glucose. T2DM patients were then randomized to receive 4 mo of treatment with pioglitazone (45 mg/day), rosiglitazone (8 mg/day), or placebo. Pioglitazone and rosiglitazone similarly improved FPG, mean plasma glucose during OGTT, Hb A1c, and insulin-mediated total body glucose disposal (Rd) and decreased mean plasma FFA during OGTT (all P<0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [DeltaISR(AUC)/Deltaglucose(AUC)/IR] was significantly improved in all TZD-treated groups: +1.8+/-0.7 (PIO+drug-naïve diabetics), +0.7+/-0.3 (PIO+sulfonylurea-treated diabetics), and 0.7+/-0.2 (ROSI+sulfonylurea-withdrawn diabetics) vs. -0.2+/-0.3 in the two placebo groups (P<0.01, all TZDs vs. placebo, ANOVA). Improved insulin secretion correlated positively with increased body weight, fat mass, and Rd and inversely with decreased plasma glucose and FFA during the OGTT. In T2DM patients, TZD treatment leads to improved beta-cell function, which correlates strongly with improved glycemic control.",
"title": "Thiazolidinediones improve beta-cell function in type 2 diabetic patients."
},
{
"docid": "29366489",
"text": "Deleted in liver cancer 1 (DLC-1), as its name implied, was originally isolated as a potential tumor suppressor gene often deleted in hepatocellular carcinoma. Further studies have indicated that down-expression of DLC-1 either by genomic deletion or DNA methylation is associated with a variety of cancer types including lung, breast, prostate, kidney, colon, uterus, ovary, and stomach. Re-expression of DLC-1 in cancer cells regulates the structure of actin cytoskeleton and focal adhesions and significantly inhibits cell growth, supporting its role as a tumor suppressor. This tumor suppressive function relies on DLC-1's RhoGTPase activating protein (RhoGAP) activity and steroidogenic acute regulatory (StAR)-related lipid transfer (START) domain, as well as its focal adhesion localization, which is recruited by the Src Homology 2 (SH2) domains of tensins in a phosphotyrosine-independent fashion. Therefore, the expression and subcellular localization of DLC-1 could be a useful molecular marker for cancer prognosis, whereas DLC-1 and its downstream signaling molecules might be therapeutic targets for the treatment of cancer.",
"title": "Deleted in liver cancer-1 (DLC-1): a tumor suppressor not just for liver."
},
{
"docid": "27167110",
"text": "BACKGROUND Androgens play a critical role in the growth of both androgen dependent and castration-resistant prostate cancer (CRPC). Only a few micro-RNAs (miRNAs) have been suggested to be androgen regulated. We aim to identify androgen regulated miRNAs. METHODS We utilized LNCaP derived model, we have established, and which overexpresses the androgen receptor (AR), the VCaP cell line, and 13 intact-castrated prostate cancer (PC) xenograft pairs, as well as clinical specimens of untreated (PC) and CRPC. The expression of miRNAs was analyzed by microarrays and quantitative RT-PCR (Q-RT-PCR). Transfection of pre-miR-141 and anti-miR-141 was also used. RESULTS Seventeen miRNAs were > 1.5-fold up- or downregulated upon dihydrotestosterone (DHT) treatment in the cell lines, and 42 after castration in the AR-positive xenografts. Only four miRNAs (miR-10a, miR-141, miR-150*, and miR-1225-5p) showed similar androgen regulation in both cell lines and xenografts. Of those, miR-141 was found to be expressed more in PC and CRPC compared to benign prostate hyperplasia. Additionally, the overexpression of miR-141 enhanced growth of parental LNCaP cells while inhibition of miR-141 by anti-miR-141 suppressed the growth of the LNCaP subline overexpressing AR. CONCLUSIONS Only a few miRNAs were found to be androgen-regulated in both cell lines and xenografts models. Of those, the expression of miR-141 was upregulated in cancer. The ectopic overexpression of miR-141 increased growth of LNCaP cell suggesting it may contribute to the progression of PC.",
"title": "Androgen regulation of micro-RNAs in prostate cancer."
},
{
"docid": "24873253",
"text": "Patients with metastatic bone disease are at risk for developing skeletal-related events that can negatively influence quality of life, contributing to loss of autonomy and functional capabilities. Bisphosphonates have become an important component in the treatment of patients with bone metastases as they delay the onset and reduce the risk of skeletal-related events and also palliate or control bone pain in multiple cancer types, thus preserving quality of life. Zoledronic acid has proven efficacy and safety in patients with bone lesions from breast cancer, prostate cancer, lung cancer, and other solid tumors, as well as in patients with multiple myeloma. Current data suggest that early treatment with zoledronic acid (before the onset of bone pain) may provide additional clinical benefits and also positive effects on survival in subsets of patients who have elevated levels of N-telopeptide of type I collagen (NTX), a biochemical marker of bone resorption. Studies have shown that in patients with breast cancer, prostate cancer, lung cancer, or other solid tumors, normalization of elevated levels of NTX was observed in the majority of patients who received zoledronic acid. Furthermore, normalization of NTX values correlated with extended survival.",
"title": "Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease."
},
{
"docid": "25513319",
"text": "Metabolic pathway reprogramming is a hallmark of cancer cell growth and survival and supports the anabolic and energetic demands of these rapidly dividing cells. The underlying regulators of the tumor metabolic program are not completely understood; however, these factors have potential as cancer therapy targets. Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor cell survival and eventual metastasis. SRC-2 was highly elevated in a variety of tumors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the metastatic tumors evaluated. In prostate cancer cells, SRC-2 stimulated reductive carboxylation of α-ketoglutarate to generate citrate via retrograde TCA cycling, promoting lipogenesis and reprogramming of glutamine metabolism. Glutamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then triggered downstream transcriptional responses by coactivating SREBP-1, which subsequently enhanced lipogenic enzyme expression. Metabolic profiling of human prostate tumors identified a massive increase in the SRC-2-driven metabolic signature in metastatic tumors compared with that seen in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer metastasis. Moreover, SRC-2 inhibition in murine models severely attenuated the survival, growth, and metastasis of prostate cancer. Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for prostate cancer.",
"title": "Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis."
},
{
"docid": "25121903",
"text": "The number of cancer survivors continues to increase due to the aging and growth of the population and improvements in early detection and treatment. In order for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborated to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results (SEER) program registries. In addition, current treatment patterns for the most common cancer types are described based on information in the National Cancer Data Base and the SEER and SEER-Medicare linked databases; treatment-related side effects are also briefly described. Nearly 14.5 million Americans with a history of cancer were alive on January 1, 2014; by January 1, 2024, that number will increase to nearly 19 million. The 3 most common prevalent cancers among males are prostate cancer (43%), colorectal cancer (9%), and melanoma (8%), and those among females are cancers of the breast (41%), uterine corpus (8%), and colon and rectum (8%). The age distribution of survivors varies substantially by cancer type. For example, the majority of prostate cancer survivors (62%) are aged 70 years or older, whereas less than one-third (32%) of melanoma survivors are in this older age group. It is important for clinicians to understand the unique medical and psychosocial needs of cancer survivors and to proactively assess and manage these issues. There are a growing number of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship.",
"title": "Cancer treatment and survivorship statistics, 2014."
},
{
"docid": "21009874",
"text": "CONTEXT Whether immunosuppressive treatment adversely affects survival is unclear. OBJECTIVE To assess whether immunosuppressive drugs increase mortality. DESIGN Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases. Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage. The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios. Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis. SETTING Five tertiary ocular inflammation clinics. Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up. Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors. MAIN OUTCOME MEASURES Overall mortality, cancer mortality. RESULTS Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer. For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population. Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs. In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased. Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01). CONCLUSIONS Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality. Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.",
"title": "Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study."
},
{
"docid": "22180793",
"text": "The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology. Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC. Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis. Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro. In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression. N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion. These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance. Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.",
"title": "Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance"
},
{
"docid": "5372432",
"text": "BACKGROUND There is some previous evidence that diagnosis of cancer at death, recorded as registry death certificate only records, is associated with problems of access to care. METHODS Records from the Northern and Yorkshire Cancer Registry for patients registered with breast, colorectal, lung, ovarian or prostate cancer between 1994 and 2002 were supplemented with measures of travel time to general practitioner and hospital services, and social deprivation. Logistic regression was used to identify predictors of records where diagnosis was at death. RESULTS There was no association between the odds diagnosis at death and access to primary care. For all sites except breast, the highest odds of being a cancer diagnosed at death fell among those living in the highest quartile of hospital travel time, although it was only statistically significant for colorectal and ovary tumours. Those in the most deprived and furthest travel time to hospital quartile were 2.6 times more likely to be a diagnosis at death case compared with those in the most affluent and proximal areas. CONCLUSIONS There is some evidence that poorer geographical access to tertiary care, in particular when coupled with social disadvantages, may be associated with increased odds of diagnosis at death.",
"title": "Geographical access to healthcare in Northern England and post-mortem diagnosis of cancer."
},
{
"docid": "9956893",
"text": "OBJECTIVE Advances made in the past ten years highlight the notion that peroxisome proliferator-activated receptors gamma (PPARγ) has protective properties in the pathophysiology of osteoarthritis (OA). The aim of this study was to define the roles of PPARγ in AGEs-induced inflammatory response in human chondrocytes. METHODS Primary human chondrocytes were stimulated with AGEs in the presence or absence of neutralizing antibody against RAGE (anti-RAGE), MAPK specific inhibitors and PPARγ agonist pioglitazone. The expression of IL-1, MMP-13, TNF-α, PPARγ, nuclear NF-κB p65 and cytosol IκBα was determined by western blotting and real-time PCR. RESULTS AGEs could enhance the expression of IL-1, TNF-α, and MMP-13, but the level of PPARγ was decreased in a time- and dose-dependent manner, which was inhibited by anti-RAGE, SB203580 (P38 MAPK specific inhibitor) and SP600125 (a selective inhibitor of JNK). PPARγ agonist pioglitazone could inhibit the effects of AGEs-induced inflammatory response and PPARγ down-regulation. In human chondrocytes, AGEs could induce cytosol IκBα degradation and increase the level of nuclear NF-κB p65, which was inhibited by PPARγ agonist pioglitazone. CONCLUSIONS In primary human chondrocytes, AGEs could down-regulate PPARγ expression and increase the inflammatory mediators, which could be reversed by PPARγ agonist pioglitazone. Activation of RAGE by AGEs triggers a cascade of downstream signaling, including MAPK JNK/ p38, PPARγ and NF-κB. Taken together, PPARγ could be a potential target for pharmacologic intervention in the treatment of OA.",
"title": "The Role of PPARγ in Advanced Glycation End Products-Induced Inflammatory Response in Human Chondrocytes"
},
{
"docid": "308862",
"text": "BACKGROUND The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer. We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer. METHODS We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05. An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429. RESULTS A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression. After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority). Adverse events in both groups included fatigue, diminished sexual function, and hot flushes. CONCLUSIONS The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer. (ClinicalTrials.gov number, NCT00003026.)",
"title": "Duration of androgen suppression in the treatment of prostate cancer."
},
{
"docid": "46617075",
"text": "Lung cancer is the leading cause of cancer related deaths accounting for more deaths than breast, colon and prostate cancers combined. The Rb-p16 regulatory pathway plays an essential role in tumor suppression in the lung epithelium. This is evidenced by the nearly universal alterations in Rb-p16 pathway components in lung cancer, and the increased incidence of pulmonary carcinomas in persons with germline Rb mutations. Interestingly, p16 loss and Rb mutations preferentially occur in phenotypically distinct lung cancer subtypes. Analysis of human tumors has identified progressive preneoplastic lesions that accumulate molecular alterations in an orderly sequence. Epigenetic p16 gene modifications represent an early event in lung cancer progression. This review summarizes the human studies that demonstrate a critical role for the Rb-p16 tumor suppressor pathway in lung carcinogenesis, and discusses how these findings in combination with genetically engineered mouse models have significantly contributed to our understanding of lung cancer pathogenesis.",
"title": "Retinoblastoma regulatory pathway in lung cancer."
},
{
"docid": "52188256",
"text": "This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.",
"title": "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries."
},
{
"docid": "18473550",
"text": "Bisphosphonates are widely used agents for the treatment of malignant bone disease. They inhibit osteoclast-mediated bone resorption and can have direct effects on cancer cells. In this study, we investigated whether the anticancer activity of the third-generation bisphosphonate zoledronic acid (ZOL) could be enhanced by combination with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). We found that ZOL and SAHA cooperated to induce cell death in the prostate cancer cell lines LNCaP and PC-3. The effect was synergistic, as evidenced by combination index isobologram analysis. ZOL and SAHA synergized to induce dissipation of the mitochondrial transmembrane potential, to activate caspase-3, and to trigger DNA fragmentation, showing that the combination of ZOL and SAHA resulted in the initiation of apoptosis. Because ZOL acts by inhibiting the mevalonate pathway, thereby preventing protein prenylation, we explored whether the mevalonate pathway was also the target of the cooperative action of ZOL and SAHA. We found that geranylgeraniol, but not farnesol, significantly reduced ZOL/SAHA-induced cell death, indicating that the synergistic action of the agents was due to the inhibition of geranylgeranylation. Consistently, a direct inhibitor of geranylgeranylation, GGTI-298, synergized with SAHA to induce cell death, whereas an inhibitor of farnesylation, FTI-277, had no effect. In addition, SAHA synergized with mevastatin, an inhibitor of the proximal enzyme in the mevalonate pathway. These in vitro findings provide a rationale for an in vivo exploration into the potential of combining SAHA and ZOL, or other inhibitors of the mevalonate pathway, as an effective strategy for anticancer therapy.",
"title": "Synergistic activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid and the bisphosphonate zoledronic acid against prostate cancer cells in vitro."
},
{
"docid": "15113221",
"text": "Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in solid tumors; however, currently, no reliable test for PI3K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of PI3K, results in robust activation of this pathway, we developed and validated a microarray gene expression signature for immunohistochemistry (IHC)-detectable PTEN loss in breast cancer (BC). The most significant signature gene was PTEN itself, indicating that PTEN mRNA levels are the primary determinant of PTEN protein levels in BC. Some PTEN IHC-positive BCs exhibited the signature of PTEN loss, which was associated to moderately reduced PTEN mRNA levels cooperating with specific types of PIK3CA mutations and/or amplification of HER2. This demonstrates that the signature is more sensitive than PTEN IHC for identifying tumors with pathway activation. In independent data sets of breast, prostate, and bladder carcinoma, prediction of pathway activity by the signature correlated significantly to poor patient outcome. Stathmin, encoded by the signature gene STMN1, was an accurate IHC marker of the signature and had prognostic significance in BC. Stathmin was also pathway-pharmacodynamic in vitro and in vivo. Thus, the signature or its components such as stathmin may be clinically useful tests for stratification of patients for anti-PI3K pathway therapy and monitoring therapeutic efficacy. This study indicates that aberrant PI3K pathway signaling is strongly associated with metastasis and poor survival across carcinoma types, highlighting the enormous potential impact on patient survival that pathway inhibition could achieve.",
"title": "Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity."
}
] |
7352
|
Relationship between liquidity and an efficient market
|
[
{
"docid": "510328",
"text": "\"Liquidity is highly correlated to efficiency primarily because if an asset's price is not sampled during the time of a trade, it's price is unknown therefore inefficient. Past prices can be referenced, but they are not the price of the present. Prices of substitutes are even worse. SPY is extremely efficient for an equity. If permitted, it could easily trade with much lower ticks and still have potential for a locked market. Ideal exchange An ideal exchange has no public restrictions on trade. This is not to say that private restrictions would need to be put in place for various reasons, but one would only do that if it were responsible for its own survival instead of being too big to fail. In this market, trades would be approximately continuous for the largest securities and almost always locked because of continuous exchange fee competition with ever dropping minimum ticks. A market that can provide continuous locked orders with infinite precision is perfectly efficient from the point of view of the investor because the value of one's holdings are always known. EMH In terms of the theory the Efficient Market Hypothesis this is irrelevant to the rational investor. The rational investor will invest in the market at large of a given asset class, only increasing risk as wealth increases thus moving to more volatile asset classes when the volatility can be absorbed by excess wealth. Here, liquidity is also helpful, the \"\"two heads are better than one\"\" way of thinking. The more invested in an asset class, the lower the class's variance and vice versa. Bonds, the least variant, dwarf equities which dwarf options, all in order of the least variance. Believe it or not, there was a day when bonds were almost as risky as equities. For those concerned with EMH, liquidity is also believed to increase efficiency in some forms because liquidity is proportional to the number of individuals invested thus reducing the likelihood of an insufficient number of participants. External inefficiency In the case of ETFs that do not perfectly track their underlying index less costs at all times between index changes, this is because they are forbidden from directly trading in the market on their own behalf. If they were allowed and honest, the price would always be perfect and much more liquid than it otherwise should be since the combined frequency of all index members is much higher than any one alone. If one was dishonest, it would try to defraud with higher or lower numbers; however, if insider trading were permitted, both would fail due to the prisoner's dilemma that there is no honor among thieves. Here, the market would detect the problem much sooner because the insiders would arbitrage the false price away. Indirect internal efficiency Taking emerging market ETFs as an example, the markets that those are invested into are heavily restricted, so their ETF to underlying price inefficiencies are more pronounced even though the ETFs are actually working to make those underlying markets more efficient because a price for them altogether is known.\"",
"title": ""
}
] |
[
{
"docid": "169013",
"text": "Very important. Returning again to the example of the farmer, efficient, liquid markets that fairly reflect the price of a given asset allow that farmer to run his business as cost effectively as he can. That (in theory) lowers the price of his goods for the consumer. If he wasn't able to efficiently hedge, he would have to charge a premium to reflect the price risk he takes on between planting and harvesting his corn. Being pedantic here but single stock futures markets are extremely quiet. If you were the owner of a company and you traded *options* on your company stock (a hilariously common form of insider trading) yes, that would be illegal and the SEC would certainly come after you.",
"title": ""
},
{
"docid": "124038",
"text": "Some liquidity Since you're using IB, and you seem to be an investor not a trader, so you won't notice especially if you walk your orders, but you will suffer the bid/ask spread as everyone else albeit wider. If buying, the best strategy unless if one is time constrained is to walk the entire bid from the best bid to the best ask. It is highly likely that someone will hit your order before you hit the best ask. If they don't, as a long term investor, the few pennies won't make or break you, especially if the price per share is 100 USD equivalent, but it is an excellent habit to form and fun. Since you're buying ETFs, even though your orders are small, you would be adding liquidity to your market, helping it become more efficient because your orders could be used to arbitrage against all of the ETF's holdings, in turn providing liquidity for those holdings. No liquidity This could only be done with an extremely low cost broker like IB because the trading commissions would make it prohibitively expensive. There are huge risks when trading an illiquid security such as VEUR. EWL would be much less risky thus less expensive. Securities with no liquidity can be traded, but they must be traded very carefully. In the case of a security that can only attract about 20 shares per day in volume, only single shares should be bid. The market makers, suffering from a dearth in volume may not even be willing to haggle; therefore, the only recourse is a statistical arbitrageur, who will attempt to profit from the spread between other more liquid versions of the security. Considering the available alternative, VEUR is not recommended to trade.",
"title": ""
},
{
"docid": "135216",
"text": "\"The market capitalization of a stock is the number of shares outstanding (of each stock class), times the price of last trade (of each stock class). In a liquid market (where there are lots of buyers and sellers at all price points), this represents the price that is between what people are bidding for the stock and what people are asking for the stock. If you offer any small amount more than the last price, there will be a seller, and if you ask any small amount less than the last price, there will be a buyer, at least for a small amount of stock. Thus, in a liquid market, everyone who owns the stock doesn't want to sell at least some of their stock for a bit less than the last trade price, and everyone who doesn't have the stock doesn't want to buy some of the stock for a bit more than the last trade price. With those assumptions, and a low-friction trading environment, we can say that the last trade value is a good midpoint of what people think one share is worth. If we then multiply it by the number of shares, we get an approximation of what the company is worth. In no way, shape or form does it not mean that there is 32 billion more invested in the company, or even used to purchase stock. There are situations where a 32 billion market cap swing could mean 32 billion more money was invested in the company: the company issues a pile of new shares, and takes in the resulting money. People are completely neutral about this gathering in of cash in exchange for dilluting shares. So the share price remains unchanged, the company gains 32 billion dollars, and there are now more shares outstanding. Now, in some sense, there is zero dollars currently invested in a stock; when you buy a stock, you no longer have the money, and the money goes to the person who no longer has the stock. The issue here is the use of the continuous tense of \"\"invested in\"\"; the investment was made at some point, but the money doesn't really stay in this continuous state of being. Unless you consider the investment liquid, and the option to take money out being implicit, it being a continuous action doesn't make much sense. Sometimes the money is invested in the company, when the company causes stocks to come into being and sells them. The owners of stocks has invested money in stocks in that they spent that money to buy the stocks, but the total sum of money ever spent on stocks for a given company is not really a useful value. The market capitalization is an approximation, which under the efficient market hypothesis (that markets find the correct price for things nearly instantly) is reasonably accurate, of the value the company has collectively to its shareholders. The efficient market hypothesis isn't accurate, but it is an acceptable rule of thumb. Now, this value -- market capitalization -- is arguably not the total value of a company: other stakeholders include bond holders, labour, management, various contract counter-parties, government and customers. Some companies are structured so that almost all value is captured not by the stock owners, but by contract counter-parties (this is sometimes used for hiding assets or debts). But for most large publically traded companies, it (in theory) shouldn't be far off.\"",
"title": ""
},
{
"docid": "291327",
"text": "Option liquidity and underlying liquidity tend to go hand in hand. According to regulation, what kinds of issues can have options even trading are restricted by volume and cost due to registration with the authorities. Studies have shown that the introduction of option trading causes a spike in underlying trading. Market makers and the like can provide more option liquidity if there is more underlying and option liquidity, a reflexive relationship. The cost to provide liquidity is directly related to the cost for liquidity providers to hedge, as evidenced by the bid ask spread. Liquidity providers in option markets prefer to hedge mostly with other options, hedging residual greeks with other assets such as the underlying, volatility, time, interest rates, etc because trading costs are lower since the two offsetting options hedge most of each other out, requiring less trading in the other assets.",
"title": ""
},
{
"docid": "220327",
"text": "\"Beta is the correct answer. It is THE measure of the risk relationship of a stock with the broad market. R squared is incorrect unless you mean something very odd by \"\"co-efficiency.\"\" A stock that goes up each time the market goes down has very low co-efficiency (negative risk as you have defined it) but very high R squared. A stock that goes the same direction as the market but twice as far (with a lot of noise) has a very low R squared but contains a lot of market risk. A stock that always goes in the same direction as the market but only a 100th as far is very safe but has a very high R squared. You can calculate beta using \"\"slope\"\" in excel or doing a regression, but the easiest thing is just to look up the beta in yahoo finance or elsewhere. You don't need to calculate it for yourself normally.\"",
"title": ""
},
{
"docid": "505213",
"text": "Having a highly liquid emergency fund can lubricate the wheels for disaster recovery. For example, several years ago I returned from a vacation to discover that, during my absence, a plumbing fixture had broken and my house was flooded. Since we had sufficient liquidity to cover the cost of the repairs in our emergency fund, the insurance company was much easier to deal with, and the relationships between the contractor, bank, and insurance company were much smoother. The bank was able to approve the insurance in minutes versus days. Ironically, we didn't actually have to touch our emergency fund precisely because we had it. Clarification - I make it a point to have no debt.",
"title": ""
},
{
"docid": "575834",
"text": "\"Suppose you have a bar of gold and are hungry. I buy the gold from you for cash, which you then use to buy food, clothes and generally support yourself. Would it be fair to say that I paid for your food, clothes etc? I don't think so - I think *you* paid for them, in gold. I facilitated the exchange of gold into money, and without me or someone like me around to provide liquidity for your gold, you'd still be hungry. But fundamentally, it was the gold that was valuable. Now, suppose there is a lack of liquidity in gold - there's a shortage of gold buyers. I take advantage of this distortion to offer to buy your gold for half its free market value. You don't want to accept this deal, but since your only alternative is starvation, you accept. I say this is wrong, not because of socialism, but because of capitalism. The efficiency of capitalism arises from the price system of value. Goods and services command a fair market price, and buyers and sellers have access to both liquidity and good information about the relative value of things. When distortions are allowed to interfere with free market pricing - as inevitably happens under lassiez-faire capitalism - this efficiency is lost. Good government regulation is necessary to keep markets free and efficient, and this is good for everyone. So what does this have to do with David Siegel? First, nothing in my example above changes when you substitute \"\"labor\"\" for \"\"gold.\"\" If I am hungry but I have a skill, and I sell you some of my labor for cash, then use the cash to buy food, *you did not give me the food*. You did not \"\"pay for my food,\"\" you did not \"\"make it possible for me to get food,\"\" or anything of the sort. *I paid for it myself*, by trading labor for cash in exactly the same way that you could trade gold for cash. Second, the price system of value allows you to earn a \"\"normal profit,\"\" which means sufficient profit for resources to remain within an industry. But \"\"excess profit\"\" harms market efficiency and thus the price system. This is pure capitalist theory, straight from Adam Smith; it is nothing to do with socialism or communism. It is quite clear that David Siegel is taking excess profit. This is no different from the sort of profiteering I described when there's only one gold dealer in town. It is parasitic behavior according to *capitalist* theory. And finally, David Siegel is the guy who invented high-pressure selling of timeshares by inviting familes to a \"\"free\"\" vacation, trapping them in a room, and basically holding them hostage until they sign on the dotted line. His business is near-criminal. You can argue that drug kingpins also create thousands of jobs - that doesn't make them good people, or their actions beneficial to society. I already thought David Siegel was a parasite on society before I ever heard of his opinion on Obama. And quite frankly, I'm shocked and appalled that people are actually defending him.\"",
"title": ""
},
{
"docid": "469819",
"text": "While theoretically it works it's not a realistic trade because of market efficiency. It's realistic for brokers to advertise trades like this so they can earn more customers and commission. These sorts of trades will be priced in to highly liquid big ticket names like KO and the vast majority of the market. The possibility exists with small names with less liquidity, less trading volume; however, the very execution of this trade will alter the behavior of impending traders thus minimizing any potential profits.",
"title": ""
},
{
"docid": "251715",
"text": "Market Capitalization is the product of the current share price (the last time someone sold a share of the stock, how much?) times the number of outstanding shares of stock, summed up over all of the stock categories. Assuming the efficient market hypothesis and a liquid market, this gives the current total value of the companies' assets (both tangible and intangible). Both the EMH and perfect liquidity may not hold at all times. Beyond those theoretical problems, in practice, someone trying to buy or sell the company at that price is going to be in for a surprise; the fact that someone wants to sell that many stocks, or buy that many stocks, will move the price of the company stock.",
"title": ""
},
{
"docid": "47542",
"text": "Zhongshan Opaye Industry Co.,Ltd. is a professional home appliances manufacturer in China. Opaye company is a one of the leading companies to produce the professional portable clothes dryer, electric thermo pot, electric water boiler, electric kettle, soymilk maker, juice extractor, slow juicer, screw juice extractor, soup maker, commercial blender, food processor etc. Opaye's products are sold well in worldwide markets, including the USA, Europe,Southeast Asia, Japan and Taiwan area. Opaye keeps the stable business relationships with such our world partners as Metro Germany, Sunbeam Europe and QVC UK. As an ISO9001/2000 certified company, opaye is highly focused on quality control, just-in-time delivery, cost control,provision of innovative and tailored products and good service to attain total customer satisfaction and maintain a win-win relationship with customers on a long-term basis. As a must to enter our target markets, most of our products are CE/GS, ETL, CB and CCC approved and Rosh compliant. To keep our advantage in the industry,we registered technology and design patent for our products and keep improving our quality and production efficiency. The in-house tooling workshop, metal department, plastic injection department and more than 1000 workers enable our cost efficiency and productivity. Repeating orders by our clients is the best proof that we have matched their demands in terms of quality and reliability. Welcome and find out how you will enjoy working with Opaye. Further information pls feel free to visit our website: www.opaye.com",
"title": ""
},
{
"docid": "189289",
"text": "It seems ideal to have the employment be all about both income and ethics, but the problem is that for most people in the industry more often at one point or another they will have to choose between their income or their ethics. Ethics should always hold supremacy over personal gain. Because ethics maintain the relationships (formal and informal) between entities involved in the markets. Without those long term relationships, there is no room for trust and therefore no reason to be willingness for entities to exchange with one another **fairly**. If you don't have a overall fair financial markets, on the long term it will hurt the overall economy, why? Because people will have no trust in buying equity prices, there will be no trust in prospects. People will save most of their money in cash and outright avoid anything or everything about investing. If there are less clients, there is less capital for the entire industry. The trust of the aggregate non-active investing clients with the capital range between 100k-500 million matters. And to make it common knowledge to hold personal gain above them is not a good way to have them keep their money in the markets.",
"title": ""
},
{
"docid": "569206",
"text": "\"I would let them get their hands dirty, learn by practicing. Below you can find a simple program to generate your own efficient frontier, just 29 lines' python. Depending on the age, adult could help in the activity but I would not make it too lecturing. With child-parent relationship, I would make it a challenge, no easy money anymore -- let-your-money work-for-you -attitude, create the efficient portfolio! If there are many children, I would do a competition over years' time-span or make many small competitions. Winner is the one whose portfolio is closest to some efficient portfolio such as lowest-variance-portfolio, I have the code to calculate things like that but it is trivial so build on the code below. Because the efficient frontier is a good way to let participants to investigate different returns and risk between assets classes like stocks, bonds and money, I would make the thing more serious. The winner could get his/her designed portfolio (to keep it fair in your budget, you could limit choices to index funds starting with 1EUR investment or to ask bottle-price-participation-fee, bring me a bottle and you are in. No money issue.). Since they probably don't have much money, I would choose free software. Have fun! Step-by-step instructions for your own Efficient Frontier Copy and run the Python script with $ python simple.py > .datSimple Plot the data with $ gnuplot -e \"\"set ylabel 'Return'; set xlabel 'Risk'; set terminal png; set output 'yourEffFrontier.png'; plot '.datSimple'\"\" or any spreadsheet program. Your first \"\"assets\"\" could well be low-risk candies and some easy-to-stale products like bananas -- but beware, notice the PS. Simple Efficient-frontier generator P.s. do not stagnate with collectibles, such as candies and toys, and retailer products, such as mangos, because they are not really good \"\"investments\"\" per se, a bit more like speculation. The retailer gets a huge percentage, for further information consult Bogleheads.org like here about collectible items.\"",
"title": ""
},
{
"docid": "584633",
"text": "It seems that you're interested in an asset which you can hold that would go up when the gold price went down. It seems like a good place to start would be an index fund, which invests in the general stock market. When the gold market falls, this would mainly affect gold mining companies. These do not make up a sizable portion of any index fund, which is invested broadly in the market. Unfortunately, in order to act on this, you would also have to believe that the stock market was a good investment. To test this theory, I looked at an ETF index fund which tracks the S&P 500, and compared it to an ETF which invests in gold. I found that the daily price movements of the stock market were positively correlated with the price of gold. This result was statistically significant. The weekly price movements of the stock market were also correlated with the price of gold. This result was also statistically significant. When the holding period was stretched to one month, there was still a positive relationship between the stock market's price moves and the price of gold. This result was not statistically significant. When the holding period was stretched to one year, there was a negative relationship between the price changes in the stock market and the price of gold. This result was not statistically significant, either.",
"title": ""
},
{
"docid": "423978",
"text": "> There are plenty of people that consistently beat the market. If the market were truly efficient, then everyone should just passively invest, which would make the market inefficient, leading to active investment. Passive investing a.) Doesn't mark the market *less* efficient, I don't know how you came to that conclusion. b.) There is not a big group of people who consistently beat the markets. There's a tiny, *tiny* sliver of a fraction of a portion of a group of people that beat the market over any ten year period, which is *consistent* with pure randomness. You're statistically likely to say those kinds of anomalies. In fact, it'd be stranger if we *didn't*. c.) The markets aren't *truly* efficient. They can't. There's imperfect information. The point is the potential exploits cannot 1.) be exploited on scale, because that creates market efficiency, and cannot 2.) be public, because that also creates efficiency. As more and more exploits are found, we're eliminating all these black swans. If you compare all 400 professionally managed mutual funds, only 2 have ever beaten the market, and by less than 50 basis points. That's 0.5%. That's not even consistent with randomness, that's worse than random. It goes to show how few and far between any potential exploits exist. It's simply not worth your time as an investor, because if giant firms employing hundreds cannot find them, a handful of people won't be able to find them by anything other than chance. It's almost always better to passively invest. You can read more about this, because while intuitively you may feel active investment can be better, the numbers don't lie and I promise you you're very wrong.",
"title": ""
},
{
"docid": "351976",
"text": "We have a very mixed economy. If takeovers were all a case of a more competent organization taking over a less competent organizations then there would be no need for vetting. But that is not the case. We have companies that are monopolies thanks to their relationship with governments. They are not more efficient, better run, more visionary, or more capable. Indeed, they are often dependent on a single monopoly, in a single market. Everything else they touch turns to crap. They acquire other companies trying to stave off their own collapse. Do you want to invite companies like that come into your market and link important companies, in vital markets to that house of cards?",
"title": ""
},
{
"docid": "486692",
"text": "Not all limit orders add liquidity, but all market orders remove liquidity presuming there is liquidity to remove. A liquidity providing order is one that is posted to the limit book. If an order, even a limit order, is filled before being posted to the limit book, it removes liquidity. Liquidity is measured by a balance and abundance of quantities posted on the limit book and the best spread between the lowest ask and the highest bid.",
"title": ""
},
{
"docid": "516596",
"text": "? The guy claimed that BTC had intrinsic value so I asked him what instrinsic value BTC had. BTC has literally 0 intrinsic value, it doesn't even exist physically. I'm not saying the technology is worthless or that it doesn't have value, but it certainly doesn't have intrinsic value. Gold--you can create things with gold, silver--silver is important in medical applications, can be made into things. These things have value, even in circumstances where the market disappears or the demand ceases. A company has intrinsic value in that its assets can be sold off and liquidated for cash--even if they don't generate a single penny. Gold has intrinsic value in that even if there is no one demanding gold, it can still be useful for something. If no one wants BTC, you literally can't do anything with it except look at the numbers. It's the equivalent of hoarding a pile of dust that the market valued for some reason and then the market crashes--what are you going to do with a pile of dust? Literally nothing except watch it fly in the wind. It was only worth something because other people valued it. Block chain is revolutionary tech, but there is no IV with BTC. BTC and block-chain aren't really even interchangeable--it's like the relationship between a square and a rectangle; a square is a rectangle but a rectangle is not necessarily a square. BTC is block chain but block chain isn't BTC. Even if BTC fails and dies, there will be something else that takes its place but there is no IV with BTC. Trying to assign BTC some sort of IV is a misleading. There are many reasons BTC is revolutionary but it's not because there is some sort of huge IV attached to it. And where did I ever call BTC a ponzi scheme? You sound like you got a chip on your shoulder.",
"title": ""
},
{
"docid": "66716",
"text": "\"n1. go to tradeworx.com and you can read some papers. 2. Revenues of hft have gone down substantially. About 15 years ago the total market was around 7 billion, it has dropped to 1 billion this year. 3. \"\"no goods or valuable services are produced.- That is false. hft provides liquidity and low spreads. There is a reason why you can buy or sell a share of a stock and the spread is 1 penny. One of the main reasons to go public is to have the secondary market liquid. There is a reason you can instantly sell or buy a stock... Do you realize you used to have to actually call your broker and he had to negotiate an order on the floor? hft makes the markets more efficient. The average person can sign up an online acct and trade/invest for basically nothing. Why do you think that is? finally who are you to say how I can or can not allocate my money. If I develop my own strategy that trades every second why can't I?\"",
"title": ""
},
{
"docid": "78053",
"text": "\"Joke warning: These days, it seems that rogue trading programs are the big market makers (this concludes the joke) Historically, exchange members were market makers. One or more members guaranteed a market in a particular stock, and would buy whatever you wanted to sell (or vice-versa). In a balanced market -- one where there were an equal number of buyers and sellers -- the spread was indeed profit for them. To make this work, market makers need an enormous amount of liquidity (ability to hold an inventory of stocks) to deal with temporary imbalances. And a day like October 29, 1929, can make that liquidity evaporate. I say \"\"historically,\"\" because I don't think that any stock market works this way today (I was discussing this very topic with a colleague last week, went to Wikipedia to look at the structure of the NYSE, and saw no mention of exchange members as market makers -- in fact, it appears that the NYSE is no longer a member-based exchange). Instead, today most (all?) trading happens on \"\"electronic crossing networks,\"\" where the spread is simply the difference between the highest bid and lowest ask. In a liquid stock, there will be hundreds if not thousands of orders clustered around the \"\"current\"\" price, usually diverging by fractions of a cent. In an illiquid stock, there may be a spread, but eventually one bid will move up or one ask will move down (or new bids will come in). You could claim that an entity with a large block of stock to move takes the role of market maker, but it doesn't have the same meaning as an exchange market maker. Since there's no entity between the bidder and asker, there's no profit in the spread, just a fee taken by the ECN. Edit: I think you have a misconception of what the \"\"spread\"\" is. It's simply the difference between the highest bid and the lowest offer. At the instant a trade takes place, the spread is 0: the highest bid equals the lowest offer, and the bidder and seller exchange shares for money. As soon as that trade is completed, the spread re-appears. The only way that a trade happens is if buyer and seller agree on price. The traditional market maker is simply an entity that has the ability to buy or sell an effectively unlimited number of shares. However, if the market maker sets a price and there are no buyers, then no trade takes place. And if there's another entity willing to sell shares below the market maker's price, then the buyers will go to that entity unless the market's rules forbid it.\"",
"title": ""
},
{
"docid": "113871",
"text": "I would just take $2000 and multiply by your marginal tax rate, weight that between the 5 other people according to their share of the prize money and ask them to give you that. From your question it seems like you all have a good working relationship, I'm sure the other partners would agree to that. I think it's the simplest solution that is also fair and equitable. Basically, you pay the tax on 2000 and they pay you back for their share of the tax. Much easier than trying to pass it through your tax return for 5 separate people for a minimal amount of $'s. In hindsight, the best way to do it would have been to 1099 the person with the lowest marginal tax rate for the year to minimize the total tax paid on the 2000. Probably only would've been a few dollars difference but still the most efficient way to do it.",
"title": ""
},
{
"docid": "474896",
"text": "On the one hand, it's a great idea to open a Roth IRA now, once you've got the cash to contribute. It's a tax designation sounds like it would fit your meager earnings this year. The main reason to open one now rather than later is that some types of withdrawls require the account be aged 5 years. But you can also withdraw the amount you've contributed tax free any time. Student loans right now are pricey, so if you're carrying a balance at say 6.8 percent fixed you should pay that down ASAP. Beyond that, I'd keep the rest liquid for now. Having that kind of liquid cash is extremely reassuring, and many of the biggest returns on investment are going to be in your personal life. More fuel efficient vehicles, energy efficient appliances, computer backups, chest freezers and bulk meat purchases, etc. One example I see every six months is car insurance: I can pay for six months in full or I can pay a smaller monthly bill plus a small fee. That fee is well above current market rates. You see this everywhere; people searching for lower minimum payments rather than lower total costs. Save your money up and be the smart buyer. It's too damn expensive to be broke.",
"title": ""
},
{
"docid": "505244",
"text": "\"- In a quote driven market, must every investor trade with a market maker? In other words, two parties that are both not market makers cannot trade between themselves directly? In a way yes, all trades go through a market maker but those trades can be orders put in place by a \"\"person\"\" IE: you, or me. - Does a quote driven market only display the \"\"best\"\" bid and ask prices proposed by the market makers? In other words, only the highest bid price among all the market makers is displayed, and other lower bid prices by other market makers are not? Similarly, only the lowest ask price over all market makers is displayed, and other higher ask prices by other market makers are not? No, you can see other lower bid and higher ask prices. - In a order-driven market, is it meaningful to talk about \"\"the current stock price\"\", which is the price of last transaction? Well that's kind of an opinion. Information is information so it won't be bad to know it. Personally I would say the bid and ask price is more important. However in the real world these prices are changing constantly and quickly so realistically it is easier to keep track of the quote price and most likely the bid/ask spread is small and the quote will fall in between. The less liquid a security is the more important the bid/ask is. -- This goes for all market types. - For a specific asset, will there be several transactions happened at the same time but with different prices? Today with electronic markets, trades can happen so quickly it's difficult to say. In the US stock market trades happen one at a time but there is no set time limit between each trade. So within 1 second you can have a trade be $50 or $50.04. However it will only go to $50.04 when the lower ask prices have been exhausted. - Does an order driven market have market makers? By definition, no. - What are some examples of quote driven and order driven financial markets, in which investors are commonly trading stocks and derivatives, especially in U.S.? Quote driven market: Bond market, Forex. Order driven market: NYSE comes from an order driven market but now would be better classified as a \"\"hybird market\"\" Conclusion: If you are asking in order to better understand today's stock markets then these old definitions of Quote market or Order market may not work. The big markets in the real world are neither. (IE: Nasdaq, NYSE...) The NYSE and Nasdaq are better classified as a \"\"hybird market\"\" as they use more then a single tactic from both market types to insure market liquidity, and transparency. Markets these days are strongly electronic, fast, and fairly liquid in most cases. Here are some resources to better understand these markets: An Introduction To Securities Markets The NYSE And Nasdaq: How They Work Understanding Order Execution\"",
"title": ""
},
{
"docid": "474449",
"text": "\"Are you talking long-term institutional or retail investors? Long-term *retail* investors look for *orderly markets*, the antithesis of HFT business models, which have a direct correlation between market volatility and profits. To a lesser extent, some \"\"dumb money\"\"/\"\"muppet\"\" institutionals do as well. HFT firms tout they supply liquidity into markets, when in fact the opposite is true. Yes, HFTs supply liquidity, *but only when the liquidity's benefits runs in their direction*. That is, they are applying the part of the liquidity definition that mentions \"\"high trading activity\"\", and conveniently ignoring the part that simultaneously requires \"\"*easily* buying *or* selling an asset\"\". If HFT's are the new exchange floor, then they need to be formalized as such, *and become bound to market maker responsibilities*. If they are actually supplying liquidity, like real Designated Market Makers in the NYSE for example, they become responsible to supply a specified liquidity for specified ticker symbols in exchange for their informational advantage on those tickers. The indisputable fact is that HFT cannot exist at their current profit levels without the information advantage they gain with preferential access to tick-by-tick data unavailable to investors who cannot afford the exchange fees ($1M per exchange 10 years ago, more now). Restrict the entire market, including HFTs, to only second-by-second price data without the tick-by-tick depth, and they won't do so well. Don't get me wrong, I'm not knocking HFTs *per se*; I think they are a marvelous development, so long as they really do \"\"supply liquidity\"\". Right now, they aren't doing so, and especially in an orderly manner. If you want retail investors to keep out of the water as they are doing now, by all means let HFT (and regulatory capture, and a whole host of other financial service industry ills) run as they are. There are arguments to be made about \"\"only let the professionals play the market\"\", where there is no role for retail and anyone who doesn't know how to play the long-term investment game needs to get out of the kitchen. But if you are making such an argument, come out and say so.\"",
"title": ""
},
{
"docid": "186928",
"text": "The relationship is not linear, and depends on a lot of factors. The term you're looking for is efficient frontier, the optimal rate of return for a given level of risk. The goal is to be on the efficient frontier, meaning that for the given level of risk, you're receiving the greatest possible rate of return (reward). http://www.investopedia.com/terms/e/efficientfrontier.asp",
"title": ""
},
{
"docid": "146204",
"text": "There is economic value added to the marketplace, by having many investors trading stocks. The stock market itself can be thought of as a tool which provides additional 'liquidity' to the marketplace. Liquidity is the ease with which you can convert your assets into cash (for example, how quickly could you sell your car if you needed money to pay a medical bill?). Without a stock market, funds would be very illiquid - an investor would likely need to post advertisements to have other people consider buying his/her shares. Until the match between a buyer and seller is found, the person with the shares can't use the cash they need. On the other side of the transaction, are people who have an appetite for risk. This means that, for various reasons, they are willing to take on more risk than you, if it pays off on average (they are young [and have many years of salary earnings in front of them], or they are rich [can afford to lose money sometimes if it pays off on average]). Consider this like a transaction between your insurance broker - you don't want to pay for a new car if you get in an accident, and you're willing to pay total annual premiums that, on average, will cost more than that same car over time. You don't want the risk, but the insurance company does - that's how they make money. So by participating in any marketplace, you are providing value, in the form of liquidity, and by allowing the market to allocate risk to those willing to take it on.",
"title": ""
},
{
"docid": "490540",
"text": "Limited transactions: what's to stop a firm from having thousands of bank accounts to avoid the limit. This of course is costly. Tax on transactions: some trades are worth $00.001 and some are $190,000. They shouldn't be taxed the same. Both increase costs of capital and literally everyone in America pays for it. Investment is more expensive. And our beautiful liquid market is no longer as efficient and can no longer responds as quickly to market forces. Investors now go to other foreign markets that don't limit or charge for transactions. Both plans will cost the economy billions of dollars and for what? So some computers don't trade almost instantaneously? Exactly why is that a problem other than class warfare? A lot of the risks that people have about flash crashes have been mitigated with better algorithms and rules.",
"title": ""
},
{
"docid": "69696",
"text": "You said the decision will be made by EOD. If you've made the decision prior to the market close, I'd execute on the closing price. If you are trading stocks with any decent volume, I'd not worry about the liquidity. If your strategy's profits are so small that your gains are significantly impacted by say, the bid/ask spread (a penny or less for liquid stocks) I'd rethink the approach. You'll find the difference between the market open and prior night close is far greater than the normal bid/ask.",
"title": ""
},
{
"docid": "554996",
"text": "\"First, note that a share represents a % of ownership of a company. In addition to the right to vote in the management of the company [by voting on the board of directors, who hires the CEO, who hires the VPs, etc...], this gives you the right to all future value of the company after paying off expenses and debts. You will receive this money in two forms: dividends approved by the board of directors, and the final liquidation value if the company closes shop. There are many ways to attempt to determine the value of a company, but the basic theory is that the company is worth a cashflow stream equal to all future dividends + the liquidation value. So, the market's \"\"goal\"\" is to attempt to determine what that future cash flow stream is, and what the risk related to it is. Depending on who you talk to, a typical stock market has some degree of 'market efficiency'. Market efficiency is basically a comment about how quickly the market reacts to news. In a regulated marketplace with a high degree of information available, market efficiency should be quite high. This basically means that stock markets in developed countries have enough traders and enough news reporting that as soon as something public is known about a company, there are many, many people who take that information and attempt to predict the impact on future earnings of the company. For example, if Starbucks announces earnings that were 10% less than estimated previously, the market will quickly respond with people buying Starbucks shares lowering their price on the assumption that the total value of the Starbucks company has decreased. Most of this trading analysis is done by institutional investors. It isn't simply office workers selling shares on their break in the coffee room, it's mostly people in the finance industry who specialize in various areas for their firms, and work to quickly react to news like this. Is the market perfectly efficient? No. The psychology of trading [ie: people panicking, or reacting based on emotion instead of logic], as well as any inadequacy of information, means that not all news is perfectly acted upon immediately. However, my personal opinion is that for large markets, the market is roughly efficient enough that you can assume that you won't be able to read the newspaper and analyze stock news in a way better than the institutional investors. If a market is generally efficient, then it would be very difficult for a group of people to manipulate it, because someone else would quickly take advantage of that. For example, you suggest that some people might collectively 'short AMZN' [a company worth half a trillion dollars, so your nefarious group would need to have $5 Billion of capital just to trade 1% of the company]. If someone did that, the rest of the market would happily buy up AMZN at reduced prices, and the people who shorted it would be left holding the bag. However, when you deal with smaller items, some more likely market manipulation can occur. For example, when trading penny stocks, there are people who attempt to manipulate the stock price and then make a profitable trade afterwards. This takes advantage of the low amount of information available for tiny companies, as well as the limited number of institutional investors who pay attention to them. Effectively it attempts to manipulate people who are not very sophisticated. So, some manipulation can occur in markets with limited information, but for the most part prices are determined by the 'market consensus' on what the future profits of a company will be. Additional example of what a share really is: Imagine your neighbor has a treasure chest on his driveway: He gathers the neighborhood together, and asks if anyone wants to buy a % of the value he will get from opening the treasure chest. Perhaps it's a glass treasure chest, and you can mostly see inside it. You see that it is mostly gold and silver, and you weigh the chest and can see that it's about 100 lbs all together. So in your head, you take the price of gold and silver, and estimate how much gold is in the chest, and how much silver is there. You estimate that the chest has roughly $1,000,000 of value inside. So, you offer to buy 10% of the chest, for $90k [you don't want to pay exactly 10% of the value of the company, because you aren't completely sure of the value; you are taking on some risk, so you want to be compensated for that risk]. Now assume all your neighbors value the chest themselves, and they come up with the same approximate value as you. So your neighbor hands out little certificates to 10 of you, and they each say \"\"this person has a right to 10% of the value of the treasure chest\"\". He then calls for a vote from all the new 'shareholders', and asks if you want to get the money back as soon as he sells the chest, or if you want him to buy a ship and try and find more chests. It seems you're all impatient, because you all vote to fully pay out the money as soon as he has it. So your neighbor collects his $900k [$90k for each 10% share, * 10], and heads to the goldsmith to sell the chest. But before he gets there, a news report comes out that the price of gold has gone up. Because you own a share of something based on the price of gold, you know that your 10% treasure chest investment has increased in value. You now believe that your 10% is worth $105k. You put a flyer up around the neighborhood, saying you will sell your share for $105k. Because other flyers are going up to sell for about $103-$106k, it seems your valuation was mostly consistent with the market. Eventually someone driving by sees your flyer, and offers you $104k for your shares. You agree, because you want the cash now and don't want to wait for the treasure chest to be sold. Now, when the treasure chest gets sold to the goldsmith, assume it sells for $1,060,000 [turns out you underestimated the value of the company]. The person who bought your 10% share will get $106k [he gained $2k]. Your neighbor who found the chest got $900k [because he sold the shares earlier, when the value of the chest was less clear], and you got $104k, which for you was a gain of $14k above what you paid for it. This is basically what happens with shares. Buy owning a portion of the company, you have a right to get a dividend of future earnings. But, it could take a long time for you to get those earnings, and they might not be exactly what you expect. So some people do buy and sell shares to try and earn money, but the reason they are able to do that is because the shares are inherently worth something - they are worth a small % of the company and its earnings.\"",
"title": ""
},
{
"docid": "580757",
"text": "If you do not understand the volatility of the fx market, you need to stop trading it, immediately. There are many reasons that fx is riskier than other types of investing, and you bear those risks whether you understand them or not. Below are a number of reasons why fx trading has high levels of risk: 1) FX trades on the relative exchange rate between currencies. That means it is a zero-sum game. Over time, the global fx market cannot 'grow'. If the US economy doubles in size, and the European economy doubles in size, then the exchange rate between the USD and the EUR will be the same as it is today (in an extreme example, all else being equal, yes I know that value of currency /= value of total economy, but the general point stands). Compare that with the stock market - if the US economy doubles in size, then effectively the value of your stock investments will double in size. That means that stocks, bonds, etc. tied to real world economies generally increase when the global economy increases - it is a positive sum game, where many players can be winners. On the long term, on average, most people earn value, without needing to get into 'timing' of trades. This allows many people to consider long-term equity investing to be lower risk than 'day-trading'. With FX, because the value of a currency is in its relative position compared with another currency, 1 player is a winner, 1 player is a loser. By this token, most fx trading is necessarily short-term 'day-trading', which by itself carries inherent risk. 2) Fx markets are insanely efficient (I will lightly state that this is my opinion, but one that I am not alone in holding firmly). This means that public information about a currency [ie: economic news, political news, etc.] is nearly immediately acted upon by many, many people, so that the revised fx price of that currency will quickly adjust. The more efficient a market is, the harder it is to 'time a trade'. As an example, if you see on a news feed that the head of a central bank authority made an announcement about interest rates in that country [a common driver of fx prices], you have only moments to make a trade before the large institutional investors already factor it into their bid/ask prices. Keep in mind that the large fx players are dealing with millions and billions of dollars; markets can move very quickly because of this. Note that some currencies trade more frequently than others. The main currency 'pairs' are typically between USD and / or other G10 country-currencies [JPY, EUR, etc.]. As you get into currencies of smaller countries, trading of those currencies happens less frequently. This means that there may be some additional time before public information is 'priced in' to the market value of that currency, making that currency 'less efficient'. On the flip side, if something is infrequently traded, pricing can be more volatile, as a few relatively smaller trades can have a big impact on the market. 3) Uncertainty of political news. If you make an fx trade based on what you believe will happen after an expected political event, you are taking risk that the event actually happens. Politics and world events can be very hard to predict, and there is a high element of chance involved [see recent 'expected' election results across the world for evidence of this]. For something like the stock market, a particular industry may get hit every once in a while with unexpected news, but the fx market is inherently tied to politics in a way that may impact exchange rates multiple times a day. 4) Leveraging. It is very common for fx traders to borrow money to invest in fx. This creates additional risk because it amplifies the impact of your (positive or negative) returns. This applies to other investments as well, but I mention it because high degrees of debt leveraging is extremely common in FX. To answer your direct question: There are no single individual traders who spike fx prices - that is the impact you see of a very efficient market, with large value traders, reacting to frequent, surprising news. I reiterate: If you do not understand the risks associated with fx trade, I recommend that you stop this activity immediately, at least until you understand it better [and I would recommend personally that any amateur investor never get involved in fx at all, regardless of how informed you believe you are].",
"title": ""
},
{
"docid": "346339",
"text": "> Why would the executives take accept a salary at 80% of the market wage when they could just get a job at 100% of the market wage. This may be true for managers, but research has found little to no evidence of a relationship between executive pay and performance. There is no market for executives. They're all on each others boards. They get much of their pay in stock options, diluting the wealth of those shareholders you're fighting for, without telling shareholders how much they're costing them.",
"title": ""
}
] |
9248
|
Why is silver so volatile compared to the S&P 500?
|
[
{
"docid": "450899",
"text": "Silver is a commodity. It's valuable for certain kinds of manufacturing, jewelry, and as a speculative financial instrument or hedge against the dollar. The S&P 500 includes companies which make money off of mining, manufacturing, medicine, media, technology, banking, dining, agriculture... There's a lot more variety there.",
"title": ""
},
{
"docid": "187089",
"text": "The S&P 500 represents a broadly diversified basket of stocks. Silver is a single metal. If all else is equal, more diversification means less volatility. A better comparison would be the S&P 500 vs. a commodities index, or silver vs. some individual stock.",
"title": ""
}
] |
[
{
"docid": "520963",
"text": "\"Your bank's fund is not an index fund. From your link: To provide a balanced portfolio of primarily Canadian securities that produce income and capital appreciation by investing primarily in Canadian money market instruments, debt securities and common and preferred shares. This is a very broad actively managed fund. Compare this to the investment objective listed for Vanguard's VOO: Invests in stocks in the S&P 500 Index, representing 500 of the largest U.S. companies. There are loads of market indices with varying formulas that are supposed to track the performance of a market or market segment that they intend to track. The Russel 2000, The Wilshire 1000, The S&P 500, the Dow Industrial Average, there is even the SSGA Gender Diversity Index. Some body comes up with a market index. An \"\"Index Fund\"\" is simply a Mutual Fund or Exchange Traded Fund (ETF) that uses a market index formula to make it's investment decisions enabling an investor to track the performance of the index without having to buy and sell the constituent securities on their own. These \"\"index funds\"\" are able to charge lower fees because they spend $0 on research, and only make investment decisions in order to track the holdings of the index. I think 1.2% is too high, but I'm coming from the US investing world it might not be that high compared to Canadian offerings. Additionally, comparing this fund's expense ratio to the Vanguard 500 or Total Market index fund is nonsensical. Similarly, comparing the investment returns is nonsensical because one tracks the S&P 500 and one does not, nor does it seek to (as an example the #5 largest holding of the CIBC fund is a Government of Canada 2045 3.5% bond). Everyone should diversify their holdings and adjust their investment allocations as they age. As you age you should be reallocating away from highly volatile common stock and in to assets classes that are historically more stable/less volatile like national government debt and high grade corporate/local government debt. This fund is already diversified in to some debt instruments, depending on your age and other asset allocations this might not be the best place to put your money regardless of the fees. Personally, I handle my own asset allocations and I'm split between Large, Mid and Small cap low-fee index funds, and the lowest cost high grade debt funds available to me.\"",
"title": ""
},
{
"docid": "546075",
"text": "\"Brendan, The short answer is no, there is no need to get into any other funds. For all intents and purposes the S&P 500 is \"\"The Stock Market\"\". The news media may quote the Dow when the market reaches new highs or crashes but all of the Dow 30 stocks are included in the S&P 500. The S&P is also marketcap weighted, which means that it owns in higher proportion the big \"\"Blue Chip\"\" stocks more than the smaller less known companies. To explain, the top 10 holdings in the S&P represent 18% of the total index, while the bottom 10 only represent 0.17% (less than 1 percent). They do have an equal weighted S&P in which all 500 companies represent only 1/500th of the index and that is technically even more diversified but in actuality it makes it more volatile because it has a higher concentration of those smaller less known companies. So it will tend to perform better during up markets and worse during down markets. As far as diversification into different asset classes or other countries, that's non-sense. The S&P 500 has companies in it that give you that exposure. For example, it includes companies that directly benefit from rising oil prices, rising gold prices, etc known as the Energy and Materials sector. It also includes companies that own malls, apartment complexes, etc. known as the Real Estate sector. And as far as other countries, most of the companies in the S&P are multi-national companies, meaning that they do business over seas in many parts of the world. Apple and FaceBook for example sell their products in many different countries. So you don't need to invest any of your money into an Emerging Market fund or an Asia Fund because most of our companies are already doing business in those parts of the world. Likewise, you don't need to specifically invest into a real estate or gold fund. As far as bonds go, if you're in your twenties you have no need for them either. Why, because the S&P 500 also pays you dividends and these dividends grow over time. So for example, if Microsoft increases its dividend payment by 100% over a ten year period , all of the shares you buy today at a 2.5% yield will, in 10 years, have a higher 5% yield. A bond on the other hand will never increase its yield over time. If it pays out 4%, that's all it will ever pay. You want to invest because you want to grow your money and if you want to invest passively the fastest way to do that is through index ETFs like the $SPY, $IVV, and $RSP. Also look into the $XIV, it's an inverse VIX ETF, it moves 5x faster than the S&P in the same direction. If you want to actively trade your money, you can grow it even faster by getting into things like options, highly volatile penny stocks, shorting stocks, and futures. Don't get involved in FX or currency trading, unless it through futures.\"",
"title": ""
},
{
"docid": "176161",
"text": "\"To understand the VXX ETF, you need to understand VIX futures, to understand VIX futures you need to understand VIX, to understand VIX you need to understand options pricing formulas such as the \"\"Black Scholes\"\" formula Those are your prerequisites. Learn at your own pace. Short Answer: When you buy VXX you are buying the underlying are front month VIX futures. Limited by the supply of the ETF's NAV (Net Asset Value) units. It is assumed that the ETF manager is actually buying and selling more VIX front month futures to back the underlying ETF. Long Answer: Assume nobody knows what an options contract should be worth. Therefore formulas have been devised to standardize how to price an options contract. The Black-Scholes formula is widely used, one of the variables in this formula is \"\"Implied Volatility\"\", which basically accounts for the mispricing of options when the other variables (Intrinsic Value, delta, gamma, theta...) don't completely explain how much the option is worth. People are willing to pay more for options when the perception is that they will be more profitable, \"\"implied volatility\"\" tracks these changes in an option's demand, where the rest of the black-scholes formula creates a price for an option that will always be the same. Each stock in the market that also trades standardized options will have implied volatility which can be computed from the price of those options. The \"\"Volatility Index\"\" (VIX), looks at the implied volatility of MANY STOCK's options contracts. Specifically the \"\"implied volatility of out the money puts on the S&P 500\"\". If you don't know what that quoted part of the sentence means, then you have at least five other individual questions to ask before you re-read this answer and understand the relevance of these followup questions: Why would people buy out-the-money puts on the S&P 500? Why would people pay more for out-the-money puts on the S&P 500 on some days and pay less for them on other days? This is really the key to the whole puzzle. Anyway, now that we have this data, people wanted to speculate on the future value of the VIX. So VIX futures contracts began trading and with it there came a liquid market. There doesn't need to be anything physical to back a financial product anymore. A lot of people don't trade futures, retail investors have practically only heard of \"\"the stock market\"\". So one investment bank decided to make a fund that only holds VIX futures that expire within a month. (front month futures). They split that fund up into shares and listed it on the stock market, like alchemy the VXX was formed. Volatility studies are fascinating, and get way more complex than this now that the VXX ETF also has liquid options contracts trading on it too, and there are leveraged VIX ETF funds that also trade options\"",
"title": ""
},
{
"docid": "572574",
"text": "Generally S&P 500 will be used as the benchmark for US investors because it represents how's the US market performs as a whole. If you've outperformed the S&P 500 during the last couple years, great. However, at the end of day, you would want to look at the total growth percent that your portfolio has achieved, as compared with that of S&P 500. Anyway, your portfolio might actually ride along with the bull market during the 2009-2010 period (more-so for the small caps).",
"title": ""
},
{
"docid": "459078",
"text": "Let's start with the chart comparing LS80 to the S&P - Both have dividends not reflected in these returns. After adding 10% or so, the S&P during these 5 years was +55% or a bit more. As a result, the advisor lags the S&P by about 1% which makes sense. One of the problems with the nature of the question is not being able to analyze the portfolios, your's vs the VG80, for risk-adjusted return. The return your advisor got you is great if the risk (volatility) is lower than the funds or indexes you're comparing to. In the end, 4 years may not be long enough to make a proper comparison.",
"title": ""
},
{
"docid": "599255",
"text": "Around Oct 03 2010 the SPY closed at 113. Today it is trading at 130. After four months, that means that the S&P is up 15% over that particular 4 month period. You said you need something pretty low maintenance, and you are comparing your returns to the S&P 500 (which as @duffbeer703 points out is a good thing to compare against because of its diversification). To kill two birds with one stone, I would sell your fund that you have and take the proceeds and purchase the ETF SPY. SPY trades like a stock but mirrors the S&P 500's performance. It has extremely low fees (as opposed to what I suspect your BlackRock fund has). You can own it in an Etrade or Fidelity or other low cost broker account. Then you will be extremely low maintenance, fully diversified (among stocks) and you don't have to compare your performance against the S&P :)",
"title": ""
},
{
"docid": "67472",
"text": "One reason it matters whether or not you're beating the S&P 500 (or the Wilshire 5000, or whatever benchmark you choose to use) is to determine whether or not you'd be better off investing in an index fund (or some other investment vehicle) instead of pursuing whatever your current investment strategy happens to be. Even if your investment strategy makes money, earning what the S&P 500 has averaged over multiple decades (around 10%) with an index fund means a lot more money than a 5% return with an actively managed portfolio (especially when you consider factors like compound interest and inflation). I use the S&P 500 as one of my criteria for judging how well (or poorly) my financial adviser is doing for me. If his recommendations (or trading activity on my behalf, if authorized) are inferior to the S&P 500, for too long, then I have a basis to discontinue the relationship. Check out this Wikipedia entry on stock market indices. There are legitimate criticisms, but on the whole I think they are useful. As an aside, the reason I point to index funds specifically is that they are the one of the lowest-cost, fire-and-forget investment strategies around. If you compare the return of the S&P 500 index over multiple decades with most actively managed mutual funds, the S&P 500 index comes out ahead.",
"title": ""
},
{
"docid": "99568",
"text": "\"The majority (about 80%) of mutual funds are underperforming their underlying indexes. This is why ETFs have seen massive capital inflows compared to equity funds, which have seen significant withdrawals in the last years. I would definitively recommend going with an ETF. In addition to pure index based ETFs that (almost) track broad market indexes like the S&P 500 there are quite a few more \"\"quant\"\" oriented ETFs that even outperformed the S&P. I am long the S&P trough iShares ETFs and have dividend paying ETFs and some quant ETFS on top (Invesco Powershares) in my portfolio.\"",
"title": ""
},
{
"docid": "163354",
"text": "Victor, Yes the drop in price does completely cancel the dividend at first. However, as others have noted, there are other forces working on the price as well. If dividends were pointless then the following scenario would be true: Let's assume, hypothetically, two identical stocks, only one of which pays a 2% annual dividend quarterly. At the end of the year we would expect the share price of the dividend stock to be 2% lower than the non-dividend stock. And an equal investment in both stocks would yield exactly the same amount of money. So that is a hypothetical, and here is real market example: I compared, i.e. took the ratio of Vanguard's S&P 500 ETF (VOO) closing price to the S&P 500 Index closing price from sep 9, (2010-2014), after accounting for the VOO 2013 split. The VOO pays a quarterly dividend(about 2%/year), the S&P is an index, hence no dividend. The VOO share price, reduced each quarter by the dividend, still grew more than the S&P each year except 2012 to 2013, but looking at the entire 4yr period the VOO share price grew 80.3987% while S&P grew 80.083% (1/3 of 1% more for VOO). VOO does drop about 1/2% relative to S&P on every ex date, but obviously it makes it up. There are other forces working on VOO. VOO is trade-able, therefore subject to supply/demand pressures, while the S&P 500 is not. So for the VOO ETF the data does not indicate pointless dividends but instead implies dividends are free money. StockCharts.com supports this. S&P500 for last 1244 days (9/8/2010) shows 90% growth http://stockcharts.com/freecharts/perf.php?%24SPX while VOO for last 1244 days shows 105% growth http://stockcharts.com/freecharts/perf.php?VOO",
"title": ""
},
{
"docid": "511455",
"text": "Though a fan of ETFs (esp. high volume commission-free ones) recently a single, new fund VQT appeared on my radar of interest. It's based on dynamic hedging that has sort of build-in diversification and adapts to the market climate, pulling in and out varying amounts from cash, the S&P 500 and volatility futures based on VIX. I've been Long VQT and it's followed the S&P500 during good times, though not at far, but crucially disconnected with much milder losses when the general market was nose diving. You can lookup and compare to SPY at http://finance.google.com Not trying to give investment advice, in case that upsets some rules.",
"title": ""
},
{
"docid": "445526",
"text": "Options pricing is based on the gap between strike and the current market, and volatility. That's why the VIX, a commonly accepted volatility index, is actually just a weighted blend of S&P 500 future options prices. A general rise in the price of options indicates people don't know whether it will go up or down next, and are therefore less willing to take that risk. But your question is why everything underwater in the puts chain went higher, and that's simple: now that Apple's down, the probability of falling a few more points is higher. Especially since Apple has gone through some recent rough times, and stocks in general are seen as risky these days.",
"title": ""
},
{
"docid": "516214",
"text": "\"TL;DR - go with something like Barry Ritholtz's All Century Portfolio: 20 percent total U.S stock market 5 percent U.S. REITs 5 percent U.S. small cap value 15 percent Pacific equities 15 percent European equities 10 percent U.S. TIPs 10 percent U.S. high yield corp bonds 20 percent U.S. total bond UK property market are absurdly high and will be crashing a lot very soon The price to rent ratio is certainly very high in the UK. According to this article, it takes 48 years of rent to pay for the same apartment in London. That sounds like a terrible deal to me. I have no idea about where prices will go in the future, but I wouldn't voluntarily buy in that market. I'm hesitant to invest in stocks for the fear of losing everything A stock index fund is a collection of stocks. For example the S&P 500 index fund is a collection of the largest 500 US public companies (Apple, Google, Shell, Ford, etc.). If you buy the S&P 500 index, the 500 largest US companies would have to go bankrupt for you to \"\"lose everything\"\" - there would have to be a zombie apocalypse. He's trying to get me to invest in Gold and Silver (but mostly silver), but I neither know anything about gold or silver, nor know anyone who takes this approach. This is what Jeremy Siegel said about gold in late 2013: \"\"I’m not enthusiastic about gold because I think gold is priced for either hyperinflation or the end of the world.\"\" Barry Ritholtz also speaks much wisdom about gold. In short, don't buy it and stop listening to your friend. Is buying a property now with the intention of selling it in a couple of years for profit (and repeat until I have substantial amount to invest in something big) a bad idea? If the home price does not appreciate, will this approach save you or lose you money? In other words, would it be profitable to substitute your rent payment for a mortgage payment? If not, you will be speculating, not investing. Here's an articles that discusses the difference between speculating and investing. I don't recommend speculating.\"",
"title": ""
},
{
"docid": "264490",
"text": "\"The VIX is a mathematical aggregate of the implied volatilities of the S&P 500 Index components. It itself cannot be traded as there currently is no way to only hold a position on an implied volatility alone. Implied volatility can only currently be derived from an option relative to its underlying. Further, the S&P 500 index itself cannot be traded only the attempts to replicate it. For assets that are not tradable, derivatives can be \"\"cash settled\"\" where the value of the underlying is delivered in cash. Cash settlement can be used for underlyings that in fact due trade but are frequently only elected if the underlying is costly to deliver or there is an incentive to circumvent regulation. Currently, only futures that settle on the value of the VIX at the time of delivery trade; in other words, VIX futures holders must deliver on the value of the VIX in cash upon settlement. Options in turn trade on those futures and in turn are also cash settled on the value of the underlying future at expiration. The VXX ETF holds one to two month VIX futures that it trades out of before delivery, so while it is impossible to know exactly what is held in the VXX accounts unless if one had information from an insider or the VXX published such details, one can assume that it holds VIX futures contracts no later than two settlements from the preset. It should be noted that the VXX does not track the VIX over the long run because of the cost to roll the futures and that the futures are more stable than the VIX, so it is a poor substitute for the VIX over time periods longer than one day. \"\"Underlying\"\" now implies any abstract from which a financial product derives its value.\"",
"title": ""
},
{
"docid": "436904",
"text": "This is Ellie Lan, investment analyst at Betterment. To answer your question, American investors are drawn to use the S&P 500 (SPY) as a benchmark to measure the performance of Betterment portfolios, particularly because it’s familiar and it’s the index always reported in the news. However, going all in to invest in SPY is not a good investment strategy—and even using it to compare your own diversified investments is misleading. We outline some of the pitfalls of this approach in this article: Why the S&P 500 Is a Bad Benchmark. An “algo-advisor” service like Betterment is a preferable approach and provides a number of advantages over simply investing in ETFs (SPY or others like VOO or IVV) that track the S&P 500. So, why invest with Betterment rather than in the S&P 500? Let’s first look at the issue of diversification. SPY only exposes investors to stocks in the U.S. large cap market. This may feel acceptable because of home bias, which is the tendency to invest disproportionately in domestic equities relative to foreign equities, regardless of their home country. However, investing in one geography and one asset class is riskier than global diversification because inflation risk, exchange-rate risk, and interest-rate risk will likely affect all U.S. stocks to a similar degree in the event of a U.S. downturn. In contrast, a well-diversified portfolio invests in a balance between bonds and stocks, and the ratio of bonds to stocks is dependent upon the investment horizon as well as the individual's goals. By constructing a portfolio from stock and bond ETFs across the world, Betterment reduces your portfolio’s sensitivity to swings. And the diversification goes beyond mere asset class and geography. For example, Betterment’s basket of bond ETFs have varying durations (e.g., short-term Treasuries have an effective duration of less than six months vs. U.S. corporate bonds, which have an effective duration of just more than 8 years) and credit quality. The level of diversification further helps you manage risk. Dan Egan, Betterment’s Director of Behavioral Finance and Investing, examined the increase in returns by moving from a U.S.-only portfolio to a globally diversified portfolio. On a risk-adjusted basis, the Betterment portfolio has historically outperformed a simple DIY investor portfolio by as much as 1.8% per year, attributed solely to diversification. Now, let’s assume that the investor at hand (Investor A) is a sophisticated investor who understands the importance of diversification. Additionally, let’s assume that he understands the optimal allocation for his age, risk appetite, and investment horizon. Investor A will still benefit from investing with Betterment. Automating his portfolio management with Betterment helps to insulate Investor A from the ’behavior gap,’ or the tendency for investors to sacrifice returns due to bad timing. Studies show that individual investors lose, on average, anywhere between 1.2% to 4.3% due to the behavior gap, and this gap can be as high as 6.5% for the most active investors. Compared to the average investor, Betterment customers have a behavior gap that is 1.25% lower. How? Betterment has implemented smart design to discourage market timing and short-sighted decision making. For example, Betterment’s Tax Impact Preview feature allows users to view the tax hit of a withdrawal or allocation change before a decision is made. Currently, Betterment is the only automated investment service to offer this capability. This function allows you to see a detailed estimate of the expected gains or losses broken down by short- and long-term, making it possible for investors to make better decisions about whether short-term gains should be deferred to the long-term. Now, for the sake of comparison, let’s assume that we have an even more sophisticated investor (Investor B), who understands the pitfalls of the behavior gap and is somehow able to avoid it. Betterment is still a better tool for Investor B because it offers a suite of tax-efficient features, including tax loss harvesting, smarter cost-basis accounting, municipal bonds, smart dividend reinvesting, and more. Each of these strategies can be automatically deployed inside the portfolio—Investor B need not do a thing. Each of these strategies can boost returns by lowering tax exposure. To return to your initial question—why not simply invest in the S&P 500? Investing is a long-term proposition, particularly when saving for retirement or other goals with a time horizon of several decades. To be a successful long-term investor means employing the core principles of diversification, tax management, and behavior management. While the S&P might look like a ‘hot’ investment one year, there are always reversals of fortune. The goal with long-term passive investing—the kind of investing that Betterment offers—is to help you reach your investing goals as efficiently as possible. Lastly, Betterment offers best-in-industry advice about where to save and how much to save for no fee.",
"title": ""
},
{
"docid": "91179",
"text": "If you are worried about an increase in volatility, then go long volatility. Volatility itself can be traded. Here in the US there is an index VIX that is described as tracking volatility. What VIX actually tracks is the premium of S&P 500 options, which become more expensive when traders want to hedge against volatility. In the US you can trade VIX options or invest in VIX tracking ETFs like VXX. Apparently there are similar ETFs listed in Canada, such as HUV. Volatility itself is quite volatile so it is possible that a small volatility long position would cover the losses of a larger long position in stocks. If you do choose to invest in a volatility ETF, be aware that they experience quite a lot of decay. You will not want to hold it for very long.",
"title": ""
},
{
"docid": "403017",
"text": "\"Most financial \"\"advisors\"\" are actually financial-product salesmen. Their job is to sweet-talk you into parting with as much money as possible - either in management fees, or in commissions (kickbacks) on high-fee investment products** (which come from fees charged to you, inside the investment.) This is a scrappy, cutthroat business for the salesmen themselves. Realistically that is how they feed their family, and I empathize, but I can't afford to buy their product. I wish they would sell something else. These people prey on people's financial lack of knowledge. For instance, you put too much importance on \"\"returns\"\". Why? because the salesman told you that's important. It's not. The market goes up and down, that's normal. The question is how much of your investment is being consumed by fees. How do you tell that (and generally if you're invested well)? You compare your money's performance to an index that's relevant to you. You've heard of the S&P 500, that's an index, relevant to US investors. Take 2015. The S&P 500 was $2058.20 on January 2, 2015. It was $2043.94 on December 31, 2015. So it was flat; it dropped 0.7%. If your US investments dropped 0.7%, you broke even. If you made less, that was lost to the expenses within the investment, or the investment performing worse than the S&P 500 index. I lost 0.8% in 2015, the extra 0.1% being expenses of the investment. Try 2013: S&P 500 was $1402.43 on December 28, 2012 and $1841.10 on Dec. 27, 2013. That's 31.2% growth. That's amazing, but it also means 31.2% is holding even with the market. If your salesman proudly announced that you made 18%... problem! All this to say: when you say the investments performed \"\"poorly\"\", don't go by absolute numbers. Find a suitable index and compare to the index. A lot of markets were down in 2015-16, and that is not your investment's fault. You want to know if were down compared to your index. Because that reflects either a lousy funds manager, or high fees. This may leave you wondering \"\"where can I invest that is safe and has sensible fees? I don't know your market, but here we have \"\"discount brokers\"\" which allow self-selection of investments, charge no custodial fees, and simply charge by the trade (commonly $10). Many mutual funds and ETFs are \"\"index funds\"\" with very low annual fees, 0.20% (1 in 500) or even less. How do you pick investments? Look at any of numerous books, starting with John Bogle's classic \"\"Common Sense on Mutual Funds\"\" book which is the seminal work on the value of keeping fees low. If you need the cool, confident professional to hand-hold you through the process, a fee-only advisor is a true financial advisor who actually acts in your best interest. They honestly recommend what's best for you. But beware: many commission-driven salespeople pretend to be fee-only advisors. The good advisor will be happy to advise investment types, and let you pick the brand (Fidelity vs Vanguard) and buy it in your own discount brokerage account with a password you don't share. Frankly, finance is not that hard. But it's made hard by impossibly complex products that don't need to exist, and are designed to confuse people to conceal hidden fees. Avoid those products. You just don't need them. Now, you really need to take a harder look at what this investment is. Like I say, they make these things unnecessarily complex specifically to make them confusing, and I am confused. Although it doesn't seem like much of a question to me. 1.5% a quarter is 6% a year or 60% in 10 years (to ignore compounding). If the market grows 6% a year on average so growth just pays the fees, they will consume 60% of the $220,000, or $132,000. As far as the $60,000, for that kind of money it's definitely worth talking to a good lawyer because it sounds like they misrepresented something to get your friend to sign up in the first place. Put some legal pressure on them, that $60k penalty might get a lot smaller. ** For instance they'll recommend JAMCX, which has a 5.25% buy-in fee (front-end load) and a 1.23% per year fee (expense ratio). Compare to VIMSX with zero load and a 0.20% fee. That front-end load is kicked back to your broker as commission, so he literally can't recommend VIMSX - there's no commission! His company would, and should, fire him for doing so.\"",
"title": ""
},
{
"docid": "195089",
"text": "Willis Group Holdings Set to Join the S&P 500; Fossil Group to Join S&P MidCap 400; Adeptus Health to Join S&P SmallCap 600 notes in part for the S & P case: Willis Group Holdings plc (NYSE:WSH) will replace Fossil Group Inc. (NASD:FOSL) in the S&P 500, and Fossil Group will replace Towers Watson & Co. (NASD:TW) in the S&P MidCap 400 after the close of trading on Monday, January 4. Willis Group is merging with Towers Watson in a deal expected to be completed on or about that date pending final conditions. Post merger, Willis Group Holdings will change its name to Willis Towers Watson plc and trade under the ticker symbol “WLTW”. Fossil has a market capitalization that is more representative of the midcap market space. As of Jan. 8, Fossil is about $1.44B in market cap and Willis is $21.02B for those wondering. Apple with a market cap of $540.58B is 3.26% of the index making the entire index worth approximately $16,582.21B, so Fossil is worth .00868% of the overall index for those wanting some numbers here. Thus, if a company acquires another and becomes bigger than there can be replacements made in those indices that have an artificial number of small members. Alternatively, a member may be removed for lack of representation where it is just so small compared to other companies that may be a better fit as some indices could be viewed as actively managed in a sense. In contrast, there are indices like those from Russell, known for the Russell 2000 small-cap index: Q: Why don't you reconstitute the indexes more often than once a year? A: Maintaining representative indexes must be weighed against the costs associated with making frequent changes to index constituents (namely, buying and selling stocks). The Russell Indexes are annually reconstituted because our research has shown that this strikes a reasonable balance between accuracy and cost. We originally reconstituted our indexes quarterly, then semi-annually, but found these options to be suboptimal. Our extensive research demonstrates that annual reconstitution accurately represents the capitalization segments and minimizes the turnover required to reflect the segments as they change. Thus there can be different scenarios. Then there can be the effect on index funds when price-weighted indices like the Dow Jones Industrial Average has a member that does a stock split that causes some rebalancing too. On the DJIA Divisor: The Dow Jones Industrial Average (DJIA) is a price-weighted index that is calculated by dividing the sum of the prices of the 30 component stocks (Dow Jones Industrial Average components) by a number called the DJIA Divisor or Dow Divisor . The index divisor is updated periodically and adjusted to offset the effect of stock splits, bonus issues or any change in the component stocks included in the DJIA. This is done in order to keep the index value consistent.",
"title": ""
},
{
"docid": "178875",
"text": "You are correct that over a short term there is no guarantee that one index will out perform another index. Every index goes through periods of feat and famine. That uis why the advice is to diversify your investments. Every index does have some small amount of management. For the parent index (the S&P 500 in this case) there is a process to divide all 500 stocks into growth and value, pure growth and pure value. This rebalancing of the 500 stocks occurs once a year. Rebalancing The S&P Style indices are rebalanced once a year in December. The December rebalancing helps set the broad universe and benchmark for active managers on an annual cycle consistent with active manager performance evaluation cycles. The rebalancing date is the third Friday of December, which coincides with the December quarterly share changes for the S&P Composite 1500. Style Scores, market-capitalization weights, growth and value midpoint averages, and the Pure Weight Factors (PWFs), where applicable across the various Style indices, are reset only once a year at the December rebalancing. Other changes to the U.S. Style indices are made on an as-needed basis, following the guidelines of the parent index. Changes in response to corporate actions and market developments can be made at any time. Constituent changes are typically announced for the parent index two-to-five days before they are scheduled to be implemented. Please refer to the S&P U.S. Indices Methodology document for information on standard index maintenance for the S&P 500, the S&P MidCap 400,the S&P SmallCap 600 and all related indices. As to which is better: 500, growth,value or growth and value? That depends on what you the investor is trying to do.",
"title": ""
},
{
"docid": "161445",
"text": "The S&P 500 is a stock market index, which is a list of 500 stocks from the largest companies in America. You could open a brokerage account with a broker and buy shares in each of these companies, but the easiest, least expensive way to invest in all these stocks is to invest in an S&P 500 index mutual fund. Inside an index mutual fund, your money will be pooled together with everyone else in the fund to purchase all the stocks in the index. These types of funds are very low expense compared to managed mutual funds. Most mutual fund companies have an S&P 500 index fund; two examples are Vanguard and Fidelity. The minimum investment in most of these mutual funds is low enough that you will be able to open an account with your $4000. Something you need to keep in mind, however: investing in any stock mutual fund is not non-risk. It's not even low-risk, really. It is very possible to lose money by investing in the stock market. An S&P 500 index fund is diversified in the sense that you have money in lots of different stocks, but it is also not diversified, in a sense, because it is all in large cap American stocks. Before investing in the stock market, you should have a goal for the money you are investing. If you are investing for something several years away, an index fund can be a good place to invest, but if you will need this money within the next few years, the stock market might be too risky for you.",
"title": ""
},
{
"docid": "220486",
"text": "\"You cannot actually buy an index in the true sense of the word. An index is created and maintained by a company like Standard and Poor's who licenses the use of the index to firms like Vanguard. The S&P 500 is an example of an index. The S&P 500 \"\"index includes 500 leading companies\"\", many finical companies sell products which track to this index. The two most popular products which track to indexes are Mutual Funds (as called Index Funds and Index Mutual Funds) and Exchange Traded Funds (as called ETFs). Each Index Mutual Fund or ETF has an index which it tracks against, meaning they hold securities which make up a sample of the index (some indexes like bond indexes are very hard to hold everything that makes them up). Looking at the Vanguard S&P 500 Index Mutual Fund (ticker VFINX) we see that it tracks against the S&P 500 index. Looking at its holdings we see the 500-ish stocks that it holds along with a small amount of bonds and cash to handle cash flow for people buying and sell shares. If we look at the Vanguard S&P 500 ETF (ticker VOO) we see that it also tracks against the S&P 500 index. Looking at its holdings we see they are very similar to the similar Index Mutual Fund. Other companies like T. Rowe Price have similar offering. Look at the T. Rowe Price Equity Index 500 Fund (ticker PREIX) its holdings in stocks are the same as the similar Vanguard fund and like the Vanguard fund it also holds a small amount of bonds and cash to handle cash flow. The only real difference between different products which track against the same index is in the expense ratio (fees for managing the fund) and in the small differences in the execution of the funds. For the most part execution of the funds do not really matter to most people (it has a very small effect), what matters is the expense (the fees paid to own the fund). If we just compare the expense ratio of the Vanguard and T. Rowe Price funds we see (as of 27 Feb 2016) Vanguard has an expense ratio of 0.17% for it Index Mutual Fund and 0.05% for its ETF, while T. Rowe Price has an expense ratio of 0.27%. These are just the fees for the funds themselves, there are also account maintenance fees (which normally go down as the amount of money you have invested at a firm go up) and in the case of ETFs execution cost (cost to trade the shares along with the difference between the bid and ask on the shares). If you are just starting out I would say going with the Index Mutual Fund would easier and most likely would cost less over-all if you are buying a small amount of shares every month. When choosing a company look at the expense ratio on the funds and the account maintenance fees (along with the account minimals). Vanguard is well known for having low fees and they in fact were the first to offer Index Mutual Funds. For more info on the S&P 500 index see also this Investopedia entry on the S&P 500 index. Do not worry if this is all a bit confusing it is to most people (myself included) at first.\"",
"title": ""
},
{
"docid": "414470",
"text": "I hate to point to Wikipedia as an answer, but it does describe exactly what you are looking for... The S&P 500 is a free-float capitalization-weighted index published since 1957 of the prices of 500 large-cap common stocks actively traded in the United States. The stocks included in the S&P 500 are those of large publicly held companies that trade on either of the two largest American stock market exchanges; the New York Stock Exchange and the NASDAQ. The components of the S&P 500 are selected by committee... The committee selects the companies in the S&P 500 so they are representative of the industries in the United States economy. In addition, companies that do not trade publicly (such as those that are privately or mutually held) and stocks that do not have sufficient liquidity are not in the index. The S&P is a capitalization weighted index. If a stock price goes up, then it comprises more of the total index. If a stock goes down, it comprises less, and if it goes down too much, the committee will likely replace it. So to answer your question, if one stock were to suddenly skyrocket, nothing would happen beyond the fact that the index was now worth more and that particular stock would now make up a larger percentage of the S&P 500 index.",
"title": ""
},
{
"docid": "586029",
"text": "I agree with others here that suggest that you should be taking higher risk since it is repaid with higher returns. You have 40 years or so to go before you might switch to safer but lower return funds. I suggest that you look at the Morningstar rating for the funds you are considering: http://www.morningstar.com/ A fund rated five stars means that the fund performs in the top 20% compared to all similar funds. I prefer five star funds. Next, check the management fees. Here is an example from one of the funds you mentioned; https://www.google.com/finance?cid=466533039917726 Next, I suggest you compare how each fund has performed compared to a benchmark. Here are some common indices: Compare an equity fund to, for example, the S&P 500. Has your fund beat or closely matched the S&P for 1, 5 and 10 years? If not, you may as well buy an index fund, such as SPY.",
"title": ""
},
{
"docid": "370281",
"text": "\"I went to Morningstar's \"\"Performance\"\" page for FUSEX (Fideltiy's S&P 500 index fund) and used the \"\"compare\"\" tool to compare it with FOSFX and FWWFX, as well as FEMKX (Fidelity Emerging Markets fund). According to the data there, FOSFX outperformed FUSEX in 2012, FEMKX outperformed FUSED in 2010, and FWWFX outperformed FUSEX in both 2010 and 2012. When looking at 10- and 15-year trailing returns, both FEMKX and FWWFX outperformed FUSEX. What does this mean? It means it matters what time period you're looking at. US stocks have been on an almost unbroken increase since early 2009. It's not surprising that if you look at recent returns, international markets will not stack up well. If you go back further, though, you can find periods where international funds outperformed the US; and even within recent years, there have been individual years where international funds won. As for correlation, I guess it depends what you mean by \"\"low\"\". According to this calculator, for instance, FOSFX and FUSEX had a correlation of about 0.84 over the last 15 years. That may seem high, but it's still lower than, say, the 0.91 correlation between FUSEX and FSLCX (Fideltiy Small Cap). It's difficult to find truly low correlations among equity funds, since the interconnectedness of the global economy means that bull and bear markets tend to spread from one country to another. To get lower correlations you need to look at different asset classes (e.g., bonds). So the answer is basically that some of the funds you were already looking at may be the ones you were looking for. The trick is that no category will outperform any other over all periods. That's exactly what volatility means --- it means the same category that overperforms in some periods will underperform in others. If international funds always outperformed, no one would ever buy US funds. Ultimately, if you're trying to decide on investments for yourself, you need to take all this information into account and combine it with your own personal preferences, risk tolerance, etc. Anecdotally, I recently did some simulation-based analyses of Vanguard funds using data from the past 15 years. Over this period, Vanguard's emerging markets fund (VEIEX) comes out far ahead of US funds, and is also the least-correlated with the S&P 500. But, again, this analysis is based only on a particular slice of time.\"",
"title": ""
},
{
"docid": "553634",
"text": "The answer would depend on the equities held. Some can weather inflation better than others (such as companies that have solid dividend growth) and even outpace inflation. Some industries are also safer against inflation than others, such as consumer staples and utilities since people usually have to purchase these regardless of how much $ they have. In looking over the data comparing S&P 500 returns, dividends, and inflation, the results are all over the map. In the 50's the total return was 19.3% with inflation at 2.2%. Then in the 70's returns were 5.8% with inflation at 7.4 percent, leading one to think that inflation diminished returns. But then in the 80's inflation was 5.1%, yet the return on the S&P was up to 17.3% Either way, aside from the 70's every other decade since 1950 has outpaced inflation (as long as you are including dividends; hence my first paragraph). S&P 500: Total and Inflation-Adjusted Historical Returns Also, the 7% average stock appreciation you mention is just that, an average. You are comparing a year-over-year number (7% inflation) with an aggregated one (stock performance over x number of years) and that is a misrepresentation and is not being weighted for the difference in what those numbers mean. Finally, there are thousands of things that have an effect on the stock market and stocks. Some are controllable and others are not. The idea that any one of them, such as inflation, has any sort of long-term, everlasting effect on prices that they cannot outmaneuver is improbable. This is where researching your stocks comes in...and if done prudently, who cares what the inflation rate is?",
"title": ""
},
{
"docid": "169408",
"text": "If you want to trade to gain from short-term volatility, you can use Derivative-based ETFs that try to track the inverse of a broad index like the S&P 500. Note that these ETFs only track the index over a 1 day period, so you shouldn't hold these. If you're looking for a longer-term investment strategy, look at low-beta stocks, which often do well or produce dividend income during volatile times. Examples include McDonald's Corp and utilities like Consolidated Edison.",
"title": ""
},
{
"docid": "448511",
"text": "The compound annual growth rate of the S&P 500 over the last 20 years is in excess of 7% annually. http://www.moneychimp.com/features/market_cagr.htm Several index funds mirror the S&P 500 such as, but not limited to SPDR S&P 500 ETF Trust. An annual growth rate of 7% on a $5,000,000 portfolio implies gains of $350,000 per year, every year investing passively. Most of us can live reasonably well on $350,000 per year! I will argue that the chances of all 500 companies in the S&P 500 going bankrupt or nearly so at once is slight and less likely than the same for Google.",
"title": ""
},
{
"docid": "479461",
"text": "\"The S&P 500 is an index. This refers to a specific collection of securities which is held in perfect proportion. The dollar value of an index is scaled arbitrarily and is based off of an arbitrary starting price. (Side note: this is why an index never has a \"\"split\"\"). Lets look at what assumptions are included in the pricing of an index: All securities are held in perfect proportion. This means that if you invest $100 in the index you will receive 0.2746 shares of IBM, 0.000478 shares of General Motors, etc. Also, if a security is added/dropped from the list, you are immediately rebalancing the remaining money. Zero commissions are charged. When the index is calculated, they are using the current price (last trade) of the underlying securities, they are not actually purchasing them. Therefore it assumes that securities may be purchased without commission or other liquidity costs. Also closely related is the following. The current price has full liquidity. If the last quoted price is $20 for a security, the index assumes that you can purchase an arbitrary amount of the security at that price with a counterparty that is willing to trade. Dividends are distributed immediately. If you own 500 equities, and most distributed dividends quarterly, this means you will receive on average 4 dividends per day. Management is free. All equities can be purchased with zero research and administrative costs. There is no gains tax. Trading required by the assumptions above would change your holdings constantly and you are exempt from short-term or long-term capital gains taxes. Each one of these assumptions is, of course, invalid. And the fund which endeavors to track the index must make several decisions in how to closely track the index while avoiding the problems (costs) caused by the assumptions. These are shortcuts or \"\"approximations\"\". Each shortcut leads to performance which does not exactly match the index. Management fees. Fees are charged to the investor as load, annual fees and/or redemptions. Securities are purchased at real prices. If Facebook were removed from the S&P 500 overnight tonight, the fund would sell its shares at the price buyers are bidding the next market day at 09:30. This could be significantly different than the price today, which the index records. Securities are purchased in blocks. Rather than buying 0.000478 shares of General Motors each time someone invests a dollar, they wait for a few people and then buy a full share or a round lot. Securities are substituted. With lots of analysis, it may be determined that two stocks move in tandem. The fund may purchase two shares of General Motors rather than one of General Motors and Ford. This halves transaction costs. Debt is used. As part of substitution, equities may be replaced by options. Option pricing shows that ownership of options is equivalent to holding an amount of debt. Other forms of leverage may also be employed to achieve desired market exposure. See also: beta. Dividends are bundled. VFINX, the largest S&P 500 tracking fund, pays dividends quarterly rather than immediately as earned. The dividend money which is not paid to you is either deployed to buy other securities or put into a sinking fund for payment. There are many reasons why you can't get the actual performance quoted in an index. And for other more exotic indices, like VIX the volatility index, even more so. The best you can do is work with someone that has a good reputation and measure their performance.\"",
"title": ""
},
{
"docid": "158006",
"text": "There are multiple ETFs which inversely track the common indices, though many of these are leveraged. For example, SDS tracks approximately -200% of the S&P 500. (Note: due to how these are structured, they are only suitable for very short term investments) You can also consider using Put options for the various indices as well. For example, you could buy a Put for the SPY out a year or so to give you some fairly cheap insurance (assuming it's a small part of your portfolio). One other option is to invest against the market volatility. As the market makes sudden swings, the volatility goes up; this tends to be true more when it falls than when it rises. One way of invesing in market volatility is to trade options against the VIX.",
"title": ""
},
{
"docid": "237305",
"text": "\"They don't, actually. Though in some time frames S&P 500 growth out performs S&P 500, it often lags. This is because \"\"growth\"\" doesn't refer to what happens to your account, but rather the type of stock in the index -- roughly speaking, it's the half of the S&P with the best earnings growth. That would be great, except it's not looking for is to see if that growth is worth buying. A stock with a 20% growth rate is a great buy at a P/E of 15, but a terrible buy at P/E/ 50. That leads to what JB King was talking about -- there's also the S&P 500 Value, which is roughly the cheapest stocks relative to earnings. Value does tend to beat the broad index over the long haul, because there's nothing like getting a good deal (note a stock can be in both the growth and value categories). This holds true with other indexes as well like the Russel 2000. All that said, you're not going to see a huge difference between S&P 500 and S&P 500 Growth. I believe this is because the S&P 500 itself leans a bit to the growthy side. PS: With VOOG Vanguard is tracking the S&P 500 Growth Index, which is actually a thing and not Vanguard itself filtering stocks.\"",
"title": ""
},
{
"docid": "53244",
"text": "The one thing we know for certain is that holding large amounts of cash isn't ideal - inflation will eat away at your wealth. It's understandable that you're hesitant to put all your wealth in common stock. The S&P 500's price/earnings is 18.7 right now - a little high by historical standards. But consider that the S&P 500 has given a CAGR of approximately 10% (not inflation-adjusted) since 1970. If you don't time the market correctly, you could miss out on considerable gains. So it's probably best to invest at least a portion of your wealth in common stocks, and just accept the risk of short-term losses. You'll likely come out ahead in the long run, compared to an investor who tries to time the market and ends up holding cash positions for too long. If you really think US stocks are overpriced, you could look at other markets, but you'll find similar P/Es in Europe and Japan. You could try an emerging market fund like VEMAX if you have the risk tolerance. Let's say you're not convinced, and don't want to invest heavily in stocks right now. In the current market, safe cash alternatives like Treasury bills offer very low yields - not enough to offset inflation tax. So I would invest in a diversified portfolio of long-term bonds, real estate, maybe precious metals, and whatever amount of stock you're comfortable with.",
"title": ""
}
] |
529
|
Human embryonic stem cells give rise to cell types from all three embryonic germ layers.
|
[
{
"docid": "36651210",
"text": "Embryonic stem cells have the ability to remain undifferentiated and proliferate indefinitely in vitro while maintaining the potential to differentiate into derivatives of all three embryonic germ layers. These cells have, therefore, potential for in vitro differentiation studies, gene function, and so on. The aim of this study was to produce a human embryonic stem cell line. An inner cell mass of a human blastocyst was separated and cultured on mouse embryonic fibroblasts in embryonic stem cell medium with related additives. The established line was evaluated by morphology; passaging; freezing and thawing; alkaline phosphatase; Oct-4 expression; anti-surface markers including Tra-1-60 and Tra-1-81; and karyotype and spontaneous differentiation. Differentiated cardiomyocytes and neurons were evaluated by transmission electron microscopy and immunocytochemistry. Here, we report the derivation of a new embryonic stem cell line (Royan H1) from a human blastocyst that remains undifferentiated in morphology during continuous passaging for more than 30 passages, maintains a normal XX karyotype, is viable after freezing and thawing, and expresses alkaline phosphatase, Oct-4, Tra-1-60, and Tra-1-81. These cells remain undifferentiated when grown on mouse embryonic fibroblast feeder layers in the presence or absence of recombinant human leukemia inhibitory factor. Royan H1 cells can differentiate in vitro in the absence of feeder cells and can produce embryoid bodies that can further differentiate into beating cardiomyocytes as well as neurons. These results define Royan H1 cells as a new human embryonic stem cell line.",
"title": "Establishment and in vitro differentiation of a new embryonic stem cell line from human blastocyst."
},
{
"docid": "25413327",
"text": "Embryonic stem (ES) cell lines derived from human blastocysts have the developmental potential to form derivatives of all three embryonic germ layers even after prolonged culture. Here we describe the clonal derivation of two human ES cell lines, H9.1 and H9.2. At the time of the clonal derivation of the H9.1 and H9.2 ES cell lines, the parental ES cell line, H9, had already been continuously cultured for 6 months. After an additional 8 months of culture, H9.1 and H9.2 ES cell lines continued to: (1) actively proliferate, (2) express high levels of telomerase, and (3) retain normal karyotypes. Telomere lengths, while somewhat variable, were maintained between 8 and 12 kb in high-passage H9.1 and H9.2 cells. High-passage H9.1 and H9.2 cells both formed teratomas in SCID-beige mice that included differentiated derivatives of all three embryonic germ layers. These results demonstrate the pluripotency of single human ES cells, the maintenance of pluripotency during an extended period of culture, and the long-term self-renewing properties of cultured human ES cells. The remarkable developmental potential, proliferative capacity, and karyotypic stability of human ES cells distinguish them from adult cells.",
"title": "Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture."
},
{
"docid": "10546779",
"text": "Somatic cell nuclear transfer (SCNT) technology has recently been used to generate animals with a common genetic composition. In this study, we report the derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell morphology and cell surface markers and were capable of differentiating into embryoid bodies in vitro and of forming teratomas in vivo containing cell derivatives from all three embryonic germ layers in severe combined immunodeficient mice. After continuous proliferation for more than 70 passages, SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to the somatic nuclear donor cells. Although we cannot completely exclude the possibility that the cells had a parthenogenetic origin, imprinting analyses support a SCNT origin of the derived human ES cells.",
"title": "Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst."
}
] |
[
{
"docid": "3360421",
"text": "We describe the derivation of pluripotent embryonic stem (ES) cells from human blastocysts. Two diploid ES cell lines have been cultivated in vitro for extended periods while maintaining expression of markers characteristic of pluripotent primate cells. Human ES cells express the transcription factor Oct-4, essential for development of pluripotential cells in the mouse. When grafted into SCID mice, both lines give rise to teratomas containing derivatives of all three embryonic germ layers. Both cell lines differentiate in vitro into extraembryonic and somatic cell lineages. Neural progenitor cells may be isolated from differentiating ES cell cultures and induced to form mature neurons. Embryonic stem cells provide a model to study early human embryology, an investigational tool for discovery of novel growth factors and medicines, and a potential source of cells for use in transplantation therapy.",
"title": "Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro"
},
{
"docid": "26374799",
"text": "Human embryonic stem cells (hESCs) self-renew indefinitely and give rise to derivatives of all three primary germ layers, yet little is known about the signaling cascades that govern their pluripotent character. Because it plays a prominent role in the early cell fate decisions of embryonic development, we have examined the role of TGFbeta superfamily signaling in hESCs. We found that, in undifferentiated cells, the TGFbeta/activin/nodal branch is activated (through the signal transducer SMAD2/3) while the BMP/GDF branch (SMAD1/5) is only active in isolated mitotic cells. Upon early differentiation, SMAD2/3 signaling is decreased while SMAD1/5 signaling is activated. We next tested the functional role of TGFbeta/activin/nodal signaling in hESCs and found that it is required for the maintenance of markers of the undifferentiated state. We extend these findings to show that SMAD2/3 activation is required downstream of WNT signaling, which we have previously shown to be sufficient to maintain the undifferentiated state of hESCs. Strikingly, we show that in ex vivo mouse blastocyst cultures, SMAD2/3 signaling is also required to maintain the inner cell mass (from which stem cells are derived). These data reveal a crucial role for TGFbeta signaling in the earliest stages of cell fate determination and demonstrate an interconnection between TGFbeta and WNT signaling in these contexts.",
"title": "TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells."
},
{
"docid": "11335860",
"text": "Pluripotent human embryonic stem (hES) cells can differentiate into various cell types derived from the three embryonic germ layers and extraembryonic tissues such as trophoblasts. The mechanisms governing lineage choices of hES cells are largely unknown. Here, we report that we established two independent hES cell clones lacking a group of cell surface molecules, glycosyl-phosphatidyl-inositol-anchored proteins (GPI-APs). The GPI-AP deficiency in these two hES clones is due to the deficiency in the gene expression of PIG-A (phosphatidyl-inositol-glycan class A), which is required for the first step of GPI synthesis. GPI-AP-deficient hES cells were capable of forming embryoid bodies and initiating cell differentiation into the three embryonic germ layers. However, GPI-AP-deficient hES cells failed to form trophoblasts after differentiation induction by embryoid body formation or by adding exogenous BMP4. The defect in trophoblast formation was due to the lack of GPI-anchored BMP coreceptors, resulting in the impairment of full BMP4 signaling activation in the GPI-AP-deficient hES cells. These data reveal that GPI-AP-enhanced full activation of BMP signaling is required for human trophoblast formation.",
"title": "Trophoblast differentiation defect in human embryonic stem cells lacking PIG-A and GPI-anchored cell-surface proteins."
},
{
"docid": "19770974",
"text": "Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.",
"title": "Prev | Table of Contents Reports Embryonic Stem Cell Lines Derived from Human"
},
{
"docid": "4325137",
"text": "Murine embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo1,2 which can contribute differentiated progeny to all adult tissues, including the germ-cell lineage3, after re-incorporation into the normal embryo. They provide both a cellular vector for the generation of transgenic animals4 and a useful system for the identification of polypeptide factors controlling differentiation processes in early development5. In particular, medium conditioned by Buffalo rat liver cells contains a polypeptide factor, ES cell differentiation inhibitory activity (DIA), which specifically suppresses the spontaneous differentiation of ES cells in vitro, thereby permitting their growth as homogeneous stem cell populations in the absence of heterologous feeder cells6. ES cell pluripotentiality, including the ability to give rise to functional gametes, is preserved after prolonged culture in Buffalo rat liver media as a source of DIA7. Here, we report that purified DIA is related in structure and function to the recently identified haemopoetic regulatory factors human interleukin for DA cells8,9 and leukaemia inhibitory factor10. DIA and human interleukin DA/leukaemia inhibitory factor have thus been identified as related multifunctional regulatory factors with distinct biological activities in both early embryonic and haemopoetic stem cell systems.",
"title": "Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides"
},
{
"docid": "36398420",
"text": "The purpose of this study was to determine the lineage progression of human and murine very small embryonic-like (HuVSEL or MuVSEL) cells in vitro and in vivo. In vitro, HuVSEL and MuVSEL cells differentiated into cells of all three embryonic germ layers. HuVSEL cells produced robust mineralized tissue of human origin compared with controls in calvarial defects. Immunohistochemistry demonstrated that the HuVSEL cells gave rise to neurons, adipocytes, chondrocytes, and osteoblasts within the calvarial defects. MuVSEL cells were also able to differentiate into similar lineages. First round serial transplants of MuVSEL cells into irradiated osseous sites demonstrated that ∼60% of the cells maintained their VSEL cell phenotype while other cells differentiated into multiple tissues at 3 months. Secondary transplants did not identify donor VSEL cells, suggesting limited self renewal but did demonstrate VSEL cell derivatives in situ for up to 1 year. At no point were teratomas identified. These studies show that VSEL cells produce multiple cellular structures in vivo and in vitro and lay the foundation for future cell-based regenerative therapies for osseous, neural, and connective tissue disorders.",
"title": "Human and murine very small embryonic-like cells represent multipotent tissue progenitors, in vitro and in vivo."
},
{
"docid": "4427392",
"text": "The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1+ (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages. To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDRlow/C-KIT(CD117)neg population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDRlow/C-KITneg cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDRlow/C-KITneg fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.",
"title": "Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population"
},
{
"docid": "86129154",
"text": "Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.",
"title": "Induced pluripotent stem cell lines derived from human somatic cells."
},
{
"docid": "27588420",
"text": "Human induced pluripotent stem cells (HiPSCs) appear to be highly similar to human embryonic stem cells (HESCs). Using two genetic lineage-tracing systems, we demonstrate the generation of iPSC lines from human pancreatic islet beta cells. These reprogrammed cells acquired markers of pluripotent cells and differentiated into the three embryonic germ layers. However, the beta cell-derived iPSCs (BiPSCs) maintained open chromatin structure at key beta-cell genes, together with a unique DNA methylation signature that distinguishes them from other PSCs. BiPSCs also demonstrated an increased ability to differentiate into insulin-producing cells both in vitro and in vivo, compared with ESCs and isogenic non-beta iPSCs. Our results suggest that the epigenetic memory may predispose BiPSCs to differentiate more readily into insulin producing cells. These findings demonstrate that HiPSC phenotype may be influenced by their cells of origin, and suggest that their skewed differentiation potential may be advantageous for cell replacement therapy.",
"title": "Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells."
},
{
"docid": "4452318",
"text": "Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.",
"title": "Divergent reprogramming routes lead to alternative stem-cell states"
},
{
"docid": "4423327",
"text": "Nanog is a divergent homeodomain protein found in mammalian pluripotent cells and developing germ cells. Deletion of Nanog causes early embryonic lethality, whereas constitutive expression enables autonomous self-renewal of embryonic stem cells. Nanog is accordingly considered a core element of the pluripotent transcriptional network. However, here we report that Nanog fluctuates in mouse embryonic stem cells. Transient downregulation of Nanog appears to predispose cells towards differentiation but does not mark commitment. By genetic deletion we show that, although they are prone to differentiate, embryonic stem cells can self-renew indefinitely in the permanent absence of Nanog. Expanded Nanog null cells colonize embryonic germ layers and exhibit multilineage differentiation both in fetal and adult chimaeras. Although they are also recruited to the germ line, primordial germ cells lacking Nanog fail to mature on reaching the genital ridge. This defect is rescued by repair of the mutant allele. Thus Nanog is dispensible for expression of somatic pluripotency but is specifically required for formation of germ cells. Nanog therefore acts primarily in construction of inner cell mass and germ cell states rather than in the housekeeping machinery of pluripotency. We surmise that Nanog stabilizes embryonic stem cells in culture by resisting or reversing alternative gene expression states.",
"title": "Nanog safeguards pluripotency and mediates germline development"
},
{
"docid": "4457834",
"text": "The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.",
"title": "Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells"
},
{
"docid": "22428640",
"text": "Embryonic stem cells have an unlimited potential for self-renewal yet are pluripotent, capable of differentiating into three different germ layers and ultimately into multiple cell lineages. Key pluripotency specific factors maintain an undifferentiated ES cell phenotype while lineage specific factors work in opposition to promote cell specialization. In addition to these important transcriptional regulators, epigenetic modifiers play a defining role in regulating the balance between pluripotency and differentiation by promoting changes in chromatin structure.",
"title": "Chromatin remodeling in embryonic stem cells: regulating the balance between pluripotency and differentiation."
},
{
"docid": "40087494",
"text": "Imprinting is an epigenetic modification leading to monoallelic expression of some genes, and disrupted imprinting is believed to be a barrier to human stem cell transplantation, based on studies that suggest that epigenetic marks are unstable in mouse embryonic germ (EG) and embryonic stem (ES) cells. However, stem cell imprinting has not previously been examined directly in humans. We found that three imprinted genes, TSSC5, H19, and SNRPN, show monoallelic expression in in vitro differentiated human EG-derived cells, and a fourth gene, IGF2, shows partially relaxed imprinting at a ratio from 4:1 to 5:1, comparable to that found in normal somatic cells. In addition, we found normal methylation of an imprinting control region (ICR) that regulates H19 and IGF2 imprinting, suggesting that imprinting may not be a significant epigenetic barrier to human EG cell transplantation. Finally, we were able to construct an in vitro mouse model of genomic imprinting, by generating EG cells from 8.5-day embryos of an interspecific cross, in which undifferentiated cells show biallelic expression and acquire preferential parental allele expression after differentiation. This model should allow experimental manipulation of epigenetic modifications of cultured EG cells that may not be possible in human stem cell studies.",
"title": "Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages."
},
{
"docid": "17685207",
"text": "The fate of cells in the epiblast at prestreak and early primitive streak stages has been studied by injecting horseradish peroxidase (HRP) into single cells in situ of 6.7-day mouse embryos and identifying the labelled descendants at midstreak to neural plate stages after one day of culture. Ectoderm was composed of descendants of epiblast progenitors that had been located in the embryonic axis anterior to the primitive streak. Embryonic mesoderm was derived from all areas of the epiblast except the distal tip and the adjacent region anterior to it: the most anterior mesoderm cells originated posteriorly, traversing the primitive streak early; labelled cells in the posterior part of the streak at the neural plate stage were derived from extreme anterior axial and paraxial epiblast progenitors; head process cells were derived from epiblast at or near the anterior end of the primitive streak. Endoderm descendants were most frequently derived from a region that included, but extended beyond, the region producing the head process: descendants of epiblast were present in endoderm by the midstreak stage, as well as at later stages. Yolk sac and amnion mesoderm developed from posterolateral and posterior epiblast. The resulting fate map is essentially the same as those of the chick and urodele and indicates that, despite geometrical differences, topological fate relationships are conserved among these vertebrates. Clonal descendants were not necessarily confined to a single germ layer or to extraembryonic mesoderm, indicating that these lineages are not separated at the beginning of gastrulation. The embryonic axis lengthened up to the neural plate stage by (1) elongation of the primitive streak through progressive incorporation of the expanding lateral and initially more anterior regions of epiblast and, (2) expansion of the region of epiblast immediately cranial to the anterior end of the primitive streak. The population doubling time of labelled cells was 7.5 h; a calculated 43% were in, or had completed, a 4th cell cycle, and no statistically significant regional differences in the number of descendants were found. This clonal analysis also showed that (1) growth in the epiblast was noncoherent and in most regions anisotropic and directed towards the primitive streak and (2) the midline did not act as a barrier to clonal spread, either in the epiblast in the anterior half of the axis or in the primitive streak. These results taken together with the fate map indicate that, while individual cells in the epiblast sheet behave independently with respect to their neighbours, morphogenetic movement during germ layer formation is coordinated in the population as a whole.",
"title": "Clonal analysis of epiblast fate during germ layer formation in the mouse embryo."
},
{
"docid": "28071965",
"text": "The earliest aspects of human embryogenesis remain mysterious. To model patterning events in the human embryo, we used colonies of human embryonic stem cells (hESCs) grown on micropatterned substrate and differentiated with BMP4. These gastruloids recapitulate the embryonic arrangement of the mammalian germ layers and provide an assay to assess the structural and signaling mechanisms patterning the human gastrula. Structurally, high-density hESCs localize their receptors to transforming growth factor β at their lateral side in the center of the colony while maintaining apical localization of receptors at the edge. This relocalization insulates cells at the center from apically applied ligands while maintaining response to basally presented ones. In addition, BMP4 directly induces the expression of its own inhibitor, NOGGIN, generating a reaction-diffusion mechanism that underlies patterning. We develop a quantitative model that integrates edge sensing and inhibitors to predict human fate positioning in gastruloids and, potentially, the human embryo.",
"title": "A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization."
},
{
"docid": "14296612",
"text": "BACKGROUND Pluripotent embryonic stem (ES) cells, which have the capacity to give rise to all tissue types in the body, show great promise as a versatile source of cells for regenerative therapy. However, the basic mechanisms of lineage specification of pluripotent stem cells are largely unknown, and generating sufficient quantities of desired cell types remains a formidable challenge. Small molecules, particularly those that modulate key developmental pathways like the bone morphogenetic protein (BMP) signaling cascade, hold promise as tools to study in vitro lineage specification and to direct differentiation of stem cells toward particular cell types. METHODOLOGY/ PRINCIPAL FINDINGS We describe the use of dorsomorphin, a selective small molecule inhibitor of BMP signaling, to induce myocardial differentiation in mouse ES cells. Cardiac induction is very robust, increasing the yield of spontaneously beating cardiomyocytes by at least 20 fold. Dorsomorphin, unlike the endogenous BMP antagonist Noggin, robustly induces cardiomyogenesis when treatment is limited to the initial 24-hours of ES cell differentiation. Quantitative-PCR analyses of differentiating ES cells indicate that pharmacological inhibition of BMP signaling during the early critical stage promotes the development of the cardiomyocyte lineage, but reduces the differentiation of endothelial, smooth muscle, and hematopoietic cells. CONCLUSIONS/ SIGNIFICANCE Administration of a selective small molecule BMP inhibitor during the initial stages of ES cell differentiation substantially promotes the differentiation of primitive pluripotent cells toward the cardiomyocytic lineage, apparently at the expense of other mesodermal lineages. Small molecule modulators of developmental pathways like dorsomorphin could become versatile pharmacological tools for stem cell research and regenerative medicine.",
"title": "Dorsomorphin, a Selective Small Molecule Inhibitor of BMP Signaling, Promotes Cardiomyogenesis in Embryonic Stem Cells"
},
{
"docid": "26612216",
"text": "ATP-dependent chromatin remodeling complexes are a notable group of epigenetic modifiers that use the energy of ATP hydrolysis to change the structure of chromatin, thereby altering its accessibility to nuclear factors. BAF250a (ARID1a) is a unique and defining subunit of the BAF chromatin remodeling complex with the potential to facilitate chromosome alterations critical during development. Our studies show that ablation of BAF250a in early mouse embryos results in developmental arrest (about embryonic day 6.5) and absence of the mesodermal layer, indicating its critical role in early germ-layer formation. Moreover, BAF250a deficiency compromises ES cell pluripotency, severely inhibits self-renewal, and promotes differentiation into primitive endoderm-like cells under normal feeder-free culture conditions. Interestingly, this phenotype can be partially rescued by the presence of embryonic fibroblast cells. DNA microarray, immunostaining, and RNA analyses revealed that BAF250a-mediated chromatin remodeling contributes to the proper expression of numerous genes involved in ES cell self-renewal, including Sox2, Utf1, and Oct4. Furthermore, the pluripotency defects in BAF250a mutant ES cells appear to be cell lineage-specific. For example, embryoid body-based analyses demonstrated that BAF250a-ablated stem cells are defective in differentiating into fully functional mesoderm-derived cardiomyocytes and adipocytes but are capable of differentiating into ectoderm-derived neurons. Our results suggest that BAF250a is a key component of the gene regulatory machinery in ES cells controlling self-renewal, differentiation, and cell lineage decisions.",
"title": "ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a."
},
{
"docid": "7808055",
"text": "BACKGROUND It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. RESULTS I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. CONCLUSIONS I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.",
"title": "DNA methylation age of human tissues and cell types"
},
{
"docid": "16375102",
"text": "The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.",
"title": "Direct reprogramming of mouse fibroblasts to neural progenitors."
},
{
"docid": "4335423",
"text": "Despite decades of research, the identity of the cells generating the first haematopoietic cells in mammalian embryos is unknown. Indeed, whether blood cells arise from mesodermal cells, mesenchymal progenitors, bipotent endothelial–haematopoietic precursors or haemogenic endothelial cells remains controversial. Proximity of endothelial and blood cells at sites of embryonic haematopoiesis, as well as their similar gene expression, led to the hypothesis of the endothelium generating blood. However, owing to lacking technology it has been impossible to observe blood cell emergence continuously at the single-cell level, and the postulated existence of haemogenic endothelial cells remains disputed. Here, using new imaging and cell-tracking methods, we show that embryonic endothelial cells can be haemogenic. By continuous long-term single-cell observation of mouse mesodermal cells generating endothelial cell and blood colonies, it was possible to detect haemogenic endothelial cells giving rise to blood cells. Living endothelial and haematopoietic cells were identified by simultaneous detection of morphology and multiple molecular and functional markers. Detachment of nascent blood cells from endothelium is not directly linked to asymmetric cell division, and haemogenic endothelial cells are specified from cells already expressing endothelial markers. These results improve our understanding of the developmental origin of mammalian blood and the potential generation of haematopoietic stem cells from embryonic stem cells.",
"title": "Continuous single-cell imaging of blood generation from haemogenic endothelium"
},
{
"docid": "104130",
"text": "Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial-bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the main MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population. Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair.",
"title": "The suture provides a niche for mesenchymal stem cells of craniofacial bones"
},
{
"docid": "10273147",
"text": "Human induced pluripotent stem cells (iPSCs) present exciting opportunities for studying development and for in vitro disease modeling. However, reported variability in the behavior of iPSCs has called their utility into question. We established a test set of 16 iPSC lines from seven individuals of varying age, sex and health status, and extensively characterized the lines with respect to pluripotency and the ability to terminally differentiate. Under standardized procedures in two independent laboratories, 13 of the iPSC lines gave rise to functional motor neurons with a range of efficiencies similar to that of human embryonic stem cells (ESCs). Although three iPSC lines were resistant to neural differentiation, early neuralization rescued their performance. Therefore, all 16 iPSC lines passed a stringent test of differentiation capacity despite variations in karyotype and in the expression of early pluripotency markers and transgenes. This iPSC and ESC test set is a robust resource for those interested in the basic biology of stem cells and their applications.",
"title": "A functionally characterized test set of human induced pluripotent stem cells"
},
{
"docid": "13244602",
"text": "CD133+ populations of human glioblastoma multiforme (GBM) cells are reportedly enriched for tumor stem cells (TSCs) or tumor-initiating cells (TICs). Approximately 40% of freshly isolated GBM specimens, however, do not contain CD133+ tumor cells, raising the possibility that CD133 may not be a universal enrichment marker for GBM TSCs/TICs. Here we demonstrate that stage-specific embryonic antigen 1(SSEA-1/LeX)+ GBM cells fulfill the functional criteria for TSC/TIC, since (1) SSEA-1+ cells are highly tumorigenic in vivo, unlike SSEA-1- cells; (2) SSEA-1+ cells can give rise to both SSEA-1+ and SSEA-1- cells, thereby establishing a cellular hierarchy; and (3) SSEA-1+ cells have self-renewal and multilineage differentiation potentials. A distinct subpopulation of SSEA-1+ cells was present in all but one of the primary GBMs examined (n = 24), and most CD133+ tumor cells were also SSEA-1+, suggesting that SSEA-1 may be a general TSC/TIC enrichment marker in human GBMs.",
"title": "SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma."
},
{
"docid": "21272977",
"text": "This review summarizes our current understanding of exocrine pancreas development, including the formation of acinar, ductal and centroacinar cells. We discuss the transcription factors associated with various stages of exocrine differentiation, from multipotent progenitor cells to fully differentiated acinar and ductal cells. Within the branching epithelial tree of the embryonic pancreas, this involves the progressive restriction of multipotent pancreatic progenitor cells to either a central \"trunk\" domain giving rise to the islet and ductal lineages, or a peripheral \"tip\" domain giving rise to acinar cells. This review also discusses the soluble morphogens and other signaling pathways that influence these events. Finally, we examine centroacinar cells as an enigmatic pancreatic cell type whose lineage remains uncertain, and whose possible progenitor capacities continue to be explored.",
"title": "Exocrine ontogenies: on the development of pancreatic acinar, ductal and centroacinar cells."
},
{
"docid": "19204979",
"text": "Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP+ cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient–X-linked, mouse muscular dystrophy (scid–mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.",
"title": "Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells"
},
{
"docid": "27279525",
"text": "The present study was undertaken to detect, characterize, and study differentiation potential of stem cells in adult rabbit, sheep, monkey, and menopausal human ovarian surface epithelium (OSE). Two distinct populations of putative stem cells (PSCs) of variable size were detected in scraped OSE, one being smaller and other similar in size to the surrounding red blood cells in the scraped OSE. The smaller 1-3 μm very small embryonic-like PSCs were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4, whereas the bigger 4-7 μm cells with cytoplasmic localization of Oct-4 and minimal expression of SSEA-4 were possibly the tissue committed progenitor stem cells. Pluripotent gene transcripts of Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 in human and sheep OSE were detected by reverse transcriptase-polymerase chain reaction. The PSCs underwent spontaneous differentiation into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype, and embryonic stem cell-like colonies, whereas the epithelial cells transformed into mesenchymal phenotype by epithelial-mesenchymal transition in 3 weeks of OSE culture. Germ cell markers like c-Kit, DAZL, GDF-9, VASA, and ZP4 were immuno-localized in oocyte-like structures. In conclusion, as opposed to the existing view of OSE being a bipotent source of oocytes and granulosa cells, mammalian ovaries harbor distinct very small embryonic-like PSCs and tissue committed progenitor stem cells population that have the potential to develop into oocyte-like structures in vitro, whereas mesenchymal fibroblasts appear to form supporting granulosa-like somatic cells. Research at the single-cell level, including complete gene expression profiling, is required to further confirm whether postnatal oogenesis is a conserved phenomenon in adult mammals.",
"title": "Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary."
},
{
"docid": "19970015",
"text": "Down syndrome (DS), or Trisomy 21 (T21) syndrome, one of the most common chromosomal abnormalities, is caused by an extra duplication of chromosome 21. In studies of neuron development, experimental models based on human cells are considered to be the most desired and accurate for basic research. The generation of diseased induced pluripotetn stem (iPS) cell is a critical step in understanding the developmental stages of complex neuronal diseases. Here, we generated human DS iPS cell lines from second trimester amniotic fluid (AF) cells with T21 by co-expressing Yamanaka factors through lentiviral delivery and subsequently differentiated them into neuronal progenitor cells (NPCs) for further analyses. T21 AF-iPS cells were characterized for the expression of pluripotent markers and for their ability to differentiate into all three germ layers by forming embryoid bodies in vitro and teratomas in vivo. The T21 AF-iPS cells maintained their unique pattern of chromosomal karyotypes: three pairs of chromosome 21. The level of amyloid precursor protein was significantly increased in NPCs derived from T21 AF-iPS cells compared with NPCs from normal AF-iPS cells. The expression levels of miR-155 and miR-802 in T21 AF-iPS-NPCs were highly elevated in the presence of low expression of MeCP2. We observed that T21 iPS-NPCs generated fewer neurons compared with controls. T21 iPS-NPCs exhibit developmental defects during neurogenesis. Our findings suggest that T21 AF-iPS cells serve as a good source to further elucidate the impairment neurogenesis of DS and the onset of Alzheimer's disease.",
"title": "Modeling neurogenesis impairment in Down syndrome with induced pluripotent stem cells from Trisomy 21 amniotic fluid cells."
},
{
"docid": "5002665",
"text": "The embryonic cell lineage of Caenorhabditis elegans has been traced from zygote to newly hatched larva, with the result that the entire cell lineage of this organism is now known. During embryogenesis 671 cells are generated; in the hermaphrodite 113 of these (in the male 111) undergo programmed death and the remainder either differentiate terminally or become postembryonic blast cells. The embryonic lineage is highly invariant, as are the fates of the cells to which it gives rise. In spite of the fixed relationship between cell ancestry and cell fate, the correlation between them lacks much obvious pattern. Thus, although most neurons arise from the embryonic ectoderm, some are produced by the mesoderm and a few are sisters to muscles; again, lineal boundaries do not necessarily coincide with functional boundaries. Nevertheless, cell ablation experiments (as well as previous cell isolation experiments) demonstrate substantial cell autonomy in at least some sections of embryogenesis. We conclude that the cell lineage itself, complex as it is, plays an important role in determining cell fate. We discuss the origin of the repeat units (partial segments) in the body wall, the generation of the various orders of symmetry, the analysis of the lineage in terms of sublineages, and evolutionary implications.",
"title": "The embryonic cell lineage of the nematode Caenorhabditis elegans."
},
{
"docid": "87610599",
"text": "Objective To explore the in vitro maintenance and characterization of human embryonic stem cells(hESCs).Methods hESCs were cultured on feeder layer with ES culture medium,which consists of 20% Knockout Serum Replacement,Knockout DMEM and 10 ng/mL bFGF.Undifferentiated status of hESCs was identified by cell morphology,and the expressions of cell surface marker SSEA-1,SSEA-3 and TRA-1-60.G banding technique was employed for cell karyotype analysis. Pluropotency of cells were analyzed via in vitro embyoid body(EB) formation and in vivo terotoma formation. Results Most of cells showed undifferentiated properties in cell morphology and normal karyotype throughout extended culture periods. They maintained undifferentiated status with positive immunoreactivity to SSEA-3,SSEA-4 and TRA-1-60.in vitro EB formation and in vivo teratoma formation demonstrated the pluripotency of human ES cells. Conclusion The fundamental requirement to hESCs for research and clinical application were their undifferentiated status and pluropotency in culture. Our result demonstrated their potential for these purposes.",
"title": "Characterization and culture of human embryonic stem cells"
}
] |
5adfda3b55429925eb1afabd
|
What album was was released on September 26th,1995 and was Emmylou Harris's career-redefining album?
|
[
{
"docid": "3478327",
"text": "Wrecking Ball is the eighteenth studio album by American country artist Emmylou Harris, released on September 26, 1995 through Elektra Records. Moving away from the traditional acoustic sound for which she had become known, Harris collaborated with rock producer Daniel Lanois (best known for his production work with U2) and engineer Mark Howard. The album has been noted for atmospheric feel, and featured guest performances by Steve Earle, Larry Mullen, Jr., Lucinda Williams and Neil Young, who wrote the title song.",
"title": ""
},
{
"docid": "7736701",
"text": "Spyboy is a 1998 live album by Emmylou Harris and her backing band, Spyboy, which she formed for a tour to perform songs from her 1995 career-redefining album, \"Wrecking Ball\". Taking a stripped-down approach, Harris is backed by a trio comprising country singer-songwriter Buddy Miller on guitar and New Orleans musicians Daryl Johnson on bass and Brady Blade on drums. Along with songs from \"Wrecking Ball\", such as \"Where Will I Be\" and \"Deeper Well\", Harris performs other songs from earlier in her career, such as \"Born to Run\" from \"Cimarron\", \"Love Hurts\", which she first performed with Gram Parsons, \"I Ain't Living Long Like This\" from \"Quarter Moon in a Ten Cent Town\" and her ode to Parsons, \"Boulder to Birmingham\", from her 1975 debut album, \"Pieces of the Sky\". The album is currently out of print.",
"title": ""
}
] |
[
{
"docid": "13432090",
"text": "The American singer Emmylou Harris has released 26 studio albums (including four albums of collaborations with other artists), three live albums, 11 compilation albums, three video albums, and 70 singles. After recording with Gram Parsons and releasing a debut folk album on the Jubilee label, Harris signed with Reprise Records in 1974.",
"title": ""
},
{
"docid": "3732040",
"text": "Thirteen is a 1986 Emmylou Harris album. The title came from its status as her thirteenth studio album (if one does not count her 1969 first album, released on an independent label, which Harris herself rarely acknowledges).",
"title": ""
},
{
"docid": "123572",
"text": "Emmylou Harris (born April 2, 1947) is an American singer, songwriter and musician. She has released many popular albums and singles over the course of her career, and she has won 13 Grammys as well as numerous other awards, including induction into the Country Music Hall of Fame.",
"title": ""
},
{
"docid": "8685896",
"text": "Songs of the West is a compilation of \"western\"-themed songs by Emmylou Harris taken from eight of her previous albums originally released between 1975 and 1992.",
"title": ""
},
{
"docid": "31599398",
"text": "Hard Bargain is the twenty-sixth studio album by American country music singer-songwriter Emmylou Harris, released on April 26, 2011, and recorded at Tragedy/Tragedy, TN. The album is her fourth solo recording for Nonesuch Records.",
"title": ""
},
{
"docid": "11911530",
"text": "Train a Comin' is the fifth studio album by Steve Earle (his first in five years), released in 1995. In addition to Earle, it features Peter Rowan, Norman Blake, Roy Huskey, and Emmylou Harris. The album was nominated for a Grammy for Best Contemporary Folk Album.",
"title": ""
},
{
"docid": "3669511",
"text": "Blue Kentucky Girl is an album by country music artist Emmylou Harris, released in 1979. The album features delving more traditional country than the country-rock sound of Harris' previous releases. Songs include work by Willie Nelson and Gram Parsons. Rodney Crowell's \"Even Cowgirls Get the Blues\" featured harmonies by Dolly Parton and Linda Ronstadt, and came out of the women's ill-fated 1978 recording sessions, where they first attempted to record a \"trio\" album (nearly a full decade before they actually succeeded in doing so).",
"title": ""
},
{
"docid": "8663631",
"text": "Profile: Best of Emmylou Harris is a compilation of hits by Emmylou Harris from her first four Reprise/Warner albums: \"Pieces of the Sky\", \"Elite Hotel\", \"Luxury Liner\" and \"Quarter Moon in a Ten Cent Town\". The album rose as high as #9 on the Billboard country albums chart in 1978.",
"title": ""
},
{
"docid": "21010165",
"text": "See What You Want to See is American country music artist Radney Foster's third studio album. It was released in 1999 on Arista Records. The record features a number of notable guests, such as Darius Rucker from Hootie & the Blowfish, as well as Abra Moore and Emmylou Harris. Singles from this album were \"I'm In\" and \"Godspeed (Sweet Dreams).\"",
"title": ""
},
{
"docid": "8666356",
"text": "Profile II: The Best of Emmylou Harris is a compilation of hits by Emmylou Harris originally from five of her albums released between 1979 and 1983 (\"Blue Kentucky Girl\", \"Roses in the Snow\", \"Cimarron\", \"Last Date\", and \"White Shoes\"), plus two singles, \"Mister Sandman\" from 1981, and \"Someone Like You\", a new tune which became a Billboard #26 country hit in early 1985. \"Mister Sandman\" is a different recording from the one which appeared on Harris's 1981 \"Evangeline\" album, and lacks the backup vocals of Dolly Parton and Linda Ronstadt featured on \"Evangeline\".",
"title": ""
},
{
"docid": "9292453",
"text": "Flyer is a 15-track studio album, primarily of original material by the singer-songwriter Nanci Griffith, released in 1994. It was nominated for Best Contemporary Folk Album in the 37th Annual Grammy Awards (March 1, 1995). The album has contributions from Peter Buck, Mark Knopfler, Emmylou Harris, Larry Mullen Jr., Adam Clayton, Adam Duritz, The Chieftains and the Indigo Girls.",
"title": ""
},
{
"docid": "2082334",
"text": "Trio (Dolly Parton, Linda Ronstadt and Emmylou Harris album)",
"title": ""
},
{
"docid": "3926399",
"text": "Last Date is a live Emmylou Harris album, released in October 1982. Recorded at a series of honky tonks and other small venues on the west coast, Harris conceived the album as a showcase for her Hot Band. It was composed mostly of country standards. Harris reached #1 on the U.S. country charts with the title single, written by Floyd Cramer, who originally took it to the top ten on the U.S. pop and country charts, as an instrumental in 1960. In 2000, Eminent Records reissued \"Last Date\" for the first time on CD, complete with new liner notes and two bonus tracks.",
"title": ""
},
{
"docid": "25738410",
"text": "\"'Til I Gain Control Again\" is a country song written by Rodney Crowell and originally recorded by Emmylou Harris in 1975. The song was included on her 1975 studio album \"Elite Hotel\" and was performed by Alison Krauss in 2016 as part of a tribute album to Harris titled: \"The Life & Songs of Emmylou Harris\". The song was later covered by Crystal Gayle in 1982 and Blue Rodeo in 1993. Crowell recorded his own version of the song on his 1981 self-titled album. It was also covered by Van Morrison on his Pay the Devil Album out in 2006. The gothic band This Mortal Coil covered this song on their album Blood released on April 22, 1991.",
"title": ""
},
{
"docid": "20605966",
"text": "Redefine is the third full-length album by Canadian hip hop duo Dragon Fli Empire, released in North America on Makebelieve Records in early 2009. Teekay has explained the album title by saying: \"\"We 'redefine' by using our creativity to bust free from any boxes placed on what we can accomplish.\"\"",
"title": ""
},
{
"docid": "17290818",
"text": "All I Intended to Be is the 25th studio album from Emmylou Harris and her third release on Nonesuch Records. It was released in the United States on June 10, 2008. The album debuted at number 22 on the Billboard 200, and number four on Top Country Albums, which makes the album Harris’ highest charting solo record on the Billboard 200 since \"Evangeline\" was released in 1981.",
"title": ""
},
{
"docid": "3483412",
"text": "Cowgirl's Prayer is a 1993 Emmylou Harris album. Coming immediately after 1992's live acoustic \"At the Ryman\" album, \"Cowgirl's Prayer\" is a collection of similarly subdued material (with a couple of rockers thrown in, notably \"High Powered Love\", the album's first single). Released at a time when older artists (i.e. anyone over 40) were being dropped from country radio playlists, the album received little airplay, despite positive reviews, and its relative commercial failure is said to have served as a catalyst for Harris' decision to change course with the harder edged sound of her subsequent work, beginning with 1995's rockish \"Wrecking Ball\", thus rendering \"Cowgirl's Prayer\" Harris' last mainstream country album.",
"title": ""
},
{
"docid": "24917060",
"text": "My Lord What a Mornin' is an album by Harry Belafonte, released by RCA Victor in 1960. The album was reissued in 1995 with additional bonus tracks.",
"title": ""
},
{
"docid": "8541920",
"text": "Children Running Through is Patty Griffin's sixth commercially released album, and fifth studio album. It was released on 6 February 2007. The album features vocals from Emmylou Harris on \"Trapeze\". \"Heavenly Day\" was the album's first single.",
"title": ""
},
{
"docid": "38644958",
"text": "Old Yellow Moon is a Grammy Award-winning collaborative album by American country music singer-songerwriters Emmylou Harris and Rodney Crowell, released on February 26, 2013 in the United States by Nonesuch Records. It is the twenty-seventh and tenth studio albums for both Harris and Crowell, respectively, as well as Harris's fifth album for Nonesuch Records.",
"title": ""
},
{
"docid": "32620524",
"text": "\"One of These Days\" is a song written by Earl Montgomery, and recorded by American country music artist Emmylou Harris. It was released in March 1976 as the second single from the album \"Elite Hotel\". The song reached number 3 on the \"Billboard\" Hot Country Singles & Tracks chart.",
"title": ""
},
{
"docid": "32621662",
"text": "\"In My Dreams\" is a song written by Paul Kennerley, and recorded by American country music artist Emmylou Harris. It was released in March 1984 as the second single from the album \"White Shoes\". The song reached number 9 on the \"Billboard\" Hot Country Singles & Tracks chart.",
"title": ""
},
{
"docid": "35832763",
"text": "\"Heaven Only Knows\" is a song written by Paul Kennerley, and recorded by American country music singer Emmylou Harris. It was released in April 1989 as the second single from the album \"Bluebird\". The song reached Number 16 on the \"Billboard\" Hot Country Singles & Tracks chart.",
"title": ""
},
{
"docid": "3722509",
"text": "Evangeline is a 1981 album by Emmylou Harris that was composed mostly of leftover material from past recording sessions and which did not fit into any of her other albums. Songs included a remake of \"Mister Sandman\" (from the much-lauded \"Trio\" sessions with Dolly Parton and Linda Ronstadt), \"Evangeline\" (also featuring vocals by Parton and Ronstadt), which she had previously performed with The Band, Rodney Crowell's \"Ashes By Now\", and a cover of John Fogerty's \"Bad Moon Rising\". Though it received mixed reviews upon its release, the album was yet another commercial success for Harris. It was certified Gold in less than a year after its release. A single release of \"Mister Sandman\" (Top 10 country/Top 40 pop) did well on the charts, though neither Ronstadt's nor Parton's record companies would allow their artists' vocals to be used on the single, so Harris rerecorded the song, singing all three parts for the single release. Rodney Crowell's \"I Don't Have to Crawl\" was released as the album's second single. (Music videos were produced for both \"Mister Sandman\" and \"I Don't Have to Crawl\".)",
"title": ""
},
{
"docid": "36049857",
"text": "All Fall Down is the eighth studio album by recording artist Shawn Colvin, released in 2012.The album is Colvin's second studio release on Nonesuch Records and features collaborations with Emmylou Harris and Patty Griffin.",
"title": ""
},
{
"docid": "4607001",
"text": "Quarter Moon in a Ten Cent Town is an album by country music artist Emmylou Harris, released in 1978. The album reached number 3 on the Billboard charts, with three charting singles: \"To Daddy\" (written by Dolly Parton) at #3, \"Two More Bottles of Wine\" at #1 (the third #1 of Harris' career), and \"Easy from Now On\" (co-written by Carlene Carter, and the song from which the album's title comes) at #12. Also featured are \"One Paper Kid\", a duet with Willie Nelson, and \"Leaving Louisiana in the Broad Daylight\", which the Oak Ridge Boys would reach #1 with in 1980. The painting used for the album cover is by Susanna Clark.",
"title": ""
},
{
"docid": "4606905",
"text": "Elite Hotel is an album by country music artist Emmylou Harris, released in 1975. \"Elite Hotel\" was Harris' second album to be released in 1975, preceded by the widely acclaimed \"Pieces of the Sky\", \"Elite Hotel\" surpassed it on the Billboard Music Charts, becoming Harris' first #1 country album. The album yielded two #1 country singles: \"Together Again\" and Harris' version of the Patsy Cline hit \"Sweet Dreams\", and \"One of These Days\" made it to the #3 spot. A performance of The Beatles's \"Here, There and Everywhere\" entered the pop charts at #65. Harris' eclectic musical tastes were reflected in her choice of material by Hank Williams, The Beatles, Gram Parsons and Buck Owens.",
"title": ""
},
{
"docid": "51551623",
"text": "The Complete Trio Collection is compilation album by American singer-songwriters Dolly Parton, Emmylou Harris and Linda Ronstadt. It brings together newly remastered versions of their two award-winning albums, 1987's \"Trio\" and 1999's \"Trio II\", with a third disc compiling 20 alternate takes and unreleased material. It was released worldwide on September 9, 2016, by Rhino Entertainment.",
"title": ""
},
{
"docid": "9155202",
"text": "Winter Marquee is a live album by folk singer Nanci Griffith. Recorded live during the \"Clock Without Hands\" tour in spring 2002, this album grew from the original wish to capture just one live song (Phil Ochs' \"What's That I Hear\") into a 14 track live CD album , Griffith's first live recording since \"One Fair Summer Evening\" (1988). On May 29, 2002, at the historic Tennessee Theatre, Knoxville a live performance was filmed, and released on DVD under the same name. During the recording of both the album and the DVD, Griffith is joined on stage by Emmylou Harris, Tom Russell and Andrew Hardin.",
"title": ""
},
{
"docid": "31436977",
"text": "Belladonna is a 2005 studio album by the Canadian singer-songwriter and producer Daniel Lanois who, according to his website, took the techniques he developed with Brian Eno and went on to produce career albums for Bob Dylan, Peter Gabriel, and Emmylou Harris. This journey comes full circle on \"Belladonna\", an instrumental record that captures the often tense emotional dynamics of Eno's pioneering releases. Dense textures evolve into delicate Mexican melodies, capturing the disquieting serenity of American southwest landscapes. This is Lanois' self-proclaimed defining moment.",
"title": ""
}
] |
172
|
Basophils promote disease development in patients with systemic lupus erythematosus (SLE).
|
[
{
"docid": "12670680",
"text": "In systemic lupus erythematosus (SLE), self-reactive antibodies can target the kidney (lupus nephritis), leading to functional failure and possible mortality. We report that activation of basophils by autoreactive IgE causes their homing to lymph nodes, promoting T helper type 2 (T(H)2) cell differentiation and enhancing the production of self-reactive antibodies that cause lupus-like nephritis in mice lacking the Src family protein tyrosine kinase Lyn (Lyn(-/-) mice). Individuals with SLE also have elevated serum IgE, self-reactive IgEs and activated basophils that express CD62 ligand (CD62L) and the major histocompatibility complex (MHC) class II molecule human leukocyte antigen-DR (HLA-DR), parameters that are associated with increased disease activity and active lupus nephritis. Basophils were also present in the lymph nodes and spleen of subjects with SLE. Thus, in Lyn(-/-) mice, basophils and IgE autoantibodies amplify autoantibody production that leads to lupus nephritis, and in individuals with SLE IgE autoantibodies and activated basophils are factors associated with disease activity and nephritis.",
"title": "BASOPHILS AND THE T HELPER 2 ENVIRONMENT CAN PROMOTE THE DEVELOPMENT OF LUPUS NEPHRITIS"
}
] |
[
{
"docid": "14938990",
"text": "Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.",
"title": "Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene"
},
{
"docid": "28015516",
"text": "Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a breakdown of tolerance to nuclear antigens and the development of immune complexes. Genomic approaches have shown that human SLE leukocytes homogeneously express type I interferon (IFN)-induced and neutrophil-related transcripts. Increased production and/or bioavailability of IFN-α and associated alterations in dendritic cell (DC) homeostasis have been linked to lupus pathogenesis. Although neutrophils have long been shown to be associated with lupus, their potential role in disease pathogenesis remains elusive. Here, we show that mature SLE neutrophils are primed in vivo by type I IFN and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). SLE NETs contain DNA as well as large amounts of LL37 and HMGB1, neutrophil proteins that facilitate the uptake and recognition of mammalian DNA by plasmacytoid DCs (pDCs). Indeed, SLE NETs activate pDCs to produce high levels of IFN-α in a DNA- and TLR9 (Toll-like receptor 9)-dependent manner. Our results reveal an unsuspected role for neutrophils in SLE pathogenesis and identify a novel link between nucleic acid-recognizing antibodies and type I IFN production in this disease.",
"title": "Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus."
},
{
"docid": "28149602",
"text": "PURPOSE OF REVIEW Recent discoveries implicate neutrophils as important regulators of innate and adaptive immunity and in the development of organ damage in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). RECENT FINDINGS Various putative SLE biomarkers are neutrophil-related, including neutrophil granular proteins and histones undergoing post-translational modifications during neutrophil extracellular trap (NET) formation. In the bone marrow, lupus neutrophils can drive B and T cell abnormalities, at least in part, by their enhanced production of type-I interferons, tumor necrosis factor-alpha (TNFα) and the B-cell stimulating factors B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Lupus neutrophils and, in particular, lupus low-density granulocytes (a distinct pathogenic subset) display epigenetic modifications and genomic alterations that may be relevant to their deleterious roles in SLE. Proteins and enzymes externalized by lupus NETs can affect vascular health by inducing endothelial apoptosis and oxidizing lipoproteins. Hampering NET formation through peptidylarginine deiminase inhibitors abrogates lupus phenotype and atherosclerosis in murine studies. SUMMARY Recent discoveries support the notion that neutrophils, low-density granulocytes and aberrant NET formation and clearance play important roles in lupus pathogenesis. Future studies should focus on how to selectively target these immunostimulatory pathways in this disease.",
"title": "The role of neutrophils in the pathogenesis of systemic lupus erythematosus."
},
{
"docid": "5448119",
"text": "Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 × 10−8): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P≤ 1 × 10−5. A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 × 10−3) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.",
"title": "A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus"
},
{
"docid": "1834762",
"text": "Research on the human microbiome has established that commensal and pathogenic bacteria can influence obesity, cancer, and autoimmunity through mechanisms mostly unknown. We found that a component of bacterial biofilms, the amyloid protein curli, irreversibly formed fibers with bacterial DNA during biofilm formation. This interaction accelerated amyloid polymerization and created potent immunogenic complexes that activated immune cells, including dendritic cells, to produce cytokines such as type I interferons, which are pathogenic in systemic lupus erythematosus (SLE). When given systemically, curli-DNA composites triggered immune activation and production of autoantibodies in lupus-prone and wild-type mice. We also found that the infection of lupus-prone mice with curli-producing bacteria triggered higher autoantibody titers compared to curli-deficient bacteria. These data provide a mechanism by which the microbiome and biofilm-producing enteric infections may contribute to the progression of SLE and point to a potential molecular target for treatment of autoimmunity.",
"title": "Amyloid-DNA Composites of Bacterial Biofilms Stimulate Autoimmunity."
},
{
"docid": "27466734",
"text": "Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.",
"title": "Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study"
},
{
"docid": "14853989",
"text": "Autoantibodies to DNA and histones (chromatin) are the defining antigen specificity in systemic lupus erythematosus (SLE) and related musculoskeletal disorders but the mechanisms responsible for their induction remain mysterious. That situation rapidly changed once neutrophil extracellular chromatin traps (NETs) were discovered and observed to play a conserved role in innate immune responses to a broad variety of microbial pathogens. At the center of an infectious process, neutrophils exert various antimicrobial defenses, including the release of nuclear chromatin into the extracellular space. The externalized NETs, a complex meshwork of nuclear chromatin and antimicrobial proteins, serve to immobilize and degrade microbial pathogens. Here, we critically evaluate the evidence supporting NETs versus apoptotic bodies as a source for nuclear antigens in autoimmunity. We also discuss the possibility that NET chromatin forms an essential component of immune deposits in the pathogenesis of glomerulonephritis in SLE and other autoimmune immune complex diseases.",
"title": "Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity"
},
{
"docid": "7115651",
"text": "IL-21 is a pleiotropic type 1 cytokine that shares the common cytokine receptor γ-chain, γ(c), with IL-2, IL-4, IL-7, IL-9, and IL-15. IL-21 is most homologous to IL-2. These cytokines are encoded by adjacent genes, but they are functionally distinct. Whereas IL-2 promotes development of regulatory T cells and confers protection from autoimmune disease, IL-21 promotes differentiation of Th17 cells and is implicated in several autoimmune diseases, including type 1 diabetes and systemic lupus erythematosus. However, the roles of IL-21 and IL-2 in CNS autoimmune diseases such as multiple sclerosis and uveitis have been controversial. Here, we generated Il21-mCherry/Il2-emGFP dual-reporter transgenic mice and showed that development of experimental autoimmune uveitis (EAU) correlated with the presence of T cells coexpressing IL-21 and IL-2 into the retina. Furthermore, Il21r(-/-) mice were more resistant to EAU development than wild-type mice, and adoptive transfer of Il21r(-/-) T cells induced much less severe EAU, underscoring the need for IL-21 in the development of this disease and suggesting that blocking IL-21/γ(c)-signaling pathways may provide a means for controlling CNS auto-inflammatory diseases.",
"title": "Key role for IL-21 in experimental autoimmune uveitis."
},
{
"docid": "1049501",
"text": "Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.",
"title": "Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease"
},
{
"docid": "13106686",
"text": "Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3' repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.",
"title": "Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing."
},
{
"docid": "5476778",
"text": "One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS). There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5,6,7). HAM/TSP patients develop antibodies to neurons. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.",
"title": "Autoimmunity due to molecular mimicry as a cause of neurological disease"
},
{
"docid": "22852120",
"text": "Type 2 immune responses are defined by the cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, which can either be host protective or have pathogenic activity. Type 2 immunity promotes antihelminth immunity, suppresses type 1-driven autoimmune disease, neutralizes toxins, maintains metabolic homeostasis, and regulates wound repair and tissue regeneration pathways following infection or injury. Nevertheless, when type 2 responses are dysregulated, they can become important drivers of disease. Type 2 immunity induces a complex inflammatory response characterized by eosinophils, mast cells, basophils, type 2 innate lymphoid cells, IL-4-and/or IL-13-conditioned macrophages and T helper 2 (TH2) cells, which are crucial to the pathogenesis of many allergic and fibrotic disorders. As chronic type 2 immune responses promote disease, the mechanisms that regulate their maintenance are thought to function as crucial disease modifiers. This Review discusses the many endogenous negative regulatory mechanisms that antagonize type 2 immunity and highlights how therapies that target some of these pathways are being developed to treat type 2-mediated disease.",
"title": "Type 2 cytokines: mechanisms and therapeutic strategies"
},
{
"docid": "13717103",
"text": "INTRODUCTION Mutations in the FUS gene have been shown to be a rare cause of amyotrophic lateral sclerosis (ALS-FUS) and whilst well documented clinically and genetically there have been relatively few neuropathological studies. Recent work suggested a possible correlation between pathological features such as frequency of basophilic inclusions in neurons and rate of clinical decline, other studies have revealed a discrepancy between the upper motor neuron features detected clinically and the associated pathology. The purpose of this study was to describe the pathological features associated with more recently discovered FUS mutations and reinvestigate those with well recognised mutations in an attempt to correlate the pathology with mutation and/or clinical phenotype. The brains and spinal cords of seven cases of ALS-FUS were examined neuropathologically, including cases with the newly described p. K510E mutation and a case with both a known p. P525L mutation in the FUS gene and a truncating p. Y374X mutation in the TARDBP gene. RESULTS The neuropathology in all cases revealed basophilic and FUS inclusions in the cord. The density and type of inclusions varied markedly between cases, but did not allow a clear correlation with clinical progression. Only one case showed significant motor cortical pathology despite the upper motor neuron clinical features being evident in 4 patients. The case with both a FUS and TARDBP mutation revealed FUS positive inclusions but no TDP-43 pathology. Instead there were unusual p62 positive, FUS negative neuronal and glial inclusions as well as dot-like neurites. CONCLUSIONS The study confirms cases of ALS-FUS to be mainly a lower motor neuron disease and to have pathology that does not appear to neatly correlate with clinical features or genetics. Furthermore, the case with both a FUS and TARDBP mutation reveals an intriguing pathological profile which at least in part involves a very unusual staining pattern for the ubiquitin-binding protein p62.",
"title": "ALS-FUS pathology revisited: singleton FUS mutations and an unusual case with both a FUS and TARDBP mutation"
},
{
"docid": "18429416",
"text": "Food allergy is a major public health concern in westernized countries, estimated to affect 5 % of children and 3–4 % of adults. Allergen-specific immunotherapy for food allergy is currently being actively evaluated, but is still experimental. The optimal protocol, in terms of the route of administration of the food, target maintenance dose, and duration of maintenance therapy, and the optimal patient for these procedures are still being worked out. The mechanisms underlying successful food desensitization are also unclear, in part, because there is no standard immunotherapy protocol. The mechanisms involved, however, may include mast cell and basophil suppression, development of food-specific IgG4 antibodies, reduction in the food-specific IgE/IgG4 ratio, up-regulation and expansion of natural or inducible regulatory T cells, a skewing from a Th2 to a Th1 profile, and the development of anergy and/or deletion in antigen-specific cells. Additional studies are required to elucidate and understand these mechanisms by which desensitization and tolerance are achieved, which may reveal valuable biomarkers for evaluating and following food allergic patients on immunotherapy.",
"title": "Immunological mechanisms for desensitization and tolerance in food allergy"
},
{
"docid": "25726838",
"text": "The role of immune responses in tumor development is a central issue for tumor biology and immunology. IL-17 is an important cytokine for inflammatory and autoimmune diseases. Although IL-17-producing cells are detected in cancer patients and tumor-bearing mice, the role of IL-17 in tumor development is controversial, and mechanisms remain to be fully elucidated. In the current study, we found that the development of tumors was inhibited in IL-17R-deficient mice. A defect in IFN-gammaR increased tumor growth, whereas tumor growth was inhibited in mice that were deficient in both IL-17R and IFN-gammaR compared with wild-type animals. Further experiments showed that neutralization of IL-17 by Abs inhibited tumor growth in wild-type mice, whereas systemic administration of IL-17 promoted tumor growth. The IL-17R deficiency increased CD8 T cell infiltration, whereas it reduced the infiltration of myeloid-derived suppressor cells (MDSCs) in tumors. In contrast, administration of IL-17 inhibited CD8 T cell infiltration and increased MDSCs in tumors. Further analysis indicated that IL-17 was required for the development and tumor-promoting activity of MDSCs in tumor-bearing mice. These data demonstrate that IL-17-mediated responses promote tumor development through the induction of tumor-promoting microenvironments at tumor sites. IL-17-mediated regulation of MDSCs is a primary mechanism for its tumor-promoting effects. The study provides novel insights into the role of IL-17 in tumor development and has major implications for targeting IL-17 in treatment of tumors.",
"title": "IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells."
},
{
"docid": "11328820",
"text": "The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.",
"title": "NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis."
},
{
"docid": "15707049",
"text": "Interstitial lung disease (ILD) is a common manifestation of systemic autoimmunity characterized by progressive inflammation or scarring of the lungs. Patients who develop these complications can exhibit significantly impaired gas exchange that may result in hypoxemia, pulmonary hypertension, and even death. Unfortunately, little is understood about how these diseases arise, including the role of specific defects in immune tolerance. Another key question is whether autoimmune responses targeting the lung parenchyma are critical to ILD pathogenesis, including that of isolated idiopathic forms. We show that a specific defect in central tolerance brought about by mutations in the autoimmune regulator gene (Aire) leads to an autoreactive T cell response to a lung antigen named vomeromodulin and the development of ILD. We found that a human patient and mice with defects in Aire develop similar lung pathology, demonstrating that the AIRE-deficient model of autoimmunity is a suitable translational system in which to unravel fundamental mechanisms of ILD pathogenesis.",
"title": "Identification of an autoantigen demonstrates a link between interstitial lung disease and a defect in central tolerance."
},
{
"docid": "19464037",
"text": "OBJECTIVE To describe outcomes and identify variables associated with hospital and 1-year survival for patients admitted to an intensive care unit (ICU) with an acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN Prospective, multicenter, inception cohort study. SETTING Forty-two ICUs at 40 US hospitals. PATIENTS A total of 362 admissions for COPD exacerbation selected from the Acute Physiology and Chronic Health Evaluation (APACHE) III database of 17,440 ICU admissions. MEASUREMENTS AND RESULTS Hospital mortality for the 362 admissions was 24%. For the 167 patients aged 65 years or older, mortality was 30% at hospital discharge, 41% at 90 days, 47% at 180 days, and 59% at 1 year. Median survival for all patients was 224 days, and median survival for the patients who died within 1 year was 30.5 days. On multiple regression analysis, variables associated with hospital mortality included age, severity of respiratory and nonrespiratory organ system dysfunction, and hospital length of stay before ICU admission. Development of nonrespiratory organ system dysfunction was the major predictor of hospital mortality (60% of total explanatory power) and 180-day outcomes (54% of explanatory power). Respiratory physiological variables (respiratory rate, serum pH, PaCO2, PaO2, and alveolar-arterial difference in partial pressure of oxygen [PAO2-PaO2]) indicative of advanced dysfunction were more strongly associated with 180-day mortality rates (22% of explanatory power) than hospital death rates (4% of explanatory power). After controlling for severity of illness, mechanical ventilation at ICU admission was not associated with either hospital mortality or subsequent survival. CONCLUSIONS Patients with COPD admitted to an ICU for an acute exacerbation have a substantial hospital mortality (24%). For patients aged 65 years or older, mortality doubles in 1 year from 30% to 59%. Hospital and longer-term mortality is closely associated with development of nonrespiratory organ system dysfunction; severity of the underlying respiratory function substantially influences mortality following hospital discharge. The need for mechanical ventilation at ICU admission did not influence either short- or long-term outcomes. Physicians should be aware of these relationships when making treatment decisions or evaluating new therapies.",
"title": "Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease."
},
{
"docid": "24712186",
"text": "The two membrane proteins, STIM1 and Orai1, have each been shown to be essential for the activation of store-operated channels (SOC). Yet, how these proteins functionally interact is not known. Here, we reveal that STIM1 and Orai1 expressed together reconstitute functional SOCs. Expressed alone, Orai1 strongly reduces store-operated Ca(2+) entry (SOCE) in human embryonic kidney 293 cells and the Ca(2+) release-activated Ca(2+) current (I(CRAC)) in rat basophilic leukemia cells. However, expressed along with the store-sensing STIM1 protein, Orai1 causes a massive increase in SOCE, enhancing the rate of Ca(2+)entry by up to 103-fold. This entry is entirely store-dependent since the same coexpression causes no measurable store-independent Ca(2+) entry. The entry is completely blocked by the SOC blocker, 2-aminoethoxydiphenylborate. Orai1 and STIM1 coexpression also caused a large gain in CRAC channel function in rat basophilic leukemia cells. The close STIM1 homologue, STIM2, inhibited SOCE when expressed alone but coexpressed with Orai1 caused substantial constitutive (store-independent) Ca(2+) entry. STIM proteins are known to mediate Ca(2+) store-sensing and endoplasmic reticulum-plasma membrane coupling with no intrinsic channel properties. Our results revealing a powerful gain in SOC function dependent on the presence of both Orai1 and STIM1 strongly suggest that Orai1 contributes the PM channel component responsible for Ca(2+) entry. The suppression of SOC function by Orai1 overexpression likely reflects a required stoichiometry between STIM1 and Orai1.",
"title": "Orai1 and STIM reconstitute store-operated calcium channel function."
},
{
"docid": "3093512",
"text": "AIM Peripheral artery disease (PAD) is a vascular disease affecting peripheral circulation. Recently, genome-wide association studies revealed a relationship between single nucleotide polymorphisms (SNPs) in ADAMTS7 (a disintegrin and metalloprotease with thrombospondin motif 7) and atherosclerosis. In this study, we aimed to determine ADAMTS7 expression in peripheral blood mononuclear cells (PBMCs) and the frequency of ADAMTS7 rs1994016 and rs3825807 polymorphisms in a sample of Turkish patients with PAD, and to evaluate the association of matrix metalloproteinase (MMP) levels with PAD development. METHODS In this case-control study, ADAMTS7mRNA and protein expression was determined using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively, and rs1994016 and rs3825807 variants in ADAMTS7 were determined by real-time PCR in 115 PAD patients and 116 healthy controls. Plasma levels of nine MMPs were determined using a multiplex immunoassay system. RESULTS ADAMTS7mRNA levels were significantly higher in PAD patients than in controls (t=-2.75, P=.007). There was no significant difference in the frequencies of rs1994016 and rs3825807 between PAD patients and controls (P>.05). In PAD patients, ADAMTS7mRNA levels were significantly increased for the CC genotype of rs1994016 (t=-2.31, P=.026) and TT genotype of rs3825807 (t=-2.23, P=.032). Furthermore, plasma levels of MMP-1, MMP-3, MMP-7, MMP-10, MMP-12, and MMP-13 were significantly higher in PAD patients than in controls (P<.05). CONCLUSION This is the first report of the relationship between PAD and ADAMTS7 expression and the effects of the rs1994016 and rs3825807 variants on PAD development. ADAMTS7 may be associated with PAD development.",
"title": "Genetic variants rs1994016 and rs3825807 in ADAMTS7 affect its mRNA expression in atherosclerotic occlusive peripheral arterial disease"
},
{
"docid": "35777860",
"text": "Induced pluripotent stem (iPS) cells derived from disease patients are an invaluable resource for biomedical research and may provide a source for replacement therapies. In this study, we have generated iPS cells from Asian patients with chronic degenerative diseases of the nervous system, including spinal muscular atrophy (SMA), Parkinson disease (PD) and amyotrophic lateral sclerosis (ALS) by transduction with four factors (KLF4, SOX2, OCT4 and c-MYC). All of the iPS cells showed pluripotency similar to that of human embryonic stem cells (hESCs) and were able to differentiate into various somatic cell types in vitro and in vivo. Furthermore, the iPS cells also can be committed to differentiate into neural cells, the cell type that is affected in chronic degenerative diseases. Therefore, the patient-specific iPS cells we generated offer a cellular model in which to investigate disease mechanisms, discover and test novel drugs and develop new therapies for chronic neurodegenerative diseases.",
"title": "Generation of induced pluripotent stem cells from Asian patients with chronic neurodegenerative diseases."
},
{
"docid": "803312",
"text": "The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.",
"title": "Cerebral organoids model human brain development and microcephaly"
},
{
"docid": "20310709",
"text": "Mice lacking the transcription factor T-bet in the innate immune system develop microbiota-dependent colitis. Here, we show that interleukin-17A (IL-17A)-producing IL-7Rα(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice. TNF-α produced by CD103(-)CD11b(+) dendritic cells synergized with IL-23 to drive IL-17A production by ILCs, demonstrating a previously unrecognized layer of cellular crosstalk between dendritic cells and ILCs. We have identified Helicobacter typhlonius as a key disease trigger driving excess TNF-α production and promoting colitis in TRUC mice. Crucially, T-bet also suppressed the expression of IL-7R, a key molecule involved in controlling intestinal ILC homeostasis. The importance of IL-7R signaling in TRUC disease was highlighted by the dramatic reduction in intestinal ILCs and attenuated colitis following IL-7R blockade. Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota.",
"title": "The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor+ Innate Lymphoid Cells"
},
{
"docid": "5511240",
"text": "Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are key contributors of host defense against enteroinvasive bacteria. Here, we found that infection by Listeria monocytogenes induced the early necroptotic death of Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial type 1 inflammatory response. Kupffer cell death also triggered a type 2 response that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil-derived interleukin-4 (IL-4). This led to the alternative activation of the monocyte-derived macrophages recruited to the liver, which thereby replaced ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is therefore a key signal orchestrating type 1 microbicidal inflammation and type-2-mediated liver repair upon infection. This indicates that beyond the classical dichotomy of type 1 and type 2 responses, these responses can develop sequentially in the context of a bacterial infection and act interdependently, orchestrating liver immune responses and return to homeostasis, respectively.",
"title": "Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection."
},
{
"docid": "44562904",
"text": "BACKGROUND Many patients with lung cancer report delays in diagnosing their disease. This may contribute to advanced stage at diagnosis and poor long term survival. This study explores the delays experienced by patients referred to a regional cancer centre with lung cancer. METHODS A prospective cohort of patients referred with newly diagnosed lung cancer were surveyed over a 3 month period to assess delays in diagnosis. Patients were asked when they first experienced symptoms, saw their doctor, what tests were done, when they saw a specialist and when they started treatment. Descriptive statistics were used to summarize the different time intervals. RESULTS 56 of 73 patients consented (RR 77%). However only 52 patients (30M, 22F) were interviewed as 2 died before being interviewed and two could not be contacted. The mean age was 68yrs. Stage distribution was as follows (IB/IIA 10%, stage IIIA 20%, IIIB/IV 70%). Patients waited a median of 21 days (iqr 7-51d) before seeing a doctor and a further 22d (iqr 0-38d) to complete any investigations. The median time from presentation to specialist referral was 27d (iqr 12-49d) and a further 23.5d (iqr 10-56d) to complete investigations. The median wait to start treatment once patients were seen at the cancer centre was 10d (iqr 2-28d). The overall time from development of first symptoms to starting treatment was 138d (iqr 79-175d). CONCLUSIONS Lung cancer patients experience substantial delays from development of symptoms to first initiating treatment. There is a need to promote awareness of lung cancer symptoms and develop and evaluate rapid assessment clinics for patients with suspected lung cancers.",
"title": "Delays in the diagnosis of lung cancer."
},
{
"docid": "13814480",
"text": "Alzheimer's disease (AD) is the most common cause of dementia in those over the age of 65. While a numerous of disease-causing genes and risk factors have been identified, the exact etiological mechanisms of AD are not yet completely understood, due to the inability to test theoretical hypotheses on non-postmortem and patient-specific research systems. The use of recently developed and optimized induced pluripotent stem cells (iPSCs) technology may provide a promising platform to create reliable models, not only for better understanding the etiopathological process of AD, but also for efficient anti-AD drugs screening. More importantly, human-sourced iPSCs may also provide a beneficial tool for cell-replacement therapy against AD. Although considerable progress has been achieved, a number of key challenges still require to be addressed in iPSCs research, including the identification of robust disease phenotypes in AD modeling and the clinical availabilities of iPSCs-based cell-replacement therapy in human. In this review, we highlight recent progresses of iPSCs research and discuss the translational challenges of AD patients-derived iPSCs in disease modeling and cell-replacement therapy.",
"title": "Induced pluripotent stem cells in Alzheimer’s disease: applications for disease modeling and cell-replacement therapy"
},
{
"docid": "471921",
"text": "Air pollution is a heterogeneous, complex mixture of gases, liquids, and particulate matter. Epidemiological studies have demonstrated a consistent increased risk for cardiovascular events in relation to both short- and long-term exposure to present-day concentrations of ambient particulate matter. Several plausible mechanistic pathways have been described, including enhanced coagulation/thrombosis, a propensity for arrhythmias, acute arterial vasoconstriction, systemic inflammatory responses, and the chronic promotion of atherosclerosis. The purpose of this statement is to provide healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease. In addition, the implications of these findings in relation to public health and regulatory policies are addressed. Practical recommendations for healthcare providers and their patients are outlined. In the final section, suggestions for future research are made to address a number of remaining scientific questions.",
"title": "Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association."
},
{
"docid": "10374686",
"text": "Although 65% of people with cancer want to die at home, only about 30% are successful in doing so.1,2 A government committed to choice for patients must improve this figure.3 Developing palliative care services in primary care is essential for realising the expectations of dying people. Such services could also offer important opportunities for extending supportive humane care at an earlier stage, and to people not only with cancer but with chronic obstructive pulmonary disease, motor neurone disease, and cardiac failure, for example, who also often have palliative care needs. Primary care professionals have the potential and ability to provide end of life care for most patients, given adequate training, resources, and, when needed, specialist advice.4,5 They share common values with palliative care specialists—holistic, patient centred care, delivered in the context of families and friends.6 However, until recently, apart from Macmillan general practitioners and nurse facilitators, few comprehensive workforce initiatives have been undertaken in primary care that focus on end of life care. Many cancer patients and their carers experience existential distress long before they die.7 Recognising and alleviating such suffering is important, but it often goes unrecognised or is overlooked by services focusing on the terminal phase of illnesses. Primary care teams may know patients over long periods of time. They can readily identify patients from cancer and chronic disease registers who might benefit from an early palliative care approach. Such patients could be identified by clinicians asking one simple question of themselves: “Would I be surprised if my patient were to die in the next 12 months?”8 By identifying such patients proactively we could deliver, simultaneously, active treatment and patient centred supportive care, through a team with whom many patients have a valued long term relationship. Palliative care services need to be extended to patients with non-malignant conditions who have comparable concerns to and in some cases even greater unmet needs than cancer patients.9 Progress by palliative medicine specialists is hampered by issues such as uncertainty about the most effective models of care, lack of non-cancer expertise, and concerns about pressure on specialist services. General practitioners and community nurses can lead the way in providing a palliative care approach for patients with terminal organ failure illness. The first step in such an approach is for the goals of care to be discussed and agreed. Management plans are adjusted accordingly. Effective control of symptoms and maintaining quality of life are prioritised. In the light of these important opportunities it is regrettable that the new general medical services contract has not prioritised palliative care. By day, other developments to achieve the quality indicators are taking precedence. By night and at weekends, the new unscheduled care services (which are responsible for providing care for 75% of the hours in the week) are even less well configured than previous out of hours provision to facilitate dying at home. Such services specialise in dealing with acute emergencies and, as such, often struggle to meet the medical, nursing, and social care needs of dying people and their families. These changes will greatly affect care for dying people and may increase the number of hospital admissions. However, one important initiative is gaining momentum within primary care. The Gold Standards Framework is a resource for organising proactive palliative care in the community and is supported by funding from the Cancer Services Collaborative, Macmillan Cancer Relief, and the National Lottery.10 The framework provides a detailed guide to providing holistic, patient centred care and thereby facilitates effective care in the community. Other recently initiated mechanisms for developing primary palliative care include the training of general practitioners with a special interest in palliative care and the new end of life initiative in England to improve palliative care provision by generalists and to share examples of good practice. To support such developments it is essential that primary palliative care is supported by an adequate academic base.11 This is admittedly a challenging arena in which to undertake research, but progress has been made in recent years in developing conceptual models and research architectures for studying end of life issues. Now we need to build on this work to ensure that the understanding and insights gleaned can be translated into effective interventions. Every person with a progressive illness has a right to palliative care.12 Patients desire a reassuring professional presence in the face of death. General practitioners and community nurses are trusted by patients and are in a position to provide effective, equitable, and accessible palliative care. This will happen only if they have adequate time and resources and work in a system that encourages such care. Patients who receive holistic support in the community may be less likely to require expensive admission to hospital and often futile treatments at the end of their lives.",
"title": "Developing primary palliative care."
},
{
"docid": "72580164",
"text": "Background: Family doctors play an important role in the health care for terminal ill and patients. The current level of palliative care in Germany is strongly criticised, however, empirical data is scare, particularly with respect to family doctors. Methods: Therefore, the attitudes of family doctors (sample: n= 257) in four representative regions in Lower Saxony were studied by using semi-structured telephone interviews. This was part of a health system researchers’ expert report. Results: 71doctors could be interviewed (28%). On the average, they cared for four palliative patients with cancer diseases and eight palliative patients with other diseases than cancer at that time. Many of the doctors were available for their patients around the clock, particularly in the final phase. The main area for improvement was considered to be the psychosocial support – rather than pain therapy, which is usually focussed. Furthermore, a considerable openness for the establishment of new palliative care structures was shown. Conclusion: Family doctors are highly motivated for palliative care and open for improvements. In the process, the diversity of opinion among professions and disciplines about the current situation and the further development of palliative care should be respected and considered.",
"title": "Ansichten von Hausärzten zur Versorgung von unheilbar kranken Patienten am Lebensende - Ergebnisse einer Befragung in Niedersachsen"
},
{
"docid": "1191830",
"text": "OBJECTIVE The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. METHODS A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct 'RA'. RESULTS In the new criteria set, classification as 'definite RA' is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0-5), serological abnormality (range 0-3), elevated acute-phase response (range 0-1) and symptom duration (two levels; range 0-1). CONCLUSION This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct 'RA'.",
"title": "2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative."
}
] |
PLAIN-2262
|
transglutaminase
|
[
{
"docid": "MED-2672",
"text": "To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.",
"title": "Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks."
},
{
"docid": "MED-2671",
"text": "Microbiology of meats has been a subject of great concern in food science and public health in recent years. Although many articles have been devoted to the microbiology of beef, pork, and poultry meats, much less has been written about microbiology of lamb meat and even less on restructured lamb meat. This article presents data on microbiology and shelf-life of fresh lamb meat; restructured meat products, restructured lamb meat products, bacteriology of restructured meat products, and important foodborne pathogens such as Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential use of sodium and potassium lactates to control foodborne pathogens in meats and restructured lamb meat is reviewed This article should be of interest to all meat scientists, food scientists, and public health microbiologists who are concerned with the safety of meats in general and lamb meat in particular.",
"title": "Microbiology of fresh and restructured lamb meat: a review."
},
{
"docid": "MED-2673",
"text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.",
"title": "Determination of microbial transglutaminase in meat and meat products."
}
] |
[
{
"docid": "MED-4881",
"text": "The effects of microbial transglutaminase (MTGase) at different levels (0 to 0.8 units/g sample) on the properties of gels from lizardfish (Saurida undosquamis) mince set at 25 degrees C for 2 h or 40 degrees C for 30 min prior to heating at 90 degrees C for 20 min were studied. Breaking force and deformation of gels increased with increasing MTGase amount added (P<0.05). At the same MTGase level used, gels with the prior setting at 40 degrees C for 30 min showed a higher breaking force compared with those subjected to prior setting at 25 degrees C for 2 h (P<0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoretic study revealed that myosin heavy chain (MHC) underwent polymerization to a higher extent in the presence of MTGase. Regardless of setting condition, microstructure of gel added with MTGase was finer with a smaller void compared with that of gel without MTGase. Therefore, setting temperature affected the property of gels added with MTGase. Gel properties of mince obtained from lizardfish stored in ice for different times (0 to 10 d) with and without MTGase at a level 0.6 units/g were determined. Irrespective of MTGase addition, breaking force and deformation of all gels decreased as the storage time of lizardfish increased (P<0.05). The addition of MTGase was able to increase both breaking force and deformation of the resulting gel produced from lizardfish kept in ice for all storage times used. Therefore, both freshness and MTGase addition had the direct impact on gel properties of lizardfish mince.",
"title": "Improvement of gelling properties of lizardfish mince as influenced by microbial transglutaminase and fish freshness."
},
{
"docid": "MED-2024",
"text": "Celiac disease (CD) is a gluten-dependent immune-mediated disease with a prevalence in the general population estimated between 0.3% and 1.2%. Large-scale epidemiological studies have shown that only 10-20% of cases of CD are identified on the basis of clinical findings and that laboratory tests are crucial to identify subjects with subtle or atypical symptoms. The correct choice and clinical use of these diagnostic tools may enable accurate diagnosis and early recognition of silent CD cases. In this review, we have considered some relevant aspects related to the laboratory diagnosis of CD and, more extensively, of gluten intolerance, such as the best combination of tests for early and accurate diagnosis, the diagnostic role of new tests for detecting antibodies against neoepitopes produced by the transglutaminase-gliadin complex, the forms of non-celiac gluten intolerance (gluten sensitivity), and the use and significance of measuring cytokines in CD.",
"title": "Cutting-edge issues in celiac disease and in gluten intolerance."
},
{
"docid": "MED-2026",
"text": "OBJECTIVES: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample. METHODS: This study included 7,798 persons aged 6 years or older who participated in the National Health and Nutrition Examination Survey 2009-2010. Serum samples from all participants were tested for immunoglobulin A (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for IgA endomysial antibodies. Information about prior diagnosis of CD and use of a gluten-free diet (GFD) was obtained by direct interview. CD was defined as having either double-positive serology (serologically diagnosed CD) or a reported diagnosis of CD by a doctor or other health-care professional and being on a GFD (reported clinical diagnosis of CD). RESULTS: CD was found in 35 participants, 29 of whom were unaware of their diagnosis. Median age was 45 years (interquartile range, 23-66 years); 20 were women and 29 were non-Hispanic white. The prevalence of CD in the United States was 0.71% (95% confidence interval (CI), 0.58-0.86%), with 1.01% (95% CI, 0.78-1.31%) among non-Hispanic whites. In all, 55 participants reported following a GFD, which corresponded to a prevalence of 0.63% (95% CI, 0.36-1.07%). CONCLUSIONS: The prevalence of CD in the United States was 0.71% (1 in 141), similar to that found in several European countries. However, most cases were undiagnosed. CD was rare among minority groups but affected 1% of non-Hispanic whites. Most persons who were following a GFD did not have a diagnosis of CD.",
"title": "The prevalence of celiac disease in the United States."
},
{
"docid": "MED-2021",
"text": "AIM: To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms. METHODS: We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years. RESULTS: One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died. CONCLUSION: In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.",
"title": "Celiac disease: Management of persistent symptoms in patients on a gluten-free diet"
},
{
"docid": "MED-4918",
"text": "Background & Aims The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. Methods This study included 9,133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 sex-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n=5,558) or age at sampling (n=7,210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. Results Of 9,133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio=3.9; 95% CI, 2.0–7.5; P<.001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts (respectively) than in the Air Force cohort (both P ≤ .0001). Conclusions During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD appears to have increased dramatically in the United States during the past 50 years.",
"title": "Increased Prevalence and Mortality in Undiagnosed Celiac Disease"
},
{
"docid": "MED-4920",
"text": "BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.",
"title": "Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study."
},
{
"docid": "MED-4663",
"text": "Hyperthyroidism results from excessive production of thyroid hormones. This is usually caused by Graves disease, but exogenous thyroid hormones can lead to similar symptoms. Recognition of the latter is difficult as excessive intake of thyroid hormone is not usually admitted nor recognised. To our knowledge, exogenous hyperthyroidism caused by thyroid-contaminated food has been described twice, but not in the Netherlands. A 77-year-old man presented at the Outpatient Department of Internal Medicine with lab values revealing hyperthyroidism. There were no abnormal findings at the physical examination. Antibodies against the thyroidstimulating hormone (TSH) receptor were not detectable. Thyroid scintigraphy with 123I showed an uptake of less than 1%. Silent thyroiditis was diagnosed and the natural course was awaited, but with no improvement in the thyroid values. The thyroglobulin was very low. Further anamnesis revealed an excessive daily consumption of sausages. Thyroid hormones were detectable in these sausages. After the patient stopped eating them, he became and remained euthyroid. The case stipulates the importance of a thorough anamnesis.",
"title": "Hyperthyroidism caused by excessive consumption of sausages."
},
{
"docid": "MED-1862",
"text": "BACKGROUND: The main 6-month results from the PREMIER trial showed that comprehensive behavioral intervention programs improve lifestyle behaviors and lower blood pressure. OBJECTIVE: To compare the 18-month effects of 2 multicomponent behavioral interventions versus advice only on hypertension status, lifestyle changes, and blood pressure. DESIGN: Multicenter, 3-arm, randomized trial conducted from January 2000 through November 2002. SETTING: 4 clinical centers and a coordinating center. PATIENTS: 810 adult volunteers with prehypertension or stage 1 hypertension (systolic blood pressure, 120 to 159 mm Hg; diastolic blood pressure, 80 to 95 mm Hg). INTERVENTIONS: A multicomponent behavioral intervention that implemented long-established recommendations (\"established\"); a multicomponent behavioral intervention that implemented the established recommendations plus the Dietary Approaches to Stop Hypertension (DASH) diet (\"established plus DASH\"); and advice only. MEASUREMENTS: Lifestyle variables and blood pressure status. Follow-up for blood pressure measurement at 18 months was 94%. RESULTS: Compared with advice only, both behavioral interventions statistically significantly reduced weight, fat intake, and sodium intake. The established plus DASH intervention also statistically significantly increased fruit, vegetable, dairy, fiber, and mineral intakes. Relative to the advice only group, the odds ratios for hypertension at 18 months were 0.83 (95% CI, 0.67 to 1.04) for the established group and 0.77 (CI, 0.62 to 0.97) for the established plus DASH group. Although reductions in absolute blood pressure at 18 months were greater for participants in the established and the established plus DASH groups than for the advice only group, the differences were not statistically significant. LIMITATIONS: The exclusion criteria and the volunteer nature of this cohort may limit generalizability. Although blood pressure is a well-accepted risk factor for cardiovascular disease, the authors were not able to assess intervention effects on clinical cardiovascular events in this limited time and with this sample size. CONCLUSIONS: Over 18 months, persons with prehypertension and stage 1 hypertension can sustain multiple lifestyle modifications that improve control of blood pressure and could reduce the risk for chronic disease.",
"title": "Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial."
},
{
"docid": "MED-2202",
"text": "The overall objective of this chapter is to review the past, present, and future role of the sweet potato (Ipomoea batatas [L.] Lam) in human nutrition. Specifically, the chapter describes the role of the sweet potato in human diets; outlines the biochemical and nutritional composition of the sweet potato with emphasis on its beta-carotene and anthocyanin contents; highlights sweet potato utilization, and its potential as value-added products in human food systems; and demonstrates the potential of the sweet potato in the African context. Early records have indicated that the sweet potato is a staple food source for many indigenous populations in Central and South Americas, Ryukyu Island, Africa, the Caribbean, the Maori people, Hawaiians, and Papua New Guineans. Protein contents of sweet potato leaves and roots range from 4.0% to 27.0% and 1.0% to 9.0%, respectively. The sweet potato could be considered as an excellent novel source of natural health-promoting compounds, such as beta-carotene and anthocyanins, for the functional food market. Also, the high concentration of anthocyanin and beta-carotene in sweet potato, combined with the high stability of the color extract make it a promising and healthier alternative to synthetic coloring agents in food systems. Starch and flour processing from sweet potato can create new economic and employment activities for farmers and rural households, and can add nutritional value to food systems. Repositioning sweet potato production and its potential for value-added products will contribute substantially to utilizing its benefits and many uses in human food systems. Multidisciplinary, integrated research and development activities aimed at improving production, storage, postharvest and processing technologies, and quality of the sweet potato and its potential value-added products are critical issues, which should be addressed globally.",
"title": "Sweet potato: a review of its past, present, and future role in human nutrition."
},
{
"docid": "MED-4096",
"text": "A variety of statistics are used to quantify the burden (occurrence and outcome) of cancer generally and of breast cancer specifically. When undertaking any cancer control program, understanding these statistics, their source, and their quality is important for assessing the current situation, allocating resources to different control strategies, and evaluating progress. Two core statistics are the cancer incidence rate and the cancer mortality rate, which provide estimates of the average risk of acquiring and of dying from the disease, respectively. About 16% of the world's population is covered by registration systems that produce cancer incidence statistics, while mortality data are available for about 29%. Breast cancer incidence and mortality vary considerably by world region. In general, the incidence is high (greater than 80 per 100,000) in developed regions of the world and low (less than 30 per 100,000), though increasing, in developing regions; the range of mortality rates is much less (approximately 6-23 per 100,000) because of the more favorable survival of breast cancer in (high-incidence) developed regions. The incidence of breast cancer is increasing almost everywhere. This unfavorable trend is due in part to increases in risk factors (decreased childbearing and breast-feeding, increased exogenous hormone exposure, and detrimental dietary and lifestyle changes, including obesity and less physical activity). On the other hand, mortality is now decreasing in many high-risk countries due to a combination of intensified early detection efforts and the introduction of mammographic screening, resulting in the diagnosis of more small, early stage tumors, and advances in treatment.",
"title": "Use of statistics to assess the global burden of breast cancer."
},
{
"docid": "MED-3518",
"text": "Compared with other industrialized countries, the lower incidence of chronic-degenerative disorders in Mediterranean populations has been emphasized in recent decades. The health-promoting effects arising from Mediterranean dietary habits have been attributed to the large intake of plant foodstuffs rich in bioactive phytochemicals, such as melatonin. Recently, it has been suggested that melatonin present in edible plants may improve human health, by virtue of its biological activities and its good bioavailability. Plant melatonin, besides contributing to optimize the physiological functions regulated, in humans, by endogenous melatonin, may be involved in nutritional therapy to reduce the risk of cancer, cardiovascular and neurodegenerative diseases in western populations. In this view, the presence of melatonin in some Mediterranean foods and beverages adds a new element to the hypothesis of health benefits associated to Mediterranean dietary patterns, although the available data are still preliminary and incomplete.",
"title": "Melatonin in traditional Mediterranean diets."
},
{
"docid": "MED-1198",
"text": "BACKGROUND: Ascorbic acid (AA) modulates catecholaminergic activity, decreases stress reactivity, approach anxiety and prolactin release, improves vascular function, and increases oxytocin release. These processes are relevant to sexual behavior and mood. METHODS: In this randomized double-blind, placebo-controlled 14 day trial of sustained-release AA (42 healthy young adults; 3000 mg/day Cetebe) and placebo (39 healthy young adults), subjects with partners recorded penile-vaginal intercourse (FSI), noncoital partner sex, and masturbation in daily diaries, and also completed the Beck Depression Inventory before and after the trial. RESULTS: The AA group reported greater FSI (but, as hypothesized, not other sexual behavior) frequency, an effect most prominent in subjects not cohabiting with their sexual partner, and in women. The AA but not placebo group also experienced a decrease in Beck Depression scores. CONCLUSIONS: AA appears to increase FSI, and the differential benefit to noncohabitants suggests that a central activation or disinhibition, rather than peripheral mechanism may be responsible.",
"title": "High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial."
},
{
"docid": "MED-1831",
"text": "In children, omega-3 polyunsaturated fatty acids (PUFAs) may elicit a suite of health benefits including enhancement of cognitive development. Subsequently, dietary supplements containing omega-3 PUFAs have become increasingly popular. Often, the largest source of beneficial PUFAs in these supplements is fish oil, which may contain significant levels of contaminants such as polychlorinated biphenyls (PCBs). The objectives of this study were to evaluate congener-specific PCB concentrations in 13 over-the-counter children's dietary supplements containing fish oils/powders and assess potential PCB exposures through ingestion of these products on a daily basis. Every supplement analysed contained PCBs, with a mean concentration of 9 ± 8 ng PCBs/g supplement. When following serving size suggestions, mean daily exposure values ranged from 2.5 to 50.3 ng PCBs/day. Daily exposures for children's supplements were significantly lower than those previously reported for adult supplements and may be explained, in part, by the variability in the amount of fish oil (and PUFA content) in a serving size. Based on this study, factors such as fish oil purification methods (e.g., molecular distillation) and the trophic level of the fish species used to make the fish oil cannot be used as indicators of PCB levels within children's supplements. Fish supplements may decrease or increase daily PCB exposure compared with ingestion of fresh fish. However, eating fish high in omega-3 PUFAs and low in PCBs may reduce PCB exposure compared with daily supplementation with fish oils for some products studied.",
"title": "Children's daily exposure to polychlorinated biphenyls from dietary supplements containing fish oils."
},
{
"docid": "MED-2360",
"text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.",
"title": "STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness."
},
{
"docid": "MED-981",
"text": "There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B₁₂ can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B₁₂ deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B₁₂ levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B₁₂ of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B₁₂ did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B₁₂, from which it can be concluded that the usual dietary source of vitamin B₁₂ is animal products and those who choose to omit or restrict these products are destined to become vitamin B₁₂ deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.",
"title": "Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis."
},
{
"docid": "MED-4520",
"text": "Evidence suggests that endothelial dysfunction is on the causal pathway for both atherogenesis and destabilization of established plaques. In this review, the role of flow-mediated dilatation (FMD) as a non-invasive method to assess endothelial function is discussed. Technical modifications and development of analysis software have significantly improved the variability of the method. Following a strict standardized protocol enables reproducible measurements to be achieved and export of the technique from specialized laboratories to population studies and multicentre settings. Endothelial function assessed by FMD has been shown to be affected by cardiovascular risk factors, to be related to structural arterial disease and to cardiovascular outcome, validating its use for studying the pathophysiology of arterial disease. Numerous studies have also demonstrated that it is responsive to physiological and pharmacological interventions. Flow-mediated dilatation provides unique opportunities in drug development programmes to assess an early rapidly responsive signal of risk or benefit, complementing endpoints of structural arterial disease and cardiovascular outcomes that take much longer and are more expensive.",
"title": "Assessment of atherosclerosis: the role of flow-mediated dilatation."
},
{
"docid": "MED-1138",
"text": "PURPOSE: We compared the effect of 3 animal protein sources on urinary stone risk. MATERIALS AND METHODS: A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. RESULTS: Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). CONCLUSIONS: Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Animal protein and the risk of kidney stones: a comparative metabolic study of animal protein sources."
},
{
"docid": "MED-2509",
"text": "DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.",
"title": "Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR"
},
{
"docid": "MED-1717",
"text": "BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.",
"title": "Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies."
},
{
"docid": "MED-4573",
"text": "Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D3 (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D2 (ergocalciferol) and D3. An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D [25(OH)D] concentration. Though controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be ~30-32 ng/ml or above. Using this definition, it has been is estimated that approximately three quarters of all adults in the United States are low. Classically, low vitamin D status has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various non-skeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with “high” amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D3 may be preferable to vitamin D2.",
"title": "Low Vitamin D Status: Definition, Prevalence, Consequences and Correction"
},
{
"docid": "MED-2804",
"text": "Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.",
"title": "Epidemiology of OA"
},
{
"docid": "MED-2580",
"text": "Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.",
"title": "High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial"
},
{
"docid": "MED-4598",
"text": "OBJECTIVE: The present study aimed to evaluate the knowledge and practices of public-sector primary-care health professionals and final-year students regarding the role of nutrition, physical activity and smoking cessation (lifestyle modification) in the management of chronic diseases of lifestyle within the public health-care sector. DESIGN: A comparative cross-sectional descriptive quantitative study was conducted in thirty primary health-care facilities and four tertiary institutions offering medical and/or nursing programmes in Cape Town in the Western Cape Metropole. Stratified random sampling, based on geographical location, was used to select the health facilities while convenience sampling was used to select students at the tertiary institutions. A validated self-administered knowledge test was used to obtain data from the health professionals. RESULTS: Differential lifestyle modification knowledge exists among both health professionals and students, with less than 10 % achieving the desired scores of 80 % or higher. The majority of health professionals seem to be promoting the theoretical concepts of lifestyle modification but experience difficulty in providing practical advice to patients. Of the health professionals evaluated, doctors appeared to have the best knowledge of lifestyle modification. Lack of time, lack of patient adherence and language barriers were given as the main barriers to providing lifestyle counselling. CONCLUSIONS: The undergraduate curricula of medical and nursing students should include sufficient training on lifestyle modification, particularly practical advice on diet, physical activity and smoking cessation. Health professionals working at primary health-care facilities should be updated by providing lifestyle modification education as part of continuing medical education.",
"title": "They think they know but do they? Misalignment of perceptions of lifestyle modification knowledge among health professionals."
},
{
"docid": "MED-1018",
"text": "OBJECTIVE: To determine the magnitude of the decrease in the risk of retinopathy progression observed with intensive treatment and its relationship to baseline retinopathy severity and duration of follow-up. DESIGN: Randomized clinical trial, with 3 to 9 years of follow-up. SETTING AND PATIENTS: Between 1983 and 1989, 29 centers enrolled 1441 patients with insulin-dependent diabetes mellitus aged 13 to 39 years, including 726 patients with no retinopathy and a duration of diabetes of 1 to 5 years (primary prevention cohort) and 715 patients with very mild to moderate nonproliferative diabetic retinopathy and a duration of diabetes of 1 to 15 years (secondary intervention cohort). Ninety-five percent of all scheduled examinations were completed. INTERVENTIONS: Intensive treatment consisted of the administration of insulin at least three times a day by injection or pump, with doses adjusted based on self-blood glucose monitoring and with the goal of normoglycemia. Conventional treatment consisted of one or two daily insulin injections. OUTCOME MEASURES: Change between baseline and follow-up visits on the Early Treatment Diabetic Retinopathy Study retinopathy severity scale, assessed with masked gradings of stereoscopic color fundus photographs obtained every 6 months. RESULTS: Cumulative 8.5-year rates of retinopathy progression by three or more steps at two consecutive visits were 54.1% with conventional treatment and 11.5% with intensive treatment in the primary prevention cohort and 49.2% and 17.1% in the secondary intervention cohort. At the 6- and 12-month visits, a small adverse effect of intensive treatment was noted (\"early worsening\"), followed by a beneficial effect that increased in magnitude with time. Beyond 3.5 years of follow-up, the risk of progression was five or more times lower with intensive treatment than with conventional treatment. Once progression occurred, subsequent recovery was at least two times more likely with intensive treatment than with conventional treatment. Treatment effects were similar in all baseline retinopathy severity subgroups. CONCLUSIONS: The results of the Diabetes Control and Complications Trial strongly support the recommendation that most patients with insulin-dependent diabetes mellitus use intensive treatment, aiming for levels of glycemia as close to the nondiabetic range as is safely possible.",
"title": "The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control ..."
},
{
"docid": "MED-5310",
"text": "Background Addition of capsaicin (CAPS) to the diet has been shown to increase energy expenditure; therefore capsaicin is an interesting target for anti-obesity therapy. Aim We investigated the 24 h effects of CAPS on energy expenditure, substrate oxidation and blood pressure during 25% negative energy balance. Methods Subjects underwent four 36 h sessions in a respiration chamber for measurements of energy expenditure, substrate oxidation and blood pressure. They received 100% or 75% of their daily energy requirements in the conditions ‘100%CAPS’, ‘100%Control’, ‘75%CAPS’ and ‘75%Control’. CAPS was given at a dose of 2.56 mg (1.03 g of red chili pepper, 39,050 Scoville heat units (SHU)) with every meal. Results An induced negative energy balance of 25% was effectively a 20.5% negative energy balance due to adapting mechanisms. Diet-induced thermogenesis (DIT) and resting energy expenditure (REE) at 75%CAPS did not differ from DIT and REE at 100%Control, while at 75%Control these tended to be or were lower than at 100%Control (p = 0.05 and p = 0.02 respectively). Sleeping metabolic rate (SMR) at 75%CAPS did not differ from SMR at 100%CAPS, while SMR at 75%Control was lower than at 100%CAPS (p = 0.04). Fat oxidation at 75%CAPS was higher than at 100%Control (p = 0.03), while with 75%Control it did not differ from 100%Control. Respiratory quotient (RQ) was more decreased at 75%CAPS (p = 0.04) than at 75%Control (p = 0.05) when compared with 100%Control. Blood pressure did not differ between the four conditions. Conclusion In an effectively 20.5% negative energy balance, consumption of 2.56 mg capsaicin per meal supports negative energy balance by counteracting the unfavorable negative energy balance effect of decrease in components of energy expenditure. Moreover, consumption of 2.56 mg capsaicin per meal promotes fat oxidation in negative energy balance and does not increase blood pressure significantly. Trial Registration Nederlands Trial Register; registration number NTR2944",
"title": "Acute Effects of Capsaicin on Energy Expenditure and Fat Oxidation in Negative Energy Balance"
},
{
"docid": "MED-4414",
"text": "Prospective epidemiological studies have reported that a higher fruit and vegetable intake is associated with a lower risk of CHD. The aim of the present study was to examine associations between fruit and vegetable consumption, in particular the subgroupings citrus fruits, apples and cruciferous vegetables, and the risk of acute coronary syndrome (ACS). During a median follow-up of 7.7 years, 1075 incident ACS cases were identified among 53 383 men and women, aged 50-64 years at recruitment into the Diet, Cancer and Health cohort study in 1993-7. Fruit and vegetable intake was estimated from a validated FFQ, and ACS incidence rate ratios (IRR) were estimated using Cox proportional hazards models. Overall, a tendency towards a lower risk of ACS was observed for both men and women with higher fruit and vegetable consumption. For men, we found an inverse association for apple intake (IRR per 25 g/d: 0.97; 95 % CI 0.94, 0.99). This association was also seen among women, albeit borderline significant. However, a higher risk was seen among women with higher fruit juice intake (IRR per 25 g/d: 1.04; 95 % CI 1.00, 1.08). The present results provide some support for previously observed inverse associations between fresh fruit intake, particularly apples, and ACS risk.",
"title": "Fruit and vegetable intake and risk of acute coronary syndrome."
},
{
"docid": "MED-4181",
"text": "Exposure of pregnant women to organochlorine (OC) pesticides largely derives from contaminated food, but environmental, occupational, and domestic factors have also been implicated. We investigated the presence of nine OC residues in the umbilical cord blood of newborns in Southern Spain and analyzed the relationship of this exposure with maternal and pregnancy variables, including maternal adherence to the Mediterranean Diet (MD). OCs were detected in 95% of umbilical cord blood samples from the 318 mothers, who had a mean degree of adherence to the MD of 56.77 (SD: 16.35) (range, 0-100). The MD prioritizes consumption of vegetable and fruit over meat and dairy products, and OCs are generally lipophilic molecules that accumulate in foods of animal origin. Consumption of meat, fish, and dairy products was associated with dichlorodiphenyldichloroethylene (DDE) in umbilical cord serum, and dairy product intake with lindane. Vegetable consumption was also associated with lindane and fruit intake with endosulfan I. We found no significant association between MD adherence and the presence of OC residues in serum. However, closer adherence to the MD may offer greater protection against OC exposure because of its reduced content in meat and dairy products. Copyright (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Organochlorine pesticides in umbilical cord blood serum of women from Southern Spain and adherence to the Mediterranean diet."
},
{
"docid": "MED-3949",
"text": "In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.",
"title": "Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia."
},
{
"docid": "MED-2738",
"text": "Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers.",
"title": "Trends in U.S. consumers' safe handling and consumption of food and their risk perceptions, 1988 through 2010."
},
{
"docid": "MED-1162",
"text": "Consumers are frequently urged to avoid imported foods as well as specific fruits and vegetables due to health concerns from pesticide residues and are often encouraged to choose organic fruits and vegetables rather than conventional forms. Studies have demonstrated that while organic fruits and vegetables have lower levels of pesticide residues than do conventional fruits and vegetables, pesticide residues are still frequently detected on organic fruits and vegetables; typical dietary consumer exposure to pesticide residues from conventional fruits and vegetables does not appear to be of health significance. Similarly, research does not demonstrate that imported fruits and vegetables pose greater risks from pesticide residues than do domestic fruits and vegetables or that specific fruits and vegetables singled out as being the most highly contaminated by pesticides should be avoided in their conventional forms.",
"title": "Pesticide residues in imported, organic, and \"suspect\" fruits and vegetables."
}
] |
139
|
At least 85% of patients exposed to radiation have activated markers of myofibroblasts.
|
[
{
"docid": "22080671",
"text": "Previous studies investigating the role of smooth muscle cells (SMCs) and macrophages in the pathogenesis of atherosclerosis have provided controversial results owing to the use of unreliable methods for clearly identifying each of these cell types. Here, using Myh11-CreERT2 ROSA floxed STOP eYFP Apoe−/− mice to perform SMC lineage tracing, we find that traditional methods for detecting SMCs based on immunostaining for SMC markers fail to detect >80% of SMC-derived cells within advanced atherosclerotic lesions. These unidentified SMC-derived cells exhibit phenotypes of other cell lineages, including macrophages and mesenchymal stem cells (MSCs). SMC-specific conditional knockout of Krüppel-like factor 4 (Klf4) resulted in reduced numbers of SMC-derived MSC- and macrophage-like cells, a marked reduction in lesion size, and increases in multiple indices of plaque stability, including an increase in fibrous cap thickness as compared to wild-type controls. On the basis of in vivo KLF4 chromatin immunoprecipitation–sequencing (ChIP-seq) analyses and studies of cholesterol-treated cultured SMCs, we identified >800 KLF4 target genes, including many that regulate pro-inflammatory responses of SMCs. Our findings indicate that the contribution of SMCs to atherosclerotic plaques has been greatly underestimated, and that KLF4-dependent transitions in SMC phenotype are critical in lesion pathogenesis.",
"title": "KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis"
}
] |
[
{
"docid": "31293581",
"text": "Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with lifelong delayed repair and regeneration of irradiated tissues. We hypothesized that IR-induced senescence markers could persist long-term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here, we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analyzed) DNA damage foci and increased p16(INK4a) expression, two hallmarks of cellular senescence and aging. BrdU-labeling experiments revealed that IR-induced damaged cells are preferentially eliminated, at least partially, in a tissue-dependent manner. Unexpectedly, the accumulation of damaged cells was found to occur independent from the DNA damage response modulator p53, and from an intact immune system, as their levels were similar in wild-type and Rag2(-/-) gammaC(-/-) mice, the latter being deficient in T, B, and NK cells. Together, our results provide compelling evidence that exposure to IR induces long-term expression of senescence markers in vivo, an effect that may contribute to the reduced tissue functionality observed in cancer survivors.",
"title": "Ionizing radiation-induced long-term expression of senescence markers in mice is independent of p53 and immune status."
},
{
"docid": "26067999",
"text": "The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) See the Clinical Considerations section for suggestions for implementation in practice. See the Figure for a summary of the recommendation and suggestions for clinical practice. Figure. Screening for lung cancer: clinical summary of U.S. Preventive Services Task Force recommendation. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit. Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit Supplement. Consumer Fact Sheet. Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States (1). The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases (2). Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers (2). The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer. Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage nonsmall cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection. Detection Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer (3). Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population (4). The magnitude of benefit to the person depends on that person's risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancerrelated deaths, and smoking cessation remains essential. Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures. The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosedthat is, they would not have been detected in the patient's lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation, particularly other medical imaging. USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the NLST (National Lung Screening Trial), and the resolution of most false-positive results without invasive procedures (4). Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking. The best evidence for the benefit of screening comes from the NLST, which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years. As with all screening trials, the NLST tested a specific intervention over a finite period. Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans, the oldest participants in the trial were aged 77 years. The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals, age ranges, smoking histories, and times since quitting. A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms. The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening. This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years. Screening may not be appropriate for patients with substantial comorbid conditions, particularly those at the upper end of the screening age range. The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial. The baseline characteristics of the NLST showed a relatively healthy sample, and fewer than 10% of enrolled participants were older than 70 years (5). Persons with serious comorbid conditions may experience net harm, no net benefit, or at least substantially less net benefit. Similarly, persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program. Assessment of Risk Age, total exposure to tobacco smoke, and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST. Other risk factors include specific occupational exposures, radon exposure, family history, and history of pulmonary fibrosis or chronic obstructive lung disease. The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age, especially after age 60 years. In current and former smokers, age-specific incidence rates increase with age and cumulative exposure to tobacco smoke. Smoking cessation substantially reduces a person's risk for developing and dying of lung cancer. Among persons enrolled in the NLST, those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit (6). A validated multivariate model showed that persons in the highest 60% of risk accounted for 88% of all deaths preventable by screening. Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons. Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests. Therefore, LDCT is currently the only recommended screening test for lung cancer. Treatment Surgical resection is the current standard of care for localized NSCLC. This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy. Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be candidates for surgery. Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC. Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer. Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments. Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions. Useful Resources Clinicians have many resources to help patients stop smoking. The Centers for Disease Control and Prevention has developed a Web site with many such resources, including information on tobacco quit lines, available in several languages (www.cdc.gov/tobacco/campaign/tips). Quit l",
"title": "Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement"
},
{
"docid": "6807122",
"text": "Activated fibroblasts are associated with many different tumors. Myofibroblasts, activated fibroblasts, and perivascular mesenchymal cells such as pericytes play a role in cancer progression. Many studies suggest that myofibroblasts facilitate tumor growth and cancer progression. The source for myofibroblasts and other activated fibroblasts within the tumors is still debated. Although de novo activation of quiescent fibroblasts into alpha-smooth muscle actin (alpha SMA)-positive myofibroblasts is one likely source, epithelial to mesenchymal transition and bone marrow recruitment are also evolving as possible mechanisms for the emergence of a heterogeneous population of carcinoma-associated fibroblasts. Here, we show that transforming growth factor-beta1 could induce proliferating endothelial cells to undergo a phenotypic conversion into fibroblast-like cells. Such endothelial to mesenchymal transition (EndMT) is associated with the emergence of mesenchymal marker fibroblast-specific protein-1 (FSP1) and down-regulation of CD31/PECAM. Additionally, we show EndMT in tumors using the B16F10 melanoma model and the Rip-Tag2 spontaneous pancreatic carcinoma model. Crossing Tie2-Cre mice with R26Rosa-lox-Stop-lox-LacZ mice allows for irreversible tagging of endothelial cells. We provide unequivocal evidence for EndMT at the invasive front of the tumors in these transgenic mice. Collectively, our results show that EndMT is a unique mechanism for the accumulation of carcinoma-associated fibroblasts and suggest that antiangiogenic treatment of tumors may have a direct effect in decreasing activated fibroblasts that likely facilitate cancer progression.",
"title": "Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts."
},
{
"docid": "12991445",
"text": "OBJECTIVE To determine the effects of smoking, plasma lipids, lipoproteins, apolipoproteins, and fibrinogen on the patency of saphenous vein femoropopliteal bypass grafts at one year. DESIGN Prospective study of patients with saphenous vein femoropopliteal bypass grafts entered into a multicentre trial. SETTING Surgical wards, outpatient clinics, and home visits coordinated by two tertiary referral centres in London and Birmingham. PATIENTS 157 Patients (mean age 66.6 (SD 8.2) years), 113 with patent grafts and 44 with occluded grafts one year after bypass. MAIN OUTCOME MEASURE Cumulative percentage patency at one year. RESULTS Markers for smoking (blood carboxyhaemoglobin concentration (p less than 0.05) and plasma thiocyanate concentration (p less than 0.01) and plasma concentrations of fibrinogen (p less than 0.001) and apolipoproteins AI (p less than 0.04) and (a) (p less than 0.05) were significantly higher in patients with occluded grafts. Serum cholesterol concentrations were significantly higher in patients with grafts that remained patent one year after bypass (p less than 0.005). Analysis of the smoking markers indicated that a quarter of patients (40) were untruthful in their claims to have stopped smoking. Based on smoking markers, patency of grafts in smokers was significantly lower at one year by life table analysis than in non-smokers (63% v 84%, p less than 0.02). Patency was significantly higher by life table analysis in patients with a plasma fibrinogen concentration below the median than in those with a concentration above (90% v 57%, p less than 0.0002). Surprisingly, increased plasma low density lipoprotein cholesterol concentration was significantly associated with improved patency at one year (85%) at values above the median compared with patency (only 68%) at values in the lower half of the range (p less than 0.02). CONCLUSIONS Plasma fibrinogen concentration was the most important variable predicting graft occlusion, followed by smoking markers. A more forceful approach is needed to stop patients smoking; therapeutic measures to improve patency of vein grafts should focus on decreasing plasma fibrinogen concentration rather than serum cholesterol concentration.",
"title": "Influence of smoking and plasma factors on patency of femoropopliteal vein grafts."
},
{
"docid": "15678772",
"text": "OBJECTIVE To determine whether exposure to low doses of ionising radiation in infancy affects cognitive function in adulthood. DESIGN Population based cohort study. SETTING Sweden. PARTICIPANTS 3094 men who had received radiation for cutaneous haemangioma before age 18 months during 1930-59. MAIN OUTCOME MEASURES Radiation dose to frontal and posterior parts of the brain, and association between dose and intellectual capacity at age 18 or 19 years based on cognitive tests (learning ability, logical reasoning, spatial recognition) and high school attendance. RESULTS The proportion of boys who attended high school decreased with increasing doses of radiation to both the frontal and the posterior parts of the brain from about 32% among those not exposed to around 17% in those who received > 250 mGy. For the frontal dose, the multivariate odds ratio was 0.47 (95% confidence interval 0.26 to 0.85, P for trend 0.0003) and for the posterior dose it was 0.59 (0.23 to 1.47, 0.0005). A negative dose-response relation was also evident for the three cognitive tests for learning ability and logical reasoning but not for the test of spatial recognition. CONCLUSIONS Low doses of ionising radiation to the brain in infancy influence cognitive abilities in adulthood.",
"title": "Effect of low doses of ionising radiation in infancy on cognitive function in adulthood: Swedish population based cohort study."
},
{
"docid": "37912677",
"text": "With the acknowledged problems associated with assessment of functioning thyroid mass and hence radiation dose, our policy had been to give 75 MBq iodine-131 at 6-monthly intervals to patients with Graves' disease until they became euthyroid. Since positron emission tomography (PET) has been available at this hospital, the radiation dose to the thyroid has been calculated with an accuracy of ∼20%, the thyroid mass being determined from an iodine-124 PET scan. A dose-response study has been carried out on 65 patients who have received single or cumulative radiation doses of <80 Gy. The results show that patients who receive a low radiation dose (<20 Gy) at their first treatment have a high probability of remaining toxic at 12 months. In contrast, patients who receive higher radiation doses (>40 Gy) at their first treatment have a high probability of control. The probability of becoming euthyroid increases more rapidly with increasing radiation dose than the probability of becoming hypothyroid. Following this dose-response study, a new treatment protocol has been introduced. A 124I PET tracer study prior to 131I therapy will be performed to enable a prescribed thyroid dose of 50 Gy to be delivered to patients with Graves' disease. Further 131I therapy will only be considered if patients are still toxic at 12 months.",
"title": "Dose-response study on thyrotoxic patients undergoing positron emission tomography and radioiodine therapy"
},
{
"docid": "49556906",
"text": "Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs1. Cellular metabolism regulates tissue repair and remodelling responses to injury2-4. AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism5. However, the role of AMPK in fibrosis is not well understood. Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts. Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis. In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner. These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts.",
"title": "Metformin reverses established lung fibrosis in a bleomycin model"
},
{
"docid": "35314705",
"text": "BACKGROUND Cerebellar glioblastoma multiforme (cGBM) is rare, and although there is a general belief that these tumors have a worse prognosis than supratentorial GBM (sGBM), few studies have been published to support this belief. OBJECTIVE To investigate the effect of cerebellar location on survival through a case-control design comparing overall survival time of cGBM and sGBM patients. METHODS The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify 132 patients with cGBM (1973-2008). Each cGBM patient was matched with an sGBM patient from among 20,848 sGBM patients on the basis of age, extent of resection, decade of diagnosis, and radiation therapy using propensity score matching. RESULTS Within the cGBM, 37% were older than 65 years of age, 62% were men, and 87% were white. Most patients underwent surgery and radiation (74%), whereas only 26% underwent surgical resection only. The median survival time for the cGBM and sGBM matched cohort was 8 months; however, the survival distributions differed (log-rank P = .04). Survival time for cGBM vs sGBM at 2 years was 21.5% vs 8.0%, and 12.7% vs 5.3% at 3 years. Multivariate analysis of survival among cGBM patients showed that younger age (P < .0001) and having radiation therapy (P < .0001) were significantly associated with reduced hazard of mortality. Among all patients, multivariate analysis showed that tumor location (P = .03), age (P < .0001), tumor size (P = .009), radiation (P < .0001), and resection (P < .0001) were associated with survival time in the unmatched cohort. CONCLUSION Median survival time for cGBM and sGBM patients was 8 months, but cGBM patients had a survival time advantage as the study progressed. These findings suggest that cGBM patients should be treated as aggressively as sGBM patients with surgical resection and radiation therapy.",
"title": "Comparison of survival between cerebellar and supratentorial glioblastoma patients: surveillance, epidemiology, and end results (SEER) analysis."
},
{
"docid": "3847200",
"text": "Direct induction of induced hepatocytes (iHeps) from fibroblasts holds potential as a strategy for regenerative medicine but until now has only been shown in culture settings. Here, we describe in vivo iHep formation using transcription factor induction and genetic fate tracing in mouse models of chronic liver disease. We show that ectopic expression of the transcription factors FOXA3, GATA4, HNF1A, and HNF4A from a polycistronic lentiviral vector converts mouse myofibroblasts into cells with a hepatocyte phenotype. In vivo expression of the same set of transcription factors from a p75 neurotrophin receptor peptide (p75NTRp)-tagged adenovirus enabled the generation of hepatocyte-like cells from myofibroblasts in fibrotic mouse livers and reduced liver fibrosis. We have therefore been able to convert pro-fibrogenic myofibroblasts in the liver into hepatocyte-like cells with positive functional benefits. This direct in vivo reprogramming approach may open new avenues for the treatment of chronic liver disease.",
"title": "Direct Reprogramming of Hepatic Myofibroblasts into Hepatocytes In Vivo Attenuates Liver Fibrosis."
},
{
"docid": "11569583",
"text": "DNA polymerase β (Pol β) is an error-prone enzyme which has been found to be overexpressed in several human tumors. By using a couple of recombinant CHO cells differing only from the exogenous expression of Pol β, we showed here that cells overexpressing Pol β are much more sensitive to IR treatments by increasing apoptosis. We also found that the surviving cells displayed an hypermutator phenotype which could be explained by different pathways involving Pol β, such as (i) an increased capacity to incorporate into DNA the mutagenic dGTP analog, 8-oxo-dGTP, one of the most abundant purine-derived nucleotides exposed to γ-irradiation, (ii) the induction of IR-induced DNA breaks and (iii) accumulation of chromosome aberrations induced by radiation. Alteration of Pol β expression in irradiated cells thus appears to strengthen both cell death and genetic changes associated with a malignant phenotype. These data provide new insights into the cellular response to radiations and the associated carcinogenic consequences.",
"title": "Deregulated DNA polymerase β strengthens ionizing radiation-induced nucleotidic and chromosomal instabilities"
},
{
"docid": "24640046",
"text": "Diabetic nephropathy is the leading cause of chronic renal failure. Myofibroblasts play a major role in the synthesis and secretion of extracellular matrix in diabetic renal fibrosis. Increasing evidence suggests that endothelial cells may undergo endothelial-myofibroblast transition under physiological and pathophysiological circumstances. Therefore, this study investigates whether endothelial-myofibroblast transition occurs and contributes to the development of diabetic renal interstitial fibrosis. Diabetes was induced by administration of streptozotocin to Tie2-Cre;LoxP-EGFP mice, an endothelial lineage-traceable mouse line generated by crossbreeding B6.Cg-Tg(Tek-cre)12F1v/J mice with B6.Cg-Tg(ACTB-Bgeo/GFP)21Lbe/J mice. The endothelial-myofibroblast transition was also studied in MMECs (a mouse pancreatic microvascular endothelial cell line) and primary cultures of CD31+/EYFP- (enhanced yellow fluorescent protein) endothelial cells isolated from adult normal alpha-smooth muscle actin promoter-driven-EYFP (alpha-SMA/EYFP) mouse kidneys. Confocal microscopy demonstrated that 10.4 +/- 4.2 and 23.5 +/- 7.4% of renal interstitial myofibroblasts (alpha-SMA+) in 1- and 6-month streptozotocin-induced diabetic kidneys were of endothelial origin (EGFP+/alpha-SMA+ cells), compared with just 0.2 +/- 0.1% of myofibroblasts in vehicle-treated Tie2-Cre;LoxP-EGFP mice (P < 0.01). Confocal microscopy and real-time PCR showed that transforming growth factor (TGF)-beta1 induced de novo expression of alpha-SMA and loss of expression of VE-cadherin and CD31 in MMECs and primary cultures of renal endothelial cells in a time- and dose-dependent fashion. These findings demonstrate that the endothelial-myofibroblast transition occurs and contributes to the early development and progression of diabetic renal interstitial fibrosis and suggest that the endothelial-myofibroblast transition may be a therapeutic target.",
"title": "Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice."
},
{
"docid": "75636923",
"text": "Metabolic syndrome is diagnosed when three or more of the following criteria are met: abdominal obesity (waist circumference more than 102 cm in men and 88 cm in women); hypertriglyceridemia of 150 mg/dl or above; a high-density lipoprotein (HDL) cholesterol level less than 40 mg/dl in men or 50 mg/dl in women; blood pressure of 130/85 mm Hg or higher; or fasting glucose of at least 110 mg/dl. Individuals with metabolic syndrome are likelier than others to develop diabetes and cardiovascular disease and have increased mortality from all causes (and from cardiovascular disease in particular). The investigators attempted to determine the prevalence of the syndrome in the United States by analyzing data on 8814 men and women 20 years of age or older who took part in the Third National Health and Nutrition Examination Survey in the years 1988 to 1994. This is a cross-sectional health survey of a sample of the noninstitutionalized civilian American population. The overall age-adjusted prevalence of metabolic syndrome was 23.7%. The prevalence rose from 6.7% in persons 20 to 29 years of age to 42% in those aged 70 years and more. There was virtually no gender-related difference in prevalence rates for the combined racial groups. Metabolic syndrome was most prevalent in Mexican Americans and least prevalent in whites, African Americans, and \"others. \" Among both African Americans and Mexican Americans, women had higher prevalence rates than men. Extrapolating from age-specific prevalence rates and US census counts from the year 2000, 47 million US residents have metabolic syndrome. Considering its prevalence, it seems important to estimate the direct medical costs of metabolic syndrome. In the great majority of cases the critical causes are improper nutrition and insufficient physical activity, emphasizing the importance of controlling obesity and encouraging physical activity in the United States.",
"title": "Prevalence of the Metabolic Syndrome Among Us Adults: Findings From the Third National Health and Nutrition Examination Survey"
},
{
"docid": "16532419",
"text": "BACKGROUND Carbon nanotubes (CNT) hold great promise to create new and better products for commercial and biomedical applications, but their long-term adverse health effects are a major concern. The objective of this study was to address human lung cancer risks associated with chronic pulmonary exposure to single-walled (SW) CNT through the fundamental understanding of cellular and molecular processes leading to carcinogenesis. We hypothesized that the acquisition of cancer stem cells (CSC), a subpopulation that drive tumor initiation and progression, may contribute to CNT carcinogenesis. METHODS Non-tumorigenic human lung epithelial cells were chronically exposed to well-dispersed SWCNT for a period of 6 months at the physiologically relevant concentration of 0.02 μg/cm2 surface area dose. Chronic SWCNT-exposed cells were evaluated for the presence of CSC-like cells under CSC-selective conditions of tumor spheres and side population (SP). CSC-like cells were isolated using fluorescence-activated cell sorting and were assessed for aggressive behaviors, including acquired apoptosis resistance and increased cell migration and invasion in vitro, and tumor-initiating capability in vivo. Non-small cell lung cancer cells served as a positive control. RESULTS We demonstrated for the first time the existence of CSC-like cells in all clones of chronic SWCNT-exposed lung epithelial cells. These CSC-like cells, in contrary to their non-CSC counterpart, possessed all biological features of lung CSC that are central to irreversible malignant transformation, self-renewal, aggressive cancer behaviors, and in vivo tumorigenesis. These cells also displayed aberrant stem cell markers, notably Nanog, SOX-2, SOX-17 and E-cadherin. Restored expression of tumor suppressor p53 abrogated CSC properties of CSC-like cells. Furthermore, we identified specific stem cell surface markers CD24low and CD133high that are associated with SWCNT-induced CSC formation and tumorigenesis. CONCLUSIONS Our findings provide new and compelling evidence for the acquisition of CSC-like cells induced by chronic SWCNT exposure, which are likely to be a major driving force for SWCNT tumorigenesis. Thus, our study supports prudent adoption of prevention strategies and implementation of exposure control for SWCNT. We also suggest that the detection of CSC and associated surface markers may provide an effective screening tool for prediction of the carcinogenic potential of SWCNT and related nanoparticles.",
"title": "Induction of stem-like cells with malignant properties by chronic exposure of human lung epithelial cells to single-walled carbon nanotubes"
},
{
"docid": "4468861",
"text": "Immune checkpoint inhibitors result in impressive clinical responses, but optimal results will require combination with each other and other therapies. This raises fundamental questions about mechanisms of non-redundancy and resistance. Here we report major tumour regressions in a subset of patients with metastatic melanoma treated with an anti-CTLA4 antibody (anti-CTLA4) and radiation, and reproduced this effect in mouse models. Although combined treatment improved responses in irradiated and unirradiated tumours, resistance was common. Unbiased analyses of mice revealed that resistance was due to upregulation of PD-L1 on melanoma cells and associated with T-cell exhaustion. Accordingly, optimal response in melanoma and other cancer types requires radiation, anti-CTLA4 and anti-PD-L1/PD-1. Anti-CTLA4 predominantly inhibits T-regulatory cells (Treg cells), thereby increasing the CD8 T-cell to Treg (CD8/Treg) ratio. Radiation enhances the diversity of the T-cell receptor (TCR) repertoire of intratumoral T cells. Together, anti-CTLA4 promotes expansion of T cells, while radiation shapes the TCR repertoire of the expanded peripheral clones. Addition of PD-L1 blockade reverses T-cell exhaustion to mitigate depression in the CD8/Treg ratio and further encourages oligoclonal T-cell expansion. Similarly to results from mice, patients on our clinical trial with melanoma showing high PD-L1 did not respond to radiation plus anti-CTLA4, demonstrated persistent T-cell exhaustion, and rapidly progressed. Thus, PD-L1 on melanoma cells allows tumours to escape anti-CTLA4-based therapy, and the combination of radiation, anti-CTLA4 and anti-PD-L1 promotes response and immunity through distinct mechanisms.",
"title": "Radiation and Dual Checkpoint Blockade Activates Non-Redundant Immune Mechanisms in Cancer"
},
{
"docid": "39281140",
"text": "CONTEXT Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. OBJECTIVE To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. DESIGN, SETTING, AND PATIENTS Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. INTERVENTION Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. MAIN OUTCOME MEASURES The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). RESULTS Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration. CONCLUSION In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.",
"title": "Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial."
},
{
"docid": "13106686",
"text": "Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3' repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.",
"title": "Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing."
},
{
"docid": "13223957",
"text": "OBJECTIVE The cardinal indication for surgical treatment of gallstones is pain attacks. However, following cholecystectomy, 20% of patients remain symptomatic. It is unclear to what extent post-cholecystectomy symptoms can be ascribed to persistence of preoperative symptoms or to new pathology. The pain and digestive pattern in gallstone patients has not been defined in a recent setting with ultrasonography as the diagnostic method. The aim of this study was to characterize a pain pattern that is typical for gallstone disease and to describe the extent of associated dyspepsia. MATERIAL AND METHODS A total of 220 patients with symptomatic gallstone disease including complicated disease (acute cholecystitis and common bile duct stones) were interviewed using detailed questionnaires to disclose pain patterns and symptoms of indigestion. RESULTS All patients had pain in the right upper quadrant (RUQ) including the upper midline epigastrium. The pain was localized to the right subcostal area in 20% and to the upper epigastrium in 14%, and in the rest (66%) it was more evenly distributed. An area of maximal pain could be defined in 90%. Maximal pain was located under the costal arch in 51% of patients and in the epigastrium in 41%, but in 3% behind the sternum and in 5% in the back. The pain was referred to the back in 63% of the patients. The mean visual analogue scale (VAS) score was very high: 90 mm on a 0-100 scale. A pattern of incipient or low-grade warning pain with a subsequent relatively steady state until subsiding in the same fashion was present in 90% of the patients. An urge to walk around was experienced by 71%. Pain attacks usually occurred in the late evening or at night (77%), with 85% of the attacks lasting for more than one hour and almost never less than half an hour. Sixty-six percent of the patients were intolerant to at least one kind of food, but only 48% to fatty foods. Symptoms of functional indigestion (gastroesophageal reflux, dyspepsia or irritable bowel symptoms) were seen in the vast majority in association with attacks. CONCLUSIONS Gallstone-associated pain follows a certain pattern in the majority of patients. The pain is located in a defined area with a point of maximum intensity, is usually referred, and occurs mainly at night with duration of more than one hour. The majority of patients experience functional indigestion, mainly of the reflux type or dyspepsia.",
"title": "Pain attacks in non-complicated and complicated gallstone disease have a characteristic pattern and are accompanied by dyspepsia in most patients: the results of a prospective study."
},
{
"docid": "25028913",
"text": "BACKGROUND In patients with unstable coronary artery disease, there is a relation between the short-term risk of death and blood levels of troponin T (a marker of myocardial damage) and C-reactive protein and fibrinogen (markers of inflammation). Using information obtained during an extension of the follow-up period in the Fragmin during Instability in Coronary Artery Disease trial, we evaluated the usefulness of troponin T, C-reactive protein, and fibrinogen levels and other indicators of risk as predictors of the long-term risk of death from cardiac causes. METHODS Levels of C-reactive protein and fibrinogen at enrollment and the maximal level of troponin T during the first 24 hours after enrollment were analyzed in 917 patients included in a clinical trial of low-molecular-weight heparin in unstable coronary artery disease. The patients were followed for a mean of 37.0 months (range, 1.6 to 50.6). RESULTS During follow-up, 1.2 percent of the 173 patients with maximal blood troponin T levels of less than 0.06 microg per liter died of cardiac causes, as compared with 8.7 percent of the 367 patients with levels of 0.06 to 0.59 microg per liter and 15.4 percent of the 377 patients with levels of at least 0.60 microg per liter (P=0.007 and P=0.001, respectively). The rates of death from cardiac causes were 5.7 percent among the 314 patients with blood C-reactive protein levels of less than 2 mg per liter, 7.8 percent among the 294 with levels of 2 to 10 mg per liter, and 16.5 percent among the 309 with levels of more than 10 mg per liter (P=0.29 and P=0.001, respectively). The rates of death from cardiac causes were 5.4 percent among the 314 patients with blood fibrinogen levels of less than 3.4 g per liter, 12.0 percent among the 300 with levels of 3.4 to 3.9 g per liter, and 12.9 percent among the 303 with levels of at least 4.0 g per liter (P=0.004 and P=0.69, respectively). In a multivariate analysis, levels of troponin T and C-reactive protein were independent predictors of the risk of death from cardiac causes. CONCLUSIONS In unstable coronary artery disease, elevated levels of troponin T and C-reactive protein are strongly related to the long-term risk of death from cardiac causes. These markers are independent risk factors, and their effects are additive with respect to each other and other clinical indicators of risk.",
"title": "Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease."
},
{
"docid": "39892135",
"text": "OBJECTIVE To assess the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of spondylarthropathy. METHODS We conducted a 6-month randomized, placebo-controlled, double-blind, multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs. Patients were treated with SSZ (3 gm/day) or placebo. The primary efficacy variables were the physician's and patient's overall assessments, pain, and morning stiffness. End points were analyzed in the intent-to-treat and completer patient populations; the time course of effect was analyzed in the completer patient population. RESULTS Of the 351 patients enrolled, 263 (75%) completed the 6-month treatment period. The withdrawal rates were 35 (20%) and 53 (30%) in the placebo and SSZ groups, respectively. In the intent-to-treat analysis of end point efficacy, the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables, the patient's overall assessment of disease activity, for which 60% of the patients taking SSZ improved by at least 1 point on a 5-point scale, in contrast to 44% of the patients taking placebo. Laboratory markers of inflammation also showed statistically significant change in favor of SSZ. In subgroup analysis, the most impressive effects were seen in patients with psoriatic arthritis, both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints. Adverse events were more frequent in the SSZ group than the placebo group, but all were transient or reversible after cessation of treatment. CONCLUSION The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy, notably in patients with psoriatic arthritis.",
"title": "Sulfasalazine in the treatment of spondylarthropathy. A randomized, multicenter, double-blind, placebo-controlled study."
},
{
"docid": "10699587",
"text": "PURPOSE Gleason score (GS), T stage, and pathologic lymph node status have been described as major independent predictors of death due to prostate cancer in men treated with external beam radiotherapy (XRT). In this analysis we combine these three factors to define prognostic subgroups that correlate with disease-specific survival (DSS) death from prostate cancer. METHODS AND MATERIALS Men entered on one of four Radiation Therapy Oncology Group (RTOG) Phase III randomized trials between 1975 and 1992, for clinically localized prostate cancer (CAP) (n = 1557), were selected for this analysis. Patients were included if: 1) they were evaluable, and eligible for the trial; 2) they received no hormonal therapy with their initial treatment; and 3) follow-up was available. For this study a DSS event was declared if: 1) death was certified as due to CAP; 2) death was due to complications of treatment; or 3) death was from unknown causes with active malignancy. The median follow-up for patients treated on early and late RTOG studies exceeded 11 and 6 years respectively. Subgroups were identified based on their pretreatment GS, T-stage, and lymph node such that patients with similar risk of dying from prostate cancer were combined. RESULTS By combining patients with similar DSS, four subgroups were identified. Risk Group 1 patients had a GS = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The 5-, 10-, and 15-year DSS was 96%, 86%, and 72%; 94%, 75%, and 61%; 83%, 62%, and 39%; and 64%, 34%, and 27% for Groups 1 through 4, respectively. CONCLUSIONS Recognition of these four risk groups provides a basis for estimating the long-term DSS for men treated with XRT alone and should facilitate the design of future prospective randomized trials.",
"title": "Four prognostic groups predict long-term survival from prostate cancer following radiotherapy alone on Radiation Therapy Oncology Group clinical trials."
},
{
"docid": "3056682",
"text": "Unstable angina is a critical phase of coronary heart disease with widely variable symptoms and prognosis. A decade ago, a classification of unstable angina based on clinical symptoms was introduced. This system was then validated by prospective clinical studies to correlate with the prognosis and was linked to angiographic and histological findings. It has been used to categorize patients in many large clinical trials. In recent years, the pathophysiological roles of platelet activation and inflammation in unstable angina have been elucidated. Subsequently, improved markers of myocardial injury, acute-phase proteins, and hemostatic markers that may be associated with clinical outcomes have been identified. Particularly, cardiac-specific troponin T and troponin I have been shown to represent the best predictors of early risk in patients with angina at rest. Accordingly, it is suggested that the original classification be extended by subclassifying one large group of unstable angina patients, ie, those with angina at rest within the past 48 hours (class IIIB), into troponin-positive (T(pos)) and troponin-negative (T(neg)) patients. The 30-days risk for death and myocardial infarction is considered to be up to 20% in class IIIB-T(pos) but <2% in class IIIB-T(neg) patients. Initial results suggest that troponins may function as surrogate markers for thrombus formation and can effectively guide therapy with glycoprotein IIb/IIIa antagonists or low-molecular-weight heparins. These observations provide additional impetus for adding the measurement of these markers to the clinical classification and represent a novel concept of treating these high-risk patients.",
"title": "A classification of unstable angina revisited."
},
{
"docid": "14082855",
"text": "PURPOSE To investigate and relate the ultrashort-term and long-term courses of determinants for foreign body reaction as biocompatibility predictors for meshes in an animal model. MATERIALS AND METHODS Three different meshes (TVT, UltraPro, and PVDF) were implanted in sheep. Native and plasma coated meshes were placed bilaterally: (a) interaperitoneally, (b) as fascia onlay, and (c) as muscle onlay (fascia sublay). At 5 min, 20 min, 60 min, and 120 min meshes were explanted and histochemically investigated for inflammatory infiltrate, macrophage infiltration, vessel formation, myofibroblast invasion, and connective tissue accumulation. The results were related to long-term values over 24 months. RESULTS Macrophage invasion reached highest extents with up to 60% in short-term and decreased within 24 months to about 30%. Inflammatory infiltrate increased within the first 2 hours, the reached levels and the different extents and ranking among the investigated meshes remained stable during long-term follow up. For myofibroblasts, connective tissue, and CD31+ cells, no activity was detected during the first 120 min. CONCLUSION The local inflammatory reaction is an early and susceptible event after mesh implantation. It cannot be influenced by prior plasma coating and does not depend on the localisation of implantation.",
"title": "Inflammatory Reaction as Determinant of Foreign Body Reaction Is an Early and Susceptible Event after Mesh Implantation"
},
{
"docid": "596817",
"text": "From Darwin's study of the Galapagos and Wallace's study of Indonesia, islands have played an important role in evolutionary investigations, and radiations within archipelagos are readily interpreted as supporting the conventional view of allopatric speciation. Even during the ongoing paradigm shift towards other modes of speciation, island radiations, such as the Lesser Antillean anoles, are thought to exemplify this process. Geological and molecular phylogenetic evidence show that, in this archipelago, Martinique anoles provide several examples of secondary contact of island species. Four precursor island species, with up to 8 mybp divergence, met when their islands coalesced to form the current island of Martinique. Moreover, adjacent anole populations also show marked adaptation to distinct habitat zonation, allowing both allopatric and ecological speciation to be tested in this system. We take advantage of this opportunity of replicated island coalescence and independent ecological adaptation to carry out an extensive population genetic study of hypervariable neutral nuclear markers to show that even after these very substantial periods of spatial isolation these putative allospecies show less reproductive isolation than conspecific populations in adjacent habitats in all three cases of subsequent island coalescence. The degree of genetic interchange shows that while there is always a significant genetic signature of past allopatry, and this may be quite strong if the selection regime allows, there is no case of complete allopatric speciation, in spite of the strong primae facie case for it. Importantly there is greater genetic isolation across the xeric/rainforest ecotone than is associated with any secondary contact. This rejects the development of reproductive isolation in allopatric divergence, but supports the potential for ecological speciation, even though full speciation has not been achieved in this case. It also explains the paucity of anole species in the Lesser Antilles compared to the Greater Antilles.",
"title": "Genetic Tests for Ecological and Allopatric Speciation in Anoles on an Island Archipelago"
},
{
"docid": "4911006",
"text": "Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named \"immunogenic cell death\" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.",
"title": "Consensus guidelines for the detection of immunogenic cell death."
},
{
"docid": "11943989",
"text": "The \"ba, ba, ba\" sound universal to babies' babbling around 7 months captures scientific attention because it provides insights into the mechanisms underlying language acquisition and vestiges of its evolutionary origins. Yet the prevailing mystery is what is the biological basis of babbling, with one hypothesis being that it is a non-linguistic motoric activity driven largely by the baby's emerging control over the mouth and jaw, and another being that it is a linguistic activity reflecting the babies' early sensitivity to specific phonetic-syllabic patterns. Two groups of hearing babies were studied over time (ages 6, 10, and 12 months), equal in all developmental respects except for the modality of language input (mouth versus hand): three hearing babies acquiring spoken language (group 1: \"speech-exposed\") and a rare group of three hearing babies acquiring sign language only, not speech (group 2: \"sign-exposed\"). Despite this latter group's exposure to sign, the motoric hypothesis would predict similar hand activity to that seen in speech-exposed hearing babies because language acquisition in sign-exposed babies does not involve the mouth. Using innovative quantitative Optotrak 3-D motion-tracking technology, applied here for the first time to study infant language acquisition, we obtained physical measurements similar to a speech spectrogram, but for the hands. Here we discovered that the specific rhythmic frequencies of the hands of the sign-exposed hearing babies differed depending on whether they were producing linguistic activity, which they produced at a low frequency of approximately 1 Hz, versus non-linguistic activity, which they produced at a higher frequency of approximately 2.5 Hz - the identical class of hand activity that the speech-exposed hearing babies produced nearly exclusively. Surprisingly, without benefit of the mouth, hearing sign-exposed babies alone babbled systematically on their hands. We conclude that babbling is fundamentally a linguistic activity and explain why the differentiation between linguistic and non-linguistic hand activity in a single manual modality (one distinct from the human mouth) could only have resulted if all babies are born with a sensitivity to specific rhythmic patterns at the heart of human language and the capacity to use them.",
"title": "Baby hands that move to the rhythm of language: hearing babies acquiring sign languages babble silently on the hands"
},
{
"docid": "3944632",
"text": "CONTEXT In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. OBJECTIVE To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. DESIGN, SETTING, AND PATIENTS Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. INTERVENTIONS Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients). MAIN OUTCOME MEASURES The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. RESULTS The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. CONCLUSIONS Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used. TRIAL REGISTRATION umin.ac.jp/ctr Identifier: C000000412.",
"title": "Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial."
},
{
"docid": "22488511",
"text": "To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) - lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor - SB431542 and/or JAK2/STAT3 inhibitor - JSI-124. MFs were stimulated by TGF-β, cancer cell-CM or cancer cells, with or without SB431542 and JSI-124. Cell proliferation, the levels of cytokines, expression of mRNA and protein were determined. Mice bearing xenograft tumors were intraperitoneally treated with SB431542 or JSI-124 and monitored for up to 45 days. In co-culture systems, MFs secreted high levels of IL-6, while cancer cells produced high levels of TGF-β. Recombinant IL-6 and MF-CM activated STAT3 and upregulated TGF-β in cancer cells. In contrast, cancer cell-CM or TGF-β stimulated MFs to produce IL-6. Blockade of JAK2/STAT3 and TGF-β signaling by specific inhibitors significantly inhibited cell proliferation in vitro and tumor growth in vivo of lung cancer cells. Our study demontrated that the TGF-β and IL-6/JAK2/STAT3 signaling pathways form a positive feedback signaling loop that mediated the interactions between MFs and lung cancer cells. Targeted inhibiton of this signaling loop could be a new approach for lung cancer prevention and therapy.",
"title": "Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts"
},
{
"docid": "11328820",
"text": "The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.",
"title": "NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis."
},
{
"docid": "25238950",
"text": "Fibroblast growth factors (FGFs) have mitogenic activity toward a wide variety of cells of mesenchymal, neuronal, and epithelial origin and regulate events in normal embryonic development, angiogenesis, wound repair, and neoplasia. FGF-2 is expressed in many normal adult tissues and can regulate migration and replication of intestinal epithelial cells in culture. However, little is known about the effects of FGF-2 on intestinal epithelial stem cells during either normal epithelial renewal or regeneration of a functional epithelium after injury. In this study, we investigated the expression of FGF-2 in the mouse small intestine after irradiation and determined the effect of exogenous FGF-2 on crypt stem cell survival after radiation injury. Expression of FGF-2 mRNA and protein began to increase at 12 h after gamma-irradiation, and peak levels were observed from 48 to 120 h after irradiation. At all times after irradiation, the higher molecular mass isoform ( approximately 24 kDa) of FGF-2 was the predominant form expressed in the small intestine. Immunohistochemical analysis of FGF-2 expression after radiation injury demonstrated that FGF-2 was predominantly found in the mesenchyme surrounding regenerating crypts. Exogenous recombinant human FGF-2 (rhFGF-2) markedly enhanced crypt stem cell survival when given before irradiation. We conclude that expression of FGF-2 is induced by radiation injury and that rhFGF-2 can enhance crypt stem cell survival after subsequent injury.",
"title": "FGF-2 enhances intestinal stem cell survival and its expression is induced after radiation injury."
},
{
"docid": "13578199",
"text": "Human transglutaminase 2 (TG2), a member of a large family of enzymes that catalyze protein crosslinking, plays an important role in the extracellular matrix biology of many tissues and is implicated in the gluten-induced pathogenesis of celiac sprue. Although vertebrate transglutaminases have been studied extensively, thus far all structurally characterized members of this family have been crystallized in conformations with inaccessible active sites. We have trapped human TG2 in complex with an inhibitor that mimics inflammatory gluten peptide substrates and have solved, at 2-A resolution, its x-ray crystal structure. The inhibitor stabilizes TG2 in an extended conformation that is dramatically different from earlier transglutaminase structures. The active site is exposed, revealing that catalysis takes place in a tunnel, bridged by two tryptophan residues that separate acyl-donor from acyl-acceptor and stabilize the tetrahedral reaction intermediates. Site-directed mutagenesis was used to investigate the acyl-acceptor side of the tunnel, yielding mutants with a marked increase in preference for hydrolysis over transamidation. By providing the ability to visualize this activated conformer, our results create a foundation for understanding the catalytic as well as the non-catalytic roles of TG2 in biology, and for dissecting the process by which the autoantibody response to TG2 is induced in celiac sprue patients.",
"title": "Transglutaminase 2 Undergoes a Large Conformational Change upon Activation "
}
] |
5ae141145542997b2ef7d183
|
George Wylie Hutchinson illustrated the works of which English journalist and short-story writer?
|
[
{
"docid": "51340394",
"text": "George Wylie Hutchinson (1852–1942) was a painter and leading illustrator in Britain and was from Great Village, Nova Scotia, Canada. He illustrated the works of Arthur Conan Doyle, Rudyard Kipling, Hall Caine, Robert Louis Stevenson and Israel Zangwill. His paintings inspired the poem \"Large Bad Picture\" and \"Poem\", both by Elizabeth Bishop, his great grand niece. Hutchinson was a contributor to and subject of the novel \"The Master\" (1895) by Israel Zangwill, with whom he was a close friend.",
"title": ""
},
{
"docid": "26308",
"text": "Joseph Rudyard Kipling ( ; 30 December 1865 – 18 January 1936) was an English journalist, short-story writer, poet, and novelist.",
"title": ""
}
] |
[
{
"docid": "18221934",
"text": "Ida Alexa Ross Wylie (16 March 1885 – 4 November 1959), known by her pen name I. A. R. Wylie, was an Australian-British-American novelist, screenwriter, short story writer, and poet who was honored by the journalistic and literary establishments of her time, and was known around the world. Between 1915 and 1953, more than thirty of her novels and stories were adapted into films, including \"Keeper of the Flame\" (1942), which was directed by George Cukor and starred Spencer Tracy and Katharine Hepburn.",
"title": ""
},
{
"docid": "30840242",
"text": "Georges Hausemer (born 1957) is a Luxembourg writer who has published short stories, novels, travelogues and non-fictional works and has also translated a considerable number of works from French, English, Spanish and Luxembourgish into German. Sometimes using the \"nom de plume\" Theo Selmer, he has also worked as an illustrator.",
"title": ""
},
{
"docid": "2153647",
"text": "Edward George Dyson (4 March 1865 – 22 August 1931) was an Australian journalist, poet, playwright and short story writer. He was the elder brother of talented illustrators Will Dyson and Ambrose Dyson.",
"title": ""
},
{
"docid": "29375767",
"text": "Eugen Binder von Krieglstein (July 6, 1873 – September 17, 1914) was an Austrian journalist, war correspondent and travel writer; he sometimes used the pen names of Eugen Krieglstein or Eugen Binder-Krieglstein. In addition to his journalistic work, he also gave lectures about his war experiences illustrated with photographs which we took at the various locations. Von Krieglstein also published numerous travel narratives, and works of fiction, including collections of short-stories and novels.",
"title": ""
},
{
"docid": "42848020",
"text": "I, James Blunt is a 1942, wartime alternate history short-story by English journalist H. V. Morton. It takes the form of a diary written by an English tradesman chronicling the Nazi occupation of Great Britain in the fall of 1944. The short-story was commissioned by the Ministry of Information as propaganda and is Morton's only work of fiction beside his travel journalism writings for which he is better known. George Orwell described the novel as \"a good flesh creeper, founded on the justified assumption that the mass of the English people haven't heard of fascism.\"",
"title": ""
},
{
"docid": "31046507",
"text": "Mayfa' Abdel Rahman al-Qiyadi (born 1951) is a Yemeni short story writer and journalist. He studied at the Gorky Institute in Moscow and obtained an MA in 1982. He is known for his short stories which explore the social and political realities of Yemen. His first collection of short stories appeared in 1975, followed by a second one in 1983. His work has appeared in English translation in a 1988 anthology called \"The Literature of Modern Arabia\" (edited by Salma Khadra Jayyusi).",
"title": ""
},
{
"docid": "25769987",
"text": "George Charles Haité (8 June 1855 – 31 March 1924) was an English designer, painter, illustrator and writer. His most famous work is the iconic cover design of the \"Strand Magazine\", launched in 1891, which helped popularise the Sherlock Holmes stories of Arthur Conan Doyle. Haité was also a founder member and the first president of the London Sketch Club.",
"title": ""
},
{
"docid": "164993",
"text": "Algernon Henry Blackwood, CBE (14 March 1869 – 10 December 1951) was an English short story writer and novelist, one of the most prolific writers of ghost stories in the history of the genre. He was also a journalist and a broadcasting narrator. S. T. Joshi has stated that \"his work is more consistently meritorious than any weird writer's except Dunsany's\" and that his short story collection \"Incredible Adventures\" (1914) \"may be the premier weird collection of this or any other century\".",
"title": ""
},
{
"docid": "757120",
"text": "Hutchinson began as Hutchinson & Co. (Publishers) Ltd., an English book publisher, founded in 1887 by Sir George Hutchinson and later run by his son, Walter Hutchinson (1887–1950). Hutchinson's published books and magazines such as \"The Lady's Realm\", \"Adventure-story Magazine\", \"Hutchinson's Magazine\" and \"Woman\".",
"title": ""
},
{
"docid": "32188930",
"text": "Siba'i Ahmad Uthman (born 1938) is a Saudi journalist, author and short story writer. He was born in 1938 in the Sudan and studied at the College of Arts in Khartoum before commencing a career in journalism. Among Uthman's works are several volumes of short stories including \"Silence and the Walls\" and \"Circles in the Book of Time\". His short story \"Silence and the Walls\" appeared in English translation in a 1988 anthology of Arabian literature edited by Salma Khadra Jayyusi.",
"title": ""
},
{
"docid": "22524944",
"text": "Vugar Aslanov (born 1964 in Goranboy, Azerbaijan) is a writer and journalist from Azerbaijan. In college he studied literature. By the 1990s he was working in Baku for various newspapers. He and the information agency Səmt (Drift) founded the newspaper, Kompas, which he ran from 1995 to 1998. During that time he edited a book of short stories and also wrote short stories. Many of his stories were published by the writers union of Azerbaijan in its literary magazines. He emigrated from Azerbaijanin in 1998 to Germany. In Germany he was able to continue his journalistic and literary work. He lectured and wrote about the various republics in the former Soviet Union. In 2007 he wrote a book in German called \"The Cotton Fields.\" \"The Cotton Fields\" is a volume of seven of his short stories on aspects of life; for example, in one story his protagonist is a hospital's very tired accountant.",
"title": ""
},
{
"docid": "31495369",
"text": "A. G. (Archibald George) Thornton (1886 – 1969) was a British novelist, short story writer and journalist. He authored three popular novels which were noted for their realism and humour.",
"title": ""
},
{
"docid": "42547505",
"text": "Chameli Memsaab (English: Madame Chameli) is a 1975 Assamese drama film directed by Abdul Majid. A love story set in a tea estate in Assam, between a British tea estate owner and local tea garden worker. It starred George Baker and Binita Borgohain as leads. The film is based on a short story by journalist and writer, Nirode Choudhury.",
"title": ""
},
{
"docid": "8894704",
"text": "Patricia Lynch (c. 1894 – 1972) was an Irish children's writer and a journalist. She was the author of some 48 novels and 200 short stories. She is best known for blending Irish rural life and fantasy fiction as in \"The Turf-Cutter's Donkey\" which was illustrated by Jack B. Yeats.",
"title": ""
},
{
"docid": "15673345",
"text": "Janos Bardi (born 1923 in Budapest, d. 1990 in Hamburg) was a journalist and writer. He worked as a journalist until after World War II, when the authoritarian government then in power no longer allowed him to write for newspapers. He then worked as a deckhand but continued to write stories and satires, one of which caused him to be arrested. After the Hungarian Revolution of 1956, he escaped to West Germany where he found work as a journalist. Bardi continued to write short stories, radio plays, and satires for cabaret until his death in Hamburg in April 1990.",
"title": ""
},
{
"docid": "7350273",
"text": "Thelma Honora Forshaw or Thelma Körting (1 August 1923 – 8 October 1995) was an Australian short story writer and journalist. In 1967 she wrote a largely autobiographical collection of short stories, \"An Affair of Clowns\". As a journalist she worked as a freelance writer and book reviewer for \"The Sydney Morning Herald\", \"The Age\", \"The Australian\", \"The Bulletin\" (since defunct), \"Meanjin\", \"Nation\", and \"Quadrant\". Forshaw died on 8 October 1995 of a stroke in her sleep, aged 72.",
"title": ""
},
{
"docid": "28270709",
"text": "Eli Waldron (January 25, 1916 to June 9, 1980) was born Gerald Cleveland Waldron in Oconto Falls, Wisconsin. Waldron was an American writer and journalist whose primary work consisted of short stories, essays, and poetry. His writings were published in literary journals (such as \"The Kenyon Review\", \"Prairie Schooner\", and \"Story\") and popular periodicals (such as \"Collier's\", \"Holiday\", \"Rolling Stone\", \"Saturday Evening Post\"). From the 1950s to 1970s he contributed stories and essays to \"\"The New Yorker\", and in the 1960s and 1970s, a number of his poems and experimental fiction works appeared in underground, alternative, and \"counter-culture\" publications, such as \"The Illustrated Paper\", \"Rat Subterranean News\", \"Underground\", \"The Village Voice\", and \"The Woodstock Times\".",
"title": ""
},
{
"docid": "38051127",
"text": "Maurice Richardson (1907–1978) was an English journalist and short story writer.",
"title": ""
},
{
"docid": "39346984",
"text": "George Dodd (1808 – 21 January 1881) was an English journalist and writer. His best known work was \"The Food of London\" (1856).",
"title": ""
},
{
"docid": "28106107",
"text": "Laura Dockrill (born 28 May 1986) is an English performance poet, author illustrator and short story writer.",
"title": ""
},
{
"docid": "1692900",
"text": "Arthur George Morrison (1 November 1863 – 4 December 1945) was an English writer and journalist known for his realistic novels and stories about working-class life in London's East End, and for his detective stories, featuring the detective Martin Hewitt. He also collected Japanese art and published several works on the subject. He left a large collection of paintings and other works of art to the British Museum after his death in 1945. Morrison's best known work of fiction is his novel \"A Child of the Jago\" (1896).",
"title": ""
},
{
"docid": "30866314",
"text": "Muhammad Asim Butt (Urdu: محمد عاصم بٹ) is an Urdu novelist, short story writer, translator, researcher, editor, critic and journalist. He has published two novels and two collections of short stories along with a number of books translated from English into Urdu and vice versa. Butt also writes in English.",
"title": ""
},
{
"docid": "34108894",
"text": "Tahir Naqvi (Urdu: ), born Tahir Riza Naqvi (Urdu: ) in 1942 in India, is a Pakistani writer. He has been writing short stories since 1972. Several of his short stories have been translated into English and some regional languages. He has been praised by several writers for his short story work.",
"title": ""
},
{
"docid": "10151331",
"text": "Joanna Briscoe is an English writer born in London in 1963. She has written four novels and several short stories, and worked as a freelance journalist. Her first novel, \"Mothers and Other Lovers\", won a Betty Trask Award in 1993, and her third, \"Sleep with Me\" (2005), was adapted for television.",
"title": ""
},
{
"docid": "419269",
"text": "The Nebula Award for Best Short Story is given each year by the Science Fiction and Fantasy Writers of America (SFWA) for science fiction or fantasy short stories. A work of fiction is defined by the organization as a short story if it is less than 7,500 words; awards are also given out for longer works in the categories of novel, novella, and novelette. To be eligible for Nebula Award consideration a short story must be published in English in the United States. Works published in English elsewhere in the world are also eligible provided they are released on either a website or in an electronic edition. The Nebula Award for Best Short Story has been awarded annually since 1966. The award has been described as one of \"the most important of the American science fiction awards\" and \"the science-fiction and fantasy equivalent\" of the Emmy Awards.",
"title": ""
},
{
"docid": "6492289",
"text": "Colin Spencer (born 1933) is an English writer and artist who has produced a prolific body of work in a wide variety of media since his first published short stories and drawings appeared in \"The London Magazine\" and \"Encounter\" when he was 22. His work includes novels, short stories, non-fiction (including histories of food and of homosexuality), cookery books, stage and television plays, paintings and drawings, book and magazine illustrations. He has written and presented a television documentary on vandalism, appeared in numerous radio and television programmes and lectured on food history, literature and social issues. For fourteen years he wrote a regular food column for \"The Guardian\".",
"title": ""
},
{
"docid": "14957506",
"text": "George Henry Hutchinson (31 October 1929 – 1996) was an English professional footballer who played for Huddersfield Town, Sheffield United, Tottenham Hotspur, Guildford City, Leeds United, Halifax Town and Skegness Town. He served in the RAF during National Service and was stationed at Ballykelly in Northern Ireland and RAF Cosford and was a PTI. He also played for the RAF team. Hutchinson was born in Allerton Bywater, West Riding of Yorkshire, the son of a miner who worked at the local colliery.",
"title": ""
},
{
"docid": "40074086",
"text": "Vakati Panduranga Rao was a short story writer and journalist who for a long time edited the popular Telugu weekly, \"Andhra Prabha\". His editorial, under the name Mitra Vakyam, made him immensely popular. A collection of these editorials was published in two volumes. Later, he worked for an English-language newspaper.",
"title": ""
},
{
"docid": "23372312",
"text": "Jan Sebastian Rabie (14 November 1920 - 15 November 2001) was an Afrikaans writer of short stories, novels and other literary works. He was born in George, and was the writer of twenty-one works. He was included under the Sestigers, a group of influential Afrikaans writers of the 1960s.",
"title": ""
},
{
"docid": "16976573",
"text": "John Ernest Bechdolt (1884–1954) was an American short story writer, novelist and journalist. He wrote under the name Jack Bechdolt as well as his full name. He worked for the \"Seattle Post-Intelligencer\" from 1909 to 1916, after which he moved to New York, where he worked for Munsey Publications for a year before freelancing. His first novel, \"The Torch\", was serialized in the magazine \"Argosy\" in 1920. Several of his stories were made into movies.",
"title": ""
}
] |
890
|
Origin gross domestic product(GDP) is negatively related to dengue virus (DENV-1) diffusion in air traffic shipments.
|
[
{
"docid": "2097256",
"text": "BACKGROUND Aedes aegypti, the major vector of dengue viruses, often breeds in water storage containers used by households without tap water supply, and occurs in high numbers even in dense urban areas. We analysed the interaction between human population density and lack of tap water as a cause of dengue fever outbreaks with the aim of identifying geographic areas at highest risk. METHODS AND FINDINGS We conducted an individual-level cohort study in a population of 75,000 geo-referenced households in Vietnam over the course of two epidemics, on the basis of dengue hospital admissions (n = 3,013). We applied space-time scan statistics and mathematical models to confirm the findings. We identified a surprisingly narrow range of critical human population densities between around 3,000 to 7,000 people/km² prone to dengue outbreaks. In the study area, this population density was typical of villages and some peri-urban areas. Scan statistics showed that areas with a high population density or adequate water supply did not experience severe outbreaks. The risk of dengue was higher in rural than in urban areas, largely explained by lack of piped water supply, and in human population densities more often falling within the critical range. Mathematical modeling suggests that simple assumptions regarding area-level vector/host ratios may explain the occurrence of outbreaks. CONCLUSIONS Rural areas may contribute at least as much to the dissemination of dengue fever as cities. Improving water supply and vector control in areas with a human population density critical for dengue transmission could increase the efficiency of control efforts. Please see later in the article for the Editors' Summary.",
"title": "Population Density, Water Supply, and the Risk of Dengue Fever in Vietnam: Cohort Study and Spatial Analysis"
}
] |
[
{
"docid": "18816720",
"text": "BACKGROUND Transmission of dengue viruses (DENV), the leading cause of arboviral disease worldwide, is known to vary through time and space, likely owing to a combination of factors related to the human host, virus, mosquito vector, and environment. An improved understanding of variation in transmission patterns is fundamental to conducting surveillance and implementing disease prevention strategies. To test the hypothesis that DENV transmission is spatially and temporally focal, we compared geographic and temporal characteristics within Thai villages where DENV are and are not being actively transmitted. METHODS AND FINDINGS Cluster investigations were conducted within 100 m of homes where febrile index children with (positive clusters) and without (negative clusters) acute dengue lived during two seasons of peak DENV transmission. Data on human infection and mosquito infection/density were examined to precisely (1) define the spatial and temporal dimensions of DENV transmission, (2) correlate these factors with variation in DENV transmission, and (3) determine the burden of inapparent and symptomatic infections. Among 556 village children enrolled as neighbors of 12 dengue-positive and 22 dengue-negative index cases, all 27 DENV infections (4.9% of enrollees) occurred in positive clusters (p < 0.01; attributable risk [AR] = 10.4 per 100; 95% confidence interval 1-19.8 per 100]. In positive clusters, 12.4% of enrollees became infected in a 15-d period and DENV infections were aggregated centrally near homes of index cases. As only 1 of 217 pairs of serologic specimens tested in positive clusters revealed a recent DENV infection that occurred prior to cluster initiation, we attribute the observed DENV transmission subsequent to cluster investigation to recent DENV transmission activity. Of the 1,022 female adult Ae. aegypti collected, all eight (0.8%) dengue-infected mosquitoes came from houses in positive clusters; none from control clusters or schools. Distinguishing features between positive and negative clusters were greater availability of piped water in negative clusters (p < 0.01) and greater number of Ae. aegypti pupae per person in positive clusters (p = 0.04). During primarily DENV-4 transmission seasons, the ratio of inapparent to symptomatic infections was nearly 1:1 among child enrollees. Study limitations included inability to sample all children and mosquitoes within each cluster and our reliance on serologic rather than virologic evidence of interval infections in enrollees given restrictions on the frequency of blood collections in children. CONCLUSIONS Our data reveal the remarkably focal nature of DENV transmission within a hyperendemic rural area of Thailand. These data suggest that active school-based dengue case detection prompting local spraying could contain recent virus introductions and reduce the longitudinal risk of virus spread within rural areas. Our results should prompt future cluster studies to explore how host immune and behavioral aspects may impact DENV transmission and prevention strategies. Cluster methodology could serve as a useful research tool for investigation of other temporally and spatially clustered infectious diseases.",
"title": "Spatial and Temporal Clustering of Dengue Virus Transmission in Thai Villages"
},
{
"docid": "8665891",
"text": "Dengue virus and its four serotypes (DENV 1-4) infect approximately 390 million people worldwide each year, with most cases in tropical and subtropical regions. Because of repeated introduction of DENV from epidemic regions and suitable weather conditions, many regions have shifted from hypo-endemicity to hyper-endemicity over recent decades. Since the first dengue outbreak in 1978, it is crucial to understand the current situation in China over nearly 40 years. The purpose of the study was to examine whether dengue in China was endemic or not, which is essential for relevant dengue control and prevention strategy implementation in China. The study, combining epidemiological characteristics of dengue from the disease notification system, phylogenetic and phylogeographic analyses, showed that all four serotypes had been detected in Guangzhou, China, which was dominated by DENV 1-2. The Maximum Likelihood tree analytic results showed that the virus detected in Guangzhou localized in different clades, except of virus of 2002 and 2003 clustered together. There existed the mutual introductions between Guangzhou and Southeast Asia. Most of the viruses were imported from Southeast Asia and the sources of outbreaks in Guangzhou mainly originated from Thailand, Indonesia, and the Philippines. The study indicates that dengue in China still remains as an imported disease, with the possibility of localization.",
"title": "Dengue is still an imported disease in China: a case study in Guangzhou."
},
{
"docid": "15670968",
"text": "Many countries use the cost-effectiveness thresholds recommended by the World Health Organization's Choosing Interventions that are Cost-Effective project (WHO-CHOICE) when evaluating health interventions. This project sets the threshold for cost-effectiveness as the cost of the intervention per disability-adjusted life-year (DALY) averted less than three times the country's annual gross domestic product (GDP) per capita. Highly cost-effective interventions are defined as meeting a threshold per DALY averted of once the annual GDP per capita. We argue that reliance on these thresholds reduces the value of cost-effectiveness analyses and makes such analyses too blunt to be useful for most decision-making in the field of public health. Use of these thresholds has little theoretical justification, skirts the difficult but necessary ranking of the relative values of locally-applicable interventions and omits any consideration of what is truly affordable. The WHO-CHOICE thresholds set such a low bar for cost-effectiveness that very few interventions with evidence of efficacy can be ruled out. The thresholds have little value in assessing the trade-offs that decision-makers must confront. We present alternative approaches for applying cost-effectiveness criteria to choices in the allocation of health-care resources.",
"title": "Thresholds for the cost–effectiveness of interventions: alternative approaches"
},
{
"docid": "39984099",
"text": "BACKGROUND New WHO guidelines recommend ART initiation for HIV-positive persons with CD4 cell counts ≤500 cells/µL, a higher threshold than was previously recommended. Country decision makers must consider whether to further expand ART eligibility accordingly. METHODS We used multiple independent mathematical models in four settings-South Africa, Zambia, India, and Vietnam-to evaluate the potential health impact, costs, and cost-effectiveness of different adult ART eligibility criteria under scenarios of current and expanded treatment coverage, with results projected over 20 years. Analyses considered extending eligibility to include individuals with CD4 ≤500 cells/µL or all HIV-positive adults, compared to the previous recommendation of initiation with CD4 ≤350 cells/µL. We assessed costs from a health system perspective, and calculated the incremental cost per DALY averted ($/DALY) to compare competing strategies. Strategies were considered 'very cost-effective' if the $/DALY was less than the country's per capita gross domestic product (GDP; South Africa: $8040, Zambia: $1425, India: $1489, Vietnam: $1407) and 'cost-effective' if $/DALY was less than three times per capita GDP. FINDINGS In South Africa, the cost per DALY averted of extending ART eligibility to CD4 ≤500 cells/µL ranged from $237 to $1691/DALY compared to 2010 guidelines; in Zambia, expanded eligibility ranged from improving health outcomes while reducing costs (i.e. dominating current guidelines) to $749/DALY. Results were similar in scenarios with substantially expanded treatment access and for expanding eligibility to all HIV-positive adults. Expanding treatment coverage in the general population was therefore found to be cost-effective. In India, eligibility for all HIV-positive persons ranged from $131 to $241/DALY and in Vietnam eligibility for CD4 ≤500 cells/µL cost $290/DALY. In concentrated epidemics, expanded access among key populations was also cost-effective. INTERPRETATION Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets. FUNDING The Bill and Melinda Gates Foundation and World Health Organization.",
"title": "Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models."
},
{
"docid": "457630",
"text": "Purpose To evaluate the global trends in health burden of people visually impaired from cataract in terms of disability-adjusted life years (DALY) and its correlations with national levels of socioeconomic development. Methods Global, regional, and national DALY numbers, crude rate, and age-standardized rate of cataract vision loss by age and sex were obtained from the database of the Global Burden of Disease Study 2015. The human development index, per capita gross domestic product, and other country-level data were derived from international open databases. Regression analysis was used to assess the correlations between age-standardized DALY rate and socioeconomic variables. Results The global DALY numbers of cataract vision loss increased by 89.42%, from 2048.18 (95%CI [confidence interval]: 1457.60-2761.80) thousands in 1990 to 3879.74 (95% CI: 2766.07-5232.43) thousands in 2015 (P < 0.001). Females had higher DALY number 315.83 (95%CI: 237.17-394.4) and crude rate 38.29 (95%CI: 35.35-41.23) after adjusting for age and country (all P < 0.001). The age-standardized DALY rate was higher in countries with low human development index (HDI), with 91.03 (95%CI: 73.04-108.75) for low HDI, 81.67 (95%CI: 53.24-108.82) for medium HDI, 55.89 (95%CI: 36.87-69.63) for high HDI, and 17.10 (95%CI: 13.91-26.84) for very high HDI countries (P < 0.01), respectively. The national age-standardized DALY rates in 2015 were negatively associated with both HDI (R2 = 0.489, P < 0.001) and per capita gross domestic product (R2 = 0.331, P < 0.001). Stepwise multiple regression showed that HDI was significantly correlated with national age-standardized DALY rates in 2015 after adjusting for other confounding factors (P < 0.001). Conclusions The global health burden of vision loss due to cataract increased between 1990 and 2015 despite considerable efforts from the World Health Organization and VISION 2020 initiatives.",
"title": "Variations and Trends in Health Burden of Visual Impairment Due to Cataract: A Global Analysis."
},
{
"docid": "10300888",
"text": "Whereas domestication of livestock, pets, and crops is well documented, it is still unclear to what extent microbes associated with the production of food have also undergone human selection and where the plethora of industrial strains originates from. Here, we present the genomes and phenomes of 157 industrial Saccharomyces cerevisiae yeasts. Our analyses reveal that today's industrial yeasts can be divided into five sublineages that are genetically and phenotypically separated from wild strains and originate from only a few ancestors through complex patterns of domestication and local divergence. Large-scale phenotyping and genome analysis further show strong industry-specific selection for stress tolerance, sugar utilization, and flavor production, while the sexual cycle and other phenotypes related to survival in nature show decay, particularly in beer yeasts. Together, these results shed light on the origins, evolutionary history, and phenotypic diversity of industrial yeasts and provide a resource for further selection of superior strains. PAPERCLIP.",
"title": "Domestication and Divergence of Saccharomyces cerevisiae Beer Yeasts"
},
{
"docid": "21003930",
"text": "BACKGROUND Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults. METHODS In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured. FINDINGS Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles. INTERPRETATION Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects. FUNDING British Heart Foundation.",
"title": "Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study"
},
{
"docid": "42387637",
"text": "RATIONALE Exposure to particulate air pollution has been related to increased hospitalization and death, particularly from cardiovascular disease. Lower blood DNA methylation content is found in processes related to cardiovascular outcomes, such as oxidative stress, aging, and atherosclerosis. OBJECTIVES We evaluated whether particulate pollution modifies DNA methylation in heavily methylated sequences with high representation throughout the human genome. METHODS We measured DNA methylation of long interspersed nucleotide element (LINE)-1 and Alu repetitive elements by quantitative polymerase chain reaction-pyrosequencing of 1,097 blood samples from 718 elderly participants in the Boston area Normative Aging Study. We used covariate-adjusted mixed models to account for within-subject correlation in repeated measures. We estimated the effects on DNA methylation of ambient particulate pollutants (black carbon, particulate matter with aerodynamic diameter < or = 2.5 microm [PM2.5], or sulfate) in multiple time windows (4 h to 7 d) before the examination. We estimated standardized regression coefficients (beta) expressing the fraction of a standard deviation change in DNA methylation associated with a standard deviation increase in exposure. MEASUREMENTS AND MAIN RESULTS Repetitive element DNA methylation varied in association with time-related variables, such as day of the week and season. LINE-1 methylation decreased after recent exposure to higher black carbon (beta = -0.11; 95% confidence interval [CI], -0.18 to -0.04; P = 0.002) and PM2.5 (beta = -0.13; 95% CI, -0.19 to -0.06; P < 0.001 for the 7-d moving average). In two-pollutant models, only black carbon, a tracer of traffic particles, was significantly associated with LINE-1 methylation (beta = -0.09; 95% CI, -0.17 to -0.01; P = 0.03). No association was found with Alu methylation (P > 0.12). CONCLUSIONS We found decreased repeated-element methylation after exposure to traffic particles. Whether decreased methylation mediates exposure-related health effects remains to be determined.",
"title": "Rapid DNA methylation changes after exposure to traffic particles."
},
{
"docid": "17454301",
"text": "A small, isolated outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) due to dengue virus type 2 (DEN-2) was documented in Santiago de Cuba on the island of Cuba beginning in January 1997. There were 205 DHF/DSS cases, all in persons older than age 15 years. All but three had evidence of a prior dengue infection, with the only known opportunity being the islandwide dengue virus type 1 (DEN-1) epidemic of 1977-1979. Virtually complete clinical and laboratory surveillance of overt disease was achieved. From December 1997 to January 1998, a random, age-stratified serum sample was obtained from 1,151 persons in 40 residential clusters in Santiago. Sera were tested for DEN-1 and DEN-2 neutralizing antibodies. The prevalence of DEN-2 antibodies in children age 15 years and under, born after the 1981 DEN-2 epidemic, was taken as the 1997 DEN-2 infection rate. This was adjusted slightly to accommodate observed cases, resulting in an estimated infection rate of 4.3%. Dengue fever and DHF/DSS attack rates were calculated from estimated total primary and secondary DEN-2 infections. Only 3% of 13,116 primary infections were overt. The DHF/DSS attack rate for adults of all ages was 420 per 10,000 secondary DEN-2 infections.",
"title": "Epidemiologic studies on Dengue in Santiago de Cuba, 1997."
},
{
"docid": "34074902",
"text": "Abstract Feline leukemia virus (FeLV), Gammaretrovirus, and feline immunodeficiency virus, a Lentivirus, are members of the family Retroviridae, and may establish persistent infections in the domestic cat (Felis catus). Cytoproliferative and cytosuppressive disorders may result from infection with these viruses. Morbidity and mortality rates are high in domestic cats worldwide. Infection of endangered neotropic small felids with these viruses could be devastating. To investigate the prevalence of FeLV and feline lentiviruses in neotropic small felids kept in captivity in São Paulo state, Brazil, serum samples from 104 animals belonging to the species Leopardus pardalis, Leopardus tigrinus, Leopardus wiedii, Herpailurus yaguarondi, and Oncifelis geoffroyi were tested for FeLV and feline lentiviruses by commercially available immunoassays. All results were negative, suggesting that retrovirus infection is not an important clinical problem in these populations. Because domestic cats in São Paulo city are naturally infected with these pathogens, and feral cats are commonly found in zoologic facilities in Brazil, preventive measures should be taken to avoid transmission of retroviruses to naive populations of wild and captive neotropic felids in Brazil.",
"title": "SEROSURVEY FOR FELINE LEUKEMIA VIRUS AND LENTIVIRUSES IN CAPTIVE SMALL NEOTROPIC FELIDS IN SÃO PAULO STATE, BRAZIL"
},
{
"docid": "11238951",
"text": "Kaposi's sarcoma-associated herpesvirus (KSHV), also termed human herpesvirus type 8, is consistently identified in Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. Here we report four cases of KSHV-bearing solid lymphomas that occurred in AIDS patients (cases 1 to 3) and in a human immunodeficiency virus (HIV)-seronegative person (case 4). The patients presented extranodal masses in the abdomen (cases 1, 3, and 4) or skin (case 2), and nodal involvement, together with Kaposi's sarcoma (case 3). The gastrointestinal tract was involved in two patients (cases 1 and 3). The patients did not develop a lymphomatous effusion. KSHV was detected in the tumor cells of all cases by immunohistochemistry and by polymerase chain reaction. Epstein-Barr virus was detected in two of the HIV-related cases. All KSHV-positive solid lymphomas exhibited PEL-like cell morphology. To investigate the relationship of these disorders to PEL and to other AIDS-associated diffuse large cell lymphomas, KSHV-positive solid lymphomas were tested for the expression of a set of genes that were previously shown by gene profiling analysis to define PEL tumor cells. The results showed that expression of this set of genes in KSHV-positive lymphomas is similar to that of PEL but distinct from KSHV-negative AIDS-associated diffuse large cell lymphomas. Because pathobiological features of KSHV-positive solid lymphomas closely mimic those of PEL, our results suggest that KSHV-positive solid lymphomas should be considered as a tissue-based variant of classical PEL, irrespective of HIV status.",
"title": "Kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8-positive solid lymphomas: a tissue-based variant of primary effusion lymphoma."
},
{
"docid": "301838",
"text": "The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we showed that emergence of the first cohorts of Aire(+) mTECs at this key developmental stage, prior to αβ T cell repertoire selection, was jointly directed by Rankl(+) lymphoid tissue inducer cells and invariant Vγ5(+) dendritic epidermal T cell (DETC) progenitors that are the first thymocytes to express the products of gene rearrangement. In turn, generation of Aire(+) mTECs then fostered Skint-1-dependent, but Aire-independent, DETC progenitor maturation and the emergence of an invariant DETC repertoire. Hence, our data attributed a functional importance to the temporal development of Vγ5(+) γδ T cells during thymus medulla formation for αβ T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire(+) mTEC maturation.",
"title": "Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire+ Medullary Epithelium"
},
{
"docid": "3662510",
"text": "OBJECTIVE To estimate the lost investment of domestically educated doctors migrating from sub-Saharan African countries to Australia, Canada, the United Kingdom, and the United States. DESIGN Human capital cost analysis using publicly accessible data. SETTINGS Sub-Saharan African countries. PARTICIPANTS Nine sub-Saharan African countries with an HIV prevalence of 5% or greater or with more than one million people with HIV/AIDS and with at least one medical school (Ethiopia, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe), and data available on the number of doctors practising in destination countries. MAIN OUTCOME MEASURES The financial cost of educating a doctor (through primary, secondary, and medical school), assuming that migration occurred after graduation, using current country specific interest rates for savings converted to US dollars; cost according to the number of source country doctors currently working in the destination countries; and savings to destination countries of receiving trained doctors. RESULTS In the nine source countries the estimated government subsidised cost of a doctor's education ranged from $21,000 (£13,000; €15,000) in Uganda to $58,700 in South Africa. The overall estimated loss of returns from investment for all doctors currently working in the destination countries was $2.17bn (95% confidence interval 2.13bn to 2.21bn), with costs for each country ranging from $2.16m (1.55m to 2.78m) for Malawi to $1.41bn (1.38bn to 1.44bn) for South Africa. The ratio of the estimated compounded lost investment over gross domestic product showed that Zimbabwe and South Africa had the largest losses. The benefit to destination countries of recruiting trained doctors was largest for the United Kingdom ($2.7bn) and United States ($846m). CONCLUSIONS Among sub-Saharan African countries most affected by HIV/AIDS, lost investment from the emigration of doctors is considerable. Destination countries should consider investing in measurable training for source countries and strengthening of their health systems.",
"title": "The financial cost of doctors emigrating from sub-Saharan Africa: human capital analysis"
},
{
"docid": "25738896",
"text": "The thymic transcription factor autoimmune regulator (Aire) prevents autoimmunity in part by promoting expression of tissue-specific self-antigens, which include many cancer antigens. For example, AIRE-deficient patients are predisposed to vitiligo, an autoimmune disease of melanocytes that is often triggered by efficacious immunotherapies against melanoma. Therefore, we hypothesized that Aire deficiency in mice may elevate immune responses to cancer and provide insights into how such responses might be triggered. In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1-specific T cells without affecting thymic numbers of regulatory T cells. Aire-deficient mice displayed elevated T-cell immune responses that were associated with suppression of melanoma outgrowth. Furthermore, transplantation of Aire-deficient thymic stroma was sufficient to confer more effective immune rejection of melanoma in an otherwise Aire wild-type host. Together, our work showed how Aire deficiency can enhance immune responses against melanoma and how manipulating TRP-1-specific T-cell negative selection may offer a logical strategy to enhance immune rejection of melanoma.",
"title": "Aire deficiency promotes TRP-1-specific immune rejection of melanoma."
},
{
"docid": "4561402",
"text": "Autoimmune polyendocrinopathy syndrome type 1 is a recessive Mendelian disorder resulting from mutations in a novel gene, AIRE, and is characterized by a spectrum of organ-specific autoimmune diseases. It is not known what tolerance mechanisms are defective as a result of AIRE mutation. By tracing the fate of autoreactive CD4+ T cells with high affinity for a pancreatic antigen in transgenic mice with an Aire mutation, we show here that Aire deficiency causes almost complete failure to delete the organ-specific cells in the thymus. These results indicate that autoimmune polyendocrinopathy syndrome 1 is caused by failure of a specialized mechanism for deleting forbidden T cell clones, establishing a central role for this tolerance mechanism.",
"title": "Aire regulates negative selection of organ-specific T cells"
},
{
"docid": "3716075",
"text": "BACKGROUND Dengue is the most common arbovirus infection globally, but its burden is poorly quantified. We estimated dengue mortality, incidence, and burden for the Global Burden of Disease Study 2013. METHODS We modelled mortality from vital registration, verbal autopsy, and surveillance data using the Cause of Death Ensemble Modelling tool. We modelled incidence from officially reported cases, and adjusted our raw estimates for under-reporting based on published estimates of expansion factors. In total, we had 1780 country-years of mortality data from 130 countries, 1636 country-years of dengue case reports from 76 countries, and expansion factor estimates for 14 countries. FINDINGS We estimated an average of 9221 dengue deaths per year between 1990 and 2013, increasing from a low of 8277 (95% uncertainty estimate 5353-10 649) in 1992, to a peak of 11 302 (6790-13 722) in 2010. This yielded a total of 576 900 (330 000-701 200) years of life lost to premature mortality attributable to dengue in 2013. The incidence of dengue increased greatly between 1990 and 2013, with the number of cases more than doubling every decade, from 8·3 million (3·3 million-17·2 million) apparent cases in 1990, to 58·4 million (23·6 million-121·9 million) apparent cases in 2013. When accounting for disability from moderate and severe acute dengue, and post-dengue chronic fatigue, 566 000 (186 000-1 415 000) years lived with disability were attributable to dengue in 2013. Considering fatal and non-fatal outcomes together, dengue was responsible for 1·14 million (0·73 million-1·98 million) disability-adjusted life-years in 2013. INTERPRETATION Although lower than other estimates, our results offer more evidence that the true symptomatic incidence of dengue probably falls within the commonly cited range of 50 million to 100 million cases per year. Our mortality estimates are lower than those presented elsewhere and should be considered in light of the totality of evidence suggesting that dengue mortality might, in fact, be substantially higher. FUNDING Bill & Melinda Gates Foundation.",
"title": "The global burden of dengue: an analysis from the Global Burden of Disease Study 2013."
},
{
"docid": "23304931",
"text": "PURPOSE Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis. PATIENTS AND METHODS We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts. RESULTS The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL. CONCLUSION These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.",
"title": "Immunophenotypic analysis of AIDS-related diffuse large B-cell lymphoma and clinical implications in patients from AIDS malignancies consortium clinical trials 010 and 034"
},
{
"docid": "29134911",
"text": "An unusual human retrovirus was isolated from two patients with persistent generalized lymphadenopathy who originate from West-Central Africa and are currently residing in Belgium. Although the virus shared a number of the same biological and morphological properties as human immunodeficiency retrovirus type 1 (HIV-1) and HIV-2, significant antigenic differences could be demonstrated. Several of the viral proteins also differed in molecular weight from the corresponding HIV-1 and HIV-2 proteins. Partial chemical cleavage of the most highly conserved viral proteins resulted in patterns which differed from those of HIV-1 and HIV-2. Furthermore, nucleic acid hybridization experiments were capable of discriminating between the virus types. Sequence analysis of the viral U3 region revealed a unique enhancer organization not found in other immunodeficiency viruses. The data indicated that the new isolate is more closely related to HIV-1 than to HIV-2 but clearly differs in a number of important respects.",
"title": "Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of west-central African origin."
},
{
"docid": "34582256",
"text": "The object of this study was to assess the role of brown adipose tissue (BAT) and the sympathetic nervous system in the rise in heat production associated with endotoxin-induced fever. Oxygen consumption (VO2) was found to be significantly increased (28%) over a 4-h period after two doses of endotoxin (Escherichia coli lipopolysaccharide, 0.3 mg/100 g body wt) given 24 h apart. Injection of a mixed beta-adrenoceptor antagonist (propranolol) reduced VO2 by 14% in endotoxin-treated rats, whereas the selective beta 1- (atenolol) or beta 2- (ICI 118551) antagonists suppressed VO2 by 10%. These drugs did not affect VO2 in control animals. BAT thermogenic activity assessed from measurements of in vitro mitochondrial guanosine 5'-diphosphate (GDP) binding was elevated by 54% in interscapular BAT and by 171% in other BAT depots. Surgical denervation of one lobe of the interscapular depot prevented these responses. Endotoxin failed to stimulate GDP binding in rats fed protein-deficient diets. This may have been because BAT thermogenic activity was already elevated in control rats fed these diets or because endotoxin caused a marked suppression of food intake in the protein-deficient animals. The results indicate that sympathetic activation of BAT is involved in the thermogenic responses to endotoxin and that these can be modified by dietary manipulation.",
"title": "Involvement of sympathetic nervous system and brown fat in endotoxin-induced fever in rats."
},
{
"docid": "22414304",
"text": "There is little information about treatment outcome in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) treated under routine programme conditions in subsaharan Africa. A prospective study was carried out to determine treatment outcome in an unselected cohort of TB patients admitted to Zomba General Hospital, Malawi. Eight hundred and twenty-seven adult TB patients (451 men and 376 women) were registered between 1 July and 31 December 1995. Standardized treatment outcomes of treatment completion, death, default, and transfer to another district were assessed in relation to type of TB, human immunodeficiency virus (HIV) serostatus, age and gender. Two hundred and fifty-four patients (31%) died by the end of treatment, half of the deaths occurring in the first month. Death rates were 19% among 386 patients with smear-positive PTB, 46% among 211 patients with smear-negative PTB, and 37% among 230 patients with EPTB; 77% of the patients were HIV seropositive. Among new patients, HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.5; 95% confidence interval [95% CI] 1.6-3.8). Smear-negative patients had the highest death rates (HR 3.9; 95% CI 2.7-5.5 compared to smear-positive patients), followed by EPTB patients (HR 2.6, 95% CI 1.8-3.7 compared to smear-positive patients). Death rates increased with age but were similar in men and women. Adult patients in Malawi with smear-negative PTB and EPTB have low treatment completion and high death rates, related to high levels of HIV infection. National TB control programmes in areas of high HIV prevalence should no longer ignore treatment outcomes in patients with smear-negative PTB or EPTB.",
"title": "Treatment outcome of an unselected cohort of tuberculosis patients in relation to human immunodeficiency virus serostatus in Zomba Hospital, Malawi."
},
{
"docid": "10627801",
"text": "The DExD/H box RNA helicase retinoic acid-inducible gene I (RIG-I) and the melanoma differentiation-associated gene 5 (MDA5) are key intracellular receptors that recognize virus infection to produce type I IFN. A third helicase gene, Lgp2, is homologous to Rig-I and Mda5 but lacks a caspase activation and recruitment domain. We generated Lgp2-deficient mice and report that the loss of this gene greatly sensitizes cells to cytosolic polyinosinic/polycytidylic acid-mediated induction of type I IFN. However, negative feedback inhibition of IFN-beta transcription was found to be normal in the absence of LGP2, indicating that LGP2 is not the primary negative regulator of type I IFN production. Our data further indicate that Lgp2-/- mice exhibited resistance to lethal vesicular stomatitis virus infection, a virus whose replicative RNA intermediates are recognized specifically by RIG-I rather than by MDA5 to trigger the production of type I IFN. However, mice lacking LGP2 were observed to exhibit a defect in type I IFN production in response to infection by the encephalomyocarditis virus, the replication of which activates MDA5-dependent innate immune responses. Collectively, our data indicate a disparate regulatory role for LGP2 in the triggering of innate immune signaling pathways following RNA virus infection.",
"title": "Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses."
},
{
"docid": "5114282",
"text": "BACKGROUND Hepatitis C virus (HCV) is estimated to affect 130-180 million people worldwide. Although its origin is unknown, patterns of viral diversity suggest that HCV genotype 1 probably originated from West Africa. Previous attempts to estimate the spatiotemporal parameters of the virus, both globally and regionally, have suggested that epidemic HCV transmission began in 1900 and grew steadily until the late 1980s. However, epidemiological data suggest that the expansion of HCV may have occurred after the Second World War. The aim of our study was to elucidate the timescale and route of the global spread of HCV. METHODS AND FINDINGS We show that the rarely sequenced HCV region (E2P7NS2) is more informative for molecular epidemiology studies than the more commonly used NS5B region. We applied phylodynamic methods to a substantial set of new E2P7NS2 and NS5B sequences, together with all available global HCV sequences with information in both of these genomic regions, in order to estimate the timescale and nature of the global expansion of the most prevalent HCV subtypes, 1a and 1b. We showed that transmission of subtypes 1a and 1b \"exploded\" between 1940 and 1980, with the spread of 1b preceding that of 1a by at least 16 y (95% confidence interval 15-17). Phylogeographic analysis of all available NS5B sequences suggests that HCV subtypes 1a and 1b disseminated from the developed world to the developing countries. CONCLUSIONS The evolutionary rate of HCV appears faster than previously suggested. The global spread of HCV coincided with the widespread use of transfused blood and blood products and with the expansion of intravenous drug use but slowed prior to the wide implementation of anti-HCV screening. Differences in the transmission routes associated with subtypes 1a and 1b provide an explanation of the relatively earlier expansion of 1b. Our data show that the most plausible route of the HCV dispersal was from developed countries to the developing world. Please see later in the article for the Editors' Summary.",
"title": "The Global Spread of Hepatitis C Virus 1a and 1b: A Phylodynamic and Phylogeographic Analysis"
},
{
"docid": "6182947",
"text": "BACKGROUND Influenza A virus (IAV) infection primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. Recent studies have shown the importance of lung antioxidant defense systems against injury by IAV. Nuclear factor-erythroid 2 related factor 2 (Nrf2) activates the majority of antioxidant genes. METHODS Alveolar type II (ATII) cells and alveolar macrophages (AM) were isolated from human lungs not suitable for transplantation and donated for medical research. In some studies ATII cells were transdifferentiated to alveolar type I-like (ATI-like) cells. Alveolar epithelial cells were infected with A/PR/8/34 (PR8) virus. We analyzed PR8 virus production, influenza A nucleoprotein levels, ROS generation and expression of antiviral genes. Immunocytofluorescence was used to determine Nrf2 translocation and western blotting to detect Nrf2, HO-1 and caspase 1 and 3 cleavage. We also analyzed ingestion of PR8 virus infected apoptotic ATII cells by AM, cytokine levels by ELISA, glutathione levels, necrosis and apoptosis by TUNEL assay. Moreover, we determined the critical importance of Nrf2 using adenovirus Nrf2 (AdNrf2) or Nrf2 siRNA to overexpress or knockdown Nrf2, respectively. RESULTS We found that IAV induced oxidative stress, cytotoxicity and apoptosis in ATI-like and ATII cells. We also found that AM can ingest PR8 virus-induced apoptotic ATII cells (efferocytosis) but not viable cells, whereas ATII cells did not ingest these apoptotic cells. PR8 virus increased ROS production, Nrf2, HO-1, Mx1 and OAS1 expression and Nrf2 translocation to the nucleus. Nrf2 knockdown with siRNA sensitized ATI-like cells and ATII cells to injury induced by IAV and overexpression of Nrf2 with AdNrf2 protected these cells. Furthermore, Nrf2 overexpression followed by infection with PR8 virus decreased virus replication, influenza A nucleoprotein expression, antiviral response and oxidative stress. However, AdNrf2 did not increase IFN-λ1 (IL-29) levels. CONCLUSIONS Our results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies.",
"title": "Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus"
},
{
"docid": "25737507",
"text": "Feline Immunodeficiency Virus (FIV) is a Lentivirus responsible for an immunodeficiency like disease in domestic cats. Based on the genetic diversity of the V3-V5 region of env gene FIV is divided in five phylogenetic subtypes (A, B, C, D and E) with a world-wide distribution. To understand the subtype diversity of FIV in Portugal a serological survey was conducted during 1 year in the Veterinary Faculty Hospital, Lisbon, Portugal to identify seropositive animals. Two viral genomic regions were amplified by a nested PCR, sequenced and the phylogenetic relationships between 24 new Portuguese FIV sequences and other previously published FIV isolates were assessed. The introduction of these sequences induced a subclustering in subtype B including most of the new Portuguese sequences. Moreover, a new cluster emerged, with two highly divergent new sequences that might represent a new subtype. The study of these new FIV isolates showed the presence in Portugal of a unique viral population subclustering within subtype B and of sequences clearly divergent from the five known subtypes, providing a contribution for the understanding of FIV's genetic diversity.",
"title": "Phylogenetic analysis of Portuguese Feline Immunodeficiency Virus sequences reveals high genetic diversity."
},
{
"docid": "37643601",
"text": "Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide beta-barrel structure covers the fusion loop in E, preventing fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.",
"title": "The flavivirus precursor membrane-envelope protein complex: structure and maturation."
},
{
"docid": "25134146",
"text": "Hepatitis C virus (HCV) is frequently encountered in human immunodeficiency virus (HIV)-infected patients because of common routes of transmission. Previous studies suggested that HIV infection impaired the natural course of chronic hepatitis C, with a more rapid progression to cirrhosis. However, these studies did not assess the HIV infection impact on chronic hepatitis C by taking into account the risk factors for liver fibrosis progression: alcohol, sex, age at the contamination, and duration of HCV infection. We studied liver biopsy specimens of 2 groups of 58 patients that were infected by both HCV and HIV or by HCV alone. The 2 groups were matched according those risk factors, and liver biopsy responses were evaluated with the METAVIR items. The METAVIR activity was higher in HIV-positive than HIV-negative patients. Cirrhosis was more frequent: (1) in HIV-positive patients with CD4 < or = 200 cells/microL (45%) than in HIV-negative patients (10%) (P = .003), (2) in HIV-positive patients with CD4 < or = 200 cells/microL (45%) than in HIV-positive patients with CD4 > 200 cells/microL (17%) (P = .04). These differences, which were linked to HIV status, might be related to the enhanced HCV replication during HIV infection or other immune mechanisms that need further studies.",
"title": "Impact of human immunodeficiency virus infection on the histological features of chronic hepatitis C: a case-control study. The MULTIVIRC group."
},
{
"docid": "39559521",
"text": "The negative selection of self-reactive thymocytes depends on the expression of tissue-specific antigens by medullary thymic epithelial cells. The autoimmune regulator (Aire) protein plays an important role in turning on these antigens, and the absence of even one Aire-induced tissue-specific antigen in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, Aire protein has been detected in peripheral lymphoid organs, suggesting that peripheral Aire plays a complementary role here. In these peripheral sites, Aire was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. Furthermore, transgenic antigen expression in extrathymic Aire-expressing cells (eTACs) can mediate deletional tolerance, but the immunological relevance of Aire-dependent, endogenous tissue-specific antigens remains to be determined.",
"title": "Control of central and peripheral tolerance by Aire."
},
{
"docid": "12580014",
"text": "Expression of the intermediate filament protein keratin 17 (K17) is robustly upregulated in inflammatory skin diseases and in many tumors originating in stratified and pseudostratified epithelia. We report that autoimmune regulator (Aire), a transcriptional regulator, is inducibly expressed in human and mouse tumor keratinocytes in a K17-dependent manner and is required for timely onset of Gli2-induced skin tumorigenesis in mice. The induction of Aire mRNA in keratinocytes depends on a functional interaction between K17 and the heterogeneous nuclear ribonucleoprotein hnRNP K. Further, K17 colocalizes with Aire protein in the nucleus of tumor-prone keratinocytes, and each factor is bound to a specific promoter region featuring an NF-κB consensus sequence in a relevant subset of K17- and Aire-dependent proinflammatory genes. These findings provide radically new insight into keratin intermediate filament and Aire function, along with a molecular basis for the K17-dependent amplification of inflammatory and immune responses in diseased epithelia.",
"title": "Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes"
},
{
"docid": "23073816",
"text": "Allogeneic umbilical cord blood (UCB) has therapeutic potential for cerebral palsy (CP). Concomitant administration of recombinant human erythropoietin (rhEPO) may boost the efficacy of UCB, as it has neurotrophic effects. The objectives of this study were to assess the safety and efficacy of allogeneic UCB potentiated with rhEPO in children with CP. Children with CP were randomly assigned to one of three parallel groups: the pUCB group, which received allogeneic UCB potentiated with rhEPO; the EPO group, which received rhEPO and placebo UCB; and the Control group, which received placebo UCB and placebo rhEPO. All participants received rehabilitation therapy. The main outcomes were changes in scores on the following measures during the 6 months treatment period: the gross motor performance measure (GMPM), gross motor function measure, and Bayley scales of infant development-II (BSID-II) Mental and Motor scales (18). F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) and diffusion tensor images (DTI) were acquired at baseline and followed up to detect changes in the brain. In total, 96 subjects completed the study. Compared with the EPO (n = 33) and Control (n = 32) groups, the pUCB (n = 31) group had significantly higher scores on the GMPM and BSID-II Mental and Motor scales at 6 months. DTI revealed significant correlations between the GMPM increment and changes in fractional anisotropy in the pUCB group. 18F-FDG-PET/CT showed differential activation and deactivation patterns between the three groups. The incidence of serious adverse events did not differ between groups. In conclusion, UCB treatment ameliorated motor and cognitive dysfunction in children with CP undergoing active rehabilitation, accompanied by structural and metabolic changes in the brain.",
"title": "Umbilical Cord Blood Therapy Potentiated with Erythropoietin for Children with Cerebral Palsy: A Double-blind, Randomized, Placebo-Controlled Trial"
},
{
"docid": "32827351",
"text": "Aqueous solutions of lead salts (1, 2) and saturated solutions of lead hydroxide (1) have been used as stains to enhance the electron-scattering properties of components of biological materials examined in the electron microscope. Saturated solutions of lead hydroxide (1), while staining more intensely than either lead acetate or monobasic lead acetate (l , 2), form insoluble lead carbonate upon exposure to air. The avoidance of such precipitates which contaminate surfaces of sections during staining has been the stimulus for the development of elaborate procedures for exclusion of air or carbon dioxide (3, 4). Several modifications of Watson's lead hydroxide stain (1) have recently appeared (5-7). All utilize relatively high pH (approximately 12) and one contains small amounts of tartrate (6), a relatively weak complexing agent (8), in addition to lead. These modified lead stains are less liable to contaminate the surface of the section with precipitated stain products. The stain reported here differs from previous alkaline lead stains in that the chelating agent, citrate, is in sufficient excess to sequester all lead present. Lead citrate, soluble in high concentrations in basic solutions, is a chelate compound with an apparent association constant (log Ka) between ligand and lead ion of 6.5 (9). Tissue binding sites, presumably organophosphates, and other anionic species present in biological components following fixation, dehydration, and plastic embedding apparently have a greater affinity for this cation than lead citrate inasmuch as cellular and extracellular structures in the section sequester lead from the staining solution. Alkaline lead citrate solutions are less likely to contaminate sections, as no precipitates form when droplets of fresh staining solution are exposed to air for periods of up to 30 minutes. The resultant staining of the sections is of high intensity in sections of Aralditeor Epon-embedded material. Cytoplasmic membranes, ribosomes, glycogen, and nuclear material are stained (Figs. 1 to 3). STAIN SOLUTION: Lead citrate is prepared by",
"title": "THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY"
}
] |
5ae5c1335542990ba0bbb2cf
|
Where is the American actor,who owns the school which Tallulah Harlech attended born in
|
[
{
"docid": "572438",
"text": "Lee Strasberg (born Israel Strasberg; November 17, 1901February 17, 1982) was a Polish-born American actor, director, and theatre practitioner. He was born in a part of Galicia, Austrian Poland, in what is now Ukraine. He co founded, with directors Harold Clurman and Cheryl Crawford, the Group Theatre in 1931, which was hailed as \"America's first true theatrical collective\". In 1951, he became director of the nonprofit Actors Studio in New York City, considered \"the nation's most prestigious acting school\", and in 1966, was involved in the creation of Actors Studio West in Los Angeles.",
"title": ""
},
{
"docid": "44632418",
"text": "Tallulah Harlech (born Tallulah Sylvia Ormsby-Gore; 16 May 1988) is an English model and actress. She is the daughter of Amanda Harlech and the late Francis Ormsby-Gore, 6th Baron Harlech. She was born in London and grew up in Shropshire as a vegan along with her bohemian cousins, the Raineys. In 2007 she went to New York City where she attended Lee Strasberg's school.",
"title": ""
}
] |
[
{
"docid": "44458637",
"text": "James Haynes (born August 9, 1960) is a former American football linebacker who played six seasons with the New Orleans Saints of the National Football League. He first enrolled at Coahoma Community College before transferring to Mississippi Valley State University. He attended Tallulah High School in Tallulah, Louisiana.",
"title": ""
},
{
"docid": "721031",
"text": "Paul Anthony Stewart is an American stage and television actor who is best known for portraying Danny Santos in the daytime soap opera \"Guiding Light\". Stewart was born Paul Anthony Tamaccio on February 23, 1970 in Philadelphia. He was raised in the nearby suburb of Wayne, Pennsylvania where he attended Radnor High School. Upon high school graduation Stewart attended prestigious Princeton University where he graduated with a degree in drama with an influence on dramatic literature.",
"title": ""
},
{
"docid": "19538977",
"text": "Garret T. Sato is an American actor who was born and raised in Oahu, Hawaii. He attended Aiea High School and Leeward Community College where he took up acting. He is \"Yonsei\" (四世) (fourth generation Japanese American). He currently resides in Los Angeles & Oahu, Hawaii.",
"title": ""
},
{
"docid": "24647186",
"text": "Nicholas Sadler is an American actor. Born in Minneapolis, Minnesota, he was raised in Apple Valley, Minnesota, where he attended Apple Valley High School. He was accepted into the Juilliard School's Drama Department while a senior in high school.",
"title": ""
},
{
"docid": "10073650",
"text": "Kentigan Peter \"Kent\" Riley (born 9 April 1984) is an English actor, born in Fazakerley, Liverpool, & brought up in Lydiate, where he attended St Gregory's Junior School, where he caught the bug for acting, starring in many of the schools performing arts projects. He went on to attend Maricourt Catholic High School in nearby Maghull.",
"title": ""
},
{
"docid": "9417453",
"text": "Troy Rutter (born August 1, 1973) is an American actor, author and programmer. He was born in Ames, Iowa where he attended Ames Senior High School and later Iowa State University where he earned a Bachelor of Arts in Journalism and Mass Communications.",
"title": ""
},
{
"docid": "35604272",
"text": "\"The Boy Who Owned a Melephant\" is a 1959 American film short directed by Saul Swimmer and featuring Tallulah Bankhead as narrator.",
"title": ""
},
{
"docid": "28086289",
"text": "Sean Michael O'Bryan (born September 10, 1963) is an American film and television actor from Louisville, Kentucky, where he attended and graduated from St. Xavier High School.",
"title": ""
},
{
"docid": "37314092",
"text": "Edward Adam Senn (born April 10, 1984) is an American model, actor and restaurateur. He studied theater as a child and through out high school. After high school Senn moved to NY to attend Atlantic Theater which he is an Alumni of. And has appeared in television shows, music videos and movies. He also owns a restaurant in New York City. Adam plays Zero a bisexual sociopath basketball player on VH1's \"Hit the Floor\".",
"title": ""
},
{
"docid": "7043850",
"text": "Mido Hamada (Egyptian Arabic: \"ميدو حمادة\" ; born 1971) is a German-Egyptian actor in film, theatre and television. He was born in Cairo; Egypt to an Egyptian family that moved to Germany, where he studied at the American Embassy School. He is fluent in German, English and Arabic. He attended the Oxford School of Drama and now lives in London.",
"title": ""
},
{
"docid": "36249642",
"text": "David Warren Gibson was born in Royal Oak, Michigan, the son of German-born Sonja Würfel, a ballerina from Leipzig, and Samuel Warren Gibson, an American diplomat for the U.S. Embassy in Berlin and the Hague. He has one brother, Stephan, who is an airline captain. His family moved to Minneapolis, Minnesota when he was 3 years old. David attended Westwood Jr. High School and studied art at the Minneapolis Art Institute. He had his first solo show of paintings when he was 13 at the Theater in the Round. At the same time, he started work at the Eleanor Moore Agency as a model for print ads. His family then moved to Dallas, Texas, where he attended Richardson High School. David acted in school plays and continued painting. He also studied dance in the evenings at S.M.U. After graduating from High School, his family moved to Houston, Texas, where David attended the University of St. Thomas and the University of Houston. He was also signed with a local male modeling agency doing print ads and runway work for fashion shows. The Wilhelmina Modeling Agency invited him to come to N.Y. city to sign with them. David took the opportunity and moved to N.Y. where he studied acting with Susan Batson from the Actors Studio, dance at the Joffrey Ballet School (New York City), and attended the Otis-Parsons School of Design.",
"title": ""
},
{
"docid": "35270349",
"text": "Patrick O'Kane is an Irish actor who was born in 1965 in Belfast, Northern Ireland. He attended St Malachy's grammar school where he discovered a love of acting and then attended Manchester University, graduating with double honours in Drama and English. This was followed by training at the Central School of Speech and Drama. He has been part of the companies of the Royal National Theatre, where he appeared in \"The Playboy of the Western World\" and \"Peer Gynt\", and the Royal Shakespeare Company, where he played the title role in \"Macbeth\". At the Royal Exchange Theatre, Manchester, he gave an \"eye-catching\", \"triumphant\" performance in the title role of Christopher Marlowe's \"Doctor Faustus\" in 2010.",
"title": ""
},
{
"docid": "27112692",
"text": "David M. Bloom (born 1954) is an American guitarist, flautist, composer/arranger, educator, author, and director. In 1975 Bloom founded the Bloom School of Jazz in Chicago where he continues to teach. Notable musicians who have attended the Bloom School include Ryan Cohan, Steve Rodby, Jon Weber, Cliff Colnot, and Rob Mazurek, with workshops from John Scofield and Mike Stern. Bloom authors jazz instruction books under his own Bloom School of Jazz Publishing which is distributed by Hal Leonard. Along with composing, arranging, writing, and running The Bloom School of Jazz, Bloom directs documentary films about essential human values. Bloom's father was the late educational psychologist Benjamin Bloom, who made major contributions to the classification of educational objectives and to the theory of mastery-learning. David Bloom's own applications of mastery-learning have made him one of the most sought after teachers in Jazz today.",
"title": ""
},
{
"docid": "15436595",
"text": "Dario Coates (born 25 April 1992, Hebden Bridge) is an English actor. He has so far portrayed the role of Alex Neeson in the television ITV soap Coronation Street. He attended Calder High School, where he studied for his GCSEs and A Levels, and also attends Calderdale Theatre School. His last role was Lord Asriel in Calderdale Theatre School's production of the Phillip Pullman novels His Dark Materials for which he received a roaring review from the local newspaper.",
"title": ""
},
{
"docid": "3740599",
"text": "Leo Cullen (born 9 January 1978) is an Irish former professional rugby union player who played at Lock for Leinster Rugby and Ireland. He was educated, firstly at Willow Park which is the junior school to Blackrock College where he attended secondary school. He attended University College Dublin after leaving school.",
"title": ""
},
{
"docid": "27650029",
"text": "Raymond Waring (born 21 July 1977) is an English actor. He was born in Liverpool and grew up in Runcorn, Cheshire, where he attended St. Chad's Secondary School. In 1994, he was accepted into the National Youth Theatre of Great Britain and, in 1997, attended the Guildhall School of Music & Drama. He also trained with the renowned Alain Knapp.",
"title": ""
},
{
"docid": "8545609",
"text": "Joshua Strickland (born October 23, 1983) is an American singer and actor from Charleston, South Carolina. He attended high school at the Charleston County School of the Arts and graduated from Middleton High School in Charleston. He attended the College of Charleston, where he studied voice with Deanna McBroom. During 5th grade Josh was \"discovered\" by teacher and Producer/Founder/CEO of The Charleston Youth Company, Chuck Long. He performed with this company for 8 years receiving drama, voice, and dance instruction. This company has been serving the talented students since 1978.",
"title": ""
},
{
"docid": "53767972",
"text": "Tallulah Morgan (b.1948) was the main plaintiff in the historical case Morgan v. Hennigan which led to the desegregation of the Boston school system in the 1970s.",
"title": ""
},
{
"docid": "2593084",
"text": "Joshua Seth (born December 2, 1968) is an American voice actor, magician, comedian, keynote speaker, mentalist, and entertainer. He was born in Kent, Ohio, and graduated from Theodore Roosevelt High School. As a child, Seth attended several experimental programs at Kent State University where he was admitted at the age of 8. Later, he attended Hampshire College as well as the New York University's film school Tisch School of the Arts where he trained as a performing artist he has lent his voice for many popular anime characters and he is also the best known for voicing as Taichi \"Tai\" Kamiya in \"Digimon Adventure\" series. He was also the announcer of \"Kids WB's Aftertoons Show\" block and \"Saturdays: Unleashed\" block. He has also recently stated on \"Did You Know Anime?\" on YouTube that he would reprise his role as Tai Kamiya's English voice actor in \"Digimon Fusion\", if Saban were to request his services. He is confirmed to be reprising his role as Tai in \"Digimon Adventure tri.\"",
"title": ""
},
{
"docid": "3882717",
"text": "Lara Custance (born 20 November 1992) is a New Zealand actress who appeared as Abi in the TV series Paradise Café. She is best known for her role as Harmony in The Tribe 'sister' series The New Tomorrow in which she acted alongside her brother Rafe Custance. She attended Chilton St James School but took time off school to film for \"Paradise Cafe\", which is currently broadcast in the UK on BBC and New Zealand television channels. She has a little sister called Lily who also attends Chilton Saint James School. She now attends the University of Auckland where she is studying a BA/BCom conjoint degree.",
"title": ""
},
{
"docid": "13333682",
"text": "Barnabas Root, born Fahma Yahny, (Sherbro Island, Sierra Leone, West Africa) was the grandson of an American-born slave who had moved to Africa through the efforts of the American Colonization Society. Yahny attended the original Mendi Mission school in Mendiland, Sierra Leone, where he was educated by Mary McIntosh, an alumna of Knox College, in Galesburg, Illinois, which was founded in the Calvinist tradition. The College and many of the Congregational churches of the city were active with the American Missionary Association.",
"title": ""
},
{
"docid": "14898098",
"text": "Ty Williams (born December 24, 1966) is an American film and television actor. Williams was born in Saginaw, Michigan, but grew up in the city of Shields in Michigan. Ty attended the Swan Valley High School, and then attended the Central Michigan University. He had moved to Los Angeles in 1998.",
"title": ""
},
{
"docid": "15267803",
"text": "Tallulah Falls School is a private boarding and day school located in the town of Tallulah Falls, Georgia, United States, within Habersham and Rabun Counties. The school is located on a wooded campus in northeast Georgia on the southern slopes of Cherokee Mountain at the foothills of the Appalachian chain. The school was founded in 1909 by Mary Ann Lipscomb of Athens.",
"title": ""
},
{
"docid": "8322081",
"text": "Nate Barlow (born Nathanael Jackson Barlow on July 6, 1975) is an American film director, actor, screenwriter and producer. Born in Middletown, Connecticut, to two musician and teaching parents, he spent two years as a child in Tanzania, where he attended the International School Moshi. He graduated with a Bachelor of Science in Electrical & Computer Engineering from Carnegie Mellon University in 1996, after which he worked as a designer engineer for Symbol Technologies on Long Island before moving to Los Angeles to pursue his filmmaking career.",
"title": ""
},
{
"docid": "10166400",
"text": "Jason Beghe (born March 12, 1960) is an American film and television actor. As a young man, he attended the Collegiate School in New York City, where he became best friends with John F. Kennedy, Jr., and David Duchovny. Beghe is married and lives in Los Angeles, California.",
"title": ""
},
{
"docid": "115664",
"text": "Tallulah is a small city in and the parish seat of Madison Parish in northeastern Louisiana, United States. The 2010 population was 7,335, a decrease of 1,854, or 20.2 percent, from the 9,189 tabulation at the 2000 census. The city is nearly 77 percent African American. Tallulah is the principal city of the Tallulah Micropolitan Statistical Area, which includes all of Madison Parish. The Madison Parish Sheriff's office operates the Steve Hoyle Rehabilitation Center in Tallulah.",
"title": ""
},
{
"docid": "4610471",
"text": "Caitlin Kinder Cahow (born May 20, 1985) is a former American ice hockey player. She attended the Foote School, where she graduated in 2000 and then attended the Hotchkiss School where she graduated in 2003 after playing soccer, field hockey, ice hockey and lacrosse.",
"title": ""
},
{
"docid": "3177075",
"text": "George \"Tip\" Thompson (born November 29, 1947) is an American former professional basketball player. A 6'2\" guard, he attended Erasmus Hall High School from which he graduated in 1965. He then attended Marquette University, where he played for coach Al McGuire.",
"title": ""
},
{
"docid": "6103136",
"text": "Daniel Kingsley Povenmire ( ; born September 18, 1963) is an American television director, writer, producer, storyboard artist, and voice actor associated with several animated television series, best known as the co-creator of the Disney animated series \"Phineas and Ferb\" in which he also voiced the show's villain, Heinz Doofenshmirtz, as well as Candace's deep voice in \"Jerk De Soleil\" and additional voices. Povenmire grew up in Mobile, Alabama, where he was a talented art student who spent summers outdoors and making movies. Povenmire attended the University of South Alabama before deciding to pursue a film career and transferring to the University of Southern California School of Cinematic Arts.",
"title": ""
},
{
"docid": "881673",
"text": "\"Men of Harlech\" or \"The March of the Men of Harlech\" (in Welsh: \"Rhyfelgyrch Gwŷr Harlech\") is a song and military march which is traditionally said to describe events during the seven-year siege of Harlech Castle between 1461 and 1468. Commanded by Constable Dafydd ap Ieuan, the garrison withstood the longest known siege in the history of the British Isles. \"Through Seven Years\" is an alternative name for the song. The song has also been associated with the earlier, briefer siege of Harlech Castle about 1408, which pitted the forces of Owain Glyndŵr against the future Henry V of England.",
"title": ""
}
] |
2692
|
Is it worth incorporating, when working in Canada as a contractor for an employer in the US?
|
[
{
"docid": "513051",
"text": "\"Interesting as I am in the exact same situations as yourself. I, in fact, just incorporated. You will be able \"\"save\"\" more in taxes in the end. The reason I put \"\"save\"\" in quotes, is that you don't necessarily save on taxes, but you can defer taxes. The driving factor behind this is that you specify your own fiscal calendar/year. Incorporating allows you to defer income for up to 6 months. Meaning that if you make your fiscal year starting in August or September, for example, you can claim that income on the following year (August + 6 months = February). It allows you to keep the current year taxes down. Also, any income left over at year end, is taxed at 15% (the Corporation rate) rather than the 30-40% personal rate you get with a sole-proprietorship. In a nutshell, with sole-proprietorship, all income is taxable (after write-offs)... in a corporation, you can take some of that income and keep it in the corporation (gives your company a \"\"value\"\"), and is only taxed at 15% - big saving there. I primarily work with US businesses. I am, however, a dual-citizen, US and Canadian, which allowed me as a sole-proprietor, to easily work with US companies. However, as a sole-proprietor or a Corporation, you simply need to get an EIN from the IRS and any US company will report earnings to that number, with no deductions. At year end, it is your responsibility to file the necessary tax forms and pay the necessary taxes to both countries. Therefore you can solicit new US business if you choose, but this is not restricted to corporations. The real benefit in incorporating is what I mentioned above. My suggestion to you is to speak with you CA, who can outline all benefits. Revenue Canada's website had some good information on this topic as well. Please let me know if you need anything else explained.\"",
"title": ""
}
] |
[
{
"docid": "209974",
"text": "They believe that it reduces the risk that Revenue Canada will deem you to be an employee and make them pay a whole pile of tax, EI, CPP and so on that should have been paid if you had been hired as an employee. It's my recollection that the employer gets dinged for both the employee and employer share of those withholdings (and generally the employer's share is larger than yours) so they really want to prevent it. There's a Revenue Canada publication about whether you're an employee or not. There's nothing on it about being incorporated, but still employers feel more protected when their contracts are incorporated. We did work as a sole proprietorship at the very beginning, so that we could deduct our losses against employment income earned earlier in the year, before we started the business. You can find clients who will take you on. We incorporated once the losses were over with (basically we had bought the equipment and office supplies we needed to get started.) It's a simple and relatively inexpensive thing to do, and gives clients a sense of protection. It won't protect you from your own poor decisions since you'll be a director of the firm.",
"title": ""
},
{
"docid": "506108",
"text": "\"LLC is, as far as I know, just a US thing, so I'm assuming that you are in the USA. Update for clarification: other countries do have similar concepts, but I'm not aware of any country that uses the term LLC, nor any other country that uses the single-member LLC that is disregarded for income tax purposes that I'm referring to here (and that I assume the recruiter also was talking about). Further, LLCs vary by state. I only have experience with California, so some things may not apply the same way elsewhere. Also, if you are located in one state but the client is elsewhere, things can get more complex. First, let's get one thing out of the way: do you want to be a contractor, or an employee? Both have advantage, and especially in the higher-income areas, contractor can be more beneficial for you. Make sure that if you are a contractor, your rate must be considerably higher than as employee, to make up for the benefits you give up, as well as the FICA taxes and your expense of maintaining an LLC (in California, it costs at least $800/year, plus legal advice, accounting, and various other fees etc.). On the other hand, oftentimes, the benefits as an employee aren't actually worth all that much when you are in high income brackets. Do pay attention to health insurance - that may be a valuable benefit, or it may have such high deductibles that you would be better off getting your own or paying the penalty for going uninsured. Instead of a 401(k), you can set up an IRA (update or various other options), and you can also replace all the other benefits. If you decide that being an employee is the way to go, stop here. If you decide that being a contractor is a better deal for you, then it is indeed a good idea to set up an LLC. You actually have three fundamental options: work as an individual (the legal term is \"\"sole proprietorship\"\"), form a single-member LLC disregarded for income tax purposes, or various other forms of incorporation. Of these, I would argue that the single-member LLC combines the best of both worlds: taxation is almost the same as for sole proprietorship, the paperwork is minimal (a lot less than any other form of incorporation), but it provides many of the main benefits of incorporating. There are several advantages. First, as others have already pointed out, the IRS and Department of Labor scrutinize contractor relationships carefully, because of companies that abused this status on a massive scale (Uber and now-defunct Homejoy, for instance, but also FedEx and other old-economy companies). One of the 20 criteria they use is whether you are incorporated or not. Basically, it adds to your legal credibility as a contractor. Another benefit is legal protection. If your client (or somebody else) sues \"\"you\"\", they can usually only sue the legal entity they are doing business with. Which is the LLC. Your personal assets are safe from judgments. That's why Donald Trump is still a billionaire despite his famous four bankruptcies (which I believe were corporate, not personal, bankrupcies). Update for clarification Some people argue that you are still liable for your personal actions. You should consult with a lawyer about the details, but most business liabilities don't arise from such acts. Another commenter suggested an E&O policy - a very good idea, but not a substitute for an LLC. An LLC does require some minimal paperwork - you need to set up a separate bank account, and you will need a professional accounting system (not an Excel spreadsheet). But if you are a single member LLC, the paperwork is really not a huge deal - you don't need to file a separate federal tax return. Your income will be treated as if it was personal income (the technical term is that the LLC is disregarded for IRS tax purposes). California still does require a separate tax return, but that's only two pages or so, and unless you make a large amount, the tax is always $800. That small amount of paperwork is probably why your recruiter recommended the LLC, rather than other forms of incorporation. So if you want to be a contractor, then it sounds like your recruiter gave you good advice. If you want to be an employee, don't do it. A couple more points, not directly related to the question, but hopefully generally helpful: If you are a contractor (whether as sole proprietor or through an LLC), in most cities you need a business license. Not only that, but you may even need a separate business license in every city you do business (for instance, in the city where your client is located, even if you don't live there). Business licenses can range from \"\"not needed\"\" to a few dollars to a few hundred dollars. In some cities, the business license fee may also depend on your income. And finally, one interesting drawback of a disregarded LLC vs. sole proprietorship as a contractor has to do with the W-9 form and your Social Security Number. Generally, when you work for somebody and receive more than $600/year, they need to ask you for your Social Security Number, using form W-9. That is always a bit of a concern because of identity theft. The IRS also recognizes a second number, the EIN (Employer Identification Number). This is basically like an SSN for corporations. You can also apply for one if you are a sole proprietor. This is a HUGE benefit because you can use the EIN in place of your SSN on the W-9. Instant identity theft protection. HOWEVER, if you have a disregarded LLC, the IRS says that you MUST use your SSN; you cannot use your EIN! Update: The source for that information is the W-9 instructions; it specifically only excludes LLCs.\"",
"title": ""
},
{
"docid": "593694",
"text": "\"1. What forms do I need to file to receive money from Europe None. Your client can pay you via wire transfer. They need to know your name, address, account number, and the name of your bank, its SWIFT number and its associated address. The addresses and names are required to make sure there are no typos in the numbers. 2. What forms do I need to file to pay people in Latin America (or any country outside the US) None. 1099s only need to be filled out when the contractor has a US tax ID. Make sure they are contractors. If they work for you for more than 2 years, that can create a problem unless they incorporate because they might look like \"\"employees\"\" to the IRS in which case you need to be reporting their identitites to the IRS via a W-8BEN form. Generally speaking any foreign contractor you have for more than 2 years should incorporate in their own country and you bill that corporation to prevent employee status from occurring. 3. Can I deduct payments I made to contractors from other countries as company expense Of course.\"",
"title": ""
},
{
"docid": "385320",
"text": "I do NOT know the full answer but I know here are some important factors that you need to consider : Do you have a physical location in the United States? Are you working directly from Canada? With a office/business location in the United States your tax obligation to the US is much higher. Most likely you will owe some to the state in which your business is located in Payroll Tax : your employer will likely want to look into Payroll tax, because in most states the payroll tax threshold is very low, they will need to file payroll tax on their full-time, part-time employees, as well as contractor soon as the total amount in a fiscal year exceeds the threshold Related to No.1 do you have a social security number and are you legally entitled to working in the States as an individual. You will be receiving the appropriate forms and tax withholding info Related to No.3 if you don't have that already, you may want to look into how to obtain permissions to conduct business within the United States. Technically, you are a one person consulting service provider. You may need to register with a particular state to obtain the permit. The agency will also be able to provide you with ample tax documentations. Chances are you will really need to piece together multiple information from various sources to resolve this one as the situation is specific. To start, look into consulting service / contractor work permit and tax info for the state your client is located in. Work from state level up to kick start your research then research federal level, which can be more complex as it is technically international business service for Canada-US",
"title": ""
},
{
"docid": "595919",
"text": "Successful technology contractors* make far more than employees. The contractor market is getting oversaturated because more people want to do it and employers like it less and less. Problem is, the only time big employers are willing to hire contractors are when they're really good, so you really only get well paid contractors who find consistent work, and then a flood of contractors that have to get whatever work they can find.",
"title": ""
},
{
"docid": "326329",
"text": "In the US we have social security taxes, where for a full time employee the company pays half and the employee pays half. When you work as a business, what we call 1099 for the form that the wages are reported on, then the contractor pays the full amount of social security tax. There are times when a contractor can negotiate a higher rate because the company does not have to pay that tax. However, most of the time the company just prefers to negotiate the rate based on your value. If you are a 60K year guy, then that is what they will pay you. From the company's perspective it does not matter what your tax rate is, only the value you can bring to the company. If you can add about 180K to the bottom line, then they will be happy to pay you 60K, and you should be happy to get it. Here in the US a contractor can expect to make about 7.5% more of an equivalent employee because of the social security tax savings to the company. However, not all companies are willing to provide that in compensation. Some companies see the legal and administrative costs of employees as normal, and the same costs with contractors as extra so they don't perceive a cost savings. There are other things that would preclude employers from giving the bump although it is logical to do so. First you will really have to feel out your employer for the attitude on the subject. Then I would make a logical case if they are open to providing extra compensation in return for tax savings. If I am an employee at 60K, you would also have to pay the government 18K. How about you pay me 75K as a contractor instead? That would be a great deal for all in the US.",
"title": ""
},
{
"docid": "586026",
"text": "Forms 1099 and W2 are mutually exclusive. Employers file both, not the employees. 1099 is filed for contractors, W2 is filed for employees. These terms are defined in the tax code, and you may very well be employee, even though your employer pays you as a contractor and issues 1099. You may complain to the IRS if this is the case, and have them explain the difference to the employer (at the employer's expense, through fines and penalties). Employers usually do this to avoid providing benefits (and by the way also avoid paying payroll taxes). If you're working as a contractor, lets check your follow-up questions: where do i pay my taxes on my hourly that means does the IRS have a payment center for the tax i pay. If you're an independent contractor (1099), you're supposed to pay your own taxes on a quarterly basis using the form 1040-ES. Check this page for more information on your quarterly payments and follow the links. If you're a salaried employee elsewhere (i.e.: receive W2, from a different employer), then instead of doing the quarterly estimates you can adjust your salary withholding at that other place of work to cover for your additional income. To do that you submit an updated form W4 there, check with the payroll department on details. Is this a hobby tax No such thing, hobby income is taxed as ordinary income. The difference is that hobby cannot be at loss, while regular business activity can. If you're a contractor, it is likely that you're not working at loss, so it is irrelevant. what tax do i pay the city? does this require a sole proprietor license? This really depends on your local laws and the type of work you're doing and where you're doing it. Most likely, if you're working from your employer's office, you don't need any business license from the city (unless you have to be licensed to do the job). If you're working from home, you might need a license, check with the local government. These are very general answers to very general questions. You should seek a proper advice from a licensed tax adviser (EA/CPA licensed in your state) for your specific case.",
"title": ""
},
{
"docid": "190011",
"text": "\">so I would like to ask you which, at this project, poor management skill of Oracle staffs or plan of Oregon are worse to be accused. **I believe there is an increased burden on the employer (Oregon) to effectively manage the scope of the work required for the project that the contractor (Oracle) is working on**. Otherwise, the contractor has plausible deniability for being able to provide deliver a quality working solution. >Or do you think that plan was made mainly by Oracle? I think the plan was **mostly made by Oracle with the requirements given by Oregon**, and that's where things seem messy. My gut tells me though that when an employer hires a contractor for the creation of a fully integrated enterprise system, that the employer essentially signs their financial life away to the project in a way that absolves the contractor of indirect or direct \"\"damages\"\" that come from the result of unforeseen implementation requirements or issues. Oracle has been around long enough to know how to legally cover their asses. If there is anything that Oregon may have traction on, it would be a few of their fraud claims, given that Oracle has made [two settlements](http://en.wikipedia.org/wiki/Oracle_corporation#Justice_Department_lawsuit) with federal agencies of ~$100 & ~$200 million since 2011 which were from allegations of fraud or false claims. Such claims by Oregon may be supported by the fact that they allegedly have a former Oracle employee who can substantiate the poor quality of the product they were giving to Oregon, but that blame might go back to Oregon's specifications which I have no insight into. As someone who has witnessed a couple of employer and contractor relationships between public & private entities, my hope out of all of this is that: * Sales people for contractors think twice before over-promising technology solutions that their company can't fully deliver on given resource constraints or lack of employer specifications. * Employers \"\"hiring\"\" such entities manage them, expectations, plus the overall project effectively while accepting personal accountability & responsibility. I think the only people who have a clear picture of what was going on were anyone from either party who were on the front lines of managing the project, developing the systems, or running them.\"",
"title": ""
},
{
"docid": "404429",
"text": "I'm not missing the point. Canada will still charge you/a corporation income taxes on worldwide income so long as you are resident in Canada. If you are incorporated in Canada but resident elsewhere, you are only subject to tax on Canadian-sourced income. In the US, where you are incorporated is the method of determining liability. Why is one method of determining jurisdiction correct and not the other? If you are a corporation residing in Canada, you still pay Canadian taxes on worldwide income, even if that income is sourced in another country.",
"title": ""
},
{
"docid": "406656",
"text": "\"My late answer is: Be aware of the difference of being a contractor and being an employee. I am not sure of the laws in Canada, but in the United States lots of small companies like to hire people as \"\"contractors\"\" but make them work under rules that fall into employee. The business is trying to avoid paying payroll taxes, which is fine, but make sure you know your rights and responsibilities as a contractor vs employee. You can check with your state's Bureau of Labor and Industry in the US, but I am sure wherever you are from there is a government agency to do the same thing.\"",
"title": ""
},
{
"docid": "524788",
"text": "\"Linkedlinked, You might want to seriously take another look at the links that Chris provided you. Specifically the ones on the IRS website: http://www.irs.gov/businesses/small/article/0,,id=99921,00.html From the IRS website: Businesses must weigh all these factors when determining whether a worker is an employee or independent contractor. Some factors may indicate that the worker is an employee, while other factors indicate that the worker is an independent contractor. There is no “magic” or set number of factors that “makes” the worker an employee or an independent contractor, and no one factor stands alone in making this determination. Also, factors which are relevant in one situation may not be relevant in another. The keys are to look at the entire relationship, consider the degree or extent of the right to direct and control, and finally, to document each of the factors used in coming up with the determination. Perhaps more importantly... pay attention to what happens if you're WRONG: Consequences of Treating an Employee as an Independent Contractor If you classify an employee as an independent contractor and you have no reasonable basis for doing so, you may be held liable for employment taxes for that worker (the relief provisions, discussed below, will not apply). See Internal Revenue Code section 3509 for more information. I would STRONGLY recommend that you and your partners give your accountant a call and discuss the matter. They will be able to help you make the right decision. One of biggest mistakes businesses make in this are is to classify their employees as independent contractors. The IRS (who happens to be hungry for money right now) comes in and says, \"\"Nooooooooo... those are employees.\"\" ...and the COMPANY gets to pay the employment taxes. I actually have person experience with this as I worked for a company this happened to. Every contractor was re-classified as an employee except for two (myself and one other). The key reason in that case was that none of the other contractors had any other clients. While I understand that you have other clients, I would still recommend talking to your accountant for an hour or so... just to be 100% sure. Sincerely, Andrew Smith TaxQueries.com\"",
"title": ""
},
{
"docid": "583817",
"text": "Software Contractors are not employees of the company that is procuring the software. Software Contractors necessarily work for another legal business entity. There is a business to business relationship between the procurer of the software and the entity producing the software. Therefore, the company procuring the software is not required to pay a minimum wage, or adhere to any other employment law. When any individual or company orders a software product and agrees to pay for it, that is a fixed priced contract. This happens millions of times a day. The amount of time taken to produce the software has no direct bearing on price. For instance, there is no minimum price for Microsoft Word based on the number of hours taken to produce it. Generally a Software Contractor will be a director and shareholder of a limited liability corporation. Directors are exempt from the standard protection offered under employment law. If the company producing the software was employing non-directors to produce the software, rather than sub-contracting to another business then employment law would apply.",
"title": ""
},
{
"docid": "44152",
"text": "Couple of points about being a consultant in the US: It sounds like the rules for what you can deduct may be more lax in Italy. For example, you can deduct a certain percentage of your home for work but the rules are relatively strict on your use of that space and how much is deductible. Also things like clothes, restaurants, phones, car use, etc must follow IRS guidelines to be deductible. This often means they are used exclusively for work and are required for work. A meal you eat by yourself is not generally deductible, for example. Any expense you would have had anyway if you were not working is generally not deductible. A contractor in the US can organize in various ways, including sole proprietorship, an S-corp, and a C-corp. Each has different tax and regulatory implications. In the simple case of a sole proprietorship, one must pay not only regular income tax but also self-employment tax, which is the part of social security and medicare tax normally paid for by one's employer. Estimated taxes must be paid to the government quarterly and then the actual amount due synced up at the end of the year (with the government sending you the difference or vice versa). Generally speaking contractors may set aside more money pre-tax for retirement and have better investment options. This is because solo 401(k) retirement accounts are cost-effective and flexible and the contractor can set aside the full $18K pre-tax as well as having the company contribute generously (pre-tax) to the retirement account. Contractors can also easily employ spouses and set aside even more. The details of how frequently you are paid as a contractor and how much notice (if any) the company must give you before terminating your relationship are negotiated between you and the company and are generally pretty flexible. You could get paid your whole year salary in a lump sum if you wanted. The company that is paying you will not normally give you any benefits whatsoever...in this way it is the same situation as it is in Italy. By the way the three points you mention in your edit are definitely not true in the US.",
"title": ""
},
{
"docid": "234436",
"text": "Another thing to consider, however, is the deductibility of business expenses. Let's assume that the employer can legitimately hire you as a 1099 contractor. (Would you be able to telecommute? Would you have a high degree of control over when you worked and when you didn't? These factors also affect whether you're a true independent 1099 contractor or not.) As a legit 1099 contractor, you're able to deduct certain business expenses directly from your income. (You can find a list of the rules at irs.gov.) As a W2 employee, by contrast, can deduct only business expenses that exceed 2% of the your AGI (adjusted gross income). So, you also have to consider your personal circumstances in making the calculus and comparing whether a legitimate 1099 contractor job is or is not good for you. It's not just a comparison of what they'd pay W2 employees versus what they'd pay 1099 contractors.",
"title": ""
},
{
"docid": "232544",
"text": "\"I agree that you should have received both a 1099 and a W2 from your employer. They may be reluctant to do that because some people believe that could trigger an IRS audit. The reason is that independent contractor vs employee is supposed to be defined by your job function, not by your choice. If you were a contractor and then switched to be an employee without changing your job description, then the IRS could claim that you should have always been an employee the entire time, and so should every one of the other contractors that work for that company with a similar job function. It's a hornet's nest that the employer may not want to poke. But that's not your problem; what should you do about it? When you say \"\"he added my Federal and FICA W/H together\"\", do you mean that total appears in box 4 of your 1099? If so, it sounds like the employer is expecting you to re-pay the employer portion of FICA. Can you ask them if they actually paid it? If they did, then I don't see them having a choice but to issue a W2, since the IRS would be expecting one. If they didn't pay your FICA, then the amount this will cost you is 7.65% of what would have been your W2 wages. IMHO it would be reasonable for you to request that they send you a check for that extra amount. Note: even though that amount will be less than $600 and you won't receive a 1099 in 2017 for it, legally you'll still have to pay tax on that amount so I think a good estimate would be to call it 10% instead. Depending on your personality and your relationship with the employer, if they choose not to \"\"make you whole\"\", you could threaten to fill out form SS-8. Additional Info: (Thank you Bobson for bringing this up.) The situation you find yourself in is similar to the concept of \"\"Contract-to-Hire\"\". You start off as a contractor, and later convert to an employee. In order to avoid issuing a 1099 and W2 to the same person in a single tax year, companies typically utilize one of the following strategies: Your particular situation is closest to situation 2, but the reverse. Instead of retroactively calling you a W2 employee the entire time, your employer is cheating and attempting to classify you as a 1099 contractor the entire time. This is frowned upon by the IRS, as well as the employee since as you discovered it costs you more money in the form of employer FICA. From your description it sounds like your employer was trying to do you a favor and didn't quite follow through with it. What they should have done was never switch you to W2 in the first place (if you really should have been a contractor), or they should have done the conversion properly without stringing you along.\"",
"title": ""
},
{
"docid": "424818",
"text": "In short - if you can't get the job without incorporating, then incorporate! Some clients will require you to be incorporated (which is why I did it 10 years ago). Essentially, for them, it's a way of distancing themselves from you to ensure they are not responsible for any monies if you don't pay your taxes. For you, there is also this idea of distancing company assets from your personal assets. If they are not requiring you to incorporate, you can simply act as a sole proprietorship. A good place to start reading up could be the sites below (for Canada/Ontario): Canada Business http://sbinfocanada.about.com/ http://sbinfocanada.about.com/od/incorporation/Incorporating_A_Business_In_Canada.htm http://sbinfocanada.about.com/cs/startup/a/incorporatadv.htm When I registered, I simply bought a book at Grand&Toy, with all the required forms for Ontario. These forms would also be available at a local Government service centre. You walk in, give the government money, and shortly thereafter you are incorporated. There are a number of others things that are required (having a minutes book, writing resolutions, creating shares, setting up a bank account, etc) - all discussed in the guide For Ontario you can start here: http://www.ontario.ca/en/services_for_business/index.htm At a high level, there are some costs for being incorporated, and some tax savings. At a minimum, costs would include: You may need the help of an account to help set things up, but it's quite easy to maintain all the records, etc that are required. Some other minor things I enjoy are writing myself expense cheques so that I get money back immediately (and effectively only pay 60% of the cost after writing it off in the company). I can decide how much to pay myself and push income from year to year.",
"title": ""
},
{
"docid": "375769",
"text": "Up until now I was looking at general European market and then dividing it up by sectors, but a country-specific distribution would also be a possibility, but I am afraid that the amount of work required to divide things up that much might be too much. Then again, it honestly might not. It could very well be that I'll come across this information during my research and if that's the case, it would certainly be worth incorporating into my paper. My intention is to take pieces of my thesis and turn them into separate specials for my employer to publish if my employer allows me to work on my thesis at work over the summer. We'll see. Hoping to be done by the end of September, so we'll see. I'll certainly be sure to keep the subreddit posted. My thesis will also certainly make it over to my [Scribd](http://www.scribd.com/dwietstruk).",
"title": ""
},
{
"docid": "468741",
"text": "If you want to subcontract some of your excess work to somebody else, you better be in business! While some kinds of employees (e.g. commissioned salespeople) are permitted to deduct some expenses on their income tax, generally only a real business can deduct wages for additional employees, or the cost of services provided by subcontractors. Do you invoice your clients and charge HST (GST)? Or do you tell your clients each pay period how many hours you worked and they compensate you through their payroll system like everybody else that walks through the door? If you're not invoicing and charging HST (GST) (assuming you exceed the threshold, and if you have too much work, you probably do!), then perhaps your clients are treating you as an employee – by default – and withholding taxes, CPP, and EI so they don't get in trouble? After all, Canada Revenue Agency is likely to consider any person providing a service to a company to be an employee unless there is sufficient evidence to the contrary, and when there isn't enough evidence, it's the company paying for the services that would be on the hook for unpaid taxes, CPP, and EI. Carefully consider what form of business you are operating, or were intending to operate. It's essential for your business to be structured appropriately if you want to hire or subcontract. You ought to be either self-employed as a sole proprietor, or perhaps incorporated if it makes more sense to your situation. Next, act accordingly. For instance, it's likely that your business should be taking care of the source deductions, CPP, and EI. In fact, self-employed individuals shouldn't even be paying into EI – an independent contractor wouldn't qualify to make an EI claim if they lost a contract. As an independent, one doesn't have a job, one has a business, and EI doesn't cover the business itself, only the employees that the business deals with at arm's length. As a business owner, you would be considered non-arms-length, and exempt from EI. Growing your business in the way that you are suggesting is an important enough a step that you should seek professional advice in advance. Find a good accountant that deals with self-employed individuals & small businesses and run all this by him. He should be able to guide you accordingly. Find a lawyer, too. A lawyer can guide you on how to properly subcontract others while protecting you and your business. Finally, be mindful of what it is you agreed to in your contract with your client: Do they expect all services to be performed by you, personally? Even if it wasn't written down who exactly would be performing the services, there may be an assumption it's you. Some negotiation may be in order if you want to use subcontractors.",
"title": ""
},
{
"docid": "37725",
"text": "\"Your comment to James is telling and can help us lead you in the right direction: My work and lifestyle will be the same either way, as I said. This is all about how it goes \"\"on the books.\"\" [emphasis mine] As an independent consultant myself, when I hear something like \"\"the work will be the same either way\"\", I think: \"\"Here thar be dragons!\"\". Let me explain: If you go the independent contractor route, then you better act like one. The IRS (and the CRA, for Canadians) doesn't take lightly to people claiming to be independent contractors when they operate in fact like employees. Since you're not going to be behaving any different whether you are an employee or a contractor, (and assuming you'll be acting more like an employee, i.e. exclusive, etc.), then the IRS may later make a determination that you are in fact an employee, even if you choose to go \"\"on the books\"\" as an independent contractor. If that happens, then you may find yourself retroactively denied many tax benefits you'd have claimed; and owe penalties and interest too. Furthermore, your employer may be liable for additional withholding taxes, benefits, etc. after such a finding. So for those reasons, you should consider being an employee. You will avoid the potential headache I outlined above, as well as the additional paperwork etc. of being a contractor. If on the other hand you had said you wanted to maintain some flexibility to moonlight with other clients, build your own product on the side, choose what projects you work on (or don't), maybe hire subcontractors, etc. then I'd have supported the independent contractor idea. But, just on the basis of the tax characteristics only I'd say forget about it. On the financial side, I can tell you that I wouldn't have become a consultant if not for the ability to make more money in gross terms (i.e. before tax and expenses.) That is: your top line revenues ought to be higher in order to be able to offset many of the additional expenses you'd incur as an independent. IMHO, the tax benefits alone wouldn't make up for the difference. One final thing to look at is Form SS-8 mentioned at the IRS link below. If you're not sure what status to choose, the IRS can actually help you. But be prepared to wait... and wait... :-/ Additional Resources:\"",
"title": ""
},
{
"docid": "139501",
"text": "\"There are a few sites out there that can give you some reasoning behind the request. LegalZoom, for instance. To quote the LZ doc in case the link dies: Employee vs. Independent Contractor If a worker is an employee, the employer is responsible for paying Social Security, unemployment insurance, Medicare, and possibly other costs like workers' compensation insurance for the employee; at the end of the tax year, the employer is responsible for compiling all necessary payroll reports, including W-2 forms. If a worker is an independent contractor, the employer is not responsible for any of the above taxes or payments, and the only added paperwork is the issuing of a 1099 to the independent contractor at the end of the tax year, if he or she has made more than $600 with the employer. As Kent suggested, you should speak with an attorney (really you need one if setting up an LLC). There are a lot of companies out there these days that try to classify people as contractors rather than full-time employees as it gets them out of paying benefits and dealing with taxes. This is being heavily cracked down on, and several \"\"contractor\"\" employees are winning lawsuits to get full-time status. If you are truly acting as a contractor, then setting up an LLC can help with a few items such as taxes and protection on certain business aspects (see comments below regarding this). It's easy and relatively cheap (cost me about $250 with extra legal advice tacked on). If you are reporting directly to a manager with the company, or really working in any way that isn't consistent with the definition of a contractor, then I'd turn down the offer and ask to be made a FT employee. Additional information: https://www.sba.gov/content/hire-contractor-or-employee\"",
"title": ""
},
{
"docid": "184977",
"text": "\"I made a throwaway for this... I work in IT for the government. I was tasked with finding a vendor that provided a particular kind of software. My bosses expected it would take me 4-6 months to source out companies, go through all the paperwork and process to work with them, try to get them to understand what we need, and them aid them in implementing their software on our stack. Well, that seemed like an enormous waste of time (and ridiculously boring), so instead I wrote the software on my own time over the course of 4 months, built a subscription model around it, and incorporated a company. I've since sold the subscription based model to a number of other government bodies and clients. The government body I work for has around 250 employees, and I recently sold a subscription to a peer government body with over 1500 employees. I built a free subscription tier that my current company uses so that i'm not taking any payment from them, to avoid any conflicts of interest, and built the entire project on my own time and resources. The funny thing is, the software product I built easily beat out all the competitors in blind tests, and no one that I work for could ever imagine that I am capable of even being employed by such a company, forget building the whole stack and founding the company. In fact, all of upper management has been impressed with the software I \"\"found\"\", and how well it has worked... there has been a ton of positive feedback on it since it was launched. I'm basically just sitting on this project (that is mostly self sustaining), until I can just cash out - which should be quite soon. **Edit** to the people warning me what i'm doing is illegal, a few key points - 1) The public sector can't legally profit from anything, my job is to limit cost, not make a profit... which leads to... - 2) I'm not charging the government body I work for, it's a free implementation devoid of contract. I also ensured I do all the work on my own time, not company time. I live somewhere where most government employees work multiple jobs, so this isn't uncommon. In fact, my government body actually does often hire contractors who are also employed. So not only did I create the service on my own time, I gave it to my employer for free (other companies pay, of course) - 3) I don't live in the US, things are different where I am. It is certainly not illegal, and I would even argue that (given this is the public sector) it is even somewhat ethical. My work saved my employer (the tax payer) a significant amount of money, which is a net positive. The service is of high quality, and I did not break any employment agreements or laws in the process. - 4) I hired a lawyer to double check everything. - 5) I absolutely am not in any way using any proprietary information for profit. I'm not even using my contacts through work as leverage for sales - everything so far has been cold calls and positive references from other clients. This was a key part of the project.\"",
"title": ""
},
{
"docid": "593197",
"text": "\"Can the companies from USA give job to me (I am from New Zealand)? Job as being employee - may be tricky. This depends on the labor laws in New Zealand, but most likely will trigger \"\"nexus\"\" clause and will force the employer to register in the country, which most won't want to do. Instead you can be hired as a contractor (i.e.: being self-employed, from NZ legal perspective). If so, what are the legal documents i have to provide to the USA for any taxes? If you're employed as a contractor, you'll need to provide form W8-BEN to your US employer on which you'll have to certify your tax status. Unless you're a US citizen/green card holder, you're probably a non-US person for tax purposes, and as such will not be paying any tax in the US as long as you work in New Zealand. If you travel to the US for work, things may become tricky, and tax treaties may be needed. Will I have to pay tax to New Zealand Government? Most likely, as a self-employed. Check how this works locally. As for recommendations, since these are highly subjective opinions that may change over time, they're considered off-topic here. Check on Yelp, Google, or any local NZ professional review site.\"",
"title": ""
},
{
"docid": "93638",
"text": "You need to clarify with Bob what your agreement is. If you and Bob are working together on these jobs as partners, you should get a written partnership agreement done by a lawyer who works with software industry entity formation. You can legally be considered a partnership if you are operating a business together, even if there is nothing in writing. The partnership will have its own tax return, and you each will be allocated 50% of the profits/losses (if that's what you agree to). This amount will be reported on your own individual 1040 as self-employment income. Since you have now lost all the expense deductions you would have taken on your Schedule C, and any home office deduction, it's a good idea to put language in the partnership agreement stating that the partnership will reimburse partners for their out-of-pocket expenses. If Bob is just hiring you as a contractor, you give him your SSN, and he issues you a 1099, like any other client. This should be a situation where you invoice him for the amount you are charging. Same thing with Joe - figure out if you're hiring him as an independent contractor, or if you have a partnership. Either way, you will owe income and self-employment tax on your profits. In the case of a partnership, the amount will be on the K-1 from the partnership return. For an independent contractor who's operating as a sole proprietor, you report the income you invoiced for and received, and deduct your expenses, including independent contractors that you hired, on your Schedule C. Talk to your tax guy about quarterly estimated payments. If you don't have a tax guy, go get one. Find somebody people in your city working in your industry recommend. A good tax person will save you more money than they cost. IRS Circular 230 Notice: Please note that any tax advice contained in this communication is not intended to be used, and cannot be used, by anyone to avoid penalties that may be imposed under federal tax law.",
"title": ""
},
{
"docid": "408124",
"text": "When you start at a new job here in the U.S., the default means of payment is usually a paper check. Most folks will quickly set up direct deposit so that their employer deposits their paycheck directly into their personal bank account - the incentive to do so is that you receive your funds faster than if you deposit a paper check. Even if you set up direct deposit on your first day on the job, you may still receive your first paycheck as a paper check simply because the wheels of payroll processing turn slowly at some (large) companies. A counter example is a self-employed contractor - perhaps a carpenter or house painter. These folks are paid by their customers, homeowners and such. Many larger, well established contracters now accept credit card payments from customers, but smaller independents may be reluctant to set up a credit card merchant account to accept payment by card because of all the fees that are associated with accepting credit card payments. 3% transaction fees and monthly service fees can be scary to any businessman who already has very thin profit margins. In such cases, these contractors prefer to be paid by check or in cash for the simple reason that there are no fees deducted from cash payments. There are a few folks here who don't trust direct deposit, or more specifically, don't trust their employer to perform the deposit correctly and on time. Some feel uncomfortable giving their bank info to their employer, fearing someone at the company could steal money from their account. In my experience, the folks who prefer a paper paycheck are often the same folks who rush to the bank on payday to redeem their paychecks for cash. They may have a bank account (helps with check cashing) but they prefer to carry cash. I operate in a manner similar to you - I use a debit card or credit card (I only have one of each) for nearly all transactions in daily life, I use electronic payments through my bank to pay my regular bills and mortgage, and I receive my paycheck by direct deposit. There have been periods where I haven't written or received paper checks for so long that I have to hunt for where I put my checkbook! Even though I use a debit card for most store purchases, the bank account behind that debit card is actually a checking account according to the bank. Again, the system defaults to paper checks and you have the option of going electronic as well. Before we judge anyone who doesn't use direct deposit or who prefers to be paid in cold hard cash, consider that direct deposit is a luxury of stability. Steady job, home, etc. Direct deposit doesn't make sense for a contractor or day laborer who expect to work for a different person each day or week. I don't think this is all that unique to the US. There are people in every city and country who don't have long-term employment with a single employer and therefore prefer cash or paper check over electronic payments. I'd be willing to bet that this applies to the majority of people on the planet, actually.",
"title": ""
},
{
"docid": "85229",
"text": "Insurance - get estimate from an insurance agent who works with policies for commercial real estate. See comments below regarding incorporation. Taxes - if this was basic income for a simple LLC, estimating 25-40% and adjusting over time might work. Rental property is a whole different prospect. Financial experts who specialize in rental properties would be a good source of advice, and worth the cost. See below regarding incorporating. Real estate appreciation - not something you can count on for developed property. Appreciation used to be almost guaranteed to at least keep up with inflation. Now property values are not even guaranteed to go up. Never have been but the general rule was improved real estate in good repair appreciated in price. Even if property values increase over time, rental properties depreciate. In fact, for rental properties, you can claim a certain rate of depreciation over time as an expense on taxes. This depreciation could mean selling for less than you paid for the property after a number of years, and owing capital gains taxes, since you would owe the difference between the depreciated value and the sale price. Related to taxes are local codes. Some areas require you to have a property management license to handle buildings with more than a certain number of units. If you are going to own rental properties, you should protect your private financial life by incorporating. Form a company. The company will own the property and hire any maintenance people or property managers or security staff or any similar employment activities. The company takes out the insurance and pays taxes. The company can pay you a salary. So, bottom line, you can have the company pay all the expenses and take all the risks. Then, assuming there's any money left after expenses, the company can pay you a manager's salary. That way if the worst happens and a tenant breaks their hip in the shower and sues you for ONE MILLION DOLLARS and wins, the company folds and you walk away. You might even consider two companies. One to own the property and lease it to a property management company. The property management company can then go bankrupt in case of some sort of liability issue, in which case you still keep the property, form a new management company, repaint and rename the property and move on. TL;DR: Get insurance advice from insurance agent before you buy. Same for taxes from an accountant. Get trained as a property manager if your local codes require it (might be a good idea anyway). Incorporate and have the company take all the risks.",
"title": ""
},
{
"docid": "30351",
"text": "I think the primary reason you're being down voted is because of the way you address people who align themselves with left wing ideology. Let's either call them all foolish, or none of them. I prefer calling them all foolish, one stream lined school of thought is rather repugnant. Anyway, Your points on equality are spot on (theoretically), handicapping applicants based on values that should already be overlooked is introducing a bias to correct another bias, it's a short term strategy and for what it's worth I agree with you. That is, I would if racism/classism/genderism didn't exist in practice. The problem is what is actually observed in the real world, all too often better candidates for a job are excluded in favor for those who are of similar religion or race as the employer, when the cast offs would perform better at the job. It is virtually never the other way around, where someone of a weaker skill set is forced on the job to fill a government implemented quota, and if it is the case, it is also usually done deliberately, choosing a very weak candidate to appeal to the government in attempts to exonerate themselves from those particular laws. My focus point: And sure it's your choice as an employer to bring on whoever you want, that's piece of mind for you, the employer, you've created the company that you wanted, but it's not the BEST IT COULD BE in terms of production purposes for society because the employer hasn't assembled the best possible work force with it's available applicants. It is here that we see there are negative externalities on the public, as inefficiency rises due to class/race/gender favoritism being chosen over ability. Employing people to help create your master vision fundamentally incorporates compromise, for the betterment of society.",
"title": ""
},
{
"docid": "65407",
"text": "\"While the other answers try to quantify the value of health care the question you ask is about employee vs contractor. The delta between those regarding benefits goes way beyond health care. In fact because almost every full time employee must have health care offered by their employer the option of \"\"you can have X with healthcare, or Y with no healthcare\"\" is no longer an option. I have seen situations in the last few years where employees who had no need for healthcare coverage (retired military) were offered additional vacation days to compensate for their lower cost to the employer. For employee vs contractor what is different isn't just healthcare. It also includes holidays, vacation days, sick days, employer portion of social security, education benefits, and 401k. Insurance benefits include not just healthcare but also dental, vision, short term and long term disability, and life insurance. The rule of thumb to cover all these benefits that are lost when you are a contractor is an amount equal to your income. Of course some of these benefits depend on single vs married and kids or not. But unless the rate they are paying the contractors is approaching twice the rate they are paying employees the contractor will be hard pressed to cover the missing benefits.\"",
"title": ""
},
{
"docid": "123753",
"text": "Here's an example (US, not Canada) that shows up to a 30% increase for first 6 months after a >30 day lapse, but the best data will come from actual quotes from insurers. If you can do without driving for 2 years it's almost certainly worth dropping coverage and a car for that duration and paying an increased insurance rate for a spell after the lapse. I'm not sure how it works in Canada, but when living with my parents they could not exclude me from their insurance once I was a licensed driver. The insurance company considered me to have access to all vehicles, so my presence increased insurance rates. If you live with your mother, you'll have to check with your insurer to see how that works.",
"title": ""
},
{
"docid": "250766",
"text": "The benefits and taxes thing, in my opinion is the biggie. Most people don't realize that the cost to the company for a full-time employee with benefits can be 2x or even 3x the amount they see in their paycheck. Health plans are extremely expensive. Even if you are having money taken from your check for health insurance, it is often just a fraction of the total cost, and the employer is subsidizing the rest. More expensive benefits that contractors don't typically get are 401K matches and paid vacation days. When contractors call in sick or don't work because it is a national holiday, they don't get paid for that day. Also, see that line on your paycheck deducting for Social security and Medicare? That is only half of the tax. The employer pays an equal amount that is not shown on that statement. Also, they pay taxes that go towards unemployment benefits , and may be required to pay higher taxes if they churn through a lot of full-time employees. You can usually let contractors go with relative impunity . For the unemployment tax reasons, not paying for people's days off or benefits, a lot less paperwork, and less risk to the business associated with committing to full-time employees all provide value to the company. Thus companies are willing to pay more because they are getting more. Think of it like a cell phone-contract. If you commit to a three year contract it can be a pain/expensive to get out of the deal early, but you will probably get a better rate in exchange for the risk being shifted to your end of the deal.",
"title": ""
},
{
"docid": "377941",
"text": "\"I'm a contractor, and I usually throw in a extra few hours for free during the week. A lot of us do. You want the employer to know that you're willing to put in the effort to help them succeed. On the other hand, if they asked me to work a specific amount of OT a week, I'd get time and a half. And most companies aren't going to work you 7 days a week,, 10 hours a day. Maybe around crunch time, but the rest of the time work is pretty normal. When my company's gearing up for a new project, I usually have a few weeks where work is minimal, and I have very little to do. I figure it balances out. Although I thought the end of the article was pretty funny. Like it was a high school guy saying \"\"Oh, yeah, well I knew a guy who worked so hard he dropped dead. So there!.\"\"\"",
"title": ""
}
] |
977
|
Pro-inflammatory cytokines are up regulated during tumor development.
|
[
{
"docid": "14075252",
"text": "Paraneoplastic thrombocytosis is associated with many solid tumors and often correlates with reduced survival. Recent studies suggest that a pathogenic feed back loop may be operative between platelets and tumor cells, with reciprocal interactions between tumor growth/metastasis and thrombocytosis/platelet activation. Specific molecular pathways have been identified in which tumors can stimulate platelet production and activation; activated platelets can, in turn, promote tumor growth and metastasis. Taken together, these findings provide exciting new potential targets for therapeutic intervention.",
"title": "Paraneoplastic thrombocytosis: the secrets of tumor self-promotion."
},
{
"docid": "39264456",
"text": "OBJECTIVES We investigated the role of cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in cachexia development in newly diagnosed nonsmall cell lung cancer (NSCLC) patients. METHODS : We evaluated 44 (M/F:41/3) NSCLC patients and 12 (M/F:10/2) age matched healthy smokers. NSCLC cases with a weight loss of > or =10% consisted the cachectic group (n:23, M/F:21/2) and the ones with <10% weight loss consisted the noncachectic group (n:21, M/F:19/2). RESULTS Body mass index (BMI) of cachectics was significantly lower than that of noncachectics (21.0 +/- 2.9 versus 24.5 +/- 3.6, P = 0.02) and controls (21.0 +/- 2.9 versus 25.5 +/- 2.6, P = 0.01). Serum TNF-alpha level did not differ between cachectic and noncachectics (37.3 +/- 39.1 and 51.6 +/- 84.2 pg/mL, respectively). However, it was significantly higher in NSCLC patients compared with controls (44.1 +/- 64.3 and 15.1 +/- 14.3 pg/mL, P = 0.03). Serum IL-6 level was not different between 3 groups (6.4 +/- 4.1, 8.9 +/- 16.3, and 4.1 +/- 3.5 pg/mL, respectively) but it correlated significantly with TNF-alpha (r = 0.4, P = 0.006) and BMI (r = -0.3, P = 0.03). Erythrocyte sedimentation rate (ESR) correlated significantly with TNF-alpha (r = 0.4, P = 0.003) and BMI (r = -0.3, P = 0.03). Among 44 cases, survival of 12 and 17 patients was recorded in cachectics and noncachectics, with no statistical difference (12.2 +/- 3.7 and 11.2 +/- 1.0 months, respectively). CONCLUSIONS TNF-alpha and IL-6 levels did not differ significantly between cachectics and noncachectics. However, significant correlations between IL-6, BMI, and TNF-alpha suggested that these cytokines acted as cofactors in weight loss. Survival was neither influenced by BMI, nor the cytokine levels in the present study. The significant correlation of ESR with TNF-alpha suggested that ESR could provide valuable clue for considerable weight loss in the follow-up of NSCLC patients.",
"title": "Impact of TNF-alpha and IL-6 levels on development of cachexia in newly diagnosed NSCLC patients."
}
] |
[
{
"docid": "8702697",
"text": "AIMS Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer-associated fibroblasts (CAFs) elicit a redox-dependent epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-κB pathway and enhancing tumor aggressiveness. Here, we investigated the involvement of microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to counteract oxidative stress and metastasis dissemination. RESULTS We found that miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to direct transcriptional repression by HIF-1, a known redox-sensitive transcription factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity, and metastatic dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding fibroblasts by reducing pro-inflammatory cytokine secretion. INNOVATION Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma. CONCLUSION The evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert the oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale for developing miRNA-based approaches to prevent and treat metastatic disease.",
"title": "miR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts."
},
{
"docid": "15521377",
"text": "Cellular senescence is a stable form of cell-cycle arrest which is thought to limit the proliferative potential of premalignant cells [1]. The senescence phenotype was initially described by Hayflick and Moorhead in 1961 on human fibroblasts undergoing replicative exhaustion in culture [2]. It has been shown that senescence can be triggered in different cell types in response to diverse forms of cellular damage or stress (for review see [1]). Importantly, while senescence was denounced as a tissue culture phenomenon for many years, recent in vivo studies demonstrated that cellular senescence represents a potent failsafe mechanism against tumorigenesis and contributes to the cytotoxicity of certain anticancer agents (see for example [3-7]). Interestingly, senescent cells have also been observed in certain aged or damaged tissues and there is growing evidence that senescence checkpoints can affect the regenerative reserve of tissues and organismal aging [8-11]. However, senescence may also have positive effects on organ maintenance by limiting pathological responses to acute forms of injury such as fibrotic scarring in response to chemical induced liver injury [12]. Over the past years it was also shown that senescent cells can communicate with their environment by secreting a myriad of cytokines and growth factors. Interestingly, this \"senescence associated secretory phenotype (SASP)\" seems to be a double edged sword regarding tumor initiation and maintenance: i) On the one hand, it has been shown that the SASP can have pro-tumorigenic effects. In an experimental system it was shown that senescent mesenchymal cells can enhance the tumorigenicity of surrounding breast cancer cells [13]. ii) Similarly, it is possible that the SASP enhances selection of transformed cell clones in aged organ systems. It has been shown that loss of proliferative competition of non-transformed cells can accelerate leukemogenesis [14]. It remains to be seen whether aberrant secretion of cytokines and growth factors by the SASP can accelerated this process in aged and chronically damage organ systems. iii) In contrast to its pro-tumorigenic aspect, the SASP could also have anti-tumor effects. A recent study showed that in a mosaic liver cancer mouse model the activation of p53 induced senescence, an upregulation of inflammatory cytokines, and activation of innate immune responses leading to tumour cell clearance [15]. iv) In further support that the SASP could have anti-tumor activities, a series of recent papers showed that components of the SASP can stabilize the senescence cell cycle arrest via an autoregulatory feedback loop [16,17] or induces apoptosis of tumor cells [18]. In addition to its effects on tumorigenesis, the SASP could also influence tissue aging. Studies on aging telomere dysfunctional mice have provided direct experimental evidence for an in vivo activation of the SASP in response to telomere dysfunction [19]. Interestingly, this in vivo SASP provoked alterations in stem cell differentiation (skewing of hematopoiesis towards reduction in lymphopoiesis and enhancement of myelopoiesis) that are also characteristic signs of human aging. Figure 1. Different cellular stresses can induce senescence including telomere shortening, DNA damage, and oncogene activation. Senescence of tumor cells ... In light of the many possible roles o the SASP in aging and carcinogenesis, it appears to be of utmost importance to decipher regulatory pathways controlling the SASP. In a current publication, Bhaumik et al. have identified 2 microRNAs (miR-146a/b) that negatively regulate the secretion of IL-6 and IL-8 - two of the SASP [20]. The authors show that these microRNAs are up-regulated at late stages of senescence, many days after a permanent cell cycle arrest has been established. Interestingly, the inhibitory miRs are most strongly up-regulated in senescence of cell lines that show a strong SASP but not in cell lines characterized by a weak SASP. The authors propose a new concept indicating that miRs 146a and b function in a negative feedback loop preventing an over-activation of the SASP in senescent cells. The authors present some initial data suggesting that activation of this negative feedback loop involves IL-1 receptor, IRAK-1, and NFκB signalling leading to an up-regulation of miRs-146a and b. A direct proof that this proposed feedback loop suppresses over-activation of the SASP remains to be demonstrated in future studies. The authors show that blockage of IL-1-receptor signalling prevents both the up-regulation of miRs-146a and b as well as Il-6 secretion. To confirm their new concept, it would be important to show that a selective blockage of miRs-146a and b results in over-activation of the SASP. The work by Bhaumik et al. places mir-146a/b as central players to control IL-6 and IL-8 expression within the SASP. MicroRNAs are emerging therapeutic targets because their expression levels can be effectively modulated via the use of antagomirs (see for example [21]). Also, for increasing microRNA expression, microRNAs can be delivered into cellsin vivo (see for example [22]). Therefore, it will be interesting to functionally test the impact of mir-146 inhibition on tumorigenesis and aging in relevant mouse models. Such studies will be of particular interest, as recent work showed that IL-6 secretion by senescent cells is relevant for initiating and maintaining the senescene response via an autocrine loop [17]. A reduction of miR-146 could increase IL-6 levels in senescent cells, which should stabilize the senescence program and reduce the risk of malignant transformation. Furthermore, it can be speculated that reduction of mir-146 a/b will increase NfκB activation via IRAK1. As NfκB is modulating the expression of various inflammation associated genes, this may also lead to increased clearance of senescent tumor cells by the innate immune system. However, it should be mentioned that Il-6 secreted by senescent cells can also act as a mitogen for surrounding cells, thus potentially increasing the risk of malignant transformation [13,17]. Besides its function in SASP modulation, miR-146 was also reported to target the mRNAs of the BRCA1 and BRCA2 tumor suppressors. In a recent study a G to C polymorphism in miR-146, which leads to an increased processing and release of the mature microRNA, can predict an early onset of breast cancer [23]. Taken together, the study of Bhaumik et al. opens an interesting new research area dealing with the gene regulatory mechanisms that control activation of the SASP. Given the diverse roles of the SASP in modulating tumor progression, immune surveillance of damaged cells, and the stabilization of the senescence arrest itself, it will be of great interest to analyse the influence of SASP regulatory pathways during aging and cancer.",
"title": "Keeping your senescent cells under control"
},
{
"docid": "6397191",
"text": "Endothelin-1 (ET-1) is the predominant endothelin isopeptide generated by the vascular wall and therefore appears to be the most important peptide involved in regulation of cardiovascular events. Many pathologic conditions are associated with elevations of ET-1 in the blood vessel wall. Because these conditions are often cytokine driven, we examined the effects of a mixture of cytokines on ET-1 production in human vascular smooth muscle cells (VSMCs) derived from internal mammary artery and saphenous vein (SV). Incubation of IMA and SV VSMCs with tumor necrosis factor-alpha (10 ng/ml) and interferon-gamma (1000 U/ml) in combination for up to 48 h markedly elevated the expression of mRNA for prepro-ET-1 and the release of ET-1 into the culture medium. This cytokine-stimulated release of ET-1 was inhibited by a series of dual endothelin-converting enzyme (ECE)/neutral endopeptidase inhibitors, phosphoramidon, CGS 26303, and CGS 26393, with an accompanying increase in big ET-1 release but with no effect on expression of mRNA for prepro-ET-1. These same compounds were 10 times more potent at inhibiting the conversion of exogenously applied big ET-1 to ET-1. ECE-1b/c mRNA is present in SV VSMCs, however no ECE-1a is present in these cells. Thus VSMCs most probably contain, like endothelial cells, an intracellular ECE responsible for the endogenous synthesis of ET-1. Under the influence of pro-inflammatory mediators the vascular smooth muscle can therefore become an important site of ET-1 production, as has already been established for the dilator mediators nitric oxide, prostaglandin I2, and prostaglandin E2.",
"title": "Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme."
},
{
"docid": "21382907",
"text": "Targeting of αVβ3 and αVβ5 integrins by cilengitide may reduce growth of solid tumors including head and neck squamous cell carcinoma (HNSCC). Preclinical investigations suggest increased activity of cilengitide in combination with other treatment modalities. The only published trial in HNSCC (ADVANTAGE) investigated cisplatin, 5-fluorouracil, and cetuximab (PFE) without or with once (PFE+CIL1W) or twice weekly cilengitide (PFE+CIL2W) in recurrent/metastatic HNSCC. ADVANTAGE showed good tolerability of the cilengitide arms and even lower adverse events (AEs) compared to PFE but not the benefit in overall survival expected based on preclinical data. As we found in the FLAVINO assay, a short-time ex vivo assay for prediction of chemosensitivity, only a subgroup of HNSCC had an increased suppressive effect of cilengitide containing combination therapies on colony formation of epithelial cells (CFec) and release of pro-angiogenetic and pro-inflammatory cytokines, whereas other HNSCC failed to respond. Response to αVβ3 and αVβ5 integrin targeting by cilengitide classifies HNSCC regarding outcome. We present FLAVINO data arguing for further development of cilengitide plus cetuximab in treatment of a subgroup of HNSCC potentially identified by the FLAVINO assay using a set of biomarkers for response evaluation.",
"title": "Reduced Cytokine Release in Ex Vivo Response to Cilengitide and Cetuximab Is a Marker for Improved Survival of Head and Neck Cancer Patients"
},
{
"docid": "16488405",
"text": "Physical activity induces a subclinical inflammatory response, mediated in part by leukocytes, and manifested by elevated concentrations of circulating proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). However, the source of the cytokines that appear during exercise remains unknown. In this study, we examined exercise-induced changes in plasma cytokine concentrations and their corresponding mRNA expression in peripheral blood mononuclear cells. Ten healthy [peak oxygen uptake = 48.8 ± 6.5 (SD) ml · kg−1 · min−1] but untrained men [age = 25 ± 5 (SD) yr] undertook 3 h of exercise (cycling and inclined walking) at 60–65% peak oxygen uptake. Circulating leukocyte subset counts were elevated during and 2 h postexercise but returned to normal within 24 h. Plasma concentrations of IL-1β, IL-6, and TNF-α peaked at the end of exercise and remained elevated at 2 h (IL-6) and up to 24 h (IL-1β and TNF-α) postexercise. Cytokine gene expression in circulating mononucl...",
"title": "Downloaded from"
},
{
"docid": "4418070",
"text": "Regulatory T (Treg) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses. Foxp3 operates as a late-acting differentiation factor controlling Treg cell homeostasis and function, whereas the early Treg-cell-lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors. However, whether Foxo proteins act beyond the Treg-cell-commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1 and display reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1 nuclear exclusion. Mice with Treg-cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ∼300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings show that the evolutionarily ancient Akt–Foxo1 signalling module controls a novel genetic program indispensable for Treg cell function.",
"title": "Novel Foxo1-dependent transcriptional programs control Treg cell function"
},
{
"docid": "13070316",
"text": "Tumor angiogenesis is an essential process for supplying rapidly growing malignant tissues with essential nutrients and oxygen. An angiogenic switch allows tumor cells to survive and grow, and provides them access to vasculature resulting in metastatic disease. Monocyte-derived macrophages recruited and reprogrammed by tumor cells serve as a major source of angiogenic factors boosting the angiogenic switch. Tumor endothelium releases angiopoietin-2 and further facilitates recruitment of TIE2 receptor expressing monocytes (TEM) into tumor sites. Tumor-associated macrophages (TAM) sense hypoxia in avascular areas of tumors, and react by production of angiogenic factors such as VEGFA. VEGFA stimulates chemotaxis of endothelial cells (EC) and macrophages. In some tumors, TAM appeared to be a major source of MMP9. Elevated expression of MMP9 by TAM mediates extracellular matrix (ECM) degradation and the release of bioactive VEGFA. Other angiogenic factors released by TAM include basic fibroblast growth factor (bFGF), thymidine phosphorylase (TP), urokinase-type plasminogen activator (uPA), and adrenomedullin (ADM). The same factors used by macrophages for the induction of angiogenesis [like vascular endothelial growth factor A (VEGF-A) and MMP9] support lymphangiogenesis. TAM can express LYVE-1, one of the established markers of lymphatic endothelium. TAM support tumor lymphangiogenesis not only by secretion of pro-lymphangiogenic factors but also by trans-differentiation into lymphatic EC. New pro-angiogenic factor YKL-40 belongs to a family of mammalian chitinase-like proteins (CLP) that act as cytokines or growth factors. Human CLP family comprises YKL-40, YKL-39, and SI-CLP. Production of all three CLP in macrophages is antagonistically regulated by cytokines. It was recently established that YKL-40 induces angiogenesis in vitro and in animal tumor models. YKL-40-neutralizing monoclonal antibody blocks tumor angiogenesis and progression. The role of YKL-39 and SI-CLP in tumor angiogenesis and lymphangiogenesis remains to be investigated.",
"title": "Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis"
},
{
"docid": "17223891",
"text": "NLRP12 is a member of the intracellular Nod-like receptor (NLR) family that has been suggested to downregulate the production of inflammatory cytokines, but its physiological role in regulating inflammation has not been characterized. We analyzed mice deficient in Nlrp12 to study its role in inflammatory diseases such as colitis and colorectal tumorigenesis. We show that Nlrp12-deficient mice are highly susceptible to colon inflammation and tumorigenesis, which is associated with increased production of inflammatory cytokines, chemokines, and tumorigenic factors. Enhanced colon inflammation and colorectal tumor development in Nlrp12-deficient mice are due to a failure to dampen NF-κB and ERK activation in macrophages. These results reveal a critical role for NLRP12 in maintaining intestinal homeostasis and providing protection against colorectal tumorigenesis.",
"title": "The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis."
},
{
"docid": "16863359",
"text": "Inflammasomes are multiprotein complexes that link pathogen recognition and cellular stress to the processing of the proinflammatory cytokine interleukin-1β (IL-1β). Whereas inflammasome-mediated activation is heavily studied in hematopoietic macrophages and dendritic cells, much less is known about microglia, resident tissue macrophages of the brain that originate from a distinct progenitor. To directly compare inflammasome-mediated activation in different types of macrophages, we isolated primary microglia and hematopoietic macrophages from adult, healthy rhesus macaques. We analyzed the expression profile of NOD (nucleotide-binding oligomerization domain)-like receptors, adaptor proteins, and caspases and characterized inflammasome activation and regulation in detail. We here demonstrate that primary microglia can respond to the same innate stimuli as hematopoietic macrophages. However, microglial responses are more persistent due to lack of negative regulation on pro-IL-1β expression. In addition, we show that while caspase 1, 4, and 5 activation is pivotal for inflammasome-induced IL-1β secretion by hematopoietic macrophages, microglial secretion of IL-1β is only partially dependent on these inflammatory caspases. These results identify key cell type-specific differences that may aid the development of strategies to modulate innate immune responses in the brain.",
"title": "Inflammasome-induced IL-1β secretion in microglia is characterized by delayed kinetics and is only partially dependent on inflammatory caspases."
},
{
"docid": "13231899",
"text": "Vaccines are largely ineffective for patients with established cancer, as advanced disease requires potent and sustained activation of CD8(+) cytotoxic T lymphocytes (CTLs) to kill tumor cells and clear the disease. Recent studies have found that subsets of dendritic cells (DCs) specialize in antigen cross-presentation and in the production of cytokines, which regulate both CTLs and T regulatory (Treg) cells that shut down effector T cell responses. Here, we addressed the hypothesis that coordinated regulation of a DC network, and plasmacytoid DCs (pDCs) and CD8(+) DCs in particular, could enhance host immunity in mice. We used functionalized biomaterials incorporating various combinations of an inflammatory cytokine, immune danger signal, and tumor lysates to control the activation and localization of host DC populations in situ. The numbers of pDCs and CD8(+) DCs, and the endogenous production of interleukin-12, all correlated strongly with the magnitude of protective antitumor immunity and the generation of potent CD8(+) CTLs. Vaccination by this method maintained local and systemic CTL responses for extended periods while inhibiting FoxP3 Treg activity during antigen clearance, resulting in complete regression of distant and established melanoma tumors. The efficacy of this vaccine as a monotherapy against large invasive tumors may be a result of the local activity of pDCs and CD8(+) DCs induced by persistent danger and antigen signaling at the vaccine site. These results indicate that a critical pattern of DC subsets correlates with the evolution of therapeutic antitumor responses and provide a template for future vaccine design.",
"title": "In situ regulation of DC subsets and T cells mediates tumor regression in mice."
},
{
"docid": "29509926",
"text": "Membrane cholesterol modulates a variety of cell signaling pathways and functions. While cholesterol depletion by high-density lipoproteins (HDLs) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain elusive. Here we show overt pro-inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft disruption in murine and human primary macrophages in vitro. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I transgenic mice, which have elevated HDL levels. In line with these findings, the innate immune responses required for clearance of P. aeruginosa bacterial infection in lung were compromised in mice with low HDL levels. Expression analysis, ChIP-PCR, and combinatorial pharmacological and genetic intervention studies unveiled that both native and reconstituted HDL enhance Toll-like-receptor-induced signaling by activating a PKC-NF-κB/STAT1-IRF1 axis, leading to increased inflammatory cytokine expression. HDL's pro-inflammatory activity supports proper functioning of macrophage immune responses.",
"title": "High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-κB/STAT1-IRF1 Signaling."
},
{
"docid": "52925737",
"text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.",
"title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration"
},
{
"docid": "343052",
"text": "Curcumin, a major component of turmeric, has been shown to exhibit anti-oxidant and anti-inflammatory activities. The present study was performed to determine whether curcumin is efficacious against both collagen-induced arthritis (CIA) in mice and IL-1beta-induced activation in fibroblast-like synoviocytes (FLSs). DBA/1 mice were immunized with bovine type II collagen (CII) and treated with curcumin every other day for 2weeks after the initial immunization. For arthritis, we evaluated the incidence of disease and used an arthritis index based on paw thickness. In vitro proliferation of CII- or concanavalin A-induced splenic T cells was examined using IFN-gamma production. Pro-inflammatory cytokines TNF-alpha and IL-1beta were examined in the mouse ankle joint and serum IgG1 and IgG2a isotypes were analyzed. The expression levels of prostaglandin E(2) (PGE(2)), cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) in human FLSs were also determined. The results showed that compared with untreated CIA mice, curcumin-treated mice downregulated clinical arthritis score, the proliferation of splenic T cells, expression levels of TNF-alpha and IL-1beta in the ankle joint, and expression levels of IgG2a in serum. Additionally, by altering nuclear factor (NF)-kappaB transcription activity in FLSs, curcumin inhibited PGE(2) production, COX-2 expression, and MMP secretion. These results suggest that curcumin can effectively suppress inflammatory response by inhibiting pro-inflammatory mediators and regulating humoral and cellular immune responses.",
"title": "Curcumin attenuates inflammatory response in IL-1beta-induced human synovial fibroblasts and collagen-induced arthritis in mouse model."
},
{
"docid": "6144969",
"text": "Virally induced inflammatory responses, beta cell destruction and release of beta cell autoantigens may lead to autoimmune reactions culminating in type 1 diabetes. Therefore, viral capability to induce beta cell death and the nature of virus-induced immune responses are among key determinants of diabetogenic viruses. We hypothesised that enterovirus infection induces a specific gene expression pattern that results in islet destruction and that such a host response pattern is not shared among all enterovirus infections but varies between virus strains. The changes in global gene expression and secreted cytokine profiles induced by lytic or benign enterovirus infections were studied in primary human pancreatic islet using DNA microarrays and viral strains either isolated at the clinical onset of type 1 diabetes or capable of causing a diabetes-like condition in mice. The expression of pro-inflammatory cytokine genes (IL-1-α, IL-1-β and TNF-α) that also mediate cytokine-induced beta cell dysfunction correlated with the lytic potential of a virus. Temporally increasing gene expression levels of double-stranded RNA recognition receptors, antiviral molecules, cytokines and chemokines were detected for all studied virus strains. Lytic coxsackievirus B5 (CBV-5)-DS infection also downregulated genes involved in glycolysis and insulin secretion. The results suggest a distinct, virus-strain-specific, gene expression pattern leading to pancreatic islet destruction and pro-inflammatory effects after enterovirus infection. However, neither viral replication nor cytotoxic cytokine production alone are sufficient to induce necrotic cell death. More likely the combined effect of these and possibly cellular energy depletion lie behind the enterovirus-induced necrosis of islets.",
"title": "Enterovirus-induced gene expression profile is critical for human pancreatic islet destruction"
},
{
"docid": "43619625",
"text": "Activated T cells secrete multiple osteoclastogenic cytokines which play a major role in the bone destruction associated with rheumatoid arthritis. While the role of T cells in osteoclastogenesis has received much attention recently, the effect of T cells on osteoblast formation and activity is poorly defined. In this study, we investigated the hypothesis that in chronic inflammation activated T cells contribute to enhanced bone turnover by promoting osteoblastic differentiation. We show that T cells produce soluble factors that induce alkaline phosphatase activity in bone marrow stromal cells and elevated expression of mRNA for Runx2 and osteocalcin. This data indicate that T cell derived factors have the capacity to stimulate the differentiation of bone marrow stromal cells into the osteoblast phenotype. RANKL mRNA was undetectable under any conditions in highly purified bone marrow stromal cells. In contrast, RANKL was constitutively expressed in primary osteoblasts and only moderately up-regulated by activated T cell conditioned medium. Interestingly, both bone marrow stromal cells and osteoblasts expressed mRNA for RANK, which was strongly up-regulated in both cell types by activated T cell conditioned medium. Although, mRNA for the RANKL decoy receptor, osteoprotegerin, was also up-regulated by activated T cell conditioned medium, it's inhibitory effects may be mitigated by a simultaneous rise in the osteoprotegerin competitor TNF-related apoptosis-inducing ligand. Based on our data we propose that during chronic inflammation, T cells regulate bone loss by a dual mechanism involving both direct stimulation of osteoclastogenesis, by production of osteoclastogenic cytokines, and indirectly by induction of osteoblast differentiation and up-regulation of bone turnover via coupling.",
"title": "Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts."
},
{
"docid": "3475317",
"text": "Granulomas are the pathological hallmark of tuberculosis (TB). However, their function and mechanisms of formation remain poorly understood. To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased manner. Using laser-capture microdissection, mass spectrometry and confocal microscopy, we generated detailed molecular maps of human granulomas. We found that the centers of granulomas have a pro-inflammatory environment that is characterized by the presence of antimicrobial peptides, reactive oxygen species and pro-inflammatory eicosanoids. Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature. These findings are consistent across a set of six human subjects and in rabbits. Although the balance between systemic pro- and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma. From the protein and lipid snapshots of human and rabbit lesions analyzed here, we hypothesize that the pathologic response to TB is shaped by the precise anatomical localization of these inflammatory pathways during the development of the granuloma.",
"title": "Inflammatory signaling in human Tuberculosis granulomas is spatially organized"
},
{
"docid": "41877386",
"text": "CD4(+)CD25(+) regulatory T cells (T regs) play a major role in the maintenance of self-tolerance and immune suppression, although the mechanisms controlling T reg development and suppressor function remain incompletely understood. Herein, we provide evidence that Kruppel-like factor 10 (KLF10/TIEG1) constitutes an important regulator of T regulatory cell suppressor function and CD4(+)CD25(-) T cell activation through distinct mechanisms involving transforming growth factor (TGF)-beta1 and Foxp3. KLF10 overexpressing CD4(+)CD25(-) T cells induced both TGF-beta1 and Foxp3 expression, an effect associated with reduced T-Bet (Th1 marker) and Gata3 (Th2 marker) mRNA expression. Consistently, KLF10(-/-) CD4(+)CD25(-) T cells have enhanced differentiation along both Th1 and Th2 pathways and elaborate higher levels of Th1 and Th2 cytokines. Furthermore, KLF10(-/-) CD4(+)CD25(-) T cell effectors cannot be appropriately suppressed by wild-type T regs. Surprisingly, KLF10(-/-) T reg cells have reduced suppressor function, independent of Foxp3 expression, with decreased expression and elaboration of TGF-beta1, an effect completely rescued by exogenous treatment with TGF-beta1. Mechanistic studies demonstrate that in response to TGF-beta1, KLF10 can transactivate both TGF-beta1 and Foxp3 promoters, implicating KLF10 in a positive feedback loop that may promote cell-intrinsic control of T cell activation. Finally, KLF10(-/-) CD4(+)CD25(-) T cells promoted atherosclerosis by approximately 2-fold in ApoE(-/-)/scid/scid mice with increased leukocyte accumulation and peripheral pro-inflammatory cytokines. Thus, KLF10 is a critical regulator in the transcriptional network controlling TGF-beta1 in both CD4(+)CD25(-) T cells and T regs and plays an important role in regulating atherosclerotic lesion formation in mice.",
"title": "Kruppel-like factor KLF10 targets transforming growth factor-beta1 to regulate CD4(+)CD25(-) T cells and T regulatory cells."
},
{
"docid": "25726838",
"text": "The role of immune responses in tumor development is a central issue for tumor biology and immunology. IL-17 is an important cytokine for inflammatory and autoimmune diseases. Although IL-17-producing cells are detected in cancer patients and tumor-bearing mice, the role of IL-17 in tumor development is controversial, and mechanisms remain to be fully elucidated. In the current study, we found that the development of tumors was inhibited in IL-17R-deficient mice. A defect in IFN-gammaR increased tumor growth, whereas tumor growth was inhibited in mice that were deficient in both IL-17R and IFN-gammaR compared with wild-type animals. Further experiments showed that neutralization of IL-17 by Abs inhibited tumor growth in wild-type mice, whereas systemic administration of IL-17 promoted tumor growth. The IL-17R deficiency increased CD8 T cell infiltration, whereas it reduced the infiltration of myeloid-derived suppressor cells (MDSCs) in tumors. In contrast, administration of IL-17 inhibited CD8 T cell infiltration and increased MDSCs in tumors. Further analysis indicated that IL-17 was required for the development and tumor-promoting activity of MDSCs in tumor-bearing mice. These data demonstrate that IL-17-mediated responses promote tumor development through the induction of tumor-promoting microenvironments at tumor sites. IL-17-mediated regulation of MDSCs is a primary mechanism for its tumor-promoting effects. The study provides novel insights into the role of IL-17 in tumor development and has major implications for targeting IL-17 in treatment of tumors.",
"title": "IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells."
},
{
"docid": "45449835",
"text": "Myelin-directed autoimmunity is considered to play a key role in the pathogenesis of multiple sclerosis (MS). Increased production of both pro- and anti-inflammatory cytokines is a common finding in MS. Interleukin-17 (IL-17) is a recently described cytokine produced in humans almost exclusively by activated memory T cells, which can induce the production of proinflammatory cytokines and chemokines from parenchymal cells and macrophages. In situ hybridisation with synthetic oligonucleotide probes was adopted to detect and enumerate IL-17 mRNA expressing mononuclear cells (MNC) in blood and cerebrospinal fluid (CSF) from patients with MS and control individuals. Numbers of IL-17 mRNA expressing blood MNC were higher in patients with MS and acute aseptic meningoencephalitis (AM) compared to healthy individuals. Higher numbers of IL-17 mRNA expressing blood MNC were detected in MS patients examined during clinical exacerbation compared to remission. Patients with MS had higher numbers of IL-17 mRNA expressing MNC in CSF compared to blood. This increase in numbers of IL-17 mRNA expressing MNC in CSF was not observed in patients with AM. Our results thus demonstrate increased numbers of IL-17 mRNA expressing MNC in MS with higher numbers in CSF than blood, and with the highest numbers in blood during clinical exacerbations.",
"title": "Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis."
},
{
"docid": "19130782",
"text": "Interferon-gamma (IFN-γ) is a pleiotropic molecule with associated antiproliferative, pro-apoptotic and antitumor mechanisms. This effector cytokine, often considered as a major effector of immunity, has been used in the treatment of several diseases, despite its adverse effects. Although broad evidence implicating IFN-γ in tumor immune surveillance, IFN-γ-based therapies undergoing clinical trials have been of limited success. In fact, recent reports suggested that it may also play a protumorigenic role, namely, through IFN-γ signaling insensitivity, downregulation of major histocompatibility complexes, and upregulation of indoleamine 2,3-dioxygenase and of checkpoint inhibitors, as programmed cell-death ligand 1. However, the IFN-γ-mediated responses are still positively associated with patient's survival in several cancers. Consequently, major research efforts are required to understand the immune contexture in which IFN-γ induces its intricate and highly regulated effects in the tumor microenvironment. This review discusses the current knowledge on the pro- and antitumorigenic effects of IFN-γ as part of the complex immune response to cancer, highlighting the relevance to identify IFN-γ responsive patients for the improvement of therapies that exploit associated signaling pathways.",
"title": "Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion"
},
{
"docid": "52865789",
"text": "OBJECTIVE IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues. METHODS Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells. RESULTS Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues. CONCLUSIONS Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.",
"title": "Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues"
},
{
"docid": "120626",
"text": "Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet β-cells — the cells that release insulin — failure to control blood glucose levels results. Abnormalities in β-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.",
"title": "Mechanisms linking obesity to insulin resistance and type 2 diabetes"
},
{
"docid": "21258863",
"text": "In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to tissue destruction and fibrosis, which causes much of the morbidity and mortality associated with this disease. Here we show the importance of IL-13 in the pathogenesis of schistosomiasis, and demonstrate, perhaps for the first time, the therapeutic efficacy of an IL-13 inhibitor, sIL-13Ralpha2-Fc, in the control of hepatic fibrosis. T-helper type 2 (Th2) cytokines dominate the immune response in mice infected with Schistosoma mansoni, yet the specific contributions of IL-13 and IL-4 to the development of fibrosis were not previously investigated. Our studies demonstrate that both cytokines play redundant roles in granuloma formation, which explains the ability of IL-4-deficient mice to form granulomas around eggs. More importantly, however, these studies demonstrate that IL-13 is the dominant Th2-type cytokine regulating fibrosis. IL-13 stimulated collagen production in fibroblasts, and procollagen I and procollagen III mRNA expression was decreased in sIL-13Ralpha2-Fc-treated mice. Moreover, the reduction in fibrosis observed in IL-4-deficient mice was much less pronounced than that in sIL-13Ralpha2-Fc-treated animals. Fibrosis is a major pathological manifestation of a number of allergic, autoimmune, and infectious diseases. Thus, our findings provide evidence that IL-13 inhibitors may be of general therapeutic benefit in preventing damaging tissue fibrosis resulting from Th2-dominated inflammatory responses.",
"title": "An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response."
},
{
"docid": "6944800",
"text": "Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.",
"title": "Microenvironmental regulation of tumor progression and metastasis"
},
{
"docid": "11328820",
"text": "The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.",
"title": "NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis."
},
{
"docid": "26068103",
"text": "RSV lower respiratory tract infections (LRTI) are among the most common diseases necessitating hospital admission in children. In addition to causing acute respiratory failure, RSV infections are associated with sequelae such as secondary bacterial infections and reactive airway disease. One characteristic host response observed in severe RSV-induced LRTI and/or subsequent development of asthma is increased expression of interleukin (IL)-10. However, contradictory results have been reported regarding whether IL-10 inhibits asthmatic responses or intensifies the disease. We aimed to reconcile these discordant observations by elucidating the role of IL-10 in regulating the host response to RSV LRTI. In this study, we used a lung-specific, inducible IL-10 over-expression (OE) transgenic mouse model to address this question. Our results showed that the presence of IL-10 at the time of RSV infection not only attenuated acute inflammatory process (i.e. 24 h post-infection), but also late inflammatory changes [characterized by T helper type 2 (Th2) cytokine and chemokine expression]. While this result appears contradictory to some clinical observations where elevated IL-10 levels are observed in asthmatic patients, we also found that delaying IL-10 OE until the late immune response to RSV infection, additive effects rather than inhibitory effects were observed. Importantly, in non-infected, IL-10 OE mice, IL-10 OE alone induced up-regulation of Th2 cytokine (IL-13 and IL-5) and Th2-related chemokine [monocyte chemoattractant protein 1 (MCP-1), chemokine (C-C motif) ligand 3 (CCL3) and regulated upon activation normal T cell expressed and secreted (RANTES)] expression. We identified a subset of CD11b(+)CD11c(+)CD49b(+)F4/80(-)Gr-1(-) myeloid cells as a prinicipal source of IL-10-induced IL-13 production. Therefore, the augmented pathological responses observed in our 'delayed' IL-10 over-expression model could be attributed to IL-10 OE alone. Taken together, our study indicated dual roles of IL-10 on RSV-induced lung inflammation which appear to depend upon the timing of when elevated IL-10 is expressed in the lung.",
"title": "Dual role of interleukin-10 in the regulation of respiratory syncitial virus (RSV)-induced lung inflammation."
},
{
"docid": "1454773",
"text": "The programmed death-1 (PD-1) receptor serves as an immunologic checkpoint, limiting bystander tissue damage and preventing the development of autoimmunity during inflammatory responses. PD-1 is expressed by activated T cells and downmodulates T-cell effector functions upon binding to its ligands, PD-L1 and PD-L2, on antigen-presenting cells. In patients with cancer, the expression of PD-1 on tumor-infiltrating lymphocytes and its interaction with the ligands on tumor and immune cells in the tumor microenvironment undermine antitumor immunity and support its rationale for PD-1 blockade in cancer immunotherapy. This report details the development and characterization of nivolumab, a fully human IgG4 (S228P) anti-PD-1 receptor-blocking monoclonal antibody. Nivolumab binds to PD-1 with high affinity and specificity, and effectively inhibits the interaction between PD-1 and its ligands. In vitro assays demonstrated the ability of nivolumab to potently enhance T-cell responses and cytokine production in the mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays. No in vitro antibody-dependent cell-mediated or complement-dependent cytotoxicity was observed with the use of nivolumab and activated T cells as targets. Nivolumab treatment did not induce adverse immune-related events when given to cynomolgus macaques at high concentrations, independent of circulating anti-nivolumab antibodies where observed. These data provide a comprehensive preclinical characterization of nivolumab, for which antitumor activity and safety have been demonstrated in human clinical trials in various solid tumors.",
"title": "In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates."
},
{
"docid": "30908508",
"text": "Objective: To investigate the regulation of CD4+CD25+ Regulatory T cells (Tregs) on pro-inflammatory adhesion molecules, Krüppel-Like Factor-2 (KLF-2) and its downstream transcriptional targets in human umbilical vein endothelial cells (HUVECs) impaired by ox-LDL and the mechanisms of it. Methods and results: HUVECs were cultured in the continuous presence of ox-LDL(0 mg/L,25 mg/L,50 mg/L,100 mg/L) for 4, 6, 12 and 24 hours to allow identification of early-and late-induced genes, respectively, whereas non-stimulated controls were taken at 0 hours. The expression of pro-inflammatory adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, KLF-2 and its target genes eNOS, PAI-1 were determined by real time RT-PCR and/or western-blot analysis. Expression of pro-inflammatory adhesion molecules, KLF-2, eNOS and PAI-1 in HUVEC cultured alone or with anti-CD3 mAbs activated Tregs, followed by addition of ox-LDL (50 mg/L) for 6 hours, are compared to expression levels in control cultures. Ox-LDL treated HUVECs increased pro-inflammatory adhesion molecules expression, as well as increased PAI-1 but decreased eNOS expression accompanied with significant downregulating of KLF-2 at a dose and time dependent manner. Furthermore, ox-LDL increased pro-inflammatory adhesion molecules but inhibited KLF2 expression was reversed by addition of Tregs. Small interfering RNA reduced endogenous KLF-2 expression and partly reversed the suppressive effect of Tregs on HUVECs activation, which strongly implicate KLF-2 as a transcriptional regulator of the Tregs-mediated effects in endothelial cells. Mechanism studies reveal that Treg-mediated KLF2 expression in HUVECs impaired by ox-LDL requires cell contact as well as soluble factors. Conclusions: Tregs could protect endothelial function that is largely dependent on KLF2 and its downstream transcriptional targets regulation involving cell-to-cell contact and soluble factors.",
"title": "CD4+CD25+Foxp3+Regulatory T Cells Protect Endothelial Function Impaired by Oxidized Low Density Lipoprotein via the KLF-2 Transcription Factor"
},
{
"docid": "3943235",
"text": "During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation.",
"title": "Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress"
},
{
"docid": "364522",
"text": "OBJECTIVES Calcific aortic valve (AV) disease is known to be an inflammation-related process. High-mobility group box-1 (HMGB1) protein and Toll-like receptor 4 (TLR4) have been reported to participate in several inflammatory diseases. The purpose of the present study was to determine whether the HMGB1-TLR4 axis is involved in calcific AV disease, and to evaluate the effect of HMGB1, and its potential mechanisms, on the pro-osteogenic phenotype change of valvular interstitial cells (VICs). METHODS Expression of HMGB1 and TLR4 in human calcific AVs was evaluated using immunohistochemical staining and immunoblotting. Cultured VICs were used as an in vitro model. The VICs were stimulated with HMGB1 for analysis, with versus without TLR4 small interfering ribonucleic acid (siRNA), c-Jun N-terminal kinase mitogen-activated protein kinase (JNK MAPK), and nuclear factor kappa-B (NF-κB) inhibitors. RESULTS Enhanced accumulation of HMGB1 and TLR4 was observed in calcific valves. Moreover, we found that HMGB1 induced high levels of pro-inflammatory cytokine production and promoted the osteoblastic differentiation and calcification of VICs. In addition, HMGB1 induced phosphorylation of JNK MAPK and NF-κB. However, these effects were markedly suppressed by siRNA silencing of TLR4. In addition, blockade of JNK MAPK and NF-κB phosphorylation prohibited HMGB1-induced production of pro-osteogenic factors, and mineralization of VICs. CONCLUSIONS The HMGB1 protein may promote osteoblastic differentiation and calcification of VICs, through the TLR4-JNK-NF-κB signaling pathway.",
"title": "High-mobility group box-1 protein induces osteogenic phenotype changes in aortic valve interstitial cells."
}
] |
717
|
Low nucleosome occupancy correlates with high methylation levels across species.
|
[
{
"docid": "17587795",
"text": "Dnmt1 epigenetically propagates symmetrical CG methylation in many eukaryotes. Their genomes are typically depleted of CG dinucleotides because of imperfect repair of deaminated methylcytosines. Here, we extensively survey diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present and catalyzed by a different DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged more than a billion years ago exhibit clustered methylation, specifically in nucleosome linkers. Clustered methylation occurs at unprecedented densities and directly disfavors nucleosomes, contributing to nucleosome positioning between clusters. Dense methylation is enabled by a regime of genomic sequence evolution that enriches CG dinucleotides and drives the highest CG frequencies known. Species with linker methylation have small, transcriptionally active nuclei that approach the physical limits of chromatin compaction. These features constitute a previously unappreciated genome architecture, in which dense methylation influences nucleosome positions, likely facilitating nuclear processes under extreme spatial constraints.",
"title": "Dnmt1-Independent CG Methylation Contributes to Nucleosome Positioning in Diverse Eukaryotes"
}
] |
[
{
"docid": "175735",
"text": "MOTIVATION The nucleosome is the basic repeating unit of chromatin. It contains two copies each of the four core histones H2A, H2B, H3 and H4 and about 147 bp of DNA. The residues of the histone proteins are subject to numerous post-translational modifications, such as methylation or acetylation. Chromatin immunoprecipitiation followed by sequencing (ChIP-seq) is a technique that provides genome-wide occupancy data of these modified histone proteins, and it requires appropriate computational methods. RESULTS We present NucHunter, an algorithm that uses the data from ChIP-seq experiments directed against many histone modifications to infer positioned nucleosomes. NucHunter annotates each of these nucleosomes with the intensities of the histone modifications. We demonstrate that these annotations can be used to infer nucleosomal states with distinct correlations to underlying genomic features and chromatin-related processes, such as transcriptional start sites, enhancers, elongation by RNA polymerase II and chromatin-mediated repression. Thus, NucHunter is a versatile tool that can be used to predict positioned nucleosomes from a panel of histone modification ChIP-seq experiments and infer distinct histone modification patterns associated to different chromatin states. AVAILABILITY The software is available at http://epigen.molgen.mpg.de/nuchunter/.",
"title": "Inferring nucleosome positions with their histone mark annotation from ChIP data"
},
{
"docid": "23208167",
"text": "Pioneer transcription factors (TFs) function as genomic first responders, binding to inaccessible regions of chromatin to promote enhancer formation. The mechanism by which pioneer TFs gain access to chromatin remains an important unanswered question. Here we show that PARP-1, a nucleosome-binding protein, cooperates with intrinsic properties of the pioneer TF Sox2 to facilitate its binding to intractable genomic loci in embryonic stem cells. These actions of PARP-1 occur independently of its poly(ADP-ribosyl) transferase activity. PARP-1-dependent Sox2-binding sites reside in euchromatic regions of the genome with relatively high nucleosome occupancy and low co-occupancy by other transcription factors. PARP-1 stabilizes Sox2 binding to nucleosomes at suboptimal sites through cooperative interactions on DNA. Our results define intrinsic and extrinsic features that determine Sox2 pioneer activity. The conditional pioneer activity observed with Sox2 at a subset of binding sites may be a key feature of other pioneer TFs operating at intractable genomic loci.",
"title": "Catalytic-Independent Functions of PARP-1 Determine Sox2 Pioneer Activity at Intractable Genomic Loci."
},
{
"docid": "22038539",
"text": "In mammals, caloric restriction consistently results in extended lifespan. Epigenetic information encoded by DNA methylation is tightly regulated, but shows a striking drift associated with age that includes both gains and losses of DNA methylation at various sites. Here, we report that epigenetic drift is conserved across species and the rate of drift correlates with lifespan when comparing mice, rhesus monkeys, and humans. Twenty-two to 30-year-old rhesus monkeys exposed to 30% caloric restriction since 7-14 years of age showed attenuation of age-related methylation drift compared to ad libitum-fed controls such that their blood methylation age appeared 7 years younger than their chronologic age. Even more pronounced effects were seen in 2.7-3.2-year-old mice exposed to 40% caloric restriction starting at 0.3 years of age. The effects of caloric restriction on DNA methylation were detectable across different tissues and correlated with gene expression. We propose that epigenetic drift is a determinant of lifespan in mammals. Caloric restriction has been shown to increase lifespan in mammals. Here, the authors provide evidence that age-related methylation drift correlates with lifespan and that caloric restriction in mice and rhesus monkeys results in attenuation of age-related methylation drift.",
"title": "Caloric restriction delays age-related methylation drift"
},
{
"docid": "7808055",
"text": "BACKGROUND It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. RESULTS I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. CONCLUSIONS I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.",
"title": "DNA methylation age of human tissues and cell types"
},
{
"docid": "18895793",
"text": "The relationship between chromatin structure and gene expression is a subject of intense study. The universal transcriptional activator Gal4 removes promoter nucleosomes as it triggers transcription, but how it does so has remained obscure. The reverse process, repression of transcription, has often been correlated with the presence of nucleosomes. But it is not known whether nucleosomes are required for that effect. A new quantitative assay describes, for any given location, the fraction of DNA molecules in the population that bears a nucleosome at any given instant. This allows us to follow the time courses of nucleosome removal and reformation, in wild-type and mutant cells, upon activation (by galactose) and repression (by glucose) of the GAL genes of yeast. We show that upon being freed of its inhibitor Gal80 by the action of galactose, Gal4 quickly recruits SWI/SNF to the genes, and that nucleosome \"remodeler\" rapidly removes promoter nucleosomes. In the absence of SWI/SNF, Gal4's action also results in nucleosome removal and the activation of transcription, but both processes are significantly delayed. Addition of glucose to cells growing in galactose represses transcription. But if galactose remains present, Gal4 continues to work, recruiting SWI/SNF and maintaining the promoter nucleosome-free despite it being repressed. This requirement for galactose is obviated in a mutant in which Gal4 works constitutively. These results show how an activator's recruiting function can control chromatin structure both during gene activation and repression. Thus, both under activating and repressing conditions, the activator can recruit an enzymatic machine that removes promoter nucleosomes. Our results show that whereas promoter nucleosome removal invariably accompanies activation, reformation of nucleosomes is not required for repression. The finding that there are two routes to nucleosome removal and activation of transcription-one that requires the action of SWI/SNF recruited by the activator, and a slower one that does not-clarifies our understanding of the early events of gene activation, and in particular corrects earlier reports that SWI/SNF plays no role in GAL gene induction. Our finding that chromatin structure is irrelevant for repression as studied here-that is, repression sets in as efficiently whether or not promoter nucleosomes are allowed to reform-contradicts the widely held, but little tested, idea that nucleosomes are required for repression. These findings were made possible by our nucleosome occupancy assay. The assay, we believe, will prove useful in studying other outstanding issues in the field.",
"title": "Activator Control of Nucleosome Occupancy in Activation and Repression of Transcription"
},
{
"docid": "4305576",
"text": "Chromatin allows the eukaryotic cell to package its DNA efficiently. To understand how chromatin structure is controlled across the Saccharomyces cerevisiae genome, we have investigated the role of the ATP-dependent chromatin remodelling complex Isw2 in positioning nucleosomes. We find that Isw2 functions adjacent to promoter regions where it repositions nucleosomes at the interface between genic and intergenic sequences. Nucleosome repositioning by Isw2 is directional and results in increased nucleosome occupancy of the intergenic region. Loss of Isw2 activity leads to inappropriate transcription, resulting in the generation of both coding and noncoding transcripts. Here we show that Isw2 repositions nucleosomes to enforce directionality on transcription by preventing transcription initiation from cryptic sites. Our analyses reveal how chromatin is organized on a global scale and advance our understanding of how transcription is regulated.",
"title": "Chromatin remodelling at promoters suppresses antisense transcription"
},
{
"docid": "18074797",
"text": "BACKGROUND Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. METHODS AND FINDINGS We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained. In two of the moderate-transmission settings (EIR approximately 43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR approximately 586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels. CONCLUSIONS Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required.",
"title": "Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies"
},
{
"docid": "4455466",
"text": "Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.",
"title": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression"
},
{
"docid": "13770184",
"text": "BACKGROUND The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING Bill & Melinda Gates Foundation.",
"title": "Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015"
},
{
"docid": "29788648",
"text": "NuA4, the major H4 lysine acetyltransferase (KAT) complex in Saccharomyces cerevisiae, is recruited to promoters and stimulates transcription initiation. NuA4 subunits contain domains that bind methylated histones, suggesting that histone methylation should target NuA4 to coding sequences during transcription elongation. We show that NuA4 is cotranscriptionally recruited, dependent on its physical association with elongating polymerase II (Pol II) phosphorylated on the C-terminal domain by cyclin-dependent kinase 7/Kin28, but independently of subunits (Eaf1 and Tra1) required for NuA4 recruitment to promoters. Whereas histone methylation by Set1 and Set2 is dispensable for NuA4's interaction with Pol II and targeting to some coding regions, it stimulates NuA4-histone interaction and H4 acetylation in vivo. The NuA4 KAT, Esa1, mediates increased H4 acetylation and enhanced RSC occupancy and histone eviction in coding sequences and stimulates the rate of transcription elongation. Esa1 cooperates with the H3 KAT in SAGA, Gcn5, to enhance these functions. Our findings delineate a pathway for acetylation-mediated nucleosome remodeling and eviction in coding sequences that stimulates transcription elongation by Pol II in vivo.",
"title": "NuA4 lysine acetyltransferase Esa1 is targeted to coding regions and stimulates transcription elongation with Gcn5."
},
{
"docid": "8502193",
"text": "Traits such as clutch size vary markedly across species and environmental gradients but have usually been investigated from either a comparative or a geographic perspective, respectively. We analyzed the global variation in clutch size across 5,290 bird species, excluding brood parasites and pelagic species. We integrated intrinsic (morphological, behavioural), extrinsic (environmental), and phylogenetic effects in a combined model that predicts up to 68% of the interspecific variation in clutch size. We then applied the same species-level model to predict mean clutch size across 2,521 assemblages worldwide and found that it explains the observed eco-geographic pattern very well. Clutches are consistently largest in cavity nesters and in species occupying seasonal environments, highlighting the importance of offspring and adult mortality that is jointly expressed in intrinsic and extrinsic correlates. The findings offer a conceptual bridge between macroecology and comparative biology and provide a global and integrative understanding of the eco-geographic and cross-species variation in a core life-history trait.",
"title": "The Worldwide Variation in Avian Clutch Size across Species and Space"
},
{
"docid": "15578265",
"text": "Several lines of evidence suggest a role for the gut microbiome in type 1 diabetes. Treating diabetes-prone rodents with probiotics or antibiotics prevents the development of the disorder. Diabetes-prone rodents also have a distinctly different gut microbiome compared with healthy rodents. Recent studies in children with a high genetic risk for type 1 diabetes demonstrate significant differences in the gut microbiome between children who develop autoimmunity for the disease and those who remain healthy. However, the differences in microbiome composition between autoimmune and healthy children are not consistent across all studies because of the strong environmental influences on microbiome composition, particularly diet and geography. Controlling confounding factors of microbiome composition uncovers bacterial associations with disease. For example, in a human cohort from a single Finnish city where geography is confined, a strong association between one dominant bacterial species, Bacteroides dorei, and type 1 diabetes was discovered (Davis-Richardson et al. Front Microbiol 2014;5:678). Beyond this, recent DNA methylation analyses suggest that a thorough epigenetic analysis of the gut microbiome may be warranted. These studies suggest a testable model whereby a diet high in fat and gluten and low in resistant starch may be the primary driver of gut dysbiosis. This dysbiosis may cause a lack of butyrate production by gut bacteria, which, in turn, leads to the development of a permeable gut followed by autoimmunity. The bacterial community responsible for these changes in butyrate production may vary around the world, but bacteria of the genus Bacteroides are thought to play a key role.",
"title": "A model for the role of gut bacteria in the development of autoimmunity for type 1 diabetes"
},
{
"docid": "3230361",
"text": "Publisher Summary This chapter summarizes the development and characterization of rabbit polyclonal antibodies named histone that are directed against the methylated H3-K9 position. It provides protocols for peptide design, rabbit immunizations, and quality controls of methyl-lysine histone antibodies, followed by their in vivo characterization using indirect IF of inter-and metaphase chromatin in wild-type (wt) and mutant mouse cells that are deficient for the Suv39h histone methyltransferases (HMTases). Histone amino-termini (tails) protrude from the nucleosome core and are subject to a variety of post-translational modifications, including acetylation (on lysine residues), phosphorylation (on serine and threonine residues), methylation (on lysine and arginine residues), ubiquitination (on lysine residues), and ADP-ribosylation (on glutamic acid residues). In addition to their structural roles, histones play important functions in the control of gene expression by regulating access to the underlying nucleosomal template. It is without doubt that the development of high-quality, position-specific methyl-lysine histone antibodies can provide important tools for the further decoding of the epigenetic information, which is in part, indexed by distinct methylation states of selective lysine residues in the histone amino-termini. A comparative analysis indicates significant discrepancies in the specificity and avidity of the available methyl-lysine histone antibodies and highlights the need for extensive quality controls, such that experimental data can be correctly interpreted despite the exquisite complexity of histone lysine methylation.",
"title": "Generation and characterization of methyl-lysine histone antibodies."
},
{
"docid": "18694784",
"text": "The yeast histone variant H2AZ (Htz1) is implicated in transcription activation, prevention of the ectopic spread of heterochromatin, and genome integrity. Our genome-wide localization analysis revealed that Htz1 is widely, but nonrandomly, distributed throughout the genome in an SWR1-dependent manner. We found that Htz1 is enriched in intergenic regions compared with coding regions. Its occupancy is inversely proportional to transcription rates and the enrichment of the RNA polymerase II under different growth conditions. However, Htz1 does not seem to directly regulate transcription repression genome-wide; instead, the presence of Htz1 under the inactivated condition is essential for optimal activation of a subset of genes. In addition, Htz1 is not generally responsible for nucleosome positioning, even at those promoters where Htz1 is highly enriched. Finally, using a biochemical approach, we demonstrate that incorporation of Htz1 into nucleosomes inhibits activities of histone modifiers associated with transcription, Dot1, Set2, and NuA4 and reduces the nucleosome mobilization driven by chromatin remodeling complexes. These lines of evidence collectively suggest that Htz1 may serve to mark quiescent promoters for proper activation.",
"title": "Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling."
},
{
"docid": "6536598",
"text": "Chromatin structure is modulated during deoxyribonucleic acid excision repair, but how this is achieved is unclear. Loss of the yeast Ino80 chromatin-remodeling complex (Ino80-C) moderately sensitizes cells to ultraviolet (UV) light. In this paper, we show that INO80 acts in the same genetic pathway as nucleotide excision repair (NER) and that the Ino80-C contributes to efficient UV photoproduct removal in a region of high nucleosome occupancy. Moreover, Ino80 interacts with the early NER damage recognition complex Rad4-Rad23 and is recruited to chromatin by Rad4 in a UV damage-dependent manner. Using a modified chromatin immunoprecipitation assay, we find that chromatin disruption during UV lesion repair is normal, whereas the restoration of nucleosome structure is defective in ino80 mutant cells. Collectively, our work suggests that Ino80 is recruited to sites of UV lesion repair through interactions with the NER apparatus and is required for the restoration of chromatin structure after repair.",
"title": "The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair"
},
{
"docid": "9993008",
"text": "The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed \"bivalent domains,\" consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.",
"title": "A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells"
},
{
"docid": "751192",
"text": "BACKGROUND Open chromatin regions are correlated with active regulatory elements in development and are dysregulated in diseases. The BAF (SWI/SNF) complex is essential for development, and has been demonstrated to remodel reconstituted chromatin in vitro and to control the accessibility of a few individual regions in vivo. However, it remains unclear where and how BAF controls the open chromatin landscape to regulate developmental processes, such as human epidermal differentiation. RESULTS Using a novel \"on-plate\" ATAC-sequencing approach for profiling open chromatin landscapes with a low number of adherent cells, we demonstrate that the BAF complex is essential for maintaining 11.6 % of open chromatin regions in epidermal differentiation. These BAF-dependent open chromatin regions are highly cell-type-specific and are strongly enriched for binding sites for p63, a master epidermal transcription factor. The DNA sequences of p63 binding sites intrinsically favor nucleosome formation and are inaccessible in other cell types without p63 to prevent ectopic activation. In epidermal cells, BAF and p63 mutually recruit each other to maintain 14,853 open chromatin regions. We further demonstrate that BAF and p63 cooperatively position nucleosomes away from p63 binding sites and recruit transcriptional machinery to control tissue differentiation. CONCLUSIONS BAF displays high specificity in controlling the open chromatin landscape during epidermal differentiation by cooperating with the master transcription factor p63 to maintain lineage-specific open chromatin regions.",
"title": "A novel ATAC-seq approach reveals lineage-specific reinforcement of the open chromatin landscape via cooperation between BAF and p63"
},
{
"docid": "26673492",
"text": "AIMS Few studies have examined the role of gender and both area-level and individual socio-economic status (SES) as independent predictors of alcohol-related aggression (ARA) in and around licensed venues. METHODS The aim of the present study was to investigate the relationship between gender, area-level SES and individual SES (operationalised as occupational category) and ARA in and around licensed venues. The sample comprised 697 men and 649 women aged 16-47, who completed a patron intercept survey as part of a larger study assessing trends in harm and stakeholders' views surrounding local community level interventions in dealing with alcohol-related problems in the night-time economy. RESULTS Binary logistic regression analyses showed that age, gender, occupational category, area-level SES and level of intoxication at time of interview were all significant predictors of involvement in ARA. Being male doubled the odds of involvement in ARA, while age was a protective factor. Blue collar workers had more than double the odds of ARA involvement of professionals, while those living in the most socio-economically disadvantaged areas were over twice as likely to report experiencing ARA compared to those living in the most advantaged areas. However, assessment of the predictive model by gender revealed that effects of age, occupational category and area-level SES were restricted to male participants, with greater intoxication no longer predictive. CONCLUSIONS ARA among patrons was significantly more likely to occur among men, those in blue collar occupations, and individuals living in low SES areas, suggesting both individual and area-level disadvantage may play a role in ARA.",
"title": "Demographic Risk Factors for Alcohol-Related Aggression In and Around Licensed Venues."
},
{
"docid": "16626264",
"text": "Histone variants help specialize chromatin regions; however, their impact on transcriptional regulation is largely unknown. Here, we determined the genome-wide localization and dynamics of Htz1, the yeast histone H2A variant. Htz1 localizes to hundreds of repressed/basal Pol II promoters and prefers TATA-less promoters. Specific Htz1 deposition requires the SWR1 complex, which largely colocalizes with Htz1. Htz1 occupancy correlates with particular histone modifications, and Htz1 deposition is partially reliant on Gcn5 (a histone acetyltransferase) and Bdf1, an SWR1 complex member that binds acetylated histones. Changes in growth conditions cause a striking redistribution of Htz1 from activated to repressed/basal promoters. Furthermore, Htz1 promotes full gene activation but does not generally impact repression. Importantly, Htz1 releases from purified chromatin in vitro under conditions where H2A and H3 remain associated. We suggest that Htz1-bearing nucleosomes are deposited at repressed/basal promoters but facilitate activation through their susceptibility to loss, thereby helping to expose promoter DNA.",
"title": "Genome-Wide Dynamics of Htz1, a Histone H2A Variant that Poises Repressed/Basal Promoters for Activation through Histone Loss"
},
{
"docid": "14682243",
"text": "BACKGROUND Results of the few cohort studies from countries with low incomes or middle incomes suggest a lower incidence of dementia than in high-income countries. We assessed incidence of dementia according to criteria from the 10/66 Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders (DSM) IV, the effect of dementia at baseline on mortality, and the independent effects of age, sex, socioeconomic position, and indicators of cognitive reserve. METHODS We did a population-based cohort study of all people aged 65 years and older living in urban sites in Cuba, the Dominican Republic, and Venezuela, and rural and urban sites in Peru, Mexico, and China, with ascertainment of incident 10/66 and DSM-IV dementia 3-5 years after cohort inception. We used questionnaires to obtain information about age in years, sex, educational level, literacy, occupational attainment, and number of household assets. We obtained information about mortality from all sites. For participants who had died, we interviewed a friend or relative to ascertain the likelihood that they had dementia before death. FINDINGS 12,887 participants were interviewed at baseline. 11,718 were free of dementia, of whom 8137 (69%) were reinterviewed, contributing 34,718 person-years of follow-up. Incidence for 10/66 dementia varied between 18·2 and 30·4 per 1000 person-years, and were 1·4-2·7 times higher than were those for DSM-IV dementia (9·9-15·7 per 1000 person-years). Mortality hazards were 1·56-5·69 times higher in individuals with dementia at baseline than in those who were dementia-free. Informant reports suggested a high incidence of dementia before death; overall incidence might be 4-19% higher if these data were included. 10/66 dementia incidence was independently associated with increased age (HR 1·67; 95% CI 1·56-1·79), female sex (0·72; 0·61-0·84), and low education (0·89; 0·81-0·97), but not with occupational attainment (1·04; 0·95-1·13). INTERPRETATION Our results provide supportive evidence for the cognitive reserve hypothesis, showing that in middle-income countries as in high-income countries, education, literacy, verbal fluency, and motor sequencing confer substantial protection against the onset of dementia. FUNDING Wellcome Trust Health Consequences of Population Change Programme, WHO, US Alzheimer's Association, FONACIT/ CDCH/ UCV.",
"title": "Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study"
},
{
"docid": "4679264",
"text": "The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5′ CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts—defined by chronic neurodegeneration (Alzheimer's) or lack thereof (schizophrenia)—were included. A robust and progressive rise in DNA methylation levels across the lifespan was observed for 8/50 loci (GABRA2, GAD1, HOXA1, NEUROD1, NEUROD2, PGR, STK11, SYK) typically in conjunction with declining levels of the corresponding mRNAs. Another 16 loci were defined by a sharp rise in DNA methylation levels within the first few months or years after birth. Disease-associated changes were limited to 2/50 loci in the Alzheimer's cohort, which appeared to reflect an acceleration of the age-related change in normal brain. Additionally, methylation studies on sorted nuclei provided evidence for bidirectional methylation events in cortical neurons during the transition from childhood to advanced age, as reflected by significant increases at 3, and a decrease at 1 of 10 loci. Furthermore, the DNMT3a de novo DNA methyl-transferase was expressed across all ages, including a subset of neurons residing in layers III and V of the mature cortex. Therefore, DNA methylation is dynamically regulated in the human cerebral cortex throughout the lifespan, involves differentiated neurons, and affects a substantial portion of genes predominantly by an age-related increase.",
"title": "DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated Neurons"
},
{
"docid": "5116145",
"text": "The sequence specificity of DNA-binding proteins is the primary mechanism by which the cell recognizes genomic features. Here, we describe systematic determination of yeast transcription factor DNA-binding specificities. We obtained binding specificities for 112 DNA-binding proteins representing 19 distinct structural classes. One-third of the binding specificities have not been previously reported. Several binding sequences have striking genomic distributions relative to transcription start sites, supporting their biological relevance and suggesting a role in promoter architecture. Among these are Rsc3 binding sequences, containing the core CGCG, which are found preferentially approximately 100 bp upstream of transcription start sites. Mutation of RSC3 results in a dramatic increase in nucleosome occupancy in hundreds of proximal promoters containing a Rsc3 binding element, but has little impact on promoters lacking Rsc3 binding sequences, indicating that Rsc3 plays a broad role in targeting nucleosome exclusion at yeast promoters.",
"title": "A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters."
},
{
"docid": "8037453",
"text": "PURPOSE Three large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy. PATIENTS AND METHODS Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This exploratory cohort analysis grouped patients by baseline and most recent levels of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol creatinine), or high (> or = 100 nmol/mmol creatinine), and BAP as low (< 146 U/L) or high (> or = 146 U/L). The relative risks for negative clinical outcomes were estimated for each group using multiple-event and Cox regression models with time-varying covariates. RESULTS Patients with high and moderate Ntx levels had 2-fold increases in their risk of skeletal complications and disease progression compared with patients with low Ntx levels (P < .001 for all). High Ntx levels in each solid tumor category were associated with a 4- to 6-fold increased risk of death on study, and moderate Ntx levels a 2- to 4-fold increased risk compared with low Ntx levels (P < .001 for all). Bone alkaline phosphatase also showed some correlation with risk of negative clinical outcomes. CONCLUSION The bone resorption marker Ntx provides valuable prognostic information in patients with bone metastases receiving bisphosphonates.",
"title": "Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid."
},
{
"docid": "1791637",
"text": "In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2,000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2) genomewide in human and mouse ES cells by chromatin immunoprecipitation, followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes -- the first occupied by both PRC2 and PRC1 (PRC1-positive) and the second specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of PRC2 and PRC1 can be largely predicted from the locations, sizes, and underlying motif contents of CpG islands. We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes in pluripotent cells.",
"title": "Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains"
},
{
"docid": "21380232",
"text": "Mouse embryos undergo genome-wide methylation reprogramming by demethylation in early preimplantation development, followed by remethylation thereafter. Here we show that genome-wide reprogramming is conserved in several mammalian species and ask whether it also occurs in embryos cloned with the use of highly methylated somatic donor nuclei. Normal bovine, rat, and pig zygotes showed a demethylated paternal genome, suggesting active demethylation. In bovine embryos methylation was further reduced during cleavage up to the eight-cell stage, and this reduction in methylation was followed by de novo methylation by the 16-cell stage. In cloned one-cell embryos there was a reduction in methylation consistent with active demethylation, but no further demethylation occurred subsequently. Instead, de novo methylation and nuclear reorganization of methylation patterns resembling those of differentiated cells occurred precociously in many cloned embryos. Cloned, but not normal, morulae had highly methylated nuclei in all blastomeres that resembled those of the fibroblast donor cells. Our study shows that epigenetic reprogramming occurs aberrantly in most cloned embryos; incomplete reprogramming may contribute to the low efficiency of cloning.",
"title": "Conservation of methylation reprogramming in mammalian development: aberrant reprogramming in cloned embryos."
},
{
"docid": "15778034",
"text": "H2A.Z is an evolutionary conserved histone variant involved in transcriptional regulation, antisilencing, silencing, and genome stability. The mechanism(s) by which H2A.Z regulates these various biological functions remains poorly defined, in part due to the lack of knowledge regarding its physical location along chromosomes and the bearing it has in regulating chromatin structure. Here we mapped H2A.Z across the yeast genome at an approximately 300-bp resolution, using chromatin immunoprecipitation combined with tiling microarrays. We have identified 4,862 small regions—typically one or two nucleosomes wide—decorated with H2A.Z. Those “Z loci” are predominantly found within specific nucleosomes in the promoter of inactive genes all across the genome. Furthermore, we have shown that H2A.Z can regulate nucleosome positioning at the GAL1 promoter. Within HZAD domains, the regions where H2A.Z shows an antisilencing function, H2A.Z is localized in a wider pattern, suggesting that the variant histone regulates a silencing and transcriptional activation via different mechanisms. Our data suggest that the incorporation of H2A.Z into specific promoter-bound nucleosomes configures chromatin structure to poise genes for transcriptional activation. The relevance of these findings to higher eukaryotes is discussed.",
"title": "Variant Histone H2A.Z Is Globally Localized to the Promoters of Inactive Yeast Genes and Regulates Nucleosome Positioning"
},
{
"docid": "24746892",
"text": "Bactericidal antibiotics kill by modulating their respective targets. This traditional view has been challenged by studies that propose an alternative, unified mechanism of killing, whereby toxic reactive oxygen species (ROS) are produced in the presence of antibiotics. We found no correlation between an individual cell's probability of survival in the presence of antibiotic and its level of ROS. An ROS quencher, thiourea, protected cells from antibiotics present at low concentrations, but the effect was observed under anaerobic conditions as well. There was essentially no difference in survival of bacteria treated with various antibiotics under aerobic or anaerobic conditions. This suggests that ROS do not play a role in killing of bacterial pathogens by antibiotics.",
"title": "Killing by bactericidal antibiotics does not depend on reactive oxygen species."
},
{
"docid": "2842550",
"text": "BACKGROUND Platelet deposition and aggregation are central to the pathogenesis of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic effects of the platelet glycoprotein IIb/IIIa antagonist eptifibatide have been delineated in healthy subjects but not in patients with ACS. We assessed effects of eptifibatide on ex vivo platelet aggregation in patients enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy (PURSUIT) trial of ACS. METHODS AND RESULTS Patients were randomly assigned to an intravenous bolus (180 microgram/kg) and 72-hour infusion of eptifibatide (2.0 microgram/kg per minute, n=48) or placebo (n=50). We assessed correlations of plasma eptifibatide levels with receptor occupancy and inhibition of ex vivo platelet aggregation at 5 minutes and 1, 4, 24, 48, and 72 hours during treatment and 4 and 8 hours after termination of infusion. Blood was collected in buffered citrate and D-phenylalanyl-L-prolyl-L-arginine chloromethylketone anticoagulants. Although eptifibatide produced profound, prolonged inhibition of platelet aggregation during therapy, aggregation appeared to recover partially by 4 hours after the bolus. The aggregation response was greater with thrombin receptor agonist peptide versus ADP stimulation; inhibition of platelet aggregation was greater in blood samples anticoagulated with citrate versus D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK). Plasma eptifibatide levels correlated significantly with receptor occupancy but not with inhibition of platelet aggregation. CONCLUSIONS A bolus and infusion of eptifibatide inhibits platelet aggregation profoundly in patients with ACS and is followed by brief, partial recovery. These results enhance our understanding of the relation between pharmacodynamic and clinical effects of eptifibatide in such patients and may have important implications for its use in percutaneous interventions.",
"title": "Pharmacodynamics and pharmacokinetics of eptifibatide in patients with acute coronary syndromes: prospective analysis from PURSUIT."
},
{
"docid": "34101101",
"text": "Several species of rodents are used to investigate the metabolism of quercetin in vivo. However, it is unclear whether they are a proper animal model. Thus, we compared the metabolism of quercetin in Wistar rats (rats), Balb/c mice (mice) and Mongolian gerbils (gerbils). We determined the levels of quercetin metabolites, quercetin-3-glucuronide (Q3G), quercetin-3′-sulfate (Q3′S) and methyl-quercetin isorhamnetin (IH), in the plasma, lungs and livers of three species of animals by high-performance liquid chromatography after acute and/or chronic quercetin administration. The metabolic enzyme activities in the intestinal mucosal membrane and liver were also investigated. First, we found that after acute quercetin administration, the Q3′S level was the highest in gerbils. However, after long-term supplementation (20 weeks), Q3G was the dominant metabolite in the plasma, lungs and livers followed by IH and Q3′S in all animals, although the gerbils still had a higher Q3′S conversion ratio. The average concentrations of total quercetin concentration in the plasma of gerbils were the highest in both short- and long-term studies. The activities of uridine 5′-diphosphate-glucuronosyltransferase, phenolsulfotransferase and catechol-O-methyltransferase were induced by quercetin in a dose- and tissue-dependent manner in all animals. Taken together, in general, after long-term supplementation the metabolism of quercetin is similar in all animals and is comparable to that of humans. However, the accumulation of quercetin and Q3′S conversion ratio in gerbils are higher than those in the other animals.",
"title": "Comparing the metabolism of quercetin in rats, mice and gerbils"
},
{
"docid": "7821634",
"text": "Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ∼30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.",
"title": "Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance"
}
] |
2145
|
Are there any benefits of FMLA beyond preserving your job?
|
[
{
"docid": "598899",
"text": "How will your employer treat your pay and benefits status while you're on leave? Disability income coverage and leave policies work in tandem to solve very different problems. Disability income coverage covers your income, leave policies guarantee your status as an employee. Typically, STD coverage requires an actual loss of income and will offset it's stated benefit for any income you're receiving. In general you can't begin a STD claim after the 7 day waiting period and also draw income from vacation or sick time. Also, typically STD will cover some percentage of your covered pay (sometimes including commission/bonus income) up to some weekly maximum. FLMA requires employers to allow certain amounts of time for certain types of leave. FMLA is not necessarily an income replacement tool like STD coverage. Contrary to your post it's my understanding that if sick and vacation time accrue in to a single PTO bucket your employer is prohibited from requiring employees to exhaust accrued time prior to beginning FMLA leave. In general, you're not missing anything because the point of FMLA is to guarantee your job and status as an employee from a benefits perspective. Benefits language from the Department of Labor Website A covered employer is required to maintain group health insurance coverage, including family coverage, for an employee on FMLA leave on the same terms as if the employee continued to work.",
"title": ""
},
{
"docid": "332124",
"text": "In your situation, it sounds like the only added benefit would be insurance continuance. For employees who can't access short-term disability it is a critical protection against losing their job. I just want to emphasize that given that you are in a pretty decent employment situation.",
"title": ""
}
] |
[
{
"docid": "43438",
"text": "I do wonder if part of this is a phenomenon I've seen numerous times in the US: Woman gets pregnant, barely shows up to work for the next 5 months until birth, camps out on FMLA for three months before simply ignoring any communications from the company for the next several months. Finally, a good 6-8 months after the birth she notifies the company she won't be working anymore. Meanwhile, she's been getting insurance benefits the entire time and HR is too afraid of a lawsuit to cut her loose. Her position has either been unfilled the entire time (requiring her coworkers to cover her share of the work at expense of their own lives), or if the manager is more prescient than most, has already been backfilled, but is still in a blocking pattern preventing other hires but at least not making coworkers' lives miserable.",
"title": ""
},
{
"docid": "343913",
"text": "It could be a a way to preserve the value of your money, but depends upon various factors. If a country defaults, and it leads to hyper-inflation, by definition that means that money loses its purchasing power. In even simpler terms, it cannot buy as much tomorrow as I could today. Therefore people can be incented to either hoard physical goods, or other non-perishable items. Real-estate may well be such an item. If you are resident in the country, you have to live somewhere. It is possible that a landlord might try to raise rent beyond what your job is willing to pay. Of course, in a house, you might have a similar situation with utilities like electricity... Assuming some kind of re-stabilization of the economy and currency, even with several more zeros on the end, it is conceivable that the house would subsequently sell for an appropriately inflation adjusted amount, as other in-demand physical goods may. Lots of variables. Good Luck.",
"title": ""
},
{
"docid": "587192",
"text": "If you're under age 55 and in good health generally you cannot withdraw your funds from super and your super fund cannot provide you with any financial assistance eg lend you money. However, for a very small percentage of people with unrestricted non preserved superannuation components ( check your statement most people's superannuation is 'preserved'which means they cannot access it until they meet a 'condition of release')they may withdraw their super benefits upto the unrestricted non preserved amount. For healthy (& able) persons aged 55 and over they may access their super under the following conditions: I can understand your frustration of having your money compulsory tied up in superannuation especially given the poor investment returns of the past 5 years. However, superannuation may be more flexible than you realize, I am an adviser at Grant Thornton and I am constantly telling clients that superannuation is not an invest but it the most tax effective long term savings vehicle available to Australians for their investment savings eg max 15% tax on income and capital gains if held for a year are taxed at 10%. If you're not happy with your investment returns you may like to seek some advice or,set up your own super fund - a self managed super fund where you can invest a wide variety of assets; shares, managed funds,cash, term deposits, property( your super fund can even borrow to help acquire the property) I hope this helps",
"title": ""
},
{
"docid": "224746",
"text": ">when by definition, you are being paid less than your labour If that were true then why wouldnt the worker just work for themselves? They would make more or at least the same amount and not have to deal with their bosses bossing them around. The fact is that the worker is made more productive through the use of the entrpeneur's resources and business model structure. If there were no extra benefit to the worker in taking the job then they wouldnt take it, just like if the employer did not recieve an added benefit above and beyond what they were paying the worker, they wouldnt hire them. Extra value is created in the two voluntarily working together. No one is being generous or agreeing to the arrangement out of the goodness of their heart. They are both acting in their self interest and they are both benefitting.",
"title": ""
},
{
"docid": "135415",
"text": "\"There are several ways you can get out of paying your student loans back in the USA: You become disabled and the loan is dismissed once verified by treating doctor or the Social Security Administration. You become a peace officer. You become a teacher; generally K-12, but I have heard from the DOE that teachers at state schools qualify as well. So the \"\"malicious\"\" friend B is prescribing to the theory that if one of those conditions becomes true, friend A will not have to pay back the loan. The longer you drag it out, the more chance you have to fulfill a condition. Given that 2 of these methods require a commitment, my guess is that they are thinking more along the lines of the first one, which is horrible. Financially, it makes no sense to delay paying back your loans because deferred loans are only interest-free until you graduate and are past your grace period, after which they will begin accruing interest. Unsubsidized loans accrue interest from the day you get them, only their payback is deferred until you graduate and exhaust your grace period. Anytime you ask for forbearance, you are still accruing interest and it is capitalizing into your principal — you are just given a chance to delay payback due to financial hardship, bad health, or loss of job. Therefore, at no point are you benefiting beyond the time you are in school and getting an education, still looking for a job, or dealing with health issues. In the current market, no CD, no savings account, and no investment will give you substantially more return that will offset the loss of the interest you are accruing. Even those of us in the old days getting 4.X % rates would not do this. There was a conditional consolidation offer the DOE allowed which could bring all your loans under one roof for a competitive 5.x-6.x % rate allowing you a single payment, but even then you would benefit if you had rates that were substantially higher. From a credit worthiness aspect, you are hurt by the outstanding obligation and any default along the way, so you really want to avoid that — paying off or down your loans are a good way to ensure you don't shoot yourself in the foot.\"",
"title": ""
},
{
"docid": "31801",
"text": "There are really two answers, depending on your goal. You're either trying to preserve wealth, or increase wealth. In the case of preserving wealth, undervalued blue chip stocks are always a great move. Bonus points if they have a history of increasing dividend payments. The best example I have is bank stocks - the continuously change their dividend payouts (usually to the benefit of investors), and at the same time, many have been undervalued, or over-whelped during the downturn. Alternatively, you can let things sit, and buy high quality corporate bonds. I'm seeing (daily) offers from my brokerage's new issues list for high quality bonds paying 5.75%-7.25%. While you have to lock in your money for the period, the rate of return tends to offset lock-in worries, and you can still usually sell the shares in a secondary market, or through your broker.",
"title": ""
},
{
"docid": "584963",
"text": "Building tanks and helicopters is the use of the countries economic resources for goods that provide no net benefit to the economy beyond their construction price. If, for example, the government wanted to stimulate the economy by spending $1 trillion on something, sure, the country's GDP would by definition increase by $1 trillion, and there'd probably be some multiplier effect by those workers now having additional money to spend on other goods. There's also going to be some negative effects on other sectors of the economy because the prices for labor and raw materials will go up because of the increased demand from the government. If the government is buying $100 billion in steel and aluminum, you can bet that the spot prices of steel and aluminum is going to jump up, squeezing any private industries that need to buy those resources. Now the question is what do you spend that $1 trillion on to get the biggest bang for your buck. Military hardware accomplishes the goal of having something disposable to buy with $1 trillion, but little additional benefit to the private economy. If you instead spent $1 trillion on building infrastructure (bridges/roads/dams/pipelines/flood control), scientific research, or education, you've now generated goods that have their own intrinsic value to society beyond their cost - whether it be less traffic, new scientific discoveries, or a more educated workforce.",
"title": ""
},
{
"docid": "368698",
"text": "\"Whether your financial status is considered \"\"OK\"\" depends on your aspirations. You aren't spending more than you earn and have no debt. That puts you in the category of OK in my book, but the information in your post indicates that you would benefit from some financial advice--100 grand sounds like a lot of money to have in a bank unless you are on the verge of spending it. Financial advisors come in various shapes and sizes. Many will charge you a lot for what turns out to be helpful advice in the first meeting, but very little value-added thereafter. Some don't have the best incentives (they may be incentivized to encourage you to put your money into certain funds, for example). There are many financial advisors (of sorts) that you have access to that won't cost you anything. For example, if you have a 401(k) at work, I bet there is a representative from the plan administrator that will meet with you for free. If you open a brokerage account or IRA at any place (Fidelity, Vanguard, etc.) you can easily talk with one of their reps and get all sorts of advice. My personal take is to meet with anyone who will meet with me for free, but not to pay anyone for this service. It's too easy to get good advice and paying for it doesn't guarantee that you get better advice. Your financial situation will depend primarily on a few things you have not mentioned here. For example, How much are you setting aside for retirement and what are your retirement goals? This is something lots of people can give you advice on, but we don't know what market returns will be going forward so we don't really know. One bit of advice that may benefit you is how to set aside money for retirement in the most tax advantaged way. How much do you feel that you need saved up for large expenses? Thinking of starting a family? How many months worth of income are you comfortable having set aside? What is your tolerance of risk? If you put your money in risky assets, you may make more, but you may also actually lose money. Those are the questions a financial advisor will ask about. Once you have his/her advice--and preferrably after talking to a few advisors--you can make your own decision. Basically, your options are: Rules of thumb: Save only what makes sense to save in banks given your expected needs for cash. Put a lot in tax advantaged accounts (don't give Uncle Sam any gifts). Then look at financial and real investments. There are a number of free resources on the internet. For example FutureAdvisor. Or you can hit up the forums at BogleHeads. Those guys give and receive financial advice as a hobby. They aren't professionals, but you can get a lot of varying ideas and make up your own mind, which to me is better than (just) asking a professional. BTW, regarding the ESPP: these plans often give you a discount on stock and can therefore be a good idea. Just be sure you don't hold the stock longer than you need to. It's generally a bad idea to concentrate your wealth in any single investment, especially one highly correlated with your background risk (i.e., if the company does poorly you will already be worse off because you may lose your job or see fewer advancement opportunities. No need to add losses in your savings to that). 1 Please note: I am neither advocating nor discouraging buying guns, gold, or other controversial real assets. I'm just giving examples of items some people buy as part of their wealth-preservation strategy.\"",
"title": ""
},
{
"docid": "170613",
"text": "\"As long as you are disciplined about it, you can certainly have your emergency fund and other savings funds in one account. Multiple accounts may incur added costs, since you may not have the minimum balances to avoid the fees. Some banks provide tools or account features to help track separate \"\"buckets\"\" of funds within one account. One important principle for an emergency fund is liquidity. Those funds should be easily accessible, ideally without withdrawal penalties or transaction costs. For this reason, certificates of deposit (CD) or money market funds should be avoided for this purpose. Another important principle, for any savings fund, is capital preservation/safety. That money should not be held in risky assets. Depending on the purpose of the fund, you may consider other options beyond just a savings account. For example, you may consider placing funds for a house in CD(s) early on, before you are actually looking for the house. As you get closer to having enough for a down payment, you would shift that money into a savings account. One drawback of such an approach is the extra management that this requires on your part. A spreadsheet is a simple way to track these funds, though that requires more manual management and discipline to do that tracking. It also requires some knowledge of spreadsheets, but it provides you with flexibility so you can create a process that works well for you. Any accounting software should allow you to do this in some fashion with (hopefully) less effort than maintaining a spreadsheet, though you may have to do things in a certain way that may be awkward in some cases. Those are the basic principles that come to mind. I am sure others can provide more specific suggestions, like banks which allow you track buckets of funds or accounting software that can help you track the funds.\"",
"title": ""
},
{
"docid": "541809",
"text": "\"No, your business cannot deduct your non-business expenses. You can only deduct from your business income those reasonable expenses you paid in order to earn income for the business. Moreover, for there to be a tax benefit, your business generally has to have income (but I expect there are exceptions; HST input tax credits come to mind.) The employment income from your full-time job wouldn't count as business income for your corporation. The corporation has nothing to do with that income – it's earned personally, by you. With respect to restaurant bills: These fall under a category known as \"\"meals & entertainment\"\". Even if the expense can be considered reasonable and business-related (e.g. meeting customers or vendors) the Canada Revenue Agency decided that a business can only deduct half of those kinds of expenses for tax purposes. With respect to gasoline bills: You would need to keep a mileage and expense log. Only the portion of your automobile expenses that relate to the business can be deducted. Driving to and from your full-time job doesn't count. Of course, I'm not a tax professional. If you're going to have a corporation or side-business, you ought to consult with a tax professional. (A point on terminology: A business doesn't write off eligible business expenses — it deducts them from business income. Write off is an accounting term meaning to reduce the value of an asset to zero. e.g. If you damaged your car beyond repair, one could say \"\"the car is a write-off.\"\")\"",
"title": ""
},
{
"docid": "296844",
"text": "\"If we are only talking about a few extra months between jobs which is quite common now then how do you get to \"\"living beyond their means\"\"? Either they have unemployment insurance or they don't. It sounds like you don't like unemployment insurance. So go bring that to a vote. So far the majority of people want unemployment insurance in place because they see greater economic benefit in providing this service.\"",
"title": ""
},
{
"docid": "123366",
"text": "I'd imagine you want to keep the utility bills around to dispute any historical billing errors or anomalies for perhaps 6 months to a year. Beyond that, you always have the financial records of making the payments -- namely, your bank statements. So what benefit is there in keeping the paper receipts for utility payments around for longer than that? I say shred them, with extreme prejudice -- while wearing black Chuck Norris style.",
"title": ""
},
{
"docid": "2286",
"text": "If your uncle is looking to maintain life insurance coverage for specific shorter period of time he may want to look into hybrid life insurance. If you buy a hybrid universal life policy, the premium and death benefit can be guaranteed to last until any age. Since, most permanent policies focus on cash value accumulation it is hard for most people to find cheap whole life or affordable universal life. Consumers only looking for a longer duration have a more flexible choice with a new hybrid product that combines elements of both term life coverage and universal life. Hybrid universal policies are much cheaper then other permanent coverage such as whole life coverage because they do not emphasize cash value accumulation. However, the premiums and death benefits can still be guaranteed to a specific age (i.e. 85, 90, 95, 100). So, premiums can be scaled to coordinate with your desired budget and the face amount required for your family. Typical universal life and whole life insurance contracts only allow for lifetime coverage. However, hybrid universal life offers a much smaller premium because the coverage can be dialed into a specific age. If the policyholder does live beyond the originally selected age, the death benefit will simply begin getting smaller, while the original premium will continue to remain the same.",
"title": ""
},
{
"docid": "146276",
"text": "These days there are a lot of solutions which allow you to hire a car on the Internet itself. One of the major benefits of booking on the internet rental-car solutions is that you will preserve a fortune and ensure that things are effectively structured, thus saving sufficient time as well. We provide the Car rental services at a cheap price in the whole world. The best way to reduce costs and plan for local transportation when you are on a vacation is to book your car.",
"title": ""
},
{
"docid": "155074",
"text": "I would make this a comment, but I am not worthy...... You will need to define your objectives before you can do anything. What is the money for? What is your risk tolerance? Where do you live? Capital appreciation? Preservation? Can you eat if your savings are cut in half? How much are you currently making? How much are you currently saving? What do you already have exposure to? How secure is your job? What is the makeup of the congregation? Do you have any tax-related surprises? Do you own your home? Have you previously consulted with a financial planner? There are many many factors obviously. More than I think most people want to give out over the internet, but they are all important to making a decision. Get a recommendation from someone you know for a financial planner. Ask upfront what their background is. Education, experience credentials. You want a certified financial planner or analyst. Ask how their fees are structured and what their approach is like, and make sure they're speaking intelligibly. Feel free to shop around until you find someone you like.",
"title": ""
},
{
"docid": "295258",
"text": "\"First, you mentioned your brother-in-law has \"\"$100,000 in stock options (fully vested)\"\". Do you mean his exercise cost would be $100,000, i.e. what he'd need to pay to buy the shares? If so, then what might be the estimated value of the shares acquired? Options having vested doesn't necessarily mean they possess value, merely that they may be exercised. Or did you mean the estimated intrinsic value of those options (estimated value less exercise cost) is $100,000? Speaking from my own experience, I'd like to address just the first part of your question: Have you treated this as you would a serious investment in any other company? That is, have you or your brother-in-law reviewed the company's financial statements for the last few years? Other than hearing from people with a vested interest (quite literally!) to pump up the stock with talk around the office, how do you know the company is: BTW, as an option holder only, your brother-in-law's rights to financial information may be limited. Will the company share these details anyway? Or, if he exercised at least one option to become a bona-fide shareholder, I believe he'd have rights to request the financial statements – but company bylaws vary, and different jurisdictions say different things about what can be restricted. Beyond the financial statements, here are some more things to consider: The worst-case risk you'd need to accept is zero liquidity and complete loss: If there's no eventual buy-out or IPO, the shares may (effectively) be worthless. Even if there is a private market, willing buyers may quickly dry up if company fortunes decline. Contrast this to public stock markets, where there's usually an opportunity to witness deterioration, exit at a loss, and preserve some capital. Of course, with great risk may come great reward. Do your own due diligence and convince yourself through a rigorous analysis — not hopes & dreams — that the investment might be worth the risk.\"",
"title": ""
},
{
"docid": "229212",
"text": ">So what you're saying is if the janitor got a degree in a lesser paying field, he should be entitled to that 100k as a janitor. Ok. Nope. I did not say that. How you got that from what I said is beyond understanding. Perhaps you should really learn basic logic. Or you are just a fucking asshole who repeatedly ignores what has been said and pretends something else was said. Again because your small brain cannot comprehend this a janitor is not entitled to a better pay because special skills are not required to do his job and anyone can do it. Doesn't matter how many degrees the janitor has if he is not using those skills. >Just because you went to college doesn't mean your job takes more skill, or is harder. True. Finally you made a true statement. Here would you like a gold star and a sticker? Sadly for you noone has said that just because you went to college your job requires more skills or is harder. Alas the janitor job requires neither skill nor knowledge and is therefore going to remain a lower class job that is badly paid (compared to the area's cost of living). >My ex also has a brother who didn't go to college and got a bomb ass job at EA games as a programmer. I guess he deserves minimum wage. You are beyond retarded. There are other ways to get skills besides college. Your ex's brother acquired them, got a job that uses them and is getting a salary better than your no special skills needed janitor.",
"title": ""
},
{
"docid": "418864",
"text": "\"Keep in mind, there are too many variables to address in a single post. I could (and might) write a full book on the topic. One simple way to comprehend your perceived observation. In the 25% bracket, you have $1000 of income and two choices. Net out $750, and deposit to Roth, or deposit the full $1000 to the traditional IRA or 401(k). Sufficient time passes for the investment to grow 10 fold. For what it's worth, 8% at 30 years will do that. The Roth is now worth $7500 tax free. The traditional 401(k) is worth $10000 but subject to tax. At 25%, we're at the same $7500. For those looking to invest more than a gross $18,000, the Roth flavor is an effective $24,000, as post tax, this is $18,000. I wrote a bit more on this in the whimsically titled The Density of Your IRA. This is really a top 10%er issue, as it takes quite a bit of income for the $23,000 combined IRA and 401(k) limits to be a problem. In my writing, the larger case to be made is for taking advantage of the tax rate difference between the time of deposit and withdrawal. A look at the 2016 tax rates is in order. Let's stick with 25% while working. Now, at retirement, but before social security, as that's another story, the couple has $20,600 in standard deduction and exemption, and both the 10 and 15% brackets to enjoy. Ignoring any other deductions, potential credits, etc, let's look at a gross $80,000 withdrawal. The numbers happen to work out to an average 10%, with the couple being in a marginal 15% bracket. A full 25% or $20,000 tax would be the break-even to the \"\"same bracket in/out\"\" analysis, so this produces a $12,000 benefit. This issue is often treated as if there were 2 points in time, the deposit, and the withdrawal. For most people, that may be the case. Keep in mind, current law allows a conversion to Roth any time in between. This gives an opportunity to make a deposit while in the 25% bracket, and convert in any year the marginal rate drops back to 15% for whatever reason. Last - I can't ignore the Social Security problem. Simply put, when half of your Social Security benefits plus other income exceed $25,000 ($32,000 if married filing joint) your benefits start to become taxable, until 85% of your benefits are fully taxed. This issue is worthy of multiple posts by itself. It's not a deal killer, just another point to consider. A very high income earner might be beyond these levels already, in which case the point is moot. A low income earner, not impacted at all. It's those who are in the range to navigate this that would benefit to take advantage of the scenario I presented above and spend down pre-tax accounts, while planning to use the Roths when Social Security starts. This should make it clear - it's not all or none. Those retiring with $2M in 100% pretax, or $1.5M 100% in Roth have both missed the chance to have the optimal mix.\"",
"title": ""
},
{
"docid": "241158",
"text": "\"You'd be mistaken to this there is any morality involved in (most) corporations - neither positive nor negative; running a business is amoral. Some business missions have a moral intent - such as pharmaceuticals, health organization, etc. - but all have an amoral underbelly. It's fairly simplistic - the purpose of a business is to produce a profit. At some point, all successful, well functioning businesses will work down their list of ways to produce a profit - after they've established market share, a lasting brand, customer loyalty, finances well in the black - and eventually look towards capital preservation. In most bodies with a large monetary wealth, capital preservation becomes a key focus (in other words, once you master the art of making money, you then need to master the art of keeping it). Thus the ability to then focus on these things. To continue to just pay taxes is like running an efficient, but leaky ship. The more you preserve, the longer you'll be around and the more power you'll yield to stick around. This last point is also important to keep in mind - unlike you or I - a company will basically last forever (well at least until society collapses). You or I are only here until we die - and whatever wealth we have we may try to preserve for our kids or next of kin. A corporation is always here, the people in the corporation & it's owners change hands, but the corporation survives. Frankly any business that isn't aiming to make a profit, is either going to fail quickly or is by definition a \"\"non-profit\"\". Here is where I would believe the government plays a balancing role - to reign in the power of corporations (lest they rival their own). But, any good corporation will handle that problem as well (Regulatory capture, anyone?). Also, consider that for the most wealthy among us, it's probably not about the money anymore. It's now probably about the game. This is certainly where the psychopaths get that manic edge on the rest of us.\"",
"title": ""
},
{
"docid": "384541",
"text": "\"An employee costs the company in four ways: Salary, taxes, benefits, and capital. Salary: The obvious one, what they pay you. Taxes: There are several taxes that an employer has to pay for the privilege of hiring someone, including social security taxes (which goes to your retirement), unemployment insurance tax (your unemployment benefits if they lay you off), and workers compensation tax (pays if you are injured on the job). (There may be other taxes that I'm not thinking of, but in any case those are the main ones.) Benefits: In the U.S. employers often pay for medical insurance, sometimes for dental, life, and disability. There's usually some sort of retirement plan. They expect to give you some number of vacation days, holidays, and sick days where they pay you even though you're not working. Companies sometimes offer other benefits, like discounts on buying company products, membership in health clubs, etc. Capital: Often the company has to provide you with some sort of equipment, like a computer; furniture, like a chair and desk; etc. As far as the company is concerned, all of the above are part of the cost of having you as an employee. If they would pay a domestic employee $60,000 in salary and $20,000 in taxes, then assuming the same benefits and capital investment, if a foreign employee would cost them $0 in taxes they should logically be willing to pay $80,000. Any big company will have accountants who figure out the total cost of a new employee in excruciating detail, and they will likely be totally rational about this. A smaller company might think, \"\"well, taxes don't really count ...\"\" This is irrational but people are not always rational. I don't know what benefits they are offering you, if any, and what equipment they will provide you with, if any. I also don't know what taxes, if any, a U.S. company has to pay when hiring a remote employee in a foreign country. If anybody on here knows the answer to that, please chime in. Balanced against that, the company likely sees disadvantages to hiring a foreign remote employee, too. Communication will be more difficult, which may result in inefficiency. My previous employer used some contractors in India and while there were certainly advantages, the language and time zone issues caused difficulties. There are almost certainly some international bureaucratic inconveniences they will have to deal with. Etc. So while you should certainly calculate what it would cost them to have a domestic employee doing the same job, that's not necessarily the end of the story. And ultimately it all comes down to negotiations. Even if the company knows that by the time they add in taxes and benefits and whatever, a domestic employee will cost them $100,000 a year, if they are absolutely convinced that they should be able to hire an Austrian for $60,000 a year, that might be the best offer you will get. You can point out the cost savings, and maybe they will concede the point and maybe not.\"",
"title": ""
},
{
"docid": "536212",
"text": "\"Essentially, yes. Any and all decisions a business make are for one reason: $$$ Your paid vacation? That's an incentive to get better, more productive workers. Your company has done a cost/benefit analysis and they've figured out that it's worth their money to pay you to do nothing for a week because that paid vacation is a perk of the job that will get them better job applicants. OR they want you taking a vacation because you'll come back rested and refreshed. And that makes them money. (See also: every other job benefit.) \"\"Oh, well my company is a great civic member who does good work for the community.\"\" And I bet they never pass up an opportunity to tell people about it. Because they don't care about feeding the homeless kittens. They care about customers KNOWING they feed the homeless kittens. Because it makes them money. The point of a business is to make money, not employ people.\"",
"title": ""
},
{
"docid": "563277",
"text": "You've convinced me with your capital letters. How could I have been so blind? The average person on unemployment is there for 39 weeks. Not permanent. So, you're basing your argument on false data. Further, a certain portion of these are there not because of stigma, but because the industry in which they worked doesn't need the labor. Another portion is only actually looking for work in order to continue qualifying for unemployment, and will retire after the benefits run out. You're talking about making a truly significant policy change with real negative effects on many, many real people in order to help a part of the population that doesn't necessarily exist in the manner you imagine it does. From what I can tell, you have done nothing to arrive at your conclusions beyond feeling an emotional reaction with no actual sense of the data. Or any actual knowledge of economics.",
"title": ""
},
{
"docid": "447415",
"text": "I certainly think there is some truth here but a lot of those jobs have become more competitive because of schooling requirements. You don’t have to study to be electrician but It’s 2017, it will certainly give you a leg up. Everyone requires some kind of schooling. Unions are great but those dying or dead in most places. It’s nice your husband’s place offers apprenticeships because those are few and far between today. I think it’s partially true that people don’t look in the right places. I don’t think people are lazy. Then you also have to keep in mind socio-economic status. A lot of people are very poor and mildly educated and those jobs just aren’t there for them. It’s beyond a jobs problem at this point. A lot of people are studying people in grinding poverty like PTSD victims. This is why I was trying to say that I don’t really know how to fix it. A lot of people are beyond help at this point and telling them to get off their lazy ass and get a job isn’t as easy as it sounds. It’s great your husband has a union and a good job but that’s not the case for everyone. There are a lot of moving parts there. Check out a little background research on that. It brings a little more perspective. It’s complex. Edit: I’m reading that a lot of trade unions will sponsor apprenticeships which goes to my other point that unions are dead. Come to Wisconsin and try to find a union job. Good fucking luck.",
"title": ""
},
{
"docid": "485217",
"text": "There actually wouldn't be a need to increase prices in order to provide Wal-mart employees with a living wage though. There is another way. Cut executive pay. In fact, I'd like to see a law on the books that makes maximum executive pay, including bonuses and stock, a certain percentage or multiple of the pay of the lowest paid employee. Before you can raise the pay of an executive beyond a certain point, the pay of all the employees simply has to go up. This would give executives another incentive to raise the pay of their employees, since their ability to get a raise would depend on it. I'm thinking something along the lines of executive pay being capped at 100x the pay of the lowest paid employee. Your employees make $20,000 a year? Your executives make no more than $2,000,000 a year. Want that to go up? Guess it's time for raises then. The main point of such a law would be to make sure that employees are paid for the benefits they bring in to the company, along with having a living wage. As it stands, employees might get a 25 cent/hour raise a year in low wage jobs, if they get anything at all. This way, if there's enough money to go around to the people at the top, the people at the bottom also see some of that money.",
"title": ""
},
{
"docid": "217006",
"text": "Am I correct in understanding that a Scrip Dividend involves the issue of new shares instead of the purchase of existing shares? Yes. Instead of paying a cash dividend to shareholders, the company grants existing shareholders new shares at a previously determined price. This allows shareholders who join the program to obtain new shares without incurring transaction costs that would normally occur if they purchased these shares in the market. Does this mean that if I don't join this program, my existing shares will be diluted every time a Scrip Dividend is paid? Yes, because the number of shares has increased, so the relative percentage of shares in the company you hold will decrease if you opt-out of the program. The price of the existing shares will adjust so that the value of the company is essentially unchanged (similar to a stock split), but the number of outstanding shares has increased, so the relative weight of your shares declines if you opt out of the program. What is the benefit to the company of issuing Scrip Dividends? Companies may do this to conserve their cash reserves. Also, by issuing a scrip dividend, corporations could avoid the Advanced Corporation Tax (ACT) that they would normally pre-pay on their distributions. Since the abolition of the ACT in 1999, preserving cash reserves is the primary reason for a company to issue scrip dividends, as far as I know. Whether or not scrip dividends are actually a beneficial strategy for a company is debatable (this looks like a neat study, even though I've only skimmed it). The issue may be beneficial to you, however, because you might receive a tax benefit. You can sell the scrip dividend in the market; the capital gain from this sale may fall below the annual tax-free allowance for capital gains, in which case you don't pay any capital gains tax on that amount. For a cash dividend, however, there isn't a minimum taxable amount, so you would owe dividend tax on the entire dividend (and may therefore pay more taxes on a cash dividend).",
"title": ""
},
{
"docid": "295384",
"text": "\"It depends on what kind of pension you get and your anticipated retirement income. If you have one of those nice defined benefit plans that pays 90% of your last 5 years' average salary annually, you might not want to bother with a separate RRSP and put your money into other use instead. While most Canadians should worry about not having enough to retire on, some might end up with too much and costing them in the form current purchases and entitlements to government retirement benefits. Figuring out how much you need for retirement is not trivial either. A lot of people talks about planning for needing 70% of what you made now as a way to preserve your lifestyle. Well, my opinion is that those type of generalization might work for the people in the middle of the income band and is too little for those in the low-income and possibly too much for those with high income. My own approach is estimate your retirement income requirement by listing out your anticipated expenses as if you were doing budget. I would agree that's not the best approach either (back to my comment about no one size fits all), but it's one that I feel most comfortable with. Once you have that figure, factor in what you think you will get from the government (OAS, CPP and etc) and you will have the amount of money you need for retirement. I will warn against using \"\"average life expectancy\"\" to forecast your retirement needs, 'cos 50% of the people will end up with extra money (not a bad problem) and the other 50% will run out of money (bad but very true problem) if you use that approach. Instead of going on and write an essay on this topic, I will simply say this - everyone's situation is different and, just like solving any other complex problems, you need to start with \"\"end\"\" in mind and work things backward, with a ton of different scenario to be able to cope with whatever curveballs life might throw at you. If you spend enough time in the library/bookstore looking through books on the topic of \"\"estate planning\"\" and \"\"retirement planning\"\", you will find people arguing back and fro on these topics - this is a sign that this is complex and no one has the one \"\"good\"\" answer for. Do a bit of reading by yourself and, if still unsure or just want to be sure, go spend the money and review your plan with a fee-only advisor. They will be able to provide another opinion on your situation after thoroughly studying your situation.\"",
"title": ""
},
{
"docid": "125171",
"text": "Until you find a job, I would recommend doing nothing more than a bank checking account or a checking and savings account. Some alternatives, such as savings bonds, would be okay if you were perfectly sure you did not need the money in the next six months. Consider working for a place such as McDonald's in the meantime. Once you have stable employment, there are two paths you could take. The first is a bond fund. It would provide fair market returns for the time between now and the collection of social security. The second would be a traditional annuity. You have to be careful with them. If it sounds much better than what others are offering, it is probably a scam. Your interest in an annuity is that it will pay you money for as long as you live. If you live to be 105 you will still be getting payments. A bond fund would have run out of money long ago by that time. The biggest thing for you right now is getting to when Medicare takes over from private health. Looking for any job is important right now to preserve cash. Although I do not normally recommend annuities, I do with smaller amounts of cash. It is unlikely you will ever recover this sum again and the time remaining to save is very short. The greatest challenge with an annuity is regret. You can't get the money back once you have turned it into an income stream. On the other hand, it will last as long as you live. The only important caveat is that if you are in poor health, then the bond fund would be better for you because you may not live to be very old.",
"title": ""
},
{
"docid": "224530",
"text": "\"Logic fail. The qty of shares is irrelevant. What matters is the value, which is, of course, quite high -- and, what's more, the P/E ratio, which is extremely favorable. Having worked in operations at Apple for 7 years, I can tell you that the company is very lean and efficient. 25% matching is extremely generous. 25% contribution rates are standard in corporate jobs (contribution rates are what maximum percentage of your pre-tax income you can opt to set aside into a 401K; this is different than matching). It absolutely is not bare bones to be given 25% matching. Although I no longer work at Apple, I still have my 401K, and the administration of it is good, as is the choice of funds. Back to the matching... It's free money. For every $1 you put in your 401K (pretax, btw), Apple puts in a quarter. Having worked in other corporations over my career, I can tell you that this level of matching is pretty much as good as it gets. For a good part of the time I worked there I made around $30K (not in Retail, but in Operations, as mentioned before). I maxed out the Employee Stock Purchase Program contribution and mostly maxed out my 401K contribution. Now, 12 years later, my stock appreciated beyond my wildest expectations. I have made well over six figures on it over the years. If I never sold any, it would be worth over $500,000 by now. All that from 10% contributions on a salary that ranged from about $26K when I started out to about $46K when I left 7 years later. My 401K holdings are worth about $60K, I think, invested extremely conservatively. I have had it in money market funds since right before the 2008/2009 crash, which I anticipated. So the investment benefits at Apple served me extremely well. My stock appreciation paid for my car, and it will soon cover the down payment on a house. I was essentially able to \"\"retire\"\" to be a stay-at-home-mom when my son was born, thanks to the safety net I have from my Apple stock. Regarding health benefits... I think you meant to say copays, not deductibles. When I was there, there were no copays. I forgot what the deductibles were, but for most routine visits, you wouldn't need to pay out of pocket. Annual physicals are included in the health plan, up to $250. The health plan works with various local providers to ensure that the $250 allotment will cover all expenses needed for an annual physical. This physical is separate and in addition to a women's health annual exam (pap smear/pelvic exam/etc) that is also included without copay. I'm pretty sure annual mammograms are covered. All prenatal visits are covered with zero copay. All child well checks, including immunizations, covered with zero copay. Two dental checks a year. Dental Xrays at regular intervals included. Annual vision exams and, I think $300 annually towards glasses or contacts included, IIRC. Time off was pretty standard and accrued by the hour worked, which was nice. There was no \"\"you have to be with the company for X length of time\"\" before time off benefits began to accrue, or before any benefits kicked in, for that matter. By about Year 5, I had easily racked up enough vacation days to take 3 weeks off at a time. The longer you have been with the company, the faster your time off accrues. And each summer they'd offer a cash-out program, where you could double up on time off, where if you took off a week, you could opt to deplete your accrued vacation time by two weeks and get double pay for it. A lot of people liked this option. The points for absenteeism thing seemed a bit silly -- and seemed to only have been implemented in one store and then only for a brief time. From what I gathered in the article, it was an experiment that failed miserably. The other corporation I have spent a significant amount of time working at is Whole Foods Market, in their corporate office. While both Apple and Whole Foods always are selected as two of the top companies to work for by Forbes in their annual report, as far as benefits went, Apple's were far superior in most aspects. With respect to company culture, I personally found Whole Foods to be better, but that was sort of a personal preference. Both were dream jobs, and I consider myself very fortunate to have had the opportunity to work for two outstanding companies that both treated me very well. Oh- and incidentally, Ron Johnson, who was VP of Retail at Apple from the inception of the stores until like a year ago, now is CEO of JC Penny, and, I suspect, is fully behind JCP's ad campaigns which include images of families with same-sex parents. JCP has stepped deliberately and full-on into what is, unfortunately, still a controversial topic and has taken a firm stand in support of all types of loving families. I have to wonder if part of this might have been inspired by the fact that Apple's new CEO, Tim Cook, is gay. Ron Johnson would have worked closely alongside Cook during his tenure. I met Ron once and found him to be a great guy, and I worked with the Retail operations folks from the time the stores launched. They were a great team that worked hard and were very sincere and dedicated. You could see his leadership reflecting in each member of the team.\"",
"title": ""
},
{
"docid": "237204",
"text": "COBRA is with regards to any termination, not only if you're laid off. If you leave your job voluntarily you're still eligible for COBRA, at least from my experience in California. Once you start working at the new job that provides health benefits - you're expected to roll-off of COBRA. No. Once you run out of the COBRA period - you're on your own.",
"title": ""
},
{
"docid": "352794",
"text": "\"First of all, one thing that is very important: Match is always better than no match. So, you should definitely use that match on your HSA if you've already maxed out the company match on your 401(k). In fact, for most people there won't be much reason to invest in your 401(k) above the company match at all. If, for example, your company matches only up to 5%, and you want to invest 15% of income into retirement, you ought to open an IRA instead (Roth or standard depending on your situation) and put the extra 10% in there. Beyond that, you're right, HSA's (the accounts themselves) have all the benefits of a 401(k). I wouldn't invest there for retirement instead an IRA, though. There is just no reason. The only built-in downside of an HSA is the HDHP attachment, which may be undesirable to some employees or in certain situations. If you want to get down to raw dollar figures and your company is offering both a standard health plan and a HDHP+HSA, the calculation will be dependent on the premiums and benefits of each and your projected costs of your health care (which is always a crystal ball estimation anyway). Those costs and benefits can vary wildly, from a completely obvious choice on either the HDHP or standard plan, or pretty much a wash where you decide based on your comfort level with a high deductible. To illustrate... Standard plan: Your company might offer a standard plan that costs you $100 out of pocket for an individual. That means you pay a minimum of $1200 a year for health care. Most plans will have copays (a flat amount like $15 you pay for standard doctor consultations), a deductible (you pay 100% of fees up to this, co-pays don't count), a percentage you pay beyond the deductible (20% is typical), and a maximum (like $1000 per individual per year - beyond this, up to a \"\"lifetime\"\" maximum benefit of like $2 million, you won't be charged anything). In a standard plan where you have no expenses, you might pay $1200 a year plus a couple co-pays, for a total of $1230. In a bad year with surgery, you might max out, so $1200 + $30 + $1000 = $2230. HDHP/HSA: These plans are very different. You might still pay a premium, I.E. $30 a month. They will still have a deductible and maximum, but they might be the same amount. You will probably not have copays (I didn't when I had one, but I could be wrong), which means a standard doctor visit will cost more like $80-100. In a good year, this will mean that you pocket $500 from your company, but pay back $360 in premiums. A couple doctor visits would mean there's only $300 left in your account at the end of the year. But, that's still a net cost of only $60, compared to $1230. Big win! In a bad year, you would end up out of pocket the max (say $2000) plus premiums, minus the $500, for a total of $1860. In this case, still better than the standard plan. The important difference will come in an in-between year. You will reach the max quicker on an HDHP than you will on a standard plan. With a family, where all of these numbers are higher, and you have more people to be getting sick/injured this might make the standard plan a better benefit. However, since whatever you build up in an HSA account stays with you forever, while you're single and have only your own health to be concerned about, that is probably a good choice. When you have a family, things might change and you switch to a standard plan, but you still have that war-chest to offset copays and hospital visits in future years. I was forced onto an HSA for 2 years with a smaller company. They had a really good contribution, $2500 if I remember right, and we saved up big time. Later, when my wife was pregnant, we were on a low-deductible standard plan and paid all our fees out of the HSA. It worked out great. I say, as long as the averaged yearly expected costs make sense after doing calculations illustrated above, go for it!\"",
"title": ""
}
] |
710
|
Long chain polyunsaturated fatty acids supplementation reduces wheezing and asthma.
|
[
{
"docid": "22442133",
"text": "OBJECTIVE To determine whether dietary n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation of pregnant women with a fetus at high risk of allergic disease reduces immunoglobulin E associated eczema or food allergy at 1 year of age. DESIGN Follow-up of infants at high hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome (DOMInO) randomised controlled trial. SETTING Adelaide, South Australia. PARTICIPANTS 706 infants at high hereditary risk of developing allergic disease whose mothers were participating in the DOMInO trial. INTERVENTIONS The intervention group (n=368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n=338) received matched vegetable oil capsules without n-3 LCPUFA. MAIN OUTCOME MEASURE Immunoglobulin E associated allergic disease (eczema or food allergy with sensitisation) at 1 year of age. RESULTS No differences were seen in the overall percentage of infants with immunoglobulin E associated allergic disease between the n-3 LCPUFA and control groups (32/368 (9%) v 43/338 (13%); unadjusted relative risk 0.68, 95% confidence interval 0.43 to 1.05, P=0.08; adjusted relative risk 0.70, 0.45 to 1.09, P=0.12), although the percentage of infants diagnosed as having atopic eczema (that is, eczema with associated sensitisation) was lower in the n-3 LCPUFA group (26/368 (7%) v 39/338 (12%); unadjusted relative risk 0.61, 0.38 to 0.98, P=0.04; adjusted relative risk 0.64, 0.40 to 1.02, P=0.06). Fewer infants were sensitised to egg in the n-3 LCPUFA group (34/368 (9%) v 52/338 (15%); unadjusted relative risk 0.61, 0.40 to 0.91, P=0.02; adjusted relative risk 0.62, 0.41 to 0.93, P=0.02), but no difference between groups in immunoglobulin E associated food allergy was seen. CONCLUSION n-3 LCPUFA supplementation in pregnancy did not reduce the overall incidence of immunoglobulin E associated allergies in the first year of life, although atopic eczema and egg sensitisation were lower. Longer term follow-up is needed to determine if supplementation has an effect on respiratory allergic diseases and aeroallergen sensitisation in childhood. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry ACTRN12610000735055 (DOMInO trial: ACTRN12605000569606).",
"title": "Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants’ allergies in first year of life: randomised controlled trial"
}
] |
[
{
"docid": "24269361",
"text": "There are two main families of polyunsaturated fatty acids (PUFAs), the n-6 and the n-3 families. It has been suggested that there is a causal relationship between n-6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n-6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n-3 PUFAs and these fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n-3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n-3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.",
"title": "Atopy risk in infants and children in relation to early exposure to fish, oily fish, or long-chain omega-3 fatty acids: a systematic review."
},
{
"docid": "33912748",
"text": "OBJECTIVE To determine if n-3 polyunsaturated fatty acid (PUFA) supplementation (versus treatment with n-6 polyunsaturated or other fatty acid supplements) affects the metabolism of osteoarthritic (OA) cartilage. METHODS The metabolic profile of human OA cartilage was determined at the time of harvest and after 24-hour exposure to n-3 PUFAs or other classes of fatty acids, followed by explant culture for 4 days in the presence or absence of interleukin-1 (IL-1). Parameters measured were glycosaminoglycan release, aggrecanase and matrix metalloproteinase (MMP) activity, and the levels of expression of messenger RNA (mRNA) for mediators of inflammation, aggrecanases, MMPs, and their natural tissue inhibitors (tissue inhibitors of metalloproteinases [TIMPs]). RESULTS Supplementation with n-3 PUFA (but not other fatty acids) reduced, in a dose-dependent manner, the endogenous and IL-1-induced release of proteoglycan metabolites from articular cartilage explants and specifically abolished endogenous aggrecanase and collagenase proteolytic activity. Similarly, expression of mRNA for ADAMTS-4, MMP-13, and MMP-3 (but not TIMP-1, -2, or -3) was also specifically abolished with n-3 PUFA supplementation. In addition, n-3 PUFA supplementation abolished the expression of mRNA for mediators of inflammation (cyclooxygenase 2, 5-lipoxygenase, 5-lipoxygenase-activating protein, tumor necrosis factor alpha, IL-1alpha, and IL-1beta) without affecting the expression of message for several other proteins involved in normal tissue homeostasis. CONCLUSION These studies show that the pathologic indicators manifested in human OA cartilage can be significantly altered by exposure of the cartilage to n-3 PUFA, but not to other classes of fatty acids.",
"title": "Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids."
},
{
"docid": "20148808",
"text": "The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4 (IL4)-producing CD4+ T cells and decreased levels of circulating immunoglobulin E (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less motile in response to CCL19 in vitro, and exhibit a dampened ability to transport inhaled allergens to lung draining nodes. Our data thus demonstrate that gut dysbiosis can exacerbate allergic lung inflammation through both T cell- and DC-dependent mechanisms that are inhibited by SCFAs.",
"title": "Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids"
},
{
"docid": "3866315",
"text": "Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with ω-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array of bioactive lipid signals. Human endothelial cells with upregulated COX-2 treated with ASA converted C20:5 ω-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Each was used by polymorphonuclear leukocytes to generate separate classes of novel trihydroxy-containing mediators, including 5-series 15R-LX5 and 5,12,18R-triHEPE. These new compounds proved to be potent inhibitors of human polymorphonuclear leukocyte transendothelial migration and infiltration in vivo (ATL analogue > 5,12,18R-triHEPE > 18R-HEPE). Acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant COX-2 as well as ω-5 and ω-9 oxygenations of other fatty acids that act on hematologic cells. These findings establish new transcellular routes for producing arrays of bioactive lipid mediators via COX-2–nonsteroidal antiinflammatory drug–dependent oxygenations and cell–cell interactions that impact microinflammation. The generation of these and related compounds provides a novel mechanism(s) for the therapeutic benefits of ω-3 dietary supplementation, which may be important in inflammation, neoplasia, and vascular diseases.",
"title": "Novel Functional Sets of Lipid-Derived Mediators with Antiinflammatory Actions Generated from Omega-3 Fatty Acids via Cyclooxygenase 2–Nonsteroidal Antiinflammatory Drugs and Transcellular Processing"
},
{
"docid": "25974070",
"text": "The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.",
"title": "Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function."
},
{
"docid": "34733465",
"text": "BACKGROUND Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.",
"title": "Association of cystic fibrosis with abnormalities in fatty acid metabolism."
},
{
"docid": "23388442",
"text": "Research describing fatty acids as modulators of inflammation and immune responses abounds. Many of these studies have focused on one particular group of fatty acids, omega-3. The data from animal studies have shown that these fatty acids can have powerful anti-inflammatory and immunomodulatory activities in a wide array of diseases (e.g., autoimmunity, arthritis, and infection). However, the evidence from human trials is more equivocal. In this review, a historical framework for understanding how and why fatty acids may affect the immune system is provided. Second, highlights of two recent landmark reports from the Agency for Healthcare Research and Quality are presented. These reports critically evaluate the evidence from human clinical trials of omega-3 fatty acids and rheumatoid arthritis, asthma, and a few other immune-mediated diseases. Third, the data from human clinical trials investigating the impact of various bioactive fatty acids on ex vivo and in vivo immune response are reviewed. Limitations in experimental design and immune assays commonly used are discussed. The discordance between expectation and evidence in this field has been a disappointment. Recommendations for improving both animal-based and human studies are provided.",
"title": "Fatty acids as modulators of the immune response."
},
{
"docid": "25761154",
"text": "Exercise-induced asthma is defined as an intermittent narrowing of the airways, demonstrated by a decrease in some measure of flow, that the patient experiences as wheezing, chest tightness, coughing, and difficulty breathing that is triggered by exercise. Exercise will trigger asthma in most individuals who have chronic asthma, as well as in some who do not otherwise have asthma. Definitive diagnosis requires demonstration of a drop in flow rate, typically > or = 13-15% for forced expiratory volume in one second (FEV1) and > or = 15-20% for peak expiratory flow rate (PEFR), after exercise, associated with symptoms. Prevalence data indicate that this disorder is very common in those who participate in recreational sports as well as in highly competitive athletes, with at least 12-15% of unselected athletes having positive exercise challenges. Treatment of exercise induced asthma involves use of nonpharmacological measures (such as the use of the refractory period after exercise and prewarming air) as well as use of medications (beta-agonists, cromolyn, and nedocromil). With treatment, those who suffer from exercise-induced asthma may be able to participate and compete at the highest levels of performance.",
"title": "Exercise-induced asthma: a practical guide to definitions, diagnosis, prevalence, and treatment."
},
{
"docid": "4641348",
"text": "BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.",
"title": "Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease"
},
{
"docid": "8458567",
"text": "PEROXISOMES are cytoplasmic organelles which are important in mammals in modulation of lipid homeostasis, including the metabolism of long-chain fatty acids and conversion of cholesterol to bile salts (reviewed in refs 1 and 2). Amphipathic carboxylates such as clofibric acid have been used in man as hypolipidaemic agents and in rodents they stimulate the proliferation of peroxisomes. These agents, termed peroxisome proliferators, and all-trans retinoic acid activate genes involved in peroxisomal-mediated β-oxidation of fatty acids1–4. Here we show that the receptor activated by peroxisome proliferators5 and the retinoid X receptor-α (ref. 6) form a heterodimer that activates acyl-CoA oxidase gene expression in response to either clofibric acid or the retinoid X receptor-α ligand, 9-cis retinoic acid, an all-trans retinoic acid metabolite7,8; simultaneous exposure to both activators results in a synergistic induction of gene expression. These data demonstrate the coupling of the peroxisome proliferator and retinoid signalling pathways and provide evidence for a physiological role for 9-cis retinoic acid in modulating lipid metabolism.",
"title": "Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors"
},
{
"docid": "17163294",
"text": "BACKGROUND Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. However, up to now it is not clear whether different cancer types are characterized by a specific metabolite profile. Therefore, this study aims to evaluate whether the plasma metabolic phenotype allows to discriminate between lung and breast cancer. PATIENTS AND METHODS The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 80 female breast cancer patients and 54 female lung cancer patients, all with an adenocarcinoma. The validity of the model was examined by permutation testing and by classifying an independent validation cohort of 60 female breast cancer patients and 81 male lung cancer patients, all with an adenocarcinoma. RESULTS The model allows to classify 99% of the breast cancer patients and 93% of the lung cancer patients correctly with an area under the curve (AUC) of 0.96 and can be validated in the independent cohort with a sensitivity of 89%, a specificity of 82% and an AUC of 0.94. Decreased levels of sphingomyelin and phosphatidylcholine (phospholipids with choline head group) and phospholipids with short, unsaturated fatty acid chains next to increased levels of phospholipids with long, saturated fatty acid chains seem to indicate that cell membranes of lung tumors are more rigid and less sensitive to lipid peroxidation. The other discriminating metabolites are pointing to a more pronounced response of the body to the Warburg effect for lung cancer. CONCLUSION Metabolic phenotyping of plasma allows to discriminate between lung and breast cancer, indicating that the metabolite profile reflects more than a general cancer marker. CLINICAL TRIAL REGISTRATION NUMBER NCT02362776.",
"title": "Metabolic phenotyping of human blood plasma: a powerful tool to discriminate between cancer types?"
},
{
"docid": "20672596",
"text": "Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by 'resting' macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.",
"title": "Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages."
},
{
"docid": "19278208",
"text": "Background/Objectives:Folic acid supplementation has been suggested to reduce the risk of preeclampsia. However, results from few epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of preeclampsia. Subjects/Methods:A birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. A total of 10 041 pregnant women without chronic hypertension or gestational hypertension were enrolled. Results:Compared with nonusers, folic acid supplement users had a reduced risk of preeclampsia (OR=0.61, 95% CI: 0.43–0.87). A significant dose–response of duration of use was observed among women who used folic acid supplemention during pregnancy only (P-trend=0.007). The reduced risk associated with folic acid supplement was similar for mild or severe preeclampsia and for early- or late-onset preeclampsia, although the statistical significant associations were only observed for mild (OR=0.50, 95% CI: 0.30–0.81) and late-onset (OR=0.60, 95% CI: 0.42–0.86) preeclampsia. The reduced risk associated with dietary folate intake during pregnancy was only seen for severe preeclampsia (OR=0.52, 95% CI: 0.31–0.87, for the highest quartile of dietary folate intake compared with the lowest).Conclusions:Our study results suggest that folic acid supplementation and higher dietary folate intake during pregnancy reduce the risk of preeclampsia. Future studies are needed to confirm the associations.",
"title": "Folic acid supplementation and dietary folate intake, and risk of preeclampsia"
},
{
"docid": "25510546",
"text": "Increased lipid supply causes beta cell death, which may contribute to reduced beta cell mass in type 2 diabetes. We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present in islets of an animal model of diabetes and of humans with type 2 diabetes. Expression of genes involved in ER stress was evaluated in insulin-secreting MIN6 cells exposed to elevated lipids, in islets isolated from db/db mice and in pancreas sections of humans with type 2 diabetes. Overproduction of the ER chaperone heat shock 70 kDa protein 5 (HSPA5, previously known as immunoglobulin heavy chain binding protein [BIP]) was performed to assess whether attenuation of ER stress affected lipid-induced apoptosis. We demonstrated that the pro-apoptotic fatty acid palmitate triggers a comprehensive ER stress response in MIN6 cells, which was virtually absent using non-apoptotic fatty acid oleate. Time-dependent increases in mRNA levels for activating transcription factor 4 (Atf4), DNA-damage inducible transcript 3 (Ddit3, previously known as C/EBP homologous protein [Chop]) and DnaJ homologue (HSP40) C3 (Dnajc3, previously known as p58) correlated with increased apoptosis in palmitate- but not in oleate-treated MIN6 cells. Attenuation of ER stress by overproduction of HSPA5 in MIN6 cells significantly protected against lipid-induced apoptosis. In islets of db/db mice, a variety of marker genes of ER stress were also upregulated. Increased processing (activation) of X-box binding protein 1 (Xbp1) mRNA was also observed, confirming the existence of ER stress. Finally, we observed increased islet protein production of HSPA5, DDIT3, DNAJC3 and BCL2-associated X protein in human pancreas sections of type 2 diabetes subjects. Our results provide evidence that ER stress occurs in type 2 diabetes and is required for aspects of the underlying beta cell failure.",
"title": "Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes"
},
{
"docid": "21636085",
"text": "BACKGROUND Increased plasma homocysteine is associated with coronary artery disease, peripheral vascular disease and venous thrombosis. Folic acid is the most effective therapy for reducing homocysteine levels. The lowest effective supplement of folic acid is not known, particularly for the elderly who have the highest prevalence of these conditions. AIM To explore the effects of daily supplements of 0, 50, 100, 200, 400 and 600 microg folic acid on plasma homocysteine in an elderly population. DESIGN Randomized double-blind placebo-controlled trial. METHODS Participants (n=368) aged 65-75 years were randomly allocated to receive one of the treatments for 6 weeks. Plasma homocysteine was recorded after 3 weeks and 6 weeks of supplementation. RESULTS Only the 400 microg and 600 microg groups had significantly lower homocysteine levels compared to placebo (p=0.038 and p<0.001, respectively). Using multiple linear regression and each individual's total folic acid intake (diet plus supplement), a total daily folic acid intake of 926 microg per day would be required to ensure that 95% of the elderly population would be without cardiovascular risk from folate deficiency. DISCUSSION A daily folic acid intake of 926 microg is unlikely to be achieved by diet alone. Individual supplementation or fortification of food with folic acid will be required to reach this target.",
"title": "The effect of folic acid supplementation on plasma homocysteine in an elderly population."
},
{
"docid": "6372244",
"text": "Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including the primary bile acid taurocholate for germination, and carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.",
"title": "Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection"
},
{
"docid": "39558597",
"text": "Aging is associated with impaired fasted oxidation of nonesterified fatty acids (NEFA) suggesting a mitochondrial defect. Aging is also associated with deficiency of glutathione (GSH), an important mitochondrial antioxidant, and with insulin resistance. This study tested whether GSH deficiency in aging contributes to impaired mitochondrial NEFA oxidation and insulin resistance, and whether GSH restoration reverses these defects. Three studies were conducted: (i) in 82-week-old C57BL/6 mice, the effect of naturally occurring GSH deficiency and its restoration on mitochondrial (13) C1 -palmitate oxidation and glucose metabolism was compared with 22-week-old C57BL/6 mice; (ii) in 20-week C57BL/6 mice, the effect of GSH depletion on mitochondrial oxidation of (13) C1 -palmitate and glucose metabolism was studied; (iii) the effect of GSH deficiency and its restoration on fasted NEFA oxidation and insulin resistance was studied in GSH-deficient elderly humans, and compared with GSH-replete young humans. Chronic GSH deficiency in old mice and elderly humans was associated with decreased fasted mitochondrial NEFA oxidation and insulin resistance, and these defects were reversed with GSH restoration. Acute depletion of GSH in young mice resulted in lower mitochondrial NEFA oxidation, but did not alter glucose metabolism. These data suggest that GSH is a novel regulator of mitochondrial NEFA oxidation and insulin resistance in aging. Chronic GSH deficiency promotes impaired NEFA oxidation and insulin resistance, and GSH restoration reverses these defects. Supplementing diets of elderly humans with cysteine and glycine to correct GSH deficiency could provide significant metabolic benefits.",
"title": "Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione."
},
{
"docid": "198309074",
"text": "Introduction: Among the inflammatory mediators involved in the pathogenesis of obesity, the cell adhesion molecules Pselectin, E-selectin, VCAM-1, ICAM-1 and the chemokine MCP-1 stand out. They play a crucial role in adherence of cells to endothelial surfaces, in the integrity of the vascular wall and can be modulated by body composition and dietary pattern. Objectives: To describe and discuss the relation of these cell adhesion molecules and chemokines to anthropometric, body composition, dietary and biochemical markers. Methods: Papers were located using scientific databases by topic searches with no restriction on year of publication. Results: All molecules were associated positively with anthropometric markers, but controversial results were found for ICAM-1 and VCAM-1. Not only obesity, but visceral fat is more strongly correlated with E-selectin and MCP-1 levels. Weight loss influences the reduction in the levels of these molecules, except VCAM-1. The distribution of macronutrients, excessive consumption of saturated and trans fat and a Western dietary pattern are associated with increased levels. The opposite could be observed with supplementation of w-3 fatty acid, healthy dietary pattern, high calcium diet and high dairy intake. Regarding the biochemical parameters, they have inverse relation to HDLC and positive relation to total cholesterol, triglycerides, blood glucose, fasting insulin and insulin resistance. Conclusion: Normal anthropometric indicators, body composition, biochemical parameters and eating pattern positively modulate the subclinical inflammation that results from obesity by reducing the cell adhesion molecules and chemokines.",
"title": "Adhesion molecules and chemokines: relation to anthropometric, body composition, biochemical and dietary variables"
},
{
"docid": "4319174",
"text": "All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue. Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner. Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.",
"title": "Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis"
},
{
"docid": "4550036",
"text": "The authors investigated the association between folic acid supplementation and gestational hypertension. The study population included women with nonmalformed infants in the United States and Canada who were participating in the Slone Epidemiology Center Birth Defects Study between 1993 and 2000. Women were interviewed within 6 months after delivery about sociodemographic and medical factors, the occurrence of hypertension with or without preeclampsia, and multivitamin use in pregnancy. Relative risks, adjusted for weight, parity, twin pregnancy, diabetes, smoking, education, and family income, were estimated using Cox regression models. Of 2,100 women, 204 (9.7%) reported gestational hypertension (onset after the 20th week of gestation). The multivariate-adjusted relative risk of developing gestational hypertension during the month after folic acid supplementation, compared with not using folic acid during that same month, was 0.55 (95% confidence interval: 0.39, 0.79). This finding suggests that folic acid-containing multivitamins may reduce the risk of gestational hypertension.",
"title": "Risk of gestational hypertension in relation to folic acid supplementation during pregnancy."
},
{
"docid": "18375089",
"text": "Angiogenesis is a necessary step in tumor growth and metastasis. It is well established that the metabolites of omega-6 and omega-3 fatty acids, which must be obtained through the diet and cannot be synthesized de novo in mammals, have differential effects on cellular processes. Omega-6 fatty acid (n−6 FA)-derived metabolites promote angiogenesis by increasing growth factor expression whereas omega-3 fatty acids (n−3 FA) have anti-angiogenic and antitumor properties. However, most studies thus far have failed to account for the role of the n−6 FA/n−3 FA ratio in angiogenesis and instead examined the absolute levels of n−6 and n−3 FA. This review highlights the biochemical interactions between n−6 and n−3 FA and focuses on how the n−6/n−3 FA ratio in tissues modulates tumor angiogenesis. We suggest that future work should consider the n−6/n−3 FA ratio to be a key element in experimental design and analysis. Furthermore, we recommend that clinical interventions should aim to both reduce n−6 metabolites and simultaneously increase n−3 FA intake.",
"title": "The role of the tissue omega-6/omega-3 fatty acid ratio in regulating tumor angiogenesis"
},
{
"docid": "15551129",
"text": "Many species of mycobacteria form structured biofilm communities at liquid–air interfaces and on solid surfaces. Full development of Mycobacterium smegmatis biofilms requires addition of supplemental iron above 1 μM ferrous sulphate, although addition of iron is not needed for planktonic growth. Microarray analysis of the M. smegmatis transcriptome shows that iron-responsive genes – especially those involved in siderophore synthesis and iron uptake – are strongly induced during biofilm formation reflecting a response to iron deprivation, even when 2 μM iron is present. The acquisition of iron under these conditions is specifically dependent on the exochelin synthesis and uptake pathways, and the strong defect of an iron–exochelin uptake mutant suggests a regulatory role of iron in the transition to biofilm growth. In contrast, although the expression of mycobactin and iron ABC transport operons is highly upregulated during biofilm formation, mutants in these systems form normal biofilms in low-iron (2 μM) conditions. A close correlation between iron availability and matrix-associated fatty acids implies a possible metabolic role in the late stages of biofilm maturation, in addition to the early regulatory role. M. smegmatis surface motility is similarly dependent on iron availability, requiring both supplemental iron and the exochelin pathway to acquire it.",
"title": "The role of iron in Mycobacterium smegmatis biofilm formation: the exochelin siderophore is essential in limiting iron conditions for biofilm formation but not for planktonic growth"
},
{
"docid": "13774178",
"text": "BACKGROUND Schisandra, a globally distributed plant, has been widely applied for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China. In the present work, a rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics was conducted to investigate the intervention effect of Schisandra chinensis lignans (SCL) on hyperlipidemia mice induced by high-fat diet (HFD). METHODS Hyperlipidemia mice were orally administered with SCL (100 mg/kg) once a day for 4 weeks. Serum biochemistry assay of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) was conducted to confirm the treatment of SCL on lipid regulation. Metabolomics analysis on serum samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of liver lipid metabolism, sterol regulatory element-binding proteins (SREBPs) and its related gene expressions were measured by quantitative real-time polymerase chain reaction (RT-PCR) for investigating the underlying mechanism. RESULTS Oral administration of SCL significantly decreased the serum levels of TC, TG and LDL-c and increased the serum level of HDL-c in the hyperlipidemia mice, and no effect of SCL on blood lipid levels was observed in control mice. Serum samples were scattered in the PCA scores plots in response to the control, HFD and SCL group. Totally, thirteen biomarkers were identified and nine of them were recovered to the normal levels after SCL treatment. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, the anti-hyperlipidemia mechanisms of SCL may be involved in the following metabolic pathways: tricarboxylic acid (TCA) cycle, synthesis of ketone body and cholesterol, choline metabolism and fatty acid metabolism. Meanwhile, SCL significantly inhibited the mRNA expression level of hepatic lipogenesis genes such as SREBP-1c, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), and decreased the mRNA expression of liver X receptor α (LXRα). Moreover, SCL also significantly decreased the expression level of SREBP-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in the liver of hyperlipidemia mice. CONCLUSION Anti-hyperlipidemia effect of SCL was confirmed by both serum biochemistry and metabolomics analysis. The mechanism may be related to the down-regulation of LXRα/SREBP-1c/FAS/ACC and SREBP2/HMGCR signaling pathways.",
"title": "Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice"
},
{
"docid": "37424881",
"text": "OBJECTIVE Folate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk. DESIGN Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk. SETTING The meta-analysis included fourteen randomized controlled trials, SUBJECTS A total of 39 420 patients. RESULTS Homocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification. CONCLUSIONS Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.",
"title": "The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis."
},
{
"docid": "38028419",
"text": "White adipose tissue (WAT) secretes adipokines, which critically regulate lipid metabolism. The present study investigated the effects of alcohol on adipokines and the mechanistic link between adipokine dysregulation and alcoholic fatty liver disease. Mice were fed alcohol for 2, 4, or 8 weeks to document changes in adipokines over time. Alcohol exposure reduced WAT mass and body weight in association with hepatic lipid accumulation. The plasma adiponectin concentration was increased at 2 weeks, but declined to normal at 4 and 8 weeks. Alcohol exposure suppressed leptin gene expression in WAT and reduced the plasma leptin concentration at all times measured. There is a highly positive correlation between plasma leptin concentration and WAT mass or body weight. To determine whether leptin deficiency mediates alcohol-induced hepatic lipid dyshomeostasis, mice were fed alcohol for 8 weeks with or without leptin administration for the last 2 weeks. Leptin administration normalized the plasma leptin concentration and reversed alcoholic fatty liver. Alcohol-perturbed genes involved in fatty acid β-oxidation, very low-density lipoprotein secretion, and transcriptional regulation were attenuated by leptin. Leptin also normalized alcohol-reduced phosphorylation levels of signal transducer Stat3 and adenosine monophosphate-activated protein kinase. These data demonstrated for the first time that leptin deficiency in association with WAT mass reduction contributes to the pathogenesis of alcoholic fatty liver disease.",
"title": "Leptin deficiency contributes to the pathogenesis of alcoholic fatty liver disease in mice."
},
{
"docid": "19185192",
"text": "The shift in substrate preference away from fatty acid oxidation (FAO) towards increased glucose utilization in heart failure has long been interpreted as an oxygen-sparing mechanism. Inhibition of FAO has therefore evolved as an accepted approach to treat heart failure. However, recent data indicate that increased reliance on glucose might be detrimental rather than beneficial for the failing heart. This review discusses new insights into metabolic adaptations in heart failure. A particular focus lies on data obtained from mouse models with modulations of cardiac FA metabolism at different levels of the FA metabolic pathway and how these differently affect cardiac function. Based on studies in which these mouse models were exposed to ischaemic and non-ischaemic heart failure, we discuss whether and when modulations in FA metabolism are protective against heart failure.",
"title": "Good and bad consequences of altered fatty acid metabolism in heart failure: evidence from mouse models."
},
{
"docid": "11705328",
"text": "BACKGROUND Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.",
"title": "Randomized trial of folic acid supplementation and serum homocysteine levels."
},
{
"docid": "12805683",
"text": "Mammalian nuclear hormone receptors (NHRs), such as liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs), precisely control energy metabolism. Consequently, these receptors are important targets for the treatment of metabolic diseases, including diabetes and obesity. A thorough understanding of NHR fat regulatory networks has been limited, however, by a lack of genetically tractable experimental systems. Here we show that deletion of the Caenorhabditis elegans NHR gene nhr-49 yielded worms with elevated fat content and shortened life span. Employing a quantitative RT-PCR screen, we found that nhr-49 influenced the expression of 13 genes involved in energy metabolism. Indeed, nhr-49 served as a key regulator of fat usage, modulating pathways that control the consumption of fat and maintain a normal balance of fatty acid saturation. We found that the two phenotypes of the nhr-49 knockout were linked to distinct pathways and were separable: The high-fat phenotype was due to reduced expression of enzymes in fatty acid β-oxidation, and the shortened adult life span resulted from impaired expression of a stearoyl-CoA desaturase. Despite its sequence relationship with the mammalian hepatocyte nuclear factor 4 receptor, the biological activities of nhr-49 were most similar to those of the mammalian PPARs, implying an evolutionarily conserved role for NHRs in modulating fat consumption and composition. Our findings in C. elegans provide novel insights into how NHR regulatory networks are coordinated to govern fat metabolism.",
"title": "Nuclear Hormone Receptor NHR-49 Controls Fat Consumption and Fatty Acid Composition in C. elegans"
},
{
"docid": "21956124",
"text": "BACKGROUND Prebiotics are short-chain carbohydrates that alter the composition, or metabolism, of the gut microbiota in a beneficial manner. It is therefore expected that prebiotics will improve health in a way similar to probiotics, whilst at the same time being cheaper, and carrying less risk and being easier to incorporate into the diet than probiotics. AIM To review published evidence for prebiotic effects on gut function and human health. METHODS We searched the Science Citation Index with the terms prebiotic, microbiota, gut bacteria, large intestine, mucosa, bowel habit, constipation, diarrhoea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, calcium and cancer, focussing principally on studies in humans and reports in the English language. Search of the Cochrane Library did not identify any clinical study or meta-analysis on this topic. RESULTS Three prebiotics, oligofructose, galacto-oligosaccharides and lactulose, clearly alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus numbers. These carbohydrates are fermented and give rise to short-chain fatty acid and intestinal gas; however, effects on bowel habit are relatively small. Randomized-controlled trials of their effect in a clinical context are few, although animal studies show anti-inflammatory effects in inflammatory bowel disease, while calcium absorption is increased. CONCLUSIONS It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.",
"title": "Review article: prebiotics in the gastrointestinal tract."
},
{
"docid": "12009265",
"text": "CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer. OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men. DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled. INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. MAIN OUTCOME MEASURES Prostate and total cancer. RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk. CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.",
"title": "Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial."
}
] |
5ac0696c554299012d1db5ef
|
How many professional footballers participate in a musical project that includes a player who began his career with Norwegian club Tromsø?
|
[
{
"docid": "6081428",
"text": "The Players is a Norwegian musical project consisting of five professional footballers: Freddy dos Santos, Morten Gamst Pedersen, Raymond Kvisvik, Kristofer Hæstad and Øyvind Svenning.",
"title": ""
},
{
"docid": "1360727",
"text": "Morten Gamst Pedersen (born 8 September 1981) is a Norwegian professional footballer who plays as a winger for Norwegian club Tromsø, the club with which he began his career.",
"title": ""
}
] |
[
{
"docid": "3329342",
"text": "Helge Haugen (born 15 February 1982) is a Norwegian footballer who plays as a midfielder for Sogndal. Born in Bergen, Haugen started his professional career in the local Tippeligaen club Brann. During his time at the club, he won the 2004 Norwegian Football Cup and the 2007 Tippeligaen. He has later played for Tromsø and Hønefoss, before he joined Sogndal ahead of the 2014 season. Haugen played one match for the Norwegian under-21 team in 2003.",
"title": ""
},
{
"docid": "3955209",
"text": "Miika Johannes Koppinen (born 5 July 1978 in Kokkola) is a Finnish football coach and former player who is currently assistant coach at Finnsnes IL. Koppinen played professional football as a central defender from 1998 to 2014. He started his career i Finland before moving to Norway to play for Tromsø IL and Rosenborg BK. Koppinen won 18 caps for the Finland national football team, and made 337 appearances for Tromsø, the third-highest number of appearances by any player for the club.",
"title": ""
},
{
"docid": "86957",
"text": "Tromsø Idrettslag is a Norwegian professional football club founded in 1920, based in the city of Tromsø. They play their home games at Alfheim Stadion. Tromsø currently play in the Tippeligaen and holds the position as the northernmost top-level football club in the world. The club was first promoted to the Norwegian Premier League in 1985, where they have played since with the exception of the 2001 and 2014 seasons which were spent in the First Division.",
"title": ""
},
{
"docid": "14017821",
"text": "David John \"Dave\" Shearer (born Inverness, 16 October 1958) is a Scottish former professional football (soccer) player. Shearer began his professional football career at his local club, Clachnacuddin in the Scottish Highland Football League. His other professional clubs, all in the English Football League, included Middlesbrough, Scunthorpe United and Gillingham. He made over 230 Football League appearances. He is the older brother of fellow former professional and Highland Football League player Duncan Shearer.",
"title": ""
},
{
"docid": "32057965",
"text": "George Albert Howes (5 January 1906 – 31 July 1993) was an English professional footballer who played as a right-half. Born in Jarrow, County Durham, he began his footballing career with his hometown club before joining Football League Second Division side Barnsley in the summer of 1928. He spent two seasons with the Yorkshire-based club but did not make a senior appearance for them.",
"title": ""
},
{
"docid": "1207980",
"text": "Sigurd Rushfeldt (born 11 December 1972) is a Norwegian footballer who is working as an assistant coach for Tromsø as well as a player for Lyngen/Karnes. During his playing career, he played for Tromsø, Birmingham City, Rosenborg, Racing de Santander, and Austria Wien. As a forward, he is well known for his strength and for being a prolific goalscorer. Rushfeldt is the all-time top goal scorer of Tippeligaen.",
"title": ""
},
{
"docid": "20783477",
"text": "William Donald Grigg (born 3 July 1991) is a professional footballer who plays as a striker for League One club Wigan Athletic. He represents Northern Ireland at international level. Grigg began his professional career at Walsall and came to prominence during the 2012–13 season, winning the club's Player of the Season and Players' Player of the Season awards.",
"title": ""
},
{
"docid": "38730230",
"text": "The 2012 season was Tromsø's 10th consecutive year in Tippeligaen, and their 26th season in the top flight of Norwegian football. It was Per Mathias Høgmo's third and final season as the club's manager. Tromsø participated in the Tippeligaen finishing 4th, the 2012 Norwegian Football Cup where they were beaten in the final by Hødd. They also tool part in the 2012–13 UEFA Europa League, entering at the Second qualifying round stage against Olimpija Ljubljana before being eliminated by Partizan on away goals at the Play Off stage.",
"title": ""
},
{
"docid": "31882346",
"text": "Jean-Luc Lambourde (born 10 April 1980) is a French football player who plays for Amical Club on the island of Guadeloupe in the Guadeloupe Division d'Honneur. He plays as a Defender and began his football career playing for amateur club Avion in 2002. After spending three seasons with the club, Lambourde ventured to his native homeland joining his current club, where he currently remains. In his second season with the club, he won the Coupe de Guadeloupe. Lambourde is also a member of the Guadeloupe national football team. He is one of a few players in the team to have participated in all three of the team's appearances as the CONCACAF Gold Cup.",
"title": ""
},
{
"docid": "14465887",
"text": "Idrettsforeningen Skarp is a Norwegian association football club from Tromsø, which currently plays in the Third Division, the fourth tier of Norwegian football. The club was founded 30 June 1919 and its colors are black and white. It is the third best football team in Tromsø, after Tromsø IL and Tromsdalen UIL.",
"title": ""
},
{
"docid": "28901977",
"text": "Hawley Pierce was an early professional football player for the Philadelphia Athletics of the first National Football League and later for the Syracuse Athletic Club during the 1902 and 1903 World Series of Football. In 1901, he began his professional career playing on the 1901 Homestead Library & Athletic Club football team. Prior to his professional career, Pierce, a Seneca Native American, played for the Carlisle Indian School, located in Carlisle, Pennsylvania. He was the brother of college and professional football's Bemus Pierce.",
"title": ""
},
{
"docid": "2827510",
"text": "Bjørn \"Bummen\" Johansen (born 7 September 1969) is a former Norwegian footballer, who played as a midfielder for Tromsø IL for most of his career. He has later worked as head coach of Finnsnes.",
"title": ""
},
{
"docid": "10393307",
"text": "Jeremy Marcus Illingworth (born 20 May 1977) is an English former professional footballer who played as a midfielder in the Football League for Huddersfield Town. He began his career as a trainee with his home-town club, then, after trials at clubs including Cambridge United, went on to forge a lengthy career in non-league football with Wisbech Town, Ashton United, where he scored 29 goals from 103 games in all competitions, Altrincham (1 from 15), Stocksbridge Park Steels (17 from 91), Guiseley, Bradford Park Avenue and A.F.C. Emley. Currently playing for Birkby FC in the Huddersfield Soccer City Tuesday premier league= 2011–present, 347 apps, 589 goals whilst finishing frequently behind The Bramble in overall league standings he is frequently voted players player of the season.",
"title": ""
},
{
"docid": "22528284",
"text": "Ruben Yttergård Jenssen (born 4 May 1988) is a Norwegian footballer who plays as a midfielder for FC Groningen and the Norwegian national team. He was playing regularly for Tromsø in the Tippeligaen since 2008, and became one of the team's most important players before transferring to Kaiserslautern. Early in his career, Jenssen played as a winger, but he has later played as a central midfielder. Jenssen made his international debut for Norway in May 2010, and has since then been a member of the national team squad, and a regular starter since September 2012. He is the son of former footballer Truls Jenssen.",
"title": ""
},
{
"docid": "42113174",
"text": "Luke John Muldowney (born 31 July 1986) is an English semi-professional football midfielder who plays for Hanworth Villa. He began his career at Brentford, for whom he made one professional appearance before dropping into non-league football upon his release in 2005. He probably best remembered for his six years as player, captain and manager at non-league club Egham Town.",
"title": ""
},
{
"docid": "38007847",
"text": "George Arthur Ephgrave (29 April 1918 – 12 December 2004) was an English footballer who played as a goalkeeper. Born in Reading, Ephgrave began his professional career with Aston Villa in 1936, and later played for a number of Football League clubs including Southampton and Norwich City before retiring from professional football in 1954.",
"title": ""
},
{
"docid": "24437199",
"text": "Sam Oliver Slocombe (born 5 June 1988) is an English professional footballer who plays as a goalkeeper for Bristol Rovers. He began his career with Bottesford Town in the Northern Counties East Football League. In 2008, he moved to his hometown club Scunthorpe United. Slocombe had made over 130 for Scunthorpe and was the club's longest-serving player, before being released by them in 2015.",
"title": ""
},
{
"docid": "11145725",
"text": "Iørn Peter Uldbjerg (born February 1, 1968) is a retired Danish football (soccer) player, who most prominently won the 1993 Danish football championship with FC København. He began his senior career at Tårnby Boldklub and played six games for the Denmark national under-21 football team in 1988, before signing a professional contract with B 1903. He started playing for FC København when the club was founded in 1992, and after leaving the club in 1998, he ended his career at Herfølge BK and Farum BK.",
"title": ""
},
{
"docid": "2609142",
"text": "Christoph Paul Daum (born 24 October 1953) is a German professional football coach and former player who last managed the Romania national team. Daum played as a midfielder and was a junior for several clubs from the region of Duisburg. He began his senior career with Hamborn 07 and Eintracht Duisburg, before joining 1. FC Köln in 1975 and being part of the reserve team that won the 1980–81 German amateur football championship. As a manager, he won 8 trophies with clubs from Germany, Turkey and Austria. Daum began his football career in 1971 in the youth league with Hamborn 07. He transferred in 1972 to Eintracht Duisburg and then in 1975 to 1. FC Köln, where he played in the amateur league until his retirement.",
"title": ""
},
{
"docid": "4056952",
"text": "Neil James Cox (born 8 October 1971) is an English former professional footballer and manager. A defender capable of playing at centre or right-back, he made over 500 appearances in the Football League during his career and was capped at Under-21 level by England. He began his career at Scunthorpe United as a youth player and was eventually offered a professional contract by the club, breaking into the first-team soon after. In 1991, Cox joined First Division side Aston Villa for a fee of £400,000, going on to make over 50 appearances for the side in all competitions, including playing in the club's victory over Manchester United in the 1994 Football League Cup Final, but struggled to establish himself in the first-team.",
"title": ""
},
{
"docid": "4699284",
"text": "Allan Gaarde (born 25 January 1975) is a Danish former professional football player in the midfielder position, who played 227 games and scored 48 goals for AaB , and won the 1999 Danish Superliga championship with the club. He also played abroad for Italian club Udinese Calcio and Norwegian club Viking FK, before ending his career with Vejle Boldklub in Denmark.",
"title": ""
},
{
"docid": "11426624",
"text": "Robbie Thomas Kruse (born 5 October 1988) is an Australian professional football (soccer) player who plays as a forward for 2. Bundesliga club VfL Bochum and the Australian national team. He played his junior football with Albany Creek in the Pine Rivers district to the near north of Brisbane and began his professional career with A-League side Brisbane Roar and later Melbourne Victory before moving to Germany in 2011.",
"title": ""
},
{
"docid": "31759453",
"text": "Philip Jonathan Hadland (born 20 October 1980) is an English professional footballer who plays as a Winger. He played for a variety of Football League clubs including Reading, where he began his career and made his debut at the age of 17. He then joined Rochdale, where he made 32 appearances (his highest total for a league club), Leyton Orient, Carlisle, Brighton, Darlington and Colchester.",
"title": ""
},
{
"docid": "14835159",
"text": "George Albert Handley (1886–1952) was an English professional footballer who played most of his career as a winger with Bradford City. Born in Totley, Sheffield, he began his professional career with Chesterfield Town before moving to Bradford in 1906. After five years at Bradford, Handley left for Southampton in 1911 but his stay was only a brief one as he moved on to become player-manager of Goole Town in 1912. He re-joined Bradford in 1913 but was released at the end of the season and signed for Barrow with whom he remained for the duration of World War I, occasionally guesting for his home town club Sheffield United. After the war Handley returned to Bradford for a third spell, ending his playing career with the club, and later spent some time as coach of Swiss side Brühl.",
"title": ""
},
{
"docid": "52966192",
"text": "Gezim Ljalja (, ; born July 25, 1956) is a Kosovar Albanian retired professional footballer of who spent his entire career at FK Zemun and became one of the greatest and most notable players of the club.He has also served as a football coach at many clubs abroad.",
"title": ""
},
{
"docid": "52008302",
"text": "Leif Andersen (born 19 April 1971) is a Norwegian retired professional footballer who played as a defender. He spent most of his career in Norwegian domestic football, but also spent one-and-a-half seasons with English Football League club Crystal Palace.",
"title": ""
},
{
"docid": "3714550",
"text": "The Paraguayan Footballer of the Year is an award given to the best Paraguayan professional football player every year. The award began officially in 1997 and it is presented by Paraguayan newspaper Diario ABC Color. Players that participate in this award can play in any professional football club in the world (they don't necessarily have to be Paraguayan football clubs) and have to be either Paraguayan-born or Paraguayan-naturalised players.",
"title": ""
},
{
"docid": "1799179",
"text": "Donald Howe (12 October 1935 – 23 December 2015) was an English football player, coach, manager and pundit. Howe who played as a defender, featured for clubs West Bromwich Albion and Arsenal and the English national football team in his playing career. He also went on to manage sides West Brom, Galatasaray, Queens Park Rangers and Coventry City. Howe who was as well a highly successful coach, has been described as one of the most influential figures of the English footballing game.",
"title": ""
},
{
"docid": "20804858",
"text": "Vegard Båtnes Braaten (born 30 June 1987 in Tromsø) is a Norwegian professional footballer playing for PostNord-ligaen club Alta.",
"title": ""
},
{
"docid": "25144476",
"text": "Charles Robert \"Bob\" Shiring (1870 – July 23, 1957) was a professional football player from Pittsburgh, Pennsylvania. He began his playing career with the Pittsburgh Athletic Club during the late 1890s and the Homestead Library & Athletic Club in 1901. In 1902, he played for the Pittsburgh Stars of the first National Football League, who ended up winning the league title. Since the Stars consisted of the best professional players from western Pennsylvania at the time, it can be said that Shiring was considered the best at his position, center, in the region (and probably in the country). However Shring is best known for playing for the Massillon Tigers from 1903 until 1907. He finally served from 1907 to 1909 as a player-coach for the Pittsburgh Lyceum, Pittsburgh's last championship professional football team, until the 1970s.",
"title": ""
}
] |
902
|
PD-1 triggering on monocytes enhances IL-10 production by monocytes.
|
[
{
"docid": "10648422",
"text": "Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.",
"title": "Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection"
}
] |
[
{
"docid": "5752492",
"text": "Chronic immune activation that persists despite anti-retroviral therapy (ART) is the strongest predictor of disease progression in HIV infection. Monocyte/macrophages in HIV-infected individuals are known to spontaneously secrete cytokines, although neither the mechanism nor the molecules involved are known. Here we show that overexpression of the newly described co-stimulatory molecule, PD1 homologue (PD-1H) in human monocyte/macrophages is sufficient to induce spontaneous secretion of multiple cytokines. The process requires signaling via PD-1H as cytokine secretion could be abrogated by deletion of the cytoplasmic domain. Such overexpression of PD-1H, associated with spontaneous cytokine expression is seen in monocytes from chronically HIV-infected individuals and this correlates with immune activation and CD4 depletion, but not viral load. Moreover, antigen presentation by PD-1H-overexpressing monocytes results in enhanced cytokine secretion by HIV-specific T cells. These results suggest that PD-1H might play a crucial role in modulating immune activation and immune response in HIV infection.",
"title": "Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals"
},
{
"docid": "9334631",
"text": "OBJECTIVE C-Reactive protein (CRP), a cardiovascular risk marker, could also participate in atherosclerosis. Atherosclerotic plaques express CRP and interleukin (IL)-10, a major antiinflammatory cytokine. IL-10 deficiency results in increased lesion formation, whereas IL-10 delivery attenuates lesions. We tested the effect of CRP on lipopolysaccharide (LPS)-induced IL-10 secretion in human monocyte-derived macrophages (HMDMs). METHODS AND RESULTS Incubation of HMDMs with CRP significantly decreased LPS-induced IL-10 mRNA and intracellular and secreted IL-10 protein and destabilized IL-10 mRNA. Also, CRP alone increased secretion of IL-8, IL-6, and tumor necrosis factor from HMDMs and did not inhibit LPS-induced secretion of these cytokines. Fc gamma receptor I antibodies significantly reversed CRP-mediated IL-10 inhibition. CRP significantly decreased intracellular cAMP, phospho-cAMP response element binding protein (pCREB), and adenyl cyclase activity. cAMP agonists reversed CRP-mediated IL-10 inhibition. Overexpression of wild-type and constitutively active CREB in THP-1 cells revealed attenuation of the inhibitory effect of CRP on LPS-induced IL-10 levels. CRP also inhibited hemoglobin:haptoglobin-induced IL-10 and heme oxygenase-1. Furthermore, administration of human CRP to rats significantly decreased IL-10 levels. CONCLUSIONS This study provides novel evidence that CRP, by decreasing IL-10 alters the antiinflammatory/proinflammatory balance, accentuating inflammation, which is pivotal in atherothrombosis.",
"title": "C-reactive protein decreases interleukin-10 secretion in activated human monocyte-derived macrophages via inhibition of cyclic AMP production."
},
{
"docid": "5372773",
"text": "Human cytomegalovirus (HCMV) expresses several homologues of human interleukin 10 (hIL-10) possessing immunomodulatory properties which may promote viral infection by modulating the function of myeloid cells. We examined the phenotype and phagocytic capability of human monocytes exposed to hIL-10, an HCMV-encoded hIL-10 homologue expressed during the productive phase of infection (cmvIL-10), and a differentially spliced form of cmvIL-10 expressed during latent and productive phases of infection, (LAcmvIL-10). hIL-10 and cmvIL-10 upregulated expression of Fcgamma receptors, stimulated phagocytosis of IgG-opsonised erythrocytes and decreased MHC class II (HLA-DR) expression on purified monocytes within 24 h. In contrast, LAcmvIL-10 decreased HLA-DR expression at later times (48 h and 72 h) but did not increase Fcgamma receptor expression. We conclude that cmvIL-10 promotes differentiation of monocytes towards a pro-phagocytic phenotype and that LAcmvIL-10 does not affect monocytes by the same mechanism as cmvIL-10. The significance of these properties to cytomegalovirus pathogenesis is discussed.",
"title": "Enhanced monocyte Fc phagocytosis by a homologue of interleukin-10 encoded by human cytomegalovirus."
},
{
"docid": "34469966",
"text": "Interleukin-1β (IL-1β) is a cytokine whose bioactivity is controlled by activation of the inflammasome. However, in response to lipopolysaccharide, human monocytes secrete IL-1β independently of classical inflammasome stimuli. Here, we report that this constituted a species-specific response that is not observed in the murine system. Indeed, in human monocytes, lipopolysaccharide triggered an \"alternative inflammasome\" that relied on NLRP3-ASC-caspase-1 signaling, yet was devoid of any classical inflammasome characteristics including pyroptosome formation, pyroptosis induction, and K(+) efflux dependency. Genetic dissection of the underlying signaling pathway in a monocyte transdifferentiation system revealed that alternative inflammasome activation was propagated by TLR4-TRIF-RIPK1-FADD-CASP8 signaling upstream of NLRP3. Importantly, involvement of this signaling cascade was limited to alternative inflammasome activation and did not extend to classical NLRP3 activation. Because alternative inflammasome activation embraces both sensitivity and promiscuity of TLR4, we propose a pivotal role for this signaling cascade in TLR4-driven, IL-1β-mediated immune responses and immunopathology in humans.",
"title": "Human Monocytes Engage an Alternative Inflammasome Pathway."
},
{
"docid": "21439640",
"text": "Tumor-associated macrophages and high levels of cyclooxygenase-2 (COX-2) are associated with poor prognosis in breast cancer patients, but their potential interdependence has not been evaluated. The objective of this study was to determine whether macrophages regulate COX-2 expression in breast cancer cells. For this purpose, THP-1 cells were cocultured with HCC1954 breast cancer cells. Coculture led to increased COX-2 expression in the HCC1954 cells and elevated prostaglandin E(2) levels in conditioned media. Similar results were observed when THP-1 cells were incubated with HCC1937 breast cancer cells or when human monocyte-derived macrophages were cocultured with HCC1954 cells. Coculture triggered production of reactive oxygen species (ROS) in HCC1954 cells. COX-2 induction was blocked in cells preincubated with an reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor or by silencing p67PHOX, a subunit of NADPH oxidase. ROS production triggered activation of Src and mitogen-activated protein kinases (MAPKs). Blocking Src or MAPK activities or antagonizing the activator protein-1 (AP-1) transcription factor attenuated COX-2 induction in HCC1954 cells. Coculture caused rapid induction of interleukin-1β (IL-1β) in both breast cancer cells and macrophages. Increased IL-1β expression was blocked by an interleukin-1 receptor antagonist (IL-1Ra), suggesting autocrine and paracrine effects. Importantly, macrophage-induced COX-2 expression was blocked in HCC1954 cells preincubated with IL-1Ra or anti-IL-1β IgG. Together, these results indicate that macrophage-mediated induction of COX-2 in breast cancer cells is a consequence of IL-1β-mediated stimulation of ROS→Src→MAPK→AP-1 signaling. IL-1β-dependent induction of COX-2 in breast cancer cells provides a mechanism whereby macrophages contribute to tumor progression and potential therapeutic targets in breast cancer.",
"title": "Macrophages induce COX-2 expression in breast cancer cells: role of IL-1β autoamplification."
},
{
"docid": "21498497",
"text": "Leprosy enables investigation of mechanisms by which the innate immune system contributes to host defense against infection, because in one form, the disease progresses, and in the other, the infection is limited. We report that Toll-like receptor (TLR) activation of human monocytes induces rapid differentiation into two distinct subsets: DC-SIGN+ CD16+ macrophages and CD1b+ DC-SIGN− dendritic cells. DC-SIGN+ phagocytic macrophages were expanded by TLR-mediated upregulation of interleukin (IL)-15 and IL-15 receptor. CD1b+ dendritic cells were expanded by TLR-mediated upregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor, promoted T cell activation and secreted proinflammatory cytokines. Whereas DC-SIGN+ macrophages were detected in lesions and after TLR activation in all leprosy patients, CD1b+ dendritic cells were not detected in lesions or after TLR activation of peripheral monocytes in individuals with the progressive lepromatous form, except during reversal reactions in which bacilli were cleared by T helper type 1 (TH1) responses. In tuberculoid lepromatous lesions, DC-SIGN+ cells were positive for macrophage markers, but negative for dendritic cell markers. Thus, TLR-induced differentiation of monocytes into either macrophages or dendritic cells seems to crucially influence effective host defenses in human infectious disease.",
"title": "TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells"
},
{
"docid": "26068103",
"text": "RSV lower respiratory tract infections (LRTI) are among the most common diseases necessitating hospital admission in children. In addition to causing acute respiratory failure, RSV infections are associated with sequelae such as secondary bacterial infections and reactive airway disease. One characteristic host response observed in severe RSV-induced LRTI and/or subsequent development of asthma is increased expression of interleukin (IL)-10. However, contradictory results have been reported regarding whether IL-10 inhibits asthmatic responses or intensifies the disease. We aimed to reconcile these discordant observations by elucidating the role of IL-10 in regulating the host response to RSV LRTI. In this study, we used a lung-specific, inducible IL-10 over-expression (OE) transgenic mouse model to address this question. Our results showed that the presence of IL-10 at the time of RSV infection not only attenuated acute inflammatory process (i.e. 24 h post-infection), but also late inflammatory changes [characterized by T helper type 2 (Th2) cytokine and chemokine expression]. While this result appears contradictory to some clinical observations where elevated IL-10 levels are observed in asthmatic patients, we also found that delaying IL-10 OE until the late immune response to RSV infection, additive effects rather than inhibitory effects were observed. Importantly, in non-infected, IL-10 OE mice, IL-10 OE alone induced up-regulation of Th2 cytokine (IL-13 and IL-5) and Th2-related chemokine [monocyte chemoattractant protein 1 (MCP-1), chemokine (C-C motif) ligand 3 (CCL3) and regulated upon activation normal T cell expressed and secreted (RANTES)] expression. We identified a subset of CD11b(+)CD11c(+)CD49b(+)F4/80(-)Gr-1(-) myeloid cells as a prinicipal source of IL-10-induced IL-13 production. Therefore, the augmented pathological responses observed in our 'delayed' IL-10 over-expression model could be attributed to IL-10 OE alone. Taken together, our study indicated dual roles of IL-10 on RSV-induced lung inflammation which appear to depend upon the timing of when elevated IL-10 is expressed in the lung.",
"title": "Dual role of interleukin-10 in the regulation of respiratory syncitial virus (RSV)-induced lung inflammation."
},
{
"docid": "37762357",
"text": "Cytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection.",
"title": "Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10."
},
{
"docid": "5511240",
"text": "Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are key contributors of host defense against enteroinvasive bacteria. Here, we found that infection by Listeria monocytogenes induced the early necroptotic death of Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial type 1 inflammatory response. Kupffer cell death also triggered a type 2 response that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil-derived interleukin-4 (IL-4). This led to the alternative activation of the monocyte-derived macrophages recruited to the liver, which thereby replaced ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is therefore a key signal orchestrating type 1 microbicidal inflammation and type-2-mediated liver repair upon infection. This indicates that beyond the classical dichotomy of type 1 and type 2 responses, these responses can develop sequentially in the context of a bacterial infection and act interdependently, orchestrating liver immune responses and return to homeostasis, respectively.",
"title": "Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection."
},
{
"docid": "1360607",
"text": "Exercise increases plasma TNF-alpha, IL-1beta, and IL-6, yet the stimuli and sources of TNF-alpha and IL-1beta remain largely unknown. We tested the role of oxidative stress and the potential contribution of monocytes in this cytokine (especially IL-1beta) response in previously untrained individuals. Six healthy nonathletes performed two 45-min bicycle exercise sessions at 70% of Vo(2 max) before and after a combination of antioxidants (vitamins E, A, and C for 60 days; allopurinol for 15 days; and N-acetylcysteine for 3 days). Blood was drawn at baseline, end-exercise, and 30 and 120 min postexercise. Plasma cytokines were determined by ELISA and monocyte intracellular cytokine level by flow cytometry. Before antioxidants, TNF-alpha increased by 60%, IL-1beta by threefold, and IL-6 by sixfold secondary to exercise (P < 0.05). After antioxidants, plasma IL-1beta became undetectable, the TNF-alpha response to exercise was abolished, and the IL-6 response was significantly blunted (P < 0.05). Exercise did not increase the percentage of monocytes producing the cytokines or their mean fluorescence intensity. We conclude that in untrained humans oxidative stress is a major stimulus for exercise-induced cytokine production and that monocytes play no role in this process.",
"title": "Antioxidants attenuate the plasma cytokine response to exercise in humans."
},
{
"docid": "14386505",
"text": "Myeloid cells play pivotal roles in chronic inflammatory diseases through their broad proinflammatory, destructive, and remodeling capacities. CD200 is widely expressed on a variety of cell types, while the recently identified CD200R is expressed on myeloid cells and T cells. CD200 deletion in vivo results in myeloid cell dysregulation and enhanced susceptibility to autoimmune inflammation, suggesting that the CD200-CD200R interaction is involved in immune suppression. We demonstrate in this study that CD200R agonists suppress mouse and human myeloid cell function in vitro, and also define a dose relationship between receptor expression and cellular inhibition. IFN-gamma- and IL-17-stimulated cytokine secretion from mouse peritoneal macrophages was inhibited by CD200R engagement. Inhibitory effects were not universal, as LPS-stimulated responses were unaffected. Inhibition of U937 cell cytokine production correlated with CD200R expression levels, and inhibition was only observed in low CD200R expressing cells, if the CD200R agonists were further cross-linked. Tetanus toxoid-induced human PBMC IL-5 and IL-13 secretion was inhibited by CD200R agonists. This inhibition was dependent upon cross-linking the CD200R on monocytes, but not on cross-linking the CD200R on CD4+ T cells. In all, we provide direct evidence that the CD200-CD200R interaction controls monocyte/macrophage function in both murine and human systems, further supporting the potential clinical application of CD200R agonists for the treatment of chronic inflammatory diseases.",
"title": "Regulation of myeloid cell function through the CD200 receptor."
},
{
"docid": "11837657",
"text": "Mycobacterium tuberculosis (Mtb) infects lung macrophages, which instead of killing the pathogen can be manipulated by the bacilli, creating an environment suitable for intracellular replication and spread to adjacent cells. The role of host cell death during Mtb infection is debated because the bacilli have been shown to be both anti-apoptotic, keeping the host cell alive to avoid the antimicrobial effects of apoptosis, and pro-necrotic, killing the host macrophage to allow infection of neighboring cells. Since mycobacteria activate the NLRP3 inflammasome in macrophages, we investigated whether Mtb could induce one of the recently described inflammasome-linked cell death modes pyroptosis and pyronecrosis. These are mediated through caspase-1 and cathepsin-B, respectively. Human monocyte-derived macrophages were infected with virulent (H37Rv) Mtb at a multiplicity of infection (MOI) of 1 or 10. The higher MOI resulted in strongly enhanced release of IL-1β, while a low MOI gave no IL-1β response. The infected macrophages were collected and cell viability in terms of the integrity of DNA, mitochondria and the plasma membrane was determined. We found that infection with H37Rv at MOI 10, but not MOI 1, over two days led to extensive DNA fragmentation, loss of mitochondrial membrane potential, loss of plasma membrane integrity, and HMGB1 release. Although we observed plasma membrane permeabilization and IL-1β release from infected cells, the cell death induced by Mtb was not dependent on caspase-1 or cathepsin B. It was, however, dependent on mycobacterial expression of ESAT-6. We conclude that as virulent Mtb reaches a threshold number of bacilli inside the human macrophage, ESAT-6-dependent necrosis occurs, activating caspase-1 in the process.",
"title": "Human Macrophages Infected with a High Burden of ESAT-6-Expressing M. tuberculosis Undergo Caspase-1- and Cathepsin B-Independent Necrosis"
},
{
"docid": "7948486",
"text": "Kruppel-like factor 2 (KLF2) plays an important role in the regulation of a variety of immune cells, including monocytes. We have previously shown that KLF2 inhibits proinflammatory activation of monocytes. However, the role of KLF2 in arthritis is yet to be investigated. In the current study, we show that recruitment of significantly greater numbers of inflammatory subset of CD11b(+)F4/80(+)Ly6C+ monocytes to the inflammatory sites in KLF2 hemizygous mice compared to the wild type littermate controls. In parallel, inflammatory mediators, MCP-1, Cox-2 and PAI-1 were significantly up-regulated in bone marrow-derived monocytes isolated from KLF2 hemizygous mice, in comparison to wild-type controls. Methylated-BSA and IL-1β-induced arthritis was more severe in KLF2 hemizygous mice as compared to the littermate wild type controls. Consistent with this observation, monocytes isolated from KLF2 hemizygous mice showed an increased number of cells matured and differentiated towards osteoclastic lineage, potentially contributing to the severity of cartilage and bone damage in induced arthritic mice. The severity of arthritis was associated with the higher expression of proteins such as HSP60, HSP90 and MMP13 and attenuated levels of pPTEN, p21, p38 and HSP25/27 molecules in bone marrow cells of arthritic KLF2 hemizygous mice compared to littermate wild type controls. The data provide new insights and evidences of KLF2-mediated transcriptional regulation of arthritis via modulation of monocyte differentiation and function.",
"title": "Kruppel-like factor 2 (KLF2) regulates monocyte differentiation and functions in mBSA and IL-1β-induced arthritis."
},
{
"docid": "22483580",
"text": "Bipolar disorder is a severe psychiatric disorder that is associated with persistent changes in the quality, duration and architecture of sleep. Currently there is no unifying hypothesis explaining the alterations in sleep observable in patients with bipolar disorder and management is often difficult though vital. Sleep is modified by various cytokines including IL-6. Elevated levels of IL-6 are associated with a poorer quality of sleep and changes in the architecture of sleep similar to those observed in bipolar disorder. Therapeutic administration of Interferon causes elevations of intrathecal IL-6 concentrations and appears to provoke a deteriorating quality of sleep. The blockade of IL-6 with tocilizumab in rheumatoid arthritis is associated with improvements in the quality of sleep. Bipolar disorder is associated with elevated levels of IL-6 and in particular elevated levels of mRNA coding for IL-6 in peripheral monocytes. We propose that the changes observed in the sleep of patients with bipolar disorder are related to the elevation of IL-6 and that this correlates with an elevated expression of mRNA coding for IL-6 expression in peripheral monocytes.",
"title": "Disturbed sleep in bipolar disorder is related to an elevation of IL-6 in peripheral monocytes."
},
{
"docid": "13902570",
"text": "OBJECTIVE TGR5 is a G-protein-coupled receptor for bile acids. So far, little is known about the function of TGR5 in vascular endothelial cells. APPROACH AND RESULTS In bovine aortic endothelial cells, treatment with a bile acid having a high affinity to TGR5, taurolithocholic acid (TLCA), significantly increased NO production. This effect was abolished by small interfering RNA-mediated depletion of TGR5. TLCA-induced NO production was also observed in human umbilical vein endothelial cells measured via intracellular cGMP accumulation. TLCA increased endothelial NO synthase(ser1177) phosphorylation in human umbilical vein endothelial cells. This response was accompanied by increased Akt(ser473) phosphorylation and intracellular Ca(2+). Inhibition of these signals significantly decreased TLCA-induced NO production. We next examined whether TGR5-mediated NO production affects inflammatory responses of endothelial cells. In human umbilical vein endothelial cells, TLCA significantly reduced tumor necrosis factor-α-induced adhesion of monocytes, vascular cell adhesion molecule-1 expression, and activation of nuclear factor-κB. TLCA also inhibited lipopolysaccharide-induced monocyte adhesion to mesenteric venules in vivo. These inhibitory effects of TLCA were abrogated by NO synthase inhibition. CONCLUSIONS TGR5 agonism induces NO production via Akt activation and intracellular Ca(2+) increase in vascular endothelial cells, and this function inhibits monocyte adhesion in response to inflammatory stimuli.",
"title": "Bile acid receptor TGR5 agonism induces NO production and reduces monocyte adhesion in vascular endothelial cells."
},
{
"docid": "39084565",
"text": "Experimental autoimmune myocarditis (EAM) represents a Th17 T cell-mediated mouse model of postinflammatory heart disease. In BALB/c wild-type mice, EAM is a self-limiting disease, peaking 21 days after alpha-myosin H chain peptide (MyHC-alpha)/CFA immunization and largely resolving thereafter. In IFN-gammaR(-/-) mice, however, EAM is exacerbated and shows a chronic progressive disease course. We found that this progressive disease course paralleled persistently elevated IL-17 release from T cells infiltrating the hearts of IFN-gammaR(-/-) mice 30 days after immunization. In fact, IL-17 promoted the recruitment of CD11b(+) monocytes, the major heart-infiltrating cells in EAM. In turn, CD11b(+) monocytes suppressed MyHC-alpha-specific Th17 T cell responses IFN-gamma-dependently in vitro. In vivo, injection of IFN-gammaR(+/+)CD11b(+), but not IFN-gammaR(-/-)CD11b(+), monocytes, suppressed MyHC-alpha-specific T cells, and abrogated the progressive disease course in IFN-gammaR(-/-) mice. Finally, coinjection of MyHC-alpha-specific, but not OVA-transgenic, IFN-gamma-releasing CD4(+) Th1 T cell lines, together with MyHC-alpha-specific Th17 T cells protected RAG2(-/-) mice from EAM. In conclusion, CD11b(+) monocytes play a dual role in EAM: as a major cellular substrate of IL-17-induced inflammation and as mediators of an IFN-gamma-dependent negative feedback loop confining disease progression.",
"title": "CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis."
},
{
"docid": "13905670",
"text": "The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient's life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn's disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses.",
"title": "Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway"
},
{
"docid": "2436602",
"text": "Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.",
"title": "β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat."
},
{
"docid": "195683603",
"text": "Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses.",
"title": "Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A."
},
{
"docid": "2824347",
"text": "The introduction in 1996 of the HAART raised hopes for the eradication of HIV-1. Unfortunately, the discovery of latent HIV-1 reservoirs in CD4+ T cells and in the monocyte-macrophage lineage proved the optimism to be premature. The long-lived HIV-1 reservoirs constitute a major obstacle to the eradication of HIV-1. In this review, we focus on the establishment and maintenance of HIV-1 latency in the two major targets for HIV-1: the CD4+ T cells and the monocyte-macrophage lineage. Understanding the cell-type molecular mechanisms of establishment, maintenance, and reactivation of HIV-1 latency in these reservoirs is crucial for efficient therapeutic intervention. A complete viral eradication, the holy graal for clinicians, might be achieved by strategic interventions targeting latently and productively infected cells. We suggest that new approaches, such as the combination of different kinds of proviral activators, may help to reduce dramatically the size of latent HIV-1 reservoirs in patients on HAART.",
"title": "HIV-1 regulation of latency in the monocyte-macrophage lineage and in CD4+ T lymphocytes."
},
{
"docid": "623486",
"text": "Centrifugal elutriation was used further to isolate human peripheral blood monocytes (HPBM) from mononuclear-enriched cells harvested as a secondary component following platelet concentration collection samples. HPBM were recovered in either one or two populations consisting of either total HPBM or small (SM) and large monocytes (LM). The elutriation was carried out at 3,500 +/- 5 rpm for the separation of lymphocytes and HPBM in Ca++- and Mg++-free PBS without EDTA. An average of 5.05 +/- 1.50 X 10(8) HPBM were recovered in the total HPBM with a purity of 95% +/- 3%. The SM and LM were obtained by splitting the total HPBM into two equal populations with an HPBM purity of 92% +/- 3% and 93% +/- 3, respectively, by nonspecific esterase staining. The elutriation media were shown to have no effect on viability by trypan blue exclusion. All three HPBM populations were shown to be histochemically (lack of reactivity to leu-1 and leu-7) and functionally (depletion of NK cell activity) purified from the lymphocyte population. The HPBM populations were enriched in HLA-Dr, OKM-1, OKM-5, MY-8, and leu M-3 monoclonal antibody marker staining. There were no differences in percent positive cells between SM and LM populations for any of the monocyte-specific monoclonal antibodies. All three monocyte populations mediated antibody-dependent cell-mediated cytotoxicity to human red blood cells, with LM mediating more lysis (27.0% +/- 5%) than SM (7% +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Centrifugal elutriation as a method for isolation of large numbers of functionally intact human peripheral blood monocytes."
},
{
"docid": "22406695",
"text": "Macrophages are distributed in tissues throughout the body and contribute to both homeostasis and disease. Recently, it has become evident that most adult tissue macrophages originate during embryonic development and not from circulating monocytes. Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state. This new understanding also prompts reconsideration of the function of circulating monocytes. Classical Ly6c(hi) monocytes patrol the extravascular space in resting organs, and Ly6c(lo) nonclassical monocytes patrol the vasculature. Inflammation triggers monocytes to differentiate into macrophages, but whether resident and newly recruited macrophages possess similar functions during inflammation is unclear. Here, we define the tools used for identifying the complex origin of tissue macrophages and discuss the relative contributions of tissue niche versus ontological origin to the regulation of macrophage functions during steady state and inflammation.",
"title": "Origin and functions of tissue macrophages."
},
{
"docid": "12370881",
"text": "AIM To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. MATERIALS & METHODS Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. RESULTS Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6C(hi) monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. CONCLUSION Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.",
"title": "Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice."
},
{
"docid": "7386360",
"text": "Infectious pathogens can selectively stimulate activation or suppression of T cells to facilitate their survival within humans. In this study we demonstrate that the trematode parasite Schistosoma mansoni has evolved with two distinct mechanisms to suppress T cell activation. During the initial 4- to 12-wk acute stages of a worm infection both CD4(+) and CD8(+) T cells are anergized. In contrast, infection with male and female worms induced T cell anergy at 4 wk, which was replaced after egg laying by T cell suppression via a known NO-dependent mechanism, that was detected for up to 40 wk after infection. Worm-induced anergy was mediated by splenic F4/80(+) macrophages (Mphi) via an IL-4-, IL-13-, IL-10-, TGF-beta-, and NO-independent, but cell contact-dependent, mechanism. F4/80(+) Mphi isolated from worm-infected mice were shown to induce anergy of naive T cells in vitro. Furthermore, naive Mphi exposed to live worms in vitro also induced anergy in naive T cells. Flow cytometry on in vivo and in vitro worm-modulated Mphi revealed that of the family of B7 costimulatory molecules, only programmed death ligand 1 (PD-L1) was selectively up-regulated. The addition of inhibitory mAb against PD-L1, but not PD-L2, to worm-modulated Mphi completely blocked the ability of these cells to anergize T cells. These data highlight a novel mechanism through which S. mansoni worms have usurped the natural function of PD-L1 to reduce T cell activation during early acute stages of infection before the subsequent emergence of egg-induced T cell suppression in the chronic stages of infection.",
"title": "Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages."
},
{
"docid": "25148216",
"text": "Several members of the Kruppel-like factor (KLF) family of transcription factors play important roles in differentiation, survival, and trafficking of blood and immune cell types. We demonstrate in this study that hematopoietic cells from KLF4(-/-) fetal livers (FL) contained normal numbers of functional hematopoietic progenitor cells, were radioprotective, and performed as well as KLF4(+/+) cells in competitive repopulation assays. However, hematopoietic \"KLF4(-/-) chimeras\" generated by transplantation of KLF4(-/-) fetal livers cells into lethally irradiated wild-type mice completely lacked circulating inflammatory (CD115(+)Gr1(+)) monocytes, and had reduced numbers of resident (CD115(+)Gr1(-)) monocytes. Although the numbers and function of peritoneal macrophages were normal in KLF4(-/-) chimeras, bone marrow monocytic cells from KLF4(-/-) chimeras expressed lower levels of key trafficking molecules and were more apoptotic. Thus, our in vivo loss-of-function studies demonstrate that KLF4, previously shown to mediate proinflammatory signaling in human macrophages in vitro, is essential for differentiation of mouse inflammatory monocytes, and is involved in the differentiation of resident monocytes. In addition, inducible expression of KLF4 in the HL60 human acute myeloid leukemia cell line stimulated monocytic differentiation and enhanced 12-O-tetradecanoylphorbol 13-acetate induced macrophage differentiation, but blocked all-trans-retinoic acid induced granulocytic differentiation of HL60 cells. The inflammation-selective effects of loss-of-KLF4 and the gain-of-KLF4-induced monocytic differentiation in HL60 cells identify KLF4 as a key regulator of monocytic differentiation and a potential target for translational immune modulation.",
"title": "Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo."
},
{
"docid": "23913146",
"text": "In Drosophila, three types of endogenous small RNAs-microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), and endogenous small-interfering RNAs (endo-siRNAs or esiRNAs)-function as triggers in RNA silencing. Although piRNAs are produced independently of Dicer, miRNA and esiRNA biogenesis pathways require Dicer1 and Dicer2, respectively. Recent studies have shown that among the four isoforms of Loquacious (Loqs), Loqs-PB and Loqs-PD are involved in miRNA and esiRNA processing pathways, respectively. However, how these Loqs isoforms function in their respective small RNA biogenesis pathways remains elusive. Here, we show that Loqs-PD associates specifically with Dicer2 through its C-terminal domain. The Dicer2-Loqs-PD complex contains R2D2, another known Dicer2 partner, and excises both exogenous siRNAs and esiRNAs from their corresponding precursors in vitro. However, Loqs-PD, but not R2D2, enhanced Dicer2 activity. The Dicer2-Loqs-PD complex processes esiRNA precursor hairpins with long stems, which results in the production of AGO2-associated small RNAs. Interestingly, however, small RNAs derived from terminal hairpins of esiRNA precursors are loaded onto AGO1; thus, they are classified as a new subset of miRNAs. These results suggest that the precursor RNA structure determines the biogenesis mechanism of esiRNAs and miRNAs, thereby implicating hairpin structures with long stems as intermediates in the evolution of Drosophila miRNA.",
"title": "Molecular mechanisms that funnel RNA precursors into endogenous small-interfering RNA and microRNA biogenesis pathways in Drosophila."
},
{
"docid": "17708753",
"text": "Whilst data recognise both myeloid cell accumulation during choroidal neovascularisation (CNV) as well as complement activation, none of the data has presented a clear explanation for the angiogenic drive that promotes pathological angiogenesis. One possibility that is a pre-eminent drive is a specific and early conditioning and activation of the myeloid cell infiltrate. Using a laser-induced CNV murine model, we have identified that disruption of retinal pigment epithelium (RPE) and Bruch's membrane resulted in an early recruitment of macrophages derived from monocytes and microglia, prior to angiogenesis and contemporaneous with lesional complement activation. Early recruited CD11b(+) cells expressed a definitive gene signature of selective inflammatory mediators particularly a pronounced Arg-1 expression. Accumulating macrophages from retina and peripheral blood were activated at the site of injury, displaying enhanced VEGF expression, and notably prior to exaggerated VEGF expression from RPE, or earliest stages of angiogenesis. All of these initial events, including distinct VEGF (+) Arg-1(+) myeloid cells, subsided when CNV was established and at the time RPE-VEGF expression was maximal. Depletion of inflammatory CCR2-positive monocytes confirmed origin of infiltrating monocyte Arg-1 expression, as following depletion Arg-1 signal was lost and CNV suppressed. Furthermore, our in vitro data supported a myeloid cell uptake of damaged RPE or its derivatives as a mechanism generating VEGF (+) Arg-1(+) phenotype in vivo. Our results reveal a potential early driver initiating angiogenesis via myeloid-derived VEGF drive following uptake of damaged RPE and deliver an explanation of why CNV develops during any of the stages of macular degeneration and can be explored further for therapeutic gain.",
"title": "Myeloid Cells Expressing VEGF and Arginase-1 Following Uptake of Damaged Retinal Pigment Epithelium Suggests Potential Mechanism That Drives the Onset of Choroidal Angiogenesis in Mice"
},
{
"docid": "27602752",
"text": "Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.",
"title": "CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS."
},
{
"docid": "1454773",
"text": "The programmed death-1 (PD-1) receptor serves as an immunologic checkpoint, limiting bystander tissue damage and preventing the development of autoimmunity during inflammatory responses. PD-1 is expressed by activated T cells and downmodulates T-cell effector functions upon binding to its ligands, PD-L1 and PD-L2, on antigen-presenting cells. In patients with cancer, the expression of PD-1 on tumor-infiltrating lymphocytes and its interaction with the ligands on tumor and immune cells in the tumor microenvironment undermine antitumor immunity and support its rationale for PD-1 blockade in cancer immunotherapy. This report details the development and characterization of nivolumab, a fully human IgG4 (S228P) anti-PD-1 receptor-blocking monoclonal antibody. Nivolumab binds to PD-1 with high affinity and specificity, and effectively inhibits the interaction between PD-1 and its ligands. In vitro assays demonstrated the ability of nivolumab to potently enhance T-cell responses and cytokine production in the mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays. No in vitro antibody-dependent cell-mediated or complement-dependent cytotoxicity was observed with the use of nivolumab and activated T cells as targets. Nivolumab treatment did not induce adverse immune-related events when given to cynomolgus macaques at high concentrations, independent of circulating anti-nivolumab antibodies where observed. These data provide a comprehensive preclinical characterization of nivolumab, for which antitumor activity and safety have been demonstrated in human clinical trials in various solid tumors.",
"title": "In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates."
},
{
"docid": "8639034",
"text": "IL-10 gene transcription and IL-10 protein production was assessed in both type 1 (Th1) and type 2 (Th2) CD4+ human T cell clones by polymerase chain reaction and ELISA, respectively. Although Th2 clones apparently showed higher IL-10 mRNA levels, IL-10 mRNA expression was consistently found in Th1 clones, as well. Likewise, measurable IL-10 levels were found in the supernatants of both Th1 and Th2 clones. The effect of human IL-10 (h-IL-10) and viral IL-10 (v-IL-10) on the proliferative response and cytokine production by Th1 and Th2 human clones was also investigated. Addition in culture of h-IL-10 and v-IL-10 significantly reduced the proliferation of both Th1 and Th2 clones in response to the specific Ag and to PHA, but it had no inhibitory effect on the proliferative response of Th1 and Th2 clones to IL-2. h-IL-10 and v-IL-10 also inhibited the Ag-induced production of gamma-interferon (IFN-gamma) by Th1 clones and the production of IL-4 and IL-5 by Th2 clones, whereas they had no effect on the cytokine synthesis by the same clones stimulated with PMA plus anti-CD3 antibody. Preincubation of APC, but not of clonal T blasts, with h-IL-10 resulted in the inhibition of Ag-induced proliferation of both Th1 and Th2 clones, supporting the view that h-IL-10 primarily affects APC. These data demonstrate that, unlike the murine system where IL-10 is a product of Th2 (but not Th1) cells and seems to mainly down-regulate the Th1 response, in the human system, IL-10 is produced by, and down-regulates the function of, both Th1 and Th2 cells.",
"title": "Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production."
}
] |
769
|
(Almost) no credit unions in New York City, why?
|
[
{
"docid": "413722",
"text": "There are 2 credit unions in the Metro NY area that are open to everyone: You might also want to check out aSmarterChoice.org to see if there are other credit union options based on where you live, work, worship & more.",
"title": ""
},
{
"docid": "149258",
"text": "I would have been tempted to dismiss your claim, but the data I found shows that you're correct. On the plus side, the growth rate in credit union market share is higher in New York than it is in California. While there is no question that bankers hate credit unions, I can't tell you why credit unions have a smaller market share in NY. Maybe the regulatory environment is part of it. Banks have a big lobby, and they pay a lot of taxes in NYC.",
"title": ""
}
] |
[
{
"docid": "489070",
"text": "He cannot get money from someone else account. Your US resident friend in New York can send money to your Indian friend in Atlanta via Western Union which has presence in almost every corner of the US. Most definitely in the city of Atlanta. Your Indian friend can receive the Western Union transfer, in cash, within minutes after the friend in New York sends it. Here's the site for location search. The sender doesn't need to go anywhere, can send online, so your New York friend doesn't even need to waste much time. In fact - you don't need to bother your friend in New York, you can send it online yourself (assuming you're American/have US bank account). In order to receive the money, your Indian friend will obviously need a proper identification (i.e.: passport).",
"title": ""
},
{
"docid": "387749",
"text": "\"*\"\"At our current rate of pay, New York City Police officers are still among the lowest paid big city police officers in the nation,\"\" said Patrick Lynch, head of the New York City Patrolmen's Benevolent Association, the city's largest police union.* *The special-ops sergeant who made $265,059 is the highest paid policeman so far this year. His pay includes $115,394 in overtime. Besides the aviation director's pay, it also outstrips Chief Financial Officer Michael Fabiano's earnings of $257,814.* $265,059-115,394=$149,665. (not including OT) Assuming they work 40h/w @ $149,665 = $71/hour... whereas a $35,000 salary puts you at $16/hour. Even $70,000 puts you at $32/h. How much do big city cops make??\"",
"title": ""
},
{
"docid": "419589",
"text": "Jesus you're impossibly dense. >I know that the Port Authority employees don't work for the city, so that's a straw man. Then why did you write the quote below? What is the point of bringing up city workers that are not involved in the article unless you believe that the cops in the article are city workers? The only other reason would be to mislead the reader. >Presidential and statewide elections have no bearing on employment contracts for city workers. . >The reason you've been disingenuous is because you implied that the fact that New York City is overwhelmingly Democratic has any bearing over the control of the New York State Legislature, or the Governorship, when this is clearly not the case. Are you serious? NYC has 8mm of the 19mm NY state residents. This equates to almost half of the votes in statewide races, not to mention the majority of the political funding. This has a large bearing on who gets elected to statewide office. >Even so, the current state of the Port Authority was shaped by more than the past 5 years, and to imply otherwise is also disingenuous. To imply that the executive director for the last 5 years should shoulder some of the blame is disingenuous? Who is to blame then? The last executive director, Anthony Shorris was also appointed by a democrat. You're going to have to do a lot of lying and reaching to falsely blame this on a republican. You've clearly made up your mind without knowing any of the facts, and are too stubborn to learn from reality. Pretty sad. You also seem to have a very high standard for other people's posts while you outright lie in yours.",
"title": ""
},
{
"docid": "559852",
"text": "Of course, 100k a year is middle to upper middle in almost every location except the global hubs of America (la, San Fran, new york, etc etc). I know where i live a family making 100k is just 227$ away from upper class (according to Washington posts calculator). Hell growing up my mother made 38k and she was able to afford a 150k house, yearly vacation trips abroad, and a new car paid off in 1 year. By all means of the article that is the aspirations Joe Biden quoted. The only difference is we live in the midwest. I think no one living in California, New York city, miami, etc. should get delusional and believe that our most demanded locations will have room for everyone, especially at a reasonable rate. People are willing to spend 5k for a studio in New York because it is a city of opportunity, San Francisco is not a place to let life come to you. What i love about the Midwest is that living is incredibly cheap, and if you have established yourself soon enough there is a fortune to be made, especially in real estate. Not to mention we have Chicago, Detroit, Cedar Point which almost every family is close enough and earns enough to visit at least once a year. We may not have enough to afford Lamborghini's, multi million dollar houses, or to visit paris on a whim but I feel most in the midwest have enough to love comfortably and save for retirement atleast (minus maybe the bible belt)",
"title": ""
},
{
"docid": "493872",
"text": "As a resident of New York State you will, in addition to the Federal income tax handled by the IRS, be responsible for state and local income taxes. For New York the state tax forms are also used to determine your New York city tax. If HR was either not aware of the local tax requirement for New York or you filled out the New York State version of the W-4 incorrectly you may have had too little tax withheld for New York state. The refund from the IRS is not dependent on the refund/owe status for state and local taxes. It is possible that your state taxes are fine but that you owe taxes to the city. That tax you owe to the city will reduce the refund from the state and may require you to pay money to New York. Of course if you do itemize, what you pay to the state and city may result in deductions on your federal form. If you owe back taxes to the state or local government this could result in the IRS seizing a federal refund, but that doesn't happen right away.",
"title": ""
},
{
"docid": "501206",
"text": "I know very well how my local government works, and you either don't or are being disingenuous. At the state level, New York is split between Democrats and Republicans, with the Republicans almost always in control of the state Senate, and controlling the Governor's office for 10 of the last 20 years. So it doesn't matter that Republicans haven't won in New York City at the State level, since the State Government is mostly evenly split between Democrats and Republicans in terms of control.",
"title": ""
},
{
"docid": "563974",
"text": "\">Of course, this is true as long as you ignore issues like New York policeman spiking their overtime by working as flagmen on construction projects. A POLICEMAN.. dont you know if one person gets welfare that doesnt deserve it, we should throw out the entire system.. right? >The unions have done a great job focusing anger on the banks, yeah cuase it was unions that crashed the worlds economy. IT was unions that created derivatives, it was unions that created sub prime lending, it was unions that created \"\"liar loans\"\" right? >but the states and cities are going to keep going bankrupt. Ok big quiz here, please turn down fox news for this one. WHAT HAPPENS TO STATE FINANCE'S IN A RECESSION? what happens to tax receipts? and what happens to spending on things that help the poor? I'll wait on you to think about it, I will not wait on you while you wait for fox to tell you the answer Bonus question since you are not going to bother the answer the one above. What is the program called \"\"[starve the beast](http://en.wikipedia.org/wiki/Starve_the_beast)\"\", who started it, what is its purpose, and what it it;s methodology?\"",
"title": ""
},
{
"docid": "597571",
"text": "First, if you live in/around a reasonably populated urban area, and you're in the United States, I can't see why you would choose to bank with Chase, B of A, or another large commercial bank. I think you would be much better served by banking at a reasonably large credit union. There are many differences between banks and credit unions, but in a nutshell, credit unions are owned by the members, and operate primarily to provide benefits to their members, whereas a bank is owned by the shareholders, and operates primarily to make profits for the shareholders (not to benefit the customers). The banking industry absolutely hates the credit unions, so if you've ever been nickeled-and-dimed with this fee and that charge by your bank, I have to ask why you're still banking with a company that irritates you and/or actively tries to screw you out of your money? I live in California, and I've banked at credit unions almost exclusively since I started working nearly 30 years ago. Every time I've strayed and started banking at a for-profit bank, I've regretted it. For example, a few years ago I opened a checking account at a now-defunct bank (WaMu) just for online use: eBay and so forth. It was a free checking account. When Chase bought WaMu, the account became a Chase account, and it seemed that every other statement brought new fees, new restrictions, and so forth. I finally closed it when they imposed some stupid fee for not carrying enough of a balance. I found out by logging in to their Web site and seeing a balance of zero dollars; they had imposed the fee a few statements back, and I had missed it, so they kept debiting my account until it was empty. At this point, I do about 90% of my banking at a fairly large credit union. I have a mortgage with a big bank, but that was out of my hands, as the lender/originator sold the mortgage and I had no say in the matter. My credit union has a highly functional Web site, permits me to download my account activity to Quicken, and even has mobile apps which allow me to deposit a check by taking a picture of it, or check my account activity, etc. They (my credit union) are part of a network of other credit unions, so as long as I am using a network ATM, I never pay a fee. In sum, I can't see any reason to go with a bank. Regarding checks, I write a small number of checks per year, but I recently needed to reorder them. My credit union refers members directly to Harland-Clarke, a major-league player in the check printing business. Four boxes of security checks was around $130 plus shipping, which is not small money. However, I was able to order the very same checks via Costco for less than half that amount. Costco refers members to a check printing service, which is a front/subsidiary of Harland-Clarke, and using a promo code, plus the discount given for my Costco membership, I got four boxes of security checks shipped to me for less than $54. My advice would be to look around. If you're a Costco member, use their check printing service. Wal*mart offers a similar service to anyone, as does Sam's Club, and you can search around to find other similar services. Bottom line, if you order your checks via your bank or credit union, chances are you will pay full retail. Shop around, and save a bit. I've not opened a new account at a credit union in some time, but I would not be surprised if a credit union offered a free box of checks when you open a new account with them.",
"title": ""
},
{
"docid": "258611",
"text": "The cost will be around $300-$500 if you do it correctly it in Florida and can be over a $1,000 if you do it in New York (New York is more expensive due to a publication requirement that New York has for LLC’s). The price ranges I’ve given include filing, state fees, getting a tax ID number (EIN), operating agreement, membership certificates, registered agent fees and publication fees if done in New York. Each state also have licensing boards and city fees that are applicable, so you would want to also make sure that you are keeping compliant there. Yearly paperwork to keep the LLC running won’t be so expensive, expect the state to charge a yearly fee and require some basic information to be submitted. I had a quick look at Florida, and with someone filing it for you, expect around $200 to $250 a year, plus registered agent fees. If you are late in Florida the penalty is $400 so you definitely would want a service that provides compliance calendar notifications to make sure you are on time with fees. In regards to bookkeeping and taxes, yearly tax filing will start at $250 to $500 for an LLC and move up from there depending on the services being offered and the amount of time of work. I recently referred someone to an accountant that will charge $250 to file an almost zero tax return on an LLC. I think $40 an hour is a little low for a bookkeeper but it all depends on where you are. I know in some major cities bookkeepers expect $75 an hour or higher. So the expectation in Miami and Manhattan will probably be more expensive than Jacksonville and Albany. If you doing a little business don’t expect the cost to be too much on the bookkeeping. So, breakdown: $300-$500 (FL) - $1,000 (NY) Registration of LLC + any business license, city or other registrations $250 Yearly Fee + Yearly Registered Agent + any business licenses, city or other fee $500 Tax Return + Bookkeeping Fee Banks will charge more than a personal account so expect $120 a year plus. In regards to service I would look at companies that specialize in foreigners setting up businesses in the US, because they will have services designed to help you more than services that primarily specialize with US clients. You are going to have some different needs, based on not having a Social Security Number or establishing from overseas.",
"title": ""
},
{
"docid": "433817",
"text": "\"If all of the money needs to be liquid, T-Bills from a broker are the way to go. Treasury Direct is a little onerous -- I'm not sure that you could actually get money out of there in a week. If you can sacrifice some liquidity, I'd recommend a mix of treasury, brokered CDs, agency and municipal securities. The government has implicitly guaranteed that \"\"too big to fail\"\" entities are going to be backed by the faith & credit of the United States, so investments in general obligation bonds from big states like New York, California and Florida and cities like New York City will yield you better returns, come with significant tax benefits, and represent only marginal additional short-term risk.\"",
"title": ""
},
{
"docid": "296033",
"text": "Of course, this is true as long as you ignore issues like New York policeman spiking their overtime by working as flagmen on construction projects. And, of course, pensions are determined by the highest paid years, so it's a great double dip scam. The unions have done a great job focusing anger on the banks, but the states and cities are going to keep going bankrupt.",
"title": ""
},
{
"docid": "443828",
"text": "US or EU states are sovereigns which cannot go bankrupt. US states have defaulted in the 1840's, but in most of those cases creditors were eventually repaid in full. (I'm not 100% sure, but I believe that Indiana was an exception with regard to costs incurred building a canal system) The best modern example of a true near-default was New York City in the late 1970's. Although New York City isn't a state, the size and scope of its finances is greater than many US states. What happened then in a nutshell: Basically, a default of a major state or a city like NYC where creditors took major losses would rock the financial markets and make it difficult for all states to obtain both short and long term financing at reasonable rates. That's why these entities get bailed out -- if Greece or California really collapse, it will likely create a domino effect that will have wide reaching effects.",
"title": ""
},
{
"docid": "103932",
"text": ">For instance in far upstate New York its probably cheaper to truck gas from a refinery outside of Montreal than from a refinery outside of New York City or Boston. Oddly enough, there aren't any refineries outside Boston. There aren't any in Massachusetts at all. In fact, there are also none in New York, New Hampshire, Vermont, Maine, Connecticut, or Rhode Island. There are two refineries near New York City, but they're in New Jersey.",
"title": ""
},
{
"docid": "462000",
"text": "As a tourist, you will definitely find New York to be one of the best places to visit during the summers as well as winters. Through our company website which you can save lots of money by selecting the cheap hotels and other transport. Hotels in New York are the most important thing to know about at the time when you are really willing to visit New York City. With TravelGuysOnline travelers may face not anyone difficulty in searching and selecting Cheap accommodation in New York City.",
"title": ""
},
{
"docid": "219004",
"text": "The cost of living is quite high in New York City. It has the highest CPI (Consumer Price Index) of any city in the U.S. Salaries also tend to be highest in NYC. Just about any bicycle lock sold in the U.S. has an exception in its warranty for NYC. It is the most populous American city. So, why do people deal with all the hassles of living here? Because, it is a hotbed of activity. I venture that the advantages are basically the same in Zurich:",
"title": ""
},
{
"docid": "449340",
"text": "What would be the best city matched to their criteria? Here is a list of 40 cities with international airports (one of their criteria): * Atlanta * Chicago * Los Angeles * Dallas-Fort Worth * Denver * New York * San Francisco * Charlotte * Las Vegas * Phoenix * Houston * Miami * Orlando * Newark * Seattle * Minneapolis * Detroit * Philadelphia * Boston * New York * Fort Lauderdale * Baltimore * Washington * Salt Lake City * Washington * Chicago * Honolulu * San Diego * Tampa * Cleveland * Portland * St Louis * Houston * Oakland * Kansas City * Nashville * Austin * Raleigh/Durham * Sacramento * Santa Ana",
"title": ""
},
{
"docid": "117895",
"text": "\"you could get a discover card and then just \"\"freeze\"\" it. you might need to unfreeze it for a few minutes when you sign up for a new service, but it is unlikely an ongoing subscription would process a charge in that window. i believe merchants are charged a small fee for a transaction even if it is declined, so they won't try constantly forever. discover account freeze faq capitalone offers this freeze feature on their \"\"360\"\" debit cards. you can even freeze and unfreeze your card from their mobile app. this feature is becoming more common at small banks and credit unions too. i know of 2 small local banks that offer it. in fact, almost any bank can give you a debit card, then set the daily POS limit to 0$, effectively making it an atm-only card. but you may need to call the bank to get that limit temporarily lifted whenever you want to sign up for a new service. alternatively, jejorda2's suggestion of virtual account numbers is a good idea. several banks (including discover) have discontinued that feature, but i believe citi, and boa still offer them. side notes:\"",
"title": ""
},
{
"docid": "182217",
"text": "\"Depends. If you can choose where to relocate to, then I second the \"\"no income tax\"\" states. But even of these chose wisely, some have no income taxes at all, others have taxes on some kinds of income. Some don't have neither individual nor corporate taxes, some tax businesses in some ways. Some compensate with higher property taxes, others compensate with higher sales taxes. On the other hand, you might prefer states with income taxes but no sales taxes. It can happen if your current income is going to be low, but you'll be spending your savings. If you don't have a choice (for example, your employer wants you to move closer to their office), then you're more limited. Still, you can use the tax break on moving expenses (read the fine print, there are certain employment requirements), and play with the state taxes (if you're moving to a state with less/no taxes - move earlier, if its the other way - move later). Check out for cities that have income taxes. In some states it cannot happen by law (for example, in California only the state is allowed to collect income taxes), in others it is very common (Ohio comes to mind). Many things to consider in New York. New York City has its own income tax (as well as Yonkers, as far as I remember these are the only ones in the State of New York). So if you want to save on taxes in NYS but live close to the city, consider White Plains etc. If you work in NYC its moot, you're going to pay city taxes anyway. That is also true if you live in NJ but work in the city, so tax-wise it may be more efficient not to live across state lines from your place of work.\"",
"title": ""
},
{
"docid": "378611",
"text": "Corey Rockafeler is president of Vaalk Consulting Group. He is also small business financing expert and part of leadership team at Bell Funding Solutions in New York City. Some of the city’s top businesses regard him as their first choice when it comes to securing growth and expansion capital. He offers complete financing solutions for growing business. His custom solutions include everything from multi-year terms, lines of credit, asset and collateral based loans, factoring and receivable financing to SBA and SBA bridge loans. When asked about his key to success, Corey stated, “It’s all about passion",
"title": ""
},
{
"docid": "106281",
"text": "I know that the Port Authority employees don't work for the city, so that's a straw man. The reason you've been disingenuous is because you implied that the fact that New York City is overwhelmingly Democratic has any bearing over the control of the New York State Legislature, or the Governorship, when this is clearly not the case. The fact that the current executive director was appointed by Paterson is the first relevant argument you've made. Even so, the current state of the Port Authority was shaped by more than the past 5 years, and to imply otherwise is also disingenuous.",
"title": ""
},
{
"docid": "511522",
"text": "\">The Port Authority operates New York City's airports, its seaports, a train system, and several bridges and tunnels. Newark Airport and Port Elizabeth/Newark are in NJ, not NY. And the \"\"train\"\" system, the PATH is half in NJ, as are all of the bridges and tunnels. Interesting why the article is so NY-centric.\"",
"title": ""
},
{
"docid": "113558",
"text": "\"The reason \"\"on-line\"\" savings accounts (Ally, CapitalOne, American Express, and many others) provide much higher rates than brick-and-mortar banks is because they're not brick-and-mortar. They do not need to pay for a huge amount of real estate, utilities, public-facing employees, inter-office mail, security, etc etc. All that - allows them to pay more for your money. The back office of these banks is the same as that of Chase, BOA or Wells Fargo. Its just that they don't have the enormous expense of having a branch in every neighborhood, while still reaching all the same population of depositors. So no, its not a scam, these are reputable banks. Some have physical offices (for example, I know that CapitalOne has some branches in New York), some don't (IIRC neither Ally nor American Express Federal Saving Bank have physical branches). But they're banks nonetheless, insured as required by FDIC (or NCUA, in case of credit unions), and provide all the same services for less (or all the same savings for more, if you will). IMHO, giving 0.01% APR is a scam. Not the other way around. The old-style banks want your money for free, and you're worried why would someone else treat you better... Well, that's why the US has one of the most retarded financial systems in the Western world...\"",
"title": ""
},
{
"docid": "315363",
"text": "How do credit unions work in the US? Why not just get rid of deposit insurance for commercial banks and keep it for credit unions. Restrict credit unions ability to filter money to the new 'investment bank' sector by keeping them out of repo and money markets (not sure if this is done currently) and bang - Corporates/institutions can still lend short and banks can still lend long in the professional world, while unsophisticated retail customer's checking accounts at least are protected from the inevitable crash.",
"title": ""
},
{
"docid": "555581",
"text": "\"Yes, it is possible for you to refinance your existing auto loan, and so long as you can get the loan on more favorable terms (e.g.: lower interest rate), it is absolutely a smart thing to do. In fact, you would be well advised to do so as soon as possible if the car was a new car, if you refinance a NEW car soon enough you will likely still be able to get new car interest rates. Even if it is a pre-owned vehicle you shouldn't wait too long, since your car will only depreciate in value. You will almost certainly get more favorable terms from any bank or credit union directly then you would when you go through the dealership, because the dealership is allowed to mark-up your interest rate several percentage points as profit for themselves. Your best bet would be to go to a local credit union, their rates tend to be most competitive since they are \"\"owned\"\" by their members.\"",
"title": ""
},
{
"docid": "468267",
"text": "\"I was a millennial \"\"stuck\"\" in New York. I was in law school when the crash happened. I wanted to practice in smaller cities like CLT or ATL but immediately after the crash there were very few jobs, while New York started doing deals again by about late 2009. So I had to go to NY. You end up getting \"\"stuck\"\" because of the barriers to move. For me it was the bar. But there are others like markets that recovered more slowly, experience requirements set by employers, the fact that there are simply more jobs in large urban markets. Most of my law school class started in SF, NY, Chi, and LA. Now we're on our 2nd firm or city in CLT, ATL, HOU, MIA, etc.\"",
"title": ""
},
{
"docid": "257187",
"text": "\"Sometimes 403b's contain annuities or other insurance related instruments. I know that in many New York schools the local teacher unions administer the 403b plan, and sometimes choose proprietary investments like variable annuities or other insurance products. In New York the Attorney General sued and settled with the state teacher's union for their endorsement of a high cost ING 403b plan -- I believe the maintenance fees were in excess of 3%/year! In a tax deferred plan like a 401k, 403b or 457 plan, the low risk \"\"insurance fund\"\" is generally a GIC \"\"Guaranteed Investment Contract\"\". A GIC (aka \"\"Stable Value Fund\"\") is sort of cross between a CD and a Money Market fund. It's used by insurance companies to raise short term capital. GICs usually yield a premium versus a money market and are a safe investment. If your wife is in a 403b with annuities or other life-insurance tie ins other than GICs, make sure that you understand the fee structure and ask lots of questions.\"",
"title": ""
},
{
"docid": "485860",
"text": "I purchased a used (2011, low miles) sedan in early 2014 for ~28k, 9 months before moving to the city. I put 12k down including trade in and currently own 9k on the car (1.9% APR). It's a luxury sedan (not a 3 series, hah!) and will hold it's value better than other cars for quite a while (currently worth ~23k in private sale). 1.9% APR yet it costs you 50% APR to keep it. Regarding your logistical problem: Maybe you will go home/your parent's house less. Maybe you will make New York City your home. Even if there is something very serious (or interesting) 320 miles away, the rest of us also have to deal with this. Bus, train, Uber, arrange pickup at the train station with friend's/family. You can also subsidize flights and trains with promotional credit card miles.",
"title": ""
},
{
"docid": "489160",
"text": "Most of the imports probably come from Canada and Mexico, its probably cheaper to import gasoline from Canada or Mexico in some parts of the country purely due to distance. For instance in far upstate New York its probably cheaper to truck gas from a refinery outside of Montreal than from a refinery outside of New York City or Boston.",
"title": ""
},
{
"docid": "170481",
"text": "Good credit is calculated (by many lenders) by taking your FICO score which is calculated based upon what is in your credit report. Building credit generally means building up your FICO score. Your FICO score is impacted my many factors, one small one of which is your utilization ratio of your installment loans like student loans. This is the ratio of the current balance to your original balance. To improve your score (slightly) you would want a lower ratio. I would recommend paying your student loan down to 75% ratio as fast as you can and then you can go back to $50/month. A much better way to improve your FICO score is to have revolving credit. Your student loans are not revolving, they are installment loans. Therefore, you should open at least one credit card (assuming you currently have none) right away. The longer you have had a credit card open, the better your FICO score gets. Your revolving credit utilization ratio is way more important than your installment loan ratio. Therefore, to maximize your FICO, try to never have more than 10% utilization on your revolving credit report to the credit bureaus each month. Only the current month's ratio affects your score at any given moment. You can ensure you don't go above 10% by paying your balance before the statement cuts each month to get it below 10% way before any payment would be due. (You should always pay your remaining credit card statement balance in full each month by the due date after the statement cuts to avoid any interest charges.) Note that there is a slight FICO advantage to having at least one major bank credit card instead of just only credit union credit cards. Also, never let all your revolving credit report a zero balance in a month, you must always have at least $1 reporting to the credit bureaus on at least one of your open credit cards or your FICO score will take a big negative hit. If you cannot get a normal credit card, go to a credit union and find one that offers secured credit cards, or a bank that does. A secured credit card is where you place a deposit with the bank that they hold and give you a credit limit to match your security. Ideally it would be a card that graduates to unsecured after your demonstrate good history with them. For example, the Navy Federal Credit Union secured card unsecures for many people. I also believe the Wells Fargo Bank credit card (you can join if there is a family member who served or a roomate who did) also will unsecure. The reason you want it to unsecure and not be forced to open a new account to get an unsecured account is that you want your average age and oldest age of open revolving credit accounts to be as high as possible as this is another impact on your FICO score. Credit unions that anyone can join include, Digital Federal Credit Union, the Pentagon Federal Credit Union (which offers a secured card that does not graduate), and The State Department Federal Credit Union (also offers secured card that I think does not graduate). One other method to boost your FICO score is to get added as an authorized user on one of your parent's credit cards that has been open a long time. Not all lenders will report such an authorized user, however, ones that are known to do so are: Bank of America, Citi Bank, and Capital One. It is a good sign that it will report if they ask for the social security number of the authorized user. However, note that the Authorized User addition can have no impact if the lender is using one of the newer versions of the FICO scoring model, only the older versions reward you for the age of accounts for which you are an authorized user. A very long term boost is to open your first American Express card underwritten directly by Amex such as their Zync card which is pretty easy to get. The advantage of American express is that they remember the date your first credit card was opened with them and if you open new accounts in the future they will back date the date of their opening to match the date your first card was opened. If you let your membership lapse, be sure to record the account number and date opened in your personal files so that you can help them locate it again if you reopen as they can have trouble if it has been on the order of ten years or more. Finally, note that the number of accounts opened in the last twelve months is a small negative mark on your score (along with number of inquiries), so if you open a lot of accounts all at once, in addition to bringing down your average age of accounts, you will also get dinged for how many were opened in the last year.",
"title": ""
},
{
"docid": "191925",
"text": "Several things to do: Change your bank. $2 for a check? Why?? When shopping for a new bank: ask for a free checking account. College students can get free checking in almost any bank. At least the first box of checks will be free, which will give you enough checks for the next several years (I'm still not half done with the box I got from WaMu 5 years ago). Check out your neighborhood credit union. Most of them have free checking and free checks for students as well. If still no luck - check online check printing services, they'll send you a box for less than $25, that's for sure. Walmart for example (1 box - $7). Also, you can use banks' bill-pay service for any check you write, if you know the address of the person, the amount and the sum a couple of days ahead of time. That should cover rent, and probably most of your other checks.",
"title": ""
}
] |
5a83035555429966c78a6ae4
|
Robbie Rogers was the second male soccer player in Britain to come out as gay, the first being the first black footballer to command a transfer fee of how much?
|
[
{
"docid": "950473",
"text": "Justinus Soni \"Justin\" Fashanu ( ; 19 February 1961 – 2 May 1998) was an English footballer who played for a variety of clubs between 1978 and 1997. He was known by his early clubs to be gay, and came out to the press later in his career, becoming the first professional footballer to be openly gay. He was also the first black footballer to command a £1million transfer fee, with his transfer from Norwich City to Nottingham Forest in 1981, but had little success as a player afterwards, although he continued to play at senior level until 1994.",
"title": ""
},
{
"docid": "9485388",
"text": "Robert Hampton \"Robbie\" Rogers III (born May 12, 1987) is an American professional soccer player who plays for LA Galaxy in Major League Soccer. He plays as a winger and as a left back. Rogers has also represented the United States men's national soccer team. In February 2013, Rogers came out as gay, becoming the second male soccer player in Britain to do so after Justin Fashanu in 1990. On May 26, 2013, he became the first openly gay man to compete in a top North American professional sports league when he played his first match for the Galaxy.",
"title": ""
}
] |
[
{
"docid": "38372578",
"text": "Few American football players have come out as gay. Six former National Football League (NFL) players have come out publicly after they retired. There has never been anyone who has been publicly out while playing in the NFL. Michael Sam was selected by the St. Louis Rams in 2014 NFL Draft, and became the first publicly gay player drafted in the league, but was released before the start of the regular season. He became the first publicly gay player to play in the Canadian Football League in August 2015. In college football, Division III player Conner Mertens came out as bisexual in January 2014, becoming the first active college football player at any level to publicly come out. In August 2014, Arizona State player Chip Sarafin became the first publicly out active Division I player.",
"title": ""
},
{
"docid": "1037246",
"text": "David Testo (born August 7, 1981, in Winston-Salem, North Carolina) is an American retired soccer player who, after his playing career ended in 2011, became the first male American professional player of that sport to come out as gay. Testo played professionally from 2003 to 2011, including two years in Major League Soccer with the Columbus Crew from 2004 to 2005. He began his career with the second division side Richmond Kickers, and also played for the Vancouver Whitecaps and Montreal Impact (also second division teams at the time), before he was released by the Impact in 2011. He played collegiately for South Carolina and North Carolina.",
"title": ""
},
{
"docid": "23956953",
"text": "Homophobia has been widespread in association football throughout the world. Journalist Matt Williams stated that being a gay professional player in football is still a taboo, which journalist Simon Barnes has said will never change. In February 2013, football magazine \"When Saturday Comes\" described homosexuality as a \"continuing taboo\" in the sport. John Amaechi, the first NBA player to come out, has blamed football's \"toxic\" culture for the lack of openly gay players, while Clarke Carlisle has called for more education to be given to players to combat homophobia.",
"title": ""
},
{
"docid": "11980585",
"text": "10% QTV is a Canadian television newsmagazine series, which aired on Rogers Television stations in Ontario from 1995 to 2001. It was the first multiseason television series in Canada targeted specifically to the lesbian, gay, bisexual and transgender community, being preceded only by short run series such as \"Coming Out\" in 1972, and \"Out of the Closets\" and \"Gay News and Views\" in 1977-78.",
"title": ""
},
{
"docid": "27871729",
"text": "Eric Anderson (born January 18, 1968) is an American sociologist and sexologist specializing in adolescent men's gender and sexualities. He holds the position of Professor of Masculinities, Sexualities and Sport at the University of Winchester, in England. His research has been recognized for excellence by the British Academy of Social Sciences and he is an elected Fellow of the International Academy of Sex Research. Anderson is an advocate for the inclusion of gay men in sport and is America's first openly gay high-school coach coming out at Huntington Beach High School, the same high-school that produced the nation's first openly gay, actively playing, professional team sport athlete, Robbie Rogers who currently plays for LA Galaxy.",
"title": ""
},
{
"docid": "37963848",
"text": "Jason Ball (born 16 January 1988) is an Australian LGBTI and mental health advocate and former political candidate. In 2012 he came out as gay, becoming the first male Australian rules football player at any level to publicly come out in the national media. In 2016 he stood for the Australian Greens as a candidate in the House of Representatives seat of Higgins at the federal election.",
"title": ""
},
{
"docid": "4891000",
"text": "Roy Franklin Simmons (November 8, 1956 – February 20, 2014) was an American football player who played as guard National Football League (NFL) with the New York Giants and the Washington Redskins. With the Redskins he played in Super Bowl XVIII. He became the second former NFL player to come out as gay and the first to disclose that he was HIV-positive.",
"title": ""
},
{
"docid": "1645671",
"text": "Alf Common (25 May 1880 in Millfield – 3 April 1946 in Darlington) was an English footballer who played at inside forward or centre forward. He is most famous for being the first player to be transferred for a fee of £1,000 on his transfer to Middlesbrough from Sunderland in 1905.",
"title": ""
},
{
"docid": "53515458",
"text": "Edward \"Chip\" Sarafin is a former American football Offensive Lineman from Gilbert, Arizona. He was the first active college football player in Football Bowl Subdivision to publicly come out as gay.",
"title": ""
},
{
"docid": "3870319",
"text": "John Blankenstein (12 February 1949 in De Bilt – 25 August 2006 in The Hague) was a Dutch football referee and gay rights activist. He was notable for being one of the first homosexual athletes to come out in the Netherlands.",
"title": ""
},
{
"docid": "394047",
"text": "Réal Ménard (born May 13, 1962 in Montreal, Quebec) is a Canadian politician, who was a Bloc Québécois member of the Canadian House of Commons from 1993 to 2009. He was the second Canadian Member of Parliament to come out as gay (the first being Svend Robinson).",
"title": ""
},
{
"docid": "2850589",
"text": "Charles Adolphus Williams, MBE (23 December 1927 – 2 September 2006) was an English professional footballer who was one of the first black players in British football after the Second World War, and later became Britain's first well-known black stand-up comedian.",
"title": ""
},
{
"docid": "41520795",
"text": "The Rugby league transfer record is the highest-ever sum of money paid by a club to purchase the contract, and therefore the playing services, of another club's player. It has been re-set almost every decade since the sport became professional around the start of the 20th century. Between the 1930s, and 1980s international transfer bans were imposed, removed and renewed at different times due to the sport's governing bodies' fears of excessive talent drain overseas. In 1998, the sport's transfer system was changed to allow any player aged 24 or over to move between clubs at the end of their contract without a fee being paid. As a result, transfer fees in rugby league became much more uncommon. The current record fee was paid for Sam Tomkins, for whom the New Zealand Warriors paid £700,000 to the Wigan Warriors in 2013.",
"title": ""
},
{
"docid": "44615134",
"text": "Writing Black Britain 1948-1998 is an anthology of black British writings published in 2000 and edited by James Procter. The selection of writings includes many well-known writers such as Stuart Hall and Paul Gilroy. This is an interdisciplinary collection and contains a variety of writings that discuss different forms of representation, i.e. films, music, and photography. It is centered on works of the diaspora, including Caribbean, African, and South Asian experiences. This collection is the first of its kind and critically engages with both the construction and community of \"black Britain\" and power relations. Every writer has something to say about their own positionality and how they've come to theorize black Britain.",
"title": ""
},
{
"docid": "1132159",
"text": "Edward John Frank Howe ( ; born 29 November 1977) is an English former professional footballer and manager. A defender before retirement who spent much of his career at Bournemouth, he was the youngest manager in the Football League when appointed Bournemouth manager in January 2009. Howe rescued Bournemouth from relegation out of the Football League in his first season in charge, after the club started the season on −17 points, then led them to promotion the next. After a brief spell as manager at Burnley, Howe returned to Bournemouth and led them to two further promotions in three seasons resulting in the club playing in the top flight of English football for the first time in their history. Howe's successes with Bournemouth resulted in him being given the inaugural Football League Manager of the Decade Award in 2015.",
"title": ""
},
{
"docid": "5400821",
"text": "One More River to Cross: Black and Gay in America is a 1996 book written by Keith Boykin, who ran a now-defunct national black gay and lesbian organization. He begins the book by describing his life, including coming out at Harvard Law School, working for President Bill Clinton, and his first sexual experience. He interviews many famous African-American gay men and lesbians such as Cleo Manago, Perry Watkins, and Cheryl Clarke.",
"title": ""
},
{
"docid": "1386074",
"text": "David Bone Nightingale Jack (3 April 1898 – 10 September 1958) was an English footballer who played as an inside forward. As a player, Jack featured for clubs Plymouth Argyle, Bolton Wanderers and Arsenal. He was the first footballer to be transferred for a fee in excess of £10,000, together with being the first to score at the Wembley in the 1923 FA Cup Final. He also featured for the England national football team. Jack is Arsenal's 10th highest ever goalscorer and as well Bolton Wanderers's third highest goalscorer of all time.",
"title": ""
},
{
"docid": "935938",
"text": "Denis Law, CBE (born 24 February 1940) is a Scottish former footballer who played as a forward. His career as a football player began at Second Division Huddersfield Town in 1956. After four years at Huddersfield, he was signed by Manchester City for a transfer fee of £55,000, which set a new British record. Law spent one year there before Torino bought him for £110,000, this time setting a new record fee for a transfer involving a British player. Although he played well in Italy, he found it difficult to settle there and signed for Manchester United in 1962, setting another British record transfer fee of £115,000.",
"title": ""
},
{
"docid": "30426657",
"text": "The 1991–92 season was Port Vale's 80th season of football in the Football League, and third successive (35th overall) season in the Second Division. For only the third time in their history they competed in a division above rivals Stoke City. However it was not a happy campaign, John Rudge was forced to deal with star players Darren Beckford and Robbie Earle being sold for combined fees of £1.7 million. He spent just £375,000 to bring future-legend Martin Foyle to the club, whilst reliable goalkeeper Mark Grew was handed the club's Player of the Year award. Vale were relegated in bottom place, just five points short of safety. They exited the League Cup at the Third Round, despite a credible 2–2 draw with Liverpool at Anfield. Leaving the FA Cup at the Third Round, they were knocked out at the Second Round stage of the Full Members Cup.",
"title": ""
},
{
"docid": "26351207",
"text": "In the United Kingdom, football clubs sometimes choose to enter administration when they are unable to pay off outstanding debts. Under the Insolvency Act 1986, a business will face a winding-up order bringing them to court and if it is shown that a business cannot pay debts as they fall due or cannot repay outstanding debts then the company will be classified as insolvent. Administration puts accountants \"in charge of pretty much everything apart from coaching the players and picking the team\". For a football club in administration, the \"football creditors rule\" requires football-related debts such as wages owed to players and staff, and transfer fees owed to other clubs to be paid first.",
"title": ""
},
{
"docid": "50738556",
"text": "A genre of romance novels with male homosexual main characters. The category ranges from young adult, sci-fi, contemporary, paranormal, historical and erotic. After gaining popularity over the past ten years, male/male romance (aka mm romance or m/m romance) novels are now hitting mainstream best-seller lists. Although traditionally written by and for gay men, most contemporary gay romance novels have high female readerships. According to best selling author Aria Grace, approximately 90% of her readers are female. There is also an disproportionate number of female authors in this genre with more than half of the titles on Amazon's current best-selling list written by women. Some of the sub-niche categories include 'gay-for-you', 'first-time gay', coming out, and traditional contemporary love stories in which men find their happily ever after with other men.",
"title": ""
},
{
"docid": "34889868",
"text": "Marcus Urban (born 4 August 1971, earlier \"Marcus Schneider\") is a former German soccer player. He played with the East German national youth football team and in the second division club Rot-Weiß Erfurt in the 1980s and early 1990s. Several years afterwards he came out as a gay man. He has spoken publicly about the difficulties that gay footballers experience, and he is now a spokeperson and campaigner on diversity issues in sport and the workplace.",
"title": ""
},
{
"docid": "33725744",
"text": "Pito Villanon was a Cuban football (soccer) player who spent eleven seasons with Brookhattan in the American Soccer League. At the time, he was one of a handful of black professional athletes, playing in an integrated American sports league. He is reputedly the first black player in the American Soccer League.",
"title": ""
},
{
"docid": "49057960",
"text": "Christopher Voth (born (1990--)27 1990 ) is a Canadian male volleyball player. He is part of the Canada men's national volleyball team. On club level he played left side for Abiant Lycurgus. Voth is openly gay and came out as the first openly gay national athlete from Canada.",
"title": ""
},
{
"docid": "995343",
"text": "Andrew Watson (24 May 1856 – 8 March 1921) is widely considered to be the world's first black person to play association football at international level. He played three matches for Scotland between 1881 and 1882. Arthur Wharton was commonly thought to be Britain's first black player, as he was the first black professional footballer and the first to play in the Football League, but Watson's career predated him by over a decade.",
"title": ""
},
{
"docid": "45213766",
"text": "The 2009 Australian Open Men's Singles final was the championship tennis match of the Men's Singles tournament at the 2009 Australian Open. It was contested between the world's top two players for much of the previous four years, Rafael Nadal and Roger Federer, then ranked first and second in the world respectively. It was their seventh (out of nine) meeting in a Grand Slam final, but their first outside of either the French Open or Wimbledon, followed by their most recent meeting at the final of the 2017 Australian Open. This was Rafael Nadal's first Grand Slam hard court final while it was Roger Federer's ninth and at the time he was yet to lose in a Grand Slam hard court final.",
"title": ""
},
{
"docid": "382341",
"text": "National Coming Out Day (NCOD) is an annual LGBTQ awareness day observed on October 11. Founded in the United States in 1988, the initial idea was grounded in the feminist and gay liberation spirit of the personal being political, and the emphasis on the most basic form of activism being coming out to family, friends and colleagues, and living life as an openly lesbian or gay person. The foundational belief is that homophobia thrives in an atmosphere of silence and ignorance, and that once people know that they have loved ones who are lesbian or gay, they are far less likely to maintain homophobic or oppressive views.",
"title": ""
},
{
"docid": "31699469",
"text": "Michael Dos Santos (born 30 April 1983 in Birigui) is a Brazilian volleyball player who currently plays for Vôlei Futuro men's team. He became the first player in professional volleyball history to come out as gay.",
"title": ""
},
{
"docid": "20876803",
"text": "The 1870 college football season is considered to be the second season ever played of intercollegiate football competition. Much like in the first year, 1869, the rules were still considered in flux, and were decided on in a game-to-game basis. However, the rules used likely did not resemble anything that a modern football observer would recognize, being that of a mix of soccer and rugby.",
"title": ""
},
{
"docid": "320692",
"text": "David Marquette Kopay (born June 28, 1942) is a former American football running back in the National Football League who in 1975 became one of the first professional athletes to come out as gay.",
"title": ""
}
] |
398
|
Exhaustion of B cells contributes to poor Ab response in HIV-infected individuals.
|
[
{
"docid": "8883846",
"text": "The Global HIV Vaccine Enterprise convened a two-day workshop in May of 2007 to discuss humoral immune responses to HIV and approaches to design vaccines that induce viral neutralizing and other potentially protective antibody responses. The goals of this workshop were to identify key scientific issues, gaps, and opportunities that have emerged since the Enterprise Strategic Plan was first published in 2005 [1], and to make recommendations that Enterprise stakeholders can use to plan new activities. Most effective viral vaccines work, at least in part, by generating antibodies that inactivate or neutralize the invading virus, and the existing data strongly suggest that an optimally effective HIV-1 vaccine should elicit potent antiviral neutralizing antibodies. However, unlike acute viral pathogens, HIV-1 chronically replicates in the host and evades the antibody response. This immune evasion, along with the large genetic variation among HIV-1 strains worldwide, has posed major obstacles to vaccine development. Current HIV vaccine candidates do not elicit neutralizing antibodies against most circulating virus strains, and thus the induction of a protective antibody response remains a major priority for HIV-1 vaccine development. For an antibody-based HIV-1 vaccine, progress in vaccine design is generally gauged by in vitro assays that measure the ability of vaccine-induced antibodies to neutralize a broad spectrum of viral isolates representing the major genetic subtypes (clades) of HIV-1 [2]. Although it is not known what magnitude and breadth of neutralization will predict protection in vaccine recipients, it is clear that current vaccine immunogens elicit antibodies that neutralize only a minority of circulating isolates. Thus, much progress needs to be made in this area. Also, though virus neutralization is considered a critical benchmark for a vaccine, this may not be the only benchmark for predicting success with antibody-based HIV-1 vaccine immunogens. The main targets for neutralizing antibodies to HIV-1 are the surface gp120 and trans-membrane gp41 envelope glycoproteins (Env) that mediate receptor and coreceptor binding and the subsequent membrane fusion events that allow the virus to gain entry into cells [3]. Antibodies neutralize the virus by binding these viral spikes and blocking virus entry into susceptible cells, such as CD4+ T cells [4,5]. In order to chronically replicate in the host, the virus exploits several mechanisms to shield itself against antibody recognition, including a dense outer coating of sugar molecules (N-linked glycans) and the strategic positioning of cysteine–cysteine loop structures on the gp120 molecule [6–8]. These shielding mechanisms, although highly effective, have vulnerabilities imposed by fitness constraints. Information on the precise location and molecular structure of these vulnerable regions could be valuable for the rational design of improved vaccine immunogens. Participants in the workshop identified four areas that, if given proper attention, could provide key information that would bring the field closer to an effective antibody-based HIV-1 vaccine: (1) structure-assisted immunogen design, (2) role of Fc receptors and complement, (3) assay standardization and validation, and (4) immunoregulation of B cell responses.",
"title": "Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions"
}
] |
[
{
"docid": "20261352",
"text": "OBJECTIVE To define the impact of chronic viremia and associated immune activation on B-cell exhaustion in HIV infection. DESIGN Progressive HIV infection is marked by B-cell anergy and exhaustion coupled with dramatic hypergammaglobulinemia. Although both upregulation of CD95 and loss of CD21 have been used as markers of infection-associated B-cell dysfunction, little is known regarding the specific profiles of dysfunctional B cells and whether persistent viral replication and its associated immune activation play a central role in driving B-cell dysfunction. METHODS Multiparameter flow cytometry was used to define the profile of dysfunctional B cells. The changes in the expression of CD21 and CD95 were tracked on B-cell subpopulations in patients with differential control of viral replication. RESULTS : Although the emergence of exhausted, CD21 tissue-like memory B cells followed similar patterns in both progressors and controllers, the frequency of CD21 activated memory B cells was lower in spontaneous controllers. CONCLUSION Our results suggest that the loss of CD21 and the upregulation of CD95 occur as separate events during the development of B-cell dysfunction. The loss of CD21 is a marker of B-cell exhaustion induced in the absence of appreciable viral replication, whereas the upregulation of CD95 is tightly linked to persistent viral replication and its associated immune activation. Thus, these dysfunctional profiles potentially represent two functionally distinct states within the B-cell compartment.",
"title": "Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection."
},
{
"docid": "14657344",
"text": "Leishmania mexicana (Lm) causes localized (LCL) and diffuse (DCL) cutaneous leishmaniasis. DCL patients have a poor cellular immune response leading to chronicity. It has been proposed that CD8 T lymphocytes (CD8) play a crucial role in infection clearance, although the role of CD8 cytotoxicity in disease control has not been elucidated. Lesions of DCL patients have been shown to harbor low numbers of CD8, as compared to patients with LCL, and leishmanicidal treatment restores CD8 numbers. The marked response of CD8 towards Leishmania parasites led us to analyze possible functional differences between CD8 from patients with LCL and DCL. We compared IFNγ production, antigen-specific proliferation, and cytotoxicity of CD8 purified from PBMC against autologous macrophages (MO) infected with Leishmania mexicana (MOi). Additionally, we analyzed tissue biopsies from both groups of patients for evidence of cytotoxicity associated with apoptotic cells in the lesions. We found that CD8 cell of DCL patients exhibited low cytotoxicity, low antigen-specific proliferation and low IFNγ production when stimulated with MOi, as compared to LCL patients. Additionally, DCL patients had significantly less TUNEL+ cells in their lesions. These characteristics are similar to cellular \"exhaustion\" described in chronic infections. We intended to restore the functional capacity of CD8 cells of DCL patients by preincubating them with TLR2 agonists: Lm lipophosphoglycan (LPG) or Pam3Cys. Cytotoxicity against MOi, antigen-specific proliferation and IFNγ production were restored with both stimuli, whereas PD-1 (a molecule associated with cellular exhaustion) expression, was reduced. Our work suggests that CD8 response is associated with control of Lm infection in LCL patients and that chronic infection in DCL patients leads to a state of CD8 functional exhaustion, which could facilitate disease spread. This is the first report that shows the presence of functionally exhausted CD8 T lymphocytes in DCL patients and, additionally, that pre-stimulation with TLR2 ligands can restore the effector mechanisms of CD8 T lymphocytes from DCL patients against Leishmania mexicana-infected macrophages.",
"title": "CD8 Cells of Patients with Diffuse Cutaneous Leishmaniasis Display Functional Exhaustion: The Latter Is Reversed, In Vitro, by TLR2 Agonists"
},
{
"docid": "25045244",
"text": "Our previous studies in volunteers immunized with Salmonella enterica serovar Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host defense. In this study we describe a novel subset of nonclassical human HLA-E-restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid vaccinees. CD3+CD8+CD4-CD56- T cells effectively killed S. Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions. The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S. Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E Abs partially blocked these responses. We also demonstrated that presentation of S. Typhi Ags via HLA-E could stimulate IFN-gamma production. Increases in the net frequency of IFN-gamma spot-forming cells were observed in the presence of targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs. These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections.",
"title": "Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine."
},
{
"docid": "5398179",
"text": "HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection.",
"title": "Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication."
},
{
"docid": "40473317",
"text": "In this report, we demonstrate that CD28(-/-) mice are severely impaired in the initial expansion of D(b)/NP366-374-specific CD8 T cells in response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)(-/-) mice show no defect in primary T cell expansion to influenza virus. In contrast, 4-1BBL(-/-) mice show a decrease in D(b)/NP366-374-specific T cells late in the primary response. Upon secondary challenge with influenza virus, 4-1BBL(-/-) mice show a decrease in the number of D(b)/NP366-374-specific T cells compared to wild-type mice such that the level of the CD8 T cell expansion during the in vivo secondary response is reduced to the level of a primary response, with concomitant reduction of CTL effector function. In contrast, Ab responses, as well as secondary CD4 T cell responses, to influenza are unaffected by 4-1BBL deficiency. Thus, CD28 is critical for initial T cell expansion, whereas 4-1BB/4-1BBL signaling affects T cell numbers much later in the response and is essential for the survival and/or responsiveness of the memory CD8 T cell pool.",
"title": "Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection."
},
{
"docid": "11784947",
"text": "Short interfering RNAs (siRNAs) have been used to inhibit HIV-1 replication. The durable inhibition of HIV-1 replication by RNA interference has been impeded, however, by a high mutation rate when viral sequences are targeted and by cytotoxicity when cellular genes are knocked down. To identify cellular proteins that contribute to HIV-1 replication that can be chronically silenced without significant cytotoxicity, we employed a shRNA library that targets 54,509 human transcripts. We used this library to select a comprehensive population of Jurkat T-cell clones, each expressing a single discrete shRNA. The Jurkat clones were then infected with HIV-1. Clones that survived viral infection represent moieties silenced for a human mRNA needed for virus replication, but whose chronic knockdown did not cause cytotoxicity. Overall, 252 individual Jurkat mRNAs were identified. Twenty-two of these mRNAs were secondarily verified for their contributions to HIV-1 replication. Five mRNAs, NRF1, STXBP2, NCOA3, PRDM2, and EXOSC5, were studied for their effect on steps of the HIV-1 life cycle. We discuss the similarities and differences between our shRNA findings for HIV-1 using a spreading infection assay in human Jurkat T-cells and results from other investigators who used siRNA-based screenings in HeLa or 293T cells.",
"title": "A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication."
},
{
"docid": "5752492",
"text": "Chronic immune activation that persists despite anti-retroviral therapy (ART) is the strongest predictor of disease progression in HIV infection. Monocyte/macrophages in HIV-infected individuals are known to spontaneously secrete cytokines, although neither the mechanism nor the molecules involved are known. Here we show that overexpression of the newly described co-stimulatory molecule, PD1 homologue (PD-1H) in human monocyte/macrophages is sufficient to induce spontaneous secretion of multiple cytokines. The process requires signaling via PD-1H as cytokine secretion could be abrogated by deletion of the cytoplasmic domain. Such overexpression of PD-1H, associated with spontaneous cytokine expression is seen in monocytes from chronically HIV-infected individuals and this correlates with immune activation and CD4 depletion, but not viral load. Moreover, antigen presentation by PD-1H-overexpressing monocytes results in enhanced cytokine secretion by HIV-specific T cells. These results suggest that PD-1H might play a crucial role in modulating immune activation and immune response in HIV infection.",
"title": "Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals"
},
{
"docid": "23915841",
"text": "The study of the evolution and specificities of neutralizing antibodies during the course of human immunodeficiency virus type 1 (HIV-1) infection may be important in the discovery of possible targets for vaccine design. In this study, we assessed the autologous and heterologous neutralization responses of 14 HIV-1 subtype C-infected individuals, using envelope clones obtained within the first 2 months postinfection. Our data show that potent but relatively strain-specific neutralizing antibodies develop within 3 to 12 months of HIV-1 infection. The magnitude of this response was associated with shorter V1-to-V5 envelope lengths and fewer glycosylation sites, particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced (CD4i) epitopes developed to high titers in 12 participants, in most cases before the development of autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificity conferred neutralization breadth. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection.",
"title": "Neutralizing antibody responses in acute human immunodeficiency virus type 1 subtype C infection."
},
{
"docid": "26038789",
"text": "3BNC117 is a broad and potent neutralizing antibody to HIV-1 that targets the CD4 binding site on the viral envelope spike. When administered passively, this antibody can prevent infection in animal models and suppress viremia in HIV-1–infected individuals. Here we report that HIV-1 immunotherapy with a single injection of 3BNC117 affects host antibody responses in viremic individuals. In comparison to untreated controls that showed little change in their neutralizing activity over a 6-month period, 3BNC117 infusion significantly improved neutralizing responses to heterologous tier 2 viruses in nearly all study participants. We conclude that 3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1.",
"title": "HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1"
},
{
"docid": "23304931",
"text": "PURPOSE Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis. PATIENTS AND METHODS We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts. RESULTS The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL. CONCLUSION These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.",
"title": "Immunophenotypic analysis of AIDS-related diffuse large B-cell lymphoma and clinical implications in patients from AIDS malignancies consortium clinical trials 010 and 034"
},
{
"docid": "26124606",
"text": "Liver disease secondary to hepatitis C virus (HCV) infection is a rising cause of morbidity and mortality among individuals who have been infected parenterally with human immunodeficiency virus (HIV) such as injection drug users, hemophiliacs, and transfused patients. We analyzed both the efficacy of interferon (IFN) alpha therapy in these patients and the predictors of response to this agent. A total of 119 patients with chronic hepatitis C (90 of whom were infected with HIV and 29 of whom were not) were included in a multicenter, prospective, open, nonrandomized observational study. IFN-alpha was given subcutaneously in a dosage of 5 million units three times a week during a 3-month period; those patients who responded received a dose of 3 million units given subcutaneously three times a week for an additional 9 months. One hundred seven patients completed the study; the level of aminotransferases returned to normal and sera became negative (complete response) for HCV RNA in 26 (32.5%) of 80 HIV-infected patients and 10 (37.0%) of 27 non-HIV-infected patients (P = .666) after completion of the treatment. Two variables were independently associated with a response in HIV-infected patients: a CD4+ T lymphocyte count of > 500 x 10(6)/L and a baseline HCV viremia level of < 10(7) copies/mL. In the 12 months following treatment, relapses occurred in 30.8% of the HIV-infected patients and 12.5% of non-HIV-infected patients (P = .403).",
"title": "Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group."
},
{
"docid": "5560962",
"text": "Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly somatically mutated and generated by a fraction of HIV-1-infected individuals several years after infection. Antibodies typically accumulate mutations in the complementarity determining region (CDR) loops, which usually contact the antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that are both resistant to and less tolerant of mutations. Here, we report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most bNAbs require somatic mutations in their FWRs. Structural and functional analyses reveal that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and their unusual contribution to potency and breadth should be considered in HIV-1 vaccine design.",
"title": "Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization"
},
{
"docid": "28806780",
"text": "Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.",
"title": "Poverty, Hunger, Education, and Residential Status Impact Survival in HIV"
},
{
"docid": "44562058",
"text": "Despite complete or near-complete suppression of human immunodeficiency virus (HIV) replication with combination antiretroviral therapy, both HIV and chronic inflammation/immune dysfunction persist indefinitely. Untangling the association between the virus and the host immune environment during therapy might lead to novel interventions aimed at either curing the infection or preventing the development of inflammation-associated end-organ disease. Chronic inflammation and immune dysfunction might lead to HIV persistence by causing virus production, generating new target cells, enabling infecting of activated and resting target cells, altering the migration patterns of susceptible target cells, increasing the proliferation of infected cells, and preventing normal HIV-specific clearance mechanisms from function. Chronic HIV production or replication might contribute to persistent inflammation and immune dysfunction. The rapidly evolving data on these issues strongly suggest that a vicious cycle might exist in which HIV persistence causes inflammation that in turn contributes to HIV persistence.",
"title": "Immune activation and HIV persistence: implications for curative approaches to HIV infection."
},
{
"docid": "21700295",
"text": "Importance More than 240 million individuals worldwide are infected with chronic hepatitis B virus (HBV). Among individuals with chronic HBV infection who are untreated, 15% to 40% progress to cirrhosis, which may lead to liver failure and liver cancer. Observations Pegylated interferon and nucleos(t)ide analogues (lamivudine, adefovir, entecavir, tenofovir disoproxil, and tenofovir alafenamide) suppress HBV DNA replication and improve liver inflammation and fibrosis. Long-term viral suppression is associated with regression of liver fibrosis and reduced risk of hepatocellular carcinoma in cohort studies. The cure (defined as hepatitis B surface antigen loss with undetectable HBV DNA) rates after treatment remain low (3%-7% with pegylated interferon and 1%-12% with nucleos[t]ide analogue therapy). Pegylated interferon therapy can be completed in 48 weeks and is not associated with the development of resistance; however, its use is limited by poor tolerability and adverse effects such as bone marrow suppression and exacerbation of existing neuropsychiatric symptoms such as depression. Newer agents (entecavir, tenofovir disoproxil, and tenofovir alafenamide) may be associated with a significantly reduced risk of drug resistance compared with older agents (lamivudine and adefovir) and should be considered as the first-line treatment. Conclusions and Relevance Antiviral treatment with either pegylated interferon or a nucleos(t)ide analogue (lamivudine, adefovir, entecavir, tenofovir disoproxil, or tenofovir alafenamide) should be offered to patients with chronic HBV infection and liver inflammation in an effort to reduce progression of liver disease. Nucleos(t)ide analogues should be considered as first-line therapy. Because cure rates are low, most patients will require therapy indefinitely.",
"title": "Chronic Hepatitis B Infection: A Review"
},
{
"docid": "29023309",
"text": "Salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas HIV-infected individuals develop a life-threatening bacteremia. Here we show that simian immunodeficiency virus (SIV) infection results in depletion of T helper type 17 (TH17) cells in the ileal mucosa of rhesus macaques, thereby impairing mucosal barrier functions to S. typhimurium dissemination. In SIV-negative macaques, the gene expression profile induced by S. typhimurium in ligated ileal loops was dominated by TH17 responses, including the expression of interleukin-17 (IL-17) and IL-22. TH17 cells were markedly depleted in SIV-infected rhesus macaques, resulting in blunted TH17 responses to S. typhimurium infection and increased bacterial dissemination. IL-17 receptor–deficient mice showed increased systemic dissemination of S. typhimurium from the gut, suggesting that IL-17 deficiency causes defects in mucosal barrier function. We conclude that SIV infection impairs the IL-17 axis, an arm of the mucosal immune response preventing systemic microbial dissemination from the gastrointestinal tract.",
"title": "Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut"
},
{
"docid": "46353045",
"text": "Late presentation remains a major concern despite the dramatically improved prognosis realized by ART. We define a first presentation for HIV care during the course of HIV infection as 'late' if an AIDS-defining opportunistic disease is apparent, or if CD4+ T-cells are <200/microl. In the Western world, approximately 10 and 30% of HIV-infected individuals still present with CD4+ T-cells <50 and <200/microl, respectively; estimates are substantially higher for developing countries. Diagnosis and treatment of opportunistic diseases and intense supportive in-hospital care take precedence over ART. Benefits of starting ART without delay, that is, when opportunistic diseases are still active, include faster resolution of opportunistic diseases and a decreased risk of recurrence. The downside of starting ART without delay could include toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS). Among asymptomatic or oligosymptomatic individuals presenting late, where ART and primary prophylaxis are initiated, approximately 10-20% will become symptomatic from drug toxicity or undiagnosed opportunistic complications, including IRIS, which require appropriate therapies. In this review we describe late presentation to HIV care, the scale of the problem, the evaluation of a late-presenting patient and challenges associated with initiation of potent antiretroviral therapy (ART) in the setting of acute opportunistic infections and other comorbidities.",
"title": "Late presentation of HIV-infected individuals."
},
{
"docid": "5735492",
"text": "BACKGROUND HIV disproportionately affects African-Caribbean women in Canada but the frequency and distribution of sexually transmitted infections in this community have not been previously studied. METHODS We recruited women based on HIV status through a Toronto community health centre. Participants completed a socio-behavioural questionnaire using Audio Computer Assisted Self-Interview (ACASI) and provided blood for syphilis, HIV, hepatitis B and C, herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and human cytomegalovirus (CMV) serology, urine for chlamydia and gonorrhea molecular testing and vaginal secretions for bacterial vaginosis (BV) and human papillomavirus (HPV). Differences in prevalence were assessed for statistical significance using chi-square. RESULTS We recruited 126 HIV-positive and 291 HIV-negative women, with a median age of 40 and 31 years, respectively (p < 0.001). Active HBV infection and lifetime exposure to HBV infection were more common in HIV-positive women (4.8% vs. 0.34%, p = 0.004; and 47.6% vs. 21.2%, p < 0.0001), as was a self-reported history of HBV vaccination (66.1% vs. 44.0%, p = 0.0001). Classical STIs were rare in both groups; BV prevalence was low and did not vary by HIV status. HSV-2 infection was markedly more frequent in HIV-positive (86.3%) than HIV-negative (46.6%) women (p < 0.0001). Vaginal HPV infection was also more common in HIV-positive than in HIV-negative women (50.8% vs. 22.6%, p < 0.0001) as was infection with high-risk oncogenic HPV types (48.4% vs. 17.3%, p < 0.0001). CONCLUSIONS Classical STIs were infrequent in this clinic-based population of African-Caribbean women in Toronto. However, HSV-2 prevalence was higher than that reported in previous studies in the general Canadian population and was strongly associated with HIV infection, as was infection with hepatitis B and HPV.",
"title": "The epidemiology of sexually transmitted co-infections in HIV-positive and HIV-negative African-Caribbean women in Toronto"
},
{
"docid": "2638387",
"text": "High mutation frequency during reverse transcription has a principal role in the genetic variation of primate lentiviral populations. It is the main driving force for the generation of drug resistance and the escape from immune surveillance. G to A hypermutation is one of the characteristics of primate lentiviruses, as well as other retroviruses, during replication in vivo and in cell culture. The molecular mechanisms of this process, however, remain to be clarified. Here, we demonstrate that CEM15 (also known as apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G; APOBEC3G), an endogenous inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is a cytidine deaminase and is able to induce G to A hypermutation in newly synthesized viral DNA. This effect can be counteracted by the HIV-1 virion infectivity factor (Vif). It seems that this viral DNA mutator is a viral defence mechanism in host cells that may induce either lethal hypermutation or instability of the incoming nascent viral reverse transcripts, which could account for the Vif-defective phenotype. Importantly, the accumulation of CEM15-mediated non-lethal hypermutation in the replicating viral genome could potently contribute to the genetic variation of primate lentiviral populations.",
"title": "The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA"
},
{
"docid": "35987381",
"text": "Hyperactivation of T cells, particularly of CD8(+) T cells, is a hallmark of chronic HIV 1 (HIV-1) infection. Little is known about the antigenic specificities and the mechanisms by which HIV-1 causes activation of CD8(+) T cells during chronic infection. We report that CD8(+) T cells were activated during in vivo HIV-1 replication irrespective of their Ag specificity. Cytokines present during untreated HIV-1 infection, most prominently IL-15, triggered proliferation and expression of activation markers in CD8(+) T cells, but not CD4(+) T cells, in the absence of TCR stimulation. Moreover, LPS or HIV-1-activated dendritic cells (DCs) stimulated CD8(+) T cells in an IL-15-dependent but Ag-independent manner, and IL-15 expression was highly increased in DCs isolated from viremic HIV-1 patients, suggesting that CD8(+) T cells are activated by inflammatory cytokines in untreated HIV-1 patients independent of Ag specificity. This finding contrasts with CD4(+) T cells whose in vivo activation seems biased toward specificities for persistent Ags. These observations explain the higher abundance of activated CD8(+) T cells compared with CD4(+) T cells in untreated HIV-1 infection.",
"title": "CD8+ T cells are activated in an antigen-independent manner in HIV-infected individuals."
},
{
"docid": "15983982",
"text": "OBJECTIVES To describe the role patient expectations play in general practitioners (GPs) antibiotic prescribing for upper respiratory tract infections (URTI). METHODS Concurrent explanatory mixed methods approach using a cross-sectional survey and semistructured interviews. SETTINGS Primary care GPs in Australia. PARTICIPANTS 584 GPs (response rate of 23.6%) completed the cross-sectional survey. 32 GPs were interviewed individually. OUTCOME MEASURE Prescribing of antibiotics for URTI. RESULTS More than half the GP respondents to the survey in Australia self-reported that they would prescribe antibiotics for an URTI to meet patient expectations. Our qualitative findings suggest that 'patient expectations' may be the main reason given for inappropriate prescribing, but it is an all-encompassing phrase that includes other reasons. These include limited time, poor doctor-patient communication and diagnostic uncertainty. We have identified three role archetypes to explain the behaviour of GPs in reference to antibiotic prescribing for URTIs. The main themes emerging from the qualitative component was that many GPs did not think that antibiotic prescribing in primary care was responsible for the development of antibiotic resistance nor that their individual prescribing would make any difference in light of other bigger issues like hospital prescribing or veterinary use. For them, there were negligible negative consequences from their inappropriate prescribing. CONCLUSIONS There is a need to increase awareness of the scope and magnitude of antibiotic resistance and the role primary care prescribing plays, and of the contribution of individual prescribing decisions to the problem of antibiotic resistance.",
"title": "Why do general practitioners prescribe antibiotics for upper respiratory tract infections to meet patient expectations: a mixed methods study"
},
{
"docid": "37444589",
"text": "Although 13 years have passed since identification of human immunodeficiency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its primary target, the T cell that carries the CD4 antigen. We and others have shown an increase in the percentage of apoptotic cells among circulating CD4+ (and CD8+) T cells of HIV-seropositive individuals and an increase in frequency of apoptosis with disease progression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apoptosis occurs predominantly in bystander cells and not in the productively infected cells themselves. These data have implications for pathogenesis and therapy, namely, arguing that rational drug therapy may involve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells.",
"title": "Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes"
},
{
"docid": "24596228",
"text": "BACKGROUND/AIMS There is only limited information on the prevalence and influence of coinfection with either hepatitis B or C on the clinical course in patients infected with the human immunodeficiency virus (HIV). METHODS Follow-up was available in 232 HIV-infected patients (age 37+/-8 years, CD4 count 167+/-167 microl; 46% had AIDS). Samples were investigated for markers of HBV and HCV infection (HBsAg, HBeAg, HBV-DNA, Anti-HBs, anti-HBc, anti-HCV, HCV-RNA). RESULTS 60/232 patients (23%) were anti-HCV positive. 78% of these sera were positive for HCV-RNA. 22/232 patients (9%) suffered from chronic HBV infection (HBsAg positive), 18/22 (82%) of these sera had detectable HBeAg and 19/22 (86%) HBV-DNA. Presence of HCV-RNA, HBeAg and amount of HBV-DNA were related to the degree of immunodeficiency. In contrast to the control group without HBV or HCV infection, patients infected with HIV and either HBV or HCV showed a direct correlation between a reduction in CD4 counts and decreased cholinesterase activity. In patients with AIDS, coinfection with HBV or HCV was associated with a reduced survival compared to controls (HBV: 212 days, 95%CI, 106-317; HCV: 267, 95%CI, 112-396; controls: 439 days, 95%CI, 364-513). CONCLUSIONS Coinfection of HIV and HBV or HCV is frequently observed. Our results suggest that with prolonged survival of HIV-infected patients, coinfection with either HBV or HCV correlates with a reduced survival rate.",
"title": "Hepatitis B and C in HIV-infected patients. Prevalence and prognostic value."
},
{
"docid": "7177329",
"text": "Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.",
"title": "Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape"
},
{
"docid": "20646904",
"text": "Targeting of proteins to APCs is an attractive strategy for eliciting adaptive immune responses. However, the relationship between the choice of the targeted receptor and the quality and quantity of responses remains poorly understood. We describe a strategy for expression of Ags including hydrophobic proteins as soluble fusion proteins that are optimized for proteasome-dependent MHC class I-restricted cross-presentation and form stable complexes with a wide variety of targeting Abs. Upon s.c. immunization, these complexes were initially taken up by CD169+ lymph node subcapsular sinus macrophages. In the OVA model system, receptor-targeted antigenic complexes primed specific T and B cell responses in vitro and in vivo at least 100-fold more efficiently than Ag alone. Comparison of 10 targeting receptors allowed us to establish a ranking with respect to priming of CD8+ T cell responses and demonstrated striking differences with respect to the relative efficacy of CD8+ and CD4+ T cell subset and B cell priming. The described fusion proteins should help in developing optimized strategies for targeted delivery of protein Ags in the context of tolerization or vaccination.",
"title": "Fusion proteins for versatile antigen targeting to cell surface receptors reveal differential capacity to prime immune responses."
},
{
"docid": "27602752",
"text": "Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.",
"title": "CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS."
},
{
"docid": "10648422",
"text": "Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.",
"title": "Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection"
},
{
"docid": "7224723",
"text": "HIV causes a chronic infection characterized by depletion of CD4(+) T lymphocytes and the development of opportunistic infections. Despite drugs that inhibit viral spread, HIV infection has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy (HAART) and the immune response. Here we used CD34(+) cells from infected people as well as in vitro studies of wild-type HIV to show infection and killing of CD34(+) multipotent hematopoietic progenitor cells (HPCs). In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. A unique reporter HIV that directly detects latently infected cells in vitro confirmed the presence of distinct populations of active and latently infected HPCs. These findings have major implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.",
"title": "HIV–1 Infects Multipotent Progenitor Cells Causing Cell Death and Establishing Latent Cellular Reservoirs"
},
{
"docid": "46202852",
"text": "Several recent reports indicate that cholesterol might play an important role in human immunodeficiency virus type 1 (HIV-1) replication. We investigated the effects of HIV-1 infection on cholesterol biosynthesis and uptake using microarrays. HIV-1 increased gene expression of cholesterol genes in both transformed T-cell lines and primary CD4(+) T cells. Consistent with our microarray data, (14)C-labeled mevalonate and acetate incorporation was increased in HIV-1-infected cells. Our data also demonstrate that changes in cholesterol biosynthesis and uptake are only observed in the presence of functional Nef, suggesting that increased cholesterol synthesis may contribute to Nef-mediated enhancement of virion infectivity and viral replication.",
"title": "Nef induces multiple genes involved in cholesterol synthesis and uptake in human immunodeficiency virus type 1-infected T cells."
},
{
"docid": "6501747",
"text": "Dendritic cells (DCs) play a critical role in the immune response to viral infection through the facilitation of cell-intrinsic antiviral activity and the activation of adaptive immunity. HIV-1 infection of DCs triggers an IRF3-dependent innate immune response, which requires the activity of cyclic GAMP synthase (cGAS). We report the results of a targeted RNAi screen utilizing primary human monocyte-derived DCs (MDDCs) to identify immune regulators that directly interface with HIV-1-encoded features to initiate this innate response. Polyglutamine binding protein 1 (PQBP1) emerged as a strong candidate through this analysis. We found that PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response. MDDCs derived from Renpenning syndrome patients, who harbor mutations in the PQBP1 locus, possess a severely attenuated innate immune response to HIV-1 challenge, underscoring the role of PQBP1 as a proximal innate sensor of a HIV-1 infection.",
"title": "PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1"
}
] |
PLAIN-2971
|
Prevent Glaucoma and See 27 Miles Farther
|
[
{
"docid": "MED-4385",
"text": "The idea that normal constituents of the diet can influence visual function is not new. As early as 1782, Buzzi identified the yellow of the macula and Schulze (1866) specifically postulated that the yellow pigments led to improvements in human vision. These pigments were later found to be derived from dietary lutein and zeaxanthin that are known to be oxygenated carotenoids (xanthophylls). Walls and Judd (1933) postulated that these yellow intraocular pigments could improve visual performance by absorbing light scattered both within (for example, glare) and outside of the eye (increasing visual range by absorbing blue light scattered in the atmosphere), and by improving spatial vision through enhancing contrast and reducing chromatic blur. In this article, evidence for these ideas is reviewed with particular emphasis towards more recent data on glare effects.",
"title": "The influence of dietary lutein and zeaxanthin on visual performance."
},
{
"docid": "MED-4384",
"text": "PURPOSE: To explore the association between the consumption of fruits and vegetables and the presence of glaucoma. DESIGN: Cross-sectional cohort study. METHODS: In a sample of 1,155 women located in multiple centers in the United States, glaucoma specialists diagnosed glaucoma in at least one eye by assessing optic nerve head photographs and 76-point suprathreshold screening visual fields. Consumption of fruits and vegetables was assessed using the Block Food Frequency Questionnaire. The relationship between selected fruit and vegetable consumption and glaucoma was investigated using adjusted logistic regression models. RESULTS: Among 1,155 women, 95 (8.2%) were diagnosed with glaucoma. In adjusted analysis, the odds of glaucoma risk were decreased by 69% (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11 to 0.91) in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month, by 64% (OR, 0.36; 95% CI, 0.17 to 0.77) in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week, and by 47% (OR, 0.53; 95% CI, 0.29 to 0.97) in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month. CONCLUSIONS: A higher intake of certain fruits and vegetables may be associated with a decreased risk of glaucoma. More studies are needed to investigate this relationship.",
"title": "Glaucoma risk and the consumption of fruits and vegetables among older women in the study of osteoporotic fractures."
},
{
"docid": "MED-4383",
"text": "OBJECTIVE: We investigated the relation between plasma carotenoids, retinol and tocopherol levels and ovarian cancer risk in Korean women. DESIGN: Hospital-based case-control study. SETTING: Six tertiary medical institutes in Korea. POPULATION: Forty-five epithelial ovarian cancers and 135 age-matched controls. METHODS: Preoperative plasma concentrations of beta-carotene, lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma-tocopherol were measured by reverse-phase, gradient high-pressure liquid chromatography. MAIN OUTCOME MEASURES: Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated by tertiles to evaluate the effect of micronutrients on endometrial cancer risk after adjustment for body mass (BMI) index, menopause, parity, oral contraceptive use, smoking status, and alcohol consumption status. RESULTS: Women in the highest tertile for beta-carotene had 0.12-times the risk of ovarian cancer of in the lowest tertile (OR 0.12; 95%CI 0.04-0.36). Women with the highest tertiles of lycopene (OR 0.09; 95%CI 0.03-0.32), zeaxanthin/lutein (OR 0.21; 95%CI 0.09-0.52), retinol (OR 0.45; 95%CI 0.21-0.98), alpha-tocopherol (OR 0.23; 95%CI 0.10-0.53) and gamma-tocopherol (OR 0.28; 95%CI 0.11-0.70) had lower risk of ovarian cancer than women in the lowest tertiles. Results were consistent across strata of socio-epidemiologic factors. CONCLUSIONS: Micronutrients, specifically ss-carotene, lycopene, zeaxanthin, lutein, retinol, alpha-tocopherol, and gamma-tocopherol, may play a role in reducing the risk of ovarian cancer.",
"title": "Plasma carotenoids, retinol and tocopherol levels and the risk of ovarian cancer."
}
] |
[
{
"docid": "MED-2720",
"text": "In this study we examined the effect of physical activity based labels on the calorie content of meals selected from a sample fast food menu. Using a web-based survey, participants were randomly assigned to one of four menus which differed only in their labeling schemes (n=802): (1) a menu with no nutritional information, (2) a menu with calorie information, (3) a menu with calorie information and minutes to walk to burn those calories, or (4) a menu with calorie information and miles to walk to burn those calories. There was a significant difference in the mean number of calories ordered based on menu type (p=0.02), with an average of 1020 calories ordered from a menu with no nutritional information, 927 calories ordered from a menu with only calorie information, 916 calories ordered from a menu with both calorie information and minutes to walk to burn those calories, and 826 calories ordered from the menu with calorie information and the number of miles to walk to burn those calories. The menu with calories and the number of miles to walk to burn those calories appeared the most effective in influencing the selection of lower calorie meals (p=0.0007) when compared to the menu with no nutritional information provided. The majority of participants (82%) reported a preference for physical activity based menu labels over labels with calorie information alone and no nutritional information. Whether these labels are effective in real-life scenarios remains to be tested. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Potential effect of physical activity based menu labels on the calorie content of selected fast food meals."
},
{
"docid": "MED-2900",
"text": "Purpose To explore the association between consumption of fruits and vegetables and the presence of glaucoma in older African American women. Design Cross-sectional study. Methods Disc photographs and suprathreshold visual fields were obtained from the 662 African American participants in the Study of Osteoporotic Fractures. Masked, trained readers graded all discs, and two glaucoma specialists reviewed photos and visual fields. The Block Food Frequency Questionnaire assessed food consumption. Relationships between selected fruit/vegetable/nutrient consumption and glaucoma were evaluated using logistic regression models after adjusting for potential confounders. Results After excluding women missing Food Frequency Questionnaire and disc data, 584 African American women (88.2% of total African American cohort) were included. Glaucoma was diagnosed in at least one eye in 77 subjects (13%). Women who ate 3 or more servings/day of fruits/fruit juices were 79% (odds ratio [OR]=0.21; 95% confidence interval [CI]: 0.08–0.60) less likely to have glaucoma than women who ate less than one serving/day. Women who consumed more than 2 servings/week of fresh oranges (OR=0.18; 95%CI: 0.06–0.51) and peaches (OR=0.30; 95%CI: 0.13–0.67) had a decreased odds of glaucoma compared to those consuming less than one serving/week. For vegetables, >1 serving/week compared to ≤1 serving/month of collard-greens/kale decreased the odds of glaucoma by 57% (OR=0.43; 95%CI: 0.21–0.85). There was a protective trend against glaucoma in those consuming more fruit/fruit juices (p=0.023), fresh oranges (p=0.002), fresh peaches (p=0.002), and collard greens/kale (p=0.014). Higher consumption of carrots (p=0.061) and spinach (p=0.094) also showed some associations. Individual nutrient intake from food sources found protective trends with higher intakes of vitamin A (p=0.011), vitamin C (p=0.018), and α-carotene (p=0.021), and close to statistically significant trends with β-carotene (p=0.052), folate (p=0.056), and lutein/zeaxanthin (p=0.077). Conclusion Higher intake of certain fruits and vegetables high in Vitamins A and C and carotenoids may be associated with a decreased likelihood of glaucoma in older African American women. Randomized controlled trials are needed to determine whether the intake of specific nutrients changes the risk of glaucoma.",
"title": "The Association of Consumption of Fruits/Vegetables with Decreased Risk of Glaucoma among Older African American Women in the Study of Osteoporotic Fractures"
},
{
"docid": "MED-2901",
"text": "Purpose. To investigate the relationship between supplementary consumption of the oxidants calcium and iron and the prevalence of glaucoma. Methods. This cross-sectional study included 3833 participants in the National Health and Nutrition Examination Survey (NHANES) for 2007 and 2008, ≥40 years of age, who reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements and antacids during the preceding 30-day period. Data pertaining to the supplementary intake of calcium and iron was aggregated and divided into quintiles. Information regarding the presence or absence of glaucoma and demographics, comorbidities, and health-related behavior was obtained via interview. Results. Participants who consumed ≥800 mg/d of supplementary calcium or ≥18 mg/d of supplementary iron had significantly higher odds of having been diagnosed with glaucoma than did those who had not consumed supplementary calcium or iron, after adjustment for potential confounders (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.25–4.76 for calcium; OR 3.80, 95% CI 1.79–8.06 for iron). Concurrent consumption of both calcium and iron above these levels was associated with still greater odds of having been diagnosed with glaucoma (OR 7.24, 95% CI 2.42–21.62). A clear dose–response relationship between quintiles of supplementary calcium or iron intake and glaucoma prevalence was not found. Conclusions. These results suggest that there may be a threshold intake of iron and calcium above which there is an increased risk of development of glaucoma. Prospective longitudinal studies are needed, to assess whether oxidant intake is a risk factor for development and progression of glaucoma.",
"title": "The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron"
},
{
"docid": "MED-2896",
"text": "The relation between dietary antioxidant intake and primary open-angle glaucoma risk was examined in participants aged over 40 years in the Nurses' Health Study (n = 76,200) and the Health Professionals Follow-up Study (n = 40,284). They were followed biennially from 1980 and 1986, respectively, to 1996, during periods when they received an eye examination. Dietary intakes were measured repeatedly from 1980 in the Nurses' Health Study and from 1986 in the Health Professionals Follow-up Study using validated food frequency questionnaires. The authors analyzed 474 self-reported glaucoma cases confirmed by medical chart review to have primary open-angle glaucoma with visual field loss. The authors used Cox proportional hazards models for cohort-specific multivariate analyses, and results were pooled using random effects models. The pooled multivariate rate ratios for primary open-angle glaucoma comparing the highest versus lowest quintile of cumulative updated intake were 1.17 (95% confidence interval (CI): 0.87, 1.58) for alpha-carotene, 1.10 (95% CI: 0.82, 1.48) for beta-carotene, 0.95 (95% CI: 0.70, 1.29) for beta-cryptoxanthin, 0.82 (95% CI: 0.60, 1.12) for lycopene, 0.92 (95% CI: 0.69, 1.24) for lutein/zeaxanthin, 1.05 (95% CI: 0.59, 1.89) for vitamin C, 0.97 (95% CI: 0.62, 1.52) for vitamin E, and 1.11 (95% CI: 0.82, 1.51) for vitamin A. In conclusion, the authors did not observe any strong associations between antioxidant consumption and the risk of primary open-angle glaucoma.",
"title": "Antioxidant intake and primary open-angle glaucoma: a prospective study."
},
{
"docid": "MED-5246",
"text": "BACKGROUND: Caffeine is widely consumed, and its effect on intraocular pressure (IOP) has been reported in conflicting data. The aim of this meta-analysis was to quantitatively summarize the effect of caffeine on IOP in normal individuals and in patients with glaucoma or ocular hypertension (OHT). METHODS: A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify pertinent randomized controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and EMBASE. A systematic review and meta-analysis was performed. IOP at 0.5 hour (h), 1 h and 1.5 h after caffeine ingestion was the main outcome measurement. RESULTS: Six RCTs (two parallel-designed and four crossover-designed) evaluating 144 participants fulfilled inclusion criteria. The risk of bias for these studies was uncertain. Among the participants, 103 were normal individuals and 41 were patients with glaucoma or OHT. In normal individuals, the IOPs measured at 0.5 h, 1 h and 1.5 h post-intervention were not affected by ingestion of caffeine. The weighted mean difference (WMD) with 95% confidence intervals (95%CI) for each measurement point were -0.740 (-2.454, 0.974), 0.522 (-0.568, 1.613) and 0.580 (-1.524, 2.684). However, in patients with glaucoma or OHT, IOP increased at each measurement point, with the WMD and 95%CI being 0.347 (0.078, 0.616), 2.395 (1.741,3.049) and 1.998 (1.522,2.474) respectively. No publication bias was detected by either Begg's or Egger's test. CONCLUSION: Available evidences showed that caffeine had different effects on IOP in different groups of individuals. For normal individuals, IOP was not changed by ingestion of caffeine, while for patients with glaucoma or OHT, IOP increased significantly. More high-quality RCTs are warranted to confirm this. The mechanisms underlying this phenomenon and the clinical significance are to be explored.",
"title": "The effect of caffeine on intraocular pressure: a systematic review and meta-analysis."
},
{
"docid": "MED-5247",
"text": "Purpose We investigated whether caffeine, which transiently increases intraocular pressure (IOP) is associated with risk of primary open-angle glaucoma (POAG). Methods We followed 79,120 women from 1980 and 42,052 men from 1986 to 2004 who were 40+ years old, did not have POAG, and reported receiving eye examinations. Information on caffeine consumption, potential confounders and POAG diagnoses were repeatedly updated in validated follow-up questionnaires. We confirmed 1,011 incident POAG cases with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariable rate ratios (RR). Results Compared with daily intake of < 150 mg, the pooled multivariable RRs were 1.05 [95% Confidence Interval (CI), 0.89–1.25] for consuming 150–299 mg, 1.19 [95% CI, 0.99–1.43] for 300 – 449 mg/day, 1.13 [95% CI, 0.89–1.43] for 450–559 mg and 1.17 [95% CI, 0.90, 1.53] for 600+ mg+ [p for trend = 0.11]. However, for consuming 5+ cups of caffeinated coffee daily, RR was 1.61 [95% CI, 1.00, 2.59; p for trend=0.02]; tea or caffeinated cola intake were not associated with risk. Greater caffeine intake was more adversely associated with POAG among those reporting family history of glaucoma, particularly in relation to POAG with elevated IOP (p for trend =0.0009; p-interaction=0.04). Conclusion Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high-tension POAG among those with a family history of glaucoma; this may be due to chance, but warrants further study.",
"title": "Caffeine Consumption and the Risk of Primary Open - Angle Glaucoma: A Prospective Cohort Study"
},
{
"docid": "MED-2030",
"text": "Background Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86.",
"title": "An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity"
},
{
"docid": "MED-994",
"text": "Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer’s disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.",
"title": "Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment"
},
{
"docid": "MED-2894",
"text": "AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.",
"title": "Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma."
},
{
"docid": "MED-4457",
"text": "Sulforaphane (SFR), an isothiocyanate from cruciferous vegetables, possesses growth-inhibiting and apoptosis-inducing activities in cancer cell lines. Recently, SFR has been shown to promote the mitochondrial formation of reactive oxygen species (ROS) in human cancer cell lines. The present study was undertaken to see whether SFR-derived ROS might cause DNA damage in cultured human cells, namely T limphoblastoid Jurkat and human umbilical vein endothelial cells (HUVEC). 1-3 h treatments with 10-30 microM SFR elicited intracellular ROS formation (as assayed with dihydrorhodamine, DHR, oxidation) as well as DNA breakage (as assessed with fast halo assay, FHA). These effects lacked cell-type specificity, since could be observed in both Jurkat and HUVEC. Differential-pH FHA analysis of damaged DNA showed that SFR causes frank DNA single strand breaks (SSBs); no DNA double strand breaks (DSBs) were found within the considered treatment times (up to 3 h). SFR-derived ROS were formed at the mitochondrial respiratory chain (MRC) level: indeed rotenone or myxothiazol (MRC Complex I and III inhibitors, respectively) abrogated ROS formation. Furthermore ROS were not formed in Jurkat cells pharmacologically depleted of respiring mitochondria (MRC-/Jurkat). Formation of ROS was causally linked to the induction of SSBs: indeed all the experimental conditions capable of preventing ROS formation also prevented the damage of nuclear DNA from SFR-intoxicated cells. As to the toxicological relevance of SSBs, we found that their prevention slightly but significantly attenuated SFR cytotoxicity, suggesting that high-dose SFR toxicity is the result of a complex series of events among which GSH depletion seems to play a pivotal role. In conclusion, the present study identifies a novel mechanism contributing to SFR toxicity which - since DNA damage is a prominent mechanism underlying the cytotoxic activity of established antineoplastic agents - might help to exploit the therapeutic value of SFR in anticancer drug protocols. Copyright 2010 Elsevier B.V. All rights reserved.",
"title": "Sulforaphane induces DNA single strand breaks in cultured human cells."
},
{
"docid": "MED-1557",
"text": "AIM: To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO). METHODS: Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes. RESULTS: Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E. CONCLUSIONS: In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.",
"title": "Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a systematic review..."
},
{
"docid": "MED-4533",
"text": "CONTEXT: Lead, mercury, and arsenic intoxication have been associated with the use of Ayurvedic herbal medicine product (HMPs). OBJECTIVES: To determine the prevalence and concentration of heavy metals in Ayurvedic HMPs manufactured in South Asia and sold in Boston-area stores and to compare estimated daily metal ingestion with regulatory standards. DESIGN AND SETTING: Systematic search strategy to identify all stores 20 miles or less from Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India, Indian cities, and Indian words. An online national directory of Indian grocery stores, a South Asian community business directory, and a newspaper were also searched. We visited each store and purchased all unique Ayurvedic HMPs between April 25 and October 24, 2003. MAIN OUTCOME MEASURES: Concentrations (microg/g) of lead, mercury, and arsenic in each HMP as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion for adults and children estimated using manufacturers' dosage recommendations with comparisons to US Pharmacopeia and US Environmental Protection Agency regulatory standards. RESULTS: A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained heavy metals: lead (n = 13; median concentration, 40 microg/g; range, 5-37,000), mercury (n = 6; median concentration, 20,225 microg/g; range, 28-104,000), and/or arsenic (n = 6; median concentration, 430 microg/g; range, 37-8130). If taken as recommended by the manufacturers, each of these 14 could result in heavy metal intakes above published regulatory standards. CONCLUSIONS: One of 5 Ayurvedic HMPs produced in South Asia and available in Boston South Asian grocery stores contains potentially harmful levels of lead, mercury, and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal toxicity, and testing of Ayurvedic HMPs for toxic heavy metals should be mandatory.",
"title": "Heavy metal content of ayurvedic herbal medicine products."
},
{
"docid": "MED-1490",
"text": "OBJECTIVES: The study aimed to find the threshold of benefit for a hypothetical cholesterol-lowering drug below which the subject would not be prepared to take the drug. We also looked at whether proximity to the target event (myocardial infarction) and the subjects' views on drug taking affected this threshold. DESIGN: We studied 307 subjects using a written questionnaire and interview. Group 1 (102 subjects) had just been discharged from the coronary care unit. Group 2 (105 subjects) were taking cardio-protective drugs but had no recent history of myocardial infarction. Group 3 (100 subjects) had no history of myocardial infarction and were taking no cardio-protective drugs. RESULTS: Median values for the threshold of benefit below which the subject would not take the preventive drug were 20%, 20%, and 30% absolute risk reduction for Groups 1, 2 and 3 respectively. Median values for expectation of average prolongation of life were 12, 12 and 18 months respectively. Only 27% of subjects would take a drug offering 5% or less absolute risk reduction over five years. Subjects' views on medicinal drug taking in general and proximity to the target event were predictors of the acceptance of preventive drugs. Eighty percent of subjects wished to be told the numerical benefit of a preventive drug before starting on it. CONCLUSION: For the majority, the expectation of benefit from a preventive drug is higher than the actual benefit provided by current drug strategies. There is a tension between the patient's right to know about the chance of benefiting from a preventive drug and the likely reduction in uptake if they are so informed.",
"title": "Are preventive drugs preventive enough? A study of patients' expectation of benefit from preventive drugs."
},
{
"docid": "MED-2762",
"text": "BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of s of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.",
"title": "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. ..."
},
{
"docid": "MED-1395",
"text": "In a prospective, randomised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infarct prudent diet. After a first myocardial infarction, patients were randomly assigned to the experimental (n = 302) or control group (n = 303). Patients were seen again 8 weeks after randomisation, and each year for 5 years. The experimental group consumed significantly less lipids, saturated fat, cholesterol, and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma. Serum lipids, blood pressure, and body mass index remained similar in the 2 groups. In the experimental group, plasma levels of albumin, vitamin E, and vitamin C were increased, and granulocyte count decreased. After a mean follow up of 27 months, there were 16 cardiac deaths in the control and 3 in the experimental group; 17 non-fatal myocardial infarction in the control and 5 in the experimental groups: a risk ratio for these two main endpoints combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for prognostic variables. Overall mortality was 20 in the control, 8 in the experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p = 0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death.",
"title": "Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease."
},
{
"docid": "MED-1399",
"text": "BACKGROUND: The Lyon Diet Heart Study is a randomized secondary prevention trial aimed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infarction. An intermediate analysis showed a striking protective effect after 27 months of follow-up. This report presents results of an extended follow-up (with a mean of 46 months per patient) and deals with the relationships of dietary patterns and traditional risk factors with recurrence. METHODS AND RESULTS: Three composite outcomes (COs) combining either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events requiring hospital admission (CO 3) were studied. In the Mediterranean diet group, CO 1 was reduced (14 events versus 44 in the prudent Western-type diet group, P=0.0001), as were CO 2 (27 events versus 90, P=0.0001) and CO 3 (95 events versus 180, P=0. 0002). Adjusted risk ratios ranged from 0.28 to 0.53. Among the traditional risk factors, total cholesterol (1 mmol/L being associated with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count >9x10(9)/L), female sex (adjusted risk ratios, 0.27 to 0. 46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were each significantly and independently associated with recurrence. CONCLUSIONS: The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet. It should be associated with other (pharmacological?) means aimed at reducing modifiable risk factors. Further trials combining the 2 approaches are warranted.",
"title": "Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Di..."
},
{
"docid": "MED-1679",
"text": "BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.",
"title": "Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an..."
},
{
"docid": "MED-5299",
"text": "Background Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for Editors' Summary Editors' Summary A number of modifiable factors are responsible for many premature or preventable deaths. For example, being overweight or obese shortens life expectancy, while half of all long-term tobacco smokers in Western populations will die prematurely from a disease directly related to smoking. Modifiable risk factors fall into three main groups. First, there are lifestyle risk factors. These include tobacco smoking, physical inactivity, and excessive alcohol use (small amounts of alcohol may actually prevent diabetes and some types of heart disease and stroke). Second, there are dietary risk factors such as a high salt intake and a low intake of fruits and vegetables. Finally, there are “metabolic risk factors,” which shorten life expectancy by increasing a person's chances of developing cardiovascular disease (in particular, heart problems and strokes) and diabetes. Metabolic risk factors include having high blood pressure or blood cholesterol and being overweight or obese. Why Was This Study Done? It should be possible to reduce preventable deaths by changing modifiable risk factors through introducing public health policies, programs and regulations that reduce exposures to these risk factors. However, it is important to know how many deaths are caused by each risk factor before developing policies and programs that aim to improve a nation's health. Although previous studies have provided some information on the numbers of premature deaths caused by modifiable risk factors, there are two problems with these studies. First, they have not used consistent and comparable methods to estimate the number of deaths attributable to different risk factors. Second, they have rarely considered the effects of dietary and metabolic risk factors. In this new study, the researchers estimate the number of deaths due to 12 different modifiable dietary, lifestyle, and metabolic risk factors for the United States population. They use a method called “comparative risk assessment.” This approach estimates the number of deaths that would be prevented if current distributions of risk factor exposures were changed to hypothetical optimal distributions. What Did the Researchers Do and Find? The researchers extracted data on exposures to these 12 selected risk factors from US national health surveys, and they obtained information on deaths from difference diseases for 2005 from the US National Center for Health Statistics. They used previously published studies to estimate how much each risk factor increases the risk of death from each disease. The researchers then used a mathematical formula to estimate the numbers of deaths caused by each risk factor. Of the 2.5 million US deaths in 2005, they estimate that nearly half a million were associated with tobacco smoking and about 400,000 were associated with high blood pressure. These two risk factors therefore each accounted for about 1 in 5 deaths in US adults. Overweight–obesity and physical inactivity were each responsible for nearly 1 in 10 deaths. Among the dietary factors examined, high dietary salt intake had the largest effect, being responsible for 4% of deaths in adults. Finally, while alcohol use prevented 26,000 deaths from ischemic heart disease, ischemic stroke, and diabetes, the researchers estimate that it caused 90,000 deaths from other types of cardiovascular diseases, other medical conditions, and road traffic accidents and violence. What Do These Findings Mean? These findings indicate that smoking and high blood pressure are responsible for the largest number of preventable deaths in the US, but that several other modifiable risk factors also cause many deaths. Although the accuracy of some of the estimates obtained in this study will be affected by the quality of the data used, these findings suggest that targeting a handful of risk factors could greatly reduce premature mortality in the US. The findings might also apply to other countries, although the risk factors responsible for most preventable deaths may vary between countries. Importantly, effective individual-level and population-wide interventions are already available to reduce people's exposure to the two risk factors responsible for most preventable deaths in the US. The researchers also suggest that combinations of regulation, pricing, and education have the potential to reduce the exposure of US residents to other risk factors that are likely to shorten their lives. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000058.",
"title": "The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors"
},
{
"docid": "MED-2525",
"text": "AIMS: Guidelines for cardiovascular disease (CVD) prevention cite high levels of low-density lipoprotein cholesterol (LDL-C) as a major risk factor and recommend LDL-C goals for various risk groups. Lifestyle changes are advised as first-line treatment for patients with high cholesterol, and statins are recommended in high-risk patients. The From The Heart study investigated current practice for the diagnosis and treatment of high cholesterol, and attitudes towards management of the condition. METHODS: Physicians were randomly selected from 10 countries, and completed a confidential, semi-structured questionnaire. RESULTS: Of 2790 physicians agreeing to participate, 750 (27%) responded. Physicians rated CVD as the leading cause of death, although physicians (80%) perceived that cancer was the most feared illness among patients. Physicians (71%) believed smoking to be the greatest CVD risk factor, while only 50% thought high cholesterol was the greatest risk. Most physicians (81%) used guidelines to set cholesterol goals, primarily their national guidelines (34%) or the National Cholesterol Education Program Adult Treatment Panel III guidelines (24%). Although only 47% of patients reached and maintained their cholesterol goals, 61% of physicians believed that a sufficient number of patients achieved goals, and 53% did not feel frustrated that they could not always effectively treat patients with CVD. CONCLUSION: Results indicate discrepancies between guideline recommendations and clinical practice. Although physicians appreciate the risk of CVD, the importance of achieving healthy cholesterol levels for CVD prevention does not seem to be widely endorsed. There is a need for improved communication regarding the importance of cholesterol lowering and investigation of initiatives to improve goal achievement among physicians.",
"title": "A global survey of physicians' perceptions on cholesterol management: the From The Heart study."
},
{
"docid": "MED-748",
"text": "Questions of medical ethics are often treated as especially difficult casuistical problems or as difficult cases illustrative of paradoxes or advantages in global moral theories. I argue here, in opposition to such approaches, for the inseparability of questions of social history and social theory from any normative assessment of medical practices. The focus of the discussion is the question of the legitimacy of the social authority exercised by physicians, and the insufficiency of traditional defences of such authority in liberal societies (voluntarist, informed consent approaches), as well as traditional attacks on such strategies (ideology critique). Seeing such authority as institution bound and role based, it is argued, can help reframe, more broadly and more adequately, what is an \"ethical problem\" in medical practice and why.",
"title": "Medical practice and social authority."
},
{
"docid": "MED-2928",
"text": "Natural killer (NK) cells were discovered more than 30 years ago. NK cells are large granular lymphocytes that belong to the innate immune system because unlike T or B lymphocytes of the adaptive or antigen-specific immune system, NK cells do not rearrange T-cell receptor or immunoglobulin genes from their germline configuration. During the past 2 decades there has been a substantial gain in our understanding of what and how NK-cells “see,” lending important insights into their functions and purpose in normal immune surveillance. The most recent discoveries in NK-cell receptor biology have fueled translational research that has led to remarkable results in treating human malignancy.",
"title": "ASH 50th Anniversary Review: Human natural killer cells"
},
{
"docid": "MED-4697",
"text": "Summary With the aging of the population, we are seeing a global increase in age-related disorders, especially in developed countries. Chronic diseases disproportionately affect the older segment of the population, contributing to disability, a diminished quality of life, and an increase in healthcare costs. Increased life expectancy reflects the success of contemporary medicine, which must now respond to the challenges created by this achievement, including the growing burden of chronic illnesses, injuries, and disabilities. A well-developed theoretical framework is required to understand the molecular basis of aging. This, in turn, is a prerequisite for developing the clinical interventions that will constitute an efficient response to the challenge of age-related health issues. This review critically analyzes the experimental evidence that supports and refutes the Free Radical/Mitochondrial Theory of Aging, which has dominated the field of aging research for almost half a century.",
"title": "Is there more to aging than mitochondrial DNA and reactive oxygen species?"
},
{
"docid": "MED-1309",
"text": "Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our recent report suggested that oat, rich in beta-glucan, had a metabolic-regulating and liver-protecting effect in an animal model. In this study, we performed a clinical trial to further confirm the effect of oat. Subjects with BMI ≥27 and aged 18-65, were randomly divided into a control (n=18) and an oat-treated (n=16) group, taking a placebo or beta glucan-containing oat cereal, respectively, for 12 weeks. Our data showed that consumption of oat reduced body weight, BMI, body fat and the waist-to-hip ratio. Profiles of hepatic function, including AST, but especially ALT, were useful resources to help in the evaluation of the liver, since both showed decrements in patients with oat consumption. Nevertheless, anatomic changes were still not observed by ultrasonic image analysis. Ingestion of oat was well tolerated and there was no adverse effect during the trial. In conclusion, consumption of oat reduced obesity, abdominal fat, and improved lipid profiles and liver functions. Taken as a daily supplement, oat could act as an adjuvant therapy for metabolic disorders.",
"title": "Oat prevents obesity and abdominal fat distribution, and improves liver function in humans."
},
{
"docid": "MED-1868",
"text": "Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our previous report suggested that Hibiscus sabdariffa extracts (HSE) had a metabolic-regulating and liver-protecting potential. In this study, we performed a clinical trial to further confirm the effect of HSE. Subjects with a BMI ≧ 27 and aged 18-65, were randomly divided into control (n = 17) and HSE-treated (n = 19) groups, respectively, for 12 weeks. Our data showed that consumption of HSE reduced body weight, BMI, body fat and the waist-to-hip ratio. Serum free fatty acid (FFA) was lowered by HSE. Anatomic changes revealed that HSE improved the illness of liver steatosis. Ingestion of HSE was well tolerated and there was no adverse effect during the trial. No alteration was found for serum α-amylase and lipase. The clinical effect should mainly be attributed to the polyphenols of HSE, since composition analysis showed that branched chain-amino acids, which is associated with obesity, is not obviously high. In conclusion, consumption of HSE reduced obesity, abdominal fat, serum FFA and improved liver steatosis. HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver.",
"title": "Hibiscus sabdariffa extract inhibits obesity and fat accumulation, and improves liver steatosis in humans."
},
{
"docid": "MED-3397",
"text": "INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (Viagra(R)), tadalafil (Cialis(R)), and vardenafil (Levitra(R)) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well-known adverse effects of these drugs and occur in 3-11% of sildenafil users. Vision-threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio-retinal artery occlusion have rarely been reported in PDE5 inhibitor users. AIMS: To highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors. METHODS: Search of the peer-reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. MAIN OUTCOME MEASURES: To scientifically and objectively find out if PDE5 inhibitors are associated with vision-threatening ocular complications. RESULTS: Eight case reports of serious PDE5 inhibitor-associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio-retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use. CONCLUSION: There is lack of conclusive evidence to indicate a direct cause-effect relationship between PDE5 inhibitor use and vision-threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3-11% of users and they are transient and reversible. © 2011 International Society for Sexual Medicine.",
"title": "Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A critical analysis and review of the literature."
},
{
"docid": "MED-2597",
"text": "Since the beginning of the 1990s, increasing evidence supports beneficial effects of nut consumption on health. A new analysis of the Spanish PREDIMED trial, published in BMC Medicine, has expanded our knowledge. The study showed that individuals eating nuts more than three times per week died less often from cardiovascular disease and cancer than non-consumers. The study also adds an important finding that previous epidemiological studies could not provide: a protective effect on premature mortality was only seen in the intervention group in which nut consumption increased during the 4.8 years of follow-up, not in the intervention group with additional olive oil consumption or in the control group. Nut consumption actually decreased during follow-up in the latter two groups. Questions remain to be answered on the quantity of nuts to be consumed for health benefits, on possible mechanisms of action, and on whether some types of nuts should be favored. Please see related research: http://www.biomedcentral.com/1741-7015/11/164.",
"title": "Should we go nuts about nuts?"
},
{
"docid": "MED-912",
"text": "Prunes are used by folks as a remedy of various diseases including hepatitis. A clinical trial was designed to see the effects of prunes (Prunus domestica) on liver function. 166 healthy volunteers were divided into three groups randomly. Either three (about 11.43g) or six (23g approx.) prunes were soaked in a glass of water (250ml) overnight. Each subject from two test groups was asked to drink prune juice & eat whole fruit(single or double dose of prunes) as well, early in the morning, daily for 8 weeks; whereas each subject from control group was given a glass of water to drink. Blood samples were taken at week 0 and week 8 for chemical analysis. There was significant reduction of serum alanine transaminase (p 0.048) and serum alkaline phosphatase (p 0.017) by the lower dose of prunes. There was no change in serum aspartate transaminase and bilirubin. Alteration in liver function by use of prunes may have clinical relevance in appropriate cases and prunes might prove beneficial in hepatic disease.",
"title": "Report: prunes and liver function: a clinical trial."
},
{
"docid": "MED-1501",
"text": "BACKGROUND: Many biological, behavioral, social, and environmental factors may contribute to the delay or prevention of cognitive decline. PURPOSE: To summarize evidence about putative risk and protective factors for cognitive decline in older adults and the effects of interventions for preserving cognition. DATA SOURCES: English-language publications in MEDLINE, HuGEpedia, AlzGene, and the Cochrane Database of Systematic Reviews from 1984 through 27 October 2009. STUDY SELECTION: Observational studies with 300 or more participants and randomized, controlled trials (RCTs) with 50 or more adult participants who were 50 years or older, drawn from general populations, and followed for at least 1 year were included. Relevant, good-quality systematic reviews were also eligible. DATA EXTRACTION: Information on study design, outcomes, and quality were extracted by one researcher and verified by another. An overall rating of the quality of evidence was assigned by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. DATA SYNTHESIS: 127 observational studies, 22 RCTs, and 16 systematic reviews were reviewed in the areas of nutritional factors; medical factors and medications; social, economic, or behavioral factors; toxic environmental exposures; and genetics. Few of the factors had sufficient evidence to support an association with cognitive decline. On the basis of observational studies, evidence that supported the benefits of selected nutritional factors or cognitive, physical, or other leisure activities was limited. Current tobacco use, the apolipoprotein E epsilon4 genotype, and certain medical conditions were associated with increased risk. One RCT found a small, sustained benefit from cognitive training (high quality of evidence) and a small RCT reported that physical exercise helps to maintain cognitive function. LIMITATIONS: The categorization and definition of exposures were heterogeneous. Few studies were designed a priori to assess associations between specific exposures and cognitive decline. The review included only English-language studies, prioritized categorical outcomes, and excluded small studies. CONCLUSION: Few potentially beneficial factors were identified from the evidence on risk or protective factors associated with cognitive decline, but the overall quality of the evidence was low. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and the National Institute on Aging, through the Office of Medical Applications of Research, National Institutes of Health.",
"title": "Systematic review: factors associated with risk for and possible prevention of cognitive decline in later life."
},
{
"docid": "MED-1192",
"text": "Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.",
"title": "Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies"
},
{
"docid": "MED-4837",
"text": "BACKGROUND: Gallstone disease known as cholelithiasis is the most common digestive surgical disorder and account for an important part of health care expenditure. Attempt was made to analyse the gallstone for typing depending upon the composition. AIMS & OBJECTIVES: The main objective of this study was to see the prevalence of different types of gallstone in Nepal and to correlate them with the clinical findings. MATERIALS & METHODS: Gallstones of 80 different patients who underwent cholecystectomy for cholelithiasis were collected from 20th January 2005 to 16th May 2006 in Department of Pathology, Kathmandu Medical College Teaching Hospital. Detailed history was taken. Stones were analyzed with chemical and enzymatic methods using clinical spectrophotometer. RESULTS & CONCLUSION: The most commonly involved age group for cholelithiasis (32.5%) is found to be 30-39 years with a female predominance (M: F=1:3.2). Cholelithiasis was found more commonly among non-vegetarian with the vegetarian: non-vegetarian ratio 1:9. Mixed type stone was found to be the most common type of stone comprising 78.75%, followed by cholesterol stone 12.5%, Brown pigment stone 7.5% and Black pigment stone 1.25%.",
"title": "Prevalence of different types of gallstone in the patients with cholelithiasis at Kathmandu Medical College, Nepal."
}
] |
5a72eba75542992359bc31d5
|
Where are Muztagh Tower and Changtse mountains located?
|
[
{
"docid": "234519",
"text": "Muztagh Tower (also: Mustagh Tower; \"Muztagh\": ice tower), is a mountain in the Baltoro Muztagh, part of the Karakoram range in Baltistan on the border of the Gilgit–Baltistan region of Pakistan and the Xinjiang Uyghur Autonomous Region of China. It stands between the basins of the Baltoro and Sarpo Laggo glaciers.",
"title": ""
},
{
"docid": "1021314",
"text": "Changtse (Tibetan: \"north peak\") is a mountain situated between the Main Rongbuk and East Rongbuk Glaciers in Tibet, China, immediately north of Mount Everest. It is connected to Mount Everest via the North Col.",
"title": ""
}
] |
[
{
"docid": "1390155",
"text": "Hispar Muztagh is a sub-range of the Karakoram mountain range. It is located in the Gojal region of Gilgit-Baltistan, Pakistan, north of Hispar Glacier, south of Shimshal Valley, and east of the Hunza Valley. It is the second highest sub-range of the Karakoram, the highest being the Baltoro Muztagh. The highest mountain in the range is Distaghil Sar (7,885m/25,869 ft).",
"title": ""
},
{
"docid": "4380008",
"text": "The Batura Muztagh (Urdu: بتورا موز تاغ ) mountains are a sub-range of the Karakoram mountain range. They are located in Gojal valley in the Hunza district of the Gilgit-Baltistan province in northern Pakistan.",
"title": ""
},
{
"docid": "5609254",
"text": "Ulugh Muztagh or Ulugh Muztag (Uighur: Ulug muz tag) () and Muztag Feng (), is an extremely remote mountain group on the northern Qinghai-Tibetan Plateau. Located on the border between the Tibetan Autonomous Region and Xinjiang Uyghur Autonomous Region, it is part of the main range of the Kunlun Mountains of East-Central Asia.",
"title": ""
},
{
"docid": "234565",
"text": "The Sarpo Laggo Glacier (\"Sarpo Laggo\": young husband) is a glacier in the autonomous region Xinjiang of China, in the Karakoram mountain range of the Himalayas. It lies north of the Baltoro Muztagh range. It could be reached from the Baltoro glacier on the Pakistani side of the Karakorams via the \"Old Muztagh Pass\" northeast of the Trango Towers. It is however easier to approach the glacier from the Chinese side, starting a long hike at Kashgar on the Karakoram Highway and finally passing K2's northern base camp.",
"title": ""
},
{
"docid": "4771813",
"text": "Passu Sar (Urdu: ; or Passu Sar, Passu I) is a mountain peak in the Batura Muztagh, a sub-range of the Karakoram mountain range, located in the Gilgit District of Gilgit-Baltistan, Pakistan, west of the Hunza Valley. It is the high point of the Passu massif, which also includes Passu Diar (or \"Passu East\", \"Pasu II\"). The peak lies on the main ridge of the Batura Muztagh, about 7 km (4 mi) east of Batura Sar.",
"title": ""
},
{
"docid": "13831559",
"text": "The Mustagh Pass or Muztagh Pass is a pass across the Baltoro Muztagh range in the Karakorams which includes K2, the world's second highest mountain. The crest of the Baltoro Muztagh marks the present border between Pakistani and Chinese territory.",
"title": ""
},
{
"docid": "5022347",
"text": "The Saser Muztagh is the easternmost subrange of the Karakoram range, in the Ladakh region of India. It is bounded on the south, east and northeast by the Shyok River, which bends sharply around the southeast corner of the range. On the west it is separated from the neighboring Kailas Mountains by the Nubra River, while the Sasser Pass (Saser La) marks the boundary between this range and the Rimo Muztagh to the north. The Ladakh Range stands to the south of the Saser Muztagh, across the Shyok River.",
"title": ""
},
{
"docid": "1197175",
"text": "The Trango Towers (Urdu: ) are a family of rock towers situated in Gilgit-Baltistan, in the north of Pakistan. The Towers offer some of the largest cliffs and most challenging rock climbing in the world, and every year a number of expeditions from all corners of the globe visit Karakoram to climb the difficult granite. They are located north of Baltoro Glacier, and are part of the Baltoro Muztagh, a sub-range of the Karakoram range. The highest point in the group is the summit of \"Great Trango Tower\" at 6,286 m (20,623 ft), the east face of which features the world's greatest nearly vertical drop.",
"title": ""
},
{
"docid": "4799998",
"text": "The Baltoro Muztagh () is a subrange of the Karakoram mountain range, in Baltistan region of the Gilgit-Baltistan, northmost political entity of Pakistan; and in Xinjiang, China and the region is also claimed by India . The crest of the range forms part of the Pakistan-China border disputed by India .",
"title": ""
},
{
"docid": "366732",
"text": "Kanjut Sar (Urdu: کنجت سر ) or Kunjudh Sar as pronounced in \"Wakhi\" is a mountain located in the Hispar Muztagh, a subrange of the Karakoram mountain range. Kunjudh Sar in wakhi language mean that which overlooks Kunjudh, or above Kunjudh, while Khujudh is the wakhi name for Lower Hunza. It is the 26th highest mountain on Earth and the 11th highest in Pakistan.",
"title": ""
},
{
"docid": "40860022",
"text": "The Perret tower, also named the \"Tower to look at the mountains\", is an observation tower located in Grenoble, in the Paul Mistral public park. It is the first tower built in reinforced concrete in Europe. In 1998, it was officially declared to be a national heritage site. It was built in the field of the International Exhibition of Hydropower and Tourism where it was the orientation tower and the symbol of the exhibition. Nowadays, it is the last vestige of this exhibition.",
"title": ""
},
{
"docid": "632127",
"text": "Saser Kangri (or Sasir Kangri) is a mountain in India. It is the highest peak in the Saser Muztagh, the easternmost subrange of the Karakoram range. Sasir Kangri is located within Jammu and Kashmir, the northernmost state of India.",
"title": ""
},
{
"docid": "28492855",
"text": "The Indira Col (altitude 5,764 m ) is a col (mountain pass, also called \"La\" in the local language) on the Indira Ridge in the Siachen Muztagh in the Karakoram Range. It is within 3 km of Sia Kangri to the west, the summit of which is the tripoint where territories controlled by India, Pakistan and China meet.",
"title": ""
},
{
"docid": "4504453",
"text": "Muztagh Ata, or Muztagata (Uyghur: مۇز تاغ ئاتا, Музтаң Ата, literally \"ice-mountain-father\"; ), is the second highest (7509 metres) of the mountains which form the northern edge of the Tibetan Plateau (not the second highest of the mountains of the Tibetan Plateau). It is sometimes regarded as being part of the Kunlun Shan, although physically it is more closely connected to the Pamirs. It is also one of the relatively easier 7,000 m peaks in the world to climb, due to its gentle western slope and the comparatively drier weather of Xinjiang, though a thorough acclimatization period and a very strong physical condition are crucial for success.",
"title": ""
},
{
"docid": "1370852",
"text": "Baintha Brakk (Urdu: بائنتھا براک ) or The Ogre is a steep, craggy mountain, 7285 m high, in the Panmah Muztagh, a subrange of the Karakoram mountain range. It is located in Gilgit-Baltistan, Pakistan. It is famous for being one of the hardest peaks in the world to climb: twenty-four years elapsed between the first ascent in 1977 and the second in 2001.",
"title": ""
},
{
"docid": "4374758",
"text": "Batura Sar (Urdu: بتورا سر ), also referred to as Batura I, is the 25th highest mountain on earth and the 10th highest in Pakistan. It is the highest peak of the Batura Muztagh, which is the westernmost subrange of the Karakoram range. It forms the apex of the Batura Wall, which is a continuously high part of the backbone of the Batura Muztagh.",
"title": ""
},
{
"docid": "5090933",
"text": "Rimo I is the main summit of the Rimo massif with an elevation of 7385 m . It lies in the northern part of the remote Rimo Muztagh, a subrange of the Karakoram range. It is located about 20 km northeast of the snout of the Siachen Glacier and is the world's 71st highest mountain. \"Rimo\" means \"striped mountain\". The Rimo Glacier, originating here, drains to the Shyok river.",
"title": ""
},
{
"docid": "2465840",
"text": "The Baltoro Glacier (Urdu: ), at 63 km in length, is one of the longest glaciers outside the polar regions. It is located in the Gilgit-Baltistan region (the northernmost political entity of Pakistan). It runs through part of the Karakoram mountain range. The Baltoro Muztagh lies to the south and east of the glacier, while the Masherbrum Mountains lie to the south. At 8,611 m (28,251 ft), K2 is the highest mountain in the region, and three others within 20 km top 8,000 m.",
"title": ""
},
{
"docid": "4838156",
"text": "Trango Glacier (Urdu: ) is a glacier in the Baltoro Muztagh range of the Karakoram in Baltistan, Gilgit-Baltistan, Pakistan. It flows from north to south on the west side of the Trango Towers and joins the Baltoro Glacier. Trango towers has been declared 2nd almost vertical slope in the world and has a height of about 6200 m .",
"title": ""
},
{
"docid": "36275065",
"text": "Aq Tash is mountain, , in the Rimo Muztagh, part of the Karakorum.",
"title": ""
},
{
"docid": "11226033",
"text": "Chakragil (or Chagragil, Chakar Aghil, Kingata Tagh [or Kingata Tagh II, see below]) is a major mountain in Xinjiang, China. It is located about 100 km southwest of Kashgar, about 60 km due north of Muztagh Ata, and 37 km northwest of Kongur Tagh. It is in the subrange known as the Kingata Shan, generally included in the \"Eastern Pamirs\" as it (and the neighboring Kongur Shan range) are separated by the major Yarkand River valley from the extreme northwest end of the Kunlun Mountains, near the Pamir Mountains. The Gez River flows just south of the mountain.",
"title": ""
},
{
"docid": "5091591",
"text": "The Teram Kangri group is a mountain massif in the remote Siachen Muztagh, a subrange of the Karakoram range. The high point of the group, and of the Siachen Muztagh, is Teram Kangri I. The peak lies on the boundary between China and the disputed Siachen Glacier region near the line of control between India and Pakistan. The northeast side of the peak is in Chinese-controlled territory, the southwest side in the disputed Siachen area currently controlled by India.",
"title": ""
},
{
"docid": "643672",
"text": "Kala Patthar, meaning 'black rock' in Nepali and Hindi, is a notable landmark located on the south ridge of Pumori in the Nepalese Himalayas above Gorakshep. Although not a proper mountain, with a prominence of only , the ascent of Kala Patthar is very popular with trekkers in the region of Mount Everest since it provides the most accessible closeup view of Everest. Due to the structure of the Everest Massif, its high summit is blocked by Nuptse from much of the surrounding region. The views of Everest, Nuptse and Changtse are spectacular from Kala Patthar and there are glimpses of the northern flank and summit of Lhotse. The world's highest webcam, Mount Everest webcam, is located here.",
"title": ""
},
{
"docid": "42288724",
"text": "Watch Tower is a (12331 ft ) mountain located in the southern Wind River Range in the U.S. state of Wyoming. Watch Tower is on the west side of the Cirque of the Towers, a popular climbing area and is just southeast of Block Tower. Watch Tower is immediately east of the Continental Divide.",
"title": ""
},
{
"docid": "13642228",
"text": "The Hunter Mountain Fire Tower is located on the summit of the eponymous mountain, second highest of the Catskill Mountains in the U.S. state of New York. It was the first of 23 fire lookout towers built by the state in the region, and the next-to-last of the five still standing to be abandoned.",
"title": ""
},
{
"docid": "10022279",
"text": "Martin Hill is a mountain ridge which connects Tussey Mountain to its east and Evitts Mountain to its west. Martin Hill is located in the Martin Hill Wild Area, which is a part of the Buchanan State Forest, in Bedford County, Pennsylvania. The summit of Martin Hill is one of the few in the Commonwealth which is void of any towers or transmitters; such equipment is located instead on a lesser nearby summit in the same mountain complex. Martin Hill is the second highest in Pennsylvania's Ridge and Valley Appalachians, the highest being Wills Mountain to its west at 2780 ft . The highest mountains in the Commonwealth are located in the Allegheny Mountains in western Pennsylvania, where Mount Davis stands at 3213 ft .",
"title": ""
},
{
"docid": "39460555",
"text": "Tower Mountain, elevation 13558 ft , is a summit in the San Juan Mountains located northeast of Silverton, Colorado.",
"title": ""
},
{
"docid": "1689599",
"text": "Surveyed as K12, this mountain is in the Saltoro Muztagh which is a subrange of the Karakoram range in the Siachen region, near Jammu and Kashmir. It lies near the Line of Control. Its name comes from its designation given during the original survey of the Karakoram range.",
"title": ""
},
{
"docid": "7755861",
"text": "Talcott Mountain State Park is a 574 acre Connecticut state park located primarily in the town of Simsbury. The park is the home of the Heublein Tower, a 165 ft lookout tower atop Talcott Mountain. The park offers picnicking, scenic views, and hiking on the Metacomet Trail. The Tower Trail is 1.25 mi long; a walk to the tower takes approximately 30 to 40 minutes.",
"title": ""
},
{
"docid": "35953973",
"text": "Lima Mountain is a 2238 foot summit in Cook County, Minnesota. It is located in the Lima Mountain Unit, a 2540 acre inventoried roadless area adjacent to the Boundary Waters Canoe Area. There is a 1 mile trail to the summit, where a fire tower once stood. Lima Mountain has a 328 foot rise over the saddle connecting it with the Misquah Hills High Point and Peak 2266. A trail to the summit begins along the Lima Grade (Forest Route 315) just north of its junction with Lima Mountain Road (Forest Route 152)",
"title": ""
}
] |
349
|
Diminished ovarian reserve is a reliable indicator of infertility in a non-infertile population.
|
[
{
"docid": "13497630",
"text": "Importance Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential. Objective To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. Design, Setting, and Participants Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area. Exposures Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH. Main Outcomes and Measures The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result. Results A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n = 84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n = 579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n = 83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n = 654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n = 69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n = 737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001). Conclusions and Relevance Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics.",
"title": "Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age"
}
] |
[
{
"docid": "11109043",
"text": "BACKGROUND To compare the clinical results and the cost-effectiveness of using the aromatase inhibitor, letrozole, in conjunction with FSH and FSH alone for controlled ovarian stimulation (COS) in patients undergoing intrauterine insemination (IUI) for a variety of indications. METHODS Four hundred and thirty-two consecutive patients who underwent 872 IUI cycles were included. The study population was composed of two groups. Group I included 308 patients who underwent 589 IUI cycles with letrozole and FSH for the following indications: anovulation (143 cycles), male factor infertility (147 cycles), unexplained infertility (250 cycles), endometriosis (18 cycles) and combined indications (31 cycles). Group II included 124 patients who underwent 283 IUI cycles who received FSH only for the following indications: ovarian factor infertility (82 cycles), male factor infertility (66 cycles), unexplained infertility (114 cycles), endometriosis (13 cycles) and other indications (8 cycles). Main outcome measures included number of mature follicles >16 mm in diameter, dose of FSH used per cycle, clinical pregnancy rate and cost-effectiveness ratio per pregnancy. RESULTS FSH dose required for ovarian stimulation was significantly lower when letrozole was used (P < 0.0001). Although a significantly higher number of follicles >16 mm and endometrial thickness at the day of hCG administration (P < 0.0001) were observed in Group II, pregnancy rate per started (14.4 versus 15.9%) and per completed cycles (15.77 versus 18.07%) was the same in Group I and Group II, respectively. IUI cancellation rate was significantly lower with letrozole treatment (P = 0.05%). The cost per cycle was significantly lower in Group I versus Group II (468.93 Can dollars +/- 418.18 versus 1067.28 +/- 921.43; P < 0.0001). The cost-effectiveness ratio was 3249.42 dollars in the letrozole group and 6712.00 dollars in the FSH-only group. CONCLUSION A letrozole-FSH combination could be an effective ovarian stimulation protocol in IUI cycles. Such a protocol may be more cost-effective than FSH alone because of the difference of FSH dose and cost. A randomized controlled trial is needed to further substantiate this finding.",
"title": "Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation."
},
{
"docid": "34198460",
"text": "BACKGROUND Given the high value placed on children in sub-Saharan Africa, previous research suggests that infertility increases the risk of psychological distress and marital conflict, encourages risky sexual behavior and deprives infertile individuals and couples of an important source of economic and social capital. This paper explores the implications of infertility for women in Ghana, West Africa. METHODS Semi-structured interview data collected from 107 women (aged 21-48 years, mean 33 years) seeking treatment in gynecological and obstetric clinics in Accra, Ghana, are analyzed. Based on iterative open coding of the interviews, the focus of the analysis is on mental health, marital instability, social interaction and gendered experiences. RESULTS Infertile women report facing severe social stigma, marital strain and a range of mental health difficulties. Many women feel that they shoulder a disproportionate share of the blame for infertility and, by extension, face greater social consequences than male partners for difficulties conceiving. Women who do not self-identify as infertile corroborate these findings, asserting that the social consequences of infertility are severe, particularly for women. CONCLUSIONS Infertility in Ghana has important consequences for social interactions, marital stability and mental health. These consequences are not perceived to be shared equally by Ghanaian men.",
"title": "'Zero is not good for me': implications of infertility in Ghana."
},
{
"docid": "9997636",
"text": "The aim of this study was to confirm the presence of stem cells in the ovarian surface epithelium of patients with premature ovarian failure and no mature follicles and oocytes. In these patients, small round cells of unknown origin expressing SOX-2 marker of pluripotency were observed among the epithelial cells just after the ovarian surface epithelium scraping. These cells were an integral part of the ovarian surface epithelium. When the scraped cells were cultured in a medium with added follicular fluid to provide some ovarian niche, primitive oocyte-like cells and typical round-shaped cell clusters positively stained on alkaline phosphatase, and markers of pluripotency, such as SOX-2 and SSEA-4, were developed. These markers were expressed early and also later in the culture. Single oocyte-like cells expressed genes OCT4A, SOX-2, NANOG, NANOS, STELLA, CD9, LIN28, KLF4, GDF3, and MYC, characteristic for pluripotent stem cells. The results of this study confirmed the presence of putative stem cells in the ovarian surface epithelium of these patients and provided some basis to create a stem cell line in the future.",
"title": "Ovarian Surface Epithelium in Patients with Severe Ovarian Infertility: A Potential Source of Cells Expressing Markers of Pluripotent/Multipotent Stem Cells"
},
{
"docid": "4423220",
"text": "Male infertility is a long-standing enigma of significant medical concern. The integrity of sperm chromatin is a clinical indicator of male fertility and in vitro fertilization potential: chromosome aneuploidy and DNA decondensation or damage are correlated with reproductive failure. Identifying conserved proteins important for sperm chromatin structure and packaging can reveal universal causes of infertility. Here we combine proteomics, cytology and functional analysis in Caenorhabditis elegans to identify spermatogenic chromatin-associated proteins that are important for fertility. Our strategy employed multiple steps: purification of chromatin from comparable meiotic cell types, namely those undergoing spermatogenesis or oogenesis; proteomic analysis by multidimensional protein identification technology (MudPIT) of factors that co-purify with chromatin; prioritization of sperm proteins based on abundance; and subtraction of common proteins to eliminate general chromatin and meiotic factors. Our approach reduced 1,099 proteins co-purified with spermatogenic chromatin, currently the most extensive catalogue, to 132 proteins for functional analysis. Reduction of gene function through RNA interference coupled with protein localization studies revealed conserved spermatogenesis-specific proteins vital for DNA compaction, chromosome segregation, and fertility. Unexpected roles in spermatogenesis were also detected for factors involved in other processes. Our strategy to find fertility factors conserved from C. elegans to mammals achieved its goal: of mouse gene knockouts corresponding to nematode proteins, 37% (7/19) cause male sterility. Our list therefore provides significant opportunity to identify causes of male infertility and targets for male contraceptives.",
"title": "Sperm chromatin proteomics identifies evolutionarily conserved fertility factors"
},
{
"docid": "29504413",
"text": "Gonadal steroid hormones regulate sexually dimorphic development of brain functions and behaviors. Their nuclear receptors offer the opportunity to relate molecular events in neurons to simple instinctive mammalian behaviors. We have determined the role of estrogen receptor (ER) activation by endogenous estrogen in the development of male-typical behaviors by the use of transgenic estrogen-receptor-deficient (ERKO) mice. Surprisingly, in spite of the fact that they are infertile, ERKO mice showed normal motivation to mount females but they achieved less intromissions and virtually no ejaculations. Aggressive behaviors were dramatically reduced and male-typical offensive attacks were rarely displayed by ERKO males. Moreover, ER gene disruption demasculinized open-field behaviors. In the brain, despite the evident loss of functional ER protein, the androgen-dependent system appears to be normally present in ERKO mice. Together, these findings indicate that ER gene expression during development plays a major role in the organization of male-typical aggressive and emotional behaviors in addition to simple sexual behaviors.",
"title": "Behavioral effects of estrogen receptor gene disruption in male mice."
},
{
"docid": "87337034",
"text": "SummaryA plant expression vector pBIA9-AMF containing an antisense fragment of the CYP86MF gene and the tapetum-specific A9 promoter was constructed. Plasmid vectors were introduced by floral-dipping and pollen-tube transformation methods to Chinese cabbage pak-choi (Brassica campestris ssp. chinensis (L.) Makino var. communis Tsen et Lee, syn. B. rapa ssp. chinensis (L.) Makino var. communis Tsen et Lee) and flowering Chinese cabbage (B. campestris ssp. chinensis (L.) Makino var. parachinensis (Bailey) Tsen et Lee). Results showed that KanR seedlings could be obtained by the pollen-tube method through germination tests of T1 progeny seeds, but not by the floral-dipping method. One of the two KanR seedlings proved that the antisense fragment of the CYP86MF gene was integrated into the Chinese cabbage genome by PCR amplification and Southern blotting. Northern hybridization indicated that the CYP86MF gene, under the A9 promoter, was inhibited in the transformant, and self-infertility was found in the trans...",
"title": "Construction of an antisense CYP86MF gene plasmid vector and production of a male-sterile Chinese cabbage transformant by the pollen-tube method"
},
{
"docid": "25993718",
"text": "Traditionally, the diagnosis of male infertility has depended upon a descriptive evaluation of human semen with emphasis on the number of spermatozoa that are present in the ejaculate, their motility and their morphology. The fundamental tenet underlying this approach is that male fertility can be defined by reference to a threshold concentration of motile, morphologically normal spermatozoa that must be exceeded in order to achieve conception. Many independent studies have demonstrated that this fundamental concept is flawed and, in reality, it is not so much the absolute number of spermatozoa that determines fertility, but their functional competence. In the light of this conclusion, a range of in vitro tests have been developed to monitor various aspects of sperm function including their potential for movement, cervical mucus penetration, capacitation, zona recognition, the acrosome reaction and sperm-oocyte fusion. Such functional assays have been found to predict the fertilizing capacity of human spermatozoa in vitro and in vivo with some accuracy. Recent developments in this field include the introduction of tests to assess the degree to which human spermatozoa have suffered oxidative stress as well as the integrity of their nuclear and mitochondrial DNA. Such assessments not only yield information on the fertilizing capacity of human spermatozoa but also their ability to support normal embryonic development.",
"title": "Sperm function tests and fertility."
},
{
"docid": "14682243",
"text": "BACKGROUND Results of the few cohort studies from countries with low incomes or middle incomes suggest a lower incidence of dementia than in high-income countries. We assessed incidence of dementia according to criteria from the 10/66 Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders (DSM) IV, the effect of dementia at baseline on mortality, and the independent effects of age, sex, socioeconomic position, and indicators of cognitive reserve. METHODS We did a population-based cohort study of all people aged 65 years and older living in urban sites in Cuba, the Dominican Republic, and Venezuela, and rural and urban sites in Peru, Mexico, and China, with ascertainment of incident 10/66 and DSM-IV dementia 3-5 years after cohort inception. We used questionnaires to obtain information about age in years, sex, educational level, literacy, occupational attainment, and number of household assets. We obtained information about mortality from all sites. For participants who had died, we interviewed a friend or relative to ascertain the likelihood that they had dementia before death. FINDINGS 12,887 participants were interviewed at baseline. 11,718 were free of dementia, of whom 8137 (69%) were reinterviewed, contributing 34,718 person-years of follow-up. Incidence for 10/66 dementia varied between 18·2 and 30·4 per 1000 person-years, and were 1·4-2·7 times higher than were those for DSM-IV dementia (9·9-15·7 per 1000 person-years). Mortality hazards were 1·56-5·69 times higher in individuals with dementia at baseline than in those who were dementia-free. Informant reports suggested a high incidence of dementia before death; overall incidence might be 4-19% higher if these data were included. 10/66 dementia incidence was independently associated with increased age (HR 1·67; 95% CI 1·56-1·79), female sex (0·72; 0·61-0·84), and low education (0·89; 0·81-0·97), but not with occupational attainment (1·04; 0·95-1·13). INTERPRETATION Our results provide supportive evidence for the cognitive reserve hypothesis, showing that in middle-income countries as in high-income countries, education, literacy, verbal fluency, and motor sequencing confer substantial protection against the onset of dementia. FUNDING Wellcome Trust Health Consequences of Population Change Programme, WHO, US Alzheimer's Association, FONACIT/ CDCH/ UCV.",
"title": "Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study"
},
{
"docid": "42150015",
"text": "CONTEXT Anti-müllerian hormone (AMH) is an ovarian reserve marker that is increasingly applied in clinical practice as a prognostic and diagnostic tool. Despite increased use of AMH in clinical practice, large-scale studies addressing the influence of possible determinants on AMH levels are scarce. OBJECTIVE We aimed to address the role of reproductive and lifestyle determinants of AMH in a large population-based cohort of women. DESIGN In this cross-sectional study, age-specific AMH percentiles were calculated using general linear modeling with CG-LMS (Cole and Green, Lambda, Mu, and Sigma model, an established method to calculate growth curves for children). SETTING Women from the general community participating in the Doetinchem Cohort study were assessed. PARTICIPANTS Two thousand three hundred twenty premenopausal women were included. MAIN OUTCOME MEASURE The effect of female reproductive and lifestyle factors on shifts in age-specific AMH percentiles was studied. RESULTS In comparison to women with a regular menstrual cycle, current oral contraceptive (OC) users, women with menstrual cycle irregularity, and pregnant women had significantly lower age-specific AMH percentiles (for OC use, 11 percentiles lower; for cycle irregularity, 11 percentiles lower; and for pregnancy, 17 percentiles lower [P value for all <.0001]). Age at menarche and age at first childbirth were not associated with the age-specific AMH percentile. Higher parity was associated with 2 percentiles higher age-specific AMH (P = .02). Of the lifestyle factors investigated, current smoking was associated with 4 percentiles lower age-specific AMH percentiles (P = .02), irrespective of the smoking dose. Body mass index, waist circumference, alcohol consumption, physical exercise, and socioeconomic status were not significantly associated with age-specific AMH percentiles. CONCLUSIONS This study demonstrates that several reproductive and lifestyle factors are associated with age-specific AMH levels. The lower AMH levels associated with OC use and smoking seem reversible, as effects were confined to current use of OC or cigarettes. It is important to give careful consideration to the effect of such determinants when interpreting AMH in a clinical setting and basing patient management on AMH.",
"title": "Reproductive and lifestyle determinants of anti-Müllerian hormone in a large population-based study."
},
{
"docid": "24323369",
"text": "OBJECTIVE To determine which first-line medication is more effective in polycystic ovary syndrome (PCOS) patients for ovulation induction and pregnancy achievement and to verify whether any patient characteristic is associated with a better response to therapy. DESIGN Observational comparative study. SETTING Fertility clinic. PATIENT(S) One hundred fifty-four infertile women with oligomenorrhea and hyperandrogenism. INTERVENTION(S) Group 1 (56 patients) received clomiphene citrate (CC) 50 mg from days 5-9 of the cycle. Group 2 (57 patients) received 500 mg of metformin 3 times a day. Group 3 (41 patients) received both medications. MAIN OUTCOME MEASURE(S) Ovulation and pregnancy. RESULT(S) Patients receiving metformin alone had an increased ovulation rate compared with those receiving CC alone (75.4% vs. 50%). Patients on metformin had similar ovulation rates compared with those in the combination group (75.4% vs. 63.4%). Pregnancy rates were equivalent in the 3 groups. Response to metformin was independent of body weight and dose. Finally, nonsmoking predicted better ovulatory response overall as well as lower fasting glucose for CC and lower androgens for metformin. CONCLUSION(S) Metformin is better for ovulation induction than CC alone and equivalent for pregnancy achievement. We suggest that metformin can be used first for ovulation induction in patients with PCOS regardless of their weight and insulin levels because of its efficacy and known safety profile.",
"title": "Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome."
},
{
"docid": "17088791",
"text": "Most multiple case families of young onset breast cancer and ovarian cancer are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. However, these mutations are uncommon in the population and they probably account for only a few percent of all breast cancer incidence. A much larger fraction of breast cancer might, in principle, be due to common variants which confer more modest individual risks. There are several common polymorphisms in the BRCA1 gene which generate amino acid substitutions. We have examined the frequency of four of these polymorphisms: Gln356Arg, Pro871Leu, Glu1038Gly and Ser1613Gly in large series of breast and ovarian cancer cases and matched controls. Due to strong linkage disequilibrium, these four sites generate only three haplotypes with a frequency > 1.3%. The most common haplotypes, defined by the alleles Gln356Pro871Glu1038Ser1613 and Gln356Leu871Gly1038Gly1613, have frequencies of 0.57 and 0.32 respectively, and these frequencies do not differ significantly between patient and control groups. Thus the most common polymorphisms of the BRCA1 gene do not make a significant contribution to breast or ovarian cancer risk. However, our data suggest that the Arg356 allele may have a different genotype distribution in breast cancer patients from that in controls (Arg356 homozygotes are more frequent in the control groups, P = 0.01), indicating that it may be protective against breast cancer. If this finding can be confirmed, it may provide an insight into the structural features of the BRCA1 protein that are important for its function.",
"title": "Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population."
},
{
"docid": "841371",
"text": "OBJECTIVE To assess the robustness of patient responses to a new national survey of patient experience as a basis for providing financial incentives to doctors. DESIGN Analysis of the representativeness of the respondents to the GP Patient Survey compared with those who were sampled (5.5 million patients registered with 8273 general practices in England in January 2009) and with the general population. Analysis of non-response bias looked at the relation between practice response rates and scores on the survey. Analysis of the reliability of the survey estimated the proportion of the variance of practice scores attributable to true differences between practices. RESULTS The overall response rate was 38.2% (2.2 million responses), which is comparable to that in surveys using similar methodology in the UK. Men, young adults, and people living in deprived areas were under-represented among respondents. However, for questions related to pay for performance, there was no systematic association between response rates and questionnaire scores. Two questions which triggered payments to general practitioners were reliable measures of practice performance, with average practice-level reliability coefficients of 93.2% and 95.0%. Less than 3% and 0.5% of practices had fewer than the number of responses required to achieve conventional reliability levels of 90% and 70%. A change to the payment formula in 2009 resulted in an increase in the average impact of random variation in patient scores on payments to general practitioners compared with payments made in 2007 and 2008. CONCLUSIONS There is little evidence to support the concern of some general practitioners that low response rates and selective non-response bias have led to systematic unfairness in payments attached to questionnaire scores. The study raises issues relating to the validity and reliability of payments based on patient surveys and provides lessons for the UK and for other countries considering the use of patient experience as part of pay for performance schemes.",
"title": "Reliability of patient responses in pay for performance schemes: analysis of national General Practitioner Patient Survey data in England"
},
{
"docid": "14827874",
"text": "CONTEXT For the last 40 yr, the first line of treatment for anovulation in infertile women has been clomiphene citrate (CC). CC is a safe, effective oral agent but is known to have relatively common antiestrogenic endometrial and cervical mucous side effects that could prevent pregnancy in the face of successful ovulation. In addition, there is a significant risk of multiple pregnancy with CC, compared with natural cycles. Because of these problems, we proposed the concept of aromatase inhibition as a new method of ovulation induction that could avoid many of the adverse effects of CC. The objective of this review was to describe the different physiological mechanisms of action for CC and aromatase inhibitors (AIs) and compare studies of efficacy for both agents for ovulation induction. EVIDENCE ACQUISITION We conducted a systematic review of all the published studies, both controlled and noncontrolled, comparing CC and AI treatment, either alone or in combination with gonadotropins, for ovulation induction or augmentation, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS Because of the recent acceptance of the concept of using AIs for ovulation induction, few controlled studies were identified, and the rest of the studies were pilot or preliminary comparisons. Based on these studies, it appears that AIs are as effective as CC in inducing ovulation, are devoid of any antiestrogenic side effects, result in lower serum estrogen concentrations, and are associated with good pregnancy rates with a lower incidence of multiple pregnancy than CC. When combined with gonadotropins for assisted reproductive technologies, AIs reduce the dose of FSH required for optimal follicle recruitment and improve the response to FSH in poor responders. CONCLUSIONS Preliminary evidence suggests that AIs may replace CC in the future because of similar efficacy with a reduced side effect profile. Although worldwide experience with AIs for ovulation induction is increasing, at present, definitive studies in the form of randomized controlled trials comparing CC with AIs are lacking.",
"title": "0021-972X/06/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 91(3):760–771 Printed in U.S.A. Copyright © 2006 by The Endocrine Society doi: 10.1210/jc.2005-1923 REVIEW: Aromatase Inhibitors for Ovulation Induction"
},
{
"docid": "27391365",
"text": "The validity of the six-question World Health Organization Adult ADHD Self-Report Scale (ASRS) Screener was assessed in a sample of subscribers to a large health plan in the US. A convenience subsample of 668 subscribers was administered the ASRS Screener twice to assess test-retest reliability and then a third time in conjunction with a clinical interviewer for DSM-IV adult ADHD. The data were weighted to adjust for discrepancies between the sample and the population on socio-demographics and past medical claims. Internal consistency reliability of the continuous ASRS Screener was in the range 0.63-0.72 and test-retest reliability (Pearson correlations) in the range 0.58-0.77. A four-category version The ASRS Screener had strong concordance with clinician diagnoses, with an area under the receiver operating characteristic curve (AUC) of 0.90. The brevity and ability to discriminate DSM-IV cases from non-cases make the six-question ASRS Screener attractive for use both in community epidemiological surveys and in clinical outreach and case-finding initiatives.",
"title": "Validity of the World Health Organization Adult ADHD Self-Report Scale (ASRS) Screener in a representative sample of health plan members."
},
{
"docid": "1412089",
"text": "BACKGROUND Traditional T2 weighted MR imaging results are non-specific for the extent of underlying white matter structural abnormalities present in late life depression (LLD). Diffusion tensor imaging provides a unique opportunity to investigate the extent and nature of structural injury, but has been limited by examining only a subset of regions of interest (ROI) and by confounds common to the study of an elderly population, including comorbid vascular pathology. Furthermore, comprehensive correlation of diffusion tensor imaging (DTI) measurements, including axial and radial diffusivity measurements, has not been demonstrated in the late life depression population. METHODS 51 depressed and 16 non-depressed, age- and cerebrovascular risk factor-matched elderly subjects underwent traditional anatomic T1 and T2 weight imaging, as well as DTI. The DTI data were skeletonized using tract based spatial statistics (TBSS), and both regional and global analyses were performed. RESULTS Widespread structural abnormalities within white matter were detected in the LLD group, accounting for age, gender and education and matched for cerebrovascular risk factors and global T2 white matter hyperintensities (T2WMH). Regional differences were most prominent in uncinate and cingulate white matter and were generally characterized by an increase in radial diffusivity. Age-related changes particularly in the cingulate bundle were more advanced in individuals with LLD relative to controls. Regression analysis demonstrated significant correlations of regional fractional anisotropy and radial diffusivity with five different neuropsychological factor scores. TBSS analysis demonstrated a greater extent of white matter abnormalities in LLD not responsive to treatment, as compared to controls. CONCLUSIONS White matter integrity is compromised in late life depression, largely manifested by increased radial diffusivity in specific regions, suggesting underlying myelin injury. A possible mechanism for underlying myelin injury is chronic white matter ischemia related to intrinsic cerebrovascular disease. In some regions such as the cingulate bundle, the white matter injury related to late life depression appears to be independent of and compounded by age-related changes. The correlations with neuropsychological testing indicate the essential effects of white matter injury on functional status. Lastly, response to treatment may depend on the extent of white matter injury, suggesting a need for intact functional networks.",
"title": "Diminished performance on neuropsychological testing in late life depression is correlated with microstructural white matter abnormalities."
},
{
"docid": "22281684",
"text": "Wnt signaling has diverse actions in cardiovascular development and disease processes. Secreted frizzled-related protein 5 (Sfrp5) has been shown to function as an extracellular inhibitor of non-canonical Wnt signaling that is expressed at relatively high levels in white adipose tissue. The aim of this study was to investigate the role of Sfrp5 in the heart under ischemic stress. Sfrp5 KO and WT mice were subjected to ischemia/reperfusion (I/R). Although Sfrp5-KO mice exhibited no detectable phenotype when compared with WT control at baseline, they displayed larger infarct sizes, enhanced cardiac myocyte apoptosis, and diminished cardiac function following I/R. The ischemic lesions of Sfrp5-KO mice had greater infiltration of Wnt5a-positive macrophages and greater inflammatory cytokine and chemokine gene expression when compared with WT mice. In bone marrow-derived macrophages, Wnt5a promoted JNK activation and increased inflammatory gene expression, whereas treatment with Sfrp5 blocked these effects. These results indicate that Sfrp5 functions to antagonize inflammatory responses after I/R in the heart, possibly through a mechanism involving non-canonical Wnt5a/JNK signaling.",
"title": "Secreted Frizzled-related Protein 5 Diminishes Cardiac Inflammation and Protects the Heart from Ischemia/Reperfusion Injury."
},
{
"docid": "21053753",
"text": "The Constant-Murley shoulder assessment score has proven to be a valuable diagnostic instrument. Thus, in the literature it has been mentioned that the clinical accuracy of this score varies especially when comparing patients in larger, inhomogeneous patient groups. The \"relative Constant score\" (CS(rel)) tries to minimize these problems by using reference parameters out of healthy age and gender related control groups. The authors of this study tried to show that it is even more accurate to use the functional performance of the uninjured collateral shoulder of the same individual as reference, introducing the \"individual relative Constant score\" (CS(indiv)). The CS(indiv) and the CS(rel) were compared for 125 consecutive patients with shoulder disorders, and a group of 125 healthy volunteers as a control group. In a non-parametric comparison of the reciever operating characteristics the CS(indiv) shows the higher ability to discriminate between patients and healthy volunteers (p=0.004). This indicates that the individual relative Constant score gives a more accurate view about the functional result for shoulder disorders. It is expected to be more reliable for larger and incoherent patient populations, because specific interindividual differences, regarding the patient's age, gender and constitution are eliminated as well as other individual physiological parameters.",
"title": "Modification of the Constant-Murley shoulder score-introduction of the individual relative Constant score Individual shoulder assessment."
},
{
"docid": "28017005",
"text": "Assessment for selection in medicine and the health professions should follow the same quality assurance processes as in-course assessment. The literature on selection is limited and is not strongly theoretical or conceptual. For written testing, there is evidence of the predictive validity of Medical College Admission Test (MCAT) for medical school and licensing examination performance. There is also evidence for the predictive validity of grade point average, particularly in combination with MCAT for graduate entry but little evidence about the predictive validity of school leaver scores. Interviews have not been shown to be robust selection measures. Studies of multiple mini-interviews have indicated good predictive validity and reliability. Of other measures used in selection, only the growing interest in personality testing appears to warrant future work. Widening access to medical and health professional programmes is an increasing priority and relates to the social accountability mandate of medical and health professional schools. While traditional selection measures do discriminate against various population groups, there is little evidence on the effect of non-traditional measures in widening access. Preparation and outreach programmes show most promise. In summary, the areas of consensus for assessment for selection are small in number. Recommendations for future action focus on the adoption of principles of good assessment and curriculum alignment, use of multi-method programmatic approaches, development of interdisciplinary frameworks and utilisation of sophisticated measurement models. The social accountability mandate of medical and health professional schools demands that social inclusion, workforce issues and widening of access are embedded in the principles of good assessment for selection.",
"title": "Assessment for selection for the health care professions and specialty training: consensus statement and recommendations from the Ottawa 2010 Conference."
},
{
"docid": "8642784",
"text": "OBJECTIVE To assess the efficacy of various controlled ovarian hyperstimulation (COH) regimens in the prior poor-responder patient preparing for assisted reproductive techniques. DESIGN English-language literature review. PATIENT(S) Candidates for assisted reproductive techniques who had been defined as having a prior suboptimal response to standard COH regimens. INTERVENTION(S) A variety of regimes are reviewed, including increased gonadotropin doses, change of gonadotropins, adjunctive growth hormone (GH), luteal phase (long) GnRH agonist (GnRH-a) initiation, early follicular phase (flare) GnRH-a initiation, low-dose luteal phase (ultrashort) GnRH-a initiation, progestin pretreatment, and microdose flare GnRH-a initiation. MAIN OUTCOME MEASURE(S) Maximal serum E(2) levels, follicular development, dose, and duration of gonadotropin therapy, cycle cancellation rates, oocytes retrieved, embryos transferred, and clinical and ongoing pregnancy rates. RESULT(S) A lack of uniformity in definition of the poor responder and of prospective randomized trials make data interpretation somewhat difficult. Of the varied strategies proposed, those that seem to be more uniformly beneficial are microdose GnRH-a flare and late luteal phase initiation of a short course of low-dose GnRH-a discontinued before COH. CONCLUSION(S) No single regimen will benefit all poor responders. General acceptance of uniform definitions and performance of large-scale prospective randomized trials are critical. Development of a reliable precycle screen will allow effective differentiation among normal responders, poor responders, and those who will not conceive with their own oocytes.",
"title": "Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques."
},
{
"docid": "2787558",
"text": "BACKGROUND Lifestyle factors including cigarette smoking, alcohol consumption and nutritional habits impact on health, wellness, and the risk of chronic diseases. In the areas of in-vitro fertilization (IVF) and pregnancy, lifestyle factors influence oocyte production, fertilization rates, pregnancy and pregnancy loss, while chronic, low-grade oxidative stress may underlie poor outcomes for some IVF cases. METHODS Here, we review the current literature and present some original, previously unpublished data, obtained from couples attending the PIVET Medical Centre in Western Australia. RESULTS During the study, 80 % of females and 70 % of male partners completed a 1-week diary documenting their smoking, alcohol and fruit and vegetable intake. The subsequent clinical outcomes of their IVF treatment such as quantity of oocytes collected, fertilization rates, pregnancy and pregnancy loss were submitted to multiple regression analysis, in order to investigate the relationship between patients, treatment and the recorded lifestyle factors. Of significance, it was found that male smoking caused an increased risk of pregnancy loss (p = 0.029), while female smoking caused an adverse effect on ovarian reserve. Both alcohol consumption (β = 0.074, p < 0.001) and fruit and vegetable consumption (β = 0.034, p < 0.001) had positive effects on fertilization. CONCLUSION Based on our results and the current literature, there is an important impact of lifestyle factors on IVF clinical outcomes. Currently, there are conflicting results regarding other lifestyle factors such as nutritional habits and alcohol consumption, but it is apparent that chronic oxidative stress induced by lifestyle factors and poor nutritional habits associate with a lower rate of IVF success.",
"title": "The effect of cigarette smoking, alcohol consumption and fruit and vegetable consumption on IVF outcomes: a review and presentation of original data"
},
{
"docid": "42836872",
"text": "This study was undertaken to analyze genetic alterations in 108 sporadic serous ovarian neoplasms to elucidate ovarian serous carcinogenesis. Our results demonstrate that K-ras mutations occur in approximately 50% of serous borderline tumors (SBTs), non-invasive micropapillary serous carcinomas (MPSCs), and invasive micropapillary serous carcinomas, which represent a morphological continuum of tumor progression. Moreover, progressive increase in the degree of allelic imbalance of chromosomes 1p, 5q, 8p, 18q, 22q, and Xp was observed comparing serous borderline tumors to noninvasive and invasive micropapillary serous carcinomas. In contrast, high-grade (conventional serous carcinoma) tumors contained wild-type K-ras in all 23 cases studied and a high frequency of allelic imbalance even in small (early) primary tumors similar to that found in advanced stage tumors. Based on these findings, we propose a dualistic model for ovarian serous carcinogenesis. One pathway involves a stepwise progression from SBT to noninvasive and then invasive MPSC. The other pathway is characterized by rapid progression from the ovarian surface epithelium or inclusion cysts to a conventional (high-grade) serous carcinoma.",
"title": "Diverse tumorigenic pathways in ovarian serous carcinoma."
},
{
"docid": "9394119",
"text": "IMPORTANCE Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES Breast and ovarian cancer risks. RESULTS Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.",
"title": "Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer."
},
{
"docid": "3858268",
"text": "Lack of sensitive single-cell analysis tools has limited the characterization of metabolic activity in cancer stem cells. By hyperspectral-stimulated Raman scattering imaging of single living cells and mass spectrometry analysis of extracted lipids, we report here significantly increased levels of unsaturated lipids in ovarian cancer stem cells (CSCs) as compared to non-CSCs. Higher lipid unsaturation levels were also detected in CSC-enriched spheroids compared to monolayer cultures of ovarian cancer cell lines or primary cells. Inhibition of lipid desaturases effectively eliminated CSCs, suppressed sphere formation in vitro, and blocked tumor initiation capacity in vivo. Mechanistically, we demonstrate that nuclear factor κB (NF-κB) directly regulates the expression levels of lipid desaturases, and inhibition of desaturases blocks NF-κB signaling. Collectively, our findings reveal that increased lipid unsaturation is a metabolic marker for ovarian CSCs and a target for CSC-specific therapy.",
"title": "Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells."
},
{
"docid": "21377587",
"text": "BACKGROUND Patient experience is increasingly used to assess organizational performance, for example in public reporting or pay-for-performance schemes. Conventional approaches using 95% confidence intervals are commonly used to determine required survey samples or to report performance but these may result in unreliable organizational comparisons. METHODS We analyzed data from 2.2 million patients who responded to the English 2009 General Practice Patient Survey, which included 45 patient experience questions nested within 6 different care domains (access, continuity of care, communication, anticipatory care planning, out-of-hours care, and overall care satisfaction). For each question, unadjusted and case-mix adjusted (for age, sex, and ethnicity) organization-level reliability, and intraclass correlation coefficients were calculated. RESULTS Mean responses per organization ranged from 23 to 256 for questions evaluating primary care practices, and from 1454 to 2758 for questions evaluating out-of-hours care organizations. Adjusted and unadjusted reliability values were similar. Twenty-six questions had excellent reliability (≥0.90). Seven nurse communication questions had very good reliability (≥0.85), but 3 anticipatory care planning questions had lower reliability (<0.70). Reliability was typically <0.70 for questions with <100 mean responses per practice, usually indicating questions which only a subset of patients were eligible to answer. Nine questions had both excellent reliability and high intraclass correlation coefficients (≥0.10) indicating both reliable measurement and substantial performance variability. CONCLUSIONS High reliability is a necessary property of indicators used to compare health care organizations. Using the English General Practice Patient Survey as a case study, we show how reliability and intraclass correlation coefficients can be used to select measures to support robust organizational comparisons, and to design surveys that will both provide high-quality measurement and optimize survey costs.",
"title": "How can health care organizations be reliably compared?: Lessons from a national survey of patient experience."
},
{
"docid": "5145974",
"text": "STUDY QUESTION In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation? SUMMARY ANSWER Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation. WHAT IS KNOWN ALREADY Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E(2)) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development. STUDY DESIGN, SIZE AND DURATION Prospective preconception cohort study. One hundred and seventy-four women aged 18-45 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis. PARTICIPANTS/MATERIALS, SETTING AND METHODS Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) µg/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear dose-response association between increased urinary BPA concentrations and decreased number of oocytes (overall and mature), decreased number of normally fertilized oocytes and decreased E(2) levels (mean decreases of 40, 253 and 471 pg/ml for urinary BPA quartiles 2, 3 and 4, when compared with the lowest quartile, respectively; P-value for trend = 0.001). The mean number of oocytes and normally fertilized oocytes decreased by 24 and 27%, respectively, for the highest versus the lowest quartile of urinary BPA (trend test P < 0.001 and 0.002, respectively). Women with urinary BPA above the lowest quartile had decreased blastocyst formation (trend test P-value = 0.08). LIMITATIONS AND REASONS FOR CAUTION Potential limitations include exposure misclassification due to the very short half-life of BPA and its high variability over time; uncertainty about the generalizability of the results to the general population of women conceiving naturally and limited sample. WIDER IMPLICATIONS OF THE FINDINGS The results from this extended study, using IVF as a model to study early reproductive health outcomes in humans, indicate a negative dose-response association between urinary BPA concentrations and serum peak E(2) and oocyte yield, confirming our previous findings. In addition, we found significantly decreased metaphase II oocyte count and number of normally fertilizing oocytes and a suggestive association between BPA urinary concentrations and decreased blastocyst formation, thus indicating that BPA may alter reproductive function in susceptible women undergoing IVF. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. None of the authors has actual or potential competing financial interests. DISCLAIMER The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.",
"title": "Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF."
},
{
"docid": "104130",
"text": "Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial-bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the main MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population. Twist1(+/-) mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair.",
"title": "The suture provides a niche for mesenchymal stem cells of craniofacial bones"
},
{
"docid": "7548577",
"text": "In the yeast Saccharomyces cerevisiae, glycogen is accumulated as a carbohydrate reserve when cells are deprived of nutrients. Yeast mutated in SNF1, a gene encoding a protein kinase required for glucose derepression, has diminished glycogen accumulation and concomitant inactivation of glycogen synthase. Restoration of synthesis in an snf1 strain results only in transient glycogen accumulation, implying the existence of other SNF1-dependent controls of glycogen storage. A genetic screen revealed that two genes involved in autophagy, APG1 and APG13, may be regulated by SNF1. Increased autophagic activity was observed in wild-type cells entering the stationary phase, but this induction was impaired in an snf1 strain. Mutants defective for autophagy were able to synthesize glycogen upon approaching the stationary phase, but were unable to maintain their glycogen stores, because subsequent synthesis was impaired and degradation by phosphorylase, Gph1p, was enhanced. Thus, deletion of GPH1 partially reversed the loss of glycogen accumulation in autophagy mutants. Loss of the vacuolar glucosidase, SGA1, also protected glycogen stores, but only very late in the stationary phase. Gph1p and Sga1p may therefore degrade physically distinct pools of glycogen. Pho85p is a cyclin-dependent protein kinase that antagonizes SNF1 control of glycogen synthesis. Induction of autophagy in pho85 mutants entering the stationary phase was exaggerated compared to the level in wild-type cells, but was blocked in apg1 pho85 mutants. We propose that Snf1p and Pho85p are, respectively, positive and negative regulators of autophagy, probably via Apg1 and/or Apg13. Defective glycogen storage in snf1 cells can be attributed to both defective synthesis upon entry into stationary phase and impaired maintenance of glycogen levels caused by the lack of autophagy.",
"title": "Antagonistic Controls of Autophagy and Glycogen Accumulation by Snf1p, the Yeast Homolog of AMP-Activated Protein Kinase, and the Cyclin-Dependent"
},
{
"docid": "3360428",
"text": "Kras mutation is a common phenomenon in many human neoplasms. We aimed to assess the Kras mutational status along the histological continuum from normal ovaries to the development of benign, borderline and malignant ovarian mucinous neoplasms. We analyzed 41 cases of malignant, 10 cases of borderline, 7 cases of benign mucinous ovarian tumors and 7 cases of normal ovarian tissue. The prevalence of Kras mutations in the normal ovary was 0.00% (n=0/7), while the prevalence in benign, borderline and malignant mucinous neoplasms was 57.14% (n=4/7), 90.00% (n=9/10) and 75.61% (n=31/41), respectively. Multiple Kras mutations were detected in 6 cases of mucinous carcinoma, including 5 double mutations with G13D/V14I (n=1), G12V/G13S (n=1), G12D/G13S (n=3) and one triple mutation with A11V/G13N/V14I (n=1). We identified six cases with 3 novel Kras mutations not previously described in the COSMIC database, which included A11V (n=3) and V14I (n=2) in mucinous carcinomas, and A11T (n=1) in a mucinous borderline tumor. In conclusion, Kras mutation appears to be one of the imperative events in the ovarian mucinous adenoma-borderline tumor-carcinoma sequence, as increased numbers of Kras mutations have been shown to be the strongest predictor of unequivocal malignancy in ovarian mucinous neoplasms.",
"title": "Multipoint Kras oncogene mutations potentially indicate mucinous carcinoma on the entire spectrum of mucinous ovarian neoplasms"
},
{
"docid": "25628793",
"text": "Endometriosis is an estrogen-dependent disease affecting up to 10% of all premenopausal women. There is evidence that different endometriosis sites show distinct local estrogen concentration, which, in turn, might be due to a unique local estrogen metabolism. We aimed to investigate whether there was a site-specific regulation of selected enzymes responsible for the oxidative metabolism of estrogens in biopsy samples and endometrial and endometriotic stromal cells. Cytochrome P450 (CYP) 1A1 and CYP1B1 mRNA and protein expressions in deep-infiltrating (rectal, retossigmoidal, and uterossacral) lesions, superficial (ovarian and peritoneal) lesions, and eutopic and healthy (control) endometrium were evaluated by real-time PCR and western blot. Using a cross-sectional study design with 58 premenopausal women who were not under hormonal treatment, we were able to identify an overall increased CYP1A1 and CYP1B1 mRNA expression in superficial lesions compared with the healthy endometrium. CYP1A1 mRNA expression in superficial lesions was also greater than in the eutopic endometrium. Interestingly, we found a similar pattern of CYP1A1 and CYP1B1 expression in in vitro stromal cells isolated from ovarian lesions (n=3) when compared with stromal cells isolated from either rectum lesions or eutopic endometrium. In contradiction, there was an increased half-life of estradiol (measured by HPLC-MS-MS) in ovarian endometriotic stromal cells compared with paired eutopic stromal endometrial cells. Our results indicate that there is a site-dependent regulation of CYP1A1 and CYP1B1 in ovarian/peritoneal lesions and ovarian endometriotic stromal cells, whereas a slower metabolism is taking place in these cells.",
"title": "Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions."
},
{
"docid": "53211308",
"text": "BACKGROUND microRNAs (miRNAs) stably exist in circulating blood and are encapsulated in extracellular vesicles such as exosomes. The aims of this study were to identify which exosomal miRNAs are highly produced from epithelial ovarian cancer (EOC) cells, to analyze whether serum miRNA can be used to discriminate patients with EOC from healthy volunteers, and to investigate the functional role of exosomal miRNAs in ovarian cancer progression. METHODS Exosomes were collected from the culture media of serous ovarian cancer cell lines, namely TYK-nu and HeyA8 cells. An exosomal miRNA microarray revealed that several miRNAs including miR-99a-5p were specifically elevated in EOC-derived exosomes. Expression levels of serum miR-99a-5p in 62 patients with EOC, 26 patients with benign ovarian tumors, and 20 healthy volunteers were determined by miRNA quantitative reverse transcription-polymerase chain reaction. To investigate the role of exosomal miR-99a-5p in peritoneal dissemination, neighboring human peritoneal mesothelial cells (HPMCs) were treated with EOC-derived exosomes and then expression levels of miR-99a-5p were examined. Furthermore, mimics of miR-99a-5p were transfected into HPMCs and the effect of miR-99a-5p on cancer invasion was analyzed using a 3D culture model. Proteomic analysis with the tandem mass tag method was performed on HPMCs transfected with miR-99a-5p and then potential target genes of miR-99a-5p were examined. RESULTS The serum miR-99a-5p levels were significantly increased in patients with EOC, compared with those in benign tumor patients and healthy volunteers (1.7-fold and 2.8-fold, respectively). A receiver operating characteristic curve analysis showed with a cut-off of 1.41 showed sensitivity and specificity of 0.85 and 0.75, respectively, for detecting EOC (area under the curve = 0.88). Serum miR-99a-5p expression levels were significantly decreased after EOC surgeries (1.8 to 1.3, p = 0.002), indicating that miR-99a-5p reflects tumor burden. Treatment with EOC-derived exosomes significantly increased miR-99a-5p expression in HPMCs. HPMCs transfected with miR-99a-5p promoted ovarian cancer invasion and exhibited increased expression levels of fibronectin and vitronectin. CONCLUSIONS Serum miR-99a-5p is significantly elevated in ovarian cancer patients. Exosomal miR-99a-5p from EOC cells promotes cell invasion by affecting HPMCs through fibronectin and vitronectin upregulation and may serve as a target for inhibiting ovarian cancer progression.",
"title": "Exosomal miR-99a-5p is elevated in sera of ovarian cancer patients and promotes cancer cell invasion by increasing fibronectin and vitronectin expression in neighboring peritoneal mesothelial cells"
}
] |
106
|
Ambulatory blood pressure monitoring is inaccurate at diagnosing hypertension.
|
[
{
"docid": "25515907",
"text": "OBJECTIVE To determine the relative accuracy of clinic measurements and home blood pressure monitoring compared with ambulatory blood pressure monitoring as a reference standard for the diagnosis of hypertension. DESIGN Systematic review with meta-analysis with hierarchical summary receiver operating characteristic models. Methodological quality was appraised, including evidence of validation of blood pressure measurement equipment. DATA SOURCES Medline (from 1966), Embase (from 1980), Cochrane Database of Systematic Reviews, DARE, Medion, ARIF, and TRIP up to May 2010. Eligibility criteria for selecting studies Eligible studies examined diagnosis of hypertension in adults of all ages using home and/or clinic blood pressure measurement compared with those made using ambulatory monitoring that clearly defined thresholds to diagnose hypertension. RESULTS The 20 eligible studies used various thresholds for the diagnosis of hypertension, and only seven studies (clinic) and three studies (home) could be directly compared with ambulatory monitoring. Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% (95% confidence interval 60.7% to 84.8%) and 74.6% (47.9% to 90.4%), respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% (78.0% to 91.0%) and 62.4% (48.0% to 75.0%). CONCLUSIONS Neither clinic nor home measurement had sufficient sensitivity or specificity to be recommended as a single diagnostic test. If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis. Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.",
"title": "Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review"
},
{
"docid": "5151024",
"text": "BACKGROUND The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. METHODS We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies-further blood pressure measurement in the clinic, at home, and with an ambulatory monitor-in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. FINDINGS Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from -£56 [95% CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. INTERPRETATION Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. FUNDING National Institute for Health Research and the National Institute for Health and Clinical Excellence.",
"title": "Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study."
}
] |
[
{
"docid": "45447613",
"text": "OBJECTIVE Previous studies have shown increases in ambulatory short-term blood pressure (BP) variability to be related to cardiovascular disease. In this study, we examined whether an angiotensin II type 1 receptor blocker losartan would improve ambulatory short-term BP variability in hypertensive patients on hemodialysis. METHODS Forty hypertensive patients on hemodialysis therapy were randomly assigned to the losartan treatment group (n=20) or the control treatment group (n=20). At baseline and 6 and 12 months after the treatment, 24-h ambulatory BP monitoring was performed. Echocardiography and measurements of brachial-ankle pulse wave velocity (baPWV) and biochemical parameters were also performed before and after therapy. RESULTS After 6- and 12-months of treatment, nighttime short-term BP variability, assessed on the basis of the coefficient of variation of ambulatory BP, was significantly decreased in the losartan group, but remained unchanged in the control group. Compared with the control group, losartan significantly decreased left ventricular mass index (LVMI), baPWV, and the plasma levels of brain natriuretic peptide and advanced glycation end products (AGE). Furthermore, multiple regression analysis showed significant correlations between changes in LVMI and changes in nighttime short-term BP variability, as well as between changes in LVMI and changes in the plasma levels of AGE. CONCLUSION These results suggest that losartan is beneficial for the suppression of pathological cardiovascular remodeling though its inhibitory effect on ambulatory short-term BP variability during nighttime.",
"title": "Effect of losartan on ambulatory short-term blood pressure variability and cardiovascular remodeling in hypertensive patients on hemodialysis."
},
{
"docid": "54490092",
"text": "Blood pressure variability is one of the characteristic features of hypertension in the elderly. However, its clinical significance remains to be determined. We therefore examined the impact of blood pressure variability on the development of cardiovascular events in elderly hypertensive patients. A total of 106 consecutive hypertensive patients aged more than 60 years old (mean age, 73.9 +/- 8.1 years old; male, 54%), all of whom underwent 24-h ambulatory blood pressure monitoring, were followed up (median, 34 months; range, 3-60 months). During the follow-up period, 39 cardiovascular events were observed, including 14 cases of cerebral infarction and 7 cases of acute myocardial infarction. The coefficient of variation (CV) of 24-h systolic blood pressure (SBP) values was used as an index of blood pressure variability. The patients showed a mean CV value of 10.6%, and were divided into two groups according to this mean value as a cut-off point: a high CV group (n = 46) and a low CV group (n = 60). Although baseline clinical characteristics were similar in the two groups, Kaplan-Meier plots for event-free survival revealed that the rate of cardiovascular events was significantly higher in high CV group than in low CV group (p < 0.05). Cox's proportional hazards analysis showed that increased blood pressure variability (a high CV value of 24-h SBP) was an independent predictive variable for cardiovascular events. The CV value of daytime SBP and the SD value of both 24-h SBP and daytime SBP also had positive correlations with the onset of cardiovascular events. These results suggest that increased blood pressure variability may be an independent risk factor for cardiovascular events in elderly hypertensive patients.",
"title": "Impact of blood pressure variability on cardiovascular events in elderly patients with hypertension."
},
{
"docid": "44030361",
"text": "Accumulated evidence suggests that an altered ambulatory blood pressure (BP) profile, particularly elevated nighttime BP, reflects target organ injury and is a better predictor of further cardiorenal risk than the clinic BP or daytime BP in hypertensive patients complicated by chronic kidney disease (CKD). In this study, we examined the beneficial effects of olmesartan, an angiotensin II type 1 receptor blocker (ARB), on ambulatory BP profiles and renal function in hypertensive CKD patients. Forty-six patients were randomly assigned to the olmesartan add-on group (n=23) or the non-ARB group (n=23). At baseline and after the 16-week treatment period, ambulatory BP monitoring was performed and renal function parameter measurements were collected. Although the baseline clinic BP levels and the after-treatment/baseline (A/B) ratios of clinic BP levels were similar in the olmesartan add-on and non-ARB groups, the A/B ratios of ambulatory 24-h and nighttime BP levels in the olmesartan add-on group were significantly lower. Furthermore, the A/B ratios of urinary protein, albumin and type IV collagen excretion in the olmesartan add-on group were significantly lower than those in the non-ARB group (urinary protein excretion, 0.72±0.41 vs. 1.45±1.48, P=0.030; urinary albumin excretion, 0.73±0.37 vs. 1.50±1.37, P=0.005; urinary type IV collagen excretion, 0.87±0.42 vs. 1.48±0.87, P=0.014) despite comparable A/B ratios for the estimated glomerular filtration rate in the two groups. These results indicate that in hypertensive patients with CKD, olmesartan add-on therapy improves the ambulatory BP profile via a preferential reduction in nighttime BP with concomitant renal injury inhibition.",
"title": "The angiotensin II type 1 receptor blocker olmesartan preferentially improves nocturnal hypertension and proteinuria in chronic kidney disease"
},
{
"docid": "8318922",
"text": "Strict blood pressure (BP) control is reportedly important for the management of hypertensive patients with chronic kidney disease (CKD). The purpose of this cross-sectional study was to examine whether the variables of ambulatory BP and the heart rate (HR) profile, central hemodynamics, and arterial stiffness were closely related to the renal function parameters (urine albumin excretion rate [UACR] and estimated glomerular filtration rate [eGFR]) observed in 25 consecutive hospitalized hypertensive patients with CKD. There were significant positive relationships between UACR and 24-hour, daytime, and nighttime ambulatory systolic BP. In addition, there were significant negative relationships between UACR and 24-hour and daytime HR variability. The circulating B-type natriuretic peptide level and hemoglobin A1c were also positively related to UACR. With respect to eGFR, although the 24-hour and nighttime HR variability were positively associated with eGFR, the circulating pentosidine and nighttime HR had a negative relationship with eGFR. On the other hand, central hemodynamics and arterial stiffness did not exhibit any significant association with renal function parameters. These results indicate that ambulatory BP and the HR profile are closely modulated by renal function deterioration. Further studies are needed to investigate the causal relationship between ambulatory BP and the HR profile and renal function parameters in hypertensive patients with CKD.",
"title": "Relationship of ambulatory blood pressure and the heart rate profile with renal function parameters in hypertensive patients with chronic kidney disease."
},
{
"docid": "22730024",
"text": "OBJECTIVE To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European). METHODS After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks. RESULTS In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [-2.8 (-4.9, -0.8) mmHg], whereas ramipril did not [+1.5 (-0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]. CONCLUSIONS Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intake.",
"title": "Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies."
},
{
"docid": "25974070",
"text": "The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.",
"title": "Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function."
},
{
"docid": "30639847",
"text": "CONTEXT Vascular stiffness increases with advancing age and is a major risk factor for age-related morbidity and mortality. Vascular stiffness and blood pressure pulsatility are related; however, temporal relationships between vascular stiffening and blood pressure elevation have not been fully delineated. OBJECTIVE To examine temporal relationships among vascular stiffness, central hemodynamics, microvascular function, and blood pressure progression. DESIGN, SETTING, AND PARTICIPANTS Longitudinal community-based cohort study conducted in Framingham, Massachusetts. The present investigation is based on the 2 latest examination cycles (cycle 7: 1998-2001; cycle 8: 2005-2008 [last visit: January 25, 2008]) of the Framingham Offspring study (recruited: 1971-1975). Temporal relationships among blood pressure and 3 measures of vascular stiffness and pressure pulsatility derived from arterial tonometry (carotid-femoral pulse wave velocity [CFPWV], forward wave amplitude [FWA], and augmentation index) were examined over a 7-year period in 1759 participants (mean [SD] age: 60 [9] years; 974 women). MAIN OUTCOME MEASURES The primary outcomes were blood pressure and incident hypertension during examination cycle 8. The secondary outcomes were CFPWV, FWA, and augmentation index during examination cycle 8. RESULTS In a multivariable-adjusted regression model, higher FWA (β, 1.3 [95% CI, 0.5-2.1] mm Hg per 1 SD; P = .002) and higher CFPWV (β, 1.5 [95% CI, 0.5-2.6] mm Hg per 1 SD; P = .006) during examination cycle 7 were jointly associated with systolic blood pressure during examination cycle 8. Similarly, in a model that included systolic and diastolic blood pressure and additional risk factors during examination cycle 7, higher FWA (odds ratio [OR], 1.6 [95% CI, 1.3-2.0] per 1 SD; P < .001), augmentation index (OR, 1.7 [95% CI, 1.4-2.0] per 1 SD; P < .001), and CFPWV (OR, 1.3 [95% CI, 1.0-1.6] per 1 SD; P = .04) were associated with incident hypertension during examination cycle 8 (338 cases [32%] in 1048 participants without hypertension during examination cycle 7). Conversely, blood pressure during examination cycle 7 was not associated with CFPWV during examination cycle 8. Higher resting brachial artery flow (OR, 1.23 [95% CI, 1.04-1.46]) and lower flow-mediated dilation (OR, 0.80 [95% CI, 0.67-0.96]) during examination cycle 7 were associated with incident hypertension (in models that included blood pressure and tonometry measures collected during examination cycle 7). CONCLUSION In this cohort, higher aortic stiffness, FWA, and augmentation index were associated with higher risk of incident hypertension; however, initial blood pressure was not independently associated with risk of progressive aortic stiffening.",
"title": "Aortic stiffness, blood pressure progression, and incident hypertension."
},
{
"docid": "11071351",
"text": "The National High Blood Pressure Education Program Coordinating Committee published its first statement on the primary prevention of hypertension in 1993. This article updates the 1993 report, using new and further evidence from the scientific literature. Current recommendations for primary prevention of hypertension involve a population-based approach and an intensive targeted strategy focused on individuals at high risk for hypertension. These 2 strategies are complementary and emphasize 6 approaches with proven efficacy for prevention of hypertension: engage in moderate physical activity; maintain normal body weight; limit alcohol consumption; reduce sodium intake; maintain adequate intake of potassium; and consume a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat. Applying these approaches to the general population as a component of public health and clinical practice can help prevent blood pressure from increasing and can help decrease elevated blood pressure levels for those with high normal blood pressure or hypertension.",
"title": "Primary prevention of hypertension: clinical and public health advisory from The National High Blood Pressure Education Program."
},
{
"docid": "12206390",
"text": "CONTEXT The long-term risk for developing hypertension is best described by the lifetime risk statistic. The lifetime risk for hypertension and trends in this risk over time are unknown. OBJECTIVES To estimate the residual lifetime risk for hypertension in older US adults and to evaluate temporal trends in this risk. DESIGN, SETTING, AND PARTICIPANTS Community-based prospective cohort study of 1298 participants from the Framingham Heart Study who were aged 55 to 65 years and free of hypertension at baseline (1976-1998). MAIN OUTCOME MEASURES Residual lifetime risk (lifetime cumulative incidence not adjusted for competing causes of mortality) for hypertension, defined as blood pressure of 140/90 mm Hg or greater or use of antihypertensive medications. RESULTS The residual lifetime risks for developing hypertension and stage 1 high blood pressure or higher (greater-than-or-equal to 140/90 mm Hg regardless of treatment) were 90% in both 55- and 65-year-old participants. The lifetime probability of receiving antihypertensive medication was 60%. The risk for hypertension remained unchanged for women, but it was approximately 60% higher for men in the contemporary 1976-1998 period compared with an earlier 1952-1975 period. In contrast, the residual lifetime risk for stage 2 high blood pressure or higher (greater-than-or-equal to 160/100 mm Hg regardless of treatment) was considerably lower in both sexes in the recent period (35%-57% in 1952-1975 vs 35%-44% in 1976-1998), likely due to a marked increase in treatment of individuals with substantially elevated blood pressure. CONCLUSION The residual lifetime risk for hypertension for middle-aged and elderly individuals is 90%, indicating a huge public health burden. Although the decline in lifetime risk for stage 2 high blood pressure or higher represents a major achievement, efforts should be directed at the primary prevention of hypertension.",
"title": "Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study."
},
{
"docid": "12451492",
"text": "OBJECTIVE One of the theories involved in the pathogenesis of pregnancy induced hypertension involves salt and water retention. We aimed to measure the proenzyme convertase corin, responsible for pro-atrial natriuretic peptide (ANP) cleavage to active ANP, in plasma of hypertensive pregnant females. STUDY DESIGN Sixty pregnant females suffering from pregnancy induced hypertension in second and third trimesters of pregnancy were compared to twenty eight healthy pregnant females of the same gestational period. Concomitant urine and plasma samples were collected for the determination of some biochemical parameters. Plasma soluble corin and N-terminal (NT) pro-ANP (1-98) values were determined in both groups using enzyme immunoassays. RESULTS Plasma soluble corin mean value was significantly higher in the patient group compared to the control group. Upon dividing the patient group according to blood pressure, plasma NT pro-ANP showed significantly higher mean value in the group with blood pressure⩾140/90mmHg compared to the group with blood pressure<140/90mmHg and control group. CONCLUSIONS High plasma soluble corin and NT pro-ANP values in hypertensive pregnant females particularly those with blood pressure⩾140/90mmHg speculates an ANP receptor/ post receptor signaling defect, which would aggravate the pregnancy induced hypertensive state.",
"title": "Plasma soluble corin and N-terminal pro-atrial natriuretic peptide levels in pregnancy induced hypertension."
},
{
"docid": "39368721",
"text": "OBJECTIVE to investigate the role of glucose tolerance in the development of hypertension. DESIGN Retrospective analysis of the results of a health check up in a group of clinically healthy middle aged men in the late 1960s (median year 1968). The subjects were invited to enter into a primary prevention trial for cardiovascular disease in 1974, when they underwent clinical examination for risk factors. The trial was completed in 1979, when the men were re-examined. Follow up was in 1986. SETTING Institute of Occupational Health, Helsinki, Finland and second department of medicine, University of Helsinki. SUBJECTS In all, 3490 men born during 1919-34 participated in a health check up in the late 1960s. In 1974, 1815 of these men who were clinically healthy were entered into a primary prevention trial for cardiovascular disease. On clinical examination 1222 of the men were considered at high risk of cardiovascular disease. Of these, 612 received an intervention and were excluded from the study. A total of 593 men were without risk factors. The study comprised all of the men who did not have an intervention (n = 1203). In 1979, 1120 men were re-examined, and in 1986 945 men attended follow up. There were two groups for analysis: one comprising all subjects and the other comprising only men who were normotensive in 1968 and for whom complete information was available. INTERVENTIONS By 1979, 103 men were taking antihypertensive drugs, and by 1986, 131 were taking antihypertensive drugs and 12 were taking drugs for hyperglycaemia. MAIN OUTCOME MEASURES Blood glucose concentration one hour after a glucose load, blood pressure, and body weight were measured in 1968, 1974, and 1979. In 1986 blood pressure and body weight were recorded. RESULTS Men who were hypertensive in 1986 had significantly higher blood pressures (p less than 0.0001) and (after adjustment for body mass index and alcohol intake) significantly higher blood glucose concentrations one hour after a glucose load at all examinations than those who were normotensive in 1986. Regression analysis showed that the higher the blood glucose concentration after a glucose load in 1968 the higher the blood pressure during the following years. Those men between the second and third tertiles of blood glucose concentration in 1968 had a significantly higher risk of developing hypertension (odds ratio 1.71, 95% confidence interval 1.05 to 2.77) compared with those below the first tertile. CONCLUSION In this study men who developed hypertension tended to have shown an increased intolerance to glucose up to 18 years before the clinical manifestation of their disorder. Blood glucose concentration one hour after a glucose load was an independent predictor of future hypertension.",
"title": "Glucose tolerance and blood pressure: long term follow up in middle aged men."
},
{
"docid": "4506414",
"text": "BACKGROUND The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. METHODS We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. FINDINGS During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. INTERPRETATION The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. FUNDING Medical Research Council, National Institute for Health Research, and Wellcome Trust.",
"title": "Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people"
},
{
"docid": "3067015",
"text": "BACKGROUND Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour. METHODS AND FINDINGS We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66-3.55, p = 4.8 x 10(-6)) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17-2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39-9.49, p = 1.1 x 10(-12)) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18-6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes. CONCLUSIONS These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.",
"title": "Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach"
},
{
"docid": "31889025",
"text": "OBJECTIVES - To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. DESIGN - Inception cohort study. SETTING - General community. PARTICIPANTS - Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. EXPOSURE MEASURES - Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations. OUTCOME MEASURE - The development of CHF. RESULTS - A total of 5143 eligible subjects contributed 72422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years. CONCLUSIONS - Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality.",
"title": "The progression from hypertension to congestive heart failure."
},
{
"docid": "44660616",
"text": "OBJECTIVE To determine the prevalence of hypertension and pre-hypertension on the basis of the 2004 National High Blood Pressure Education Program Working Group guidelines in an adolescent school-screening population. STUDY DESIGN Cross-sectional assessment of blood pressure (BP) in 6790 adolescents (11-17 years) in Houston schools was conducted from 2003 to 2005. Initial measurements included height, weight, and 4 oscillometric BP readings. Repeat measurements were obtained on 2 subsequent occasions in students with persistently elevated BP. Final prevalence was adjusted for loss to follow-up and logistic regression used to assess risk factors. RESULTS BP distribution at initial screen was 81.1% normal, 9.5% pre-hypertension, and 9.4% hypertension (8.4% Stage 1; 1% Stage 2). Prevalence after 3 screenings was 81.1% normal, 15.7% pre-hypertension, and 3.2% hypertension (2.6% Stage 1; 0.6% Stage 2). Hypertension and pre-hypertension increased with increasing body mass index. Sex, race, and classification as either at-risk for overweight or overweight were independently associated with pre-hypertension. Only classification as overweight was associated with hypertension. CONCLUSIONS Application of new classification guidelines for adolescents with elevated BP reveals approximately 20% are at risk for hypertension. Further research determining the significance of each BP category and refining definitions to account for BP variability is warranted.",
"title": "Prevalence of hypertension and pre-hypertension among adolescents."
},
{
"docid": "15041758",
"text": "OBJECTIVE To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life. DESIGN A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people SETTING Fourteen primary care clinics in Seattle, Washington. PARTICIPANTS Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of ≥ 10. INTERVENTION A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a \"treat to target\" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression. The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia. MAIN OUTCOME MEASURES Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance). RESULTS Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%). Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group. There was a trend toward greater improvement in disabilities in activities of daily living (-1.5, -3.3 to 0.4; P = 0.10). CONCLUSIONS Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life. Trial registration Clinical Trials NCT00468676.",
"title": "Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial"
},
{
"docid": "5323845",
"text": "BACKGROUND Direct recordings from peripheral sympathetic nerves have shown an increased sympathetic drive in pregnancy-induced hypertension (PIH) and preeclampsia (PE). It is unknown whether sympathetic drive is altered in normal pregnancy, when arterial blood pressure can be normal or relatively low. The aim of this study was to measure and compare peripheral sympathetic discharge, its vasoconstrictor effect and its baroreceptor control, during pregnancy and postpartum in women with normal pregnancy (NP) and PIH and in normotensive nonpregnant (NN) women. METHODS AND RESULTS Twenty-one women with NP, 18 women with PIH, and 21 NN women had muscle sympathetic nerve activity assessed from multiunit discharges (MSNA) and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in NP (38+/-6.6 impulses/100 beats) was greater (P<0.05) than in NN women (19+/-1.8 impulses/100 beats) despite similar age and body weight but less than in PIH women (P<0.001) (146+/-23.5 impulses/100 beats). MSNA followed a similar trend. Cardiac baroreceptor reflex sensitivity (BRS) was impaired in NP and PIH women relative to NN. After delivery, sympathetic activity decreased to values similar to those obtained in NN, and there was an increase in BRS. In women with NP, the decrease in sympathetic output occurred despite an insignificant change in blood pressure. CONCLUSIONS Central sympathetic output was increased in women with normal pregnancy and was even greater in the hypertensive pregnant group. The findings suggest that the moderate sympathetic hyperactivity during the latter months of normal pregnancy may help to return the arterial pressure to nonpregnant levels, although when the increase in activity is excessive, hypertension may ensue.",
"title": "Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans."
},
{
"docid": "24998764",
"text": "Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure: 151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312; P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001), mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper-limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.",
"title": "Relation between renal function within the normal range and central and peripheral arterial stiffness in hypertension."
},
{
"docid": "26710772",
"text": "Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.",
"title": "Sympathetic activation during early pregnancy in humans."
},
{
"docid": "10072941",
"text": "Epidemiological studies demonstrate that a lower blood pressure and decline in blood pressure over months or years are associated with higher mortality in dialysis patients. In contrast, randomized, controlled trials lack power to establish benefits of antihypertensive therapy. Patients on long-term dialysis participating in randomized, controlled trials and receiving antihypertensive drug therapy were the subject of this meta-analysis. Outcomes assessed were the hazard ratio of cardiovascular events and all-cause mortality in treated group compared with controls. Among 1202 patients who we identified in 5 studies, the overall benefit of antihypertensive therapy compared with the control or placebo group had a combined hazard ratio for cardiovascular events of 0.69 (95% CI: 0.56 to 0.84) using a fixed-effects model and 0.62 (95% CI: 0.45 to 0.86) using a random-effects model. In a sensitivity analysis, we found that the hypertensive group had a pooled hazard ratio of 0.49 (95% CI: 0.35 to 0.67), but when normotensives were included in the trial, lesser cardiovascular protection was seen (pooled hazard ratio of 0.86 [95% CI: 0.67 to 1.12]). Test for heterogeneity between hypertensive and \"normotensive-included\" groups was significant (P<0.006). Similar results were seen for risk ratio for death and cardiovascular events. There was evidence of publication bias based on Egger's test and funnel plot. Randomized trials suggested a benefit of antihypertensive therapy among hemodialysis patients. Adequately powered randomized trials are required to confirm these observations, especially among those with hypertension.",
"title": "Cardiovascular protection with antihypertensive drugs in dialysis patients: systematic review and meta-analysis."
},
{
"docid": "2522977",
"text": "The main purpose in hypertension treatment is the reduction of cardiovascular disease burden. Among different first-line antihypertensive drug classes, angiotensin-receptor blockers are characterized by their both good effectiveness and tolerability. Furthermore, the interruption of the renin-angiotensin cascade is related with several benefits in target organ protection and cardiovascular prevention. Among different angiotensin-receptor blockers, olmesartan has been examined in several trial of organ protection, showing improvements in several disease markers, such as microinflammation, regression of both plaque volume and vascular hypertrophy, as well as microalbuminuria prevention. Olmesartan has been also widely examined in combination of either hydrochlorothiazide or amlodipine, as well as with both drugs in a single-pill triple combination, showing improvements in antihypertensive efficacy without significant effects on tolerability. This treatment strategy based on a drug with such characteristics and the availability of different types of combinations with other first-line drug classes may represent an effective way for achieving blood pressure control in a majority of hypertensive patients and this could also be related with a better cardiovascular disease prevention.",
"title": "Olmesartan-based therapies: an effective way to improve blood pressure control and cardiovascular protection."
},
{
"docid": "3801693",
"text": "BACKGROUND Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine. There is growing evidence that TGF-β1 is involved in the pathogenesis of hypertension and the development of target organ damage in hypertensives. Although several studies have shown that TGF-β1 induced vascular hypertrophy and remodelling in various vascular diseases, there are no longitudinal data on hypertension in the epidemiological studies. The present study tested the hypothesis whether elevated TGF-β1 levels can predict the development of hypertension. METHODS In 2002-2004, 528 subjects received health examinations in Uku town, southwestern Japan. We examined blood pressure (BP), body mass index, and blood test. Data on fasting plasma TGF-β1 were obtained from 528 individuals. Of these, 149 normotensives (BP <140/90 mm Hg without antihypertensive medications) at baseline were followed-up for 14 years. RESULTS The receiver-operating characteristic curve was used and the calculated cutoff value was 8.9 ng/ml. Of 149 normotensives at baseline, 59 subjects developed hypertension. Plasma TGF-β1 levels were significantly associated with the development of hypertension after adjustment for confounding factors. To further examine the association between them, we performed logistic regression analysis. We divided the baseline plasma TGF-β1 levels into 2 groups using a cutoff value. The significant high odds ratio [3.582 (95% confidence interval, 1.025-12.525)] for the development of hypertension was found in the highest group of TGF-β1 level vs. the lowest group after adjustment for confounders. CONCLUSIONS This is the first report demonstrating the causal relationship between them. Elevated plasma TGF-β1 levels predicted the development of hypertension in normotensives in a population of community-dwelling Japanese.",
"title": "Elevated Plasma Transforming Growth Factor &bgr;1 Levels Predict the Development of Hypertension in Normotensives: The 14-Year Follow-Up Study"
},
{
"docid": "46328296",
"text": "Patients with essential hypertension exhibit blunted endothelium-dependent vasodilator responses, which may be largely attributable to reduced bioactivity of nitric oxide (NO). Therefore, we measured the end product of NO, nitrate plus nitrite (nitrogen oxide), and examined the relationship between the degree of hypertension and plasma nitrate plus nitrite levels in patients with essential hypertension. The combined plasma concentration of nitrate plus nitrite, end products of NO metabolism, was reduced in individuals with essential hypertension relative to that in control subjects (15.7+/-1.1 versus 22.8+/-1.4 mmol x L(-1), P<.001); individuals with borderline hypertension showed values that were intermediate between those of the other two groups (18.2+/-1.2 mmol x L(-1), P<.001). The plasma nitrogen oxide concentration showed significant inverse correlations with both systolic and diastolic blood pressures. The basal concentration of nitrogen oxide in the plasma was reduced, at least in the peripheral circulation, in individuals with essential hypertension.",
"title": "Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension."
},
{
"docid": "43557480",
"text": "The aim of this study was the long-term retrospective analysis of chronic kidney disease (CKD) progression in children, especially with regard to the presence of hypertension (HTN). The average rate of progression of CKD was higher in patients with HTN than without HTN. Hypertension treatment requires multidrug schemes which need to be intensified with extended time of CKD duration.",
"title": "Arterial hypertension and progression of chronic kidney disease in children during 10-year ambulatory observation."
},
{
"docid": "25562234",
"text": "BACKGROUND Corin has been suggested to be associated with hypertension by cell- and animal-based studies. However, the association still lacks population-based evidence which critically promotes translation from basic research to clinical and preventive practice. Here, we aimed to explore the association in a general population of China. METHODS From January to May 2010, we conducted a cross-sectional study in 2,498 participants aged above 30 years, residing in Gusu district of Suzhou. Serum soluble corin and blood pressure were measured. RESULTS Hypertensive participants had a higher level of serum corin than nonhypertensive participants (median (interquartile range): 1,836.83 (1,497.85-2,327.87) pg/ml vs. 1,579.14 (1,322.18-1,956.82) pg/ml, P < 0.001). Higher serum corin was positively associated with prevalent hypertension (odds ratio (OR) = 2.01, P < 0.001). In the multiple analysis, participants in the third (OR = 1.43, P = 0.007) and fourth (OR = 1.96, P < 0.001) quartiles had significantly increased odds of hypertension compared to those in the lowest quartile of serum corin. ORs of hypertension positively and significantly increased with serum corin levels (P for trend <0.001). Further subgroup analysis showed that ORs of hypertension associated with high corin (over the median level of serum corin: 1,689.20 pg/ml) were still significant in subgroups by age, body mass index, total cholesterol, low-density lipoprotein cholesterol, and fasting plasma glucose (all P < 0.05). CONCLUSIONS Our study showed that hypertensive participants had an increased serum corin level compared to those without hypertension. This finding suggests that corin may play a role in the pathology of hypertension.",
"title": "Association Between High Serum Soluble Corin and Hypertension: A Cross-Sectional Study in a General Population of China."
},
{
"docid": "8596837",
"text": "Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response. Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA). The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06). Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.",
"title": "Sympathetic neural and cardiovascular responses during static handgrip exercise in women with a history of hypertensive pregnancy"
},
{
"docid": "3825750",
"text": "BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. We evaluated the renoprotective effects of dual blockade of the renin-angiotensin-aldosterone system by adding treatment with aliskiren, an oral direct renin inhibitor, to treatment with the maximal recommended dose of losartan (100 mg daily) and optimal antihypertensive therapy in patients who had hypertension and type 2 diabetes with nephropathy. METHODS We enrolled 599 patients in this multinational, randomized, double-blind study. After a 3-month, open-label, run-in period during which patients received 100 mg of losartan daily, patients were randomly assigned to receive 6 months of treatment with aliskiren (150 mg daily for 3 months, followed by an increase in dosage to 300 mg daily for another 3 months) or placebo, in addition to losartan. The primary outcome was a reduction in the ratio of albumin to creatinine, as measured in an early-morning urine sample, at 6 months. RESULTS The baseline characteristics of the two groups were similar. Treatment with 300 mg of aliskiren daily, as compared with placebo, reduced the mean urinary albumin-to-creatinine ratio by 20% (95% confidence interval, 9 to 30; P<0.001), with a reduction of 50% or more in 24.7% of the patients who received aliskiren as compared with 12.5% of those who received placebo (P<0.001). A small difference in blood pressure was seen between the treatment groups by the end of the study period (systolic, 2 mm Hg lower [P=0.07] and diastolic, 1 mm Hg lower [P=0.08] in the aliskiren group). The total numbers of adverse and serious adverse events were similar in the groups. CONCLUSIONS Aliskiren may have renoprotective effects that are independent of its blood-pressure-lowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment. (ClinicalTrials.gov number, NCT00097955 [ClinicalTrials.gov].).",
"title": "Aliskiren combined with losartan in type 2 diabetes and nephropathy."
},
{
"docid": "21616324",
"text": "BACKGROUND Control of blood pressure (BP) following renal transplantation may improve allograft and patient survival. Our aims were (i) to describe the distribution of BP and the prevalence of systolic and/or diastolic hypertension in children over the first 5 years following renal transplantation and (ii) to evaluate clinical risk factors and centre-specific factors associated with hypertension in this population. METHODS We conducted a retrospective case note review of all current paediatric kidney transplant patients in the UK, with data collected at 6 months, 1, 2 and 5 years following transplantation in subjects with hypertension (systolic and/or diastolic BP > 95th > ) and non-hypertensive subjects BP ≤ 95th > . RESULTS In total, 27.3% (117/428), 27.6% (118/428), 26.0% (95/365) and 25.6% (50/195) of the patients were hypertensive (systolic and/or diastolic BP > 95th > ) at 6 months, 1, 2 and 5 years following transplantation, respectively. A total of 58.4% of the patients at 6 months, 52.8% at 1 year, 48.2% at 2 years and 48.2% at 5 years were receiving anti-hypertensive therapy, of whom 31.6-36.6% remained hypertensive. When subjects were identified as being hypertensive, on anti-hypertensive medication or had untreated hypertension (systolic and/or diastolic BP > 95th > ), 66.4, 61.0, 56.4 and 55.9% of patients were hypertensive at 6 months, 1, 2 and 5 years, respectively. In a multivariate model, odds ratios for systolic hypertension were 4.16 (deceased versus living donor), 2.65 (lowest versus highest quartile of height z-score) and 2.07 (if on anti-hypertensive; yes versus no). There was significant variation in prevalent rates of hypertension between centres (P < 0.0001) that remained significant (P = 0.003) after adjustment for all the factors in the multivariate model. CONCLUSIONS Control of BP after kidney transplantation remains sub-optimal in paediatric centres in the UK. Just over 25% of patients remain hypertensive 5 years following transplantation. Significant differences between centres remain unexplained and may reflect differences in assessment and management of hypertension.",
"title": "Systemic arterial hypertension in children following renal transplantation: prevalence and risk factors."
},
{
"docid": "6157837",
"text": "Angiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs. Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies. Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of “functional renal insufficiency” and/or hyperkalemia. This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects. ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent. Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures. The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient. Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor–induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion. Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs.1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system. When renal perfusion pressure falls (as in …",
"title": "Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association."
},
{
"docid": "44586415",
"text": "QUESTION Do clinical tests accurately diagnose rotator cuff pathology? DESIGN A systematic review of investigations into the diagnostic accuracy of clinical tests for rotator cuff pathology. PARTICIPANTS People with shoulder pain who underwent clinical testing in order to diagnose rotator cuff pathology. OUTCOME MEASURES The diagnostic accuracy of clinical tests was determined using likelihood ratios. RESULTS Thirteen studies met the inclusion criteria. The 13 studies evaluated 14 clinical tests in 89 separate evaluations of diagnostic accuracy. Only one evaluation, palpation for supraspinatus ruptures, resulted in significant positive and negative likelihood ratios. Eight of the 89 evaluations resulted in either significant positive or negative likelihood ratios. However, none of these eight positive or negative likelihood ratios were found in other studies. Of the 89 evaluations of clinical tests 71 (80%) did not result in either significant positive or negative likelihood ratio evaluations across different studies. CONCLUSION Overall, most tests for rotator cuff pathology were inaccurate and cannot be recommended for clinical use. At best, suspicion of a rotator cuff tear may be heightened by a positive palpation, combined Hawkins/painful arc/infraspinatus test, Napoleon test, lift-off test, belly-press test, or drop-arm test, and it may be reduced by a negative palpation, empty can test or Hawkins-Kennedy test.",
"title": "Most clinical tests cannot accurately diagnose rotator cuff pathology: a systematic review."
}
] |
5adfc6e8554299603e4183aa
|
What do Kino and Porcupine Tree have in common?
|
[
{
"docid": "364934",
"text": "Porcupine Tree were an English rock band formed by musician Steven Wilson in 1987. The band began essentially as a solo project for Wilson, who created all of the band's music. However, by 1993, Wilson desired to work in a band environment, and so brought on frequent collaborators Richard Barbieri on keyboards, Colin Edwin on bass and Chris Maitland on drums as permanent band members. With Wilson still in charge of guitar and lead vocals, this would remain the lineup until 2001, when the band recruited Gavin Harrison to replace Maitland on drums.",
"title": ""
},
{
"docid": "4725294",
"text": "Kino was a British neo-progressive rock band made up of members from other progressive rock acts (John Mitchell from Arena and The Urbane; Pete Trewavas from Marillion and Transatlantic; John Beck from It Bites; Bob Dalton also from It Bites; Chris Maitland formerly of Porcupine Tree).",
"title": ""
}
] |
[
{
"docid": "18993575",
"text": "Kino is the name of the plant gum produced by various plants and trees, particularly \"Eucalyptus\", in reaction to mechanical damage, and which can be tapped by incisions made in the trunk or stalk. Its red colour, together with the tendency of some species to ooze large amounts of it from wounds, is the source of the common names \"red gum\" and \"bloodwood\". The word “kino” is of West African origin.",
"title": ""
},
{
"docid": "37872706",
"text": "At The Pier is an EP by the progressive rock band Nosound, released on Kscope. The initial release was limited to 2000 copies distributed as a Digipack that included a Nosound guitar pick/plectrum that was in a stamped brown envelope. It features a new lineup of members to include drummer Chris Maitland (Porcupine Tree, No-Man, Blackfield,|Kino, and I.E.M.) and Marco Berni on Keyboards. Marianne DeChastelaine is also featured on Cello in tracks 1 and 3.",
"title": ""
},
{
"docid": "10107435",
"text": "Tarquin's Seaweed Farm, subtitled \"Words from a Hessian Sack\", is the first album to be released by Steven Wilson under the name \"Porcupine Tree\". It was originally a compiled cassette of experimental music made by Steven Wilson for his joke band he formed with his friend Malcom Stocks. The cassette was only sent out to a few people, but was enough to give the band a bit of fame in the UK underground music scene of the time, being picked up by the underground magazine Freakbeat. It was later released under Delerium Records in 1991 in a limited edition of 300 copies. Eventually, the tracks from this and the later Porcupine Tree album \"The Nostalgia Factory\" were compiled into what are considered Porcupine Tree's first true studio albums, \"On the Sunday of Life\" and \"Yellow Hedgerow Dreamscape\".",
"title": ""
},
{
"docid": "8554400",
"text": "What do the estates of film stars Vincent Price and Glenn Ford have in common? And what do each of these estates have in common with valuables owned by Laugh-In’s Arte Johnson, Partridge Family Mom Shirley Jones, and Room 222 star Karen Valentine, along with many other Hollywood stars?",
"title": ""
},
{
"docid": "2902373",
"text": "The prehensile-tailed porcupines or coendous (genus \"Coendou\") are found in Central and South America. Two other formerly recognized Neotropical tree porcupine genera, \"Echinoprocta\" and \"Sphiggurus\", have been subsumed into \"Coendou\", since \"Sphiggurus\" was shown by genetic studies to be polyphyletic, while \"Echinoprocta\" nested within \"Coendou\".",
"title": ""
},
{
"docid": "27748997",
"text": "A tree spade is a specialized machine that mechanizes the transplanting of large plants whose hand-powered transplanting (using [traditional] spades, wagons, and other equipment) would be prohibitively laborious. These include large bushes and small or medium trees. By bringing mechanized power to what was formerly only a manual process, tree spades do for transplanting what tractors and combine harvesters do for agriculture, and what excavators and other heavy equipment do for construction. Today, tree spades are widely used in the tree nursery industry to increase production rates, and in the landscaping industry for tree removal and transplanting.",
"title": ""
},
{
"docid": "8616385",
"text": "The Third Ending are an Australian progressive rock band, based in Tasmania. Their style incorporates common progressive rock/metal elements: technical proficiency, skilled songwriting, and epic, lyrical songs. The band have cited Pink Floyd, Dream Theater and Porcupine Tree as some of their strongest influences, and reviewers have likened them to Spock's Beard and Neal Morse's solo work.",
"title": ""
},
{
"docid": "11427378",
"text": "\"Sentimental\" is a Porcupine Tree song. It appears as the fourth track on the 2007 album \"Fear of a Blank Planet\".",
"title": ""
},
{
"docid": "26458969",
"text": "Anesthetize is the second live DVD by progressive rock band Porcupine Tree, released on 20 May 2010. The Blu-ray edition was released on 15 June. It is filmed in high definition and taken from two concerts given by Porcupine Tree at Tilburg, Netherlands on 15 and 16 October, at the end of the \"Fear of a Blank Planet\" tour in 2008. The film is directed and edited by Lasse Hoile and the audio track is mixed in stereo and 5.1 Surround by Steven Wilson.",
"title": ""
},
{
"docid": "9915954",
"text": "The following is a listing of officially released works by the English band Porcupine Tree. The band has released ten major studio albums, as well as many EPs, limited editions, and revamped material.",
"title": ""
},
{
"docid": "9433146",
"text": "Transmission IV is the fourth and final Transmission information service release (only available to subscribers) by British progressive rock band Porcupine Tree. It contains a complete improvisation of what would become the song \"Moonloop\", included on the 1995 release \"The Sky Moves Sideways\".",
"title": ""
},
{
"docid": "14307476",
"text": "The Nostalgia Factory, subtitled \"...and other tips for amateur golfers\", is the second album to be released by Steven Wilson under the name 'Porcupine Tree'. It was the second full-length cassette produced for his 'joke' project with friend Malcom Stocks. The album was issued by Delerium in 1991 (despite the Porcupine Tree website stating 1990) in a limited edition of 300 copies. Like its predecessor, the tracks from \"The Nostalgia Factory\" were subsequently released in the band's first studio album \"On the Sunday of Life\", and the compilation album \"Yellow Hedgerow Dreamscape\". Some tracks have been renamed and/or rearranged in later albums and performances.",
"title": ""
},
{
"docid": "12529266",
"text": "The Mexican hairy dwarf porcupine or Mexican tree porcupine (\"Coendou mexicanus\") is a species of rodent in the family Erethizontidae. It is found in Costa Rica, El Salvador, Guatemala, Honduras, Panama, Mexico, Nicaragua and Belize.",
"title": ""
},
{
"docid": "6567025",
"text": "\"What Do I Have to Do\" is a song by Kylie Minogue.",
"title": ""
},
{
"docid": "10902050",
"text": "Moongarden is an Italian Progressive rock group who tour internationally. They have been compared to Porcupine Tree, Marillion and Genesis. The group records and distributes their music on Galileo Records.",
"title": ""
},
{
"docid": "1306083",
"text": "The North American porcupine (\"Erethizon dorsatum\"), also known as the Canadian porcupine or common porcupine, is a large rodent in the New World porcupine family. The beaver is the only rodent in North America that is larger than the North American porcupine. The porcupine is a caviomorph rodent whose ancestors rafted across the Atlantic from Africa to Brazil over 30 million years ago, and then migrated to North America during the Great American Interchange after the Isthmus of Panama rose 3 million years ago.",
"title": ""
},
{
"docid": "54062128",
"text": "Kino-Eye (Anglophonic: Cine-Eye) is a film technique developed in Soviet Russia by Dziga Vertov. It was also the name of the movement and group that was defined by this technique. Kino-Eye was Vertov's means of capturing what he believed to be \"inaccessible to the human eye\"; that is, Kino-Eye films would not attempt to imitate how the human eye saw things. Rather, by assembling film fragments and editing them together in a form of montage, Kino-Eye hoped to activate a new type of perception by creating \"a new filmic, i.e., media shaped, reality and a message or an illusion of a message - a semantic field.\" Distinct from narrative entertainment cinema forms or otherwise \"acted\" films, Kino-Eye sought to capture \"life unawares\" and edit it together in such a way that it would form a new, previously unseen truth.",
"title": ""
},
{
"docid": "9474751",
"text": "\"Waiting\" is the first single of British progressive rock band Porcupine Tree, released in May 1996. It came in two formats: a regular CD and a 12\" vinyl. At the time, the single was intended to promote the forthcoming album \"Signify\". The song is divided into two parts, the second one being an instrumental follow-up",
"title": ""
},
{
"docid": "3764267",
"text": "Pterocarpus marsupium, also known as Malabar kino, Indian kino tree or vijayasar, is a medium to large, deciduous tree that can grow up to 30 m tall. It is native to India, Nepal, and Sri Lanka, where it occurs in parts of the Western Ghats in the Karnataka-Kerala region and also in the forests of Central India. It is also known by the names \"benga\", \"bijiayasal\" (in western Nepal), \"piasal\" (Oriya), \"venkai\", and many others.",
"title": ""
},
{
"docid": "30876126",
"text": "Kino's Journey: the Beautiful World (Japanese: キノの旅 -the Beautiful World- , Hepburn: Kino no Tabi -the Beautiful World- ) , shortened to Kino's Journey, is a Japanese light novel series written by Keiichi Sigsawa, with illustrations by Kouhaku Kuroboshi. The series originally started serialization in volume five of MediaWorks' now-defunct light novel magazine \"Dengeki hp\" on March 17, 2000. The first volume of the series was published on July 10, 2000 by ASCII Media Works under their Dengeki Bunko publishing imprint. As of October 2014, 18 volumes have been published, and over 8 million copies of the novels have been sold in Japan. In \"Kino's Journey\", the protagonist, Kino, accompanied by a talking motorcycle named Hermes, travels through a mystical world of many different countries and forests, each unique in its customs and people. A spin-off light novel series titled \"Gakuen Kino\" began with the first volume published on July 10, 2006 by ASCII Media Works; four volumes have been released as of July 2010.",
"title": ""
},
{
"docid": "34165695",
"text": "Hesperostipa spartea is a species of grass known by the common names porcupine grass, western porcupine grass, short-awn porcupine grass, porcupine needlegrass, and big needlegrass. It is native to North America, where it is widespread from British Columbia to Ontario in Canada and through the central and Great Lakes regions of the United States.",
"title": ""
},
{
"docid": "11714629",
"text": "Porcupine grass is a common name for several grasses and may refer to:",
"title": ""
},
{
"docid": "8838502",
"text": "XM (also known as Transmission 1.1 and Transmission 1.2) is a live-in-studio album recorded by British band Porcupine Tree in early 2003 as a live album of mostly \"In Absentia\" tracks. This was taken from a session at XM Satellite Radio in Washington D.C. on 12th November 2002, and was originally released as a limited edition tour album. It was later released online on the Porcupine Tree store.",
"title": ""
},
{
"docid": "23223006",
"text": "Maior cajueiro do mundo or Cajueiro de Pirangi (English: world's largest cashew tree or cashew tree of Pirangi ) is a cashew tree in Pirangi do Norte, Rio Grande do Norte, Brazil. In 1994, the tree entered the \"Guinness Book of Records\". It covers an area between 7300 m2 and 8400 m2 . Having the size of 70 normally sized cashew trees, it has a circumference of 500 m . The vicinity of the World's Largest Cashew Tree in North Pirangi is also main place for the sale of lace and embroidery in Rio Grande do Norte state.",
"title": ""
},
{
"docid": "3865209",
"text": "Kino is a film making movement that advocates the production of short-films on little to no budget, using small crews, and non-competitive collaboration. There are Kino Groups around the world. Kino is divided into individual cells, or chapters, most of which have a monthly screening where member directors can screen their films. Cells may also feature \"Kino kabarets\", where invited artists collaborate to create films.",
"title": ""
},
{
"docid": "5868730",
"text": "Never Stop Doing What You Love is a not-for-resale compilation of various Paul McCartney and Wings songs created for the employees and clients of Fidelity Investments, a company in the financial services industry. The ex-Beatle became the mutual fund giant's new spokesman in 2005 in a campaign entitled \"This Is Paul\", and the disc was issued in support of McCartney's U.S. tour of the same year. On the day of its release, company employees were treated to a special recorded message by Paul himself informing them that \"Fidelity and I have a lot in common\" and urging them to \"never stop doing what you love.\" McCartney received considerable criticism for his celebrity endorsement of Fidelity Investments, which some considered to be a vulgar attempt to increase his already astounding wealth.",
"title": ""
},
{
"docid": "9448867",
"text": "\"Piano Lessons\" is a single by British progressive rock band Porcupine Tree, from their album \"Stupid Dream\", released in April 1999. It came in two formats: a regular CD and a 7\" vinyl (limited to 1.000 copies). The single was accompanied by a music video directed by Mike Bennion, who would lately co-write the filmscript which inspired \"Deadwing\" along with Steven Wilson.",
"title": ""
},
{
"docid": "9432500",
"text": "\"Lazarus\" is a single by British progressive rock band Porcupine Tree, released in March 2005 in Poland and Germany only. It contains a radio edit of the title track plus two songs that were later added on the DVD audio version (\"Half-Light\") and the vinyl edition (both songs) of \"Deadwing\". It was accompanied by a music video directed by Danish longtime collaborator Lasse Hoile. The single charted in Germany at #91.",
"title": ""
},
{
"docid": "23058261",
"text": "Oh the Things Mommies Do! What Could Be Better Than Having Two?",
"title": ""
},
{
"docid": "15416170",
"text": "We Lost the Skyline (also known as Transmission 7.1) is a live recording by Porcupine Tree, recorded during an in-store performance at Park Avenue CDs in Orlando, Florida, with 200 fans in attendance. Although it was originally planned that the full band would play, lack of space dictated that only the two guitarists/singers Steven Wilson and John Wesley did. This one-off performance was captured by a remote recording facility and the complete 8 song, 33 minute show is now being released in a mail order only CD, but the band are currently negotiating a low-key release for the CD through a number of independent stores in the USA that have supported Porcupine Tree over the last few years (including Park Avenue CDs itself). However, the CD was released in Poland in small quantity.",
"title": ""
}
] |
731
|
Self Assessment UK - Goods and services for your own use
|
[
{
"docid": "521411",
"text": "The problem with your profession is that it is hard to distinguish those activities as 'services rendered' or just a 'pastime hobby'. If you believe that both of those activities constitutes a 'service rendered in a professional capacity', then you should include it into the 'Goods and services for your own use' field. However, should you believe that those services rendered was not in a professional capacity and it was in a personal one (i.e. helping out), you need not include it in the field. In addition, should you feel that the pro-bono services rendered overlaps with your professional freelance work in any way, you might want to consider the service rendered to your dad and yourself as a 'professional service' and include it in Goods and services for your own use. Such examples include (but not limited to): It might be wise to call up the HMRC to clarify on your particular situation. But what I know is, this box was created to ensure that such services rendered should be considered a profit (i.e. an advantage, adds value) and not a loss (or no value).",
"title": ""
},
{
"docid": "569455",
"text": "Work on your own site is certainly not relevant here, that's just a part of your trade, not a service you provided to yourself. The business received the benefit of that work, not you. Suppose your business sold televisions. If you took a TV from stock for your own lounge, that would be included in this box because you have effectively paid yourself with a TV rather than cash. If you take a TV from stock to use as a demo model, that's part of your trade and not goods you have taken out of the business for your own use. For services provided to your dad it's less clear. As Skaty said, it depends whether it's your business providing the service, or you personally. If you gave your dad a free TV then it would be clear that you have effectively paid yourself with another TV and then given it to your dad as a gift. With services it's less clear whether you're receiving services from the business for free. You might consider how it would be treated by your employer if you weren't self-employed. If you were just applying your skills to help your dad in your free time, your employer wouldn't care. If you used your employer's equipment or facilities, or hosted his site on a server that your employer pays for, your employer would be more likely to discipline you for effectively stealing services from them, as they would if you took a TV from their warehouse for him.",
"title": ""
}
] |
[
{
"docid": "385779",
"text": "In the UK is perfectly acceptable to use your personal bank account as a business account if your a sole trader, although it can be messy. Just record and keep all relevant transaction invoices etc documents for self assessment time. At self assessment time they will tell you the amount of tax you need to pay when you fill out the forms. Not sure how it is Canada. If you get bigger get an accountant.",
"title": ""
},
{
"docid": "374264",
"text": "I am not an accountant, but I do run a business in the UK and my understanding is that it's a threshold thing, which I believe is £2,500. Assuming you don't currently have to submit self assessment, and your additional income from all sources other than employment (for which you already pay tax) is less than £2,500, you don't have to declare it. Above this level you have to submit self assessment. More information can be found here I also find that HMRC are quite helpful - give them a call and ask.",
"title": ""
},
{
"docid": "106327",
"text": "\"That wasn't an \"\"inheritance\"\" that arrived out of the blue and the \"\"bank\"\" contacted your girlfriend by email, was it? A UK tax code is basically an assessment of how much money you can earn in the UK before you have to pay tax on it - basically it's a coding for a tax allowance and as a UK tax payer HMRC (the UK version of the IRS) gives you one for free. If your girlfriend is not a UK tax payer she should get the necessary paperwork to show that she isn't, although I'm not sure if that's got any bearing on inheritance tax. There are no lawyers involved in that process normally, any appropriately accredited accountant can do that for you in the UK if you're not in the UK. When I had to apply for a change of tax status in the UK it certainly didn't cost me $9.6k to do so via my accountant there. In fact the whole thing cost a few pounds to pay for my accountant's time and that was it. In fact, that whole thing smells fishy to me as someone who used to live in the UK. Care to divulge the name and possibly address of the bank? Here's inheritance tax information straight from the horse's mouth. That should clear up any questions if your girlfriend is even liable for any inheritance tax in the UK in the first place. And then, given the sums involved, get the recommendation for a good lawyer and a good accountant in the UK (or an accountant who can recommend a lawyer) to make sure that that end of the transfer goes smoothly.\"",
"title": ""
},
{
"docid": "503727",
"text": "There is no clear answer, it might be or not be. Depends a lot on your situation. 1)Yes it is taxable but as Italy has a double taxation agreement with UK, you might not have to pay. You can get a detailed guidance on the HMRC website. 2) Apply here for a certificate of residence 3)You can only claim back if Italy taxes you more than UK would. If it is less than you will have to pay the remaining portion to HMRC. You do this in the self assessment form/tax return/call up HMRC. 4)Tell the truth, explain your whole scenario and don't withheld relevant information assuming you may lower you tax by doing so.",
"title": ""
},
{
"docid": "242654",
"text": "Note: I am in the UK. I don't know specifically about australia but I expect the general principles will be much the same everywhere. What banks want is to be reasonablly confident that you have a steady income stream that will continue to pay the mortgate until it completes. In general employed are fairly easy to assess. Most employed people will have a steady basic pay that increases through their career. Payslips will usually seperate-out basic pay, overtime and bonuses. There is little opertunity to cook the books. The self-employed are harder to assess. Income can be bursty and there are far more opertunities for cooking the books to make it look like you are earning more than you really are. So banks are likely to be far more careful about lending to the self-employed, they will likely want to see multiple years of buisness records so that any bursts, whether natural due to the ebbs and flows of buisness or deliberatly created to cook the books average out and they can see the overall pattern. A large deposit will help because it reduces the risk to the bank in the event of a default. Similarly not being anywhere near your limit of affordability will help.",
"title": ""
},
{
"docid": "247760",
"text": "In a simple case as the sole UK resident director/shareholder of a company, with that company as your only income, you are usually best paying yourself a salary of the maximum tax free amount allowed under your tax code (~£11k for most people at present). On this you will have to pay some employer and employee National Insurance (NI) contributions (totalling around £1000). Your salary/employer NI counts as an expense, so that is taken off the company profits. You then pay corporation tax on the remainder (20%). The first £5k you take as dividends is tax free, the remainder at a lower tax rate than the equivalent combined income tax/NI (starting at 7.5% instead of 20% tax plus employee plus employer NI), giving a significant saving compared to salaried income even after corporation tax. To declare and pay the tax, you would need to complete a self-assessment tax return. Your company will also need to file a return. The Contractor UK website, although aimed at IT contractors, has some very useful information on operating Ltd companies. That said, finances are rarely that simple so I would concur with the recommendation you engage an accountant, which is a tax-deductible expense.",
"title": ""
},
{
"docid": "542022",
"text": "You need to set your status as self-employed the day you started online work. If that date is a little ambiguous (as is usually the case with online business), you can start with the day you first made any money. Yes, you can deduct expenses from your revenue. But you have to be sure that the expenses were purely business related. This is how it goes: You inform HMRC about the day you started work. HMRC will assign you a UTR (Unique Tax Reference) number. Depending on how much you make you might or might not need to pay Class 2 NI contributions. You'll need to tell HMRC how much you expect to earn in the current tax year. Finally, you'll need to complete a Self-Assessment at the end of the tax year. I highly recommend setting up a business banking account. Here is a link that discusses being part-time self-employed in the UK.",
"title": ""
},
{
"docid": "5587",
"text": "Source on GOV.UK You may be able to get tax back for some of the bills you have to pay because you have to work at home on a regular basis. You can only claim for things to do with your work, eg business telephone calls or the extra cost of gas and electricity for your work area. You can’t claim for things that you use for both private and business use, eg rent or broadband access. You don’t need to provide records for claims of up to £4 per week (£18 per month). For claims over £4 per week you’ll need to provide evidence of what you’ve spent. Claims up to £2,500 You must claim using a Self Assessment tax return if you already fill one in. If you don’t already fill in a Self Assessment tax return, and your allowable expenses are under £2,500 for the tax year, fill in form P87 and send it to the address on the form. If you’ve made a successful claim in a previous tax year and your expenses are less than £1,000 (or £2,500 for professional fees and subscriptions), you may be able to make your claim by phone. Claims over £2,500 You must claim using a Self Assessment tax return.",
"title": ""
},
{
"docid": "458535",
"text": "I think you have already outlined for yourself most of the pros and cons of each method of giving. It sounds to me like you have some desire to control how the money is spent, or at least reserve the right not to give it to a child who will waste it (according to your definition). If you set up an UTMA/UGMA account, or just give the money directly each year as a birthday gift, you are surrendering control of the money. It's a gift and is no longer yours to direct. If you set up a 529, you at least restrict the money to a particular, useful purpose. Moreover, if you retain ownership of the 529, you can take the money back, albeit with a tax penalty to yourself. If you do hold a 529 in your name, but for a child's benefit, there are a couple of things to consider with respect to future financial aid (this is from recent experience--my in-laws have 529s for our children, both of whom are currently in college). A 529 not owned by the student or the student's parent is not reported as an asset (of the child or the parent) on the Free Application for Federal Student Aid (FAFSA). However, once such a 529 is used to pay college expenses, the amount of those payments does get reported on the following year's FAFSA, and counts as untaxed income for the purposes of figuring the Expected Family Contribution (EFC). Untaxed income is assessed towards the EFC at 50%. In contrast, parental assets are assessed at around 7%, if I recall correctly, and student assets at around 35%. Student-owned 529s are assessed at the rate of parental assets, which is an advantage. If the amount you will set aside is less than the cost of one year of college, you can avoid the disadvantage of the untaxed income assessment by just using the entire 529 for the final year of school, since there will be no FAFSA for the following year. It occurs to me that there is one other way you can give to them that you did not mention, and may make you more comfortable in terms of encouraging some positive behavior. Namely, save the money in a self-owned account, then, when they are old enough to get a job that provides a W-2 showing declared, earned income, you can use the savings to fund a Traditional or Roth IRA for them, up to the limit allowed each year, until the money you set aside is exhausted. The Roth is a better long-term savings vehicle, but the Traditional would carry bigger penalties for early withdrawal and would therefore be less tempting to draw on.",
"title": ""
},
{
"docid": "111999",
"text": "Would I have to pay income tax other then TDS on interest earned on my saving bank account. No being NRI you are not taxed in India on income outside of India. I am sending money from EU to my OWN saving account. Please note this account is not NRI\\NRO\\FCNR As an NRI you CANNOT by law hold a regular Savings Account. Please convert this account to NRO ASAP. Does the channel I use to transfer money to India would make any difference? Its 3rd party transfer service. Whether you transfer the funds or not is irrelevant. As the income was during the period when your status is NRI, there is no Tax in India. sold some shares from my Indian demat account online and got some STCG. You would need to pay tax on this in India Edit: Self Assessment Tax can be paid till 30 July 2015 for the Financial Year 1 April 2014 to 31 March 2015. Tax have to be paid in advance, so if your tax obligation is more than Rs 10,000/- there will be an interest at 1% per month and penalty at 1% per month payable",
"title": ""
},
{
"docid": "266229",
"text": "\"The HMRC has a dedicated self-help/learning site that is helpful here: It's important to tell HMRC that you are self-employed as soon as possible. If you don't, you may have to pay a penalty. You don't want to pay more to HMRC than you have to as it is a waste of your money. Your business has started when you start to advertise or you have a customer to buy your goods or services. It is at this point that your business is 'trading'. You cannot register before you start trading. For example, if you advertise your business in the local newspaper on 15 January but do not get your first customer until 29 March; in this case, you have been trading since 15 January. You must tell HMRC within six months of the end of the tax year in which you start self-employment. You must therefore register by 5 October. But it's best to register well before this so that you do not forget to do so. The HMRC also has a YouTube channel with help videos, and \"\"Am I Trading or Not?\"\" might be of particular interest to you. Most of the registration is based around the concept of starting to work with the intent to make a profit. By the letter of law and regulations, you should register within six months of the end of the tax year you started to avoid any potential penalty. However note that the situation is different based upon your intent. If you begin making/putting up videos online as a hobby with the hope that you can make something to help you defray the basic costs involved, and the total amount you make is relatively small (say, less than 500 pounds), you will not be classified as \"\"trading\"\" and likely have no need to register with HMRC. As soon as you begin to get in regular payments, maybe a single payment of a significant size, or multiple payments for a similar service/item, you are vastly more likely to need to register. From my reading you would likely be safe to begin putting up videos without registration, but if you begin spending a large portion of your time over an extended period (multiple months) and/or begin getting payments of any notable size then you should likely register with the appropriate services (HMRC, etc). As is the case in both the USA and UK, simple registration is pretty cheap and the costs of little/no income are usually pretty minor. Also note that the HMRC trading and self-employment regulations are unusual compared to many US laws/institutions, in that you are explicitly permitted to begin doing something and only register later. So if you start doing videos for an entire tax year + 5 months and make nothing significant, you'd seemingly be fine to never register at all.\"",
"title": ""
},
{
"docid": "320060",
"text": "I honestly don't understand this sense of entitlement to being able to use your own device. By giving an employee access to sensitive data on their own device, you are taking a risk that the company cannot technologically or legally mitigate. In the UK it would be a de-facto breach of the Data Protection Act. If there was a rootkit on an employee's phone or laptop, and they got access to any sensitive data then game over. This is not about inconvenience, it is about not costing the companies in question billions in fines. It is simply not worth it - especially as most employees are perfectly capable of losing work computers on trains and so on, so trusting them to look after their own system security is asking a bit much. What happens if they lose their own laptop? A work laptop can be set to self destruct, but few employees are going to let their companies have that level of control over their laptop. And, here in the UK, if sensitive data is lost in that way and can be recovered using forensic tools then - bam - fines. A company has a legal obligation to ensure that their employee's and customer's data is safe, and any data accessed on a phone or laptop is still stored somewhere on that phone or laptop. Third party software like Dropbox is notoriously insecure, too, so that shouldn't ever be used on a machine containing sensitive data. It's hard enough getting employees to take security seriously before exponentially increasing these risks as you describe.",
"title": ""
},
{
"docid": "443407",
"text": "How you pay Income Tax Pay As You Earn (PAYE) Most people pay Income Tax through PAYE. This is the system your employer or pension provider uses to take Income Tax and National Insurance contributions before they pay your wages or pension. Your tax code tells your employer how much to deduct. Your tax code can take account of state benefits, so if you owe tax on them (eg the State Pension) it’s usually taken automatically from your other income. Self Assessment tax returns If your financial affairs are more complex (eg you’re self-employed or have a high income) you may pay Income Tax and National Insurance through Self Assessment. You’ll need to fill in a tax return every year. Income Tax on savings and investment interest Income Tax is usually taken from interest on savings and investments automatically. Income that’s not automatically taxed You must fill in a tax return if your untaxed income is over £2,500, or if you don’t pay tax through your wages or pension. You must contact the Income Tax helpline if it’s less than £2,500.",
"title": ""
},
{
"docid": "114908",
"text": "There are many good brokers available in the market and many spammers too. Personally I have been associated with FXCM since 2001 and have never faced any problem. But everyone has their own personal choice and I recommend you to make your own. But the question is how to find out which broker is a good broker and would provide you with a timely and reliable service? Online google check? Not really. There is so much competition between brokerage firms that they keep writing rubbish about each other on blogs and websites. Best thing is to is check with regulator's website. For US: NFA is a regulator for all forex firms. Information about any regulated forex firm could be found here. http://www.nfa.futures.org/basicnet/welcome.aspx For UK: Its FSA. Information on all regulated Uk based firm could be found here. http://www.fsa.gov.uk/register/firmSearchForm.do Remember in many countries its not compulsory for a forex firm to be regulated but being regulated ensure that the govt. has a watch on the operations of the firm. Also most of the firms out there provide accounts for large as well as small traders so there is nothing much to look for even if you are a small trader. Do keep in mind that if you are a US Citizen you are restricted by the US Govt. to trade only with a broker within US. You are not allowed to trade with any brokerage firm that is based outside the country. Forex Trading involves a significant amount of risk make sure you study the markets well and get yourself educated properly before risking your money. While I have made a lot of money trading forex I have seen a lot of people loosing everything. Please understand the risk and please make sure you only trade with the money which you can afford to loose.",
"title": ""
},
{
"docid": "103405",
"text": "Only if your work on the side is making you at least £60,000 profit a year. The overheads are just not worth it if you make less. Working as a sole trader, you can still claim for expenses incurred in the course of your business. You can also claim a percentage of your computer costs, even though you may use the computer for gaming. This is not unreasonable as the computer is necessary for your work. The Inland Revenue accept the fact that some assets are part work-related. In your case, as a web and mobile phone developer, I expect the percentage to be at least half, if not a lot more. If you need to travel in the course of your work you can claim a percentage for your car. You can include other small expenses such as telephone, stationery, electricity etc but don't go overboard. The important point to remember is that you must be able to defend the expenses claimed as work-related, so long as you can do this there is no problem. Remember to keep good records of all your expenses. This is on-going throughout the year and is much more work than filling out your tax return. The software on the IR self-assessment site is excellent, so it's conceivable that you may not need an accountant if you are prepared to do your own tax return. However, if you feel unsure employ an accountant initially and take it from there.",
"title": ""
},
{
"docid": "168796",
"text": "From your question and how you have framed it, I get you find Agressive Sales tactics disturb the buying process for you. ;) I understand because I also find the whole process of Research / Negotiating / Buying / Owning / Using is all on one continuum, so anything that ruins the process will likely lose the sale or enjoyment of the item, at the end of the day. [Very long answer .... Sorry :) ] The answer to this is to KNOW what you want before you have to deal with the Sales people. A good Sales person likes a customer who knows what they want. I would suggest that you follow my 'Buying Process' (Much you have already done) : Before you Buy: Identify the item you want and the max/min 'realistic' price you would buy at. [Stick to this price else 'Buyers Remorse' may bite later.] Write the questions you have down on paper before you visit the Dealer. Write the answers you want on the same list, if known. Decide which questions are most important and therefore must get the answer you want. These should be the questions you ask first. Mark these on the list. Re-visit points 1-3 are they complete and to your satisfaction ? Would you buy if all the answers & the price are right ? If NO then re-visit point 1-3 else you are not ready to buy now !!! If YES then Organise your visit to the Dealer. [Book appointment etc if needed.] At Dealer: Meet your Sales person and clearly state what you want (the item) and importantly when you intend to buy, if all your questions are answered to your satisfaction. There is no need to discuss price at this point as the 'haggling' is only possible IF the questions are answered to your satisfaction. Do not give information such as your maximum budget or similar requests, as they give the sales person the upper hand to maximise his/her pricing. If asked state that your budget is conditional on the answers you get. As the questions are answered assess the answer and assign +/- to the question on your list. If any of your most critical / important questions are answered in the negative, they are the reasons you have to call it a day and walk out. You can assess whether they are worth ignoring but you will need to factor this into your price and if you have identified your questions correctly there should be little room for debate. Assuming you have got all your questions answered you should know what you are buying and have assessed what is a reasonable price for it, if you still want it as this point. If you have lost interest, say so and let the Sales person go. Don't waste their time. They may make some sort of offer to you BUT don't forget that if you have doubts now they will not go away easily no matter what the 'great' price is. If you want it then continue. Buying your Item: [None of the following is really usefull if you have told the Sales person your Budget, as they will be aiming for the highest end of your budget. You will often find that the best price is very close to your maximum budget !!! :)] Do not forget your realistic price range, this should limit your buying price no matter what tactics are used by the Sales person. Only you know what you are prepared to pay and if an extra 1% or 50% is considered worth it to you, if you have to have the item :) Regardless, you have to have some idea of your limit and be prepared to stick to it. You must be able to walk away if the price is silly and not worth it. Assuming you have not been smitten by your item and funds are NOT unlimited, ask for the price and assess it against your price range. At this point I can only offer pointers as there are no 'magic' rules to get what you want at the lowest price. The only advice I would offer is that you will be lucky to get something at your 1st offer price unless the seller really needs to sell, because of this your 1st offer should be less than your price range lowest band. You will need to assess how much less but be prepared to get a 'No' response. If you get a 'Yes' and your research is good 'Buy It !!!' If you get too enthusiastic a response, question your research & if not sure bail out [No Sale] :) At this point you are likely to be 'Haggling' so you need to be ready for all the 'Must buy Now' tactics. If you have clearly stated your wants and timescales there is no reason to be pulled in by these tactics and they can be ignored until the price has reached the level you are happy with. If the price is not moving where you want than clearly state you cannot 'buy at that price'. If you get a total stop and no movement than you need to assess your 'need' and if priced too high then you should walk out. Remember if you stated that you had a timescale to buy of 1/2/3 weeks you should act like you have 1/2/3 weeks to keep looking. Any eagerness on your part will tell the Sales person that you have lied !!! :) You can always come back and try again, reminding the Sales person that the 'item' is still there and perhaps it is priced too high to sell and make the same offer. !!! (A bit of cheek sometimes works.) If the price is close and you still want it and the Sales person is not moving you need to try walking out while stating that you would love the 'item' if it was priced better, if no improved offer as you go, try an increased offer but again you need to assess how much and remember you can only go up, or walk out and come back another day. If the price is at a level you are happy with then you should have no reason not to buy (if you have followed this process) but this does not mean that you should be forced into buying now if you do not want to. Regardless of any 'Must buy now' tactics if the price is right and you cannot buy now, tell the Sales person when you CAN buy and see if you can get an agreement with this. It is unfair to expect a price to be held for an indeterminate time, so you do need to state when you could buy if not now when a price has been agreed. This is a point where the deal may break down if the Sales person thinks they have a sale and trys to force the Sale now. Once again you have to assess your 'need' and whether buying now is better than walking out. If the deal breaks down there is nothing stopping you from coming back and offering the same price when you can buy. A final option is to agree if a deposit can be left to reserve the item until you can buy. This gives the Sales person some assurance that you will come back and is sometimes NON-Refundable unless you agree otherwise before you pay, so check this detail first. (This tends to be smaller Dealers but generally in the UK the large companies offer refundable deposits as part of their Customer Service, the advantage of using larger Stores/Dealers etc.) Apologies for the epic reply, hope it helps.",
"title": ""
},
{
"docid": "465819",
"text": "\"My advice would be to invest that 50k in 25% batches across 4 different money markets. Batch 1: Lend using a peer-to-peer account - 12.5k The interest rates offered by banks aren't that appealing to investors anymore, at least in the UK. Peer to peer lending brokers such as ZOPA provide 5% to 6% annual returns if you're willing to hold on to your investment for a couple of years. Despite your pre-conceptions, these investments are relatively safe (although not guaranteed - I must stress this). Zopa state on their website that they haven't lost any money provided from their investors since the company's inception 10 years ago, and have a Safeguard trust that will be used to pay out investors if a large number of borrowers defaulted. I'm not sure if this service is available in Australia but aim for an interest rate of 5-6% with a trusted peer-to-peer lender that has a strong track record. Batch 2: The stock market - 12.5k An obvious choice. This is by far the most exciting way to grow your money. The next question arising from this will likely be \"\"how do I pick stocks?\"\". This 12.5k needs to be further divided into 5 or so different stocks. My strategy for picking stock at the current time will be to have 20% of your holdings in blue-chip companies with a strong track record of performance, and ideally, a dividend that is paid bi-anually/quarterly. Another type of stock that you should invest in should be companies that are relatively newly listed on the stock market, but have monopolistic qualities - that is - that they are the biggest, best, and only provider of their new and unique service. Examples of this would be Tesla, Worldpay, and Just-eat. Moreover, I'd advise another type of stock you should purchase be a 'sin stock' to hedge against bad economic times (if they arise). A sin stock is one associated with sin, i.e. cigarette manufacturers, alcohol suppliers, providers of gambling products. These often perform good while the economy is doing well, but even better when the economy experiences a 2007-2008, and 2001-dotcom type of meltdown. Finally, another category I'd advise would be large-cap energy provider companies such as Exxon Mobil, BP, Duke Energy - primarily because these are currently cheaper than they were a few months ago - and the demand for energy is likely to grow with the population (which is definitely growing rapidly). Batch 3: Funds - 12.5k Having some of your money in Funds is really a no-brainer. A managed fund is traditionally a collection of stocks that have been selected within a particular market. At this time, I'd advise at least 20% of the 12.5k in Emerging market funds (as the prices are ridiculously low having fallen about 60% - unless China/Brazil/India just self destruct or get nuked they will slowly grow again within the next 5 years - I imagine quite high returns can be had in this type of funds). The rest of your funds should be high dividend payers - but I'll let you do your own research. Batch 4: Property - 12.5k The property market is too good to not get into, but let's be honest you're not going to be able to buy a flat/house/apartment for 12.5k. The idea therefore would be to find a crowd-funding platform that allows you to own a part of a property (alongside other owners). The UK has platforms such as Property Partner that are great for this and I'm sure Australia also has some such platforms. Invest in the capital city in areas as close to the city's center as possible, as that's unlikely to change - barring some kind of economic collapse or an asteroid strike. I think the above methods of investing provide the following: 1) Diversified portfolio of investments 2) Hedging against difficult economic times should they occur And the only way you'll lose out with diversification such as this is if the whole economic system collapses or all-out nuclear war (although I think your investments will be the least of your worries in a nuclear war). Anyway, this is the method of investing I've chosen for myself and you can see my reasoning above. Feel free to ask me if you have any questions.\"",
"title": ""
},
{
"docid": "385090",
"text": "The right answer to this question really depends on the size of the transfer. For larger transfers ($10k and up) the exchange rate is the dominant factor, and you will get the best rates from Interactive Brokers (IB) as noted by Paul above, or OANDA (listed by user6714). Under $10k, CurrencyFair is probably your best bet; while the rates are not quite as good as IB or OANDA, they are much better than the banks, and the transaction fees are less. If you don't need to exchange the currency immediately, you can put in your own bids and potentially get better rates from other CurrencyFair users. Below $1000, XE Trade (also listed by user6714) has exchange rates that are almost as good, but also offers EFT transfers in and out, which will save you wire transfer fees from your bank to send or receive money to/from your currency broker. The bank wire transfer fees in the US can be $10-$30 (outgoing wires on the higher end) so for smaller transfers this is a significant consideration you need to look into; if you are receiving money in US, ING Direct and many brokerage accounts don't charge for incoming wires - but unless you have a commercial bank account with high balances, expect to spend $10-$20 minimum for outgoing. European wire transfer fees are minimal or zero in most cases, making CurrencyFair more appealing if the money stays in Europe. Below $100, it's rarely worth the effort to use any of the above services; use PayPal or MoneyBookers, whatever is easiest. Update: As of December 2013, CurrencyFair is temporarily suspending operations for US residents: Following our initial assessment of regulatory changes in the United States, including changes arising from the Dodd-Frank Act, CurrencyFair will temporarily withdraw services for US residents while we consider these requirements and how they impact our business model. This was a difficult and very regretful decision but we are confident we will be able to resume services in the future. The exact date of re-activation has not yet been determined and may take some time. We appreciate your patience and will continue communicating our status and expected return.",
"title": ""
},
{
"docid": "72984",
"text": "What you need to do is register as a sole trader. This will automatically register you for self assessment so you don't have to do that separately. For a simple business like you describe that's it. Completing your self assessment will take care of all your income tax and national insurance obligations (although as mentioned in your previous question there shouldn't be any NI to pay if you're only making £600 or so a year).",
"title": ""
},
{
"docid": "111354",
"text": "From my experience it is much easier to start as a self-employed rather than a limited company. You almost have no paperwork and self assessment can be done online in as little as 20 minutes (from personal experience). On the other hand having a limited company grants you a pile of papers to fill in from the start and almost certainly needing an accountant to do your taxes. Regarding the income tax - if you have no profits, you will pay no tax. And that will leave you only with national insurance that is only about £70 for 3 month (better check with HMRC for the exact figure). So if you don't have a good enough reason to do a Ltd, start as a self-employed, you can always change to limited company later.",
"title": ""
},
{
"docid": "112435",
"text": "It's not typically possible for someone to jointly own the house, who is not also jointly liable for the mortgage. This doesn't matter however, because it is possible for two people to get a mortgage together, where only one person's income is assessed by the lender. If that person could get a mortgage of that amount on their own, then the couple should also be able to get the same mortgage. Source: My wife and I got a mortgage like this. She is self-employed, rather than meet the very high requirements for proving her self-employment income, we simply said that we only wanted my income to be taken into consideration.",
"title": ""
},
{
"docid": "313012",
"text": "\"You are not the only one with this problem. When Intuit changed their pricing and services structure in 2015 a lot of people got angry, facing larger fees and having to go through an annoying upgrade just to get the same functionality (such as Schedule D, capital gains). You have several options: (1) Forget Turbo Tax and just use paper forms. That is what I do. Paper is reliable. (2) Use forms mode in Turbo Tax. Of course, that may be even more complicated than simply filing out paper forms. (3) Use a different service. If your income is below $64,000 the IRS has a free electronic filing service. Other online vendors have full taxes services for less than Turbo Tax. (4) Add the amount to ordinary income. Technically, as long as you report the income, you cannot be penalized, so if you add the capital gain to your ordinary income, then you have paid taxes on the income. Even if they send you a letter, you can send an answer that you added it to ordinary income and that will satisfy them. Of course you pay a higher rate on your $26 if you do that. (5) If you are in the 15% or below income bracket you are exempt from capital gains, and you can omit it. Don't believe the nervous Nellies who say the IRS will burn your house down if you don't report $26 in capital gains. Penalties are assessed on the percentage of TAXES you did not pay (0.5% penalty per month). Since 0.5% of $0 is $0 your penalty is $0. The IRS knows this. The IRS does not send out assessment letters for $0. (6) Even if you are above the 15% bracket, there is likelihood it is still a no-tax situation (see 5 above). (7) Worst case scenario: you are making a million dollars per year and you omit your $26 capital gains from your return. The IRS will send you an assessment letter for about $10. You can then send them a separate check or money order to pay it. In all honesty I have omitted documented tax items, like taxable interest, that the IRS knows about many times and never gotten an assessment letter. Once I made a serious math error on my return and they sent me an assessment letter, which I just paid, end of story. And that was for a lot more than $26. The technical verbiage for something like this in IRS lingo is CP-2000, underreported income. As you can see from this official IRS web page, basically what they do is guess how much they think you owe and send you a bill. Then you pay it. If you do so in time, you don't even get a 0.5% interest penalty on your $6.75 owed or whatever it is. (8) Go hog wild. As long as you are risking an assessment on your $26, why not go hog wild and just let the IRS compute all your taxes for you? Make a copy of your income statements, then mail them to the IRS with a letter that says, \"\"Hi, I am Mr. Odinson, my SSN is XXX-XX-XXXX. My address is XYZ. I am unable to compute my taxes due to a confused state of mind. I am hereby requesting a tax assessment for the 2016 tax year.\"\" Make sure you sign and date the letter. In all probability they will compute the full assessment and send you a bill (or refund).\"",
"title": ""
},
{
"docid": "273645",
"text": "\"In the UK there is a non-profit called the Citizen's Advice Bureau which provides free advice to people on a wide range of subjects, but including debt and budgeting. Consumer Credit Counselling Service provides explicit help but again, in the UK. A search for \"\"volunteer debt counsellor\"\" reveals a whole host of organizations that do that, but almost all based in the UK or Canada or Australia. The US seems not to be well provided with such organizations. This page advises people to volunteer as a debt counsellor, but gives no specifics of organizations, just \"\"Volunteer at local county community centers, churches and agencies. Your local faith-based organization might be a good place to start, even if you are not a member. Regrettably a search for \"\"free debt counselling\"\" produced a similar list of non-profits in UK and Canada, but mainly companies peddling consolidation loans in the US.\"",
"title": ""
},
{
"docid": "473605",
"text": "I'd certainly take a look at companies like UK Forex for transferring funds internationally. Even if you get free wire transfers, the currency rates banks offer can be bad. My experience was transferring from NatWest to an Australian bank - saved my self hundreds of pounds by not using their swift service.",
"title": ""
},
{
"docid": "290862",
"text": "My basic rule of thumb is that if the the bill come from a government office of taxation, and that if you fail to pay the amount they can put a tax lien on the property it is a tax. for you the complication is in Pub530: Assessments for local benefits. You cannot deduct amounts you pay for local benefits that tend to increase the value of your property. Local benefits include the construction of streets, sidewalks, or water and sewer systems. You must add these amounts to the basis of your property. You can, however, deduct assessments (or taxes) for local benefits if they are for maintenance, repair, or interest charges related to those benefits. An example is a charge to repair an existing sidewalk and any interest included in that charge. If only a part of the assessment is for maintenance, repair, or interest charges, you must be able to show the amount of that part to claim the deduction. If you cannot show what part of the assessment is for maintenance, repair, or interest charges, you cannot deduct any of it. An assessment for a local benefit may be listed as an item in your real estate tax bill. If so, use the rules in this section to find how much of it, if any, you can deduct. I have never seen a tax bill that said this amount is for new streets, and the rest i for things the IRS says you can deduct. The issue is that if the Center City tax bill is a separate line or a separate bill then does it count. I would go back to the first line of the quote from Pub 530: You cannot deduct amounts you pay for local benefits that tend to increase the value of your property. Then I would look at the quote from the CCD web site: The Center City District (CCD) is a business improvement district. Our mission is to keep Philadelphia's downtown, called Center City, clean, safe, beautiful and fun. We provide security, cleaning and promotional services that supplement, but do not replace, basic services provided by the City of Philadelphia and the fundamental responsibilities of property owners. CCD also makes physical improvements to the downtown, installing and maintaining lighting, > signs, banners, trees and landscape elements. and later on the same page: CCD directly bills and collects mandatory payments from properties in the district. CCD also receives voluntary contributions from the owners of tax-exempt properties that benefit from our services. The issues is that it is a business improvement district (BID), and you aren't a business: I did find this document from the city of Philadelphia explain how to establish a BID: If the nature of the BID is such that organizers wish to include residential properties within the district and make these properties subject to the assessment, it may make sense to assess these properties at a lower level than a commercial property, both because BID services and benefits are business-focused, and because owner-occupants often cannot treat NID assessments as tax-deductible business expenses, like commercial owners do. Care must be taken to ensure that the difference in commercial and residential assessment rates is equitable, and complies with the requirements of the CEIA. from the same document: Funds for BID programs and services are generated from a special assessment paid by the benefited property owners directly to the organization that manages the BID’s activities. (Note: many leases have a clause that allows property owners to pass the BID assessment on to their tenants.) Because they are authorized by the City of Philadelphia, the assessment levied by the BID becomes a legal obligation of the property owner and failure to pay can result in the filing of a lien. I have seen discussion that some BIDS can accept tax deductible donations. This means if a person itemizes they can deduct the donation. I would then feel comfortable deducting the tax because: If you can't deduct it that would mean the only people who can't deduct it are home owners. So deduct it. (keep in mind I am not a tax professional)",
"title": ""
},
{
"docid": "51203",
"text": "\"Brokers need to assess your level of competency to ensure that they don't allow you to \"\"bite off more than you can chew\"\" and find yourself in a bad situation. Some brokers ask you to rate your skills, others ask you how long you've been trading, it always varies based on broker. I use IB and they gave me a questionairre about a wide range of instruments, my skill level, time spent trading, trades per year, etc. Many brokers will use your self-reported experience to choose what types of instruments you can trade. Some will only allow you to start with stocks and restrict access to forex, options, futures, etc. until you ask for readiness and, for some brokers, even pass a test of knowledge. Options are very commonly restricted so that you can only go long on an option when you own the underlying stock when you are a \"\"newbie\"\" and scale out from there. Many brokers adopt a four-tiered approach for options where only the most skilled traders can write naked options, as seen here. It's important to note that all of this information is self-reported and you are not legally bound to answer honestly in any way. If, for example, you are well aware of the risks of writing naked options and want to try it despite never trading one before, there is nothing stopping you from saying you've traded options for 10 years and be given the privilege by your broker. Of course, they're just looking out for your best interest, but you are by no means forced into the scheme if you do not wish to be.\"",
"title": ""
},
{
"docid": "577126",
"text": "unregister for child benefit but apparently If I do that then my wife will stop getting the automatic national insurance stamp each year and will lose years of state pension You probably got this wrong according to Citizen's Advice. You can choose not to receive any Child Benefit, if you don't want to pay the extra tax. However, HMRC is encouraging you to still fill out a Child Benefit claim form even if you choose not to actually receive any Child Benefit payments from them. This is because filling your claim form for Child Benefit can help you build up national insurance credits which can help protect your future state pension. This is particularly important if you've stopped work to look after children full time. It can also help protect your entitlement to other benefits such as Guardian's Allowance, and ensure your child is automatically issued with a National Insurance number before their 16th birthday. Completing a Child Benefit claim form will make it easier for payments to start again if your circumstances change and your income falls below the £50,000 limit. As for Self Assessment If you decide to continue getting Child Benefit, you'll have to fill in a self-assessment tax return. This is when you'll have to declare you were getting Child Benefit and pay the extra tax, known as the High Income Child Benefit Charge. You'll have to register for self-assessment if you are not already registered. You can choose to pay the tax charge either: The following is important though:- It is your responsibility to pay the extra tax, even if you don't hear from HMRC. SOURCE",
"title": ""
},
{
"docid": "569066",
"text": "\"Obviously you should aim to max out your pension, though this is a bit of a judgement call, as future growth could take it over the limit even once you stop making contributions. A public service job with a defined benefit pension won't make much difference, as they are also assessed against the lifetime limit at a multiplier of 20x the annual pension - so a similar rate to what you're looking at anyway (£500/year corresponds to a £10K notional pot). On the other hand public service pensions are protected against inflation - if you wanted an equivalent defined contribution pension, annuity rates are actually quite a bit lower than that - more like £350-£400 per £10K. Apart from a pension, I'd suggest making sure you own your own property by the time you retire. The rent you save by doing that is effectively tax-free, though you have to pay for the mortgage out of taxed income. So it's equivalent to saving in an ISA, but with the added benefit that you are effectively \"\"hedged\"\" against rental changes. After that ISAs are the next logical investment vehicle, though be aware that cash ISAs don't pay very good returns at the moment.\"",
"title": ""
},
{
"docid": "348922",
"text": "There can be a good reason if you own shares issued in a different country: For example, if you are in the UK and own US shares and take the dividend payments, you get some check in US dollars that you will have to exchange to UK£, which means you pay fees - mostly these fees are fixed, so you lose a significant percentage of your dividends. By reinvesting and selling shares accumlated over some years, you got one much bigger check and pay only one fee.",
"title": ""
},
{
"docid": "230612",
"text": "\"No you should not borrow money at 44.9%. I would recommend not borrowing money except for a home with a healthy deposit (called down payment outside UK). in December 2016, i had financial crisis So that was like 12 days ago. You make it sound like the crisis was a total random event, that you did nothing to cause it. Financial crises are rarely without fault. Common causes are failure to understand risk, borrowing too much, insuring too little, improper maintenance, improper reserves, improper planning, etc... Taking a good step or two back and really understanding the cause of your financial crisis and how it could be avoided in the future is very useful. Talk to someone who is actually wealthy about how you could have behaved differently to avoid the \"\"crisis\"\". There are some small set of crises that are no fault of your own. However in those cases the recipe to recovery is patience. Attempting to recover in 12 days is a recipe for further disaster. Your willingness to consider borrowing at 44% suggests this crisis was self-inflicted. It also indicates you need a whole lot more education in personal finance. This is reinforced by your insatiable desire for a high credit score. Credit score is no indication of wealth, and is meaningless until you desire to borrow money. From what I read, you should not be borrowing money. When the time comes for you to buy a home with a mortgage, its fairly easy to have a high enough credit score to borrow at a good rate. You get there by paying your bills on time and having a sufficient deposit. Don't chase a high credit score at the expense of building real wealth.\"",
"title": ""
}
] |
PLAIN-2368
|
whiff test
|
[
{
"docid": "MED-3657",
"text": "Bacterial vaginosis (BV) is a common condition of unknown etiology and has been linked to adverse reproductive and obstetric health outcomes. Prior dietary research on BV has focused on specific macro- and micronutrients, but not dietary indices. We assessed the relationship between BV and selected dietary indicators among a cohort of 1735 nonpregnant women ages 15–44 y from Birmingham, Alabama. Annual intake was assessed with the Block98 FFQ, and the glycemic index, glycemic load (GL), and Healthy Eating Index were calculated by the Block Dietary Data System. The Naturally Nutrient Rich (NNR) score was also calculated. Vaginal flora was evaluated using Nugent Gram-stain criteria. Crude OR and adjusted OR were determined by multinomial and logistic regression in cross-sectional and prospective analyses, respectively. Participants were predominantly African American (85.5%) aged 25.3 ± 6.8 y (mean ± SD). Per 10-unit increase, GL was positively (adjusted OR = 1.01, 95% CI = 1.00–1.03) and NNR was negatively (adjusted OR = 0.93, 95% CI = 0.88–0.99) associated with BV compared to normal vaginal flora. In prospective analyses, only GL was associated with BV progression (adjusted OR = 1.03, 95% CI = 1.00–1.05) and persistence (adjusted OR = 1.02, 95% CI = 1.01–1.04) after adjustment. Both GL and NNR were associated with greater BV prevalence and GL was associated with an increase in BV persistence and acquisition. These results suggest that diet composition may contribute to vaginal flora imbalances and be important for elucidating the etiology of BV.",
"title": "Bacterial Vaginosis Is Associated with Variation in Dietary Indices"
},
{
"docid": "MED-3656",
"text": "The etiology of bacterial vaginosis is unknown, and there are no long-term therapies for preventing this frequently recurring condition. Vaginal douching has been reported to be associated with bacterial vaginosis in observational studies. However, this association may be due to confounding by indication—that is, confounding by women douching in response to vaginal symptoms associated with bacterial vaginosis. The authors used marginal structural modeling to estimate the causal effect of douching on bacterial vaginosis risk while controlling for this confounding effect. In 1999–2002, nonpregnant women (n = 3,620) were recruited into a prospective study when they visited one of 12 public health clinics in Birmingham, Alabama, for routine care. Participants were assessed quarterly for 1 year. Bacterial vaginosis was based on a Nugent's Gram stain score of 7 or higher. Thirty-two percent of participants douched in every study interval, and 43.0% never douched. Of the 12,349 study visits, 40.2% were classified as involving bacterial vaginosis. The relative risk for regular douching as compared with no douching was 1.21 (95% confidence interval: 1.08, 1.38). These findings indicate that douching confers increased risk of disruption of vaginal flora. In the absence of a large randomized trial, these findings provide the best evidence to date for a risk of bacterial vaginosis associated with douching.",
"title": "A Longitudinal Study of Vaginal Douching and Bacterial Vaginosis—A Marginal Structural Modeling Analysis"
},
{
"docid": "MED-3655",
"text": "OBJECTIVES: Bacterial vaginosis (BV), a disturbance of vaginal microflora, is a common cause of vaginal symptoms and is associated with an increased risk of acquisition of sexually transmitted infections, HIV, and with adverse pregnancy outcomes. We determined prevalence and associations with BV among a representative sample of women of reproductive age in the United States. STUDY DESIGN: Women aged 14-49 years participating in the National Health and Nutrition Examination Survey 2001-2004 were asked to submit a self-collected vaginal swab for Gram staining. BV, determined using Nugent's score, was defined as a score of 7-10. RESULTS: The prevalence of BV was 29.2% (95% confidence interval 27.2%-31.3%) corresponding to 21 million women with BV; only 15.7% of the women with BV reported vaginal symptoms. Prevalence was 51.4% among non-Hispanic blacks, 31.9% among Mexican Americans, and 23.2% among non-Hispanic whites (P <0.01 for each comparison). Although BV was also associated with poverty (P <0.01), smoking (P <0.05), increasing body mass index (chi2 P <0.0001 for trend), and having had a female sex partner (P <0.005), in the multivariate model, BV only remained positively associated with race/ethnicity, increasing lifetime sex partners (chi2 P <0.001 for trend), increasing douching frequency (chi2 P for trend <0.001), low educational attainment (P <0.01), and inversely associated with current use of oral contraceptive pills (P <0.005). CONCLUSION: BV is a common condition; 84% of women with BV did not report symptoms. Because BV increases the risk of acquiring sexually transmitted infections, BV could contribute to racial disparities in these infections.",
"title": "The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health."
},
{
"docid": "MED-3654",
"text": "Nutrient profiling of foods, described as the science of ranking foods based on their nutrient content, is fast becoming the basis for regulating nutrition labels, health claims, and marketing and advertising to children. A number of nutrient profile models have now been developed by research scientists, regulatory agencies, and by the food industry. Whereas some of these models have focused on nutrients to limit, others have emphasized nutrients known to be beneficial to health, or some combination of both. Although nutrient profile models are often tailored to specific goals, the development process ought to follow the same science-driven rules. These include the selection of index nutrients and reference amounts, the development of an appropriate algorithm for calculating nutrient density, and the validation of the chosen nutrient profile model against healthy diets. It is extremely important that nutrient profiles be validated rather than merely compared to prevailing public opinion. Regulatory agencies should act only when they are satisfied that the scientific process has been followed, that the algorithms are transparent, and that the profile model has been validated with respect to objective measures of a healthy diet.",
"title": "Nutrient profiling of foods: creating a nutrient-rich food index."
}
] |
[
{
"docid": "MED-5126",
"text": "Background The recent increased interest in consuming green vegetable sprouts has been tempered by the fact that fresh sprouts can in some cases be vehicles for food-borne illnesses. They must be grown according to proper conditions of sanitation and handled as a food product rather than as an agricultural commodity. When sprouts are grown in accordance with the criteria proposed from within the sprout industry, developed by regulatory agencies, and adhered to by many sprouters, green sprouts can be produced with very low risk. Contamination may occur when these guidelines are not followed. Methods A one year program of microbial hold-and-release testing, conducted in concert with strict seed and facility cleaning procedures by 13 U.S. broccoli sprout growers was evaluated. Microbial contamination tests were performed on 6839 drums of sprouts, equivalent to about 5 million consumer packages of fresh green sprouts. Results Only 24 (0.75%) of the 3191 sprout samples gave an initial positive test for Escherichia coli O157:H7 or Salmonella spp., and when re-tested, 3 drums again tested positive. Composite testing (e.g., pooling up to 7 drums for pathogen testing) was equally sensitive to single drum testing. Conclusion By using a \"test-and-re-test\" protocol, growers were able to minimize crop destruction. By pooling drums for testing, they were also able to reduce testing costs which now represent a substantial portion of the costs associated with sprout growing. The test-and-hold scheme described herein allowed those few batches of contaminated sprouts to be found prior to packaging and shipping. These events were isolated, and only safe sprouts entered the food supply.",
"title": "Pathogen detection, testing, and control in fresh broccoli sprouts"
},
{
"docid": "MED-4867",
"text": "Stevioside, a constituent of Stevia rebaudiana, is commonly used as a non-caloric sugar substitute in Japan. The genetic toxicities of stevioside and its aglycone, steviol, were examined with seven mutagenicity tests using bacteria (reverse mutation assay, forward mutation assay, umu test and rec assay), cultured mammalian cells (chromosomal aberration test and gene mutation assay) and mice (micronucleus test). Stevioside was not mutagenic in any of the assays examined. The aglycone, steviol, however, produced dose-related positive responses in some mutagenicity tests, i.e. the forward mutation assay using Salmonella typhimurium TM677, the chromosomal aberration test using Chinese hamster lung fibroblast cell line (CHL) and the gene mutation assay using CHL. Metabolic activation systems containing 9000 g supernatant fraction (S9) of liver homogenates prepared from polychlorinated biphenyl or phenobarbital plus 5,6-benzoflavone-pretreated rats were required for mutagenesis and clastogenesis. Steviol was weakly positive in the umu test using S.typhimurium TA1535/pSK1002 either with or without the metabolic activation system. Steviol, even in the presence of the S9 activation system, was negative in other assays, i.e. the reverse mutation assays using S.typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and Escherichia coli WP2 uvrA/pKM101 and the rec-assay using Bacillus subtilis. Steviol was negative in the mouse micronucleus test. The genotoxic risk of steviol to humans is discussed.",
"title": "Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays."
},
{
"docid": "MED-1696",
"text": "Summary To assess sources of variability in platelet function tests in normal subjects, 64 healthy young adults were tested on 2–6 occasions at 2 week intervals using 4 methods: platelet aggregation (AGG) in platelet-rich plasma (PRP) in the Bio/Data PAP-4 Aggregometer (BD) and Chrono-Log Lumi-Aggregometer (CL); and AGG in whole blood (WB) in the CL and Multiplate Platelet Function Analyzer (MP), with ATP release (REL) in CL-PRP and CL-WB. Food and medication exposures were recorded prospectively for 2 weeks prior to each blood draw. At least one AGG abnormality was seen in 21% of 81 drug-free specimens with CL-PRP, 15% with CL-WB, 13% with BD-PRP, and 6% with MP-WB, increasing with inclusion of REL to 28% for CL-PRP and 30% for CL-WB. Epinephrine AGG and REL were significantly reduced in males (P<0.0001). Ristocetin AGG and collagen and thrombin REL were significantly reduced in Blacks (P<0.0001). One-third of specimens drawn following flavonoid-rich food exposures had aberrant results, compared to 8.5% of specimens without such exposures (P=0.0035). PRP tests had less intra-individual variation than WB tests. Gender, race, diet, and test system affected results of platelet function testing in healthy subjects, suggesting caution when interpreting the results of platelet function testing in patients.",
"title": "Gender, Race, and Diet Affect Platelet Function Tests in Normal Subjects Contributing to a High Rate of Abnormal Results"
},
{
"docid": "MED-2648",
"text": "The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.",
"title": "Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals"
},
{
"docid": "MED-2910",
"text": "Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.",
"title": "Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure"
},
{
"docid": "MED-306",
"text": "Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.",
"title": "Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure"
},
{
"docid": "MED-4583",
"text": "Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.",
"title": "Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study."
},
{
"docid": "MED-1980",
"text": "Enterobacterial strains producing clavulanic-acid-inhibited extended-spectrum β-lactamases (ESBLs) are increasingly reported worldwide. Conventional detection of ESBL production remains time-consuming (24 to 48 h). Therefore, the ESBL NDP (Nordmann/Dortet/Poirel) test was developed for a rapid identification of ESBLs in Enterobacteriaceae. This biochemical test was based on the in vitro detection of a cephalosporin (cefotaxime) hydrolysis that is inhibited by tazobactam addition. The ESBL activity was evidenced by a color change (red to yellow) of a pH indicator (red phenol) due to carboxyl-acid formation resulting from cefotaxime hydrolysis that was reversed by addition of tazobactam (positive test). The ESBL NDP test was applied to cultured strains (215 ESBL producers and 40 ESBL nonproducers). Its sensitivity and specificity were 92.6% and 100%, respectively. Its sensitivity (100%) was excellent for detection of CTX-M producers. A few ESBL producers (n = 16) that remained susceptible to cefotaxime were not detected. The test was also evaluated on spiked blood cultures and showed excellent sensitivity and specificity (100% for both). The test was rapid (less than 1 h) and cost-effective. It can be implemented in any health care facility and is well adapted for infection control purposes in particular.",
"title": "Rapid Detection of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae"
},
{
"docid": "MED-3659",
"text": "We report the annual results of patch testing with lavender oil for a 9-year period from 1990 to 1998 in Japan. Using Finn Chambers and Scanpor tape, we performed 2-day closed patch testing with lavender oil 20% pet. on the upper back of each patient suspected of having cosmetic contact dermatitis. We compared the frequency of positive patch tests to lavender oil each year with those to other fragrances. We diagnosed contact allergy when patch test reactions were + or <+ at 1 day after removal. The positivity rate of lavender oil was 3.7% (0-13.9%) during the 9-year period from 1990 to 1998. The positivity rate of lavender oil increased suddenly in 1997. Recently, in Japan, there has been a trend for aromatherapy using lavender oil. With this trend, placing dried lavender flowers in pillows, drawers, cabinets, or rooms has become a new fashion. We asked patients who showed a positive reaction to lavender oil about their use of dried lavender flowers. We confirmed the use of dried lavender flowers in 5 cases out of 11 positive cases in 1997 and 8 out of 15 positive cases in 1998. We concluded that the increase in patch test positivity rates to lavender oil in 1997 and 1998 was due to the above fashion, rather than due to fragrances in cosmetic products.",
"title": "Results of patch testing with lavender oil in Japan."
},
{
"docid": "MED-960",
"text": "AIMS: Serum cobalamin (cbl, vitamin B(12)) tests are routinely ordered for investigating conditions potentially amenable to cbl supplementation. This study aimed to systematically assess the evidence of diagnostic accuracy for serum cbl tests across patient subgroups. METHODS: Seven medical databases were searched (1990 to November 2009). Studies were included that compared serum cbl to a reference standard (all reference standards employed). Study quality was assessed using QUADAS. Summary estimates of test performance were determined using the bivariate model and hierarchical summary receiver operating characteristic curves (HSROC). RESULTS: Of 2878 identified studies, 54 were included. Studies rated poorly against QUADAS criteria. Positive (PLR) and negative likelihood ratios (NLR) were 2.72 [95% confidence interval (CI) 1.95, 3.81] and 0.59 (0.49, 0.72), respectively (studies employing methylmalonic acid as the referent). In studies employing a clinical reference standard, PLR was 3.33 (0.92, 12.10) and NLR 0.34 (0.13, 0.89). Test performance did not vary by clinical indication, test method or age. CONCLUSION: This review was limited by the quality of the evidence base and lack of a gold standard. From the available evidence, diagnosis of conditions amenable to cbl supplementation on the basis of serum cbl level alone cannot be considered a reliable approach to investigating suspected vitamin deficiency.",
"title": "Diagnostic performance of serum cobalamin tests: a systematic review and meta-analysis."
},
{
"docid": "MED-1443",
"text": "SUMMARY BACKGROUND: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti-inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo. METHODS: 40 volunteers were enrolled in this monocentric,randomized,placebo-controlled double-blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV-B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place-bo.The effect of the test substances on the UV-induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non-irradiated skin. RESULTS: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV-induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent. CONCLUSIONS: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.",
"title": "Anti-inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test."
},
{
"docid": "MED-2352",
"text": "BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.",
"title": "Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose."
},
{
"docid": "MED-1726",
"text": "Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.",
"title": "Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles"
},
{
"docid": "MED-2618",
"text": "BACKGROUND: Food dyes, synthesized originally from coal tar and now petroleum, have long been controversial because of safety concerns. Many dyes have been banned because of their adverse effects on laboratory animals or inadequate testing. CONCLUSIONS: This review finds that all of the nine currently US-approved dyes raise health concerns of varying degrees. Red 3 causes cancer in animals, and there is evidence that several other dyes also are carcinogenic. Three dyes (Red 40, Yellow 5, and Yellow 6) have been found to be contaminated with benzidine or other carcinogens. At least four dyes (Blue 1, Red 40, Yellow 5, and Yellow 6) cause hypersensitivity reactions. Numerous microbiological and rodent studies of Yellow 5 were positive for genotoxicity. Toxicity tests on two dyes (Citrus Red 2 and Orange B) also suggest safety concerns, but Citrus Red 2 is used at low levels and only on some Florida oranges and Orange B has not been used for several years. The inadequacy of much of the testing and the evidence for carcinogenicity, genotoxicity, and hypersensitivity, coupled with the fact that dyes do not improve the safety or nutritional quality of foods, indicates that all of the currently used dyes should be removed from the food supply and replaced, if at all, by safer colorings. It is recommended that regulatory authorities require better and independent toxicity testing, exercise greater caution regarding continued approval of these dyes, and in the future approve only well-tested, safe dyes.",
"title": "Toxicology of food dyes."
},
{
"docid": "MED-885",
"text": "Oxalate bioavailability from sugar beet fibre (40 g), spinach (25 g) and a solution of sodium oxalate (182 mg) was tested in nine women using a triplicated 3 x 3 Latin square arrangement. Each test substance provided 120 mg oxalic acid. Throughout the study the volunteers consumed a control diet and the test substances were administered at breakfast on specified days. After an initial 2-day control period, oxalate was administered in three test periods that consisted of one test day followed by one control day. Urine collected during 24-hr periods was analysed daily for oxalate. Oxalate excretion did not differ among the five control days and was not increased significantly following the ingestion of sugar beet fibre by the volunteers. Oxalate excretion was greater (P less than 0.0001) for the mean of the spinach and sodium oxalate solution diets than for the mean of the sugar beet fibre and control diets. Oxalate bioavailability from sugar beet fibre was 0.7% compared with bioavailabilities of 4.5 and 6.2% for spinach and oxalate solutions, respectively. The low bioavailability of oxalate from sugar beet fibre may be attributable to its high ratio of minerals (calcium and magnesium) to oxalate, its complex fibre matrix or the loss of the soluble oxalate during processing of sugar beets.",
"title": "Bioavailability of oxalic acid from spinach, sugar beet fibre and a solution of sodium oxalate consumed by female volunteers."
},
{
"docid": "MED-4605",
"text": "Sorbic acid, sodium sorbate and potassium sorbate were tested for their genotoxic potential in the Syrian hamster embryo (SHE) fibroblast micronucleus assay and the SHE cell transformation test in vitro. Sorbic acid and potassium sorbate showed no activity in either test system. When freshly prepared sodium sorbate solutions were used, no genotoxic or cell-transforming activity was detected. However, sodium sorbate as stored solution, which previously had been heated and sonicated to facilitate solubilization, yielded a positive response in both test systems. It is concluded that oxidation products of sodium sorbate that possess genotoxic and cell-transforming properties are formed under conditions of heating, sonication and storage.",
"title": "Genotoxicity and cell transformation studies with sorbates in Syrian hamster embryo fibroblasts."
},
{
"docid": "MED-4091",
"text": "In this study, six common tests for measuring antioxidant activity were evaluated by comparing four antioxidants and applying them to beverages (tea and juices): Trolox equivalent antioxidant capacity assay (TEAC I-III assay), Total radical-trapping antioxidant parameter assay (TRAP assay), 2,2-diphenyl-l-picrylhydrazyl assay (DPPH assay), N,N-dimethyl-p-phenylendiamine assay (DMPD assay), Photochemiluminescence assay (PCL assay) and Ferric reducing ability of plasma assay (FRAP assay). The antioxidants included gallic acid representing the group of polyphenols, uric acid as the main antioxidant in human plasma, ascorbic acid as a vitamin widely spread in fruits and Trolox as water soluble vitamin E analogue. The six methods presented can be divided into two groups depending on the oxidising reagent. Five methods use organic radical producers (TEAC I-III, TRAP, DPPH, DMPD, PCL) and one method works with metal ions for oxidation (FRAP). Another difference between these tests is the reaction procedure. Three assays use the delay in oxidation and determine the lag phase as parameter for the antioxidant activity (TEAC I, TRAP, PCL). They determine the delay of radical generation as well as the ability to scavenge the radical. In contrast, the assays TEAC II and III, DPPH, DMPD and FRAP analyse the ability to reduce the radical cation (TEAC II and III, DPPH, DMPD) or the ferric ion (FRAP). The three tests acting by radical reduction use preformed radicals and determine the decrease in absorbance while the FRAP assay measures the formed ferrous ions by increased absorbance. Gallic acid was the strongest antioxidant in all tests with exception of the DMPD assay. In contrast, uric acid and ascorbic acid showed low activity in some assays. Most of the assays determine the antioxidant activity in the micromolar range needing minutes to hours. Only one assay (PCL) is able to analyse the antioxidant activity in the nanomolar range. Black currant juice showed highest antioxidant activity in all tests compared to tea, apple juice and tomato juice. Despite these differences, results of these in vitro assays give an idea of the protective efficacy of secondary plant products. It is strongly recommended to use at least two methods due to the differences between the test systems investigated.",
"title": "Assessment of antioxidant activity by using different in vitro methods."
},
{
"docid": "MED-3146",
"text": "Seeds of the opium poppy plant are legally sold and widely consumed as food. Due to contamination during harvesting, the seeds can contain morphine and other opiate alkaloids. The objective of this study is to review the toxicology of poppy seed foods regarding influence on opiate drug tests. Computer-assisted literature review resulted in 95 identified references. Normal poppy seed consumption is generally regarded as safe. During food processing, the morphine content is considerably reduced (up to 90%). The possibility of false-positive opiate drug tests after poppy food ingestion exists. There are no unambiguous markers available to differentiate poppy food ingestion from heroin or pharmaceutical morphine use. This is also a problem in heroin-assisted maintenance programs. A basic requirement in such substitution programs is the patients' abstinence from any other drugs, including additional illicit heroin. Also a lack of forensic ingestion trials was detected that consider all factors influencing the morphine content in biologic matrices after consumption. Most studies did not control for the losses during food processing, so that the initial morphine dosage was overestimated. The large reduction of the morphine content during past years raises questions about the validity of the \"poppy seed defence.\" However, a threshold of food use that would not lead to positive drug tests with certainty is currently unavailable. Research is needed to prove if the morphine contents in today's foods still pose the possibility of influencing drug tests. Future trials should consider processing-related morphine losses.",
"title": "Poppy seed foods and opiate drug testing--where are we today?"
},
{
"docid": "MED-2257",
"text": "Background Low-level environmental cadmium exposure and neurotoxicity has not been well studied in adults. Our goal was to evaluate associations between neurocognitive exam scores and a biomarker of cumulative cadmium exposure among adults in the Third National Health and Nutrition Examination Survey (NHANES III). Methods NHANES III is a nationally representative cross-sectional survey of the U.S. population conducted between 1988 and 1994. We analyzed data from a subset of participants, age 20–59, who participated in a computer-based neurocognitive evaluation. There were four outcome measures: the Simple Reaction Time Test (SRTT: visual motor speed), the Symbol Digit Substitution Test (SDST: attention/perception), the Serial Digit Learning Test (SDLT) trials-to-criterion, and the SDLT total-error-score (SDLT-tests: learning recall/short-term memory). We fit multivariable-adjusted models to estimate associations between urinary cadmium concentrations and test scores. Results 5662 participants underwent neurocognitive screening, and 5572 (98%) of these had a urinary cadmium level available. Prior to multivariable-adjustment, higher urinary cadmium concentration was associated with worse performance in each of the 4 outcomes. After multivariable-adjustment most of these relationships were not significant, and age was the most influential variable in reducing the association magnitudes. However among never-smokers with no known occupational cadmium exposure the relationship between urinary cadmium and SDST score (attention/perception) was significant: a 1 μg/L increase in urinary cadmium corresponded to a 1.93% (95%CI: 0.05, 3.81) decrement in performance. Conclusions These results suggest that higher cumulative cadmium exposure in adults may be related to subtly decreased performance in tasks requiring attention and perception, particularly among those adults whose cadmium exposure is primarily though diet (no smoking or work based cadmium exposure). This association was observed among exposure levels that have been considered to be without adverse effects and these levels are common in U.S. adults. Thus further research into the potential neurocognitive effects of cadmium exposure is warranted. Because cumulative cadmium exposure may mediate some of the effects of age and smoking on cognition, adjusting for these variables may result in the underestimation of associations with cumulative cadmium exposure. Prospective studies that include never-smokers and non-occupationally exposed individuals are needed to clarify these issues.",
"title": "Associations between cadmium exposure and neurocognitive test scores in a cross-sectional study of US adults"
},
{
"docid": "MED-4400",
"text": "Milk is one of the main source of biologically-active peptides that may function as regulatory substances called food hormones. After passing the gut-blood barrier, the μ-opioid receptor agonist and antagonist peptides may become the new factors influencing various functions of the human organism. The aim of the conducted research was to determine the influence of μ-opioid receptor agonist peptides: human and bovine β-casomorphin-7 (h/bBCM-7) and antagonistic peptides: casoxin-6 and- D (CXN-6/D) on proliferation and cytokine secretion of human peripheral blood mononuclear cells (PBMCs). The PBMCs proliferation was measured by the use of the BrdU test, which assesses the DNA synthesis activity and the WST-1 test which assesses the activity of mitochondrial dehydrogenase enzymes. The influence of all the investigated peptides on secretion of IL-4, IL-8, IL-13 and IFN-γ was determined by the use of the ELISA tests. Incubating the cells with the peptides has not caused any changes to their enzymatic activity, which has been proved by a WST-1 test. When using a BrdU test, however, it has been observed that there appear changes to proliferation of PBMCs correlated to amounts of bromodeoxyuridine incorporated into the cellular DNA. Moreover, changes to secretion of IL-4 and IL-13 by the cells under the influence of agonists were detected, as well as changes to secretion of IFN-gamma under the influence of all the examined substances. The obtained results provide information on immunomodulatory effects of food-derived opioid peptides, which may be of clinical significance especially in the case of allergic diseases in newborns. Copyright © 2010 Elsevier Inc. All rights reserved.",
"title": "The influence of μ-opioid receptor agonist and antagonist peptides on peripheral blood mononuclear cells (PBMCs)."
},
{
"docid": "MED-4029",
"text": "We compared the effect on enamel demineralisation in situ of both whole and juiced fruits and vegetables. Volunteers wore removable mandibular appliances carrying pre-demineralised human enamel slabs and consumed one of the test foods 7 times a day for 10 days. The test foods were apples, oranges, grapes, carrots, and tomatoes, consumed either whole (sugars located intrinsically) or as a juice (extrinsic or free sugars). Raisins containing 64% sugars, but intrinsic by definition, were also studied. The mineral profile of the enamel slabs was studied before and after the test period using transverse microradiography and showed further demineralisation for all test foods, irrespective of the form of consumption. Significant demineralisation was also observed with raisins. No significant differences were found between the solid and juiced foods. In conclusion, sugars present intrinsically on consumption had a similar demineralising potential as free sugars and could not be considered less cariogenic. Copyright © 2011 S. Karger AG, Basel.",
"title": "Comparison of the effects of whole and juiced fruits and vegetables on enamel demineralisation in situ."
},
{
"docid": "MED-2219",
"text": "Our laboratory recently reported that a 3-month exposure of rats to cola-like beverages induced sex hormone changes. The aim of the study was to investigate the effects of various types of Coca-cola intake with different composition for 6 months on oxidative status in testes and testosterone in adult male rats. Fifty adult male Wistar rats were divided into control group drinking water, and groups drinking different Coca-cola beverages (regular Coca-cola, Coca-cola caffeine-free, Coca-cola Light and Coca-cola Zero). Oxidative and carbonyl stress markers were measured in the testicular tissue to assess oxidative status together with testicular and plasma testosterone. StAR expression in testes as a marker of steroidogenesis was quantified. No significant differences were found between the groups in any of the measured parameters. In conclusion, oxidative and carbonyl stress in testicular tissue were not influenced by drinking any type of Coca-cola. Additionally, testosterone in testes and in plasma, as well as testicular StAR expression were comparable among the groups. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "No harmful effect of different Coca-cola beverages after 6 months of intake on rat testes."
},
{
"docid": "MED-1131",
"text": "To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.",
"title": "Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet."
},
{
"docid": "MED-2060",
"text": "Cow's milk protein (CMP) allergy was investigated in 25 children (age-range 3 months to 11 years) with chronic constipation. A diagnosis of constipation was made on the basis of a history of painful elimination of hard stools for at least 1 month, whether or not associated with a reduced frequency of stools or soiling. The children were evaluated using clinical parameters and the following laboratory tests: total serum immunoglobulin E (IgE); specific IgE (radioallergosorbent test [RAST]) for whole cow's milk, alpha-lactoalbumin, beta-lactoglobulin, and a food group; and skin-prick tests with whole milk, alpha-lactoalbumin, beta-lactoglobulin, and casein. Following the evaluation, the children were submitted to a CMP-free diet for a period of 4 weeks. In seven patients (28%), constipation disappeared during the CMP-free diet and reappeared within 48-72 h following challenge with cow's milk. In two infants a rectal biopsy revealed allergic colitis and they therefore did not undergo the challenge. High serum levels of total IgE were observed in five of the children who showed a clinical improvement (71%), a positive skin-test in two (29%), and detectable specific IgE in two (29%). These results suggest that CMP allergy or intolerance should be considered as a cause of chronic refractory constipation in children, although the underlying mechanism still require further investigation.",
"title": "Cow's milk protein intolerance and chronic constipation in children."
},
{
"docid": "MED-2676",
"text": "Smokehouse smoke, which is used for flavouring meat products, was investigated for its mutagenic activity in the Salmonella typhimurium assay. We were chiefly concerned with the fractions free of polycyclic aromatic hydrocarbons but containing phenol compounds, which are responsible for the preservative and aromatizing properties of the smoke. The most abundantly occurring phenol compounds (phenol, cresols, 2,4-dimethylphenol, brenzcatechine, syringol, eugenol, vanilline and guaiacol) gave negative results when they were tested for mutagenicity at five concentrations up to 5000 micrograms/plate, with and without S-9 mix, using five strains of S. typhimurium. Even when phenol was further investigated in a variety of test conditions, no induction of his+ revertants was observed. When smokehouse smoke was condensed and fractionated the majority of the various phenolic fractions also gave negative results when tested at five concentrations using five strains of S. typhimurium. However there was a slight increase in the number of revertants in a few cases. The presence in the phenolic fractions of very small amounts of mutagenic impurities, the nature of which needs further investigation, cannot be excluded. These results support the further development of non-hazardous smoke-aroma preparations, based on the phenolic components of smokehouse smoke.",
"title": "Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates."
},
{
"docid": "MED-3808",
"text": "Methylchavicol (or estragole), a natural flavouring substance present in tarragon, was confirmed as a genotoxic chemical in the in vitro UDS test in cultured rat hepatocytes and in the in vivo UDS test in hepatocytes of exposed rats. Deep-frozen tarragon was clearly less genotoxic than methylchavicol at equivalent dose levels, and desiccated tarragon was negative. Both forms of tarragon tested in vitro have the ability to decrease significantly the genotoxicity of methylchavicol added to the culture medium at concentrations </=10 muM for deep-frozen and </=55 muM for desiccated tarragon. The decrease may be attributed to antimutagenic properties of tarragon leaves and/or to adsorption of methylchavicol, which would decrease its bioavailability. Desiccated tarragon powder was not genotoxic in the in vivo UDS test when administered up to the maximum dose of 6.25 g/kg bw (18.75 mg/kg bw of methylchavicol). In vivo, desiccated tarragon did not show antimutagenic properties, because it did not decrease the genotoxicity of methylchavicol added at high concentrations. Considering the low exposure level at the maximum daily tarragon consumption, the rapid detoxification and excretion in humans and the no-genotoxic-effect-level of methylchavicol by the oral route when given to rats as tarragon leaves, a high margin of exposure exists. We can conclude that tarragon consumption presents no genotoxic risk to humans. Copyright © 2009 Elsevier B.V. All rights reserved.",
"title": "Risk assessment of consumption of methylchavicol and tarragon: the genotoxic potential in vivo and in vitro."
},
{
"docid": "MED-709",
"text": "The sub-chronic effect of Hibiscus sabdariffa (HS) calyx aqueous extract on the rat testes was investigated with a view to evaluate the pharmacological basis for the use of HS calyx extract as an aphrodisiac. Three test groups received different doses of 1.15, 2.30, and 4.60 g/kg based on the LD(50). The extracts were dissolved in the drinking water. The control group was given equivalent volume of water only. The animals were allowed free access to drinking solution during the 12-week period of exposure. At the expiration of the treatment period, animals were sacrificed, testes excised and weighed, and epididymal sperm number recorded. The testes were processed for histological examination. Results did not show any significant (P>0.05) change in the absolute and relative testicular weights. There was, however, a significant (P<0.05) decrease in the epididymal sperm counts in the 4.6 g/kg group, compared to the control. The 1.15 g/kg dose group showed distortion of tubules and a disruption of normal epithelial organization, while the 2.3 g/kg dose showed hyperplasia of testis with thickening of the basement membrane. The 4.6 g/kg dose group, on the other hand, showed disintegration of sperm cells. The results indicate that aqueous HS calyx extract induces testicular toxicity in rats.",
"title": "Testicular effects of sub-chronic administration of Hibiscus sabdariffa calyx aqueous extract in rats."
},
{
"docid": "MED-2713",
"text": "OBJECTIVES: The objective of this study was to evaluate the potential anxiolytic effect of sweet orange (Citrus sinensis) aroma in healthy volunteers submitted to an anxiogenic situation. DESIGN: Forty (40) male volunteers were allocated to five different groups for the inhalation of sweet orange essential oil (test aroma: 2.5, 5, or 10 drops), tea tree essential oil (control aroma: 2.5 drops), or water (nonaromatic control: 2.5 drops). Immediately after inhalation, each volunteer was submitted to a model of anxiety, the video-monitored version of the Stroop Color-Word Test (SCWT). OUTCOME MEASURES: Psychologic parameters (state-anxiety, subjective tension, tranquilization, and sedation) and physiologic parameters (heart rate and gastrocnemius electromyogram) were evaluated before the inhalation period and before, during, and after the SCWT. RESULTS: Unlike the control groups, the individuals exposed to the test aroma (2.5 and 10 drops) presented a lack of significant alterations (p>0.05) in state-anxiety, subjective tension and tranquillity levels throughout the anxiogenic situation, revealing an anxiolytic activity of sweet orange essential oil. Physiologic alterations along the test were not prevented in any treatment group, as has previously been observed for diazepam. CONCLUSIONS: Although more studies are needed to find out the clinical relevance of aromatherapy for anxiety disorders, the present results indicate an acute anxiolytic activity of sweet orange aroma, giving some scientific support to its use as a tranquilizer by aromatherapists.",
"title": "Effect of sweet orange aroma on experimental anxiety in humans."
},
{
"docid": "MED-3458",
"text": "The single cell gel electrophoresis (SCG) assay (comet assay) is a sensitive technique for detecting the presence of DNA strand-breaks and alkali-labile damage in individual cells. This technique was used to study peripheral blood cells from three volunteers after physical activity. The test subjects had to run on a treadmill and were checked for blood pressure and ECG, lactate concentration and creatine kinase activity. Blood was taken before and several times during and after the run. In a first multiple step test, the volunteers ran as long as possible with increasing speed. In a second test they had to run for 45 min with a fixed individual speed which was defined to ensure an aerobic metabolism. In the first test, the white blood cells of all subjects showed increased DNA migration in the SCG assay. The effect was seen 6 h after the end of the exercise and reached its maximum 24 h later. After 72 h, DNA migration decreased to about control level. The distribution of DNA migration among cells clearly demonstrated that the majority of white blood cells exhibited increased DNA migration and that the effect was not only due to a small fraction of damaged cells. From the same blood samples, blood cultures were set up to study a possible effect on the frequency of sister chromatid exchanges (SCE), another indicator for genotoxic effects. However, there was no significant increase in SCE in any of the cultures. In the second exercise, during aerobic metabolism, the effect on DNA migration was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Does physical activity induce DNA damage?"
},
{
"docid": "MED-4137",
"text": "Swine have been identified as the primary reservoir of pathogenic Yersinia enterocolitica (YE), but little research has focused on the epidemiology of YE at the farm level. The objective of this study was to describe the prevalence of YE in different production phases on swine farms. In this cross-sectional study, individual pigs on eight swine operations were sampled for the presence of YE. On each farm, both feces and oral-pharyngeal swabs were collected from pigs in five different production phases: gestating, farrowing, suckling, nursery, and finishing. A pig was considered positive if either sample tested positive. Samples were cultured with cold enrichment followed by isolation on selective media plates. Presumptive isolates were confirmed as YE and assayed for the presence of ail with a multiplex PCR. Of the 2,349 pigs sampled, 120 (5.1%) tested positive, and of those, 51 were ail positive (42.5% of YE isolates). On all farms, there was a trend of increasing prevalence as pigs mature. Less than 1% of suckling piglets tested positive for YE. Only 1.4% (44.4% of which were ail positive) of nursery pigs tested positive, but 10.7% (48.1% of which were ail positive) of finishing pigs harbored YE. Interestingly, gestating sows had the second highest prevalence of YE at 9.1% (26.7% of which were ail positive), yet YE was never detected from the farrowing sows. These results represent the first on-farm description of YE in U.S. herds and provide the initial step for designing future studies of YE.",
"title": "Prevalence of Yersinia enterocolitica in different phases of production on swine farms."
}
] |
PLAIN-340
|
Do Walnuts Really Improve Artery Function?
|
[
{
"docid": "MED-4292",
"text": "There is currently no single dietary or lifestyle intervention that is effective in long-term weight loss. Traditional weight loss diets tend to be low in total fat and therefore often restrict nut consumption. However, nuts are an important source of many vitamins, minerals, monounsaturated and polyunsaturated fatty acids. This paper reviewed all the available evidence from the literature in relation to nut consumption and body weight. The findings show that the role of nut consumption in body weight management is varied. Nuts, when included as part of an energy-controlled diet, were found in some instances to assist with weight loss. However, when nuts were added to an existing diet without controlling for energy intake, body weight increased, although to a lesser extent than theoretically predicted. There is limited evidence on the effect nut consumption has on type 2 diabetes, although available evidence indicates that nuts as part of a healthy diet do not cause weight gain and can have a positive influence on the fatty acid profile of a person with diabetes. This review shows there is a lack of evidence to support the restriction of nut consumption in weight management, indicating that further research is needed to assess the role of nuts in weight management.",
"title": "A review of the evidence: nuts and body weight."
},
{
"docid": "MED-2384",
"text": "BACKGROUND: Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS: The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS: Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION: Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit. Copyright © 2013 National Lipid Association. All rights reserved.",
"title": "Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects."
},
{
"docid": "MED-2596",
"text": "BACKGROUND Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. METHODS We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses’ Health Study (1980–2010) and 42,498 men in the Health Professionals Follow-up Study (1986–2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. RESULTS During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. CONCLUSIONS In two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death. (Funded by the National Institutes of Health and the International Tree Nut Council Nutrition Research and Education Foundation.)",
"title": "Association of Nut Consumption with Total and Cause-Specific Mortality"
},
{
"docid": "MED-2380",
"text": "BACKGROUND AND AIMS: High blood pressure (BP) is considered a major risk factor for cardiovascular disease. Among lifestyle factors, diet plays a key role in the prevention and control of high BP. Therefore, it is important to elucidate which dietary components can exert beneficial effects on BP through modulation of endothelial function (EF) or by other mechanisms. In this paper we review the role of nutrients, foods, particularly nuts, and dietary patterns on BP control. DATA SYNTHESIS: Because nuts are low in sodium and contain significant amounts of mono- and polyunsaturated fatty acids, fiber, minerals such as magnesium, potassium and calcium, and antioxidants, they have been suggested as potentially protective foods against hypertension. Limited evidence from prospective studies and clinical trials suggests that nut consumption has a beneficial effect on both BP and EF. However, BP changes were a secondary outcome in nut feeding trials and no study used ambulatory BP monitoring as the standard for BP measurements. CONCLUSIONS: Further clinical trials, ideally using ambulatory BP monitoring, are needed to establish the potential protective effect of nut consumption on hypertension and vascular reactivity. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Nuts, hypertension and endothelial function."
},
{
"docid": "MED-4291",
"text": "BACKGROUND AND AIMS: Short-term trials support that adding tree nuts or peanuts to usual diets does not induce weight gain. We reviewed the available epidemiological evidence on long-term nut consumption and body weight changes. We also report new results from the SUN (\"Seguimiento Universidad de Navarra\") cohort. METHODS AND RESULTS: Published epidemiologic studies with ≥1-yr follow-up were located. Two published reports from large cohorts (SUN and Nurses Health Study-2) showed inverse associations between frequency of nut consumption and long-term weight changes. A beneficial effect of a Mediterranean diet supplemented with tree nuts on waist circumference was reported after 1-yr follow-up in the first 1224 high-risk participants in the PREDIMED (\"PREvencion DIeta MEDiterranea\") trial. After assessing 11,895 participants of the SUN cohort, a borderline significant (p value for trend = 0.09) inverse association between baseline nut consumption and average yearly weight gain (multivariate-adjusted means = 0.32 kg/yr (95% confidence interval: 0.22-0.42) and 0.24 (0.11-0.37) kg/yr for participants with no consumption and >4 servings/week, respectively) was found after a 6-yr follow-up. CONCLUSIONS: Consumption of nuts was not associated with a higher risk of weight gain in long-term epidemiologic studies and clinical trials. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Nut consumption, weight gain and obesity: Epidemiological evidence."
},
{
"docid": "MED-2382",
"text": "BACKGROUND: Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal allergic reactions in the United States, and the prevalence appears to be increasing. OBJECTIVES: We sought to determine the US prevalence of self-reported peanut, TN, and sesame allergy in 2008 and compare results with comparable surveys conducted in 1997 and 2002. METHODS: A nationwide, cross-sectional, random telephone survey for peanut and TN allergy was conducted with a previously used questionnaire, with additional questions about sesame. RESULTS: A total of 5,300 households (13,534 subjects) were surveyed (participation rate, 42% vs 52% in 2002 and 67% in 1997). Peanut allergy, TN allergy, or both was reported by 1.4% of subjects (95% CI, 1.2% to 1.6%) compared with 1.2% in 2002 and 1.4% in 1997. For adults, the prevalence was 1.3% (95% CI, 1.1% to 1.6%), which was not significantly different from prior surveys. However, the prevalence of peanut or TN allergy for children younger than 18 years was 2.1% (95% CI, 1.6% to 2.7%) compared with 1.2% in 2002 (P = .007) and 0.6% in 1997 (P < .001). The prevalence of peanut allergy in children in 2008 was 1.4% (95% CI, 1.0% to 1.9%) compared with 0.8% in 2002 (P = not significant) and 0.4% in 1997 (P < .0001). The prevalence of childhood TN allergy increased significantly across the survey waves (1.1% in 2008, 0.5% in 2002, and 0.2% in 1997). Sesame allergy was reported by 0.1% (95% CI, 0.0% to 0.2%). CONCLUSIONS: Although caution is required in comparing surveys, peanut allergy, TN allergy, or both continue to be reported by more than 1% of the US population (eg, >3 million subjects) and appear to be increasingly reported among children over the past decade. Sesame allergy is reported much less commonly. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.",
"title": "US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up."
},
{
"docid": "MED-2595",
"text": "Nuts are an integral part of the Mediterranean food patterns, and their incorporation into the regular diets of human beings is believed to provide many health benefits. The recent recognition of nuts as \"heart-healthy\" foods by the U.S. Food and Drug Administration has given a major boost to the positive image of nuts. Nut consumption has been associated with several health benefits, such as antioxidant, hypocholesterolemic, cardioprotective, anticancer, anti-inflammatory, and antidiabetic benefits, among other functional properties. However, although nuts possess these many health benefits, their consumption has been hampered by a lack of adequate information regarding those benefits. In addition, because nuts are energy-dense foods with high-fat content, there is a misconception among consumers that increased consumption may lead to unwanted gain in body weight with the risk of developing overweight/obesity. Nonetheless, available epidemiologic studies and short-term controlled feeding trials have supported the theory that the inclusion of nuts in the typical diet does not induce weight gain, despite an expected increase in total caloric intake. To address the misperception about nuts and body weight gain, the present review focuses mainly on the relation between nut consumption and body weight gain, in the context of the many health benefits of nuts. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Health benefits of nut consumption with special reference to body weight control."
},
{
"docid": "MED-4287",
"text": "OBJECTIVE: To study the effects of snacking based on fast acting carbohydrates (candy) or fat and protein (peanuts) in a prospective randomized, parallel intervention study. METHODS: Basal metabolic rate (BMR) and cardiovascular risk factors were measured before and after hyper-alimentation by addition of 20 kcal/kg (84 kJ/kg) body weight of either candy or roasted peanuts, to the regular caloric intake, for two weeks in healthy subjects. Eleven men and 14 women completed the randomized study. RESULTS: Energy-intake increased similarly in the groups (candy: +46.1+/-35%, peanuts: +46.8+/-28% p=0.96). Body-weight (candy: from 67.3+/-7.6 kg to 68.1+/-7.3 kg, p=0.01, nuts: from 68.7+/-6.1 kg to 69.0+/-5.7 kg p=0.3) and waist circumference increased significantly only in the candy group. At the end of the study LDL cholesterol (candy: 2.6+/-0.4 mmol/l peanuts: 2.1+/-0.4 mmol/l, p=0.005) and ApoB/ApoA-1-ratio (candy: 0.68+/-0.16 peanuts 0.53+/-0.11, p=0.01) were higher in the candy group than in the peanut group. On the other hand, BMR increased only in the peanut group (candy: from 6.657+/-1.1 MJ/24 h to 6.762+/-1.1 MJ/24 h, p=0.3 nuts: from 6.896+/-0.98 MJ/24 h to 7.256+/-1.1 MJ/24 h, p=0.02). CONCLUSION: Two weeks of snacking based on peanuts does not cause the same negative metabolic effects as an isocaloric diet in which the snacking is based on short acting carbohydrates in the form of candy in non-obese healthy subjects.",
"title": "Two weeks of overfeeding with candy, but not peanuts, increases insulin levels and body weight."
},
{
"docid": "MED-2597",
"text": "Since the beginning of the 1990s, increasing evidence supports beneficial effects of nut consumption on health. A new analysis of the Spanish PREDIMED trial, published in BMC Medicine, has expanded our knowledge. The study showed that individuals eating nuts more than three times per week died less often from cardiovascular disease and cancer than non-consumers. The study also adds an important finding that previous epidemiological studies could not provide: a protective effect on premature mortality was only seen in the intervention group in which nut consumption increased during the 4.8 years of follow-up, not in the intervention group with additional olive oil consumption or in the control group. Nut consumption actually decreased during follow-up in the latter two groups. Questions remain to be answered on the quantity of nuts to be consumed for health benefits, on possible mechanisms of action, and on whether some types of nuts should be favored. Please see related research: http://www.biomedcentral.com/1741-7015/11/164.",
"title": "Should we go nuts about nuts?"
},
{
"docid": "MED-2378",
"text": "Background Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. Objective To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). Design Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n = 12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). Results The ALA and LA diets significantly reduced diastolic blood pressure (−2 to −3 mm Hg) and total peripheral resistance (−4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. Conclusions These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.",
"title": "Effects of Diets High in Walnuts and Flax Oil on Hemodynamic Responses to Stress and Vascular Endothelial Function"
},
{
"docid": "MED-2383",
"text": "During the last decades, nuts have attracted the attention of researchers for their potential benefits in cardiovascular prevention. We discuss here some aspects of the assumed beneficial effects of nuts, weighing them against potential harm. Epidemiological observations and controlled intervention trials consistently suggest that nuts consumption is associated with improved serum lipid profile, thus helping decrease cardiovascular risk. Being nuts an energy dense food, their impact on energy balance and body weight should be considered. In particular, the claim that adding nuts to the habitual diet, thus increasing calorie intake, does not cause body fat accumulation still needs evidence and biological plausibility. The potential risk associated with the relatively frequent occurrence of allergic reactions following the consumption of nuts is also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "The role of nuts in the optimal diet: time for a critical appraisal?"
},
{
"docid": "MED-2381",
"text": "The inverse association of nut consumption and risk markers of coronary heart disease (lipids) has sparked the interest of the scientific and lay community. The objective of this study was to conduct a systematic review to investigate the effects of nuts on the lipid profile. Medline and Web of Science databases were searched from the start of the database to August 2004 and supplemented by cross-checking reference lists of relevant publications. Human intervention trials with the objective of investigating independent effects of nuts on lipid concentrations were included. From the literature search, 415 publications were screened and 23 studies were included. These papers received a rating based upon the methodology as it appeared in the publication. No formal statistical analysis was performed due to the large differences in study designs of the dietary intervention trials. The results of 3 almond (50-100 g/d), 2 peanut (35-68 g/d), 1 pecan nut (72 g/d), and 4 walnut (40-84 g/d) studies showed decreases in total cholesterol between 2 and 16% and LDL cholesterol between 2 and 19% compared with subjects consuming control diets. Consumption of macadamia nuts (50-100 g/d) produced less convincing results. In conclusion, consumption of approximately 50-100 g (approximately 1.5-3.5 servings) of nuts > or = 5 times/wk as part of a heart-healthy diet with total fat content (high in mono- and/or polyunsaturated fatty acids) of approximately 35% of energy may significantly decrease total cholesterol and LDL cholesterol in normo- and hyperlipidemic individuals.",
"title": "A systematic review of the effects of nuts on blood lipid profiles in humans."
},
{
"docid": "MED-2376",
"text": "Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease."
},
{
"docid": "MED-4289",
"text": "BACKGROUND: Few recent epidemiologic studies have assessed the effect that nut consumption (including tree nuts and peanuts) has on health risks, including metabolic syndrome (MetS). OBJECTIVE: This study compared the health risk for cardiovascular disease, type 2 diabetes, and MetS of nut consumers with that of nonconsumers. DESIGN: Adults 19+ years (n = 13,292) participating in the 1999-2004 National Health and Nutrition Examination Survey were used. Intake from 24-hour recalls was used to determine intake. Nut/tree nut consumers consumed ≥¼; ounce per day. Covariate-adjusted means, standard errors, and prevalence rates were determined for the nut consumption groups. RESULTS: The prevalence of nut consumers was 18.6% ± 0.7% and 21.0% ± 0.9% in those 19-50 years and 51 years and older, respectively. Nut consumption was associated with a decreased body mass index (27.7 kg/m(2) ± 0.2 vs 28.1 ± 0.1 kg/m(2), p < 0.05), waist circumference (95.6 ± 0.4 cm vs 96.4 ± 0.3 cm, p < 0.05), and systolic blood pressure (121.9 ± 0.4 mmHg vs 123.20 ± 0.3 mmHg, p < 0.01) compared with nonconsumers. Tree nut consumers also had a lower weight (78.8 ± 0.7 kg vs 80.7 ± 0.3 kg, p < 0.05). Nut consumers had a lower percentage of two risk factors for MetS: hypertension (31.5% ± 1.0% vs 34.2% ± 0.8%, p < 0.05) and low high density lipoprotein-cholesterol (HDL-C) (29.6% ± 1.0% vs 34.8% ± 0.8%, p < 0.01). Tree nut consumers had a lower prevalence of four risk factors for MetS: abdominal obesity (43.6% ± 1.6% vs 49.5% ± 0.8%, p < 0.05), hypertension (31.4% ± 1.2% vs 33.9% ± 0.8%, p < 0.05), low HDL-C (27.9% ± 1.7% vs 34.5% ± 0.8%, p < 0.01), high fasting glucose (11.4% ± 1.4% vs 15.0% ± 0.7%, p < 0.05), and a lower prevalence of MetS (21.2% ± 2.1% vs 26.6% ± 0.7%, p < 0.05). CONCLUSION: Nut/tree nut consumption was associated with a decreased prevalence of selected risk factors for cardiovascular disease, type 2 diabetes, and MetS.",
"title": "Nut consumption is associated with decreased health risk factors for cardiovascular disease and metabolic syndrome in U.S. adults: NHANES 1999-2004."
},
{
"docid": "MED-2592",
"text": "Background Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content. Purpose To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome. Methods Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks. Results Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups. Conclusion Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.",
"title": "Effects of pistachios on body weight in Chinese subjects with metabolic syndrome"
},
{
"docid": "MED-2594",
"text": "BACKGROUND: Epidemiologic studies have shown an inverse association between the frequency of nut consumption and body mass index (BMI) and risk of obesity. However, clinical trials that evaluated nut consumption on adiposity have been scarce and inconclusive. OBJECTIVE: We performed a systematic review and meta-analysis of published, randomized nut-feeding trials to estimate the effect of nut consumption on adiposity measures. DESIGN: MEDLINE and the Cochrane Central Register of Controlled Trials databases were searched for relevant clinical trials of nut intake that provided outcomes of body weight, BMI (in kg/m(2)), or waist-circumference measures and were published before December 2012. There were no language restrictions. Two investigators independently selected and reviewed eligible studies. The weighted mean difference (WMD) between nut or control diets was estimated by using a random-effects meta-analysis with 95% CIs. RESULTS: Thirty-three clinical trials met our inclusion criteria. Pooled results indicated a nonsignificant effect on body weight (WMD: -0.47 kg; 95% CI: -1.17, 0.22 kg; I(2) = 7%), BMI (WMD: -0.40 kg/m(2); 95% CI: -0.97, 0.17 kg/m(2); I(2) = 49%), or waist circumference (WMD: -1.25 cm; 95% CI: -2.82, 0.31 cm; I(2) = 28%) of diets including nuts compared with control diets. These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. CONCLUSION: Compared with control diets, diets enriched with nuts did not increase body weight, body mass index, or waist circumference in controlled clinical trials.",
"title": "Nut intake and adiposity: meta-analysis of clinical trials."
},
{
"docid": "MED-2379",
"text": "Objectives Metabolic syndrome is a precursor of diabetes and cardiovascular disease (CVD). Walnut ingestion has been shown to reduce CVD risk indices in diabetes. This randomized controlled crossover trial was performed to investigate the effects of daily walnut consumption on endothelial function and other biomarkers of cardiac risk in a population of overweight individuals with visceral adiposity. Methods Forty-six overweight adults (average age, 57.4 years; 28 women, 18 men) with elevated waist circumference and 1 or more additional signs of metabolic syndrome were randomly assigned to two 8-week sequences of walnut-enriched ad libitum diet and ad libitum diet without walnuts, which were separated by a 4-week washout period. The primary outcome measure was the change in flow-mediated vasodilation (FMD) of the brachial artery. Secondary measures included serum lipid panel, fasting glucose and insulin, Homeostasis Model Assessment–Insulin Resistance values, blood pressure, and anthropometric measures. Results FMD improved significantly from baseline when subjects consumed a walnut-enriched diet as compared with the control diet (1.4% ± 2.4% versus 0.3% ± 1.5%; p = 0.019). Beneficial trends in systolic blood pressure reduction were seen, and maintenance of the baseline anthropometric values was also observed. Other measures were unaltered. Conclusion Daily ingestion of 56 g of walnuts improves endothelial function in overweight adults with visceral adiposity. The addition of walnuts to the diet does not lead to weight gain. Further study of the potential role of walnut intake in diabetes and CVD prevention is warranted.",
"title": "Effects of Walnuts on Endothelial Function in Overweight Adults with Visceral Obesity: A Randomized, Controlled, Crossover Trial"
},
{
"docid": "MED-4288",
"text": "The purpose of this study was to determine the association of out-of-hand nut (OOHN) consumption with nutrient intake, diet quality, and the prevalence of risk factors for cardiovascular disease and metabolic syndrome. Data from 24-hour recalls from individuals aged 2+ years (n = 24,385) participating in the 1999-2004 National Health and Nutrition Examination Survey were used. The population was divided into children aged 2 to 11, 12 to 18, and adults 19+ years, and each group was dichotomized into OOHN consumers and nonconsumers. Out-of-hand nut consumers were defined as those individuals consuming ¼ oz of nuts or more per d. Means, standard errors, and covariate-adjusted analyses of variance were determined using appropriate sample weights. Diet quality was determined using the Healthy Eating Index-2005. Significance was set at P < .05. The percent of OOHN consumers increased with age: 2.1% ± 0.3%, 2.6% ± 0.3%, 6.5% ± 0.5%, and 9.6% ± 0.5% those aged 2 to 11, 12 to 18, 19 to 50, and 51+ years, respectively. The 2 latter groups were combined into a single group of consumers aged 19+ years for subsequent analyses. Consumers of OOHN from all age groups had higher intakes of energy, monounsaturated and polyunsaturated fatty acids, dietary fiber, copper, and magnesium and lower intakes of carbohydrates, cholesterol, and sodium than did nonconsumers. Diet quality was higher in OOHN consumers of all age groups. In children aged 2 to 11 years, consumers had a higher prevalence of overweight/obesity. In those aged 12 to 18 years, weight and percent overweight were lower in consumers. Adult consumers had higher high-density lipoprotein cholesterol, red blood cell folate, and serum folate levels and lower insulin, glycohemoglobin, and C-reactive protein levels than did nonconsumers. Adult consumers also had a 19% decreased risk of hypertension and a 21% decreased risk of low high-density lipoprotein cholesterol levels. Data suggested that OOHN consumption was associated with improved nutrient intake, diet quality, and, in adults, a lower prevalence of 2 risk factors for metabolic syndrome. Consumption of OOHN, as part of a healthy diet, should be encouraged by health professionals. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Out-of-hand nut consumption is associated with improved nutrient intake and health risk markers in US children and adults: National Health and Nutr..."
},
{
"docid": "MED-2593",
"text": "Background Prospective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person. Methods We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality. Results During a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend <0.05, all). Compared to non-consumers, subjects consuming nuts >3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66). Conclusions Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165. Trial registration Clinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.",
"title": "Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial"
},
{
"docid": "MED-4290",
"text": "BACKGROUND AND AIMS: Nut intake has been inversely related to body mass index (BMI) in prospective studies. We examined dietary determinants of adiposity in an elderly Mediterranean population with customarily high nut consumption. METHODS AND RESULTS: A cross-sectional study was conducted in 847 subjects (56% women, mean age 67 years, BMI 29.7kg/m(2)) at high cardiovascular risk recruited into the PREDIMED study. Food consumption was evaluated by a validated semi-quantitative questionnaire, energy expenditure in physical activity by the Minnesota Leisure Time Activity questionnaire, and anthropometric variables by standard measurements. Nut intake decreased across quintiles of both BMI and waist circumference (P-trend <0.005; both). Alcohol ingestion was inversely related to BMI (P-trend=0.020) and directly to waist (P-trend=0.011), while meat intake was directly associated with waist circumference (P-trend=0.018). In fully adjusted multivariable models, independent dietary associations of BMI were the intake of nuts inversely (P=0.002) and that of meat and meat products directly (P=0.042). For waist circumference, independent dietary associations were intake of nuts (P=0.002) and vegetables (P=0.040), both inversely, and intake of meat and meat products directly (P=0.009). From the regression coefficients, it was predicted that BMI and waist circumference decreased by 0.78kg/m(2) and 2.1cm, respectively, for each serving of 30g of nuts. Results were similar in men and women. CONCLUSION: Nut consumption was inversely associated with adiposity independently of other lifestyle variables. It remains to be explored whether residual confounding related to a healthier lifestyle of nut eaters might in part explain these results. Copyright © 2009 Elsevier B.V. All rights reserved.",
"title": "Cross-sectional association of nut intake with adiposity in a Mediterranean population."
},
{
"docid": "MED-4302",
"text": "English walnuts have been shown to decrease cardiovascular disease risk; however, black walnuts do not appear to have not been studied for their cardioprotective effects. The purpose of this study was to determine the effects of English versus black walnut consumption on blood lipids, body weight, fatty-acid composition of red blood cell (RBC) membranes, and endothelial function. Consumption of 30 g of English walnuts per day for 30 days, by 36 human participants, improved blood lipids; the effects of black walnuts were dependent on the participant's sex. Addition of either nut to the diet did not result in weight gain. The fatty-acid composition of RBC membranes was favorably affected by walnut consumption. RBC polyunsaturated fatty acids increased after consumption of either type of nut; however, eicosapentaenoic acid increased significantly more after English walnut consumption. Endothelial function of 6 unmedicated humans with hypercholesterolemia was maintained after consumption of English walnuts with a meal high in high saturated fats; however, consumption of black walnuts with the same meal did not maintain endothelial function. Overall, these results support the recommendation that consumption of 1 oz of English walnuts per day may decrease cardiovascular risk, but more research on black walnut consumption is necessary before an appropriate recommendation can be made.",
"title": "Cardiovascular effects of consumption of black versus English walnuts."
}
] |
[
{
"docid": "MED-5153",
"text": "OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.",
"title": "Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function."
},
{
"docid": "MED-1785",
"text": "We tested the hypothesis that 75 g of whole-shelled walnuts/day added to the Western-style diet of healthy young men would beneficially affect semen quality. A randomized, parallel two-group dietary intervention trial with single-blind masking of outcome assessors was conducted with 117 healthy men, age 21-35 yr old, who routinely consumed a Western-style diet. The primary outcome was improvement in conventional semen parameters and sperm aneuploidy from baseline to 12 wk. Secondary endpoints included blood serum and sperm fatty acid (FA) profiles, sex hormones, and serum folate. The group consuming walnuts (n = 59) experienced improvement in sperm vitality, motility, and morphology, but no change was seen in the group continuing their usual diet but avoiding tree nuts (n = 58). Comparing differences between the groups from baseline, significance was found for vitality (P = 0.003), motility (P = 0.009), and morphology (normal forms; P = 0.04). Serum FA profiles improved in the walnut group with increases in omega-6 (P = 0.0004) and omega-3 (P = 0.0007) but not in the control group. The plant source of omega-3, alpha-linolenic acid (ALA) increased (P = 0.0001). Sperm aneuploidy was inversely correlated with sperm ALA, particularly sex chromosome nullisomy (Spearman correlation, -0.41, P = 0.002). Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility, and morphology.",
"title": "Walnuts improve semen quality in men consuming a Western-style diet: randomized control dietary intervention trial."
},
{
"docid": "MED-3250",
"text": "The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.",
"title": "Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia."
},
{
"docid": "MED-2946",
"text": "OBJECTIVE: Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians. DESIGN: Double-blind, placebo controlled, randomised crossover study. SETTING: Community dwelling vegetarians. PARTICIPANTS: Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. INTERVENTION: Vitamin B-12 (500 µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41). MEASUREMENT: Flow-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound. RESULTS: The mean age of the subjects was 45±9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150 pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09 mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09 mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (β=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028). CONCLUSIONS: Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention.",
"title": "Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status."
},
{
"docid": "MED-4708",
"text": "BACKGROUND/OBJECTIVES: Walnuts have been shown to reduce serum lipids in short-term well-controlled feeding trials. Little information exists on the effect and sustainability of walnut consumption for longer duration in a free-living situation. SUBJECTS/METHODS: A randomized crossover design in which 87 subjects with normal to moderate high plasma total cholesterol were initially assigned to a walnut-supplemented diet or habitual (control) diet for a 6-month period, then switched to the alternate dietary intervention for a second 6-month period. Each subject attended seven clinics 2 months apart. At each clinic, body weight was measured, and in five clinics (months 0, 4, 6, 10 and 12), a blood sample was collected. RESULTS: Our study showed that supplementing a habitual diet with walnuts (12% of total daily energy intake equivalent) improves the plasma lipid profile. This beneficial effect was more significant in subjects with high plasma total cholesterol at baseline. Significant changes in serum concentrations of total cholesterol (P=0.02) and triglycerides (P=0.03) were seen and nearly significant changes in low-density lipoprotein cholesterol (LDL-C) (P=0.06) were found. No significant change was detected in either high-density lipoprotein (HDL) cholesterol LDL to HDL ratio. CONCLUSIONS: Including walnuts as part of a habitual diet favorably altered the plasma lipid profile. The lipid-lowering effects of walnuts were more evident among subjects with higher lipid baseline values, precisely those people with greater need of reducing plasma total and LDL-C.",
"title": "Long-term walnut supplementation without dietary advice induces favorable serum lipid changes in free-living individuals."
},
{
"docid": "MED-3432",
"text": "Men with the metabolic syndrome demonstrate an increased prevalence of erectile dysfunction (ED). In the present study, we tested the effect of a Mediterranean-style diet on ED in men with the metabolic syndrome. Men were identified in our database of subjects participating in controlled trials evaluating the effect of lifestyle changes and were included if they had a diagnosis of ED associated with a diagnosis of metabolic syndrome, complete follow-up in the study trial, and intervention focused mainly on dietary changes. Sixty-five men with the metabolic syndrome met the inclusion/exclusion criteria; 35 out of them were assigned to the Mediterranean-style diet and 30 to the control diet. After 2 years, men on the Mediterranean diet consumed more fruits, vegetables, nuts, whole grain, and olive oil as compared with men on the control diet. Endothelial function score and inflammatory markers (C-reactive protein) improved in the intervention group, but remained stable in the control group. There were 13 men in the intervention group and two in the control group (P=0.015) that reported an IIEF score of 22 or higher. Mediterranean-style diet rich in whole grain, fruits, vegetables, legumes, walnut, and olive oil might be effective per se in reducing the prevalence of ED in men with the metabolic syndrome.",
"title": "Mediterranean diet improves erectile function in subjects with the metabolic syndrome."
},
{
"docid": "MED-967",
"text": "BACKGROUND: Observational evidence has consistently linked increased fruit and vegetable consumption with reduced cardiovascular morbidity; however, there is little direct trial evidence to support the concept that fruit and vegetable consumption improves vascular function. This study assessed the dose-dependent effects of a fruit and vegetable intervention on arterial health in subjects with hypertension. METHODS AND RESULTS: After a 4-week run-in period during which fruit and vegetable intake was limited to 1 portion per day, participants were randomized to consume either 1, 3, or 6 portions daily for the next 8 weeks. Endothelium-dependent and -independent arterial vasodilator responses were assessed by venous occlusion plethysmography in the brachial circulation before and after intervention. Compliance was monitored with serial contemporaneous 4-day food records and by measuring concentrations of circulating dietary biomarkers. A total of 117 volunteers completed the 12-week study. Participants in the 1-, 3-, and 6-portions/d groups reported consuming on average 1.1, 3.2, and 5.6 portions of fruit and vegetables, respectively, and serum concentrations of lutein and beta-cryptoxanthin increased across the groups in a dose-dependent manner. For each 1-portion increase in reported fruit and vegetable consumption, there was a 6.2% improvement in forearm blood flow responses to intra-arterial administration of the endothelium-dependent vasodilator acetylcholine (P=0.03). There was no association between increased fruit and vegetable consumption and vasodilator responses to sodium nitroprusside, an endothelium-independent vasodilator. CONCLUSIONS: The present study illustrates that among hypertensive volunteers, increased fruit and vegetable consumption produces significant improvements in an established marker of endothelial function and cardiovascular prognosis.",
"title": "Dietary intake of fruits and vegetables improves microvascular function in hypertensive subjects in a dose-dependent manner."
},
{
"docid": "MED-5278",
"text": "In recent years, endothelial dysfunction has been identified as an early feature of atherosclerosis. Endothelial function can be measured noninvasively by using brachial artery ultrasound. A variety of factors associated with atherosclerosis also impair endothelial function. Some of these factors are lipoproteins such as various forms of low-density lipoproteins, postprandial chylomicron remnants, fasting triglyceride-rich particles, and free fatty acids. A high-fat diet also has an adverse effect on endothelial function. Several interventions can improve endothelial function and, at the same time, reduce cardiovascular events. Measuring endothelial function may eventually serve as a useful index to determine an individual's risk for coronary artery disease.",
"title": "Brachial artery ultrasound: a noninvasive tool in the assessment of triglyceride-rich lipoproteins."
},
{
"docid": "MED-1499",
"text": "Nature has gifted mankind with a plethora of flora-bearing fruits, vegetables and nuts. The diverse array of bioactive nutrients present in these natural products plays a pivotal role in prevention and cure of various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and other neuronal dysfunctions. Accumulated evidence suggests that naturally occurring phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive function. Nuts such as walnut have also demonstrated neuroprotective effect against AD. The molecular mechanisms behind the curative effects rely mainly on the action of phytonutrients on distinct signalling pathways associated with protein folding and neuroinflammation. The neuroprotective effects of various naturally occurring compounds in AD is evaluating in this review.",
"title": "Neuroprotective effect of natural products against Alzheimer's disease."
},
{
"docid": "MED-1643",
"text": "AIMS: To examine the acute effect of red wine and de-alcoholized red wine on endothelial function. METHODS AND RESULTS: High frequency ultrasound was used to measure blood flow and percentage brachial artery dilatation after reactive hyperaemia induced by forearm cuff occlusion in 12 healthy subjects, less than 40 years of age, without known cardiovascular risk factors. The subjects drank 250 ml of red wine with or without alcohol over 10 min according to a randomized procedure. Brachial artery dilatation was measured again 30 and 60 min after the subjects had finished drinking. The subjects were studied a second time within a week of the first study in a cross-over design. After the red wine with alcohol the resting brachial artery diameter, resting blood flow, heart rate and plasma-ethanol increased significantly. After the de-alcoholized red wine these parameters were unchanged. Flow-mediated dilatation of the brachial artery was significantly higher (P<0.05) after drinking de-alcoholized red wine (5.6+/-3.2%) than after drinking red wine with alcohol (3.6+/-2.2%) and before drinking (3.9+/-2.5%). CONCLUSION: After ingestion of red wine with alcohol the brachial artery dilated and the blood flow increased. These changes were not observed following the de-alcoholized red wine and were thus attributable to ethanol. These haemodynamic changes may have concealed an effect on flow-mediated brachial artery dilatation which did not increase after drinking red wine with alcohol. Flow-mediated dilatation of the brachial artery increased significantly after de-alcoholized red wine and this finding may support the hypothesis that antioxidant qualities of red wine, rather than ethanol in itself, may protect against cardiovascular disease. Copyright 2000 The European Society of Cardiology.",
"title": "Does a glass of red wine improve endothelial function?"
},
{
"docid": "MED-5266",
"text": "Current National Cholesterol Education Program guidelines consider desirable total and low-density lipoprotein cholesterol levels to be < 200 and < 160 mg/dl, respectively, for healthy individuals without multiple coronary risk factors. To determine the extent to which these levels affect vascular function, we assessed flow-mediated (endothelium-dependent) brachial artery vasoactivity noninvasively before, during, and after cholesterol lowering (simvastatin 10 mg/day) in 7 healthy middle-aged men with cholesterol levels meeting current recommendations. Flow-mediated brachial artery vasoactivity was measured using 7.5 MHz ultrasound and expressed as percent diameter change from baseline to hyperemic conditions (1 minute following 5 minutes of blood pressure cuff arterial occlusion). Flow-mediated vasoactivity rose from 5.0 +/- 3.6% at baseline to 10.5 +/- 5.6%, 13.3 +/- 4.3%, and 15.7 +/- 4.9% (all p < 0.05) as cholesterol fell from 200 +/- 12 to 161 +/- 18, 169 +/- 16, and 153 +/- 11 mg/dl after 2, 4, and 12 weeks, respectively, of cholesterol-lowering therapy. Vasoactivity and cholesterol returned to baseline levels 12 weeks after simvastatin discontinuation. Overall, vasoactivity was found to correlate inversely with cholesterol levels (r = -0.47, p = 0.004). These data suggest that flow-mediated brachial artery vasoactivity responds rapidly to changes in cholesterol levels and that endothelial function improves by lowering cholesterol levels below recommendations of current guidelines.",
"title": "Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men."
},
{
"docid": "MED-4520",
"text": "Evidence suggests that endothelial dysfunction is on the causal pathway for both atherogenesis and destabilization of established plaques. In this review, the role of flow-mediated dilatation (FMD) as a non-invasive method to assess endothelial function is discussed. Technical modifications and development of analysis software have significantly improved the variability of the method. Following a strict standardized protocol enables reproducible measurements to be achieved and export of the technique from specialized laboratories to population studies and multicentre settings. Endothelial function assessed by FMD has been shown to be affected by cardiovascular risk factors, to be related to structural arterial disease and to cardiovascular outcome, validating its use for studying the pathophysiology of arterial disease. Numerous studies have also demonstrated that it is responsive to physiological and pharmacological interventions. Flow-mediated dilatation provides unique opportunities in drug development programmes to assess an early rapidly responsive signal of risk or benefit, complementing endpoints of structural arterial disease and cardiovascular outcomes that take much longer and are more expensive.",
"title": "Assessment of atherosclerosis: the role of flow-mediated dilatation."
},
{
"docid": "MED-2591",
"text": "Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1.66 (sd 0.41) v. 1.52 (sd 0.22), P= 0.037). These results were particularly strong in patients with the MS (Q1 = 1.82 (sd 0.32) v. Q4 = 1.61 (sd 027); P= 0.021) and T2D (Q1 = 1.78 (sd 0.31) v. Q4 = 1.62 (sd 0.35); P= 0.011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR -0.85; 95 % CI 0.19, 0.92; P= 0.031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.",
"title": "Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular ..."
},
{
"docid": "MED-1639",
"text": "Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease."
},
{
"docid": "MED-1647",
"text": "BACKGROUND: Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA). Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. CONCLUSIONS: Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.",
"title": "Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease."
},
{
"docid": "MED-2152",
"text": "Walnuts contain bioactive molecules that may contribute to their beneficial effects, including alpha-linolenic acid (ALA) and phytosterols. In these studies, extracts of walnut, purified compounds, or postprandial serum were examined for effects on breast cancer cell proliferation and gene expression. Extracts derived from walnut oil decreased proliferation of MCF-7 cells, as did ALA and β-sitosterol. The gene expression response of ALA in the mouse breast cancer cell line TM2H indicates this molecule has multiple cellular targets with peroxisome proliferator-activated receptor (PPAR) target genes, liver X receptor (LXR), and farnesoid X receptor (FXR) target genes being affected. In transactivation assays, walnut oil extracts increased activity of FXR to a greater extent than the other tested nuclear receptors. When examined separately, walnut components ALA and β-sitosterol were the most efficacious activators of FXR. When serum from individuals fed walnut components were applied to MCF-7 cells, there was a correlation between body mass index and breast cancer cell proliferation in vitro. Taken together, these data support an effect of walnut and its bioactive constituents on mammary epithelial cells and that multiple molecular targets may be involved.",
"title": "Mechanistic examination of walnuts in prevention of breast cancer."
},
{
"docid": "MED-2587",
"text": "Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no information is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow. Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a \"high-protein\" (high protein group/HPG) diet, which they believed would \"improve\" their overall health. Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evaluations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p<0.001) significant. Patients following recommended treatment for each of the independent variables were able to regress both the extent and severity of their coronary artery disease (CAD), as well as improve their myocardial wall motion (function) while following the prescribed medical and dietary guidelines. However, individuals receiving the same medical treatment but following a high-protein diet showed a worsening of independent risk factors, in addition to progression of CAD. These results would suggest that high-protein diets may precipitate progression of CAI) through increases in lipid deposition and inflammatory and coagulation pathways.",
"title": "The effect of high-protein diets on coronary blood flow."
},
{
"docid": "MED-3430",
"text": "BACKGROUND: Erectile dysfunction (ED) shares similar modifiable risks factors with coronary artery disease (CAD). Lifestyle modification that targets CAD risk factors may also lead to improvement in ED. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of lifestyle interventions and pharmacotherapy for cardiovascular (CV) risk factors on the severity of ED. METHODS: A comprehensive search of multiple electronic databases through August 2010 was conducted using predefined criteria. We included randomized controlled clinical trials with follow-up of at least 6 weeks of lifestyle modification intervention or pharmacotherapy for CV risk factor reduction. Studies were selected by 2 independent reviewers. The main outcome measure of the study is the weighted mean differences in the International Index of Erectile Dysfunction (IIEF-5) score with 95% confidence intervals (CIs) using a random effects model. RESULTS: A total of 740 participants from 6 clinical trials in 4 countries were identified. Lifestyle modifications and pharmacotherapy for CV risk factors were associated with statistically significant improvement in sexual function (IIEF-5 score): weighted mean difference, 2.66 (95% CI, 1.86-3.47). If the trials with statin intervention (n = 143) are excluded, the remaining 4 trials of lifestyle modification interventions (n = 597) demonstrate statistically significant improvement in sexual function: weighted mean difference, 2.40 (95% CI, 1.19-3.61). CONCLUSION: The results of our study further strengthen the evidence that lifestyle modification and pharmacotherapy for CV risk factors are effective in improving sexual function in men with ED.",
"title": "The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis."
},
{
"docid": "MED-2224",
"text": "BACKGROUND: Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. METHODS AND RESULTS: We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36+/-0.51 to 2.51+/-0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5+/-11.4% versus -4.3+/-11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) in the dark chocolate group but remained unchanged in the control group. CONCLUSIONS: Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.",
"title": "Dark chocolate improves coronary vasomotion and reduces platelet reactivity."
},
{
"docid": "MED-1348",
"text": "Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. Editors' Summary Background. Everyone feels miserable occasionally. But for some people—those with depression—these sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless, worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving). For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine. Why Was This Study Done? Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical Excellence (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy. What Did the Researchers Do and Find? The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants. What Do These Findings Mean? These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050045.",
"title": "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration"
},
{
"docid": "MED-1386",
"text": "Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet. While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior. This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored.",
"title": "Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example"
},
{
"docid": "MED-966",
"text": "BACKGROUND: In coronary artery disease, exercise training (ET) is associated with an improvement in endothelial function, but little is known about the relative effect of different types of training. The purpose of this study was to prospectively evaluate the effect of different types of ET on endothelial function in 209 patients after a first recent acute myocardial infarction. METHODS AND RESULTS: Endothelial function was evaluated before and after 4 weeks of different types of ET and after 1 month of detraining by measuring flow-mediated dilation and von Willebrand factor levels at baseline and after ET. Patients were randomized into 4 groups: group 1, aerobic ET (n=52); group 2, resistance training (n=54); group 3, resistance plus aerobic training (n=53); and group 4, no training (n=50). At baseline, flow-mediated dilation was 4.5+/-2.6% in group 1, 4.01+/-1.6% in group 2, 4.4+/-4% in group 3, and 4.3+/-2.3% in group 4 (P=NS). After ET, flow-mediated dilation increased to 9.9+/-2.5% in group 1, 10.1+/-2.6% in group 2, and 10.8+/-3% in group 3 (P<0.01 versus baseline for all groups); it also increased in group 4 but to a much lesser extent (to 5.1+/-2.5%; P<0.01 versus trained groups). The von Willebrand factor level after ET decreased by 16% (P<0.01) similarly in groups 1, 2, and 3 but remained unchanged in group 4. Detraining returned flow-mediated dilation to baseline levels (P<0.01 versus posttraining). CONCLUSIONS: In patients with recent acute myocardial infarction, ET was associated with improved endothelial function independently of the type of training, but this effect disappeared after 1 month of detraining.",
"title": "Effects of different types of exercise training followed by detraining on endothelium-dependent dilation in patients with recent myocardial infarct..."
},
{
"docid": "MED-2939",
"text": "Background: Vegetarianism is associated with a lower risk of cardiovascular disease. However, studies of arterial function in vegetarians are limited. Methods: This study investigated arterial function in vegetarianism by comparing 49 healthy postmenopausal vegetarians with 41 age-matched omnivores. The arterial function of the common carotid artery was assessed by carotid duplex, while the pulse dynamics method was used to measure brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR). Fasting blood levels of glucose, lipids, lipoprotein (a), high-sensitivity C-reactive protein, homocysteine, and vitamin B12 were also measured. Results: Vegetarians had significantly lower serum cholesterol, high-density and low-density lipoprotein, and glucose compared with omnivores. They also had lower vitamin B12 but higher homocysteine levels. Serum levels of lipoprotein (a) and high-sensitivity C-reactive protein were no different between the two groups. There were no significant differences in carotid beta stiffness index, BAC, and BAD between the two groups even after adjustment for associated covariates. However, BAR was significantly lower in vegetarians than in omnivores. Multiple linear regression analysis revealed that age and pulse pressure were two important determinants of carotid beta stiffness index and BAD. Vegetarianism is not associated with better arterial elasticity. Conclusion: Apparently healthy postmenopausal vegetarians are not significantly better in terms of carotid beta stiffness index, BAC, and BAD, but have significantly decreased BAR than omnivores. Prevention of vitamin B12 deficiency might be beneficial for cardiovascular health in vegetarians.",
"title": "Arterial function of carotid and brachial arteries in postmenopausal vegetarians"
},
{
"docid": "MED-4705",
"text": "Several studies suggest that regular consumption of nuts, mostly walnuts, may have beneficial effects against oxidative stress mediated diseases such as cardiovascular disease and cancer. Walnuts contain several phenolic compounds which are thought to contribute to their biological properties. The present study reports the total phenolic contents and antioxidant properties of methanolic and petroleum ether extracts obtained from walnut (Juglans regia L.) seed, green husk and leaf. The total phenolic contents were determined by the Folin-Ciocalteu method and the antioxidant activities assessed by the ability to quench the stable free radical 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and to inhibit the 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of human erythrocytes. Methanolic seed extract presented the highest total phenolic content (116 mg GAE/g of extract) and DPPH scavenging activity (EC(50) of 0.143 mg/mL), followed by leaf and green husk. In petroleum ether extracts, antioxidant action was much lower or absent. Under the oxidative action of AAPH, all methanolic extracts significantly protected the erythrocyte membrane from hemolysis in a time- and concentration-dependent manner, although leaf extract inhibitory efficiency was much stronger (IC(50) of 0.060 mg/mL) than that observed for green husks and seeds (IC(50) of 0.127 and 0.121 mg/mL, respectively). Walnut methanolic extracts were also assayed for their antiproliferative effectiveness using human renal cancer cell lines A-498 and 769-P and the colon cancer cell line Caco-2. All extracts showed concentration-dependent growth inhibition toward human kidney and colon cancer cells. Concerning A-498 renal cancer cells, all extracts exhibited similar growth inhibition activity (IC(50) values between 0.226 and 0.291 mg/mL), while for both 769-P renal and Caco-2 colon cancer cells, walnut leaf extract showed a higher antiproliferative efficiency (IC(50) values of 0.352 and 0.229 mg/mL, respectively) than green husk or seed extracts. The results obtained herein strongly indicate that walnut tree constitute an excellent source of effective natural antioxidants and chemopreventive agents. Copyright 2009 Elsevier Ltd. All rights reserved.",
"title": "Human cancer cell antiproliferative and antioxidant activities of Juglans regia L."
},
{
"docid": "MED-940",
"text": "Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.",
"title": "An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for t..."
},
{
"docid": "MED-4709",
"text": "BACKGROUND: Inflammation is crucial in all stages of atherosclerosis, and few studies have investigated the effect of dietary fat on markers of inflammation related to this disease during the postprandial period. OBJECTIVE: To evaluate the chronic effects of dietary fat on the postprandial expression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) in healthy subjects. DESIGN: 20 healthy men followed three different diets for 4 weeks each, according to a randomized crossover design: Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); CHO-rich and n-3 diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After 12-h fast, volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast: 35% SFA; olive oil breakfast: 36% MUFA; walnut breakfast: 16% PUFA, 4% alpha-linolenic acid (LNA). RESULTS: The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) expression than the olive oil or walnut breakfasts (P=0.014) in PBMCs. Moreover, we found a higher postprandial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast (P=0.025) in these cells. However, the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences (P=N.S.). CONCLUSION: Consumption of a butter-enriched meal elicits greater postprandial expression of proinflammatory cytokine mRNA in PBMCs, compared to the olive oil and walnut breakfasts.",
"title": "Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men."
},
{
"docid": "MED-1645",
"text": "BACKGROUND: Tea consumption is associated with decreased cardiovascular risk. Flow-mediated dilatation (FMD) of the brachial artery is related to coronary endothelial function and it is an independent predictor of cardiovascular risk. Black tea has a beneficial effect on endothelial function; the effect, however, of green tea on brachial artery reactivity has not been defined yet. DESIGN AND METHODS: We studied 14 healthy individuals (age 30+/-3 years) with no cardiovascular risk factors except from smoking (50%) on three separate occasions on which they took: (a) 6 g of green tea, (b) 125 mg of caffeine (the amount contained in 6 g of tea), or (c) hot water. FMD of the brachial artery was measured before each intervention and 30, 90, and 120 min afterward. High-sensitivity C-reactive protein, interleukins 6 (Il-6) and 1b (Il-1b), total plasma antioxidative capacity, and total plasma oxidative status/stress were measured at baseline and at 120 min after each intervention. RESULTS: Resting and hyperemic brachial artery diameter did not change either with tea or with caffeine. FMD increased significantly with tea (by 3.69%, peak at 30 min, P<0.02), whereas it did not change significantly with caffeine (increase by 1.72%, peak at 30 min, P=NS). Neither tea nor caffeine had any effect on high-sensitivity C-reactive protein, Il-6, Il-1b, total plasma antioxidative capacity, or total plasma oxidative status/stress. CONCLUSION: Green tea consumption has an acute beneficial effect on endothelial function, assessed with FMD of the brachial artery, in healthy individuals. This may be involved in the beneficial effect of tea on cardiovascular risk.",
"title": "The acute effect of green tea consumption on endothelial function in healthy individuals."
},
{
"docid": "MED-5083",
"text": "A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.",
"title": "A systematic screening of total antioxidants in dietary plants."
},
{
"docid": "MED-5013",
"text": "INTRODUCTION: Endothelial dysfunction is known to occur in patients with coronary artery disease. Flow-mediated dilation of the brachial artery using Doppler ultrasound is a non-invasive technique for the assessment of endothelial function. The objective of the study was to use the above method to evaluate the pathophysiology of high-fat (HF) intake on endothelial function in a local population. A popular local dish \"nasi-lemak\", a source of high saturated fat content from coconut milk, was chosen to represent a local high-fat meal (LHF). In addition, the effects of a Western high-fat (WHF) (\"McDonald's\") meal and a low-fat (LF) meal control on endothelial function were studied. MATERIALS AND METHODS: The study population consisted of 10 healthy male non-smoker (mean age 22 +/- 2 years) with normal body mass index, normal fasting sugar and lipid profiles. Nitric oxide dependent flow-mediated dilation and nitric oxide independent (GTN) dilation was assessed by Doppler flow in the brachial artery before and 4 hours after each meal on separate occasions by 2 experienced sonographers blinded to the type of meals. RESULTS: The baseline brachial artery size, baseline vessel flow and increase in flow after cuff deflation were similar for each of the six arterial studies. In response to reactive hyperaemia after cuff deflation, the endothelium-dependent dilation was significantly different between the meals. There was a marked decrease in endothelium-dependent dilation after the WHF meal compared to the LF meal (8.6 +/- 2.2% vs. -0.8 +/- 1.1%, P < 0.006). There was also a marked decrease in endothelium-dependent dilation after the LHF meal compared to the LF meal (7.7 +/- 2.1% vs. -0.8 +/- 1.1%, P < 0.001). When comparing between the two HF meals, the change in endothelium-dependent dilation was not significant (7.7 vs. 8.6%, P = 0.678). GTN-induced dilation was not significantly different before and after the LF, WHF or LHF (0.1 +/- 0.5% vs. 0.2 +/- 0.9% vs. 1.3 +/- 0.5%, P = 0.094). CONCLUSION: The results suggest that in a local population, impairment of endothelial function is a possible mechanism in the pathophysiology of atherosclerosis from HF intake, beyond just affecting lipid levels. This effect is observed after both a LHF and a WHF meal intake. This technique to study endothelial function may be a useful non-invasive screening tool in the study of other HF diet choices and provides further information for the education of the influence of dietary choices on atherosclerosis.",
"title": "Impairment of endothelial function--a possible mechanism for atherosclerosis of a high-fat meal intake."
},
{
"docid": "MED-4249",
"text": "BACKGROUND AND AIMS: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. METHODS AND RESULTS: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance. CONCLUSION: The results confirm the cholesterol lowering properties of nut-enriched diets. They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content, which clearly deserves further study. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers."
}
] |
712
|
Ghana scam and direct deposit scam?
|
[
{
"docid": "527433",
"text": "The reason this sort of question gets asked over and over again is because it's initially difficult to comprehend how you can possibly be scammed if you have no money in your bank account. Perhaps this would make it easier to understand: Someone approaches you in the parking lot of a mall and says, Excuse me, complete stranger, please take this $100 bill and go buy me a pair of $50 shoes at the shoe store. Then go buy whatever you'd like with the rest of the money. Sounds like a good deal, right? The $100 bill is counterfeit. If it were not, the person would buy the shoes themselves. It doesn't get any simpler than that.",
"title": ""
},
{
"docid": "101358",
"text": "The scammer is definitely up to something fishy. He (it's certain that the she is a he) may deposit some money into your father's account to gain his trust. After which, he will propose to come meet your dad. That's where the scamming begins. He will come up with a story about flight, VISA issues, or a problem he has to solve before coming over. Another is that he can use your dad's empty account to receive monies he scammed off people. That way there's no direct link with him and his other victim.",
"title": ""
},
{
"docid": "97582",
"text": "Yes, this is a scam. Tell your dad not to pay any money. There will likely be a large deposit in his account, but if he withdraws the money from his account, the bank will come after him looking for the money when the transfer to his account is reversed.",
"title": ""
},
{
"docid": "129965",
"text": "\"So Linda/Josie's initial plan was to have your dad pay money to (supposedly) help her get the gold chest. After he would have paid, there would have been another complication, and more yet (someone to bribe, a plane ticket to buy, transport to arrange, customs to handle, whatever, the list would last as long as there's money to take). Even if he does not have much money, the appeal of his share of the treasure could have been enough to tempt him to spend money he can't, or borrow, etc. Once \"\"she\"\" found out that he doesn't have any money and/or is apparently not willing to send any, \"\"she\"\" switched to a different scam: she would send him a large check, have him deposit it on his bank account, transfer most of the money (minus his generous share) to \"\"her\"\". Once the money is irreversibly transferred, the check will bounce. End result: 0 in the account before the transaction, minus a lot afterwards. It's quite simple: if an e-mail from a perfect stranger includes any of the following keywords, it's a scam:\"",
"title": ""
},
{
"docid": "28356",
"text": "\"It's a scam. Here's someone who paid \"\"Josie\"\" 2000 pounds and lost it all Here's a Google search result list of how this softcore porn actor, Josie Ann Miller, is being used as the face and name of scams\"",
"title": ""
},
{
"docid": "273307",
"text": "Sadly, people with millions of dollars rarely give it away to complete strangers that they found at random on the Internet in exchange for trivial efforts. Anyone who claims to be willing to give you millions of dollars for just about nothing in return is almost certainly pulling a scam. It doesn't matter if you can't figure out how they're going to cheat you. They have plan. Just because your father has no money doesn't mean he can't be robbed. The scammer is almost surely planning to move some money around, and leave your father with a debt that he will be legally obligated to pay. She'll then take off with the money. (Of course you figured out that the picture is fake. It may not even be a pretty young girl -- that may well just be a persona the scammer created to appeal to your father. It might really be a fat, balding old man.) Your father would be smarter to sit in his back yard and wait for money to fall from the sky.",
"title": ""
},
{
"docid": "212810",
"text": "Of course, it is a scam. Regardless of how the scam might work, you already know that the person on the other end is lying, and you also know that people in trouble don't contact perfect strangers out of the blue by e-mail for help, nor do they call up random phone numbers looking for help. Scammers prey on the gullibility, greed, and sometimes generosity of the victims. As to how this scam works, the money that the scammer would be depositing into your father's account is not real. However, it will take the bank a few days to figure that out. In the mean time, your father will be sending out real money back to the scammer. When the bank figures out what is going on, they will want your father to pay back this money.",
"title": ""
},
{
"docid": "580479",
"text": "It used to be Nigerian royalty, now it's Ghanaian porn stars. Great. This is a bog-standard 419 scam. It's probably the most lucrative single swindle in the world. It's always hard to get people to believe they have been tricked, but don't let your dad participate.",
"title": ""
}
] |
[
{
"docid": "578954",
"text": "All that's needed to deposit into your account are two things Bank identifier is could be SWIFT code, IBAN, or similar routing number. an ABA routing number a similar idendifier used by US banks. It's a scam. A variant scam deposits too much money in your account and then requests you repay the excess before canceling the deposit. If a stranger deposits money and then asks you to repay some. Do not do so. contact your bank instead.",
"title": ""
},
{
"docid": "214518",
"text": "\"It is likely a scam. In fact the whole mystery shopping \"\"job\"\" may be a scam. There is a Snopes page about cashier's check scams, as well as a US government page which specifically mentions mystery shopping as a scam angle. As for how the scam works, from the occ.gov site I just linked: However, cashier’s checks lately have become an attractive vehicle for fraud when used for payments to consumers. Although, the amount of a cashier’s check quickly becomes \"\"available\"\" for withdrawal by the consumer after the consumer deposits the check, these funds do not belong to the consumer if the check proves to be fraudulent. It may take weeks to discover that a cashier’s check is fraudulent. In the meantime, the consumer may have irrevocably wired the funds to a scam artist or otherwise used the funds—only to find out later, when the fraud is detected—that the consumer owes the bank the full amount of the cashier’s check that had been deposited. It is somewhat unusual in that, from what you say, there has been no attempt thus far to get money back. However, your sister-in-law may have received that info separately, or received it as part of her mystery shopping job but didn't mention it to you with regard to this check. Typically the scam involves telling the recipient to transfer money to a third party (e.g., by buying goods as a mystery shopper, or via wire transfer to \"\"reimburse\"\" someone associated with a sham operation). By the time the cashier's check is revealed as fraudulent, the victim has already transferred away his/her own real money. It's probably worth taking the check to your or her bank and asking them about it. They may have more info. Also, banks usually want to know about scams like this because, in the long run, they accumulate data on them and share that with law enforcement and can eventually catch some of the scammers. Edit: Just to help anyone who may be reading this later. The letter you added confirms it is absolutely a scam. My boss was once contacted via a scam operation very similar to this. The huge red flag (in addition to others already mentioned) is that you are being \"\"given\"\" a check for over $2000, of which only $25 is purportedly for actual mystery shopping and $285 is payment for you, the mystery shopper. The whole rest of the $2000+ amount is for you to wire to \"\"another Mystery/Secret Shopper in order for them to complete their assignment\"\". They are giving you $2000 to give to someone else who is supposedly another one of their own employees/contractors. Ask yourself what sane business would conduct their operations in this way. If you work at a law office, or a hamburger stand, or a school, or anything you like, does your boss ever say \"\"Here is your paycheck for $5000. I know you only earned $1000, but I'm just going to give you the whole $5000, and you're supposed to use $4000 of it to pay your coworker Joe his wages.\"\" No. There is no reason to do that except that the \"\"other mystery shopper\"\" is actually the scammer.\"",
"title": ""
},
{
"docid": "271116",
"text": "Absolute scam. Any time anyone asks you to open a bank account so they can send you money and then you have to send some portion of it back to them, it's a guarantee that it's a scam. What happens is that your dad will deposit the check and transfer it to this woman, then the check will bounce (or turn out to be fake altogether) and your dad will be on the hook for the money to the bank. These schemes are dependent on the fact that people want hope and believe in quick, easy money, and it works as long as the con artists are able to get the 'mark' (the person who deposits the check and sends them the money) to send the money before the check (always drawn on some obscure foreign bank) has a chance to clear. This is another variation of a long-running type of bank scam, and if you get involved, you'll regret it. I hope you can keep your dad from getting involved, because it will create a financial mess and affect his credit as well. The basic premise of this scam is this: In the interests of providing good customer service, most banks will make some or all of a deposit available right away, even though the check hasn't cleared. The scammer has you withdraw the money (either a cashier's check, have you send a wire transfer, etc) immediately and send it to them. Eventually the check is returned because it is The bank charges the check back against your account, often imposing pretty substantial penalties and fees, so you as the account holder are left without the money you sent the scammer and all of the fees. This is the easy version of events. You could end up in legal trouble, depending on the nature of the scam and what they determine your involvement to be. It will certainly badly affect your banking history (ChexSystems tracks how we all treat bank accounts, much like the credit agencies do with our credit), so you may have trouble opening bank accounts. So there are many consequences to this to think about, and it's why you JUST SAY NO!! Don't walk away from this -- RUN!!!",
"title": ""
},
{
"docid": "65797",
"text": "The classic Nigerian scam involves sending fraudulent cashier's checks to unwitting recipients who then deposit them in their account. The bank reverses these deposits once they discover the check is not valid. At least in the US and in the parts of the EU I'm familiar with (the Netherlands), the method of the Nigerian scam is consistent and banks will reverse the deposit after some holding period. Given this, it's unlikely that most banks will convert an arbitrary cashier's check to cash without any means to recover the amount should the check be fraudulent.",
"title": ""
},
{
"docid": "37960",
"text": "\"Well, all of the previous answers already mentioned the upcoming scam and danger situation for your financial position. I thoroughly read all answers and wanted to add a few more lines on it. Cort Ammon) already shows details of it. Any kind of financial transaction involving a complete stranger is the first big scam tag that shows up and this should always 'Never Fall In' type situation. If you open a new bank account or give away any existing bank account to this lady, other than just losing some amount, you might pay earlier than clearing checks you deposited on behalf of your 'stranger' partner. Depending on their target/plan/experience with your bank account they can make you a victim of a bigger crime. There is a full length of scam plans, like sending you false checks to deposit and ask you withdrew money to send them back to even having very big incoming transaction to your account sitting idle on your account which might originate from a crime beyond the financial domain. You can try to be smart, thinking in mind, well, let them send some, I will never send them back before bank declare the deposited checks got horned and clear (and send back the amount after keeping your share). But, still you will face problems later. Even if your account fills up with real money and after confirming with bank you find it OK and never return them (scam a scammer). Still you will not have any valid authority or answer describing how/why you got this money if someone ask you later. Depending on scammer's ability, they might even give you control over fund to spend for your own (to gain some trust from your part). On this type of scam it is a sign of an even bigger danger. I live such a country, Bangladesh, from where recently they successfully transferred out around US$10 millions using a bank account of an outsider like you keeping in between source of money and final unknown destination. The result is the owner / operator of those accounts used for these transfers are now under law enforcement pressure, not only just to find out where ultimately money has gone, but for sure they will face some degree of charge for helping transfer of illegal money overseas\"\". For someone who is not part of a full scam chain it is a big deal. It might ruin their life forever. To be on the safe side, and help protect others from falling on the same type of problem you may contact your local law enforcement agency. Depending on the situation, they might be interested to run a sting operation using your information and support to catch and stop the crime going to happen soon or later. I would give a rare chance of 2% legitimate reason for anyone to use a third-party bank account to pay some other living either different country (still it is not legal, but a lower-type crime). But obviously they will not ask randomly over the Internet/social network sites. In your case this is a real scam. Be careful and stay safe; Good Luck.\"",
"title": ""
},
{
"docid": "495032",
"text": "It is a scam, other people have given lots of details why. But online access password Is ONLY of use to someone that wishes to steal your money. Just including it in the requested information is enough to make it clear it is a scam. To deposit money into someone accounts only needs. And maybe (if the deposit is being pay by anyone that needs to report the payment to the government for income tax - at least in the UK) If the money is coming from a source that must report the payment for tax.",
"title": ""
},
{
"docid": "301161",
"text": "This is a scam, I'm adding this answer because I was scammed in this fashion. The scammer sent me a check with which I was to deposit. When the money showed up in my account, I would withdraw the scammer's share, and wire the cash to its destination. However, it takes a couple days for a check to clear. Banks, however, want you to see that money, so they might give it to you on good faith before the check actually clears. That's how the scam works, you withdraw the fake money the bank has fronted before the check clears. A couple days later, the check doesn't clear, and you wake up with an account far into the negatives, the scammer long gone.",
"title": ""
},
{
"docid": "475497",
"text": "\"This is another version of an old scam -- \"\"let me have a check deposited in your account because I can't open one for some reason, and I'll share some of the money with you.\"\" Here the scammer is promising to \"\"start a business\"\" with you as a way to gain your confidence and trust. The first danger sign is that you only know this person from online. They are not someone you are friends with in the \"\"real\"\" world. They could be anybody. They used the name of a big company as a way to make what they're doing sound legitimate, but it's all a fraud. They could be depositing a faked Exxon check into your account, which could land YOU in huge trouble. Here's the thing -- The only way Exxon (or any other company) can deposit money in a bank under someone's name is if that person provides the account and routing numbers to an account that already exists. No company can just create an account in another person's name. That's Hollywood movie stuff, but it's not how banking works. To open an account, the bank would need identification on the account holder, so your \"\"friend\"\" already has an account if Exxon has allegedly deposited money. Further, Exxon isn't going to take back money that has already been deposited. In fact, they can't take it back. If the account is in his name, they can't do anything to the account or with the account. This is a situation you should run away from and never look back. Nothing about this story sounds right or legitimate, but this is one of the oldest scams out there since the beginning of the Internet. You would be well advised to stay VERY far away from your supposed friend, because they're anything but your friend. You are being SCAMMED. Don't be a victim. Stop communicating with this person immediately, and DON'T give them any personal information of any kind. They're crooks! I hope this helps. Good luck!\"",
"title": ""
},
{
"docid": "41469",
"text": "\"Let me guess, it's a fairly large amount of money, a few thousand at least. This is a scam. This is a variation on the many fake check scams out there. You deposit the check and you think it \"\"cleared\"\" your bank, but it didn't clear. A clever fake check can take a couple weeks to bounce and the bank will demand the money back. Any money you wire back to the fraudster in the meantime will be lost forever.\"",
"title": ""
},
{
"docid": "197014",
"text": "I wonder if your rational thinking is getting confused by the prospects of getting some deposit from that person? He needs, amongst other things : •online access username •online access password Ok, so you have 1000 in your account. They deposit 500 and you are happy. Then they take out all 1500 and you're done :) How can you not think it is a scam when you're giving them your login as well. Here is an analogy. Some stranger asks you for keys of your home (while you're away) and tells you he will just go in place a gift inside your door and go away. Would you give him your keys and come home later expecting a gift to be there and nothing taken away? Is it a scam if the person only wants to deposit into my account, not make a withdrawal? Who is to tell? P.S: Sorry, please don't mind the rest of this answer but from it could also be related to a new relationship that you are in. Going ahead with this might cause you a lot of emotional harm as well. You seemingly trust that person when there are obvious signs that you are being defrauded, possibly in the name of love.",
"title": ""
},
{
"docid": "482684",
"text": "\"To add to @Dheer's answer, this is almost certainly a scam. The money deposited into your account is not from a person that made an honest mistake with account numbers. It's coming from someone that has access to \"\"send\"\" money that isn't their own. I don't know exactly what they're doing to \"\"send\"\" the money but at some point in the near future your bank will claw that money back from you on the grounds that it was illegitimately transferred to you in the first place. If you send someone money on the premise that you're returning this money then that will be a separate transaction which won't be undone when the deposit in question is undone. Another possibility is that this person has gained access to an account from which they can send domestic wires but not international wires. Their hope is to send money to someone domestically (you) and that this person will then send the money on to Nigeria. If you comply with them; you, in a worst case scenario, could be seen as a money laundering accomplice in addition to having the deposit taken back from you. It's not very likely you wouldn't be seen as another victim of a scam but people have been thrown in jail for less. You should not respond to this person at all. Don't answer the phone when they call and ignore their emails. Don't delete the emails, it's possible that someone at the bank or LE want them. Call your bank immediately and tell them what's up.\"",
"title": ""
},
{
"docid": "578941",
"text": "\"Change the password on your bank account immediately. This is certainly a scam, and while they have your login info they can cause you even bigger problems. As soon as possible, contact your bank and let them know what happened. If you look at the links in the \"\"Related\"\" list you'll see that this is a fairly common scam. It relies on the fact that some forms of fraudulent deposit take a while for the bank to detect. Sometime in the next month, the bank is going to find out that the deposit of $2500 is bogus, say from a bad check, forged money order, or some other fraudulent source. When that happens, the bank is going to undo the deposit, and demand that you make good any of the deposit that has been spent (including the $50 that has already gone to PayPal). The bank may also suspect you of being in cahoots with the depositor, so you may find yourself talking to the local police, accused of fraud. You've put yourself in a bad spot by giving your password out. Unless your can present other evidence, the bank will have a strong assumption that any activity conducted via the login is performed by you. This is why you should get in touch with your bank right away, to build up some evidence of good will on your part. More remote possibilities are that it is part of a 'long con', where somebody is trying to find out how credulous/greedy you are. This seems unlikely. Unless you are a plum target, few con artists would want to risk as much as $2500. Theoretically it could be some sort of money laundering set up, but amounts involved seem too small for that to be likely.\"",
"title": ""
},
{
"docid": "225030",
"text": "\"It's a scam. The cashier's check will be forged. Craigslist has a warning about it here (item #3). What kind of payment do you think is not fakable? Or at least not likely to be used in scams? When on craigslist - deal only locally and in person. You can ask to see the person's ID if you're being paid by check When being paid by check, how can seeing his/her ID help? In case the check isn't cashable, I can find that person by keeping record of his/her ID? If you're paid by check, the payers details should be printed on the check. By checking the ID you can verify that the details match (name/address), so you can find the payer later. Of course the ID can be faked too, but there's so much you can do to protect yourself. You'll get better protection (including verified escrow service) by selling on eBay. Is being paid by cash the safest way currently, although cash can be faked too, but it is the least common thing that is faked currently? Do you recommend to first deposit the cash into a bank (so that let the bank verify if the cash is faked), before delivering the good? For Craigslist, use cash and meet locally. That rules out most scams as a seller. What payment methods do you think are relatively safe currently? Then getting checks must be the least favorite way of being paid. Do you think cash is better than money order or cashier order? You should only accept cash. If it is a large transaction, you can meet them at your bank, have them get cash, and you receive the cash from the bank. Back to the quoted scam, how will they later manipulate me? Are they interested in my stuffs on moving sale, or in my money? They will probably \"\"accidentally\"\" overpay you and ask for a refund of some portion of the overpayment. In that case you will be out the entire amount that you send back to them and possibly some fees from your bank for cashing a bad check.\"",
"title": ""
},
{
"docid": "374988",
"text": "Yes, but it's a matter of paper trail and lifestyle. Your $600K guy may get questioned when he makes the deposit, but would show the record of having that money elsewhere. People buy cars with cash (a check) all the time. The guy filing a tax return claiming little to no income or no return at all, is more likely to get flagged than the $100K+ earning couple who happened to be able to save to buy their $25K car every 10 years with cash. On reading the article, the bank had its own concerns. The guy who was trying to withdraw the money was elderly, and the bank seemed pretty concerned to make sure he wasn't about to be scammed. It may not be spelled out as such, but a custodian of one's money does have an obligation to not be party to a potential scam, and the very request for such a huge sum of money in cash is a red flag.",
"title": ""
},
{
"docid": "35534",
"text": "\"Once upon a time (not all that long ago), British cheques used to say something like \"\"Pay to the order of ..,,,, or bearer the sum of ...,..\"\" (emphasis added) and could be cashed by anyone unless the cheque-writer drew two parallel lines in the upper left corner of the cheque. These lines converted the instrument into a crossed cheque which could only be deposited into a bank account of the payee; a bearer of the cheque could not walk into the bank and waltz out with the cash equivalent. Perhaps British banks no longer use this styling (Indian banks still do) but if that cheque for 60k is not a crossed cheque, it better be sent securely with lots of insurance. An uncrossed cheque is the same as cash since it can be cashed by anyone. That being said, I am with @mhoran_psprep in thinking that all this is just a scam with the OP (mug) being asked to send 3600 bucks to \"\"girlfriend\"\" (scammer) to cover the cost of sending the check with full insurance, and when the check arrives and is deposited by OP into his bank, it will turn out to be a dud, and \"\"girlfriend\"\" will be long gone. The description of how the girlfriend signed a contract for 90k and received 60k of this amount upfront, but in the form of a check payable to boyfriend (!) OP reeks of scam; is this scenario realistic? In the past, I have received offers (usually from Nigeria) from \"\"women\"\" wanting to be my girlfriend, and I am sure that such offers will continue to come in the future....\"",
"title": ""
},
{
"docid": "217875",
"text": "The problem is, I don't understand, how such sites work. Is that scam or not? Some of my friends told me that they've actually received the revenue after they deposited a bit of money to similar sites, and I don't have any evidence not to trust them. Yes there are scam. Stay away. Quite likely people got real money back into Bank Account. Or more likely it shows that there is more [notional] money in the sites account. If such sites really 'work', then how and why? These sites work, because there are quite a few people who believe in free / easy money. The site could be classic pyramid / Ponzi scheme. They could also be involved in some kind of Money Laundering. Why would anyone trust them so much to give them money for absolutely no reason? Okay, I'm not so clever, but they can't make profit only because of stupid people, can they? The same way you did, at times just for fun to experiment. At times because they believe there is easy get rich way. There is a reward that works so that if you see 120 you start believing in it. If you try and withdraw, there will be quite a few obstacles; under the pretext of holding period, withdrawal fees etc... but mostly they will encourage you to keep depositing small amounts and see it grow. This of it this way; if one can make 20% day on day ... one does not need someone else's money. The power of compounding would mean very quickly $ 100 would become 88 BILLION in 120 days!",
"title": ""
},
{
"docid": "545789",
"text": "\"How can I say this more clearly? SCAM, SCAM, SCAM! This is another one of the oldest scams out there, where you've won a prize or an inheritance has come in, and all you have to do is pay the taxes on it to claim it. Don't be a sucker! Ask yourself why the government couldn't (and wouldn't) just take the taxes due out of the funds they have and give the rest to the person they belong to? Wouldn't that be the smartest and easiest thing to do? As an example, let's say that you have $1,000 that belongs to me, and I owe you $100. Would you tell me to pay you the $100 and then you'll give me the $1,000 or would you take the $100 I owe you out of the $1,000 and give me the remaining $900? The fact this is someone you know from the internet and they want your \"\"help\"\" to claim their money should tell you how much of a scam this is. Stop talking to this person, and don't tell them anything personal about you. They are scam artists, and whatever you tell them could be used to steal your identity or take your money. Be careful, my friend!\"",
"title": ""
},
{
"docid": "297589",
"text": "You need a mixture of real estate, funds, and cash in the bank. Putting all your eggs in one basket is never wise. I would also stay away from land-banking period... Like you had mentioned, scam after scam after scam... Here in Tokyo, Royal Siam Trust (White Sands Beach?) is the token land-banking scam... funny enough it was hosted by the OP...",
"title": ""
},
{
"docid": "399526",
"text": "You need to stop what you are doing right now and cut off contact with them! This is an extremely common scam. Here's how it works: They give you a check, maybe even a certified check. Usually in payment for something they are buying from you. The check happens to be for more than the sales price. They ask you to refund the difference, and pressure you to do so quickly. You will see why in a second. The check deposits fine and the money shows up in your account. Assuming the bank wouldn't do that if it wasn't a good check you let your guard down and pay them. In a couple of weeks, the bank detects that it is a fake check. They remove the money from your account, and may even report you for prosecution to local authorities for passing a fraudulent check. Meanwhile the person has the money you gave them and you can't find them because they gave you a fake name. To add insult to injury they may also have the property you sold them. You feel like a chump. Variants of this scam include them asking you to cash a check for them and you get to keep a part of the proceeds for your trouble. Sometimes it is presented as a work-at-home scheme. If you feel you absolutely must complete this deal, and you shouldn't. I would suggest you ask the person for a couple of forms of picture ID and tell them you need to make sure they aren't a scammer and you are going to do a background check on them with your local police to protect yourself. I predict the person will disappear and never contact you again about the money. Also, I suggest you talk to your bank immediately and inform them you think you might have been a victim of a scamming attempt so that you don't look like an accomplice when this is all said and done.",
"title": ""
},
{
"docid": "339759",
"text": "There is no, like, false advertising or misleading that you can claim? Or even reporting them to the Better Business Bureau or something, which maybe isn't enough, but is something. Is there a way to report web scams that is actually effective? Because this seems to border on being a very widespread scam. They did actually take my money. Ebay, Amazon, and other major sites have policies that are pretty tight and can hold up. I wonder if this company can be compared to this but with very bad policies. Ebay can't just enact any policy and get away with it. If they take my money, it seems like there is legal recourse. You buy a product from me, I can't enact any policy on the purchase you make. I can't have fine print that says that you purchased this toy gun and so if it turns out to be a real gun and it kills your kid, too bad. Maybe that is a bad analogy. I'm just saying, websites are subject to reasonable questioning of their policies under the law or at least business institutions. I posted a 3 star review, but the comment (if they post it) is very direct and negative, without making any specific claims. Again, we'll see. I guess they can reject that as well.",
"title": ""
},
{
"docid": "539065",
"text": "\"That makes complete logical sense, this isn't a shutdown of cryptocurrency however. If you look at Russia, they banned Bitcoin at one point. Now they have said it is not illegal, and are looking to regulate it. It's entirely possible that the law makers don't understand it yet but eventually will. When that time comes rules will come into play possibly/hopefully will benefit the majority. The biggest factor playing against crypto right now is lack of understanding to the majority. Many people don't understand there is no security with an ICO, you have no guarantee of profit. They hear about the gains bitcoin is making and they get excited. There was an ad going around that literally said \"\"Missed the Bitcoin ICO? Don't miss this one\"\" or something along those lines. It is feeding off the uninformed. China isn't trying to ban crypto(We're talking about a large group of people), they're preventing ICOs from continuing what they are doing. A lot of ICOs are complete scams/ponzi schemes that benefit a very small percentage. They didn't just ban bitcoin, they banned scamming people. It's better to create a fast ban and change a law later, then to continue to allow people to get screwed while we debate logistics. Banning ICOs in my opinion is a step in the right direction and in no way should be seen as the start of the end.\"",
"title": ""
},
{
"docid": "313937",
"text": "The faster it dies, the fewer morons will be scammed by this pay-day-loan scam. But it's worse than a payday loan scam, because Uber drivers are stealing money from their future selves, *and paying 25% of it to Uber - and they have to work to do it.*",
"title": ""
},
{
"docid": "175545",
"text": "Other people are saying this might be a scam, or this sounds like a scam. THIS IS DEFINITELY 100% A SCAM. Do not ship your computer equipment to these people. Personally I would never sell computer equipment outside of my country, and even then would probably use escrow.",
"title": ""
},
{
"docid": "190266",
"text": "\"There is such a thing as Deposit Only. This will allow the individual's account to function only for collection of monetary deposits. NO ONE will be able to withdraw...only deposit. The account holder may still physically withdraw at their banking institution. Think of it as taking your account from a \"\"public\"\" profile to a \"\"private\"\" profile. Doing this is beneficial for ppl who may have been scammed into a program or product where there account is bieng fraudulently overdrafted, or simply to protect your funds from bieng drafted without your approval or despite your requests for ceasing the drafts. When making your account a deposit only account it's a good idea to open a NEW account at a Different banking institution, because some banks will still allow an account that is \"\"attached\"\" to the deposit only account to be drafted from it. WIth the new account you can utilize that one for paying day to day bills and just transfer funds from the deposit only account to the new account. A deposit only account is also a good way to build up a nice nest egg for yourself or even a young adult! source- Financial Adivsor 4years-\"",
"title": ""
},
{
"docid": "575918",
"text": "Is there any truth to this, or is this another niche scam that's been brewing the last few years? While it may not be an outright scam, such schemes do tend to be on borderline of scams. Technically most of what is being said claimed can be true, however in reality such windfall gains never happen to the investors. Whatever gains are there will be cornered by the growers, trades, other entities in supply chain leaving very little to the investors. It is best to stay away from such investments.",
"title": ""
},
{
"docid": "78395",
"text": "This is a typical scam. Yes, you just got listed with the terrorists as trying to launder money internationally. Terrorist organizations will try to find someone in the US who will accept deposits from overseas sources then send that money to one of their operatives. Cooperate with whichever police force comes knocking on your door. Pray that it isn't Homeland Security. They do not need warrants.",
"title": ""
},
{
"docid": "564156",
"text": "It could be that your friend is being scammed into recruiting you as another victim. So it is vaguely possible that this isn't malicious on their part. However, it is a scam if they are asking for your credit card info without a completely clear and good reason it's necessary. Which they have failed to do. That is reason enough to assume it's a scam, illegal, or both. Run. And seriously consider whether these are really people you can trust on anything, never mind money. At best they're gullible.",
"title": ""
},
{
"docid": "484875",
"text": "Westgate is a notoriously terrible employer to work for in Orlando, and their whole timeshare business model is a complete scam. Check out all of the complaints on Comsumer Affairs' website: http://www.consumeraffairs.com/travel/westgate.html?page=2 edit: More complaints http://www.ripoffreport.com/directory/westgate-resorts.aspx http://www.utahstories.com/2008/06/13/timeshare-scam-westgate-resorts-2/ http://www.complaintsboard.com/complaints/westgate-resorts-tennessee-c226610.html http://westgate-resorts.pissedconsumer.com/westgate-scam-20120926347849.html",
"title": ""
},
{
"docid": "586649",
"text": "\"Generally, yes. Rather than ask, \"\"why are these guys so cheap?\"\", you should be asking why the big names are so expensive. :) Marketing spend plays a big role there. Getting babies to shill for your company during the super bowl requires a heck of a lot of commissions. Due to the difficulties involved in setting up a brokerage, it's unlikely that you'll see a scam. A brokerage might go bankrupt for random reasons, but that's what investor insurance is for. \"\"Safeness\"\" is mostly the likelihood that you'll be able to get access to your funds on deposit with the broker. Investment funds are insured by SIPC for up to $500,000, with a lower limit on cash. The specific limits vary by broker, with some offering greater protection paid for on their own dime. Check with the broker -- it's usually on their web pages under \"\"Security\"\". Funds in \"\"cash\"\" might be swept into an interest-earning investment vehicle for which insurance is different, and that depends on the broker, too. A few Forex brokers went bankrupt last year, although that's a new market with fewer regulatory protections for traders. I heard that one bankruptcy in the space resulted in a 7% loss for traders with accounts there, and that there was a Ponzi-ish scam company as well. Luckily, the more stringent regulation of stock brokerages makes that space much safer for investors. If you want to assess the reliability of an online broker, I suggest the following: It's tempting to look at when the brokerage was founded. Fly-by-night scams, by definition, won't be around very long -- and usually that means under a few months. Any company with a significant online interface will have to have been around long enough to develop that client interface, their backend databases, and the interface with the markets and their clearing house. The two brokerages you mentioned have been around for 7+ years, so that lends strength to the supposition of a strong business model. That said, there could well be a new company that offers services or prices that fit your investment need, and in that case definitely look into their registrations and third-party reviews. Finally, note that the smaller, independent brokerages will probably have stiffer margin rules. If you're playing a complex, novel, and/or high-risk strategy that can't handle the volatility of a market crash, even a short excursion such as the 2010 flash crash, stiff margin rules might have consequences that a novice investor would rather pretend didn't exist.\"",
"title": ""
},
{
"docid": "237607",
"text": "\"A friend since July online and big business talks and trust/money forwards. Usually a question \"\"is this a scam or legitimate?\"\" is hard to answer since obviously scams are modelled after legitimate stories (or they'd easily fail). If there were bookmakers for \"\"scam or legitimate\"\", this one would easily gather odds of 10000:1. The only plausible reason for this to be legitimate would be to defraud the scam-or-legitimate bookmakers. At any rate, Exxon is a large company and has to obey labor laws. They cannot set up operations in a manner where their workers may not have access to their salary for prolonged times without easy remedy. Drop communications immediately, don't open them, don't read them. They hook you with emotional investment. They will redouble efforts if it appears you are slipping out of their reach. Explanations will become more plausible, more pressing, more emotionally charged. You are a big promising fish and they won't let you swim off without a serious struggle to rehook you. Hand your communication so far to law enforcement. That may help with not having to figure this out on your own.\"",
"title": ""
}
] |
PLAIN-2527
|
Dairy Estrogen and Male Fertility
|
[
{
"docid": "MED-4396",
"text": "There has been a remarkable paucity of evidence for an association between diet and acne. Our previous studies suggest that there is an association between milk intake and teenage acne. This is a prospective cohort study to evaluate that relationship. We studied 6,094 girls, aged 9-15 years in 1996, who reported dietary intake on up to three food frequency questionnaires from 1996 to 1998. Presence and severity of acne was assessed by questionnaire in 1999. We computed multivariate prevalence ratios (PR) and 95 percent confidence intervals for acne. After accounting for age at baseline, height and energy intake, the multivariate PRs (95 % CI; p-value for test of trend) for acne comparing highest (2 or more servings per day) to lowest (<1 per week) intake categories in 1996, were 1.20 (1.09, 1.31; <0.001) for total milk, 1.19 (1.06, 1.32; <0.001) for whole milk, 1.17 (1.04, 1.31; 0.002) for low fat milk and 1.19 (1.08, 1.31; <0.001) for skim milk. This result did not change appreciably when we excluded girls who reported use of contraceptives and when we restricted our analysis to those younger than 11 years of age at baseline. We found a positive association between intake of milk and acne. This finding supports earlier studies and suggests that the metabolic effects of milk are sufficient to elicit biological responses in consumers.",
"title": "Milk consumption and acne in adolescent girls."
},
{
"docid": "MED-2769",
"text": "The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002–2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.",
"title": "Milk Intake in Early Life and Risk of Advanced Prostate Cancer"
},
{
"docid": "MED-2774",
"text": "Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.",
"title": "Milk stimulates growth of prostate cancer cells in culture."
},
{
"docid": "MED-3935",
"text": "Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Methods In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. Results We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. Conclusions PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.",
"title": "Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007"
},
{
"docid": "MED-4681",
"text": "BACKGROUND: It has been suggested that phytoestrogens and dietary fiber can affect puberty timing. OBJECTIVE: We examined whether intake of isoflavone and fiber in healthy white children before their pubertal growth spurt [age at take-off (ATO)] was associated with puberty timing. DESIGN: Multivariate regression analyses were performed in 227 DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) Study participants with 3-d weighed dietary records and information on potential confounders at baseline (1 and 2 y before ATO). In a subsample (n = 111), urinary isoflavones were determined in 24-h urine samples by gas chromatography-mass spectrometry analysis. Puberty timing was examined by using ATO and chronologic ages at pubertal stage 2 for breast development (B2) or gonadal development, peak height velocity (PHV), and menarche or voice break. RESULTS: Girls whose diet was in the highest dietary isoflavone tertile experienced Tanner stage 2 for breast development ap 0.7 y later and reached PHV ap 0.6 y later than did girls whose diet was in the lowest isoflavone tertile [age (95% CI) at B2: 10.7 y (10.4, 10.9 y) compared with 10.0 y ( 9.7, 10.3 y), respectively; P for trend = 0.04; age at PHV: 11.9 y (11.6, 12.2 y) compared with 11.3 y (11.0, 11.6 y), respectively; P for trend = 0.04; adjusted for body mass index z score and fiber intake]. In boys, dietary isoflavones were not associated with pubertal markers. Urinary isoflavone and dietary fiber intakes were not associated with pubertal markers. CONCLUSIONS: Girls, but not boys, with higher prepubertal isoflavone intakes appear to enter puberty at a later age. Fiber intake in this sample of healthy white girls and boys was not relevant for puberty timing.",
"title": "Relation of isoflavones and fiber intake in childhood to the timing of puberty."
},
{
"docid": "MED-1764",
"text": "The decline in sperm count rates over the last 50 years appears to parallel the rising prevalence of obesity. As lipids levels are strongly associated with obesity, high lipids levels or hyperlipidemia may thus play an important role in the decline in fertility in addition to other environmental or lifestyle factors. The objective of this population based cohort study was to evaluate the association between men’s serum lipid concentrations and semen quality parameters among 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided prospectively up to two semen samples (94% of men provided one or more semen samples, and 77% of men provided a second sample approximately one month later). Linear mixed effects models were used to estimate the associations between baseline lipid concentrations and semen quality parameters, adjusted for age, body mass index, and race. We found that higher levels of serum total cholesterol, free cholesterol and phospholipids were associated with a significantly lower percentage of sperm with intact acrosome and smaller sperm head area and perimeter. Our results suggest that lipid concentrations may affect semen parameters, specifically sperm head morphology, highlighting the importance of cholesterol and lipid homeostasis for male fecundity.",
"title": "Lipid Concentrations and Semen Quality: The LIFE Study"
},
{
"docid": "MED-1781",
"text": "BACKGROUND: Saturated fat intake has been associated with both cardiovascular disease and cancer risk, and a newly published study found an association between saturated fat intake and a lower sperm concentration in infertile men. OBJECTIVE: The objective was to examine the association between dietary fat intake and semen quality among 701 young Danish men from the general population. DESIGN: In this cross-sectional study, men were recruited when they were examined to determine their fitness for military service from 2008 to 2010. They delivered a semen sample, underwent a physical examination, and answered a questionnaire comprising a quantitative food-frequency questionnaire to assess food and nutrient intakes. Multiple linear regression analyses were performed with semen variables as outcomes and dietary fat intakes as exposure variables, adjusted for confounders. RESULTS: A lower sperm concentration and total sperm count in men with a high intake of saturated fat was found. A significant dose-response association was found, and men in the highest quartile of saturated fat intake had a 38% (95% CI: 0.1%, 61%) lower sperm concentration and a 41% (95% CI: 4%, 64%) lower total sperm count than did men in the lowest quartile. No association between semen quality and intake of other types of fat was found. CONCLUSIONS: Our findings are of potentially great public interest, because changes in diet over the past decades may be part of the explanation for the recently reported high frequency of subnormal human sperm counts. A reduction in saturated fat intake may be beneficial for both general and reproductive health.",
"title": "High dietary intake of saturated fat is associated with reduced semen quality among 701 young Danish men from the general population."
},
{
"docid": "MED-1762",
"text": "Background In the United States, anabolic sex steroids are administered to cattle for growth promotion. There is concern regarding the reproductive consequences of this practice for men who eat beef. We investigated whether meat consumption was associated with semen quality parameters and reproductive hormone levels in young men. Methods Semen samples were obtained from 189 men aged 18-22 years. Diet was assessed with a previously validated food frequency questionnaire. We used linear regression to analyze the cross-sectional associations of meat intake with semen quality parameters and reproductive hormones, while adjusting for potential confounders. Results There was an inverse relation between processed red meat intake and total sperm count. The adjusted relative differences in total sperm counts for men in increasing quartiles of processed meat intake were 0 (ref), −3 (95% confidence interval = −67 to 37), −14 (−82 to 28), and −78 (−202 to −5) million (test for trend, P = 0.01). This association was strongest among men with abstinence time less than 2 days and was driven by a strong inverse relation between processed red meat intake and ejaculate volume (test for trend, P =0.003). Conclusions In our population of young men, processed meat intake was associated with lower total sperm count. We cannot distinguish whether this association is due to residual confounding by abstinence time or represents a true biological effect.",
"title": "Meat intake and reproductive parameters among young men"
},
{
"docid": "MED-1770",
"text": "Oestrogens govern reproductive functions in vertebrates, and are present in all animal tissues. The theoretical maximum daily intake (TMDI) of oestradiol-17beta by consumption of cattle meat is calculated to be 4.3 ng. Following the use of oestradiol-containing growth-promoting agents, TMDI is increased by a factor of 4.6 to 20 ng oestradiol-17beta, assuming that single dosage and 'good animal husbandry' are observed. Pork and poultry probably contain similar amounts of oestrogens as untreated cattle. The mean concentration of oestradiol-17beta in whole milk is estimated at 6.4 pg/ml. Scarce data available on eggs report up to 200 pg/g oestradiol-17beta. The risk evaluation of oestrogenic growth-promoting agents is limited by analytical uncertainties. Residues of oestradiol-17alpha and the importance of oestrogen conjugates are widely unknown. The performance of mass spectrometry still needs to be improved for confirmation of oestrogen concentrations in most food. At present, the potential relevance of oestradiol acyl esters, the actual daily production rate of oestradiol in prepubertal children, and the role of oestradiol metabolites in cancer are obscure. The presence of different cytoplasmic oestrogen receptor subtypes and potential oestradiol effects in non-reproductive functions require further examination.",
"title": "Possible health impact of animal oestrogens in food."
},
{
"docid": "MED-1774",
"text": "This study measured 21 persistent, bioaccumulative, and toxic (PBT) pollutants in the US milk supply. Since milk fat is likely to be among the highest dietary sources of exposure to PBTs, it is important to understand their levels in this food. Nationwide samples were collected from 45 dairy plants in July of 2000 and again in January 2001. The levels of all chemicals in the chlorobenzene, pesticide and other halogenated organic groups were determined to be below their detection limits in all samples. National averages were computed for 11 chemicals or chemical groups found above the detection limits. The national average CDD/CDF and PCB TEQ concentrations were 14.30 and 8.64 pg/l, respectively, for a total of 22.94 pg/l. These levels are about half the values found in a similar study conducted in 1996. If this difference is in fact indicative of declining milk levels and assuming exposure levels from nondairy pathways have remained the same over this time period, this would result in an overall decrease in adult background dioxin exposure of 14%. Six PAHs were detected with national averages ranging from 40 to 777 ng/l. Cadmium concentrations ranged from 150 to 870 ng/l with a national average of 360 ng/l. Lead concentrations were consistently higher than those of cadmium, ranging from 630 to 1950 ng/l with a national average of 830 ng/l. PAHs showed the strongest seasonal/geographic differences, with higher levels in winter than summer, north than south and east than west. Average adult daily intakes from total milk fat ingestion were computed for all detected compounds and compared to total intakes from all pathways: CDD/CDF/PCB TEQs: 8 vs. 55 pg/day, PAHs: 0.6 vs. 3 micro g/day, lead: 0.14 vs. 4-6 micro g/day, and cadmium: 0.06 vs. 30 micro g/day.",
"title": "A national survey of persistent, bioaccumulative, and toxic (PBT) pollutants in the United States milk supply."
},
{
"docid": "MED-3940",
"text": "Objective: To determine whether evidence of neuronal dysfunction or demise preceded deposition of Lewy pathology in vulnerable neurons in Parkinson disease (PD). Methods: We examined the extent of nigral dysfunction and degeneration among 63 normal, incidental Lewy body disease (ILBD), and PD cases based on tyrosine hydroxylase (TH) immunoreactivity and neuron densities, respectively. The relationship between these markers and Lewy pathology (LP) burden in the substantia nigra (SN) and Braak PD stage was assessed. Results: Compared with normal subjects, ILBD cases displayed a significantly higher percentage of TH-negative cells and lower neuronal densities in the SN as early as Braak PD stages 1 and 2, before LP deposition in the nigrostriatal system. ILBD nigral neuron densities were intermediate between normal subjects and PD cases, and TH-negative percentages were higher in ILBD than either normal or PD cases. Furthermore, neuron density and neuronal dysfunction levels remained relatively constant across Braak PD stages in ILBD. Conclusions: These results suggest that significant neurodegeneration and cellular dysfunction precede LP in the SN, challenging the pathogenic role of LP in PD and the assumption that ILBD always represents preclinical PD.",
"title": "Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease"
},
{
"docid": "MED-4678",
"text": "The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100 000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45–0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12–2.38) and 1.35 (95% CI 1.02–1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60–1.04), 0.69 (95% CI 0.54–0.88), 0.66 (95% CI 0.51–0.85) and 0.64 (95% CI 0.48–0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer. British Journal of Cancer (2002) 86, 723–727. DOI: 10.1038/sj/bjc/6600124 www.bjcancer.com © 2002 Cancer Research UK",
"title": "Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women"
},
{
"docid": "MED-4679",
"text": "OBJECTIVES The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The κ statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage ≥2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage ≥2. The prime determinant of height velocity was pubertal status. CONCLUSIONS In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.",
"title": "Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls"
},
{
"docid": "MED-4394",
"text": "Acne vulgaris, the most common skin disease of western civilization, has evolved to an epidemic affecting more than 85% of adolescents. Acne can be regarded as an indicator disease of exaggerated insulinotropic western nutrition. Especially milk and whey protein-based products contribute to elevations of postprandial insulin and basal insulin-like growth factor-I (IGF-I) plasma levels. It is the evolutional principle of mammalian milk to promote growth and support anabolic conditions for the neonate during the nursing period. Whey proteins are most potent inducers of glucose-dependent insulinotropic polypeptide secreted by enteroendocrine K cells which in concert with hydrolyzed whey protein-derived essential amino acids stimulate insulin secretion of pancreatic β-cells. Increased insulin/IGF-I signaling activates the phosphoinositide-3 kinase/Akt pathway, thereby reducing the nuclear content of the transcription factor FoxO1, the key nutrigenomic regulator of acne target genes. Nuclear FoxO1 deficiency has been linked to all major factors of acne pathogenesis, i.e. androgen receptor transactivation, comedogenesis, increased sebaceous lipogenesis, and follicular inflammation. The elimination of the whey protein-based insulinotropic mechanisms of milk will be the most important future challenge for nutrition research. Both, restriction of milk consumption or generation of less insulinotropic milk will have an enormous impact on the prevention of epidemic western diseases like obesity, diabetes mellitus, cancer, neurodegenerative diseases and acne. Copyright © 2011 S. Karger AG, Basel.",
"title": "Evidence for acne-promoting effects of milk and other insulinotropic dairy products."
},
{
"docid": "MED-5106",
"text": "Objective We sought to examine the association between dietary dairy intake and teenaged acne among boys. Methods This was a prospective cohort study. We studied 4273 boys, members of a prospective cohort study of youths and of lifestyle factors, who reported dietary intake on up to 3 food frequency questionnaires from 1996 to 1998 and teenaged acne in 1999. We computed multivariate prevalence ratios and 95% confidence intervals for acne. Results After adjusting for age at baseline, height, and energy intake, the multivariate prevalence ratios (95% confidence interval; P value for test of trend) for acne comparing highest (>2 servings/d) with lowest (<1/wk) intake categories in 1996 were 1.16 (1.01, 1.34; 0.77) for total milk, 1.10 (0.94, 1.28; 0.83) for whole/2% milk, 1.17 (0.99, 1.39; 0.08) for low-fat (1%) milk, and 1.19 (1.01, 1.40; 0.02) for skim milk. Limitations Not all members of the cohort responded to the questionnaire. Acne assessment was by self-report and boys whose symptoms might have been part of an underlying disorder were not excluded. We did not adjust for steroid use and other lifestyle factors that may affect occurrence of acne. Conclusion We found a positive association between intake of skim milk and acne. This finding suggests that skim milk contains hormonal constituents, or factors that influence endogenous hormones, in sufficient quantities to have biological effects in consumers.",
"title": "Milk consumption and acne in teenaged boys"
},
{
"docid": "MED-3937",
"text": "BACKGROUND: The goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern. METHODS: A retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors. RESULTS: Seven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3-8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called \"the magic potion\". CONCLUSIONS: Although over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).",
"title": "Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books."
},
{
"docid": "MED-1778",
"text": "Objective To examine the relationship between dairy food intake and semen parameters Design Longitudinal study Setting Men attending academic medical center fertility clinic in Boston, MA Patients 155 men Interventions None Main Outcome Measures total sperm count, sperm concentration, progressive motility, and morphology Results Low-fat dairy intake was positively related to sperm concentration and progressive motility. On average, men in the highest quartile of intake (1.22–3.54 servings/day) had 33% (95% confidence interval (CI) 1, 55) higher sperm concentration and 9.3 (95%CI 1.4, 17.2) percentage units higher sperm motility than men in the lowest quartile of intake (≤0.28 servings/day). These associations were primarily explained by intake of low-fat milk. The corresponding results for low-fat milk were 30% (95%CI 1,51) higher sperm concentration and 8.7 (95%CI 3.0, 14.4) percentage units higher sperm motility. Cheese intake was associated with lower sperm concentration among ever smokers. In this group, men in the highest tertile of intake (0.82–2.43 servings/day) had 53.2% (95%CI 9.7, 75.7) lower sperm concentration than men in the lowest tertile of cheese intake (<0.43 servings/day). Conclusions Our findings suggest that low-fat dairy intake, particularly low-fat milk, is related to higher sperm concentration and progressive motility, while cheese intake to lower sperm concentration among past or current smokers.",
"title": "Dairy intake and semen quality among men attending a fertility clinic"
},
{
"docid": "MED-2772",
"text": "Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further. Copyright 2004 Lawrence Erlbaum Associates, Inc.",
"title": "Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies."
},
{
"docid": "MED-4951",
"text": "OBJECTIVE: To evaluate the role of the environmental estrogens polychlorinated biphenyls (PCBs) and phthalate esters (PEs) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology. DESIGN: Randomized controlled study. SETTING: Tertiary care referral infertility clinic and academic research center. PATIENT(S): Twenty-one infertile men with sperm counts <20 million/mL and/or rapid progressive motility <25% and/or <30% normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception. Semen and blood samples were obtained as part of the treatment protocol. MAIN OUTCOME MEASURE(S): Evaluation of semen parameters such as ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity, sperm chromatin stability, and sperm nuclear DNA integrity. RESULT(S): PCBs were detected in the seminal plasma of infertile men but not in controls, and the concentration of PEs was significantly higher in infertile men compared with controls. Ejaculate volume, sperm count, progressive motility, normal morphology, and fertilizing capacity were significantly lower in infertile men compared with controls. The highest average PCB and PE concentrations were found in urban fish eaters, followed by rural fish eaters, urban vegetarians, and rural vegetarians. The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls. CONCLUSION(S): PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology.",
"title": "Role of environmental estrogens in the deterioration of male factor fertility."
},
{
"docid": "MED-2771",
"text": "We have previously found a positive association between milk consumption and prostate cancer risk using meta-analysis to analyze published case-control studies. In the present study, further meta-analysis was conducted to estimate the summary relative risk (RR) between the consumption of milk and dairy products and prostate cancer from cohort studies published between 1966- 2006. We found 18 relevant articles and 13 independent studies were available for our analysis. The summary RR was 1.13 (95% confidence interval = 1.02-1.24) when comparing the highest with the lowest quantile of consumption. The summary RRs by study stratification showed a positive association. A dose-response relationship was identified when combining the studies that partitioned the consumption by quintiles. We also evaluated the effects of some limitations, such as dairy classification, prostate cancer stages and publication bias, in the present study. These findings, together with the previous study, suggest that the consumption of milk and dairy products increases the risk of prostate cancer. This is biologically plausible since milk contains considerable amounts of fat, hormones, and calcium that are associated with prostate cancer risk.",
"title": "Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies."
},
{
"docid": "MED-1768",
"text": "The role of environmental compounds with estrogenic activity in the development of male reproductive disorders has been a source of great concern. Among the routes of human exposure to estrogens, we are particularly concerned about cows' milk, which contains considerable amounts of estrogens. The major sources of animal-derived estrogens in the human diet are milk and dairy products, which account for 60-70% of the estrogens consumed. Humans consume milk obtained from heifers in the latter half of pregnancy, when the estrogen levels in cows are markedly elevated. The milk that we now consume may be quite unlike that consumed 100 years ago. Modern genetically-improved dairy cows, such as the Holstein, are usually fed a combination of grass and concentrates (grain/protein mixes and various by-products), allowing them to lactate during the latter half of pregnancy, even at 220 days of gestation. We hypothesize that milk is responsible, at least in part, for some male reproductive disorders. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Is milk responsible for male reproductive disorders?"
},
{
"docid": "MED-4726",
"text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.",
"title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies."
},
{
"docid": "MED-1773",
"text": "STUDY QUESTION Is increased consumption of dairy foods associated with lower semen quality? SUMMARY ANSWER We found that intake of full-fat dairy was inversely related to sperm motility and morphology. These associations were driven primarily by intake of cheese and were independent of overall dietary patterns. WHAT IS KNOWN ALREADY It has been suggested that environmental estrogens could be responsible for the putative secular decline in sperm counts. Dairy foods contain large amounts of estrogens. While some studies have suggested dairy as a possible contributing factor for decreased semen quality, this finding has not been consistent across studies. STUDY DESIGN, SIZE, DURATION The Rochester Young Men's Study (n = 189) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS/MATERIALS, SETTING, METHODS Men aged 18–22 years were included in this analysis. Diet was assessed via food frequency questionnaire. Linear regression was used to analyze the relation between dairy intake and conventional semen quality parameters (total sperm count, sperm concentration, progressive motility, morphology and ejaculate volume) adjusting for age, abstinence time, race, smoking status, body mass index, recruitment period, moderate-to-intense exercise, TV watching and total calorie intake. MAIN RESULTS AND THE ROLE OF CHANCE Total dairy food intake was inversely related to sperm morphology (P-trend = 0.004). This association was mostly driven by intake of full-fat dairy foods. The adjusted difference (95% confidence interval) in normal sperm morphology percent was −3.2% (−4.5 to −1.8) between men in the upper half and those in the lower half of full-fat dairy intake (P < 0.0001), while the equivalent contrast for low-fat dairy intake was less pronounced [−1.3% (−2.7 to −0.07; P= 0.06)]. Full-fat dairy intake was also associated with significantly lower percent progressively motile sperm (P= 0.05). LIMITATIONS, REASONS FOR CAUTION As it was a cross-sectional study, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS Further research is needed to prove a causal link between a high consumption of full-fat dairy foods and detrimental effects on semen quality. If verified our findings would mean that intake of full-fat dairy foods should be considered in attempts to explain secular trends in semen quality and that men trying to have children should restrict their intake. STUDY FUNDING/COMPETING INTEREST(S) European Union Seventh Framework Program (Environment), ‘Developmental Effects of Environment on Reproductive Health’ (DEER) grant 212844. Grant P30 {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"DK046200\",\"term_id\":\"187635970\",\"term_text\":\"DK046200\"}}DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16 from the National Institutes of Health. None of the authors has any conflicts of interest to declare.",
"title": "Dairy food intake in relation to semen quality and reproductive hormone levels among physically active young men"
},
{
"docid": "MED-1763",
"text": "The current trends of increasing incidences of testis, breast and prostate cancers are poorly understood, although it is assumed that sex hormones play a role. Disrupted sex hormone action is also believed to be involved in the increased occurrence of genital abnormalities among newborn boys and precocious puberty in girls. In this article, recent literature on sex steroid levels and their physiological roles during childhood is reviewed. It is concluded that (i) circulating levels of estradiol in prepubertal children are lower than originally claimed; (ii) children are extremely sensitive to estradiol and may respond with increased growth and/or breast development even at serum levels below the current detection limits; (iii) no threshold has been established, below which no hormonal effects can be seen in children exposed to exogenous steroids or endocrine disruptors; (iv) changes in hormone levels during fetal and prepubertal development may have severe effects in adult life and (v) the daily production rates of sex steroids in children estimated by the Food and Drug Administration in 1999 and still used in risk assessments are highly overestimated and should be revised. Because no lower threshold for estrogenic action has been established, caution should be taken to avoid unnecessary exposure of fetuses and children to exogenous sex steroids and endocrine disruptors, even at very low levels.",
"title": "The sensitivity of the child to sex steroids: possible impact of exogenous estrogens."
},
{
"docid": "MED-1771",
"text": "Semen analysis of 66 unmarried medical students in the age group of 17-21 years was carried out. A higher liquefaction time pH, motility, lower sperm count and abnormal forms were observed compared to reported values. Liquefaction time, pH and sperm count was found significantly different in non-vegetarians and vegetarians, perhaps due to difference in their dietary proteins.",
"title": "Some observations on human semen analysis."
},
{
"docid": "MED-2775",
"text": "The incidence and mortality rates of testicular and prostatic cancers in 42 countries were correlated with the dietary practices in these countries using the cancer rates (1988-92) provided by the International Agency for Research on Cancer (IARC) and the food supply data (1961-90) provided by the Food and Agriculture Organization (FAO). Among the food items we examined, cheese was most closely correlated with the incidence of testicular cancer at ages 20-39, followed by animal fats and milk. The correlation coefficient (r) was highest (r = 0.804) when calculated for cheese consumed during the period 1961-65 (maternal or prepubertal consumption). Stepwise-multiple-regression analysis revealed that milk + cheese (1961-65) made a significant contribution to the incidence of testicular cancer (standardized regression coefficient [R] = 0.654). Concerning prostatic cancer, milk (1961-90) was most closely correlated (r = 0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk + cheese as a factor contributing to the incidence of prostatic cancer (R = 0.525). The food that was most closely correlated with the mortality rate of prostatic cancer was milk (r = 0.766), followed by coffee, cheese and animal fats. Stepwise-multiple-regression analysis revealed that milk + cheese was a factor contributing to mortality from prostatic cancer (R = 0.580). The results of our study suggest a role of milk and dairy products in the development and growth of testicular and prostatic cancers. The close correlation between cheese and testicular cancer and between milk and prostatic cancer suggests that further mechanistic studies should be undertaken concerning the development of male genital organ cancers. Copyright 2001 Wiley-Liss, Inc.",
"title": "Incidence and mortality of testicular and prostatic cancers in relation to world dietary practices."
},
{
"docid": "MED-2773",
"text": "In Japan dramatic lifestyle changes occurred after World War 2. To examine the experience of Japan as a clue to the etiology, trends in the mortality rates of testicular and prostatic cancers from 1947 to 1998 were related to changes in dietary practices. The male population born before 1945 had a peak in death from testicular cancer in their thirties or forties, whereas those born after 1946 had a peak in their twenties. The death rate of prostatic cancer increased 25-fold almost linearly after the war. The intake of milk, meat, and eggs increased 20-, 9-, and 7-fold, respectively, after the war. In connection with the development and growth of testicular and prostatic cancers in Japan, particular attention should be paid to milk, because the increase in its consumption in this country is a recent occurrence and because milk contains considerable amounts of estrogens plus saturated fats.",
"title": "The experience of Japan as a clue to the etiology of testicular and prostatic cancers."
},
{
"docid": "MED-3938",
"text": "Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.",
"title": "Association between polychlorinated biphenyls and Parkinson’s disease neuropathology"
},
{
"docid": "MED-4398",
"text": "BACKGROUND: Previous studies suggest possible associations between Western diet and acne. We examined data from the Nurses Health Study II to retrospectively evaluate whether intakes of dairy foods during high school were associated with physician-diagnosed severe teenage acne. METHODS: We studied 47,355 women who completed questionnaires on high school diet in 1998 and physician-diagnosed severe teenage acne in 1989. We estimated the prevalence ratios and 95% confidence intervals of acne history across categories of intakes. RESULTS: After accounting for age, age at menarche, body mass index, and energy intake, the multivariate prevalence ratio (95% confidence intervals; P value for test of trend) of acne, comparing extreme categories of intake, were: 1.22 (1.03, 1.44; .002) for total milk; 1.12 (1.00, 1.25; .56) for whole milk; 1.16 (1.01, 1.34; .25) for low-fat milk; and 1.44 (1.21, 1.72; .003) for skim milk. Instant breakfast drink, sherbet, cottage cheese, and cream cheese were also positively associated with acne. CONCLUSION: We found a positive association with acne for intake of total milk and skim milk. We hypothesize that the association with milk may be because of the presence of hormones and bioactive molecules in milk.",
"title": "High school dietary dairy intake and teenage acne."
},
{
"docid": "MED-3939",
"text": "Excerpt This Statistical Brief presents data from the Healthcare Cost and Utilization Project (HCUP) on the treatment of TBI in U.S. hospitals in 2004. Hospital utilization and costs for TBI admissions are compared with hospital stays for all other injuries. Additionally, trends in hospital stays for TBI and differences in the distribution of TBI admissions by various patient characteristics are examined. Finally, common causes of TBIs resulting in hospital admission, as well as the coexisting conditions often associated with these injuries, are described. All differences between estimates noted in the text are statistically significant at the 0.05 level or better.",
"title": "Hospital Admissions for Traumatic Brain Injuries, 2004: Statistical Brief #27"
},
{
"docid": "MED-1766",
"text": "We studied 19 male patients with primary hyperlipoproteinaemia, a control group of 28 healthy men and 44 infertile males before any treatment was undertaken. Spermiogram, seminal biochemical studies, measurements of plasma hormone levels and lipid determinations were carried out. Most hyperlipoproteinaemic patients showed abnormalities in the spermiograms and the mean values were lower than in the controls except for semen volume. Seminal biochemical determinations were normal in the majority and the hormone profile showed some abnormal values, mainly for E2. Lipid abnormalities were more common in azoospermic infertile men and mean lipid levels were higher. Correlation studies suggest that high levels of C and/or Tg are associated with poor semen quality and higher FSH levels. The results of our studies suggest that high lipid levels exert adverse direct effects at the testicular level.",
"title": "Lipids and testicular function."
},
{
"docid": "MED-2770",
"text": "Although breast and ovarian cancers are rare in Japan compared with other developed countries, the death rates for both are increasing. In Japan, dramatic lifestyle changes occurred after World War II. Over the past 50 years (1947-1997), the age-standardized death rates of breast and ovarian cancers increased about 2- and 4-fold, respectively, and the respective intake of milk, meat, and eggs increased 20-, 10-, and 7-fold. The increase in the annual death rates from breast and ovarian cancers might be due to the lifestyle changes (increased consumption of animal-derived food) that occurred after 1945. Among the food, milk and dairy products should receive particular attention since they contain considerable amounts of estrogens.",
"title": "The experience of Japan as a clue to the etiology of breast and ovarian cancers: relationship between death from both malignancies and dietary prac..."
},
{
"docid": "MED-1765",
"text": "Inhibition of cholesterol biosynthesis by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors could, in theory, adversely affect male gonadal function because cholesterol is a precursor of steroid hormones. The objective of this randomized double-blind trial was to compare the effects of simvastatin, pravastatin, and placebo on gonadal testosterone production and spermatogenesis. After a 6-week placebo and lipid-lowering diet run-in period, 159 male patients aged 21 to 55 years with type IIa or IIb hypercholesterolemia, low-density lipoprotein (LDL) cholesterol between 145 and 240 mg/dL, and normal basal levels of testosterone were randomly assigned to treatment with simvastatin 20 mg (n = 40), simvastatin 40 mg (n = 41), pravastatin 40 mg (n = 39), or placebo (n = 39) once daily. After 24 weeks of treatment, mean total cholesterol levels were decreased 24% to 27% and mean LDL cholesterol was decreased 30% to 34% in the 3 active-treatment groups (P < .001 for all comparisons to placebo). At 24 weeks, there were no statistically significant differences between the placebo group and any of the active-treatment groups for the change from baseline in testosterone, human chorionic gonadotropin (hCG)stimulated testosterone, free testosterone index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or sex hormone-binding globulin (SHBG). Moreover, there were no statistically significant differences at week 12 or week 24 for the change from baseline in sperm concentration, ejaculate volume, or sperm motility for any active treatment relative to placebo. Both simvastatin and pravastatin were well tolerated. In summary, we found no evidence for clinically meaningful effects of simvastatin or pravastatin on gonadal testosterone production, testosterone reserve, or multiple parameters of semen quality.",
"title": "Effects of simvastatin and pravastatin on gonadal function in male hypercholesterolemic patients."
},
{
"docid": "MED-4680",
"text": "OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.",
"title": "Diet throughout childhood and age at menarche in a contemporary cohort of British girls."
},
{
"docid": "MED-3936",
"text": "Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.",
"title": "Elevated Serum Pesticide Levels and Risk of Parkinson Disease"
}
] |
[
{
"docid": "MED-4947",
"text": "The focus of the present study was on the relationship between Hong Kong male subfertility and fish consumption. Mercury concentrations found in the hair of 159 Hong Kong males aged 25-72 (mean age = 37 years) was positively correlated with age and was significantly higher in Hong Kong subjects than in European and Finnish subjects (1.2 and 2.1 ppm, respectively). Mercury in the hair of 117 subfertile Hong Kong males (4.5 ppm, P < 0.05) was significantly higher than mercury levels found in hair collected from 42 fertile Hong Kong males (3.9 ppm). Subfertile males had approx. 40% more mercury in their hair than fertile males of similar age. Although there were only 35 female subjects, they had significantly lower levels of hair mercury than males in similar age groups. Overall, males had mercury levels that were 60% higher than females. Hair samples collected from 16 vegetarians living in Hong Kong (vegans that had consumed no fish, shellfish or meat for at least the last 5 years) had very low levels of mercury. Their mean hair mercury concentration was only 0.38 ppm.",
"title": "Hong Kong male subfertility links to mercury in human hair and fish."
},
{
"docid": "MED-1780",
"text": "Semen quality appears to have declined in recent decades in some populations, e.g. north-western Europe. At the same time, couple fertility may have increased. Hypotheses are suggested for this apparent inconsistency. Alongside the deterioration of spermatogenesis there is clear evidence of an increase in other related problems, notably testicular cancer. The sharply rising trend in this condition started a century ago--decades earlier than sometimes thought. This and other evidence clearly indicates an environmental origin, but there is also a definite genetic component. The relationship of genetics and environment is discussed in the context of the puzzle that infertility is inherited, which appears to be impossible from an evolutionary standpoint. Poor semen quality is related not only to testicular cancer but also to zygote development, in which cancer-like disruption of the genetic apparatus is observed, with serious implications for offspring health. This needs to be seen in the context that human reproduction is prone to a higher degree of impairment than that of other mammalian species, in relation to spermatogenesis, couple fertility, early pregnancy loss and embryonic aneuploidy; female- and male-mediated pathways are both implicated. It is unclear whether such human specificity originated on an evolutionary/genetic or a historico-social timescale, which is important in relation to pathogenesis. The evidence clearly indicates that the currently most popular explanation for male reproductive system impairment, the endocrine disruption hypothesis, cannot explain the main features of the descriptive epidemiology. An alternative pathogenesis is outlined, and some possible exposures considered that could be responsible.",
"title": "What has happened to human fertility?"
},
{
"docid": "MED-2647",
"text": "Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.",
"title": "Dietary exposure to xenoestrogens in New Zealand."
},
{
"docid": "MED-1787",
"text": "OBJECTIVE: To investigate whether semen quality has changed during the past 50 years. DESIGN: Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). SUBJECTS: 14,947 men included in a total of 61 papers published between 1938 and 1991. MAIN OUTCOME MEASURES: Mean sperm density and mean seminal volume. RESULTS: Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. CONCLUSIONS: There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.",
"title": "Evidence for decreasing quality of semen during past 50 years."
},
{
"docid": "MED-4752",
"text": "A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated here remain to be accurately defined, the likely link involves Insulin-like Growth Factor-1 as a general stimulant, synergized by the steroid hormones present in milk. The IGF-1 may be either absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced compound 5alpha-pregnanedione (5α-P) present in milk is a direct precursor of dihydrotestosterone and may act through that pathway in prostate cancer, but 5α-P has also recently been shown to be capable of inducing estrogen receptors in breast cancer cells, upregulating cancer cells' sensitivity to estrogen. The introduction of exogenous hormones and growth factors into tissues that have not evolved defensive feedback inhibition of their corresponding endogenous sources is postulated as a direct stimulatory threat to these organ systems, whether for hyperplasia or neoplasia.",
"title": "Acne, dairy and cancer"
},
{
"docid": "MED-4751",
"text": "The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that \"man has been drinking cows' milk for around 2000 years without apparent harm.\" However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.",
"title": "The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers."
},
{
"docid": "MED-1782",
"text": "Reactive oxygen species (ROS) have a negative impact on sperm DNA, leading to the formation of oxidative products such as 8-oxo-7,8-dihydroxyguanosine. This compound causes fragmentation and, thus, has a mutagenic effect. Patient treatment with oral antioxidant vitamins is, therefore, standard practice for male infertility, in an attempt to decrease formation of ROS and improve fertility. In this study, the DNA fragmentation index and the degree of sperm decondensation were measured using the sperm chromatin structure assay before and after 90 days treatment with antioxidant vitamins associated with zinc and selenium. Antioxidant treatment led to a decrease in sperm DNA fragmentation (-19.1%, P < 0.0004), suggesting that at least part of the decay was linked to ROS. However, it also led to an unexpected negative effect: an increase in sperm decondensation with the same order of magnitude (+22.8%, P < 0.0009). The opening of interchain disulphide bridges in protamines may explain this aspect, as antioxidant vitamins, especially vitamin C, are able to open the cystin net, thus interfering with paternal gene activity during preimplantation development. This observation might explain the discrepancy observed concerning the role of these antioxidant treatments in improving male fertility.",
"title": "Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect."
},
{
"docid": "MED-4698",
"text": "Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevity-associated genes by estrogens. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein kinase and nuclear factor kappa B signalling pathways, resulting in an up-regulation of antioxidant enzymes. Estrogen administration, however, has serious undesirable effects and of course, cannot be administered to males because of its powerful feminizing effects. Thus, we tested the effect of genistein, a phytoestrogen of high nutritional importance whose structure is similar to estradiol, on the regulation of the expression of antioxidant, longevity-related genes and consequently on oxidant levels in mammary gland tumour cells in culture. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of up-regulating antioxidant genes, by hormonal and dietary manipulations, to increase longevity is discussed.",
"title": "Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens."
},
{
"docid": "MED-3589",
"text": "OBJECTIVE: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive assisted clinic. DESIGN: An observational, analytical case-control study. SETTING: Private fertility clinics. PATIENT(S): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our fertility clinics. INTERVENTION(S): We recorded dietary habits and food consumption using a food frequency questionnaire adapted to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes were also carried out. MAIN OUTCOME MEASURE(S): Frequency of intake food items were registered in a scale with nine categories ranging from no consumption to repeated daily consumption. RESULT(S): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products. CONCLUSION(S): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality.",
"title": "Food intake and its relationship with semen quality: a case-control study."
},
{
"docid": "MED-3633",
"text": "This retrospective study was aimed at evaluating the effects of cigarette consumption on semen parameters in a group of men with idiopathic infertility. The semen quality of 2 groups of men with idiopathic infertility, smokers (n = 118) and nonsmokers (n = 153), were compared. Conventional semen analysis was performed and sperm morphology was assessed by transmission electron microscopy (TEM). TEM data were elaborated by means of a mathematical formula based on a Bayesian technique able to furnish a fertility index (FI), and the percentages of sperm apoptosis, necrosis, and immaturity. Values of normality recommended by World Health Organization guidelines were used as a control for conventional semen analysis, and values from sperm of 25 men of proven fertility were used for TEM indices. Infertile smoker and nonsmoker patients showed similar sperm parameters, although sperm motility and TEM analysis values in both groups were significantly impaired compared with controls. Smoker patients were then classified as mild (>or=1 and <or=10 cigarettes/d), moderate (>10 and <20 cigarettes/day), or heavy smokers (>or=20 cigarettes/d). Sperm concentration and FI were significantly (P < .05) different among the 3 considered smoker classes. Comparing the pairs of smoker classes, sperm concentration and FI in heavy smokers were significantly lower (P < .05) than that observed in mild smoker and nonsmoker groups. Although semen quality in males with idiopathic infertility seems not to be dramatically affected by cigarette consumption, heavy smokers show significantly lower sperm concentration and FI: another strong reason to stop smoking.",
"title": "Semen quality of male idiopathic infertile smokers and nonsmokers: an ultrastructural study."
},
{
"docid": "MED-1775",
"text": "OBJECTIVE: To measure individual antioxidants in sperm and seminal plasma from fertile and infertile men to determine if any particular antioxidant is reduced in infertile men. DESIGN: Semen samples were prepared by a discontinuous Percoll gradient to separate sperm and seminal plasma, and the antioxidant concentrations of each were assessed. Samples also were screened for phorbol ester-induced reactive oxygen species (ROS) activity. SETTING: Departments of Obstetrics and Gynaecology, and Clinical Biochemistry, The Queen's University of Belfast, Northern Ireland. PATIENT(S): Fifty-nine male patients attending our infertility center: 18 men whose wives had ongoing pregnancies from IVF with normozoospermic semen profiles, 20 infertile men with normozoospermic and 21 men with asthenozoospermic semen profiles. MAIN OUTCOME MEASURE(S): Ascorbate, urate, sulphydryl groups, tocopherol and carotenoid concentrations were measured in sperm and seminal plasma from fertile and infertile men. RESULT(S): In seminal plasma, ascorbate contributes almost twice as much as urate and thiol levels are about one third of ascorbate. Ascorbate levels in seminal plasma of asthenozoospermic individuals (+ROS) are significantly reduced. In sperm, thiols contributed most and ascorbate only a fraction of the total. CONCLUSION(S): In seminal plasma, ascorbate, urates, and thiols are the major antioxidants present. In contrast, within sperm, this group is the major contributor. In samples exhibiting ROS activity, ascorbate concentrations in the seminal plasma are significantly reduced.",
"title": "Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertile men."
},
{
"docid": "MED-4753",
"text": "BACKGROUND: Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregnant cows. The purpose of the present study was therefore to examine concentrations of serum and urine sex hormones after the intake of cow milk. METHODS: Subjects were seven men, six prepubertal children, and five women. The men and children drank 600 mL/m(2) of cow milk. Urine samples were collected 1 h before the milk intake and four times every hour after intake. In men the serum samples were obtained before and 15, 30, 45, 60, 90 and 120 min after milk intake. Women drank 500 mL of cow's milk every night for 21 days beginning on the first day of the second menstruation. In three successive menstrual cycles, the day of ovulation was examined using an ovulation checker. RESULTS: After the intake of cow milk, serum estrone (E1) and progesterone concentrations significantly increased, and serum luteinizing hormone, follicle-stimulating hormone and testosterone significantly decreased in men. Urine concentrations of E1, estradiol, estriol and pregnanediol significantly increased in all adults and children. In four out of five women, ovulation occurred during the milk intake, and the timing of ovulation was similar among the three menstrual cycles. CONCLUSIONS: The present data on men and children indicate that estrogens in milk were absorbed, and gonadotropin secretion was suppressed, followed by a decrease in testosterone secretion. Sexual maturation of prepubertal children could be affected by the ordinary intake of cow milk.",
"title": "Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows."
},
{
"docid": "MED-1779",
"text": "The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in seminal fluid indicates oxidative stress and is correlated with male infertility. A composite ROS-TAC score may be more strongly correlated with infertility than ROS or TAC alone. We measured ROS, TAC, and ROS-TAC scores in semen from 127 patients and 24 healthy controls. Of the patients, 56 had varicocele, eight had varicocele with prostatitis, 35 had vasectomy reversals, and 28 had idiopathic infertility. ROS levels were higher among infertile men, especially those with varicocele with prostatitis (mean +/- SE, 3.25 +/- 0.89) and vasectomy reversals (2.65 +/- 1.01). All infertile groups had significantly lower ROS-TAC scores than control. ROS-TAC score identified 80% of patients and was significantly better than ROS at identifying varicocele and idiopathic infertility. The 13 patients whose partners later achieved pregnancies had a mean ROS-TAC score of 47.7 +/- 13.2, similar to controls but significantly higher than the 39 patients who remained infertile (35.8 +/- 15.0; P < 0.01). ROS-TAC score is a novel measure of oxidative stress and is superior to ROS or TAC alone in discriminating between fertile and infertile men. Infertile men with male factor or idiopathic diagnoses had significantly lower ROS-TAC scores than controls, and men with male factor diagnoses that eventually were able to initiate a successful pregnancy had significantly higher ROS-TAC scores than those who failed.",
"title": "The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility."
},
{
"docid": "MED-5192",
"text": "High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for > or =2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.",
"title": "A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland)."
},
{
"docid": "MED-2136",
"text": "Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.",
"title": "The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer"
},
{
"docid": "MED-1739",
"text": "Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca(2+) concentration by opening L-type voltage-dependent Ca(2+) channels as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca(2+) overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30 min incubation of testis with glyphosate alone (36 ppm) also increased (45)Ca(2+) uptake. These events were prevented by the antioxidants Trolox and ascorbic acid. Activated protein kinase C, phosphatidylinositol 3-kinase, and the mitogen-activated protein kinases such as ERK1/2 and p38MAPK play a role in eliciting Ca(2+) influx and cell death. Roundup decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric acid-reactive species (TBARS) and protein carbonyls. Also, exposure to glyphosate-Roundup stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione S-transferase, γ-glutamyltransferase, catalase, superoxide dismutase, and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We propose that Roundup toxicity, implicated in Ca(2+) overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells."
},
{
"docid": "MED-4412",
"text": "BACKGROUND & AIMS: The aim of this study was to investigate whether nutritional risk factors, especially black tea consumptions, are inversely associated with the development of chronic obstructive pulmonary disease (COPD) in male smokers. METHODS: Forty male smokers with clinical diagnosis of COPD (Group-I (GI)) and 36 healthy smokers without COPD (Group-II (GII)) were included in this study. We compared the dietary habits and food intakes of the two groups using an adaptation of the Arizona Food Frequency Questionnaire (AFFQ). Question form included a list of 65 food items formed from five main food groups (grain, meat and alternatives, dairy products, vegetables-fruits and fat) and 25 dietary habits. The data were evaluated by binary logistic regression analysis, receiver operating characteristic (ROC) curve, Kolmogorov-Smirnov, Student's t, Mann-Whitney, and Chi-square tests. RESULTS: When both groups compared, black tea consumptions (GI-700ml; GII-1600ml (OR: 0.635, P<0.001)), vegetable fruits scores (GI-54.30; GII-63.81 (OR: 0.863, P<0.001)), regularly breakfast habit (GI-24 patients; GII-36 cases (OR: 0.549, P<0.001)) and eating salty (GI-22 patients; GII-5 cases (P<0.001)) made significant differences. In ROC curves, the area under the curve of black tea (0.898 (95% CI: 0.819-0.977) and vegetables-fruits (0.833 (95% CI: 0.727-0.938) provided high accuracy to distinguish between COPD group and controls (P<0.001). CONCLUSIONS: High intakes of black tea and vegetables-fruits consumptions may be protecting male smokers from developing COPD.",
"title": "Nutritional risk factors for the development of chronic obstructive pulmonary disease (COPD) in male smokers."
},
{
"docid": "MED-1786",
"text": "Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.",
"title": "Good semen quality and life expectancy: a cohort study of 43,277 men."
},
{
"docid": "MED-1100",
"text": "Background Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. Objective We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. Methods We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. Results Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05–0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06–0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. Conclusions Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men.",
"title": "Lower Serum Testosterone Associated with Elevated Polychlorinated Biphenyl Concentrations in Native American Men"
},
{
"docid": "MED-4954",
"text": "BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of \"high beef consumers\" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of \"high beef consumers\" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.",
"title": "Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy."
},
{
"docid": "MED-3358",
"text": "BACKGROUND & AIMS: Taste sensitivity to fatty acids influences food ingestion and may regulate fat intake and body weight status. Fatty acids are detected via homologous receptors within the mouth and gastrointestinal (GI) tract, where attenuated sensitivity may be associated with greater fat intake and BMI. This study aimed to extend observations surrounding fatty acid taste, specifically the types of foods consumed and dietary behaviours that may be associated with fatty acid taste sensitivity. METHODS: 51 subjects (41 female; BMI, 21.4 ± 0.46 kg/m², age, 20 ± 0.52 yrs, 10 male; BMI, 23.6 ± 1.4 kg/m², age, 22 ± 1 yrs) were screened for oral sensitivity to oleic acid (3.8 mM) using triplicate sensory evaluations, and classified as hypersensitive; (3/3 correct identifications), or hyposensitive, (<3/3). Fat-taste perception (using sensory-matched custards made with 0, 2, 6, 10% oil), recent diet (4-day diet record) and food habits and behaviours (food habits and behaviours questionnaire) were also established. RESULTS: 75% (n = 38) of subjects were classified as hyposensitive to oleic acid and these subjects differed from those who were classified as hypersensitive. Hyposensitive subjects consumed significantly more energy, fat, saturated fat, fatty foods (butter, meat, dairy), had greater BMI and were less perceptive of small changes in the fat content of custard (all P < 0.05), compared to hypersensitive subjects. CONCLUSION: An inability to perceive low concentrations of fatty acids in foods was associated with greater consumption of fatty foods, specifically butter, meat, dairy, and increasing BMI. 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",
"title": "Oral sensitivity to oleic acid is associated with fat intake and body mass index."
},
{
"docid": "MED-3666",
"text": "Most cases of male prepubertal gynecomastia are classified as idiopathic. We investigated possible causes of gynecomastia in three prepubertal boys who were otherwise healthy and had normal serum concentrations of endogenous steroids. In all three boys, gynecomastia coincided with the topical application of products that contained lavender and tea tree oils. Gynecomastia resolved in each patient shortly after the use of products containing these oils was discontinued. Furthermore, studies in human cell lines indicated that the two oils had estrogenic and antiandrogenic activities. We conclude that repeated topical exposure to lavender and tea tree oils probably caused prepubertal gynecomastia in these boys. 2007 Massachusetts Medical Society",
"title": "Prepubertal gynecomastia linked to lavender and tea tree oils."
},
{
"docid": "MED-1098",
"text": "The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.",
"title": "Intake of dioxins and related compounds from food in the U.S. population."
},
{
"docid": "MED-1101",
"text": "The effects exerted by three mixtures of Polychlorinated Biphenyls (PCBs) were evaluated on human fetal corpora cavernosa cells, as a model for male external genitalia development. The three mixtures feature congeners grouped according to potentially shared modes of action: one dioxin-like (DL) (Mix2) and two non dioxin-like (NDL) mixtures featuring congeners defined as estrogenic (Mix1) and highly persistent-cytochrome P-450 inducers (Mix3). Congeners concentrations used were derived from human internal exposure data. Toxicogenomic analysis revealed that all mixtures modulated critical genes involved in genitourinary development, however displaying three different expression profiles. The DL Mix2 modulated actin-related, cell-cell and epithelial-mesenchymal communication morphogenetic processes; Mix1 modulated smooth muscle function genes, whereas Mix3 mainly modulated genes involved in cell metabolism (e.g., steroid and lipid synthesis) and growth. Our data indicate that fetal exposure to environmentally relevant PCB levels modulates several patterns of genitourinary programming; moreover, NDL congener groups may have specific modes of action. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Exposure of human fetal penile cells to different PCB mixtures: transcriptome analysis points to diverse modes of interference on external genitali..."
},
{
"docid": "MED-4755",
"text": "OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.",
"title": "Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence."
},
{
"docid": "MED-1702",
"text": "Background We previously reported that the Mediterranean diet (MeDi) is related to lower risk for Alzheimer disease (AD). Whether MeDi is associated with subsequent AD course and outcomes has not been investigated. Objectives To examine the association between MeDi and mortality in patients with AD. Methods A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and body mass index. Results Eighty-five patients with AD (44%) died during the course of 4.4 (±3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence fertile, those at the middle fertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years’ longer survival), whereas subjects at the highest fertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years’ longer survival; p for trend = 0.003). Conclusion Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose–response effect.",
"title": "Mediterranean diet and Alzheimer disease mortality"
},
{
"docid": "MED-5167",
"text": "OBJECTIVES: The phytoestrogen (plant estrogen) genistein, present in soy products, is of interest because in utero exposure to genistein can cause hypospadias in our mouse model and maternal consumption of soy is prevalent in human populations. Another compound of interest is the fungicide vinclozolin, which also causes hypospadias in the mouse and rat and can occur concurrently with genistein in the diet as a residue on exposed foods. A study in the United Kingdom found no relationship between a maternal organic vegetarian diet and hypospadias frequency, but women who consumed nonorganic vegetarian diets had a greater percentage of sons with hypospadias. Because nonorganic diets can include residues of pesticides such as vinclozolin, we sought to assess the interaction of realistic daily exposures to genistein and vinclozolin and their effects on the incidence of hypospadias. METHODS: Pregnant mice were fed a soy-free diet and orally gavaged from gestational days 13 to 17 with 0.17 mg/kg/day of genistein, 10 mg/kg/day of vinclozolin, or genistein and vinclozolin together at the same doses, all in 100 microL of corn oil. The controls received the corn oil vehicle. The male fetuses were examined at gestational day 19 for hypospadias, both macroscopically and histologically. RESULTS: We identified no hypospadias in the corn oil group. The incidence of hypospadias was 25% with genistein alone, 42% with vinclozolin alone, and 41% with genistein and vinclozolin together. CONCLUSIONS: These findings support the idea that exposure to these compounds during gestation could contribute to the development of hypospadias.",
"title": "Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin."
},
{
"docid": "MED-5090",
"text": "OBJECTIVE: To examine associations between the prevalence of degenerative arthritis and soft tissue disorders and consumption of meat and other foods among participants in the Adventist Health Study. METHODS: Unconditional logistic regression analysis is used to examine cross-sectional associations, adjusting for the effects of age, smoking, alcohol consumption, body mass index, use of sex hormones and parity. RESULTS: The prevalence of degenerative arthritis and soft tissue disorders was 22.60 percent. Women had a higher prevalence than men and prevalence increased greatly with age. Smoking, higher body mass index, never use of contraceptive pills, and current hormone replacement therapy are associated with a higher prevalence of these disorders on multivariate analysis. Multivariate OR's comparing consumption of meat < 1/week; >or= 1/week; with the reference being no meat, were 1.31(95% CI: 1.21,1.43) and 1.49(1.31, 1.70) in women; and 1.19 (95% CI: 1.05,1.34) and 1.43(1.20, 1.70) in men. Dairy fat and fruit consumption were weakly associated with increased risk. There were protective associations with nut and salad consumption. CONCLUSIONS: Greater meat consumption is associated with a higher prevalence of degenerative arthritis and soft tissue disorders in both male and female subjects of this population, as is hormone replacement therapy in women.",
"title": "Associations between meat consumption and the prevalence of degenerative arthritis and soft tissue disorders in the adventist health study, Califor..."
},
{
"docid": "MED-1597",
"text": "Background Detection of estrogens in the environment has raised concerns in recent years because of their potential to affect both wildlife and humans. Objectives We compared exposures to prescribed and naturally occurring estrogens in drinking water to exposures to naturally occurring background levels of estrogens in the diet of children and adults and to four independently derived acceptable daily intakes (ADIs) to determine whether drinking water intakes are larger or smaller than dietary intake or ADIs. Methods We used the Pharmaceutical Assessment and Transport Evaluation (PhATE) model to predict concentrations of estrogens potentially present in drinking water. Predicted drinking water concentrations were combined with default water intake rates to estimate drinking water exposures. Predicted drinking water intakes were compared to dietary intakes and also to ADIs. We present comparisons for individual estrogens as well as combined estrogens. Results In the analysis we estimated that a child’s exposures to individual prescribed estrogens in drinking water are 730–480,000 times lower (depending upon estrogen type) than exposure to background levels of naturally occurring estrogens in milk. A child’s exposure to total estrogens in drinking water (prescribed and naturally occurring) is about 150 times lower than exposure from milk. Adult margins of exposure (MOEs) based on total dietary exposure are about 2 times smaller than those for children. Margins of safety (MOSs) for an adult’s exposure to total prescribed estrogens in drinking water vary from about 135 to > 17,000, depending on ADI. MOSs for exposure to total estrogens in drinking water are about 2 times lower than MOSs for prescribed estrogens. Depending on the ADI that is used, MOSs for young children range from 28 to 5,120 for total estrogens (including both prescribed and naturally occurring sources) in drinking water. Conclusions The consistently large MOEs and MOSs strongly suggest that prescribed and total estrogens that may potentially be present in drinking water in the United States are not causing adverse effects in U.S. residents, including sensitive subpopulations.",
"title": "An Assessment of Potential Exposure and Risk from Estrogens in Drinking Water"
},
{
"docid": "MED-4159",
"text": "CONTEXT: The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA). OBJECTIVE: To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers. INTERVENTIONS: In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos. MAIN OUTCOME MEASURES: Probable dementia and MCI. RESULTS: In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04). CONCLUSIONS: Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.",
"title": "Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Mem..."
}
] |
5a8d8fb0554299441c6b9fff
|
Just Wright starred an American rapper who was born in Newark, and signed with what record label in 1989?
|
[
{
"docid": "148784",
"text": "Dana Elaine Owens (born March 18, 1970), known professionally by her stage name Queen Latifah, is an American rapper, songwriter, singer, actress, model, television producer, record producer, and talk show host. Born in Newark, New Jersey, she signed with Tommy Boy Records in 1989 and released her debut album \"All Hail the Queen\" the same year, featuring the hit single \"Ladies First\". \"Nature of a Sista\" (1991) was her second and final album with Tommy Boy Records.",
"title": ""
},
{
"docid": "24021571",
"text": "Just Wright is a 2010 American romantic comedy film starring Queen Latifah and Common that tells the story of a physical therapist who falls in love with a professional basketball player.",
"title": ""
}
] |
[
{
"docid": "37882107",
"text": "La'Reonte Wright (born November 26, 1990) is an American rapper better known by his stage name Dizzy Wright. In December 2011, Wright signed to rapper Hopsin's independent record label Funk Volume. After signing he released his debut studio album \"SmokeOut Conversations\" in April 2012. He followed that with \"The First Agreement\" in December of that year, and then a mixtape \"The Golden Age\" in August 2013. Following touring with Hopsin in early 2014, Dizzy Wright released \"State of Mind\", an EP that would peak at number 54 on the \"Billboard\" 200. On May 22, 2015, He released his second full-length studio album \"The Growing Process\" which peaked at number 47 on the Billboard 200.",
"title": ""
},
{
"docid": "40183318",
"text": "Lady is the stage name of Shameka Shanta Brown (born July 31, 1989), an American rapper. She was signed to rapper Plies' record label Big Gates Records on April 1, 2010. She has released three albums. Lady's songs have been featured on TV shows including \"Girls\", \"Ray Donovan\", and \"Skins\".",
"title": ""
},
{
"docid": "16651856",
"text": "Clifford Peacock, better known by his stage name Quan or Don Ferquan, is an American rapper, affiliated with Nas and Ill Will Records. In 2008, he signed with Just Blaze label Fort Knocks as a joint venture with Ill Will. He is currently signed to Amalgam Digital, who distributed his album \"Walking Testimony\" in 2009.",
"title": ""
},
{
"docid": "36631758",
"text": "Nasir Frederick Graham (born November 23, 1991), better known by his stage name Driicky Graham, is an American rapper from Newark, New Jersey. He is currently signed to the independent record labels Nu World Era Music Group and E1 Music.",
"title": ""
},
{
"docid": "3099751",
"text": "Brian Carenard (born July 13, 1977), better known by his stage name Saigon, is an American rapper and actor. He is currently signed to Suburban Noize Records and Just Blaze's Fort Knocks Entertainment record label. After years of delay due to former record label interference, his album \"The Greatest Story Never Told\" was released on Suburban Noize Records. He is also known for his appearances on the HBO television series \"Entourage\".",
"title": ""
},
{
"docid": "11096008",
"text": "No Stars, Just Talent is a compilation album by the Seal Beach, California record label Kung Fu Records, released in 1999. It was the label's first sampler compilation and featured artists signed to the label at the time, as well as others such as blink-182 who were not signed to the label but had released a single album through them. It was followed by \"The \"Gone With the Wind\" of Punk Rock Samplers\" the following year, after which the label switched to the series name \"Punk Rock is Your Friend\" for its future compilations.",
"title": ""
},
{
"docid": "2885034",
"text": "Allido Records is a record label and production company. The company was started by DJ and producer Mark Ronson and Rich Kleiman, a television, internet and music businessman. The label got its name \"Allido\" from the Stevie Wonder song \"All I Do\". Rapper Saigon was the first artist signed to Allido Records, but left soon after, and is now signed to Just Blaze's Fort Knox Entertainment. In conjunction with Clive Davis’ J Records, Allido signed Chicago-based rapper Rhymefest, who is best known as the co-writer for Kanye West's \"Jesus Walks\". Rhymefest's first album, under Allido, was released July 11, 2006, under the title of \"Blue Collar\". Allido has also signed Australian-born soul singer Daniel Merriweather. Other projects in the works from Ronson and Kleiman are the soundtrack to Gap's latest ad campaign as well as Jay-Z's movie, \"Fade to Black\". Allido's most recent signing is Washington, D.C. hip hop artist Wale.",
"title": ""
},
{
"docid": "3102374",
"text": "Tracy Lamar Davis (born April 27, 1966), better known by his stage name Big Tray Deee, is an American rapper who was once signed to Death Row Records and later signed with Snoop Dogg's label Dogghouse Records.",
"title": ""
},
{
"docid": "42099435",
"text": "DJ Hoppa (born Lee Gresh, April 28, 1983) is an American DJ and producer from Panorama City, Los Angeles. He was signed to rapper Hopsin's now defunct record label Funk Volume, and CEO of the San Fernando Valley independent label Broken Complex. He has made beats for Dizzy Wright's \"The Golden Age\" mixtape, \"The First Agreement EP\" and \"SmokeOut Conversations\", Jarren Benton's \"My Grandma's Basement\", and also worked with SwizZz.",
"title": ""
},
{
"docid": "894013",
"text": "Jayceon Terrell Taylor (born November 29, 1979), better known by his stage name The Game (or simply Game), is an American rapper and actor. The Game is best known as a rapper in the West Coast hip hop scene and for being one of Dr. Dre's signers under Aftermath Records. Born in Compton, California, he released his first mixtape \"You Know What It Is Vol. 1\" in 2002; shortly after, he was signed to Dr. Dre's Aftermath Entertainment label. He rose to fame in 2005 with the success of his major-label debut album \"The Documentary\" and found continued success with the 2006 follow-up \"Doctor's Advocate\". The Recording Industry Association of America certified \"The Documentary\" double platinum in March 2005.",
"title": ""
},
{
"docid": "22600527",
"text": "Andre Knight (born June 4, 1980 in Canberra, Australia), better known by his stage name Bukkcity, is an Australian-American rapper who is currently signed to the Unda K9 Records record label.",
"title": ""
},
{
"docid": "999383",
"text": "Paul Michael Slayton (born March 11, 1981), better known by his stage name Paul Wall, is an American rapper from Houston, Texas. He is affiliated with Swishahouse Records. He has released several albums under the label and collaborating with other rappers signed to the label. He was musical partners with rapper Chamillionaire with whom he released several albums including the independently released \"Get Ya Mind Correct\". In 2005, he was signed to Atlantic Records and became successful with his major-label debut \"The Peoples Champ\". \"Get Money, Stay True\" followed in 2007.",
"title": ""
},
{
"docid": "34311236",
"text": "\"A Star Is Born\" is a song by American hip hop recording artist Jay-Z from his eleventh studio album \"The Blueprint 3\" (2009). The song, produced by Kanye West, Kenoe and No I.D., features a verse from American rapper J. Cole, Jay-Z's protege and the first artist to be signed to his Roc Nation label. In the song, Jay-Z recognizes rappers who have risen to fame in the last decade, such as Kanye West, Lil Wayne, T.I., Eminem and 50 Cent . Notably, Jay-Z also gives shout-outs to Mobb Deep, Nas and two artists whom he had previously insulted on his 2001 song \"Takeover\".",
"title": ""
},
{
"docid": "45469229",
"text": "Ronald Stephen \"Ronnie\" Lillard, Jr. (born March 20, 1989), known by the stage name Reconcile, is an American hip hop recording artist. Reconcile gained notoriety after releasing a free project entitled \"Abandoned Hope\" in 2012 on Full Ride Music, a label founded by rapper Thi'sl. His second album, \"Sacrifice\", was released in 2014 on the Frontline Movement label. \"Sacrifice\" was his first album to chart on the \"Billboard\" charts. Reconcile signed a production contract with Street Symphony's Track or Die production label in 2015. His follow-up release, \"Catchin' Bodies\" was released on September 18, 2015.",
"title": ""
},
{
"docid": "291702",
"text": "To the Extreme is the major label debut studio album of American rapper Vanilla Ice. The album was initially released in 1989 by independent record label Ichiban Records under the title \"Hooked\". Vanilla Ice signed to SBK Records, who reissued the album under its current title. The album contains Vanilla Ice's most successful singles, \"Ice Ice Baby\" and \"Play That Funky Music\". Although reviews of the album were mixed, \"To the Extreme\" spent 16 weeks at the top of the \"Billboard 200\", and sold 15 million copies worldwide.",
"title": ""
},
{
"docid": "42405967",
"text": "Clyde Carson (born June 2, 1981) is an American rapper from Oakland, California. He was originally known as a member of the hip hop group The Team. After the group went on hiatus, he was the one member of the group to break out as a solo artist. He was signed to rapper The Game's Black Wall Street Records and Capitol Records in 2006. While signed there he released the EP \"Doin' That\". However, he wasn't signed to them for long, before deciding to go back to releasing music independently via Moe Doe Entertainment. After returning to just that label, he has released two EPs: \"Bass Rock\" and \"Playboy\". He also released the song \"Slow Down\", which was featured on the video game \"Grand Theft Auto V\".",
"title": ""
},
{
"docid": "21429855",
"text": "Johnny Reed McKinzie, Jr., (born March 31, 1985), better known by his stage name Jay Rock, is an American hip hop recording artist from Watts, California. Rock ultimately chose to pursue a career as a rapper over a life of street crime, after Anthony Tiffith, the founder and CEO of the independent record label Top Dawg Entertainment (TDE), found Rock in 2005 and signed him to his label. In 2007, alongside TDE, Rock secured a recording contract with Warner Bros. Records and later Asylum Records, but after both mergers fell through, the label signed with Strange Music, after Tech N9ne, Missouri-based rapper and founder of the label, met with them and offered Rock a record deal.",
"title": ""
},
{
"docid": "50795176",
"text": "Alvin Worthy (born July 27, 1982), better known by his stage name Westside Gunn, is an American rapper from Buffalo, New York. He is the brother of fellow rapper Conway with whom he forms the duo Hall N' Nash. He records for his own record label, Griselda Records, which he founded in 2014, as well as The Purist's Daupe! Records. In 2016, he released his debut studio album, \"FLYGOD\", to critical acclaim. On March 3, 2017, Griselda Records signed a deal with Eminem's Shady Records, a subsidiary of Interscope, making Westside Gunn and his brother Conway the first rappers from Buffalo to sign with a major label distribution.",
"title": ""
},
{
"docid": "23054906",
"text": "Just What Time It Is is the second album by American-born singer/songwriter Jeb Loy Nichols, released in 2000 on the Rough Trade record label.",
"title": ""
},
{
"docid": "38472615",
"text": "Brianna Perry (born January 11, 1992), also known as Lil' Brianna, is an American rapper and actress from Miami-Dade County, Florida. She was the youngest act signed to Missy Elliott's label The Goldmind Inc. as well as the youngest to be affiliated with Slip-N-Slide Records, home to rappers Trina and Rick Ross. Perry made her debut on Trina's album \"Diamond Princess\" on the track \"Kandi\". Since then, she has released several mixtapes and starred as a regular cast-member on the reality-television series \"Sisterhood of Hip Hop\".In 2016 Brianna left major label Atlantic records due to low promotion and moved forward with her indie label poe boy entertainment",
"title": ""
},
{
"docid": "36701362",
"text": "Adam Briggs (born 28 August 1986), who performs as Briggs, is an Indigenous Australian rapper, record label owner, comedy writer, and actor. Briggs became well known as a solo rapper, signing with Golden Era Records in 2009, before co-founding the hip hop duo A.B. Original in 2016.",
"title": ""
},
{
"docid": "28011482",
"text": "Timothy Lee \"Tim\" McKenzie (born 4 January 1989), better known by his stage name Labrinth, is an English musician, singer, songwriter, rapper and record producer. Initially, he was tipped to work as a producer, but Simon Cowell signed him to his record label Syco Music as a solo act. In the process, Labrinth became Cowell's first non-talent show signing in six years.",
"title": ""
},
{
"docid": "30212898",
"text": "Julissa Alexandria Veloz (born in Newark, New Jersey) is a Dominican-American recording artist and songwriter. She first achieved fame as \"Tiara Girl\" in Season 8 of \"American Idol\". After being eliminated in the group rounds, Veloz was signed to record label Carrillo Music owned by Rod Carrillo.",
"title": ""
},
{
"docid": "19583036",
"text": "Scott Ramon Seguro Mescudi (born January 30, 1984), better known by his stage name Kid Cudi ( , often stylized KiD CuDi), is an American recording artist and actor from Cleveland, Ohio. Cudi first gained major recognition following the release of his first official full-length project, a mixtape titled \"A Kid Named Cudi\" (2008). The mixtape caught the attention of American rapper-producer Kanye West, who subsequently signed Cudi to his GOOD Music label imprint in late 2008. Cudi has since gone on to launch his own record label imprints, the now-dissolved Dream On and current independent label, Wicked Awesome Records. Initially a rapper, Cudi has since added singer, songwriter, record producer, guitarist, music video director and film composer to his repertoire.",
"title": ""
},
{
"docid": "180532",
"text": "Robert Matthew Van Winkle (born October 31, 1967), known professionally as Vanilla Ice, is an American rapper, actor, and television host. Born in South Dallas, and raised in Texas and South Florida, Ice released his debut album, \"Hooked\", in 1989 on Ichiban Records, before signing a contract with SBK Records, a record label of the EMI Group which released a reformatted version of the album under the title \"To the Extreme\". Ice's 1990 single \"Ice Ice Baby\" was the first hip hop single to top the \"Billboard\" charts.",
"title": ""
},
{
"docid": "47488618",
"text": "Richard \"Ricky\" Jones (born May 13, 1976), better known by his stage names Fiend or International Jones, is an American rapper and producer best known for his time spent with Master P's No Limit Records. Fiend was also briefly signed to the label, Ruff Ryders Entertainment, and is currently signed to Jet Life under Warner Bros. He is not signed to Jet Life.",
"title": ""
},
{
"docid": "44278876",
"text": "Majyuran Ragunathan (born 21 April 1989 in Duisburg), better known by his stage name Majoe is a German rapper of Sri Lankan Tamil descent. He is signed by the Farid Bang-owned label Banger Music Records since 2012.",
"title": ""
},
{
"docid": "13524375",
"text": "Aasim (born \"Leroy Watson\" in Jamaica, Queens, New York) is an American rapper, who first began rapping at the age of 12, and signed his first record deal with Schott Free of Loud Records at 17. While signed to the label, Aasim learned songwriting from Big Pun and Dead Prez but never released any material. When his deal with Loud Records fell through, he moved to Grind Music, and worked the mixtape and local New York radio circuits. In 2004, Puff Daddy heard him on the radio and signed him to Bad Boy Records.",
"title": ""
},
{
"docid": "17015795",
"text": "Teyana Taylor (born December 10, 1990), is an American actress, model, dancer, and a recording artist/rapper from Harlem, New York. In 2007, Taylor signed a record deal with American musician Pharrell Williams' Star Trak Entertainment imprint, before making her first national appearance on MTV's \"My Super Sweet 16\". In 2012, she signed to Kanye West's GOOD Music label through Def Jam, after asking for her release from Star Trak. As an aspiring songwriter, Taylor has worked with and written records for major artists such as Usher, Chris Brown, and Omarion. Taylor has appeared on runways during Fashion Week and has also landed high-profile features, such as on Kanye West’s \"My Beautiful Dark Twisted Fantasy\".",
"title": ""
},
{
"docid": "32783682",
"text": "Reema Major (born June 26, 1995), is a Canadian rapper. She is signed to a joint-record label venture with G7 Records / Universal Music Canada / Cherrytree Records / Interscope Records and also signed to Waka Flocka Flame's Brick Squad Monopoly label.",
"title": ""
}
] |
1079
|
How do “held” amounts appear on statements and affect balances of traditional credit cards?
|
[
{
"docid": "384892",
"text": "\"The \"\"hold\"\" is just placeholder that prevents you from overspending until the transaction is settled. The merchant isn't \"\"holding\"\" your money, your bank or card provider is protecting itself from you overdrawing. In general, it takes 1-3 days for a credit transaction to settle. With a credit card, this usually isn't an issue, unless you have a very low credit line or other unusual things going on. With pre-paid and debit cards, it is an issue, since your spending power is contingent upon you having an available balance. I'm a contrarian on this topic, but I don't see any compelling reason to use debit or stored value cards, other than preventing yourself from overspending. I've answered a few other questions in detail in this area, if you're interested.\"",
"title": ""
}
] |
[
{
"docid": "474573",
"text": "\"@Joe's original answer and the example with proportionate application of the payment to the two balances is not quite what will happen with US credit cards. By US law (CARD Act of 2009), if you make only the minimum required payment (or less), the credit-card company can choose which part of the balance that sum is applied to. I am not aware of any company that chooses to apply such payments to anything other than that part of the balance which carries the least interest rate (including the 0% rate that \"\"results\"\" from acceptance of balance transfer offers). If you make more than the minimum required payment, then the excess must, by law, be applied to paying off the highest rate balance. If the highest rate balance gets paid off completely, any remaining amount must be applied to second-highest rate balance, and so on. Thus, it is not the case that that $600 payment (in Joe's example) is applied proportionately to the $5000 and $1000 balances owed. It depends on what the required minimum payment is. So, what would be the minimum required payment? The minimum payment is the total of (i) all finance charges incurred during that month, (ii) all service fees and penalties (e.g. fee for exceeding credit limit, fee for taking a cash advance, late payment penalty) and other charges (e.g. annual card fee) and (iii) a fraction of the outstanding balance that (by law) must be large enough to allow the customer to pay off the entire balance in a reasonable length of time. The law is silent on what is reasonable, but most companies use 1% (which would pay off the balance over 8.33 years). Consider the numbers in Joe's example together with the following assumptions: $5000 and $1000 are the balances owed at the beginning of the month, no new charges or service fees during that month, and the previous month's minimum monthly payment was made on the day that the statement paid so that the finance charge for the current month is on the balances stated). The finance charge on the $5000 balance is $56.25, while the finance charge on the $1000 balance is $18.33, giving a minimum required payment of $56.25+18.33+60 = $134.58. Of the $600 payment, $134.58 would be applied to the lower-rate balance ($5000 + $56.25 = $5056.25) and reduce it to $4921.67. The excess $465.42 would be applied to the high-rate balance of $1000+18.33 = $1018.33 and reduce it to $552.91. In general, it is a bad idea to take a cash advance from a credit card. Don't do it unless you absolutely must have cash then and there to buy something from a merchant who does not accept credit cards, only cash, and don't be tempted to use the \"\"convenience checks\"\" that credit-card companies send you from time to time. All such cash advances not only carry larger rates of interest (there may also be upfront fees for taking an advance) but any purchases made during the rest of the month also become subject to finance charge. In other words, there is no \"\"grace period\"\" for new charges, and this state of affairs will last for one month beyond the first credit-card statement whose statement is paid off in full in timely fashion. Finally, turning to the question asked, viz. \"\" I am trying to determine how much I need to pay monthly to zero the balance, ....\"\", as per the above calculations, if the OP makes the minimum required payment of $134.58 plus $1018.33, that $134.58 will be applied to the low-rate balance and the rest $1018.33 will pay off the high-rate balance in full if the payment is made on the day the statement is issued. If payment is made later, but before the due date, that $1018.33 will be accruing finance charges until the date the payment is made, and these will appear as 22% rate balance on next month's statement. Similarly for the low-rate balance. What if several monthly payments will be required? The best calculator known to me is at https://powerpay.org (free but it is necessary to set up a username and password). Enter in all the credit card balances and the different interest rates, and the total amount of money that can be used to pay off the balances, and the site will lay out a payment plan. (Basically, pay off the highest-interest rate balance as much as possible while making minimum required payments on the rest). Most people are surprised at how much can be saved (and how much shorter the time to be debt-free is) if one is willing to pay just a little bit more each month.\"",
"title": ""
},
{
"docid": "479095",
"text": "\"Curious, why are you interested in building/improving your credit score? Is it better to use your card and pay off the bill completely every month? Yes. How is credit utiltization calculated? Is it average utilization over the month, or total amount owed/credit_limit per month? It depends on how often your bank reports your balances to the reporting agencies. It can be daily, when your statement cycle closes, or some other interval. How does credit utilization affect your score? Closest to zero without actually being zero is best. This translates to making some charges, even $1 so your statement shows a balance each statement that you pay off. This shows as active use. If you pay off your balance before the statement closes, then it can sometimes be reported as inactive/unused. Is too much a bad thing? Yes. Is too little a bad thing? Depends. Being debt free has its advantages... but if your goal is to raise your credit score, then having a low utilization rate is a good metric. Less than 7% utilization seems to be the optimal level. \"\"Last year we started using a number, not as a recommendation, but as a fact that most of the people with really high FICO scores have credit utilization rates that are 7 percent or lower,\"\" Watts said. Read more: http://www.bankrate.com/finance/credit-cards/how-to-bump-up-your-credit-score.aspx Remember that on-time payment is the most important factor. Second is how much you owe. Third is length of credit history. Maintain these factors in good standing and you will improve your score: http://www.myfico.com/CreditEducation/WhatsInYourScore.aspx\"",
"title": ""
},
{
"docid": "125497",
"text": "\"I too am a full-monthly-statement-balance payer and I received a balance transfer offer from my credit-card company. This one was quite different from many others that I have read about on this forum. I could do a balance transfer for any amount up to $X from another credit card, or use the enclosed \"\"checks\"\" to pay some other (non-credit-card) bills, and I would not have to pay any interest for 12 months on the amount thus borrowed. But, There would be a 2% service charge on the amount I was borrowing. This amount would be billed on the next monthly statement, and it would have to be paid in full by the due date of that month's payment, that is, within the 25-day grace period allowed for payment of monthly statements. Else, interest would start being charged on the unpaid part of the service charge at the usual humongous rate of H% per month. If I had not paid the previous month's balance in full, I would be charged interest at H% per month on the service charge starting from Day One; no free ride till the due date of the next month's statement. Of course, the balance carried over from last month would also be charged interest at H%. If I had paid last month's bill in full, but there were any other charges (purchases) during the current month, then unless the entire amount due, this month's purchases plus service charge and that \"\"interest-free-for-twelve-months loan\"\" balance was paid off within the 25-day grace period, my purchases would be deemed unpaid and would start being charged interest. In short, the only way to avoid paying interest on the amount borrowed was to start with a card showing a $0 balance due on the previous month's statement, not make any charges on that card for a whole year, and pay off that 2% service charge within the grace period. It might also have required that one-twelfth of that interest-free loan be repaid each month, but I had stopped reading the offer at this point and filed it in the round circular file. In short, while @JoeTaxpayer's tale of how \"\"As a pay-in-full user, I've used the zero rate to throw $20K at the 5.25% mortgage\"\" is undoubtedly how things worked once, it is not at all clear that they still work that way. At least, they don't work that way for me. Heck, once upon a time, for a period of about 3 months, you could earn 1.5% interest per month from the credit card company by overpaying your credit card bill considerably. Their computers then just \"\"added on\"\" 1.5% interest by multiplying your credit balance -$X by 1.015 and so you got 1.5% per month interest from the credit card company. The credit card agreements (and the software!) got changed in a hurry, and nowdays all credit-card agreements state in the fine print that if you overpay your bill, you don't earn any interest on the overpayment.\"",
"title": ""
},
{
"docid": "143844",
"text": "\"There's a difference between missing a payment and \"\"carrying a balance\"\" (making an on-time payments that are less than the full balance due). I have heard mortgage brokers claim that, if you have no other credit history, carrying a small balance here and there on a credit card may improve your score. (\"\"Small\"\" is in relation to your available credit and your ability to pay it off.) But actually missing a payment will probably hurt your score. Example: You have a card with a credit limit of $1000. In July you charge $300 worth of stuff. You get the next statement and it shows the balance due of $300 and a minimum payment of $100. If you pay the entire $300 balance in that cycle, most cards won't charge you any interest. You are not carrying a balance, so the credit scores may not reflect that you actually took a $300 loan and paid it off. If you instead pay $200, you'll be in good standing (because $200 is greater than the minimum payment). But you'll be carrying a $100 balance into the next statement cycle. Plus interest will accrue on that $100. If you do this regularly, your credit score will probably take into account that you've taken a small loan and made the payments. For those with no other credit history, this may be an appropriate way to increase your credit score. (But you're paying interest, so it's not free.) And if the average balance you carry is considered high relative to your ability to pay or to the total credit available to you, then this could adversely affect your score (or, at least, the amount of credit another provider is willing to extend to you). If you instead actually miss a payment, or make a payment that's less than the minimum payment, that will almost certainly hurt your credit score. It will also incur penalties as well as interest. You want to avoid that whenever possible. My guess is that, in the game of telephone from the banker to you, the \"\"carrying a balance\"\" was misinterpreted as \"\"missing a payment.\"\"\"",
"title": ""
},
{
"docid": "277477",
"text": "The details of credit score calculation tend to change periodically, but the fundamentals are mostly consistent. Pay your bills, keep your average account age high, overpay your credit card minimums, and keep your overall debt low. And do soft pulls on your credit report to see what's happening. First, the simplest route: pay all your bills early or on time. Automatic deduction may be useful in this regard, especially for bills with predictable amounts. A corollary to this tip is to never leave an unpaid bill. What often happens to young people is in the course of moving around they leave the final bill unpaid and it gets reported to collections. Make sure you follow up online with all bills, even after canceling the service. Second, average account age and oldest account age matter. Open an account like a credit card and never close it, so you'll have an older account (hopefully a zero-fee card). Try to keep other accounts open rather than closing them (no need to cancel a zero-fee credit card) so your average account age stays higher. A card that works on internal systems (like a gift card) is not going to show up on a credit report; a card that works like any VISA/MC is likely going to show up. The rule of thumb is if they need your SSN to run a credit check for the application, then the card will appear on a credit report. You can pull your credit report to find out if the card is listed (you may have to allow time for lag before the card appears, but I'm not sure how long that might be). Third, a tip for extra credit score is to pay more than the minimum required on credit card bills. You can achieve this by either using your credit card at least once a month or by leaving a small hanging balance each month so there's always something to overpay next month. Credit card reporting will be either: unpaid, underpaid, minimum paid, or overpaid. Minimum payment helps your score and overpayment helps more. If you can use your credit card every month, that will give you something to overpay every month. Otherwise, you can leave a small debt left on the card but still pay over the monthly minimum. However, your total debt load, especially debt carried on your cards, counts against your score; aim for less than 10% of your limit. Finally, of course, is to pull your credit report periodically. You need to know what others are seeing. Since debt load utilization matters, make sure the reported card maximum is correct on your credit report. Talk to your bank or account issuer if the limit is wrong. If a collection appears, then you need to handle it. Often you can negotiate with the collector, but be careful to negotiate how they will report the resolution. You want them to agree to remove any negative information (either in exchange for payment or because of a mistake). Failing that, you want them to mark it paid in full or satisfied in full; letting them notate your score that you only partially paid is what you want to avoid, since it most signals someone with cash flow problems and credit issues. They control their reporting to credit bureaus, so if the person on the phone demurs, ask to speak to their supervisor or someone with negotiating authority. Try to get any agreements in writing. Remember that your total debt load is a factor in your credit score. Home loans and student loans do affect credit score. If you take on a smaller home loan, then it will affect your credit less harshly (and leave you with smaller monthly payments).",
"title": ""
},
{
"docid": "434289",
"text": "\"There are some loan types where your minimum payment may be less than the interest due in the current period; this is not true of credit cards in the US. Separately, if you have a minimum payment amount due of less than the interest due in the period, the net interest amount would just become principal anyway so differentiating it isn't meaningful. With credit cards in the US, the general minimum calculation is 1% of the principal outstanding plus all interest accrued in the period plus any fees. Any overpayment is applied to the principal outstanding, because this is a revolving line of credit and unpaid interest or fees appear as a charge just like your coffee and also begin to accrue interest. The issue arises if you have multiple interest rates. Maybe you did a balance transfer at a discounted interest rate; does that balance get credited before the balance carried at the standard rate? You'll have to call your lender. While there is a regulation in place requiring payment to credit the highest rate balance first the banks still have latitude on how the payment is literally applied; explained below. When there IS an amortization schedule, the issue is not \"\"principal or interest\"\" the issue is principle, or the next payment on the amortization schedule. If the monthly payment on your car loan is $200, but you send $250, the bank will use the additional $50 to credit the next payment due. When you get your statement next month (it's usually monthly) it will indicate an amount due of $150. When you've prepaid more than an entire payment, the next payment is just farther in to the future. You need to talk to your lender about \"\"unscheduled\"\" principal payments because the process will vary by lender and by specific loan. Call your lender. You are a customer, you have a contract, they will explain this stuff to you. There is no harm that can possibly come from learning the nuances of your agreement with them. Regarding the nuance to the payment regulation: A federal credit card reform law enacted in May 2009 requires that credit card companies must apply your entire payment, minus the required minimum payment amount, to the highest interest rate balance on your card. Some credit card issuers are aggressive here and apply the non-interest portion of the minimum payment to the lowest interest rate first. You'll need to call your bank and ask them.\"",
"title": ""
},
{
"docid": "358445",
"text": "\"Many people who do transfer a balance from one credit card to another have no clue as to what is going on and how credit cards work. If you transfer a balance from one credit card to another, you are charged a fee of anywhere from 3% upwards (subject to a minimum of $10 or so) up front. If Credit Card A has balance $1000 and you transfer it to Credit Card B which is offering no interest for a year on the transferred balance, you owe Credit Card B $1050 (say). In most cases, that $50 has to be paid off as part of the following month's bill. If you are carrying a revolving balance on Credit Card B, that $50 will typically be charged interest from the day of the transfer. Your monthly bill will not (necessarily) include that $1000 you owe for one year or six months or whatever the transfer agreement you accepted says. If you tend to pay anything less (even a penny) than full payment of each month's bill on Credit Card B, your partial payment will be applied to that $1000 first, and anything left over will be applied to the monthly balance. In short, if you don't pay in full each month, that $1000 will not be \"\"yours\"\" for a year; you may end up paying $50 interest for borrowing $1000 for just one or two months, and the rest of your balance is the gift that keeps on giving as the credit card company likes to say. UPDATE: This has changed slightly in the United States. Any amount paid over the minimum amount due is charged to the higher-interest balances. So in this case, if you had $1000 at a 0% promotional rate and a regular balance of $500, and the minimum payment was $100, and you paid $150, $100 would pay down the promotional balance, and the extra $50 would pay down the regular balance. About the only way to make the deal work in your favor is to Transfer money only if you have paid the full amount due on the last two statements before the date of the transfer and are not carrying a revolving balance. Check your monthly statements to make sure they show Finance Charge of 0.00. Many people have never seen such a sight and are unaware that this can be observed in nature. Make sure that you pay each month's bill in full (not the minimum monthly payment due) each month for a whole year after that. Make sure that the bill containing that $1000 (coming out a year after the transfer date) is also paid in full. Very many credit-card users do not have the financial discipline to go through with this program. That is why credit card companies love to push transfer balances on consumers: the whole thing is a cash cow for them where they in effect get to charge usurious rates of interest without running afoul of the law. $50 interest for a one-year loan of $1000 is pretty high at current rates; $50 interest for a two or three month loan where the customer does not even notice the screwing he is getting is called laughing all the way to the bank. See also the answers to this question\"",
"title": ""
},
{
"docid": "213242",
"text": "\"In the US, if your monthly statement was issued by the credit card company on January 1 and it showed a balance of $1000, then a payment must be made towards that balance by January 25 or so, not February 1 as you say, to keep the card in good standing. The minimum payment required to keep the card in good standing is specified in your monthly statement, and failure to meet this requirement can trigger various consequences such as an increase in the interest rate charged by the credit card company. With regard to interest charges, whether your purchase of $2000 on January 3 is charged interest or not depends entirely on what happened the previous two months. If you had paid both your monthly statements dated November 1 and December 1 of the previous year in full by the their respective due dates of November 25 and December 25, and the $1000 balance on the January 1 statement is entirely due to purchases (no cash advances) made in December, then you will not be charged interest on your January purchase of $2000 as long as you pay it off in full by February 25 (the charge will appear on your February 1 statement). But, if you had not paid your December 1 statement in full by December 25, then that $1000 billed to you on January 1 will include purchases made during December finance charges on the unpaid balance from the previous month plus finance charges on the purchases made during December. The finance charges will continue to accumulate during January until such time as you pay off the bill in full (these charges will appear on your February 1 statement), hopefully by the due date of January 25. But even if you pay off that $1000 in full on January 25, your charge of $2000 on January 3 will start to accumulate finance charges as of the day it hits the account and these finance charges will appear on your February 1 statement. If you paid off that $1000 on January 10, say, then maybe there will be no further finance charges on the $2000 purchase on January 3 after January 10 but now we are getting into the real fine print of what your credit card agreement says. Ditto for the case when you pay off that $1000 on January 2 and made the $2000 charge on January 3. You most likely will not be charged interest on that $2000 charge but again it depends on the fine print. For example, it might say that you will be charged interest on the average of the daily balances for January, but will not be charged interest on purchases during the February cycle (unless you miss the February 25 payment and the whole cycle starts all over again). As a general rule, it takes two monthly cycles of payment in full by the due date before one gets into the state of no finance charges for new purchases and effectively an \"\"interest-free\"\" loan of $2000 from January 3 (date of purchase) till February 25 (due date of payment). Matters become more complicated when cash advances are taken from a credit card which are charged interest from the day they are taken but don't trigger finance charges on new purchases or the so-called \"\"zero percent balance transfer offers\"\" are accepted.\"",
"title": ""
},
{
"docid": "550166",
"text": "No, it won't affect your score until your statement is posted. Paying your bill before your statement is posted is actually a good way to keep your credit utilization low. If you're worried about high credit utilization negatively affecting your credit score, consider paying your bill several times a month to ensure that when your final monthly statement is posted, your utilization is still low. When my credit limit was very low while I was in college, I did this almost every month, and I've seen other sites recommend this practice as well. From creditkarma.com: The easiest way [to lower credit utilization] is to make credit card payments more than once a month so that your balance never gets too high. and creditcards.com: Consider making payments to creditors more than once each month. Otherwise, if you put a major expense -- like a new appliance -- on a credit card, even if you plan to pay it off, your FICO score may take a hit. The reason is that credit scores are calculated as a snapshot in time, so if that happens to be right after you charged a new $700 washing machine, your utilization ratio will look worryingly high. Remember, though, that it's best to have some balance on your card when your statement is posted (assuming you pay it off in full each month), because as the chart shows, 0% utilization is about as bad as utilization > 31-40%: Also, remember that credit utilization affects your credit score in real time, so if you have high utilization one month but a lower utilization the next month, the hit to your score will disappear once a statement with low utilization is posted.",
"title": ""
},
{
"docid": "218709",
"text": "Paying up in full before the statement is posted does not seem a good idea. I feel you should keep some small amount to be posted as a statement balance and pay that in full each month. If you keep your statements as always 0 will give creditors an impression that you have cards and you don't utilize them, so they cant really gauge how you preform being debt, whether you are able to manage your debt well etc. I always keep <100 dollar in every credit card I have to be posted a statement balance. I have >100k credit line over 3 cards. So if I take air ticket to SE Asia runs into 3000$ for my family, I pay 2900.00 a day before statement generates and keep 100 for statement to be posted. pay 100 the next day or as auto debit. This way you have some utilization + lower credit card outstanding at any point make your utilization right in single digits.",
"title": ""
},
{
"docid": "188903",
"text": "\"I am interested in seeing what happens to your report after you test this, but I don't think it's possible in practice, would not affect your credit score, and also wouldn't be worth it for you to carry a negative balance like that. Having a -1% credit utilization essentially means that you are lending the credit card company money, which isn't really something that the credit card companies \"\"do\"\". They would likely not accept an agreement where you are providing the credit to them. Having credit is a more formal agreement than just 'I paid you too much this month'. Even if your payment does post before the transaction and it says you have a negative balance and gets reported to the credit bureau like that, this would probably get flagged for human review, and a negative credit utilization doesn't really reflect what is happening. Credit utilization is 'how much do you owe / amount of credit available to you', and it's not really correct to say that you owe negative dollars. Carrying a negative balance like that is money that could be invested elsewhere. My guess is that the credit card company is not paying you the APR of your card on the amount they owe you (if they are please provide the name of your card!). They probably don't pay you anything for that negative balance and it's money that's better used elsewhere. Even if it does benefit your credit score you're losing out on any interest (each month!) you could have earned with that money to get maybe 1-2% better rate on your next home or car loan (when will that be?). TLDR: I think credit utilization approaches a limit at 0% because it's based on the amount you owe and you don't really owe negative dollars. I am very interested in seeing the results of this experiment, please update us when you find out!\"",
"title": ""
},
{
"docid": "141579",
"text": "\"Circa 2002-2005, I was able to successfully \"\"transfer\"\" a balance from a debit card linked to a bank account to a Bank of America Visa credit card. As an example, I could say do a balance transfer from the card XXXX-XXXX-XXXX-XXXX (which was a valid debit card number) to the credit card, and the funds would appear in the checking account within a few days, and also the balance on the credit card would go up the amount plus any balance transfer fee. I think they've sealed off that loophole years ago.\"",
"title": ""
},
{
"docid": "478807",
"text": "\"What you are describing sounds a lot like the way we handle our household budget. This is possible, but quite difficult to do with an Excel spreadsheet. It is much easier to do with dedicated budgeting software designed for this purpose. When choosing personal budgeting software, I've found that the available packages fall in two broad categories: Some packages take what I would call a proactive approach: You enter in your bank account balances, and assign your money into spending categories. When you deposit your paycheck, you do the same thing: you add this money to your spending categories. Then when you spend money, you assign it to a spending category, and the software keeps track of your category balances. At any time, you can see both your bank balances and your spending category balances. If you need to spend money in a category that doesn't have any more money, you'll need to move money from a different category into that one. This approach is sometimes called the envelope system, because it resembles a digital version of putting your cash into different envelopes with different purposes. A few examples of software in this category are You Need a Budget (YNAB), Mvelopes, and EveryDollar. Other packages take more of a reactive approach: You don't bother assigning a job to the money already in your bank account. Instead, you just enter your monthly income and put together a spending plan. As you spend money, you assign the transactions to a spending category, and at the end of the month, you can see what you actually spent vs. what your plan was, and try to adjust your next budget accordingly. Software that takes this approach includes Quicken and Mint.com. I use and recommend the proactive approach, and it sounds from your question like this is the approach that you are looking for. I've used several different budgeting software packages, and my personal recommendation is for YNAB, the software that we currently use. I don't want this post to sound too much like a commercial, but I believe it will do everything you are looking for. One of the great things about the proactive approach, in my opinion, is how credit card accounts are handled. Since your spending category balances only include real money actually sitting in an account (not projected income for the month), when you spend money out of a category with your credit card, the software deducts the money from the spending category immediately, as it is already spent. The credit card balance goes negative. When the credit card bill comes and you pay it, this is handled in the software as an account transfer from your checking account to your credit card account. The money in the checking account is already set aside for the purpose of paying your credit card bill. Dedicated budgeting software generally has a reconcile feature that makes verifying your bank statements very easy. You just enter the date of your bank statement and the balance, and then the software shows you a list of the transactions that fall in those dates. You can check each one against the transactions on the statement, editing the ones that aren't right and adding any that are missing from the software. After everything checks out, the software marks the transactions as verified, so you can easily see what has cleared and what hasn't. Let me give you an example to clarify, in response to your comment. This example is specific to YNAB, but other software using the same approach would work in a similar way. Let's say that you have a checking account and a credit card account. Your checking account, named CHECKING, has $2,000 in it currently. Your credit card currently has nothing charged on it, because you've just paid your bill and haven't used it yet this billing period. YNAB reports the balance of your credit card account (we'll call this account CREDITCARD), as $0. Every dollar in CHECKING is assigned to a category. For example, you've got $200 in \"\"groceries\"\", $100 in \"\"fast food\"\", $300 in \"\"rent\"\", $50 in \"\"phone\"\", $500 in \"\"emergency fund\"\", etc. If you add up the balance of all of your categories, you'll get $2,000. Let's say that you've written a check to the grocery store for $100. When you enter this in YNAB, you tell it the name of the store, the account that you paid with (CHECKING), and the category that the expense belongs to (groceries). The \"\"groceries\"\" category balance will go down from $200 to $100, and the CHECKING account balance will go down from $2,000 to $1,900. Now, let's say that you've spent $10 on fast food with your credit card. When you enter this in YNAB, you tell it the name of the restaurant, the account that you paid with (CREDITCARD), and the category that the expense belongs to (fast food). YNAB will lower the \"\"fast food\"\" category balance from $100 to $90, and your CREDITCARD account balance will go from $0 to $-10. At this point, if you add up all the category balances, you'll get $1,890. And if you add up your account balances, you'll also get $1,890, because CHECKING has $1,900 and CREDITCARD has $-10. If you get your checking account bank statement at this time, the account balance of $1,900 should match the statement and you'll see the payment to the grocery store, assuming the check has cleared. And if the credit card bill comes now, you'll see the fast food purchase and the balance of $-10. When you write a check to pay this credit card bill, you enter this in YNAB as an account transfer of $10 from CHECKING to CREDITCARD. This transfer does not affect any of your category balances; they remain the same. But now your CHECKING account balance is down to $1,890, and CREDITCARD is back to $0. This works just as well whether you have one checking account and one credit card, or 2 checking accounts, 2 savings accounts, and 3 credit cards. When you want to spend some money, you look at your category balance. If there is money in there, then the money is available to spend somewhere in one of your accounts. Then you pick an account you want to pay with, and, looking at the account balance, if there isn't enough money in that account to pay it, you just need to move some money from another account into that one, or pick a different account. When you pay for an expense with a credit card, the money gets deducted from the category balances immediately, and is no longer available to spend on something else.\"",
"title": ""
},
{
"docid": "520205",
"text": "Patience is the key here, I hate to say! There are five factors to FICO credit scores: Payment history is adversely affected by late payments - so always pay on time, otherwise your report will be haunted for seven years! 👻 Credit utilization has to do with how much of your available credit is currently in use - lower is better, but 0% isn't good either because they want to see that you're using credit. 10% or less is a good goal, and try to keep any single card balance to 30% or less when its statement close date rolls around. Credit history is based on the average age of all of your accounts, cards or otherwise, the older the better. Don't close either of your other cards (because that would cause your average account age to fall), and make sure to use the store card at least occasionally, because lenders sometimes decide to close unused lines of credit. Credit mix has to do with the different types of credit you hold and is why your bank's website suggested taking out a loan. It also has to do with the number of accounts overall; I've never found a satisfactory answer for what the sweet spot is, but I suspect it's in the 6-12 range? You wouldn't want to get several new ones at the same time because... New credit is affected by the credit inquiries (hard pulls) that occur when you apply for new cards or loans. Inquiries stay on your report for two years before falling off. This is almost certainly where your score dropped. You also mentioned not knowing if some hospital bills are still affecting your score. You'll want to review your credit reports and find out, plus checking your credit reports regularly is a really great habit to get into because errors (and fraud) can and do happen. There are three credit reporting agencies: Experian, Equifax, and TransUnion, and you'll want to review all three. You can get one free report from each of them every year: https://www.usa.gov/credit-reports It can take a couple of months for a new credit account to show up on your credit report, so your score should recover and go even higher once that happens. Sit tight, as annoying as that is!",
"title": ""
},
{
"docid": "585890",
"text": "You are in luck, I have an ANZ credit card as well. I have just checked my paper statement with online, and was able to find a matching online statement in less than a minute. You simply click on your credit card account from the list of accounts. Under Date Range it will have the Current incomplete statement period. You simply click on the down arrow and select the last complete date range ending sometime in late April (depending on your credit card cycle). You then press on View next to the drop down box. This should provide you with a list of purchases and payment/credits for that period, followed by a line with your Credit Limit, Available Funds and Closing Balance. The line below that then shows your Due Date, and Overdue/Overlimit, the Minimum Payment and Amount Due Now If you are after paying only the minimum amount then you pay this amount by the due date (you will be charged interest if you only pay this amount). If, on the otherhand, you wish to avoid paying any interest then you need to pay the full Closing Balance before the due date. You should also be able to get electronic statements sent to your email address.",
"title": ""
},
{
"docid": "474795",
"text": "Think about how loans work for you personally. When you charge a $50 dinner for two to your Visa card, you did not earn $50 in income. You did not pay income tax on that $50. The money you use to pay back that $50 at the end of the month is not tax deductible. Interest on a loan is a business expense. Repayment of principal is not a business expense, just as receiving the loan in the first place is not business income. Effectively this means the LLC repays the loan with after-tax dollars. Just like you do with your Visa card. When I do corporate accounting, payment of loan interest shows up on the expense side of the Profit/Loss statement, and it makes the Balance Sheet net assets go down. However payment of loan principal is effectively null. It doesn't appear on the Profit/Loss at all -- and it's a wash on the Balance Sheet, as both Assets and Liabilities fall by the same amount.",
"title": ""
},
{
"docid": "208169",
"text": "It's not so much a credit card, but a financial institution's online platform that either provides this functionality or not. The following Canadian financial institutions show an itemized list of pre-authorized transactions (not an exhaustive list): The following institutions show a total value of pre-authorized transactions: Most other institutions show the available credit (e.g. Chase Financial used by Amazon Rewards), which give an indication of how much you have to spend. By subtracting the current balance and the available balance from the total credit limit, you can get an indication of the total amount of pre-authorized transactions. Example: $1000 - $500 - $400 = $100 is the amount of pre-authorized transactions. From TD's EasyWeb demo (http://tdeasywebdemo.com/v2/#/en/PFS/accounts/activity/chq), it appears that they don't include pre-authorized transactions in the Available Credit. You can verify for yourself by logging in to online banking after you make a purchase and comparing the Available Credit to [Credit Limit - Current Balance]. If it is equal, then they don't include, if it is different (most likely for the value of the transaction), then they do.",
"title": ""
},
{
"docid": "271472",
"text": "\"I have some experience with this. I have had fraudulent charges appear on my credit card statement and had to change my card number several times, despite (I believe) no carelessness on my part. Every time that this has happened, I have never lost a penny due to fraud on my credit card. The bank has ultimately removed the fraudulent charges in every instance. Given this, you'd think the consumer doesn't need to worry about this at all. But it seems like credit card companies beg to differ. Yes, because although I have never lost a penny to fraud, the bank (or the merchant) loses money every time it happens. The $0 liability protects you; the card security measures protect the bank. But... why should a consumer ever bother worrying about these in the first place, when he knows he legally can't be held responsible for fraudulent charges? What exactly is this new \"\"peace of mind\"\" that he supposedly gets by (say) using features like virtual account numbers that he doesn't already have? Although you shouldn't end up out any money when this happens, it is an inconvenience. The bank will cancel your card and issue you a new number. It may take a few days for you to receive your new card. If you have another card to use, this isn't a big deal. If you are out of state the day before you need to check out of a hotel and return a rental car with no backup credit card (as I have been), it is a big deal. (In my case, I had to have the credit card company talk to the hotel to give them the new card number, and they were able to overnight me a new credit card so I could get home. I now make sure I carry a backup credit card.) Should a consumer put any effort into worrying about this at all? (Why?) In my opinion, it makes sense to be careful what you do with your credit card number, if only to avoid the inconvenience. Don't type your credit card number into an e-mail message, for example, and only use it on websites that you trust. That having been said, it is not worth it to be paranoid about it, either. No matter how careful you are, eventually you will probably use it at a store that gets hacked, or your card will get skimmed somewhere, and you'll need to get a new credit card number. The best way to protect yourself is to make sure that you go over your credit card statement each month and look for any fraudulent charges that the bank didn't catch.\"",
"title": ""
},
{
"docid": "170481",
"text": "Good credit is calculated (by many lenders) by taking your FICO score which is calculated based upon what is in your credit report. Building credit generally means building up your FICO score. Your FICO score is impacted my many factors, one small one of which is your utilization ratio of your installment loans like student loans. This is the ratio of the current balance to your original balance. To improve your score (slightly) you would want a lower ratio. I would recommend paying your student loan down to 75% ratio as fast as you can and then you can go back to $50/month. A much better way to improve your FICO score is to have revolving credit. Your student loans are not revolving, they are installment loans. Therefore, you should open at least one credit card (assuming you currently have none) right away. The longer you have had a credit card open, the better your FICO score gets. Your revolving credit utilization ratio is way more important than your installment loan ratio. Therefore, to maximize your FICO, try to never have more than 10% utilization on your revolving credit report to the credit bureaus each month. Only the current month's ratio affects your score at any given moment. You can ensure you don't go above 10% by paying your balance before the statement cuts each month to get it below 10% way before any payment would be due. (You should always pay your remaining credit card statement balance in full each month by the due date after the statement cuts to avoid any interest charges.) Note that there is a slight FICO advantage to having at least one major bank credit card instead of just only credit union credit cards. Also, never let all your revolving credit report a zero balance in a month, you must always have at least $1 reporting to the credit bureaus on at least one of your open credit cards or your FICO score will take a big negative hit. If you cannot get a normal credit card, go to a credit union and find one that offers secured credit cards, or a bank that does. A secured credit card is where you place a deposit with the bank that they hold and give you a credit limit to match your security. Ideally it would be a card that graduates to unsecured after your demonstrate good history with them. For example, the Navy Federal Credit Union secured card unsecures for many people. I also believe the Wells Fargo Bank credit card (you can join if there is a family member who served or a roomate who did) also will unsecure. The reason you want it to unsecure and not be forced to open a new account to get an unsecured account is that you want your average age and oldest age of open revolving credit accounts to be as high as possible as this is another impact on your FICO score. Credit unions that anyone can join include, Digital Federal Credit Union, the Pentagon Federal Credit Union (which offers a secured card that does not graduate), and The State Department Federal Credit Union (also offers secured card that I think does not graduate). One other method to boost your FICO score is to get added as an authorized user on one of your parent's credit cards that has been open a long time. Not all lenders will report such an authorized user, however, ones that are known to do so are: Bank of America, Citi Bank, and Capital One. It is a good sign that it will report if they ask for the social security number of the authorized user. However, note that the Authorized User addition can have no impact if the lender is using one of the newer versions of the FICO scoring model, only the older versions reward you for the age of accounts for which you are an authorized user. A very long term boost is to open your first American Express card underwritten directly by Amex such as their Zync card which is pretty easy to get. The advantage of American express is that they remember the date your first credit card was opened with them and if you open new accounts in the future they will back date the date of their opening to match the date your first card was opened. If you let your membership lapse, be sure to record the account number and date opened in your personal files so that you can help them locate it again if you reopen as they can have trouble if it has been on the order of ten years or more. Finally, note that the number of accounts opened in the last twelve months is a small negative mark on your score (along with number of inquiries), so if you open a lot of accounts all at once, in addition to bringing down your average age of accounts, you will also get dinged for how many were opened in the last year.",
"title": ""
},
{
"docid": "195726",
"text": "Hi, This is treated as a electronic balance transfer. There may be a fee for performing this. Cash advance interest will apply on the EBT. You may get a teaser rate for a limited amount of time. After it expires, the normal cash advance interest rate for the credit card will kick in. Check your credit card statement. Somewhere, you'll see a section listing the interest rates. One for retail purchases, one for cash transactions. Do not do this. If you need to borrow money to pay off a large debt, do one of the following: 1) Switch to the lowest interest rate card your bank offers 2) Apply for a credit card with another bank that is offering a great teaser rate, transfer the balance, cut your living expenses and send every penny to paying off the balance before the teaser rate expires 3) If you cannot get access new credit or switch credit cards, seek advice from a professional credit counsellor on your options and the best one to choose Sorry to ramble. I've seen far too many people fall into the debt trap. You don't want to go there. Source: I work for a bank which offers credit card products.",
"title": ""
},
{
"docid": "539859",
"text": "In general, minors cannot enter into legally binding contracts -- which is what credit accounts are -- so an individually held card is probably not an option for you right now. You will not be approved for a credit card because you are minor. The only option credit card wise for you is for your parents to add you on as an authorized user onto their accounts. The upside is that you and your parents can work out a monthly payment for the amount you spend on your equipment, the downside is that if your parents don't pay their credit card bill, your credit score/report can be negatively affected. (This also depends on the bank, however, all the banks I bank with report monthly payment activities on authorized users' credit reports as well. There might be a bank that doesn't.) In terms of credit cards, there is nothing you can do. What you could do as the comments have suggested is either save up money for the equipment you want, or buy something cheaper.",
"title": ""
},
{
"docid": "81416",
"text": "When you give your credit card number and authorize a merchant to charge your credit card, the merchant then gives the information to their merchant processor which in turns bills the bank that issued the card (it's a little more complex and it all happens instantly unless the merchant is using the very old fasion imprinting gizmos). It is possible for a merchant to attempt to charge you more than you authorized but if they do they risk a fine ($25-$50 for a chargeback) from their processor, the legitimate portion of the charge as well as increasing the processing fees charged by their processor or even the possibility of loosing their merchant account entirely and being permanently blacklisted by Visa/Mastercard. In short no legitimate business is going to intentionally over charge your credit card. There really isn't significant risk in using a reputable online retailer's order forms. There is the possibility that their database could be compromised but that risk is lower than the risk of having an employee steal your credit number when you give it to them in person. Besides in the US at least the most you can legally be held liable for is $50 assuming you notice the discrepancy within 60 days of statement the charge appears on and most banks limit liability to $0. Over the years I have had a number of different credit card numbers stolen and used fraudulently and I have never had to pay any fraudulent charges.",
"title": ""
},
{
"docid": "42044",
"text": "Credit cards are meant to be used so generally it doesn't hurt your credit score to use them. To top it off you even get an interest grace period so you don't have to rush home and pay balances as soon as they're charged. In general you accrue charges during your statement period, we'll call it September 1 through September 30. The statement due date is something like 20 days after the close of the statement period, so we'll call it October 20. As long as you habitually pay your entire statement balance by the due date you will never pay interest. You charge your laptop on September 3, it shows up on your statement as $1,300, you pay $1,300 on October 18, you pay no interest. However, if you pay $1,000 on October 18 leaving a $300 balance to be carried in to the next statement period (a carried balance) you will pay interest. Generally interest is calculated based on your average daily balance during the statement period, which is now be the October 1 to October 31 period. You'll notice that you didn't pay anything until the October 18, that means the entire $1,300 will be included in your average daily balance up to the 18th of the month. Add to that, anything else you charge on the card now will be included in your average daily balance for interest charge calculation purposes. The moral of the story is, use your card, and pay your entire statement balance before the due date. Now how much will this impact your credit score? It's tough to say. Utilization is not a bad thing until it's a big number. I've read that 70% utilization and over is really the point at which lenders will raise an eyebrow and under 30% is considered excellent. If you have one card and $1,300 is a significant portion of your available limit, then yes you should probably pay it down quickly. Spend six or so months using the card and paying it, then call your bank and ask for a credit line increase.",
"title": ""
},
{
"docid": "24138",
"text": "You're going to have a huge problem getting approved for anything as long as you have an unpaid bill on your report. Pay it and make sure its reported as paid in full - ASAP. Once that settled, your credit will start to improve slowly. Can't do anything about that, it will take time. You can make the situation improve a bit faster by lending money to yourself and having it reported regularly on your report. How? Easy. Get a secured credit card. What does it mean? You put X amount of money in a CD and the bank will issue you a credit card secured by that CD. Your credit line will be based on the amount in that CD, and you'll probably pay some fees to the bank for the service (~$20-50/year, shop around). You might get lucky and find a secured card without fees, if you look hard enough. Secured cards are reported as revolving credit (just as any other credit card) and are easy to get because the bank doesn't take the risk - you do. If you default on your payments - your CD goes to cover the debt, and the card gets cancelled. But make absolutely sure that you do not default. Charge between 10% and 30% of the credit limit each month, not more. Pay the balance shown on your credit card statement in full every month and by the due date shown on your monthly statement. It will take a while, but you would typically start noticing the improvement within ~6-12 months. Stop applying for stuff. Not store cards, not car loans, you're not going to get anything, and will just keep dragging your scores down. Each time you have a pull on your report, the score goes down. A lot of pulls, frequent pulls - the score goes down a lot. Lenders can see when one is desperate, and no-one wants to lend money to desperate people. Optimally lenders want to lend money to people who doesn't need loans, but in order to keep the business running they'll settle for slightly less - people who don't usually need loans, and pay the loans they do have on time. You fail on both, as you're desperate for a loan and you have unpaid bills on your report.",
"title": ""
},
{
"docid": "198349",
"text": "\"Check whether you're being charged a \"\"Cash advance\"\" fee with your withdrawals, because it's being withdrawn from your credit card account. If that's happening to you, then having a positive balance on your credit card account will dramatically reduce the fees. Quoting from my answer to a similar question on Travel Stack Exchange: It turns out that even though \"\"Cash advance fee - ATM\"\" has \"\"ATM\"\" in it, it doesn't mean that it's being charged by the ATM you're withdrawing from. It's still being charged by the bank of your home country. And depending on your bank, that fee can be minimized by having a positive balance in your credit card account. This isn't just for cards specially marketed at globehoppers and globeshoppers (mentioned in an answer to a similar question), but even for ordinary credit cards: Help minimise and avoid fees An administrative charge of 2% of the value of the transaction will apply to each cash advance made on your card account, where your account has a negative (debit) balance after the transaction has been posted to it. A minimum charge of $2.50 and a maximum charge of $150 will apply in these circumstances. Where your account has a positive (credit) balance after the transaction has been posted to it, a charge of $2.50 will apply to the transaction. Any such charge will appear on your credit card statement directly below the relevant cash advance. A $2.50 charge if your account is positive, versus $20 if the account is negative? That's a bit of a difference!\"",
"title": ""
},
{
"docid": "504384",
"text": "\"There are always little tricks you can play with your credit card. For example, the due date of your statement balance is not really set in stone as your bank would like you to believe. Banks have a TOS where they can make you liable to pay interest from the statement generation date (which is a good 25 days before your due date) on your balance, if you don't pay off your balance by your due date. However, you can choose to not pay your balance by your due date upto 30 days and they will not report your late payment to credit agencies. If they ask you to pay interest, you can negotiate yourself out of it as well (although not sure if it will work every-time if you make it a habit!) Be careful though: not all banks report your credit utilization based on your statement balance! DCU for example, reports your credit utilization based on your end-of-the-month balance. This can affect your short term credit score (history?) and mess around with your chances of pulling off these tricks with the bank CSRs. These \"\"little tricks\"\" can effectively net you more than 60 days of interest free loans, but I am not sure if anyone will condone this as a habit, especially on this website :-)\"",
"title": ""
},
{
"docid": "336792",
"text": "\"Its called a \"\"Grace Period\"\" and you are not paying interest on the 0% BT, you are paying interest on the amount you spent in purchases If you do not pay your balance in full by the due date your grace period ends. This means that you have to pay interest on the purchased amount from the day it is made. This is why when you do a balance transfer the card should be put in the Sock Drawer until the BT is paid off. In order to restore the grace period you must pay the balance in full and the grace period will start during the Next Payment Cycle. Lets Assume: Statement cuts on the 1st and Due date is the 20th. you make the minimum payment of $10 Balance now is $100 Since you have a balance of $100 from the previous statement and a new purchase of $50.00, when the next statement cuts you will have to pay interest according to the terms on the $50.00 portion. In order to get the grace period back you will have to pay in full and wait for the next cycle In case I did not explain it well here is a quote from creditcards dot com website: The cost of carrying a balance This is because carrying a balance of any size into the next billing cycle means there is no grace period on your purchases during that cycle. The card company will begin charging interest on your purchases the day you make them. So leaving even $1 in unpaid balance on your card will cost you considerably more than the measly finance charges on that dollar. To see how this works let's consider an imaginary card user named Sally. She's so happy she got a new credit card that she charges $1,500 in purchases on the first day of her monthly billing cycle. After the cycle ends, Sally pays off the entire $1,500 by the due date, wiping her balance to zero. As a result, her purchases during the second month are also free of interest. She has used her grace period wisely to avoid finance charges. What happens if Sally leaves just $1 of her balance from the first month unpaid? That $1 begins to accrue interest starting the first day of the billing cycle. It's just $1, so the interest is not a big deal -- but because she used up her grace period without paying off her entire debt, her new purchases during the second month also start to get hit with interest charges immediately, starting the day of the transaction. Assuming she makes another $1,500 in purchases at the average annual interest rate of about 13 percent, that means $16 in finance charges for the month. If Sally repeats this pattern, the interest costs add up to $190 over the course of a year.\"",
"title": ""
},
{
"docid": "247199",
"text": "\"As Dheer has already told you in his answer, your plan is perfectly legal, and there are no US tax issues other than making sure that you report all the interest that you earn in all your NRE accounts (not just this one) as well as all your NRO accounts, stock and mutual fund dividends and capital gains, rental income, etc to the IRS and pay appropriate taxes. (You do get a credit from the IRS for taxes paid to India on NRO account income etc) You also may also need to report the existence of accounts if the balance exceeds $10K at any time etc. But, in addition to the foreign exchange conversion risk that Dheer has pointed out to you, have you given any thought to what is going to happen with that credit card? That 0% interest balance of $5K does not mean an interest-free loan 0f $5K for a year (with $150 service charge on that transaction). Instead, consider the following. If you use the card for any purchases, then after the first month, your purchases will be charged interest from the day that you make them till the day they are paid off: there is no 25-day grace period. The only way to avoid this is to pay off the full balance ($5K 0% interest loan PLUS $150 service charge as well as any other service charges, annual fees etc PLUS all purchases PLUS any interest) shown on the first monthly statement that you receive after taking that loan. If you choose this option, then, in effect, have taken a $5K loan for only about 55 days and have paid 3% interest (sorry, I meant to write) service fee for the privilege. If you don't use the card for any purchases at all, then the first monthly statement will show a statement balance of $5130 and (most likely) a minimum required payment of $200. By law, the minimum required payment is all interest charged for that month($0) PLUS all service fees charged during that month ($150) PLUS 1% of the rest ($50). Well, actually the law says something like \"\"a sufficient fraction of the balance to ensure that a person making the required minimum payment each month can pay off the debt in a reasonable time\"\" and most credit card companies choose 1% as the sufficient fraction and 108 months as a reasonable time. OK, so you pay the $200 and feel that you have paid off the service fee and $50 of that 0% interest loan. Not so! If you make the required minimum payment, the law allows that amount to be be applied to any part of the balance owing. It is only the excess over the minimum payment that the law says must be applied to the balance being charged the highest rate. So, you have paid off $200 of that $5K loan and still owe the service fee. The following month's statement will include interest on that unpaid $150. In short, to leave only the 0% balance owing, you have to pay $350 that first month so that next month's statement balance will be $4800 at 0%. The next month's required minimum payment will be $48, and so on. In short, you really need to keep on top of things and understand how credit-card payments really work in order to pull off your scheme successfully. Note also that the remaining part of that 0% interest balance must be paid off by the end of the period or else a humongous rate of interest will be applied retroactively from Day One, more than enough to blow away all that FD interest. So make sure that you have the cash handy to pay it off in timely fashion when it comes due.\"",
"title": ""
},
{
"docid": "490529",
"text": "\"To expand on @JoeTaxpayer's answer, the devil is actually in the fine print. All the \"\"credit-card checks\"\" that I have ever received in the mail explicitly says that the checks cannot be used to pay off (or pay down) the balance on any other credit card issued by the same bank, whether the card is branded with the bank logo or is branded with a department-store or airline logo etc. The checks can be used to pay utilities, or even taxes, without paying the \"\"service fee\"\" that is charged for using a credit card for such payments. The payee is paid the face amount of the check, in contrast to charges on a credit card from a merchant who gets to collect only about 95%-98% of the amount on the \"\"charge slip\"\". Generally speaking, balance transfer offers are a bad deal regardless of whether you pay only the minimum amount due each month or whether you pay each month's statement balance in full by the due date or anything in between. The rest of this answer is an explanation in support of the above assertion. Feel free to TL;DR it if you like. If you make only the minimum payment due each month and some parts of the balance that you are carrying has different interest rates applicable than other parts, then your payment can be applied to any part of the balance at the bank's discretion. It need hardly be said that the bank invariably chooses to apply it to pay off the lowest-rate portion. By law (CARD Act of 2009), anything above the minimum payment due must be applied to pay off the highest-rate part (and then the next highest rate part, etc), but minimum payment or less is at the bank's discretion. As an illustration, suppose that you are not using your credit cards any more and are conscientiously paying down the balances due by making the minimum payment due each month. Suppose also that you have a balance of $1000 carrying 12% APR on Card A, and pay off the entire balance of $500 on Card B, transferring the amount at 0% APR to Card A for which you are billed a 2% fee. Your next minimum payment will be likely be $35; computed as $10 (interest on $1000) + $10 transfer fee + $15 (1% of balance of $1500). If you make only the minimum payment due, that payment will go towards paying off the $500, and so for next month, your balance will be $1500 of which $1035 will be charged 1% interest, and $465 will be charged 0% interest. In the months that follow, the balance on which you owe 1% interest per month will grow and the 0% balance will shrink. You have to pay more than the minimum amount due to reduce the amount that you owe. In this example, in the absence of the balance transfer, the minimum payment would have been $20 = $10 (interest on $1000 at 1% per month) + $10 (1% of balance) and would have left you with $990 due for next month. To be at the same point with the balance transfer offer, you would need to pay $30 more than the minimum payment of $35 due. This extra $30 will pay off the interest and transfer fee ($20) and the rest will be applied to the $1000 balance to reduce it to $990. There would be no balance transfer fee in future months and so the extra that you need to pay will be a little bit smaller etc. If you avoid paying interest charges on credit cards by never taking any cash advances and by paying off the monthly balance (consisting only of purchases made within the past month) in full by the due date, then the only way to avoid paying interest on the purchases made during the month of the balance transfer offer is to pay off that month's statement in full (including the balance just transferred over and the balance transfer fee) by the due date. So, depending on when in the billing cycle the transfer occurs, you are getting a loan of the balance transfer amount for 25 to 55 days and being charged 2% or 3% for the privilege. If you are getting offers of 2% balance transfer fees instead of 3%, you are probably among those who pay their balances in full each month, and the bank is trying to tempt you into doing a balance transfer by offering a lower fee. (It is unlikely that they will make a no-transfer-fee offer.) They would prefer laughing all the way to themselves by collecting a 2% transfer fee from you (and possibly interest too if you fail to read the fine print) than having you decline such offers at 3% as being too expensive. Can you make a balance transfer offer work in your favor? Sure. Don't make any purchases on the card in the month of the balance transfer or during the entire time that the 0% APR is being offered. In the month of the transfer, pay the minimum balance due plus the balance transfer fee. In succeeding months, pay the minimum balance due (typically 1% of the balance owed) each month. All of it will go to reducing the 0% APR balance because that is the only amount owing. Just before the 0% APR expires (anywhere from 6 to 24 months), pay off the remaining balance in full. But remember that you are losing the use of this card for this whole period of time. Put it away in a locked trunk in the attic because using the card to make a purchase will mean paying interest on charges from the day they post, something that might be totally alien to you.\"",
"title": ""
},
{
"docid": "65982",
"text": "There are a couple of things to consider. First, in order to avoid interest charges you generally just need to pay the statement balance before the statement due date. This is your grace period. You don't need to monitor your activity every day and send immediate payments. If you're being really tight with money, you can actually make a little profit by letting your cash sit in an interest bearing account before you pay your credit card before the due date. Second, credit card interest rates are pretty terrible, and prescribed minimum payments are comically low. If you buy furniture using your credit card you will pay some interest, be sure to pay way more than the minimum payment. You should avoid carrying a balance on a credit card. At 20% interest the approximate monthly interest charge on $1,000 is $16.67. Third, if you carry a balance on your credit card you lose the interest grace period (the first point above) on new charges. If you buy your couch, and carry the balance, when you buy a soda at 7-11, the soda begins to accrue interest immediately. If you decide to carry a balance on a credit card, stop using that card for new charges. It generally takes two consecutive billing period full balance payments to restore the grace period. Fourth, to answer your question, using a credit card to carry a balance has no impact on your score. Make your payments on time, don't exceed your limits, keep your utilization reasonable. The credit agencies have no idea if you're carrying a balance or how much interest you're paying. To Appease the people who think point four needs more words: Your credit report contains your limit, your reported balance (generally your statement balance), and approximate minimum payment. There is no indication related to whether or not the balance contains a carried balance and/or accrued interest. The mere fact of carrying a balance will not impact your credit score because the credit reporting bureaus don't know you're carrying a balance. Paying interest doesn't help or hurt your score. Obviously if your carried balance and interest charges push your utilization up that will impact your score because of the increased utilization. Make your payments on time, don't exceed your limits, keep your utilization reasonable and your score will be fine.",
"title": ""
}
] |
5ae207945542994d89d5b316
|
Palentown is a hamlet in a county named for a province of what nationality?
|
[
{
"docid": "56952",
"text": "Ulster County is a county located in the U.S. state of New York. As of the 2010 census, the population was 182,493. The county seat is Kingston. The county is named after the Irish province of Ulster.",
"title": ""
},
{
"docid": "9754378",
"text": "Palentown is a hamlet in Ulster County, New York, United States.",
"title": ""
}
] |
[
{
"docid": "3984692",
"text": "Indian Falls is a hamlet located closely within the northern border of the town of Pembroke and the western edge of Genesee County, Western New York, United States. Located in what was traditional Seneca nation territory for hundreds of years, the town was named also for a waterfall near its center, where Tonawanda Creek flows over the Onondaga escarpment.",
"title": ""
},
{
"docid": "5407657",
"text": "Apalachee Province was the area in the Panhandle of the present-day U.S. state of Florida inhabited by the Native American peoples known as the Apalachee at the time of European contact. The southernmost extent of the Mississippian culture, the Apalachee lived in what is now Leon County, Wakulla County and Jefferson County. The name was in use during the early period of European exploration. During Spanish colonization, the Apalachee Province became as one of the four major provinces in the Spanish mission system, the others being the Timucua Province, (between the St. Johns and Suwanee Rivers), the Mocama Province (along the Atlantic coast of what is now northern Florida and southern Georgia) and the Guale Province (along the Georgia coast north of the Altamaha River).",
"title": ""
},
{
"docid": "43169855",
"text": "Root Creek was a hamlet in Sections 21-22 and 27-28 of the Town of Greenfield in Milwaukee County, Wisconsin, on the Milwaukee-Janesville plank road, at what is now roughly the intersection of that thoroughfare (now Forest Home Avenue) and 68th Street. The body of water after which it was named is nowadays referred to as the Root River.",
"title": ""
},
{
"docid": "8554413",
"text": "Alfred Henry Bellot (born 1882) was a historian whose \"History of the Rockaways from the Year 1685 to 1917\", published in 1918, was probably the definitive history up to that time of the communities on the Rockaway Peninsula in Queens County, New York City and the villages and hamlets which comprise what is known today as the Five Towns of Nassau County, Long Island, New York, namely Inwood, Lawrence, Cedarhurst, Woodmere and Hewlett.",
"title": ""
},
{
"docid": "770672",
"text": "Lake Pleasant, New York is a hamlet in the Town of Lake Pleasant. This community is the county seat of Hamilton County, New York and includes the Hamilton County Courthouse Complex. The name is derived from a lake named Lake Pleasant near the community.",
"title": ""
},
{
"docid": "9762150",
"text": "\"What a piece of work is a man!\" is a phrase within a monologue by Hamlet in William Shakespeare's eponymous play. Hamlet is reflecting, at first admiringly, and then despairingly, on the human condition.",
"title": ""
},
{
"docid": "2674092",
"text": "Grafton is a community in the province of Ontario. It is in Northumberland County, in the township of Alnwick/Haldimand. It is 12 km east of Cobourg, Ontario on the former Highway 2 (now Country Road 2), with close access to Highway 401. The hamlet is near the geographically significant Oak Ridges Moraine at Rice Lake. Grafton was originally called Grover's Tavern until March, 1832. The original Grover's Tavern, the namesake building of the hamlet, still stands today as the Grafton Village Inn, a restaurant and B & B in the heart of the hamlet. It was also referred to early in its history as Haldimand, which is the name of the township it is located in.",
"title": ""
},
{
"docid": "30369912",
"text": "Raisbeck is a hamlet in the civil parish of Orton, in the Eden district, in the county of Cumbria, England. The surname Raisbeck originates from the hamlet. The name of the hamlet derives from Hrridarr, a personal name and beck, a stream or river, the surname is used by people such as Alex Raisbeck, Rosina Raisbeck and Bill Raisbeck. There is also the smaller hamlet of Sunbiggin nearby.",
"title": ""
},
{
"docid": "19286848",
"text": "Beaver River is a hamlet that is six tenths of a mile square, at the east end of Stillwater Reservoir, in the town of Webb in Herkimer County, New York. The hamlet is surrounded by the Adirondack Park. The hamlet has a year-round population of eight, that increases during the summer as many people have camps in this wilderness area. There are 125 private properties, and three commercial businesses. No roads lead to the hamlet; it is accessible only by hiking, rail car or boat in the summer and by snowmobile, snowshoes or cross country skis in the winter. There is no electrical service. The town is named for the Beaver River. The New York Central Railroad right of way, on the National Register of Historic Places passes through the hamlet; an existing bunkhouse is a part of the historic property.",
"title": ""
},
{
"docid": "18120232",
"text": "The Republic of Cospaia was a small state in Italy, located in northern Umbria, independent from 1440 to 1826. It was located in what is now the hamlet (\"frazione\") of Cospaia in the comune of San Giustino in the Province of Perugia.",
"title": ""
},
{
"docid": "29229117",
"text": "Bronant is a hamlet in the county of Ceredigion, mid Wales. It lies on the A485 road which runs north from Tregaron to Llanilar and falls within the community of Lledrod. The Cors Caron national nature reserve lies three miles to the southeast. Also of note is the Roman road of Sarn Helen which passes to the east of the hamlet. It is known to geologists as it gives its name to the Bronnant Fault.",
"title": ""
},
{
"docid": "25438253",
"text": "Barley Sheaf was an unincorporated community located within Readington Township in Hunterdon County, New Jersey, United States. It was named for the grain once grown in the region. The hamlet was on Barley Sheaf Road between County Route 629 (CR 629) and CR 523. The hamlet at one time housed a general store, a post office, blacksmith, creamery, a hotel and numerous farmsteads. Today only farms remain of the hamlet. The hamlet also carried the names of Farmersville and Campbellsville after Catherine Campbell, who ran the hotel in the area.",
"title": ""
},
{
"docid": "14448199",
"text": "What follows is an overview of the main characters in William Shakespeare's \"Hamlet\", followed by a list and summary of the minor characters from the play. Three different early versions of the play survive: known as the First Quarto (\"Q1\"), Second Quarto (\"Q2\"), and First Folio (\"F1\"), each has lines—and even scenes—missing in the others, and some character names vary.",
"title": ""
},
{
"docid": "1831873",
"text": "Botzum was a hamlet in Northampton Township, Summit County, Ohio around what is now the intersection of Bath and Riverview Roads in Akron and Cuyahoga Falls.",
"title": ""
},
{
"docid": "29464622",
"text": "White Rock (Navajo:Tséłgaii ) is a tiny Navajo settlement (hamlet) in San Juan County New Mexico in the southwestern United States. It is named after a cliff exposure to the northeast of the settlement. It is also a chapter of the Shiprock Agency of the Navajo Nation.",
"title": ""
},
{
"docid": "34682485",
"text": "Slijkplaat (English: \"Mud plate\") is a hamlet in the Dutch province of Zeeland. It is located in the municipality of Sluis. The hamlet exists of two streets (one name) and 28 houses.",
"title": ""
},
{
"docid": "9152965",
"text": "Veldhuizen is a hamlet in the Dutch province of Utrecht. It is located in the municipality of Utrecht, south of De Meern. It is also the name of a new neighbourhood of Utrecht, built close to the hamlet.",
"title": ""
},
{
"docid": "7848273",
"text": "Kosŏng County is a \"kun\", or county, in Kangwŏn province, North Korea. It lies in the southeasternmost corner of North Korea, immediately north of the Korean Demilitarized Zone. Prior to the end of the Korean War in 1953, it made up a single county, together with what is now the South Korean county of the same name. In a subsequent reorganization, the county absorbed the southern portion of Tongch'ŏn county.",
"title": ""
},
{
"docid": "26865960",
"text": "Linton is an unorganized territory in the Capitale-Nationale region of Quebec, Canada, in the north of the Portneuf Regional County Municipality. It is named after the hamlet of Linton that is located along the Canadian National Railway and the Batiscan River ().",
"title": ""
},
{
"docid": "28275225",
"text": "Lyons is a hamlet in Wayne County, New York, in the United States. The population was 3,619 at the 2010 census. It is located in the southern half of the town of Lyons. The hamlet and the town are named after Lyon (sometimes spelled Lyons), France. Originally, named \"The Forks\" , Lyons was renamed by Land agent, George Williamson.",
"title": ""
},
{
"docid": "4160227",
"text": "The Tower Division was a liberty, a historical form of local government, in the ancient county of Middlesex, England. It was also known as the Tower Hamlets, and took its name from being under the special jurisdiction of the Constable of the Tower of London. The name \"Tower Hamlets\" was subsequently used for the London Borough of Tower Hamlets created in 1965.",
"title": ""
},
{
"docid": "3870363",
"text": "Galahad is a hamlet in east-central Alberta, Canada within Flagstaff County. It is located just a few miles north of the Battle River valley on a former Canadian National rail line. The hamlet was originally incorporated as a village on May 5, 1918. It dissolved to become a hamlet under the jurisdiction of Flagstaff County on January 1, 2016.",
"title": ""
},
{
"docid": "26218034",
"text": "Guilderland is a hamlet of the town of the same name in Albany County, New York.",
"title": ""
},
{
"docid": "30558057",
"text": "Malmsmead is a hamlet on the border between the English counties of Devon and Somerset. The nearest town is Lynton, which lies approximately 4.7 mi west of the hamlet. The hamlet is situated in the Doone Valley within the Exmoor National Park.",
"title": ""
},
{
"docid": "5970997",
"text": "Childs is a hamlet in the town of Gaines in Orleans County, New York, United States. It is named after Judge Henry Childs and was previously known as \"Proctor's Corners\" and \"Fair Haven.\" Childs is the location of the Cobblestone Historic District that was listed on the National Register of Historic Places and designated a National Historic Landmark in 1993.",
"title": ""
},
{
"docid": "127198",
"text": "Pierrepont (traditionally spelled Pierpont) is a town and hamlet in St. Lawrence County, New York, in the United States. As of the 2010 census, the town population was 2,589. It was named after Hezekiah Pierrepont, the early owner of much of the town's territory. The Town of Pierrepont is centrally located in the county and is southeast of Canton. A hamlet of the same name is in the town of Pierrepont. Pierrepont Manor, however, is located in Jefferson County.",
"title": ""
},
{
"docid": "38016337",
"text": "Totmonslow is a hundred in the county of Staffordshire, England. The hundred is located in the north-east of Staffordshire, named after the hamlet of the same name, which is ½ mile east of Draycott in the Moors. The hamlet was anciently the seat of the hundred court.",
"title": ""
},
{
"docid": "27917332",
"text": "Fingland is a hamlet in the Allerdale District, in the county of Cumbria. Fingland is located on the B5307 road in between the villages of Kirkbride and Kirkbampton. There is a farm called Fingland Rigg nearby, which gives its name to Fingland Rigg National Nature Reserve.",
"title": ""
},
{
"docid": "17425837",
"text": "Breakabeen is a hamlet in the town of Fulton in Schoharie County, New York, United States. This hamlet played a role during the American Revolution and is home to a historic cemetery. Breakabeen is one of the hamlets that are situated in the Schoharie Valley. A number of structures in the hamlet are included in the Breakabeen Historic District, listed on the National Register of Historic Places in 1974.",
"title": ""
},
{
"docid": "18777303",
"text": "Kollektivtrafikförvaltningen UL (formerly Upplands Lokaltrafik until 1 January 2012) is the integrated transport authority (Swedish: \"Trafikhuvudman\" ) responsible for public transport buses and trains at the county level (Swedish: \"länstrafik\" ) in Uppsala County, Sweden. Their name is derived from the historical province of Uppland, which included the modern county along with part of what is now Stockholm County.",
"title": ""
}
] |
PLAIN-2774
|
Flaxseeds For Sensitive Skin
|
[
{
"docid": "MED-4658",
"text": "Skin functions and structure are significantly influenced by nutrients. Antioxidants protect the supportive layer of the skin against any damaging irradiation effects and the action of free radicals. A lack of suitable methods means that the pharmacokinetic properties of systemically applied carotenoids transferred into the skin remain poorly understood. In this study, a natural kale extract or placebo oil were given orally to 22 healthy volunteers for 4 weeks. Carotenoid bioaccessibility was evaluated using non-invasive resonance Raman spectroscopy on the palm and forehead skin. For the analysis of the blood serum, the standard HPLC method was used. The blood and skin levels of the carotenoids increased significantly during the study but compared to the blood serum values, increases in skin were delayed and depended on the dermal area as well as on the carotenoid. Lycopene, measured as being low in the extract, increases more in the skin compared to the blood indicating that the natural mixture of the extract stabilizes the antioxidative network in the skin. After supplementation had ended, the carotenoids decreased much faster in the blood than in the skin. The delayed decrease in the skin may indicate a peripheral buffer function of the skin for carotenoids. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Bioavailability of natural carotenoids in human skin compared to blood."
},
{
"docid": "MED-4396",
"text": "There has been a remarkable paucity of evidence for an association between diet and acne. Our previous studies suggest that there is an association between milk intake and teenage acne. This is a prospective cohort study to evaluate that relationship. We studied 6,094 girls, aged 9-15 years in 1996, who reported dietary intake on up to three food frequency questionnaires from 1996 to 1998. Presence and severity of acne was assessed by questionnaire in 1999. We computed multivariate prevalence ratios (PR) and 95 percent confidence intervals for acne. After accounting for age at baseline, height and energy intake, the multivariate PRs (95 % CI; p-value for test of trend) for acne comparing highest (2 or more servings per day) to lowest (<1 per week) intake categories in 1996, were 1.20 (1.09, 1.31; <0.001) for total milk, 1.19 (1.06, 1.32; <0.001) for whole milk, 1.17 (1.04, 1.31; 0.002) for low fat milk and 1.19 (1.08, 1.31; <0.001) for skim milk. This result did not change appreciably when we excluded girls who reported use of contraceptives and when we restricted our analysis to those younger than 11 years of age at baseline. We found a positive association between intake of milk and acne. This finding supports earlier studies and suggests that the metabolic effects of milk are sufficient to elicit biological responses in consumers.",
"title": "Milk consumption and acne in adolescent girls."
},
{
"docid": "MED-3867",
"text": "Although high alpha-linolenic acid flaxseed (Linum usitatissimum) is one of the richest dietary sources of alpha-linolenic acid and is also a good source of soluble fibre mucilage, it is relatively unstudied in human nutrition. Healthy female volunteers consumed 50 g ground, raw flaxseed/d for 4 weeks which provided 12-13% of energy intake (24-25 g/100 g total fat). Flaxseed raised alpha-linolenic acid and long-chain n-3 fatty acids in both plasma and erythrocyte lipids, as well as raising urinary thiocyanate excretion 2.2-fold. Flaxseed also lowered serum total cholesterol by 9% and low-density-lipoprotein-cholesterol by 18%. Changes in plasma alpha-linolenic acid were equivalent when 12 g alpha-linolenic acid/d was provided as raw flaxseed flour (50 g/d) or flaxseed oil (20 g/d) suggesting high bioavailability of alpha-linolenic acid from ground flaxseed. Test meals containing 50 g carbohydrate from flaxseed or 25 g flaxseed mucilage each significantly decreased postprandial blood glucose responses by 27%. Malondialdehyde levels in muffins containing 15 g flaxseed oil or flour/kg were similar to those in wheat-flour muffins. Cyanogenic glycosides (linamarin, linustatin, neolinustatin) were highest in extracted flaxseed mucilage but were not detected in baked muffins containing 150 g flaxseed/kg. We conclude that up to 50 g high-alpha-linolenic acid flaxseed/d is palatable, safe and may be nutritionally beneficial in humans by raising n-3 fatty acids in plasma and erythrocytes and by decreasing postprandial glucose responses.",
"title": "High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans."
},
{
"docid": "MED-3853",
"text": "PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.",
"title": "Serum enterolactone and prognosis of postmenopausal breast cancer."
},
{
"docid": "MED-3868",
"text": "OBJECTIVE: To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control, n-3 fatty acid status, anthropometrics, and adipokines in individuals with type 2 diabetes. DESIGN: Thirty-four participants were randomized into a parallel, controlled trial. SUBJECTS: The participants were adults with type 2 diabetes (age 52.4 +/- 1.5 years, body mass index 32.4 +/- 1.0 kg/m(2), n = 17 men and 17 women). INTERVENTIONS: Participants consumed a selection of bakery products containing no flax (control group [CTL], n = 9), milled flaxseed (FXS, n = 13; 32 g/d), or flaxseed oil (FXO, n = 12; 13 g/d) daily for 12 weeks. The FXS and FXO groups received equivalent amounts of alpha-linolenic acid (ALA; 7.4 g/day). MEASURES OF OUTCOME: The primary outcome measures were fasting plasma hemoglobin A(1c), glucose, insulin, and phospholipid fatty acid composition. The secondary outcome measures were fasting circulating leptin and adiponectin, as well as body weight, body mass index, and waist circumference. Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed. RESULTS: The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids (ALA, eicosapentaenoic acid [EPA], or decosapentaenoic acid [DPA], but not docosahexaenoic acid), and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group. All groups had similar caloric intakes; however, the CTL group experienced a 4% weight gain compared to baseline (p < 0.05), while both flax groups had constant body weights during the study period. All other parameters, including glycemic control, were unchanged by dietary treatment. CONCLUSIONS: Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes. Possible prevention of weight gain by flax consumption warrants further investigation.",
"title": "Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type ..."
},
{
"docid": "MED-3863",
"text": "The phenomenon of 'sensitive skin' is a relatively recent complaint in which certain individuals report more intense and frequent adverse sensory effects than the normal population upon use of cosmetic (personal-care) products. Originally defined as a minority complaint, sensitive skin is now claimed by a majority of women in industrialized countries and nearly half of men. Sensitive skin is self-diagnosed and typically unaccompanied by any obvious physical signs of irritation, and the number of individuals who claim sensitivity has risen steadily with the number of consumer products targeted towards this supposedly uncommon group. Believed by many dermatologists, therefore, to be a 'princess and the pea' phenomenon, the problem of sensitive skin has largely avoided focussed research. Over the last few years, however, the evidence of documentable biophysical changes associated with the largely sensory symptoms of this disorder has accumulated, including some gained by improved methods of identifying subclinical signs of skin irritation. Although the understanding of the aetiology of this phenomenon is as yet incomplete, existing research now supports a biophysical origin for this disorder. Effective methods of diagnosis, intrinsic and extrinsic contributors to exaggerated neural sensitivity, and the specific mechanisms of the discomfort associated with the compliant are required, as are appropriate means of prevention and treatment.",
"title": "Sensitive skin: closing in on a physiological cause."
},
{
"docid": "MED-4094",
"text": "BACKGROUND: Evidence from case-control studies suggest that dietary fiber may be inversely related to breast cancer risk, but it is unclear if this is supported by prospective data. We conducted a systematic review and meta-analysis of the evidence from prospective studies. METHODS: PubMed was searched for prospective studies of fiber intake and breast cancer risk until 31st August 2011. Random effects models were used to estimate summary relative risks (RRs). RESULTS: Sixteen prospective studies were included. The summary RR for the highest versus the lowest intake was 0.93 [95% confidence interval (CI) 0.89-0.98, I(2) = 0%] for dietary fiber, 0.95 (95% CI 0.86-1.06, I(2) = 4%) for fruit fiber, 0.99 (95% CI 0.92-1.07, I(2) = 1%) for vegetable fiber, 0.96 (95% CI 0.90-1.02, I(2) = 5%) for cereal fiber, 0.91 (95% CI 0.84-0.99, I(2) = 7%) for soluble fiber and 0.95 (95% CI 0.89-1.02, I(2) = 0%) for insoluble fiber. The summary RR per 10 g/day of dietary fiber was 0.95 (95% CI 0.91-0.98, I(2) = 0%, P(heterogeneity) = 0.82). In stratified analyses, the inverse association was only observed among studies with a large range (≥13 g/day) or high level of intake (≥25 g/day). CONCLUSION: In this meta-analysis of prospective studies, there was an inverse association between dietary fiber intake and breast cancer risk.",
"title": "Dietary fiber and breast cancer risk: a systematic review and meta-analysis of prospective studies."
},
{
"docid": "MED-4154",
"text": "Daily diet may have implications for skin ageing. However, data on the relationship between diet and the parameters of skin conditions are scarce. The present study aimed to examine the associations of biophysical properties of the skin of women with intakes of fats and antioxidant micronutrients as well as food groups as sources of these nutrients. In a cross-sectional study, we measured the hydration, surface lipids and elasticity of the skin of 716 Japanese women using non-invasive techniques. The extent of facial wrinkles in the crow's-foot area was determined by observation using the Daniell scale. Each subject's usual diet was determined with the use of a validated FFQ. After controlling for covariates including age, smoking status, BMI and lifetime sun exposure, the results showed that higher intakes of total fat, saturated fat and monounsaturated fat were significantly associated with increased skin elasticity. A higher intake of green and yellow vegetables was significantly associated with a decreased Daniell wrinkling score. Intake of saturated fat was significantly inversely associated with the Daniell wrinkling score after additional adjustment for green and yellow vegetable intake. Further studies with more accurate measurement methods are needed to investigate the role of daily diet in skin ageing.",
"title": "Association of dietary fat, vegetables and antioxidant micronutrients with skin ageing in Japanese women."
},
{
"docid": "MED-3869",
"text": "Diabetes mellitus is characterized by hyperglycemia and associated with aberrations in the metabolism of carbohydrate, protein, and lipid that result in development of secondary complications. Extensive studies have indicated that nutritional therapy plays a pivotal role in the controlling or postponing of development of these secondary complications. Several functional foods have been shown to possess hypoglycemic and hypolipidemic properties. Flax seed (FS) is a functional food that is rich in omega 3 fatty acids and antioxidants and is low in carbohydrates. In exploratory studies, FS was incorporated in recipes, which resulted in a reduction in the glycemic index of the food items. These observations prompted us to investigate the efficacy of FS supplementation in type 2 diabetics (n = 29). Subjects were assigned to the experimental (n = 18) or the control group (n = 11) on the basis of their desire to participate in the study. The experimental group's diet was supplemented daily with 10 g of FS powder for a period of 1 month. The control group received no supplementation or placebo. During the study, diet and drug intake of the subjects remained unaltered. The efficacy of supplementation with FS was evaluated through a battery of clinico-biochemical parameters. Supplementation with FS reduced fasting blood glucose by 19.7% and glycated hemoglobin by 15.6%. A favorable reduction in total cholesterol (14.3%), triglycerides (17.5%), low-density lipoprotein cholesterol (21.8%), and apolipoprotein B and an increase in high-density lipoprotein cholesterol (11.9%) were also noticed. These observations suggest the therapeutic potential of FS in the management of diabetes mellitus.",
"title": "An open-label study on the effect of flax seed powder (Linum usitatissimum) supplementation in the management of diabetes mellitus."
},
{
"docid": "MED-3864",
"text": "BACKGROUND: Skin sensitivity is a common problem in the Western population correlated with changes of skin properties like skin barrier function, hydration and skin physiology. Skin properties can be modulated by dietary fatty acids (FA), especially poly-unsaturated FA. The present study was performed to evaluate the effect of daily supplementation with flaxseed oil and safflowerseed oil on healthy volunteers with sensitive skin. METHODS: The study was designed as a randomized, double-blind 12-week intervention with 2 female treatment groups (n = 13). Plasma FA profile, skin sensitivity, skin hydration, transepidermal water loss (TEWL) and skin surface were evaluated on day 0, week 6 and week 12. RESULTS: Supplementation with flaxseed oil led to significant decreases in sensitivity (after nicotinate irritation), TEWL, skin roughness and scaling, while smoothness and hydration were increased. Concomitantly, the ratio of n-6/n-3 FA in plasma decreased. Upon supplementation with safflowerseed oil, only a significant improvement in skin roughness and hydration was observed; however, the effects were less pronounced and determined at a later point in time than with flaxseed oil. The plasma n-6/n-3 FA ratio increased. CONCLUSION: The data provide evidence that daily intake of flaxseed oil modulates skin condition. Copyright © 2010 S. Karger AG, Basel.",
"title": "Supplementation of flaxseed oil diminishes skin sensitivity and improves skin barrier function and condition."
},
{
"docid": "MED-3876",
"text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.",
"title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom."
},
{
"docid": "MED-3878",
"text": "Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.",
"title": "Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer"
},
{
"docid": "MED-4160",
"text": "CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.",
"title": "Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized cont..."
},
{
"docid": "MED-3860",
"text": "Purpose Evaluate the hypothesis that relation of breast cancer associated with dietary fiber intakes varies by type of fiber, menopausal, and the tumor’s hormone receptor status. Methods A case-control study of female breast cancer was conducted in Connecticut. A total of 557 incident breast cancer cases and 536 age frequency-matched controls were included in the analysis. Information on dietary intakes was collected through in-person interviews with a semi-quantitative food frequency questionnaire and was converted into nutrient intakes. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression. Results Among pre-menopausal women, higher intake of soluble fiber (highest versus lowest quartile of intake) was associated with a significantly reduced risk of breast cancer (OR = 0.38, 95% CI, 0.15–0.97, Ptrend = 0.08). When further restricted to pre-menopausal women with ER− tumors, the adjusted OR for the highest quartile of intake was 0.15 (95% CI, 0.03–0.69, Ptrend = 0.02) for soluble fiber intake. Among post-menopausal women, no reduced risk of breast cancer was observed for either soluble or insoluble fiber intakes or among ER+ or ER− tumor groups. Conclusions The results from this study show that dietary soluble fiber intake is associated with a significantly reduced risk of ER− breast cancer among pre-menopausal women. Additional studies with larger sample size are needed to confirm these results.",
"title": "Dietary fiber intake and risk of breast cancer by menopausal and estrogen receptor status"
},
{
"docid": "MED-3862",
"text": "We conducted a combined analysis of the original data to evaluate the consistency of 12 case-control studies of diet and breast cancer. Our analysis shows a consistent, statistically significant, positive association between breast cancer risk and saturated fat intake in postmenopausal women (relative risk for highest vs. lowest quintile, 1.46; P less than .0001). A consistent protective effect for a number of markers of fruit and vegetable intake was demonstrated; vitamin C intake had the most consistent and statistically significant inverse association with breast cancer risk (relative risk for highest vs. lowest quintile, 0.69; P less than .0001). If these dietary associations represent causality, the attributable risk (i.e., the percentage of breast cancers that might be prevented by dietary modification) in the North American population is estimated to be 24% for postmenopausal women and 16% for premenopausal women.",
"title": "Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies."
},
{
"docid": "MED-4158",
"text": "Background Postmenopausal conjugated equine estrogens (CEE) therapies increase the risk of cognitive impairment in women aged 65 years or older and are associated with smaller regional brain volumes; however, the link between these two phenomena has not been established. Methods Standardized magnetic resonance imaging was performed on 1,403 women, 1–4 years after they had participated in randomized placebo-controlled clinical trials of CEE-based therapies. Women included in this report were aged 65–80 years and free of dementia and mild cognitive impairment (MCI) when originally enrolled in the trials, which lasted an average of 4–6 years and were conducted at 14 academic U.S. medical centers. The associations that regional brain volumes and ischemic lesion volumes had with the development of cognitive impairment (i.e., dementia or MCI) were contrasted between treatment groups using analyses of covariance. Results Fifty-three women developed MCI or probable dementia during follow-up. Among women who had been prescribed CEE-based therapies, cognitive impairment was associated with relatively smaller hippocampal (p = .0002) and total brain volumes (p = .03). Qualitatively, these associations appeared to be independent of their level of pretreatment cognitive function. Among women who had been prescribed placebo, these relationships were not evident; instead, cognitive impairment was associated with greater ischemic lesion volume in the frontal lobe (p = .007) and overall (p = .02). Conclusion A mechanism by which CEE-based postmenopausal hormone therapy induces cognitive impairment appears to be through increased brain atrophy.",
"title": "Brain Volumes, Cognitive Impairment, and Conjugated Equine Estrogens"
},
{
"docid": "MED-4161",
"text": "We assessed the significance and nature of delusions in frontotemporal lobar degeneration (FTLD), an important cause of young-onset dementia with prominent neuropsychiatric features that remain incompletely characterised. The case notes of all patients meeting diagnostic criteria for FTLD attending a tertiary level cognitive disorders clinic over a three year period were retrospectively reviewed and eight patients with a history of delusions were identified. All patients underwent detailed clinical and neuropsychological evaluation and brain MRI. The diagnosis was confirmed pathologically in two cases. The estimated prevalence of delusions was 14 %. Delusions were an early, prominent and persistent feature. They were phenomenologically diverse; however paranoid and somatic delusions were prominent. Behavioural variant FTLD was the most frequently associated clinical subtype and cerebral atrophy was bilateral or predominantly right-sided in most cases. We conclude that delusions may be a clinical issue in FTLD, and this should be explored further in future work.",
"title": "Delusions in frontotemporal lobar degeneration"
},
{
"docid": "MED-3874",
"text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.",
"title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery"
},
{
"docid": "MED-3877",
"text": "OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.",
"title": "Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen."
},
{
"docid": "MED-3841",
"text": "Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a greater than 3-fold increase in 5 year risk, and baseline Ki-67 ≥2% in areas of hyperplasia in breast tissue sampled by random periareolar fine needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG 50 mg daily was given for 12 months, followed by repeat RPFNA. The primary endpoint was change in Ki-67. Secondary endpoints included change in cytomorphology, mammographic breast density, serum bioavailable estradiol, and testosterone IGF-I and IGFBP-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased ~ 9-fold, and total lignans 16 fold. Thirty-six (80%) of the 45 evaluable subjects demonstrated a decrease in Ki-67, from a median of 4% (range 2–16.8 %) to 2% (range 0–15.2%) (p<0.001 by Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (p=0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG vs. placebo in premenopausal women.",
"title": "Reduction in Ki-67 in Benign Breast Tissue of High Risk Women with the Lignan Secoisolariciresinol Diglycoside (SDG)"
},
{
"docid": "MED-3866",
"text": "Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.",
"title": "Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design"
},
{
"docid": "MED-3875",
"text": "BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.",
"title": "Effect of mammalian lignans on the growth of prostate cancer cell lines."
},
{
"docid": "MED-4157",
"text": "Although improvement in long-term health is no longer an indication for menopausal hormone therapy, evidence supporting fewer adverse events in younger women, combined with its high overall effectiveness, has reinforced its usefulness for short-term treatment of menopausal symptoms. Menopausal therapy has been provided not only by commercially available products but also by compounding, or creation of an individualized preparation in response to a health care provider's prescription to create a medication tailored to the specialized needs of an individual patient. The Women's Health Initiative findings, coupled with an increase in the direct-to-consumer marketing and media promotion of compounded bioidentical hormonal preparations as safe and effective alternatives to conventional menopausal hormone therapy, have led to a recent increase in the popularity of compounded bioidentical hormones as well as an increase in questions about the use of these preparations. Not only is evidence lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy, but these claims also pose the additional risks of variable purity and potency and lack efficacy and safety data. The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists and the Practice Committee of the American Society for Reproductive Medicine provide an overview of the major issues of concern surrounding compounded bioidentical menopausal hormone therapy and provide recommendations for patient counseling. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.",
"title": "Compounded bioidentical menopausal hormone therapy."
},
{
"docid": "MED-3865",
"text": "INTRODUCTION: Sensitive skin is a complex dermatological condition, defined by abnormal sensory symptoms. The aim of this epidemiological survey was to assess the prevalence of sensitive skin and collect data on sensitive skin in the US population. METHODS: A phone survey was conducted in the USA by a poll institute in 2007. A sample was drawn from a representative national cohort of the American population at least 18years of age through the quota method. Data on demographic characteristics, environmental and climatic factors, skin characteristics, dermatological disorders, cosmetics use, and visits to the dermatologist were collected. RESULTS: Of 994 subjects who answered (495 men and 499 women), 44.6% declared having \"sensitive\" or \"very sensitive\" skin. Women were more concerned than men (50.9% vs. 38.2%, P<0.0001). There was no significant difference related to geographic localization, age, or ethnic distribution. Subjects with sensitive skin had mainly dry (34.5%) or mixed skin (35.7%), fair phototypes, dermatological disorders, higher skin reactivity to cosmetics and various environmental factors in comparison with subjects who stated having only a \"slightly\" sensitive or not sensitive skin. The dermatologist had a strong influence on subjects with \"sensitive\" or \"very sensitive\" skin through the prescription of skin care products. CONCLUSION: This study, based on a representative sample of the American population, reveals a high prevalence of sensitive skin in the USA. Sensitive skin is mainly associated with dry skin, fair phototype, reactivity to climatic and environmental factors, and cosmetics. American dermatologists seem largely involved in the care of this condition. © 2011 The International Society of Dermatology.",
"title": "Sensitive skin in the American population: prevalence, clinical data, and role of the dermatologist."
},
{
"docid": "MED-4313",
"text": "BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 μg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.",
"title": "A vegetarian dietary pattern as a nutrient-dense approach to weight management: an analysis of the national health and nutrition examination survey..."
},
{
"docid": "MED-4659",
"text": "Numerous researchers have examined the effects of skin condition, including texture and color, on the perception of health, age, and attractiveness in human faces. They have focused on facial color distribution, homogeneity of pigmentation, or skin quality. We here investigate the role of overall skin color in determining perceptions of health from faces by allowing participants to manipulate the skin portions of color-calibrated Caucasian face photographs along CIELab color axes. To enhance healthy appearance, participants increased skin redness (a*), providing additional support for previous findings that skin blood color enhances the healthy appearance of faces. Participants also increased skin yellowness (b*) and lightness (L*), suggesting a role for high carotenoid and low melanin coloration in the healthy appearance of faces. The color preferences described here resemble the red and yellow color cues to health displayed by many species of nonhuman animals.",
"title": "Facial Skin Coloration Affects Perceived Health of Human Faces"
},
{
"docid": "MED-3834",
"text": "Dietary lignan intakes have been associated with reduced breast cancer risks; however, no previous studies have investigated whether lignan intake might be associated with breast cancer survival. We examined the association of dietary lignan intakes with survival in 1122 women with primary, incident, histologically confirmed breast cancer identified between 1996 and 2001, and with vital status determined through December 31, 2006. Diet in the 12–24 months before diagnosis was assessed with an extensive food frequency questionnaire, and potential confounders assessed from an extensive epidemiologic interview and abstracted clinical data. Lignan intake was calculated using published food composition data. Hazard ratios (HR), and 95% confidence intervals (CIs) for dietary lignan intakes with all cause, and breast cancer mortality were estimated using Cox proportional hazards adjusting for age, education, race, total energy intake, tumor stage, and body mass index. Of the 1122 women with complete dietary data, 160 had died by the end of follow-up. Among postmenopausal women only, those in the highest versus lowest quartile of lignan intakes had a statistically significant reduction in the risk of all cause mortality (HR 0.49, 95% CI 0.26–0.91) and a significantly reduced risk of breast cancer mortality (HR 0.29, 95% CI 0.11–0.76). Higher intakes of dried beans (HR 0.61, 95% CI 0.36–1.03), but not fruits, vegetables, or grains, were also weakly associated with overall mortality. In summary, our results suggest that higher lignan intakes may be associated with improved survival among postmenopausal women with breast cancer.",
"title": "Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study"
},
{
"docid": "MED-3845",
"text": "We previously demonstrated that high serum enterolactone levels are associated with a reduced incidence of breast cancer in healthy women. The present study was aimed at investigating whether a similar association might be found between serum enterolactone levels and the mortality of women with early breast cancer. The levels of enterolactone in cryopreserved serum aliquots obtained from 300 patients, operated on for breast cancer, were measured using a time-resolved fluoro-immunoassay. Levels were analyzed in respect to the risk of mortality following surgery. Cox proportional hazard regression models were used to check for prognostic features, to estimate hazard ratios for group comparisons and to test for the interaction on mortality hazards between the variables and enterolactone concentrations. The Fine and Gray competing risk proportional hazard regression model was used to predict the probabilities of breast cancer-related and breast cancer-unrelated mortalities. At a median follow-up time of 23 years (range 0.6-26.1), 180 patients died, 112 of whom died due to breast cancer-related events. An association between a decreased mortality risk and enterolactone levels ≥ 10 nmol/l was found in respect to both all-cause and breast cancer-specific mortality. The difference in mortality hazards was statistically significant, but it appeared to decrease and to lose significance after the first 10 years, though competing risk analysis showed that breast cancer-related mortality risk remained constantly lower in those patients with higher enterolactone levels. Our findings are consistent with those of most recent literature and provide further evidence that mammalian lignans might play an important role in reducing all-cause and cancer-specific mortality of the patients operated on for breast cancer.",
"title": "Serum enterolactone levels and mortality outcome in women with early breast cancer: a retrospective cohort study."
},
{
"docid": "MED-4398",
"text": "BACKGROUND: Previous studies suggest possible associations between Western diet and acne. We examined data from the Nurses Health Study II to retrospectively evaluate whether intakes of dairy foods during high school were associated with physician-diagnosed severe teenage acne. METHODS: We studied 47,355 women who completed questionnaires on high school diet in 1998 and physician-diagnosed severe teenage acne in 1989. We estimated the prevalence ratios and 95% confidence intervals of acne history across categories of intakes. RESULTS: After accounting for age, age at menarche, body mass index, and energy intake, the multivariate prevalence ratio (95% confidence intervals; P value for test of trend) of acne, comparing extreme categories of intake, were: 1.22 (1.03, 1.44; .002) for total milk; 1.12 (1.00, 1.25; .56) for whole milk; 1.16 (1.01, 1.34; .25) for low-fat milk; and 1.44 (1.21, 1.72; .003) for skim milk. Instant breakfast drink, sherbet, cottage cheese, and cream cheese were also positively associated with acne. CONCLUSION: We found a positive association with acne for intake of total milk and skim milk. We hypothesize that the association with milk may be because of the presence of hormones and bioactive molecules in milk.",
"title": "High school dietary dairy intake and teenage acne."
},
{
"docid": "MED-4162",
"text": "Large numbers of US women stopped taking hormone therapies (HT), especially estrogen/progestin (EP) formulations, after the Women's Health Initiative trial detected elevated risks of breast cancer in EP users and was halted in July 2002. Recent reports have indicated substantial and significant declines in population-based breast cancer incidence, particularly hormone-sensitive forms, for 2003 and 2004. Are these events linked? This commentary considers the available evidence linking the mass cessation of HT in 2002 to the breast cancer incidence declines of 2003/2004 and quantifies the potential impact of the cessation on the overall burden of breast cancer in the US.",
"title": "Declines in breast cancer after the WHI: apparent impact of hormone therapy."
},
{
"docid": "MED-4159",
"text": "CONTEXT: The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA). OBJECTIVE: To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers. INTERVENTIONS: In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos. MAIN OUTCOME MEASURES: Probable dementia and MCI. RESULTS: In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04). CONCLUSIONS: Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.",
"title": "Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Mem..."
},
{
"docid": "MED-4233",
"text": "OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.",
"title": "Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l..."
},
{
"docid": "MED-3858",
"text": "BACKGROUND: Observational and preclinical studies suggest that dietary fiber intake may reduce the risk of breast cancer, but the results are inconclusive. OBJECTIVE: We aimed to examine the association between dietary fiber intake and risk of breast cancer by conducting a meta-analysis of prospective cohort studies. DESIGN: Relevant studies were identified by a PubMed database search through January 2011. Reference lists from retrieved articles were also reviewed. We included prospective cohort studies that reported RRs with 95% CIs for the association between dietary fiber intake and breast cancer risk. Both fixed- and random-effects models were used to calculate the summary risk estimates. RESULTS: We identified 10 prospective cohort studies of dietary fiber intake and risk of breast cancer involving 16,848 cases and 712,195 participants. The combined RR of breast cancer for the highest compared with the lowest dietary fiber intake was 0.89 (95% CI: 0.83, 0.96), and little evidence of heterogeneity was observed. The association between dietary fiber intake and risk of breast cancer did not significantly differ by geographic region, length of follow-up, or menopausal status of the participants. Omission of any single study had little effect on the combined risk estimate. Dose-response analysis showed that every 10-g/d increment in dietary fiber intake was associated with a significant 7% reduction in breast cancer risk. Little evidence of publication bias was found. CONCLUSION: This meta-analysis provides evidence of a significant inverse dose-response association between dietary fiber intake and breast cancer risk.",
"title": "Dietary fiber intake and risk of breast cancer: a meta-analysis of prospective cohort studies."
}
] |
[
{
"docid": "MED-1879",
"text": "The study hypothesis was that fasting glucose, insulin, fructosamine, C-reactive protein, and interleukin-6 decrease and adiponectin increases with daily flaxseed consumption in overweight or obese individuals with pre-diabetes. In this randomized, cross-over study overweight or obese men and postmenopausal women (n = 25) with pre-diabetes consumed 0, 13, or 26 g ground flaxseed for 12 weeks. Glucose, insulin, homeostatic model assessment (HOMA-IR), and normalized percent of α-linolenic fatty acid (ALA) were significantly different by treatment (multiple analysis of variance, P = .036, P = .013, P = .008, P = .024 respectively). Paired t tests showed glucose decreased on the 13 g intervention compared to the 0 g period [13 g = -2.10 ± 1.66 mg/L (mean ± SEM), 0 g = 9.22 ± 4.44 mg/L, P = .036]. Insulin decreased on the 13 g intervention but not the 26 g (P = .021) and 0 g (P = .013) periods (13 g = -2.12 ± 1.00 mU/L, 26 g = 0.67 ± 0.84 mU/L, 0 g = 1.20 ± 1.16 mU/L). HOMA-IR decreased on the 13 g period but not on the 26 g (P = .012) and 0 g (P = .008) periods (13 g = -0.71 ± 0.31, 26 g = 0.27 ± 0.24, 0 g = 0.51 ± 0.35). The α-linolenic fatty acid decrease for the 0 g period was different than the 13 g (P = .024) and 26 g (P = .000) periods (13 g = 0.20 ± 0.04, 26 g = 0.35 ± 0.07, 0 g = -0.01 ± 0.07). Fructosamine, high sensitivity C-reactive protein, adiponectin, and high-sensitivity interleukin-6 had no significant differences. Flaxseed intake decreased glucose and insulin and improved insulin sensitivity as part of a habitual diet in overweight or obese individuals with pre-diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Daily flaxseed consumption improves glycemic control in obese men and women with pre-diabetes: a randomized study."
},
{
"docid": "MED-2445",
"text": "Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.",
"title": "Dietary polyphenols in the prevention and treatment of allergic diseases."
},
{
"docid": "MED-2345",
"text": "Anisakis simplex is a parasite that, if present in uncooked and contaminated saltwater fish, can invade the human gut. Two different clinical situations are recognized: the first, known as a gastrointestinal disease, varying from an asymptomatic episode to vomiting and diarrhea, and the second, classified as an adverse reaction to food, characterized by a wide spectrum of allergic reactions like rhinitis, conjunctivitis, or even anaphylaxis causing hypotension and/or shock. The intestinal epithelium, the major defense system against external molecules, represents an open gate for toxins and allergens if its protective function is compromised. Previous data have demonstrated a strict relationship between an altered intestinal permeability (I.P.) and worsening of the clinical manifestations in patients with adverse reactions to the food. In this article we evaluated the sensitization to A. simplex among patients who referred clinical symptoms of allergy. All subjects underwent commonly used alimentary skin prick test for food allergens, to which Ani s1, an A. simplex allergen, was added. In addition, in A. simplex-sensitized subjects, I.P. was determined upon their enrolment to the study (time 0) and after 6 months of consuming a raw fish-free diet (time 6). Five hundred and forty subjects were screened, and 170 had a positive skin prick test, 87 (51.2%) of whom were positive to Ani s1. Increased I.P. was evidenced in A. simplex-sensitized subjects with worse clinical symptoms, which receded after 6 months' elimination of raw seafood. With our data we demonstrated that the alimentary habit to eat raw fish represents a high risk for the integrity of the intestinal mucosa, and we suggest that this pathological situation may constitute an ideal, under-estimated, open gate for molecules that predispose to other, more important pathologies.",
"title": "Anisakiasis, an underestimated infection: effect on intestinal permeability of Anisakis simplex-sensitized patients."
},
{
"docid": "MED-1826",
"text": "PURPOSE: To investigate the association between intake of flaxseed-the richest source of dietary lignans (a class of phytoestrogens)-and breast cancer risk. METHODS: A food frequency questionnaire was used to measure the consumption of flaxseed and flax bread by 2,999 women with breast cancer and 3,370 healthy control women who participated in the Ontario Women's Diet and Health Study (2002-2003). Logistic regression was used to investigate associations between consumption of flaxseed and flax bread and breast cancer risk. Confounding by established and suspected breast cancer risk factors, as well as dietary factors, was assessed. RESULTS: Flaxseed or flax bread was consumed at least weekly by 21 % of control women. None of the 19 variables assessed were identified as confounders of the associations between flaxseed or flax bread and breast cancer risk. Consumption of flaxseed was associated with a significant reduction in breast cancer risk (odds ratio (OR) = 0.82, 95 % confidence interval (CI) 0.69-0.97), as was consumption of flax bread (OR = 0.77, 95 % CI 0.67-0.89). CONCLUSIONS: This Canadian study is, to our knowledge, the first to report on the association between flaxseed alone and breast cancer risk and has found that flaxseed intake is associated with a reduction in breast cancer risk. As dietary intake of flaxseed is modifiable, this finding may be of public health importance with respect to breast cancer prevention.",
"title": "Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk."
},
{
"docid": "MED-4443",
"text": "Flaxseed is one of the most important oilseed crops for industrial as well as food, feed, and fiber purposes. Almost every part of the flaxseed plant is utilized commercially, either directly or after processing. The stem yields good quality fiber having high strength and durability. The seed provides oil rich in omega-3, digestible proteins, and lignans. In addition to being one of the richest sources of α-linolenic acid oil and lignans, flaxseed is an essential source of high quality protein and soluble fiber and has considerable potential as a source of phenolic compounds. Flaxseed is emerging as an important functional food ingredient because of its rich contents of α-linolenic acid (ALA), lignans, and fiber. Lignans appear to be anti-carcinogenic compounds. The omega-3s and lignan phytoestrogens of flaxseed are in focus for their benefits for a wide range of health conditions and may possess chemo-protective properties in animals and humans. This paper presents a review of literature on the nutritional composition of flaxseed, its health benefits, and disease-prevention qualities, utilization of flaxseed for food, feed, and fiber, and processing of flaxseed.",
"title": "Flaxseed: a potential source of food, feed and fiber."
},
{
"docid": "MED-1494",
"text": "Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly different between the 2 groups at any time. SBP was ≈ 10 mm Hg lower, and DBP was ≈ 7 mm Hg lower in the flaxseed group compared with placebo after 6 months. Patients who entered the trial with a SBP ≥ 140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.",
"title": "Potent antihypertensive action of dietary flaxseed in hypertensive patients."
},
{
"docid": "MED-3836",
"text": "PURPOSE: Flaxseed, the richest source of mammalian lignan precursors, has previously been shown to reduce the growth of tumors in rats. This study examined, in a randomized double-blind placebo-controlled clinical trial, the effects of dietary flaxseed on tumor biological markers and urinary lignan excretion in postmenopausal patients with newly diagnosed breast cancer. EXPERIMENTAL DESIGN: Patients were randomized to daily intake of either a 25 g flaxseed-containing muffin (n = 19) or a control (placebo) muffin (n = 13). At the time of diagnosis and again at definitive surgery, tumor tissue was analyzed for the rate of tumor cell proliferation (Ki-67 labeling index, primary end point), apoptosis, c-erbB2 expression, and estrogen and progesterone receptor levels. Twenty-four-hour urine samples were analyzed for lignans, and 3-day diet records were evaluated for macronutrient and caloric intake. Mean treatment times were 39 and 32 days in the placebo and flaxseed groups, respectively. RESULTS: Reductions in Ki-67 labeling index (34.2%; P = 0.001) and in c-erbB2 expression (71.0%; P = 0.003) and an increase in apoptosis (30.7%; P = 0.007) were observed in the flaxseed, but not in the placebo group. No significant differences in caloric and macronutrient intake were seen between groups and between pre- and posttreatment periods. A significant increase in mean urinary lignan excretion was observed in the flaxseed group (1,300%; P < 0.01) compared with placebo controls. The total intake of flaxseed was correlated with changes in c-erbB2 score (r = -0.373; P = 0.036) and apoptotic index (r = 0.495; P < 0.004). CONCLUSION: Dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.",
"title": "Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer."
},
{
"docid": "MED-4885",
"text": "Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.",
"title": "Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery"
},
{
"docid": "MED-3842",
"text": "The mammalian lignans enterolactone and enterodiol, which are produced by the microflora in the colon of humans and animals from precursors in foods, have been suggested to have potential anticancer effects. This study determined the production of mammalian lignans from precursors in food bars containing 25 g unground whole flaxseed (FB), sesame seed (SB), or their combination (FSB; 12.5 g each). In a randomized crossover study, healthy postmenopausal women supplemented their diets with the bars for 4 wk each separated by 4-wk washout periods, and urinary mammalian lignan excretion was measured at baseline and after 4 wk as a marker of mammalian lignan production. Results showed an increase with all treatments (65.1-81.0 mumol/day; P < 0.0001), which did not differ among treatments. Lignan excretion with the whole flaxseed was similar to results of other studies using ground flaxseed. An unidentified lignan metabolite was detected after consumption of SB and FSB but not of FB. Thus, we demonstrated for the first time that 1) precursors from unground whole flaxseed and sesame seed are converted by the bacterial flora in the colon to mammalian lignans and 2) sesame seed, alone and in combination with flaxseed, produces mammalian lignans equivalent to those obtained from flaxseed alone.",
"title": "Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed."
},
{
"docid": "MED-1493",
"text": "Presence of omega-3, omega-6 rich oil, alpha-linoleic acid, dietary fibers, secoisolariciresinol diglucoside, protein and minerals in flaxseed constitute a very strong basis for the utilization of flaxseed in various food preparations as a curative agent. An extensive body of literature illustrates that flaxseed has gained a significant position in the domain of nutritional sciences owing to its pivotal role as an antioxidant agent. The review discusses at length, numerous health benefits of flaxseed typically focusing its preventive role against cardiovascular diseases, cancer, diabetes and enhancement of spatial memory. Massive increase in the size of population with a special emphasize to the developing countries, there is an urge for exploration of the alternative dietary resources that can meet the dietary and nutritional needs of forthcoming generations. With respect to its remarkable nutritional importance, the review in question enables researchers engaged in nutritional sciences to further investigate the therapeutic value of flaxseed functional components and their dietary application in various food products and availability in processed foods as well as in the human cell line.",
"title": "Flaxseed - a miraculous defense against some critical maladies."
},
{
"docid": "MED-1491",
"text": "The potential to increase n-3 fatty acid (FA) intake via flaxseed fed pork is underestimated when restricted to pure longissimus muscle, whereas a combination of muscle and adipose tissue is typically consumed. Presently, the FA content of pigs fed 0%, 5% and 10% dietary flaxseed for 11 weeks was measured in loin, picnic and butt primals (lean muscle with epimysium (L), L plus seam fat (LS), and LS plus 5 mm backfat (LSS)). The n-3 FA content necessary for an enrichment claim in Canada (300 mg/100 g serving) was exceeded in L from all primals when feeding 5% flaxseed, being 4 fold that of controls (P<0.001), with further enrichment from inclusion of associated adipose tissues (P<0.001). Increasing flaxseed feeding levels in combination with adipose tissue inclusion amplified total long chain n-3 FA (P<0.05), particularly 20:5n-3 and 22:5n-3. Flaxseed-fed n-3 FA enriched pork can contribute substantially to daily long chain n-3 FA intakes, particularly for societies with typically low seafood consumption. © 2013.",
"title": "Flaxseed fed pork: n-3 fatty acid enrichment and contribution to dietary recommendations."
},
{
"docid": "MED-2446",
"text": "BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.",
"title": "Dietary antioxidant intake, allergic sensitization and allergic diseases in young children."
},
{
"docid": "MED-5178",
"text": "Lignans, derived from flaxseed, are phyto-oestrogens being increasingly studied for their health benefits. An 8-week, randomised, double-blind, placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects, using treatments of 0 (placebo), 300 or 600 mg/d of dietary secoisolariciresinol diglucoside (SDG) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels. Significant treatment effects were achieved (P < 0.05 to < 0.001) for the decrease of total cholesterol (TC), LDL-cholesterol (LDL-C) and glucose concentrations, as well as their percentage decrease from baseline. At weeks 6 and 8 in the 600 mg SDG group, the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively (all P < 0.005 compared with placebo). For the 300 mg SDG group, only significant differences from baseline were observed for decreases of TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8, especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l (lowered 25.56 and 24.96 %; P = 0.015 and P = 0.012 compared with placebo, respectively). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan. The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED (r 0.128-0.302; P < 0.05 to < 0.001). In conclusion, dietary flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner.",
"title": "Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects."
},
{
"docid": "MED-3840",
"text": "The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.",
"title": "Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo"
},
{
"docid": "MED-2338",
"text": "BACKGROUND: Chronic urticaria (CU) may affect up to 1% of the general population. Anisakis simplex hypersensitivity is frequent in areas where raw fish is consumed and A. simplex allergy represents a relevant cause of acute urticaria. We assessed the possible association between CU and A. simplex sensitization in an area where marinated fish is very frequently eaten. METHODS: A thorough history of CU was sought in 919 adults seen at the Allergy Center, Bari. CU patients and 187 controls underwent skin-prick testing with a commercial extract of A. simplex, and reactors were recommended a 6-month raw-fish-free diet regimen. Responders were followed after a further 3 months. RESULTS: Of 919 subjects, 213 (23%) met the criteria for CU and 106/213 (49.7%) were sensitized to A. simplex with a significant difference between patients aged >65 or <65 years (56 vs. 41%, respectively; p < 0.05). All patients hypersensitive to A. simplex were regular consumers of marinated fish. In a control population without CU, the prevalence of A. simplex sensitization was 16% (p < 0.001). The 6-month diet regimen led to the disappearance of urticaria in 82/106 cases (77%) versus 1/42 (2%) subjects who did not change their dietary habits (p < 0.001). All nonresponders were sensitized to house-dust mites. Of 75 responders who were followed-up after 3 months, CU relapsed in 88% of those who had reintroduced raw fish versus 14% of those who were still on the diet (p < 0.001). CONCLUSION: In areas where raw or marinated fish is frequently eaten, A. simplex hypersensitivity is a frequent cause of CU. Copyright © 2012 S. Karger AG, Basel.",
"title": "Anisakis simplex hypersensitivity is associated with chronic urticaria in endemic areas."
},
{
"docid": "MED-3738",
"text": "The human health benefits from consumption of cranberry products have been associated with the fruits' unique flavonoid composition, including a complex profile of anthocyanins and proanthocyanidins. However, when processed by techniques such as pressing, canning, concentrating, or drying, a number of these natural components may be compromised or inactivated due to physical separation, thermal degradation, or oxidation. Fresh cranberries were compared to freeze-dried berries and individual fruit tissues (skin and peeled fruit). Products examined included cranberry juices (commercial and prepared from concentrate), cranberry sauces (commercial and homemade), and sweetened-dried cranberries (commercial). Freeze-drying resulted in no detectable losses of anthocyanins or proanthocyanidins from cranberry fruits. Anthocyanins were localized in the skin. Proanthocyanins were higher in the skin than in the flesh, with the exception of procyanidin A-2 dimer which was concentrated in the flesh. Anthocyanins were significantly higher in not-from-concentrate juice than in reconstituted juice from concentrate (8.3 mg and 4.2 mg/100 mL, respectively). Similarly, proanthocyanidins were markedly higher in not-from-concentrate juice compared to juice from concentrate (23.0 mg and 8.9 mg/100 mL, respectively). Homemade sauce contained far higher anthocyanins and proanthocyanidins (15.9 and 87.9 mg/100 g, respectively) than canned sauces processed with whole berries (9.6 and 54.4 mg/100 g, respectively) or jelled-type (1.1 and 16 mg/100 g, respectively). Sweetened-dried cranberries were quite low in anthocyanins (7.9 mg/100 g), but they still retained considerable proanthocyanidins (64.2 mg/100 g). Commercially processed products contained significantly lower levels of polyphenols as compared to fresh and home-processed preparations. Anthocyanins were more sensitive to degradation than proanthocyanidins. PRACTICAL APPLICATION: As cranberry juices and other products are increasingly consumed for their recognized health benefits (including prophylaxis against urinary tract infection), it is relevant to consider how various degrees of commercial and home processing can alter innate levels of the biologically active flavonoids (especially anthocyanins and proanthocyanidins) characteristic to the intact fruits. © 2012 Institute of Food Technologists®",
"title": "Comparison of health-relevant flavonoids in commonly consumed cranberry products."
},
{
"docid": "MED-5177",
"text": "The objective of this study was to evaluate, in a phase 2 pilot study, tolerability and the effect of 6 weeks of flaxseed therapy on hot flash scores in women not wishing to receive estrogen therapy. Eligibility included 14 hot flashes per week for at least 1 month. In the baseline week, participants took no study medication and documented the characteristics of their hot flashes. Thereafter, crushed flaxseed was administered at 40 g daily. Participants provided weekly toxicity reports and health-related quality of life information. The primary end point was a change in hot flash score prospectively reported in a daily hot flash diary. Thirty women were enrolled between June 17 and November 8, 2005. The mean decrease in hot flash scores after flaxseed therapy was 57% (median decrease 62%). The mean reduction in daily hot flash frequency was 50% (median reduction 50%), from 7.3 hot flashes to 3.6. Fourteen of the 28 participants (50%) experienced mild or moderate abdominal distention. Eight participants (29%) experienced mild diarrhea, one experienced flatulence, and six (21%) withdrew because of toxicities. This study suggests that dietary therapy decreases hot flash activity in women not taking estrogen therapy. This reduction is greater than what would be expected with placebo.",
"title": "Pilot evaluation of flaxseed for the management of hot flashes."
},
{
"docid": "MED-3846",
"text": "A HPLC method was developed for the analysis of secoisolariciresinol diglucoside (SDG) and hydroxycinnamic acid glucosides in milled defatted flaxseed flour. Direct extraction by 1 M NaOH for 1 h at 20 degrees C resulted in a higher yield than that obtained by hydrolysis of alcoholic extracts. An internal standard, o-coumaric acid, was used and the method was found to be easy, fast, and with good repeatability. On dry matter basis, different samples of flaxseeds varied considerably in their content of (+)-SDG (11.9-25.9 mg/g), (-)-SDG (2.2-5.0 mg/g), p-coumaric acid glucoside (1.2-8.5 mg/g), and ferulic acid glucoside (1.6-5.0 mg/g).",
"title": "High-performance liquid chromatographic analysis of secoisolariciresinol diglucoside and hydroxycinnamic acid glucosides in flaxseed by alkaline ex..."
},
{
"docid": "MED-2369",
"text": "Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.",
"title": "Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose"
},
{
"docid": "MED-5176",
"text": "A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from \"moderate/severe\" to \"mild\" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.",
"title": "Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia."
},
{
"docid": "MED-957",
"text": "Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to \"negative\" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)",
"title": "Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powde..."
},
{
"docid": "MED-2030",
"text": "Background Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86.",
"title": "An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity"
},
{
"docid": "MED-1495",
"text": "Response surface methodology was used to study the effect of flaxseed flour (FS) and tomato paste (TP) addition, from 0 to 10% and 0 to 20% respectively, on beef patty quality characteristics. The assessed quality characteristics were color (L, a, and b), pH and texture profile analysis (TPA). Also, sensory analysis was performed for the assessment of color, juiciness, firmness, and general acceptance. FS addition reduced L and a values and decreased weight loss of cooked products (P<0.05). An opposite effect was observed when TP was added (P<0.05). All TPA parameters decreased when percentages of FS and TP were increased in the formulation of beef patties. Furthermore, FS and TP addition adversely affected the sensory characteristics of the cooked product (P<0.05); nevertheless, all sensory characteristics evaluated had an acceptable score (>5.6). Thus FS and TP are ingredients that can be used in beef patty preparation. Copyright © 2014 Elsevier Ltd. All rights reserved.",
"title": "Response surface methodology for predicting quality characteristics of beef patties added with flaxseed and tomato paste."
},
{
"docid": "MED-5179",
"text": "OBJECTIVE: Alpha-linolenic acid (ALA) is the natural precursor of the cardioprotective long-chain n-3 fatty acids. Available data indicate a possible beneficial effect of ALA on cardiovascular disease (CVD), but the response of various CVD risk factors to increased ALA intake is not well characterized. The purpose of the present study was to examine the effect of increased ALA intake on blood pressure in man. DESIGN, SETTING, SUBJECTS AND INTERVENTIONS: We used a prospective, two-group, parallel-arm design to examine the effect of a 12-week dietary supplementation with flaxseed oil, rich in ALA (8 g/day), on blood pressure in middle-aged dyslipidaemic men (n=59). The diet of the control group was supplemented with safflower oil, containing the equivalent n-6 fatty acid (11 g/day linoleic acid (LA); n=28). Arterial blood pressure was measured at the beginning and at the end of the dietary intervention period. RESULTS: Supplementation with ALA resulted in significantly lower systolic and diastolic blood pressure levels compared with LA (P=0.016 and P=0.011, respectively, from analysis of variance (ANOVA) for repeated measures). CONCLUSIONS: We observed a hypotensive effect of ALA, which may constitute another mechanism accounting in part for the apparent cardioprotective effect of this n-3 fatty acid.",
"title": "Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients."
},
{
"docid": "MED-3923",
"text": "OBJECTIVE: Inadvertent exposure to the ubiquitous weed, Urtica dioica, called \"stinging nettles\" produces an immediate stinging and burning sensation on the skin. This investigation evaluates the structural effect that stinging nettle spicules may have on the clinical manifestation of these symptoms. This hypothesis was investigated by exposing murine skin to stinging nettles and then evaluating the skin using electron microscopy. It was hypothesized that the mechanism of action of stinging nettles is both biochemical and mechanical, which may have clinical significance regarding treatment for acute exposure. METHODS: Fresh post-mortem dermis samples from the carcasses of genetically modified hairless mice were brushed under the stem and leaf of a stinging nettle plant, mimicking the clinical method of exposure a patient might experience. Another set of mouse skin samples was obtained but not exposed to the nettles. Both sets of skin samples were imaged with scanning electron microscopy. RESULTS: The skin samples that were not exposed to nettle leaves were uniform, with occasional striated hairs on the skin surface and no nettle spicules. The skin samples exposed to nettle leaves showed many smooth nettle spicules piercing the skin surface. A few spicules retained their bases, which appear empty of any liquid contents. CONCLUSIONS: The mechanism of action of stinging nettles dermatitis appears to be both biochemical and mechanical. Impalement of spicules into the skin likely accounts for the mechanical irritation in addition to the known adverse chemical effects of stinging nettles. Further investigation of treatment modalities is warranted. Copyright © 2011 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.",
"title": "Mechanism of action of stinging nettles."
},
{
"docid": "MED-3359",
"text": "Background Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention.",
"title": "You Are What You Eat: Within-Subject Increases in Fruit and Vegetable Consumption Confer Beneficial Skin-Color Changes"
},
{
"docid": "MED-1829",
"text": "INTRODUCTION: Sex steroid exposure increases the risk of breast cancer by unclear mechanisms. Diet modifications may be one breast cancer prevention strategy. The proinflammatory cytokine family of IL-1 is implicated in cancer progression. IL-1Ra is an endogenous inhibitor of the proinflammatory IL-1α and IL-1β. OBJECTIVE: The objective of this study was to elucidate whether estrogen, tamoxifen, and/or diet modification altered IL-1 levels in normal human breast tissue. DESIGN AND METHODS: Microdialysis was performed in healthy women under various hormone exposures, tamoxifen therapy, and diet modifications and in breast cancers of women before surgery. Breast tissue biopsies from reduction mammoplasties were cultured. RESULTS: We show a significant positive correlation between estradiol and in vivo levels of IL-1β in breast tissue and abdominal sc fat, whereas IL-1Ra exhibited a significant negative correlation with estradiol in breast tissue. Tamoxifen or a dietary addition of 25 g flaxseed per day resulted in significantly increased levels of IL-1Ra in the breast. These results were confirmed in ex vivo culture of breast biopsies. Immunohistochemistry of the biopsies did not reveal any changes in cellular content of the IL-1s, suggesting that mainly the secreted levels were affected. In breast cancer patients, intratumoral levels of IL-1β were significantly higher compared with normal adjacent breast tissue. CONCLUSION: IL-1 may be under the control of estrogen in vivo and may be attenuated by antiestrogen therapy and diet modifications. The increased IL-1β in breast cancers of women strongly suggests IL-1 as a potential therapeutic target in breast cancer treatment and prevention.",
"title": "Estradiol, tamoxifen, and flaxseed alter IL-1β and IL-1Ra levels in normal human breast tissue in vivo."
},
{
"docid": "MED-4981",
"text": "Variation in the level of the carotenoid antioxidant substances beta-carotene and lycopene in the human skin of ten healthy volunteers was measured with resonance Raman spectroscopy in an in vivo experiment over the course of 12 months. Information on the lifestyle of the volunteers concerning dietary supplementation and stress factors was obtained daily by the completion of questionnaires. The results showed individual variations in the levels of carotenoid antioxidant substances in the skin of the volunteers, which strongly correlated to specific lifestyles, such as the intake of dietary supplementations rich in carotenoids, and the influence of stress factors. A carotenoid-rich nutrition, based on large amounts of fruit and vegetables, increased the measured carotenoid levels of skin, while stress factors such as fatigue, illness, smoking, and alcohol consumption gave rise to a decrease in carotenoid levels of the skin. These decreases occurred relatively quickly over the course of one day, while the subsequent increases lasted for up to 3 days. During the summer and autumn months, an increase in the level of carotenoids in the skin was measured for all volunteers. The average \"seasonal increase\" of the carotenoid content in the skin was determined to be 1.26-fold.",
"title": "One-year study on the variation of carotenoid antioxidant substances in living human skin: influence of dietary supplementation and stress factors."
},
{
"docid": "MED-2746",
"text": "Foods prepared in the kitchen can become cross-contaminated with Campylobacter by contacting raw products, particularly skinned poultry. We measured the percent transfer rate from naturally contaminated poultry legs purchased in supermarkets. Transfer of Campylobacter from skin (n = 43) and from meat (n = 12) to high-density polyethylene cutting board surfaces was quantitatively assessed after contact times of 1 and 10 min. The percent transfer rate was defined as the ratio between the number of Campylobacter cells counted on the cutting board surface and the initial numbers of Campylobacter naturally present on the skin (i.e., the sum of Campylobacter cells on the skin and board). Qualitative transfer occurred in 60.5% (95% confidence interval, 45.5 to 75.4) of the naturally contaminated legs studied and reached 80.6% (95% confidence interval, 63.0 to 98.2) in the subpopulation of legs that were in contact with the surface for 10 min. The percent transfer rate varied from 5 x 10(-2)% to 35.7% and was observed as being significantly different (Kruskall-Wallis test, P < 0.025) and inversely related to the initial counts on poultry skin. This study provides quantitative data describing the evolution of the proportion of Campylobacter organisms transferred from naturally contaminated poultry under kitchen conditions. We emphasize the linear relationship between the initial load of Campylobacter on the skin and the value of the percent transfer rate. This work confirms the need for modeling transfer as a function of initial load of Campylobacter on leg skin, the weight of poultry pieces, and the duration of contact between the skin and surface.",
"title": "Campylobacter transfer from naturally contaminated chicken thighs to cutting boards is inversely related to initial load."
},
{
"docid": "MED-4459",
"text": "Ultraviolet (UV) of sunlight is a complete carcinogen that can burn skin, enhance inflammation, and drive skin carcinogenesis. Previously, we have shown that sulforaphane (SFN) inhibited chemically induced skin carcinogenesis via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and others have shown that broccoli sprout extracts containing high SFN protected against UV-induced skin carcinogenesis in SKH-1 hairless mice. A recent study showed that there was no difference between Nrf2 knockout (Nrf2 KO) and Nrf2 wild-type (WT) BALB/C mice after exposing to high dose of UVB. Since Nrf2 plays critical roles in the anti-oxidative stress/anti-inflammatory responses, it is relevant to assess the role of Nrf2 for photoprotection against UV. In this context, the role of Nrf2 in UVB-induced skin inflammation in Nrf2 WT and Nrf2 KO C57BL/6 mice was studied. A single dose of UVB (300 mJ/cm(2)) resulted in skin inflammation in both WT and Nrf2 KO (-/-) mice (KO mice) at 8 h and 8 d following UVB irradiation. In the WT mice inflammation returned to the basal level to a greater extent when compared to the KO mice. SFN treatment of Nrf2 WT but not Nrf2 KO mice restored the number of sunburn cells back to their basal level by 8 d after UVB irradiation. Additionally, UVB-induced short-term inflammatory biomarkers (interleukin-1β and interleukin-6) were increased in the KO mice and UVB-induced apoptotic cells in the KO mice were significantly higher as compared to that in the WT. Taken together, our results show that functional Nrf2 confers a protective effect against UVB-induced inflammation, sunburn reaction, and SFN-mediated photoprotective effects in the skin. Copyright © 2010 Wiley-Liss, Inc.",
"title": "Impact of Nrf2 on UVB-induced skin inflammation/photoprotection and photoprotective effect of sulforaphane."
}
] |
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In what cases can states tax non-residents?
|
[
{
"docid": "535673",
"text": "From the Massachusetts Department of Revenue: 1st - Massachusetts Source Income That is Excluded Massachusetts gross income excludes certain items of income derived from sources within Massachusetts: non-business related interest, dividends and gains from the sale or exchange of intangibles, and qualified pension income. 2nd - Massachusetts Source Income That is Included: Massachusetts gross income includes items of income derived from sources within Massachusetts. This includes income: 3rd - Trade or business, Including Employment Carried on in Massachusetts: A nonresident has a trade or business, including any employment carried on in Massachusetts if: A nonresident generally is not engaged in a trade or business, including any employment carried on in Massachusetts if the nonresident's presence for business in Massachusetts is casual, isolated and inconsequential. A nonresident's presence for business in Massachusetts will ordinarily be considered casual, isolated and inconsequential if it meets the requirements of the Ancillary Activity Test (AAT) and Examples. When nonresidents earn or derive income from sources both within Massachusetts and elsewhere, and no exact determination can be made of the amount of Massachusetts source income, an apportionment of income must be made to determine that amount considered Massachusetts gross income. 4th - Apportionment of Income: Apportionment Methods: The three most common apportionment methods used to determine Massachusetts source income are as follows: Gross income is multiplied by a: So if you go to Massachusetts to work, you have to pay the tax. If you collect a share of the profit or revenue from Massachusetts, you have to pay tax on that. If you work from Oregon and are paid for that work, then you don't pay Massachusetts tax on that. If anything, your company might have to pay Oregon taxes on revenue you generate (you are their agent or employee in Oregon). Does the answer change depending on whether the income is reported at 1099 or W-2? This shouldn't matter legally. It's possible that it would be easier to see that the work was done in Oregon in one or the other. I.e. it doesn't make any legal difference but may make a practical difference. All this assumes that you are purely an employee or contractor and not an owner. If you are an owner, you have to pay taxes on any income from your Massachusetts business. Note that this applies to things like copyrights and real estate as well as the business. This also assumes that you are doing your work in Oregon. If you live in Oregon and travel to Massachusetts to work, you pay taxes on your Massachusetts income in Massachusetts.",
"title": ""
}
] |
[
{
"docid": "43508",
"text": "\"The examples you provide in the question are completely irrelevant. It doesn't matter where the brokerage is or where is the company you own stocks in. For a fairly standard case of an non-resident alien international student living full time in the US - your capital gains are US sourced. Let me quote the following text a couple of paragraphs down the line you quoted on the same page: Gain or loss from the sale or exchange of personal property generally has its source in the United States if the alien has a tax home in the United States. The key factor in determining if an individual is a U.S. resident for purposes of the sourcing of capital gains is whether the alien's \"\"tax home\"\" has shifted to the United States. If an alien does not have a tax home in the United States, then the alien’s U.S. source capital gains would be treated as foreign-source and thus nontaxable. In general, under the \"\"tax home\"\" rules, a person who is away (or who intends to be away) from his tax home for longer than 1 year has shifted tax homes to his new location upon his arrival in that new location. See Chapter 1 of Publication 463, Travel, Entertainment, Gift, and Car Expenses I'll assume you've read this and just want an explanation on what it means. What it means is that if you move to the US for a significant period of time (expected length of 1 year or more), your tax home is assumed to have shifted to the US and the capital gains are sourced to the US from the start of your move. For example: you are a foreign diplomat, and your 4-year assignment started in May. Year-end - you're not US tax resident (diplomats exempt), but you've stayed in the US for more than 183 days, and since your assignment is longer than 1 year - your tax home is now in the US. You'll pay the 30% flat tax. Another example: You're a foreign airline pilot, coming to the US every other day flying the airline aircraft. You end up staying in the US 184 days, but your tax home hasn't shifted, nor you're a US tax resident - you don't pay the flat tax. Keep in mind, that tax treaties may alter the situation since in many cases they also cover the capital gains situation for non-residents.\"",
"title": ""
},
{
"docid": "52622",
"text": "\"I also don't know the specific details for Finland and/or Belgium, however many countries have tax treaties, which generally prevent double taxation (i.e., paying tax in both countries on the same base income). Being that both Finland and Belgium are EU member states, I'm quite certain there's a provision that covers this, and the same would apply: You pay taxes on what you earn while in Finland to Finland, and to Belgium what you earn while in Belgium. All of this is similar to what you presented, however there's also a section where you'd declare how much taxes were paid in other countries. One other thing to note, which will be the determining factor in the above, is whether EU law requires you to change residence to BE for the time you're there. If not then you'll be paying taxes in Finland the entire time on the entire amount. This comes from an Irish governmental site: \"\"By working in another member state and by transferring your residence there, you are likely to become \"\"resident for tax purposes\"\" there. The definition of fiscal residence varies from one member state to another. You must comply with the laws of the country where you have established your residence. The laws on personal taxation vary considerably from one member state to another and you may be liable for taxation in more than one country. In general, you are subject to income tax in the country where you are living but this may not be the case if you are a “posted worker” – see below. In general, property is taxed in the country in which it is situated but, again, there are variations. Tax agreements have been concluded between most of the member states of the EU, which are intended to avoid double taxation, if you derive income from different countries. In general, national fiscal rules must respect the fundamental principle of non-discrimination against nationals of another EU country.\"\"\"",
"title": ""
},
{
"docid": "371094",
"text": "This is a common occurrence, I know people who moved and then only remember the next spring during tax season that they never filed a new state version of a W-4. Which means for 3 or 4 months in the new year money is sent to the wrong state capital, and way too much was sent the previous year. In the spring of 2016 you should have filed a non-resident tax form with Michigan. On that form you would specify your total income numbers, your Michigan income numbers, and your other-state income numbers; with Michigan + other equal to total. That should have resulted in getting all the state taxes that were sent to Michigan returned. It is possible that the online software is unable to complete the non-resident tax form. Not all forms and situations can be addressed by the software. So you may need to fill out paper forms. You should be able to find what you need on the state of Michigan website for 2015 Taxes. A quick read shows that you will probably need the Michigan 1040, schedule 1 and Schedule NR You may run into an issue if your license, car registration, voter registration, and other documentation point to you being a resident for the part of the year you earned that income. That means you will have to submit Form 3799 Statement to Determine State of Domicile You want to do this soon because there are deadlines that limit how far back you can files taxes. The state may also get tax information from the IRS and could decide that all your income from 2015 should have applied to them, so they will be sending you a tax bill plus penalties for failure to file.",
"title": ""
},
{
"docid": "318260",
"text": "\"Besides money and time lost, it is pretty clear that most tax advisors are not well versed in non-resident taxes. It seems that their main clients are either US residents or H1B workers (who are required to file as residents). I share your pain on this one. In fact, even for H1B/green card holders or Americans with income/property abroad vast majority of advisers will make mistakes (which may become quite costly). IRS licensing exams for EA/RTRP do not include a single question on non-resident taxation or potential issues, let alone handling treaties. Same goes for the AICPA unified CPA exam (the REG portion of which, in part, deals with taxes). I'm familiar with the recent versions of both exams and I am very disappointed and frustrated by that lack of knowledge requirement in such a crucial area (I am not a licensed tax preparer now though). That said, the issue is very complicated. I went through several advisers until I found the one I can trust to know her stuff, and while at it happened to learn quite a lot about the US tax code (which doesn't make me sleep any better by the least). It is my understanding that preparing a US tax return for a foreign person without a mistake is impossible, but the question is how big is the mistake you're going to make. I had returns prepared by solo working advisers where I found mistakes as ridiculous as arithmetic calculation errors (fired after two seasons), and by big-4 firms where I found mistakes that cost me quite a lot (although by the time I figured that they cost me significant amounts, it was too late to sue or change; fired after 2 seasons as well). As you can see, it is relevant to me as well, and I do not do my own tax returns. I usually ask for the conservative interpretations from my adviser, IRS is very aggressive on enforcement and the penalties, especially on foreigners are draconian (I do not know if it ever went through a judicial review, as I believe some of these penalties are unconstitutional under the 8th amendment, but that's my personal opinion). Bottom line - its hard to find a decent tax adviser, and that's why the good ones are expensive. You get what you pay for. How do I go about locating a CPA/EA who is well versed in non-resident taxes located in the Los Angeles area (Orange County area is not too far away either) These professionals are usually active in large metropolitan areas with a lot of foreigners. You should be able to find decent professionals in LA/OC, SF Bay, Seattle, New York, Boston, and other cities and metropolises attracting foreigners. Also, look for those working in the area of a major university. Specific points: If I find none, can I work with a quaified person who lives in a different state and have him file my taxes on my behalf (electronically or via scans going back and forth) Yes. But that person my have a problem representing you in California (in case you're audited), unless he's an EA (licensed by the Federal government, can practice everywhere) or is licensed as a CPA or Attorney by the State of California. Is there a central registry of such quaified people I can view (preferably with reviews) - akin to \"\"yellow pages\"\" IRS is planning on opening one some time this year, but until then - not really. There are some commercial sites claiming to have that, but they're using the FOIA access to the IRS and states' listings, and may not have updated information. They definitely don't have updated license statuses (or any license statuses) or language/experience information. Wouldn't trust them.\"",
"title": ""
},
{
"docid": "594784",
"text": "If you're a US citizen/resident - you pay taxes on your worldwide income regardless of where you live. The logic is that Americans generally don't agree to the view that there's more than one country in the world. If you're non-US person, not physically present in the US, and provide contract work for a US employer - you generally don't pay taxes in the US. The logic is that the US doesn't actually have any jurisdiction over that money, you didn't earn it in the US. That said, your employer might withheld tax and remit it to the IRS, and you'll have to chase them for refund. If you receive income from the US rental property or dividends from a US company - you pay income tax to the US on that income, and then bargain with your home tax authority on refunds of the difference between what you paid in the US and what you should have paid at home. You can also file non-resident tax return in the US to claim what you have paid in excess. The logic is that the money sourced in the US should be taxed in the US. You earned that money in the US. There are additional rules to more specific situation, and there are also bilateral treaties between countries (including a US-Canadian treaty) that supersede national laws. Bottom line, not only that each country has its own laws, there are also different laws for different situations, and if some of the international treaties apply to you - it further complicates the situation. If something is not clear - get a professional advice form a tax accountant licensed in the relevant jurisdictions (in your case - any of the US states, and the Canadian province where you live).",
"title": ""
},
{
"docid": "30343",
"text": "\"You've asked a number of questions. I can answer a few. I've quoted your question before each answer. What are the ins and outs of a foreigner like myself buying rental property in Canada? This is a pretty broad question which can address location, finances, basic suggestions etc. Here's some things to consider: Provincial considerations: Some ins and outs will depend on what province you are considering and what area in that Province. If you plan on owning in Montreal, for example, that's in the province of Quebec and that means you (or someone) will need to be able to operate in the French language. There are other things that might be different from province to province. See stat info below. Canadian vs. US Dollar: Now might be a great time to buy property in Canada since the Canada dollar is weak right now. To give you an idea, at a non-cash rate of 1.2846, a little over $76,000 US will get you over $100k Canadian. That's using the currency converter at rbcroyalbank.com. Taxes for non-resident rental property owners: According to the T4144 Income Tax Guide for Electing Under Section 216 – 2015: \"\"When you receive rental income from real or immovable property in Canada, the payer, such as the tenant or a property manager, has to withhold non-resident tax at the rate of 25% on the gross rental income paid or credited to you. The payer has to pay us the tax on or before the 15th day of the month following the month the rental income is paid or credited to you.\"\" If you prefer to send a separate Canadian tax return, you can choose to elect under section 216 of the Income Tax Act. A benefit of this way is that \"\"electing under section 216 allows you to pay tax on your net Canadian-source rental income instead of on the gross amount. If the non-resident tax withheld by the payer is more than the amount of tax payable calculated on your section 216 return, [they] will refund the excess to you.\"\" You can find this guide at Canada Revenue's site: http://www.cra-arc.gc.ca/E/pub/tg/t4144/README.html Stats: A good place for stats is the Canada Mortgage and Housing Corporation (CMHC). So, if you are interesting in vacancy rates for example, you can see a table that will show you that the vacancy rate in Ontario is 2.3% and in British Columbia it's 1.5%. However, in New Brunswick it's 8%. The rate for metropolitan areas across Canada is 2.8%. If you want to see or download this table showing the vacancy rates by province and also by metropolitan areas, go to the Canada Mortgage and Housing Corporation site http://www.cmhc.ca/housingmarketinformation/. You can get all sorts of housing information, reports and market information there. I've done well with Condos/Town-homes and would be interested in the same thing over there. Is it pretty much all the same? See the stat site mentioned above to get market info about condos, etc. What are the down payment requirements? For non-owner occupied properties, the down payment is at least 20%. Update in response to comments about being double taxed: Regarding being taxed on income received from the property, if you claim the foreign tax credit you will not be double taxed. According to the IRS, \"\"The foreign tax credit intends to reduce the double tax burden that would otherwise arise when foreign source income is taxed by both the United States and the foreign country from which the income is derived.\"\" (from IRS Topic 856 - Foreign Tax Credit) About property taxes: From my understanding, these would not be claimed for the foreign tax credit but can be deducted as business expenses. There are various exceptions and stipulations based on your circumstance, so you need to read Publication 856 - Foreign Tax Credit for Individuals. Here's an excerpt: \"\"In most cases, only foreign income taxes qualify for the foreign tax credit. Other taxes, such as foreign real and personal property taxes, do not qualify. But you may be able to deduct these other taxes even if you claim the foreign tax credit for foreign income taxes. In most cases, you can deduct these other taxes only if they are expenses incurred in a trade or business or in the production of income. However, you can deduct foreign real property taxes that are not trade or business expenses as an itemized deduction on Schedule A (Form 1040).\"\" Disclaimers: Sources: IRS Topic 514 Foreign Tax Credit and Publication 856 Foreign Tax Credit for Individuals\"",
"title": ""
},
{
"docid": "347186",
"text": "Tax liability in US: You would need to determine if you are a resident alien or non resident alien. Resident alien are taxed normally as per US citizens. For the annual remuneration you have quoted it would be in the range of 25%. Refer http://www.moneychimp.com/features/tax_brackets.htm To determine if you are resident alien or non resident alien, you need to be present for certain period in US. There is also an exemption even if you meet this you can still be treated as non resident alien if your tax home is outside US [India in this case] Refer to the link for details to determine your category, the durations are for number of days in financial year, hence it matters when you are in US and the exact durations. http://www.irs.gov/taxtopics/tc851.html Also note that if you are assessed as resident alien, even the income from India will be taxed in US unless you declare there is no income in India. Tax liability in India: The tax liability in India would be depending on your NRI status. This again is tied to the financial year and the number of days you are in country. While the year you are going out of India you need to be away for atleast 183 days for you be considred are NRI. So if you are treated as Indian resident, you would have to pay tax in India on entire income. In the worst case, depending on the period you travel and the dates you travel, you could get classified as citizen in US as well as India and have to pay tax at both places. India and US do not have a dual tax avoidance treaty for individuals. Its there for certain category like small business and certain professions like teacher, research etc.",
"title": ""
},
{
"docid": "110862",
"text": "\"For Non-Resident filers, New York taxes New York-sourced income. That includes: real or tangible personal property located in New York State (including certain gains or losses from the sale or exchange of an interest in an entity that owns real property in New York State); services performed in New York State; a business, trade, profession, or occupation carried on in New York State; and a New York S corporation in which you are a shareholder (including installment income from an IRC 453 transaction). There are some exclusions as well. It is all covered in the instructions to form IT-203. However, keep in mind that \"\"filing\"\" as non-resident doesn't make you non-resident. If you spend 184 days or more in New York State, and you have a place to stay there - you are resident. See definitions here. Even if you don't actually live there and consider yourself a CT resident.\"",
"title": ""
},
{
"docid": "272944",
"text": "\"Although there are occasional cases where simply moving money between countries results in a tax liability - for example a \"\"non-domiciled\"\" UK resident using the \"\"remittance basis\"\" - this is not the case in your situation. In general it would be extremely rare for non-residents of a country to be taxed on bringing money into that country, as it would be bad for tourism which most countries want to encourage. The requirement to declare large sums of money on entry is primarily so that the authorities can detect money laundering, rather than tax. Note that you will have to pay US tax on any interest you earn on that US bank account.\"",
"title": ""
},
{
"docid": "461435",
"text": "Well, a proper answer needs a few more details: 1) What's your marginal tax bracket? (A CD is just plain silly for someone in a high tax bracket and in a high tax state) 2) What's your state of residence? 3) Do you have a 401k to draw on for a house loan in case of badly timed volatility? 4) What does will the rest of our investment portfolio look like in case of a sudden rise in interest rates? Depending on the answers to those questions, the mix of investments could be anywhere from: Tell me more about bracket/state/other investment mix and I can suggest something.",
"title": ""
},
{
"docid": "518624",
"text": "\"The other answer has mentioned \"\"factual resident\"\", and you have raised the existence of a U.S./Canada tax treaty in your comment, and provided a link to a page about determining residency. I'd like to highlight part of the first link: You are a factual resident of Canada for tax purposes if you keep significant residential ties in Canada while living or travelling outside the country. The term factual resident means that, although you left Canada, you are still considered to be a resident of Canada for income tax purposes. Notes If you have established ties in a country that Canada has a tax treaty with and you are considered to be a resident of that country, but you are otherwise a factual resident of Canada, meaning you maintain significant residential ties with Canada, you may be considered a deemed non-resident of Canada for tax purposes. [...] I'll emphasize that \"\"considered to be a resident of Canada for income tax purposes\"\" means you do need to file Canadian income tax returns. The Notes section does indicate the potential treaty exemption that you mentioned, but it is only a potential exemption. Note the emphasis (theirs, not mine) on the word \"\"may\"\" in the last paragraph above. Please don't assume \"\"may\"\" is necessarily favorable with respect to your situation. The other side of the \"\"may\"\" coin is \"\"may not\"\". The Determining your residency status page you mentioned in your comment says this: If you want the Canada Revenue Agency's opinion on your residency status, complete either Form NR74, Determination of Residency Status (Entering Canada) or Form NR73, Determination of Residency Status (Leaving Canada), whichever applies, and send it to the International and Ottawa Tax Services Office. To get the most accurate opinion, provide as many details as possible on your form. So, given your ties to Canada, I would suggest that until and unless you have obtained an opinion from the Canada Revenue Agency on your tax status, you would be making a potentially unsafe assumption if you yourself elect not to file your Canadian income tax returns based on your own determination. You could end up liable for penalties and interest if you don't file while you are outside of Canada. Tax residency in Canada is not a simple topic. For instances, let's have a look at S5-F1-C1, Determining an Individual’s Residence Status. It's a long page, but here's one interesting piece: 1.44 The Courts have stated that holders of a United States Permanent Residence Card (otherwise referred to as a Green Card) are considered to be resident in the United States for purposes of paragraph 1 of the Residence article of the Canada-U.S. Tax Convention. For further information, see the Federal Court of Appeal's comments in Allchin v R, 2004 FCA 206, 2004 DTC 6468. [...] ... whereas you are in the U.S. on a TN visa, intended to be temporary. So you wouldn't be exempt just on the basis of your visa and the existence of the treaty. The CRA would look at other circumstances. Consider the \"\"Centre of vital interests test\"\": Centre of vital interests test [...] “If the individual has a permanent home in both Contracting States, it is necessary to look at the facts in order to ascertain with which of the two States his personal and economic relations are closer. Thus, regard will be had to his family and social relations, his occupations, his political, cultural or other activities, his place of business, the place from which he administers his property, etc. The circumstances must be examined as a whole, but it is nevertheless obvious that considerations based on the personal acts of the individual must receive special attention. If a person who has a home in one State sets up a second in the other State while retaining the first, the fact that he retains the first in the environment where he has always lived, where he has worked, and where he has his family and possessions, can, together with other elements, go to demonstrate that he has retained his centre of vital interests in the first State.” [emphasis on last sentence is mine] Anyway, I'm acquainted with somebody who left Canada for a few years to work abroad. They assumed that living in the other country for that length of time (>2 years) meant they were non-resident here and so did not have to file. Unfortunately, upon returning to Canada, the CRA deemed them to have been resident all that time based on significant ties maintained, and they subsequently owed many thousands of dollars in back taxes, penalties, and interest. If it were me in a similar situation, I would err on the side of caution and continue to file Canadian income taxes until I got a determination I could count on from the people that make the rules.\"",
"title": ""
},
{
"docid": "457455",
"text": "It essentially works the same. Some states don't have any income taxes at all (like Florida or Wyoming), some only tax income derived in the state, and some tax worldwide income (like New York or California), similarly to the Federal income taxes. However, if you're living abroad (i.e.: you're a citizen or resident of a foreign country and you live there), you're not considered resident by most of the states (check with your state for specific definitions) for most, if not all, the time of your residency abroad. In such case - you don't pay state taxes, only Federal. You have to remember that foreign income exclusion doesn't apply to the income from your 401k, so you pay the taxes as if you're in the US. You can not use foreign taxes credit as well (but depending on the tax treaty with the country you're moving to, your 401k income might not be taxable there). In some cases you may end up with double taxation: US will tax your 401k income as you're a US citizen and the income is derived from the US sources, and the foreign country will tax the income based on its own laws. This is not a tax advice, and this answer was not intended or written to be used, and it cannot be used by any taxpayer, for the purpose of avoiding penalties that may be imposed on the taxpayer.",
"title": ""
},
{
"docid": "352266",
"text": "Canada doesn't tax non-residents on income earned/incurred outside of Canada. So, your sister should start with this page to determine the residency status. If she is indeed determined to be non-resident - she should look here to see her obligations. If all she earns she earns outside of Canada - her obligations will be very little, if at all. This is similar to almost any other country in the world, with the notable exception of the United States of America. US citizens are taxed regardless of their residency status, everywhere in the world on worldwide income (unless tax treaty says otherwise).",
"title": ""
},
{
"docid": "102287",
"text": "\"I'm assuming that by saying \"\"I'm a US resident now\"\" you're referring to the residency determination for tax purposes. Should I file a return in the US even though there is no income here ? Yes. US taxes its residents for tax purposes (which is not the same as residents for immigration or other purposes) on worldwide income. If yes, do I get credits for the taxes I paid in India. What form would I need to submit for the same ? I am assuming this form has to be issued by IT Dept in India or the employer in India ? The IRS doesn't require you to submit your Indian tax return with your US tax return, however they may ask for it later if your US tax return comes under examination. Generally, you claim foreign tax credits using form 1116 attached to your tax return. Specifically for India there may also be some clause in the Indo-US tax treaty that might be relevant to you. Treaty claims are made using form 8833 attached to your tax return, and I suggest having a professional (EA/CPA licensed in your State) prepare such a return. Although no stock transactions were done last year, should I still declare the value of total stocks I own ? If so what is an approx. tax rate or the maximum tax rate. Yes, this is done using form 8938 attached to your tax return and also form 114 (FBAR) filed separately with FinCEN. Pay attention: the forms are very similar with regard to the information you provide on them, but they go to different agencies and have different filing requirements and penalties for non-compliance. As to tax rates - that depends on the types of stocks and how you decide to treat them. Generally, the tax rate for PFIC is very high, so that if any of your stocks are classified as PFIC - you'd better talk to a professional tax adviser (EA/CPA licensed in your State) about how to deal with them. Non-PFIC stocks are dealt with the same as if they were in the US, unless you match certain criteria described in the instructions to form 5471 (then a different set of rules apply, talk to a licensed tax adviser). I will be transferring most of my stock to my father this year, will this need to be declared ? Yes, using form 709. Gift tax may be due. Talk to a licensed tax adviser (EA/CPA licensed in your State). I have an apartment in India this year, will this need to be declared or only when I sell the same later on ? If there's no income from it - then no (assuming you own it directly in your own name, for indirect ownership - yes, you do), but when you sell you will have to declare the sale and pay tax on the gains. Again, treaty may come into play, talk to a tax adviser. Also, be aware of Section 121 exclusion which may make it more beneficial for you to sell earlier.\"",
"title": ""
},
{
"docid": "394059",
"text": "\"You'll need to read carefully the German laws on tax residency, in many European (and other) tax laws the loss of residency due to absence is conditioned on acquiring residency elsewhere. But in general, it is possible to use treaties and statuses so that you end up not being resident anywhere, but it doesn't mean that the income is no longer taxed. Generally every country taxes income sourced to it unless an exclusion applies, so if you can no longer apply the treaty due to not being a resident - you'll need to look for general exclusions in the tax law. I don't know how Germany taxes scholarships under the general rules, you'll have to check it. It is possible that they're not taxed. Many people try to raise the argument of \"\"I'm not a resident\"\" to avoid income taxes altogether on earnings on their work - this would not work. But with a special kind of income like scholarship, which may be exempt under the law, it may. Keep in mind, that the treaty has \"\"who is or was immediately before visiting a Contracting State a resident of the other Contracting State\"\" language in some relevant cases, so you may still apply it in the US even if no longer resident in Germany.\"",
"title": ""
},
{
"docid": "300133",
"text": "Both states will want to tax you. Your tax home is where you maintain a domicile, are registered to vote, etc. and you will probably want to keep this as MA since you state that MA is your permanent residence and you are staying in a rented place in PA. But be careful about voter registration; that is one of the items that can be used to determine your state of residence. OK, so if you and your spouse are MA residents, you should file jointly as residents in MA and as nonresidents in PA. Do the calculations on the nonresident return first, and then the calculations on the resident return. Typically, on a nonresident tax return, the calculations are effectively the following: Report all your income (usually AGI from the Federal return). Call this $X. Compute the PA state tax due on $X. Note that you follow the rules for nonresidents in doing this, not the calculations used by PA residents. Call the amount of tax you computed as $Y. What part of the total income $X is attributable to PA sources? If this amount is $Z, then you owe PA $Y times (Z/X). On the resident return in MA, you will likely get some credit for the taxes paid to PA, and this will reduce your MA tax burden. Usually the maximum credit is limited to the lesser of actual tax paid to PA and what you would have had to pay MA for the same income. As far as withholding is concerned, your employer in PA will withhold PA taxes as if you are a PA resident, but you can adjust the amount via the PA equivalent of IRS Form W4 so as to account for any additional tax that might be due because you will be filing as a nonresident. Else you can pay estimated taxes via the PA equivalent of IRS Form 1040ES. Similarly, your wife can adjust her withholding to account for the MA taxes that you will owe on the joint income, or you can pay estimated taxes to MA too. Note that it is unlikely that your employer in Pennsylvania will withhold Massachusetts taxes (and send them to Massachusetts) for you, e.g. if it is a ma-and-pa store, but there may be special deals available if your employer does business in both states, i.e. is a MA-and-PA store.",
"title": ""
},
{
"docid": "192083",
"text": "It's not just the US based mailing address for registration or US based credit-card or bank account: even if you had all these, like I do, you will find that these online filing companies do not have the infrastructure to handle non-resident taxes. The reason why the popular online filing companies do not handle non-resident taxes is because: Non-residents require a different set of forms to fill out - usually postfixed NR - like the 1040-NR. These forms have different rules and templates that do not follow the usual resident forms. This would require non-trivial programming done by these vendors All the NR forms have detailed instructions and separate set of non-resident guides that has enough information for a smart person to figure out what needs to be done. For example, check out Publication 519 (2011), U.S. Tax Guide for Aliens. As a result, by reading these most non-residents (or their accountants) seem to figure out how the taxes need to be filed. For the remaining others, the numbers perhaps are not significant enough to justify the non-trivial programming that need to be done by these vendors to incorporate the non-resident forms. This was my understanding when I did research into tax filing software. However, if you or anyone else do end up finding tax filing software that does allow non-resident forms, I wil be extremely happy to learn about them. To answer your question: you need to do it yourself or get it done by someone who knows non-resident taxes. Some people on this forum, including me for gratis, would be glad to check your work once you are done with it as long as you relieve us of any liability.",
"title": ""
},
{
"docid": "417388",
"text": "The 401(k) contribution is Federal tax free, when you make the contribution, and most likely State too. I believe that is true for California, specifically. There was a court case some years ago about people making 401(k) or IRA contributions in New York, avoiding the New York state income tax. Then they moved to Florida (no income tax), and took the money out. New York sued, saying they had to pay the New York income tax that had been deferred, but the court said no. So you should be able to avoid California state income tax, and then later if you were to move to, for example, Texas (no income tax), have no state income tax liability. At the Federal level, you will have different problems. You won't have the money; it will be held by the 401(k) trustee. When you try to access the money (cash the account out), you will have to pay the deferred taxes. Effectively, when you remove the money it becomes income in the year it is removed. You can take the money out at any time, but if you are less than 59 1/2 at the time that you take it, there is a 10% penalty. The agreement is that the Feds let you defer paying the tax because it is going to finance your retirement, and they will tax it later. If you take it out before 59 1/2, they figure you are not retired yet, and are breaking your part of the agreement. Of course you can generally leave the money in the 401(k) plan with your old employer and let it grow until you are 59.5, or roll it over into another 401(k) with a new employer (if they let you), or into an IRA. But if you have returned to your own country, having an account in the U.S. would introduce both investment risk and currency risk. If you are in another country when you want the money, the question would be where your U.S. residence would be. If you live in California, then go to, say France, your U.S. residence would still be California, and you would still owe California income tax. If you move from California to Texas and then to France, your U.S. residence would be Texas. This is pretty vague, as you might have heard in the Rahm Emanual case -- was he a resident of Chicago or Washington, D.C.? Same problem with Howard Hughes who was born in Texas, but then spent most his life in California, then to Nevada, then to Nicaragua, and the Bahamas. When he died Texas, California and Nevada all claimed him as a resident, for estate taxes. The important thing is to be able to make a reasonable case that you are a resident of where ever you want to be -- driver's license, mailing address, living quarters, and so on.",
"title": ""
},
{
"docid": "256395",
"text": "With a question like this you should talk to a tax professional who knows about international tax and knows about both the UK and the country you will be working in. They will give you up to date advice on what can be an extremely complex question. However to get you started I'll tell you what I was told when I did this nearly twenty years ago. It's all about whether you are resident in the UK for tax purposes or not. If you are, you will pay UK tax. If not, you wont (assuming you are being paid outside the UK - check with your professional exactly what is involved). In those days you could be counted as 'non resident' if you spent a complete period of twelve months outside the UK. You can make occasional visits to the UK without invalidating that. Again, check exactly how much you are allowed to return while still being not resident. Usually you will have to pay tax in the country where you are resident, but check the rules there. With some skilful timing you may be able to be considered non-resident in bouth countries, at least for some of the time. Again, your tax professional will know. The bank account question - again get a professional. I don't think it's a problem, but you may have to establish that you are being paid in the foreign country. In general you are going to need an account in the country where you work, so if its a problem get paid there and transfer any money you need in the UK.",
"title": ""
},
{
"docid": "571430",
"text": "It also depends on where you work. If you move your home and your job then the date you establish residency in the new state is the key date. All income before that date is considered income for state 1, and all income on or after that date is income for state 2. If there is a big difference in income you will want to clearly establish residency because it impacts your wallet. If they had the same rates moving wouldn't impact your wallet, but it would impact each state. So make sure when going from high tax state to low tax state that you register your vehicles, register to vote, get a new drivers license... It becomes more complex if you move your home but not your job. In that case where you work might be the deciding factor. Same states have agreed that where you live is the deciding factor; in other cases it is not. For Virginia, Maryland, and DC you pay based on where you live if the two states involved are DC, MD, VA. But if you Live in Delaware and work in Virginia Virginia wants a cut of your income tax. So before you move you need to research reciprocity for the two states. From Massachusetts information for Nonresident and Part-Year Resident Income, Exemptions, Deductions and Credits Massachusetts gross income includes items of income derived from sources within Massachusetts. This includes income: a few questions later: Massachusetts residents and part-year residents are allowed a credit for taxes due to any other jurisdiction. The credit is available only on income reported and taxed on a Massachusetts return. Nonresidents may not claim the taxes paid to other jurisdiction credit on their Massachusetts Form 1-NR/PY. The credit is allowed for income taxes paid to: The credit is not allowed for: taxes paid to the U.S. government or a foreign country other than Canada; city or local tax; and interest and penalty paid to another jurisdiction. The computation is based on comparing the Massachusetts income tax on income reported to the other jurisdiction to the actual tax paid to the other jurisdiction; the credit is limited to the smaller of these two numbers. The other jurisdiction credit is a line item on the tax form but you must calculate it on the worksheet in the instruction booklet and also enter the credit information on the Schedule OJC. So if you move your house to New Hampshire, but continue to work in Massachusetts you will owe income tax to Massachusetts for that income even after you move and establish residency in New Hampshire.",
"title": ""
},
{
"docid": "239233",
"text": "Surprisingly enough, this one isn't actually all that complicated. No, you will not be taxed twice. Dividends are paid by the company, which in this case is domiciled in Spain. As a Spanish company, the Spanish government will take dividend witholding tax from this payment before it is paid to a foreign (i.e. non-Spanish resident) shareholder. What's happening here is that a Spanish company is paying a dividend to a Malaysian resident. The fact that the Spanish stock was purchased in the form of an ADR from a US stock market using US dollars is actually irrelevant. The US has no claim to tax the dividend in this case. One brave investor/blogger in Singapore even set out to prove this point by buying a Spanish ADR just before the dividend was paid. Bravo that man! http://www.investmentmoats.com/money-management/dividend-investing/how-to-calculate-dividend-withholding-taxes-on-us-adrs-for-international-investors-my-experience-with-telefonica/",
"title": ""
},
{
"docid": "214690",
"text": "Gifts from your parents are not treated as income for tax purposes. You should not include that in your subsidy calculation. If you are here on a student-visa and have been in the US for less than 5 years, then you are considered a non-resident alien, and you are not required to buy a qualified plan through the insurance marketplace. You might be able to get a cheaper student plan through your school, but the subsidy might be enough that it's still worth it when calculated correctly. If you are a resident-alien or you are a citizen of the US, then you are required to get coverage, though you can choose not to purchase coverage and pay the tax for not having creditable coverage. That tax cannot be collected by the IRS unless you have already had federal tax withheld. They can only confiscate your tax return money to recoup that money. I don't have enough information to recommend one way or the other what you should do, but I would bet that if you recalculated your subsidy without including your parents income it would cover the majority of the cost. You should also consider applying for Medicaid if you meet the eligibility requirements in your state.",
"title": ""
},
{
"docid": "571258",
"text": "Please get a view of professional. The DTAA between US and Romaina says both can tax the Dividends. Dividends (1) Dividends paid by a corporation of one of the Contracting States to a resident of the other Contracting State may be taxed by both Contracting States. (2) The rate of tax imposed by the first-mentioned Contracting State on such dividends shall not exceed 10 percent of the gross amount of the dividend. (3) Paragraph (2) shall not apply if the recipient of the dividends, being a resident of one of the Contracting States, has a permanent establishment in the other Contracting State and the shares with respect to which the dividends are paid are effectively connected with such permanent establishment. In such a case, paragraph (6) of Article 7 (Business Profits) shall apply. Edit: Quite often the wordings are tricky, hence a opinion of qualified professional is recommended. Also realize that UK and Romania are part Euro Zone. This means there are quite a few EU laws that govern taxation and DTAA relevance may be less.",
"title": ""
},
{
"docid": "424175",
"text": "It is not a question of where you have your driver's license. It is a question of the states' tax related residency rules. (Though a driver's license can be a part of that question.) Since you likely have a residence in NYC and so can prove residency through a lease, bills, etc., you probably have to file as a NYS/NYC resident. I do have to question your maintaining a California driver's license if you are not a resident. If you are attempting to maintain dual-residency, look into both states' residency rules to see if you are liable for taxes in both states. California seems particularly picky about these types of situations, probably due to concerns that you may be trying to circumvent California taxes. That said, it usually revolves around income in the state. Of course, if you maintain residency in California as well, the argument can be made that you owe some taxes due to the fact that you take advantage of state services. (E.g. you drive on California roads.) I suggest you consult a tax professional knowledgeable in these issues to sort out the details.",
"title": ""
},
{
"docid": "570639",
"text": "\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \"\"Non-Resident\"\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \"\"Non-Resident\"\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \"\"Non-Resident\"\" then you should get your savings account converted to \"\"NRO\"\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\"",
"title": ""
},
{
"docid": "444300",
"text": "\"Read up on filing an \"\"amended tax return\"\". Essentially you'll fill out the entire return as it should have been originally, then fill out form 1040X stating what has changed (and pay the additional tax due if needed). According to TurboTax's website, they have partnered with Sprintax for non-resident tax prep. I am not vouching for the service; just offering it as information.\"",
"title": ""
},
{
"docid": "190497",
"text": "\"Sales tax and luxury tax is what you will have to pay tax wise, and they are non-refundable (in most cases but the rules vary area to area). This really tripped up some friends of mine I had come from England. The rules are complicated and regional. Sales tax is anywhere from 0% to 10.25% and are not usually applied to raw foods. Luxury taxes are usually state level and only apply to things most people consider a large purchase. Jewelry, cars, houses, etc. Not things your likely to buy. (Small, \"\"normal\"\" jewelry usually doesn't count. Diamond covered flava-flav clock ... probably has a luxury tax.) For sales tax, it can change a lot. Don't be afraid to ask. People ask all the time. It's normal. I personally add 10% to what I buy. Sales tax in my city is 7%, county is 6.5%, state is 6%. So you can get different rates depending on what side of the street you shop on some times. Under normal circumstances you do not get a refund on these taxes. Some states do give refunds. Usually however the trouble of getting that refund isn't worth it unless making a large purchase. You are not exempt from paying sales tax. (Depending on where you go you may get asked). Business are exempt if they are purchasing things to re-sell. Only the end customer pays sales tax. Depending on where you go, online purchases may not be subject to sales tax. Though they might. That, again, depends on city, county, and state laws. Normally, you will have to pay sales tax at the register. It will be calculated into your total, and show as a line item on your receipt. http://3.bp.blogspot.com/-yAvAm2BQ3xs/TudY-lfLDzI/AAAAAAAAAGs/gYG8wJeaohw/s1600/great%2Boutdoors%2Breceipt%2BQR-%2Bbefore%2Band%2Bafter.jpg Also some products have other non-refundable taxes. Rental car taxes, fuel taxes and road taxes are all likely taxes you will have to pay. Areas that have a lot of tourists, usually (but not always) have more of these kinds of taxes. Friendly note. DON'T BUY DVDs HERE! They won't work when you get home. I know you didn't ask but this catches a lot of people. Same for electronics (in many cases, specially optical drives and wireless).\"",
"title": ""
},
{
"docid": "46791",
"text": "\"ECI is relevant to non-resident aliens who are engaged in trade or business in the US. For that, you have to be present in the US, to begin with, or to own a business or property in the US. So the people to whom it is relevant are non-resident aliens in the US or business/property owners, not foreign contractors. From the IRS: The following categories of income are usually considered to be connected with a trade or business in the United States. You are considered to be engaged in a trade or business in the United States if you are temporarily present in the United States as a nonimmigrant on an \"\"F,\"\" \"\"J,\"\" \"\"M,\"\" or \"\"Q\"\" visa. The taxable part of any U.S. source scholarship or fellowship grant received by a nonimmigrant in \"\"F,\"\" \"\"J,\"\" \"\"M,\"\" or \"\"Q\"\" status is treated as effectively connected with a trade or business in the United States. If you are a member of a partnership that at any time during the tax year is engaged in a trade or business in the United States, you are considered to be engaged in a trade or business in the United States. You usually are engaged in a U.S. trade or business when you perform personal services in the United States. If you own and operate a business in the United States selling services, products, or merchandise, you are, with certain exceptions, engaged in a trade or business in the United States. For example, profit from the sale in the United States of inventory property purchased either in this country or in a foreign country is effectively connected trade or business income. Gains and losses from the sale or exchange of U.S. real property interests (whether or not they are capital assets) are taxed as if you are engaged in a trade or business in the United States. You must treat the gain or loss as effectively connected with that trade or business. Income from the rental of real property may be treated as ECI if the taxpayer elects to do so.\"",
"title": ""
},
{
"docid": "507107",
"text": "A non-resident alien is only allowed for deductions connected to producing a US-sourced income (See IRC Sec. 873). Thus you can only deduct things that qualify as business expenses, and State taxes on your wages. In addition you can deduct a bunch of stuff explicitly allowed (like tax preparation, charitable contributions, casualty losses, etc) but sales tax is not in that list.",
"title": ""
},
{
"docid": "367562",
"text": "I can only answer about the U.S. For question 2, I believe the answer is no. If you are a non-resident alien for tax purposes, then only income connected to the U.S. is reported as income on the tax return. Unless there were any non-deductible contributions to your pre-tax IRAs, when you convert to Roth IRA, the entire amount of the conversion is added to your income. So the tax consequence is the same as if you had that much additional U.S. income. If you are a non-resident alien with no other income in the U.S., then the income you have to report on your U.S. tax return will basically consist of the conversion. Non-resident aliens do not have a standard deduction. However, all people have a personal exemption. If we take 2013 as an example, the exemption is $3900 per person. We will assume that you will file as single or married filing separately (non-resident aliens cannot file as married filing jointly). The first $3900 of income is covered by the exemption, and is not counted in taxable income. For single and MFS, the next $8925 of income is taxed at 10%, then next $27325 of income is taxed at 15%, and so on. So if you convert less than the personal exemption amount every year ($3900 in 2013), then in theory you do not pay any taxes. If you convert a little bit more, then some of the conversion will be taxed at 10%, etc.",
"title": ""
}
] |
5abef9e55542990832d3a113
|
Lucky and Giant Robot were both what?
|
[
{
"docid": "7842128",
"text": "Lucky was a fashion and lifestyle magazine founded by Kim France and first published in 2000 under the Condé Nast subsidiary. The magazine folded in June 2015.",
"title": ""
},
{
"docid": "1243600",
"text": "Giant Robot was a bi-monthly magazine of Asian and Asian American popular culture founded in Southern California in 1994. It was initially created as a small, punk-minded magazine that featured Asian pop culture and Asian American alternative culture, including such varied subject matter as history, art, music, film, books, toys, technology, food and skateboarding. The publication grew from its original format—a small, photocopied zine, folded and stapled by hand—to its current full-color format.\" Giant Robot\" was one of the earliest American publications to feature prominent Asian film stars such as Chow Yun-fat and Jet Li, as well as Asian musicians from indie and punk rock bands. The coverage later expanded into art, design, Asian American issues, travel, and much more.",
"title": ""
}
] |
[
{
"docid": "2385573",
"text": "Giant Robot is the self-titled debut studio album by Giant Robot, led by guitarist Buckethead. The album was released in 1996. Buckethead had released a solo album entitled \"Giant Robot\" in 1994, and to distinguish the two albums, fans refer to this recording as \"Giant Robot NTT\", after the small recording company, NTT Records.",
"title": ""
},
{
"docid": "47807258",
"text": "Eric Nakamura is a Japanese American magazine publisher, gallerist, and entrepreneur. He is the co-founder of Giant Robot, owner of the Giant Robot store and GR2 Gallery, and curator of the Giant Robot Biennales and other museum exhibitions.",
"title": ""
},
{
"docid": "30852609",
"text": "The Giant Robot Project is an undertaking by Canadian inventor Jaimie Mantzel to construct a large six-legged robot.",
"title": ""
},
{
"docid": "10819076",
"text": "Giant Robo (ジャイアントロボ , Jaianto Robo ) is a manga by Mitsuteru Yokoyama, in which the huge robot of the same name as the title appears. Tokusatsu, Anime, etc. based on this manga were produced.",
"title": ""
},
{
"docid": "475232",
"text": "The Rest of the Robots is a collection of eight short stories and two full-length novels by American writer Isaac Asimov, published in 1964. The stories, centred on positronic robots, are all part of the \"Robot\" series, most of which take place in the \"Foundation\" universe. Another collection of short stories about robots, \"I, Robot\", was re-published in the previous year, which is why Asimov chose to title the collection as \"The Rest of the Robots\". None of the short stories in this collection were in \"I, Robot\", however all of them were later included in \"The Complete Robot\", and both novels about Elijah Baley were also published separately.",
"title": ""
},
{
"docid": "13398086",
"text": "Revenge of the Giant Robot is the debut album of Chicosci released on 2000 under EMI Philippines. It is the only album released when Chicosci was still named \"Chico Science\".",
"title": ""
},
{
"docid": "7759758",
"text": "Super Robot is a term used in manga and anime to describe a giant robot or mecha.",
"title": ""
},
{
"docid": "8004557",
"text": "Ultrabots (a.k.a. Xenobots - European title) is an MS-DOS computer game in which the player controls a group of giant robots and battles other giant robots. The game was developed by Novalogic and published by Electronic Arts.",
"title": ""
},
{
"docid": "10286562",
"text": "Daitetsujin 17 (大鉄人１７ , Daitetsujin Wan-Sebun ) is a 1977 \"tokusatsu\" series created by Shotaro Ishinomori and produced by Toei. It revolves around a giant battle robot commanded by a young boy who fights the giant robots of an evil organization bent on world conquest. It is similar to \"Giant Robo\" in premise and how it ends.",
"title": ""
},
{
"docid": "47582844",
"text": "MegaBots Inc. is an American startup company headquartered in Hayward, California that creates giant robots and real-world mecha for robotic sports competitions. In June 2015, MegaBots challenged Japan-based Suidobashi Heavy Industry to the world's first giant robot duel. Suidobashi accepted the challenge on the condition that the fight include melee combat. In August 2015, MegaBots announced plans to upgrade its Mark II robot with melee capabilities by raising funds through a Kickstarter campaign and partnering with Howe and Howe Technologies, NASA, and IHMC.",
"title": ""
},
{
"docid": "3678233",
"text": "Giant Robot is the second studio album by avant-garde guitarist Buckethead (not to be confused with the 1996 \"Giant Robot\", also featuring Buckethead) and loosely following the same \"amusement park\" concept as his previous album \"(Bucketheadland)\". It has some re-hashed songs from Buckethead's band Deli Creeps, as well his earlier demo tape \"Bucketheadland Blueprints\". One could describe this album as a more \"rock\" or \"musical\" album. Re-hashed songs have lost their \"basement\" or \"video game\" sounding beats and guitar licks compared to his debut album. Again, the album was originally a Japanese only release.",
"title": ""
},
{
"docid": "7759186",
"text": "\"The Robots\" (\"German Die Roboter\") is a single by the influential German electronic music pioneers, Kraftwerk, released in 1978. The single and its B-side, \"Spacelab\", both appeared on the band's seventh album, \"The Man-Machine\". However, the songs as they appear on the single were scaled down into shorter versions.",
"title": ""
},
{
"docid": "8289598",
"text": "The Leland Giants, originally the Chicago Union Giants, were a Negro league baseball team that competed independently during the first decade of the 20th century. The team was formed via a merge of the Chicago Unions and the Chicago Columbia Giants in 1901, and then split in 1910 to form the Chicago Giants and what would become known as the Chicago American Giants. The team was named after its owner and manager, Frank Leland.",
"title": ""
},
{
"docid": "42286339",
"text": "\"The Selfish Giant\" is a song recorded by English recording artist and songwriter and Blur frontman & Gorillaz creator, Damon Albarn, from his debut solo studio album \"Everyday Robots\". The track features Natasha Khan, known professionally as Bat for Lashes. The track is produced by both Albarn and Richard Russell, whom Albarn has previously worked with on Bobby Womack's comeback album \"The Bravest Man in the Universe\" and on the DRC Music album \"Kinshasa One Two\".",
"title": ""
},
{
"docid": "547176",
"text": "The Shogun Warriors were the main characters of a line of toys licensed by Mattel Inc. during the late 1970s. They were a series of imported Japanese toys based on several anime and tokusatsu shows featuring giant robots. They were originally manufactured in three sizes: 24 in plastic versions, 3.5 in die-cast metal versions, and slightly taller but much more detailed 5-inch (127 mm) die-cast versions. Several vehicles were also offered, as well as a set that could be put together to form the super robot Combattra. Toward the end of production, Mattel proposed the inclusion of plastic toy vehicles for the 3.5\" figures to ride in exclusively in the United States but these toys were not released for purchase.",
"title": ""
},
{
"docid": "50709",
"text": "Gundam (Japanese: ガンダム , Hepburn: Gandamu ) , also known as the Gundam Series (ガンダムシリーズ , Gandamu Shirīzu ) , is a science fiction media franchise created by Sunrise that features giant robots (mecha) with mobile suits bearing the name Gundam. It began on April 7, 1979 as \"Mobile Suit Gundam\", a TV series that defined the real robot anime genre by featuring giant robots in a militaristic setting. The popularity of the series and its merchandise spawned a franchise that includes television series, OVAs, films, manga, novels and video games.",
"title": ""
},
{
"docid": "2390786",
"text": "Roadblock was a combat robot that competed on the British television series \"Robot Wars\". Constructed in 1997 by A-level students from Bodmin Community College, the robot was initially called \"Road Rage\" but was renamed in response to a request from the programme's producers. Both names were derived from the robot's distinctive construction from metal roadsigns. Roadblock was champion of the first series of \"Robot Wars\" and finished in third place for the second series. Although Roadblock was armed with a circular saw weapon, its success was primarily due to its wedge-shaped body—Roadblock could drive underneath opponent robots and invert them, rendering many immobile.",
"title": ""
},
{
"docid": "842825",
"text": "The Iron Giant is a 1999 American animated science-fiction comedy-drama action film using both traditional animation and computer animation, produced by and directed by Brad Bird in his directorial debut. It is based on the 1968 novel \"The Iron Man\" by Ted Hughes (which was published in the United States as \"The Iron Giant\") and was scripted by Tim McCanlies from a story treatment by Bird. The film stars the voices of Eli Marienthal, Christopher McDonald, Jennifer Aniston, Harry Connick, Jr., John Mahoney, and Vin Diesel. Set during the Cold War in 1957, the film is about a young boy named Hogarth Hughes, who discovers a giant metallic robot who fell from space. With the help of beatnik artist Dean McCoppin, they attempt to prevent the U.S. military and Kent Mansley, a paranoid federal agent, from finding and destroying the Giant.",
"title": ""
},
{
"docid": "892538",
"text": "Isaac Asimov's Robot City is a series of novels written by various authors and loosely connected to Isaac Asimov's \"Robot\" series. It takes place between \"The Robots of Dawn\" and \"Robots and Empire\". Each volume is complete in itself, but they form a continuing series. The novels were written in response to a writing challenge issued by Asimov to write a series involving the Three Laws of Robotics, which brought about a collaboration of several authors. Asimov provided outlines for stories which filled in the gap between Asimov's own robot stories and his \"Foundation\" series, explaining the disappearance of the robots prior to the establishment of the galactic empire. \"Isaac Asimov's Robots and Aliens\" followed in this series, with the same protagonists and many other characters. The common theme of all books of both series is the interaction between the characters and autonomous cities run and populated by robots (the \"robot cities\" of the series title). Robot City was also released as a mystery game for the PC in 1995. The player takes the role of Derec.",
"title": ""
},
{
"docid": "4055998",
"text": "Robot software is the set of coded commands or instructions that tell a mechanical device and electronic system, known together as a robot, what tasks to perform. Robot software is used to perform autonomous tasks. Many software systems and frameworks have been proposed to make programming robots easier.",
"title": ""
},
{
"docid": "867311",
"text": "Robot Battle is a programming game for Microsoft Windows where players design and code adaptable battling robots. Robot Battle takes strategy rather than reflexes, accuracy, or timing to succeed. What differentiates one robot from the next is its programming, for which the player is responsible. The game is inspired by the similar game \"RobotWar\".",
"title": ""
},
{
"docid": "44177954",
"text": "War Robots (previously titled \"Walking War Robots\") is a freemium mobile app game developed and published by the Russian game developer Pixonic. It is a third-person shooter with real-time PvP battles in MOBA mode. Players operate mechs or giant robot on a live battlefield and they have the option to play solo or to team up with other players. It was first released on iOS in 2014 and was released to Android the following year.",
"title": ""
},
{
"docid": "37317591",
"text": "Yak: The Giant King (released as The Robot Giant in some countries and The Giant King in the U.S.) is a 2012 Thai 3D computer-animated comic science fiction children's/family film starring Santisuk Promsiri, Kreadtisuk Udomnak, Boribroon Junrieng, Weranut Tippayamontol, Pawanrat Naksuriya, Caninap Sirisawut, Udom Tarpanich, Bawriboon Chanreuang, Nathan LaVelle, Santisuk Promsiri, Udom Taephanit, Kerttisak Udomnak and Chris Wegoda, directed by Prapas Cholsaranont and Chaiporn Panichrutiwong and distributed by Workpoint Picture. The story is a futuristic adaptation of the fable of Tosakan and Hanuman the Monkey King from the Thai version of the Ramayana, with robots for the main characters. Literary reputation in Asia for the last 6 years and budget over 100 million baht. It was released on 4 October 2012",
"title": ""
},
{
"docid": "11270135",
"text": "Sleeping Giant, also known as Nounou Mountain, is a mountain ridge located west of the towns Wailua and Kapaʻ a in the Nounou Forest Reserve on the Hawaiian island of Kauaʻ i. The formation received its common English name both from its resemblance to a reclining human figure, and from a Native Hawaiian legend about a giant who, after great labor or overeating, lay to rest and is yet to awaken. Today Sleeping Giant is a major landmark for tourists visiting Kauai. Hiking trails lead to the highest point of the ridge, or what resembles a forehead. It is located at .",
"title": ""
},
{
"docid": "3183661",
"text": "Michael Andrew Hakopian, better known as Pinchface is the drummer of the Deli Creeps, Giant Robot II, and the Cornbugs. He has also appeared on numerous Buckethead albums, such as \"Population Override\" and \"Giant Robot\" (tracks \"I Come In Peace\" and \"Star Wars\"). He has also appeared on numerous occasions in Buckethead's \"Binge Clip Videos\". In 2006 he toured the United States with Buckethead and Delray Brewer. He also works as a real estate agent according to his Facebook page.",
"title": ""
},
{
"docid": "22066393",
"text": "Lucky to Be a Woman (Italian: La fortuna di essere donna and also known as What a Woman!) is a 1956 Italian comedy film directed by Alessandro Blasetti and starring Sophia Loren and Charles Boyer.",
"title": ""
},
{
"docid": "1944575",
"text": "The Smash Martians were the stars of a series of 1970s and early 1980s TV advertising campaigns for Smash instant mashed potato in the UK. They were a family of Martian robots who would watch humans laboriously preparing mashed potato the traditional way on TV. The robots would then mock what they saw by chortling as they heard how the \"Earth people peeled their own potatoes with their metal knives, boiled them for twenty of their minutes, then smashed them all to bits\" – instead of using Smash instant mash. The catchphrase 'For Mash Get Smash' is still an iconic advertising slogan in the UK. The adverts featuring the Smash Martians were voted TV ad of the century by Campaign Magazine.",
"title": ""
},
{
"docid": "37295520",
"text": "Istanbul Technical University Robot Olympics (ITURO) (Turkish: \"İstanbul Teknik Üniversitesi Robot Olimpiyatları (İTÜRO)\") is a robotic organization consisting competitions, seminars, colloquies, panel discussions, exhibitions and workshops that has been hosted by Istanbul Technical University Control and Automation Student Society since 2007. The three-day organization ITURO is organized at ITU Suleyman Demirel Cultural Center in Ayazağa Campus in every spring. In 2015, there were ten categories and the categories are being updated every year. Also, by the participation of experienced academics and industrial representatives, topics related to robotics and technology become discussed in both national and international manner.",
"title": ""
},
{
"docid": "202389",
"text": "Giant Robo, or (ジャイアントロボ , Jaianto Robo ) , known as Johnny Sokko and His Flying Robot in the United States, is a manga and tokusatsu series created by Mitsuteru Yokoyama. It is similar to Yokoyama's \"Tetsujin 28-go\" (known as \"Gigantor\" in the US), but \"Giant Robo\" has more elements of fantasy.",
"title": ""
},
{
"docid": "23321123",
"text": "RoboLogix is a robotics simulator which uses a physics engine to emulate robotics applications. The advantages of using robotics simulation tools such as RoboLogix are that they save time in the design of robotics applications and they can also increase the level of safety associated with robotic equipment since various \"what if\" scenarios can be tried and tested before the system is activated. RoboLogix provides a platform to teach, test, run, and debug programs that have been written using a five-axis industrial robot in a range of applications and functions. These applications include pick-and-place, palletizing, welding, and painting.",
"title": ""
}
] |
4904
|
What assets does the term “security” encompass?
|
[
{
"docid": "324879",
"text": "\"A good reference to what encompasses \"\"securities\"\" are detailed in the Securities Act of 1933, which was enacted by the United States federal government. One main exception, which I would still consider securities for your purposes, would be \"\"commercial paper\"\". These are exempt from the securities act because they mature in 270 days of less, but they function much like bonds or promissory notes Therefore though, it would not encompass currencies and commodities. It really comes down to the structure of the agreement for transferring or holding the particular kind of underlying asset.\"",
"title": ""
}
] |
[
{
"docid": "274870",
"text": "\"Mortgage is a (secured) debt, a combination of a promissory note, and a security interest providing the mortage holder a secured interest in the property. Yes, you are \"\"in debt\"\". But that depends upon whether you define the term \"\"in debt\"\" as a debt appearing on the balance sheet, or the net of assets - liabilities is less than zero, whether you have a \"\"debt\"\" expense on the income statement (budget), or whether the net of income - expenses is less than zero. One person might look at their budget, find the (monthly) mortgage payment listed, and judge that they have a debt payment, and thus are \"\"in debt\"\". Or they might look at their expenses, find they exceed their income, and judge that they are \"\"in debt\"\". Another person might look at their balance sheet, compare assets to liabilities, and only say they were \"\"in debt\"\" when their liabilities exceeded their assets. Some people view mortgage debt as \"\"good debt\"\", as they view certain debts as \"\"good\"\" and others as \"\"bad\"\". Trust me, having a high mortgage payment (higher 30% of your net income) is hard, and over 40% is bad. Consider you balance sheet and your income statement. On your balance sheet, the house appears on the \"\"asset\"\" side with an (estimated) value, while the \"\"mortgage\"\" (really, the promissory note part of the mortgage) appears on the \"\"liability\"\" side. On your income statement, your house does not appear on the income side, but the mortgage (promissory note) payment appears on the expense side. So, you clearly have both a \"\"liability\"\" with a clearly-defined value and an \"\"expense\"\" with a clearly-defined payment. But do you have an \"\"asset\"\"? According to an accountant, you have an \"\"asset\"\" and a \"\"liability\"\". But you do not have a business asset that is producing revenue (income), nor do you have a business asset that can be amortized and expensed to reduce taxable income. When we think about an asset, does the word have the connotation of some thing with value, something that produces income? Well, by that measure, a house only provides income when we rent it out, and only has value when we consider selling it. As millions of families discovered during the housing (price) collapse, when the market price of your \"\"asset\"\" falls substantially, your personal financial status can fall negative and you can be \"\"broke\"\".\"",
"title": ""
},
{
"docid": "27962",
"text": "\"I'd question whether a guaranteed savings instrument underperforming the stock market really is a risk, or not? Rather, you reap what you sow. There's a trade-off, and one makes a choice. If one chooses to invest in a highly conservative, low-risk asset class, then one should expect lower returns from it. That doesn't necessarily mean the return will be lower — stock markets could tank and a CD could look brilliant in hindsight — but one should expect lower returns. This is what we learn from the risk-return spectrum and Modern Portfolio Theory. You've mentioned and discounted inflation risk already, and that would've been one I'd mention with respect to guaranteed savings. Yet, one still accepts inflation risk in choosing the 3% CD, because inflation isn't known in advance. If inflation happened to be 2% after the fact, that just means the risk didn't materialize. But, inflation could have been, say, 4%. Nevertheless, I'll try and describe the phenomenon of significantly underperforming a portfolio with more higher-risk assets. I'd suggest one of: Perhaps we can sum those up as: the risk of \"\"investing illiteracy\"\"? Alternatively, if one were actually fully aware of the risk-reward spectrum and MPT and still chose an excessive amount of low-risk investments (such that one wouldn't be able to attain reasonable investing goals), then I'd probably file the risk under psychological risk, e.g. overly cautious / excessive risk aversion. Yet, the term \"\"psychological risk\"\", with respect to investing, encompasses other situations as well (e.g. chasing high returns.) FWIW, the risk of underperformance also came to mind, but I think that's mostly used to describe the risk of choosing, say, an actively-managed fund (or individual stocks) over a passive benchmark index investment more likely to match market returns.\"",
"title": ""
},
{
"docid": "280696",
"text": "\"In theory, the term of the bond does not affect the priority. It does not matter whether a \"\"Junior Subordinated Debenture\"\" is due in one year or sixty, it is still lower priority than a \"\"Secured Note\"\". On the other hand, if the \"\"Secured Note\"\" is secured by something that is not worth as much as the note, the excess is an unsecured debt. In practice, the term of the bond has two effects: Short term debt holders are more likely to get out just before the company goes broke. Sometimes their efforts to get out are exactly what causes the company to go broke! (\"\"Commercial paper\"\" is even more fickle than banks.) All other things being equal, and depending on the terms of the loan, some bonds get priority over bonds of the same type that are issued later. For example, your first mortgage usually takes precedence over your second mortgage.\"",
"title": ""
},
{
"docid": "437149",
"text": "\"Collateralized & Secured are interchangeable terms. Note the following two quotes from wikipedia (links below): \"\"A secured loan is a loan in which the borrower pledges some asset (e.g. a car or property) as collateral for the loan, which then becomes a secured debt owed to the creditor who gives the loan.\"\" http://en.wikipedia.org/wiki/Secured_loan \"\"In lending agreements, collateral is a borrower's pledge of specific property to a lender, to secure repayment of a loan.\"\" http://en.wikipedia.org/wiki/Collateral_%28finance%29 This website also uses the terms interchangeably: http://www.wisegeek.org/what-is-a-collateral-loan.htm Loan & Line of Credit are not interchangeable terms. In a loan, you receive a one time disbursement & repay it over a fixed amortization schedule. (Think home mortgage) In a line of credit, you can pay back & re-borrow from your credit line as often as you need. (Think credit card or Home Equity Line of Credit)\"",
"title": ""
},
{
"docid": "205522",
"text": "What you propose is to convert unsecured debt into secured debt. Conversion of unsecured debt into secured debt is not generally a good idea (several reasons). The debt you currently owe does not have assets securing the debt, so the creditor knows they are exposed to risk, and may be more willing to negotiate or relax terms on the debt, should you encounter problems. When you provide an asset to secure debt, you lose freedom to sell that asset. When you incur debt their is usually a spending problem that needs to be corrected, which is typically not fixed when a refinance solution is used. You do not mention interest rate, which would be one benefit to conversion of unsecured to secured debt, so you probably are not gaining adequate benefit from the conversion strategy. This strategy is often contemplated using 'cash-out' refinancing to borrow against a home you already own, and the (claimed) benefit is often to lower the interest rate on the debt. Your scenario is more complicated in that you have not purchased the home (yet). Though it may be a good idea to purchase a home, that choice depends on a different set of considerations (children, job stability, rental vs. buy costs, lifestyle, expected appreciation, etc) from how to best handle a large debt (income vs. expenses, how to increase income or reduce expenses, lifestyle, priorities, etc). Another consideration is that you already have a problem with the large debt owed to one (set of) creditor(s), and you have a plan which would shift the risk/exposure to another (set of) creditor(s) who may have been less complicit in accruing the original debt. Was the debt incurred jointly during the marriage, and something you accepted responsibility to repay? You mention that you make great income, and you specify one expense (rent), but you neither provided the amount of income, total of all your expenses, nor your free cash flow amount, nor any indication of percentages spent on rent, essential expenses, lifestyle, nor amount available to retire debt. Since you did not provide specifics, we can take a look at three scenarios, scenario #1, $4000/month income scenario #1, $6000/month income scenario #1, $8000/month income Depending upon your income and choices, you might have < $500/month to pay towards debt, or as much as $3000/month to pay towards debt, and depending upon interest rate (which OP did not provide), this debt could take < 2 years to pay or > 5 years to pay. Have you accepted the responsibility for the debt? It will be a tough task to repay the debt. And you will learn that debt comes with a cost as you repay it. One problem people often encounter when they refinance debt is they have not changed the habits which produced the debt. So they often continue their spending habits and incur new unsecured debt, landing them back in the same problem position, but with the increased secured debt combined with additional new unsecured debt. Challenge yourself to repay a specific portion of the debt in a specific time, and consider ways to reduce your expenses (and/or increase your income) to provide more money to repay the debt quicker. As you also did not disclose your assets, it is hard to know whether you could repay a portion of the debt from assets you already own. It makes sense to sell assets that have a low (or zero) return to repay debt that has a high interest rate. Perhaps you have substantial assets that you are reluctant to sell, but that you could sell to repay a large part of the debt?",
"title": ""
},
{
"docid": "16767",
"text": ">Better for you and for me, yes, but not for the disadvantaged without benefactors. That's the situation I was in. That wasn't exactly my point. I'm all for helping people, and social security does help people, and I am very happy it helped you - I'm not disputing that. What I'm saying is that what you got from social security is not as good as what you would have got from a $500,000 - $1,000,000 term life insurance policy. For people in there 20s, in good health, that kind of policy should be $20-$40/month, which could easily be bought with the money we otherwise spend on social security. (Now... whether parents would actually be responsible enough to buy term life insurance and put money towards retirement if we didn't have social security is a WHOOOOOOOOOLE nother discussion.) That's all I'm saying - I'd rather buy term life and invest for my own retirement because me and my family will come out ahead of where social security will put us. I'm really not a financial wizard, and I have to believe that this type of plan would work well for everyone else, too.",
"title": ""
},
{
"docid": "322645",
"text": "There is a measure of protection for investors. It is not the level of protection provided by FDIC or NCUA but it does exist: Securities Investor Protection Corporation What SIPC Protects SIPC protects against the loss of cash and securities – such as stocks and bonds – held by a customer at a financially-troubled SIPC-member brokerage firm. The limit of SIPC protection is $500,000, which includes a $250,000 limit for cash. Most customers of failed brokerage firms when assets are missing from customer accounts are protected. There is no requirement that a customer reside in or be a citizen of the United States. A non-U.S. citizen with an account at a brokerage firm that is a member of SIPC is treated the same as a resident or citizen of the United States with an account at a brokerage firm that is a member of SIPC. SIPC protection is limited. SIPC only protects the custody function of the broker dealer, which means that SIPC works to restore to customers their securities and cash that are in their accounts when the brokerage firm liquidation begins. SIPC does not protect against the decline in value of your securities. SIPC does not protect individuals who are sold worthless stocks and other securities. SIPC does not protect claims against a broker for bad investment advice, or for recommending inappropriate investments. It is important to recognize that SIPC protection is not the same as protection for your cash at a Federal Deposit Insurance Corporation (FDIC) insured banking institution because SIPC does not protect the value of any security. Investments in the stock market are subject to fluctuations in market value. SIPC was not created to protect these risks. That is why SIPC does not bail out investors when the value of their stocks, bonds and other investment falls for any reason. Instead, in a liquidation, SIPC replaces the missing stocks and other securities when it is possible to do so.",
"title": ""
},
{
"docid": "154697",
"text": "\"Marketing is much more than ad placement. It encompasses everything - product price, design, how it feels in your hand, how it tastes, where you buy it, what you think when you think of a product in your mind. Imagine something when you read the word \"\"soda\"\" - what comes to mind? Does it have a design? Color? A name? A label? Can you imagine the taste? Unless you live in a self sufficient commune, you are influenced by marketing to some degree.\"",
"title": ""
},
{
"docid": "491629",
"text": "\"Others have mentioned the term fiduciary but haven't really gone in to what that is. Despite the name \"\"financial advisor\"\" there is no legal (In the US) mandate as to what that means. Often times a financial advisor is little more than a sales rep whose job it is to sell particular financial instruments. These people will give you good generic advice such as \"\"make sure you have a nest egg\"\" and \"\"don't spend more than you make\"\". However when the rubber hits the road in terms of how to save they will often recommend/insist/pressure a particular asset/security which doesn't necessarily meet your risk/reward preference/tolerance. Often times the assets they pitch have high fees. These people won't charge you for their time because their time is a loss leader for the commissions they make on selling their products. In contrast a fiduciary's job responsibility is to look out for your interests. They shouldn't receive any kind of payment based on what assets you buy. This means that you have to pay them for their time. The NAPFA website seems to have good ideas on choosing an advisor. http://www.napfa.org/HowtoFindAnAdvisor.asp\"",
"title": ""
},
{
"docid": "575354",
"text": "The worst part of government induced tuition inflation wasn't even the GI Bill. Although I'm sure that started it a bit. It really took off in the late 1970s / 1980 with the establishment of the Department of Education and the Sallie Mae loan clearing house. There's a massive inflection point in historical inflation adjusted tuition prices right around 1980, when those were established. No coincidence. Also, you know whats worse than the **government** getting in the housing-price-inflation business? The freaking **central bank** getting in on the housing-price-inflation business. https://www.federalreserve.gov/monetarypolicy/quarterly-balance-sheet-developments-report.htm https://www.federalreserve.gov/monetarypolicy/files/quarterly_balance_sheet_developments_report_201708.pdf The federal reserve holds $4.4 T in total assets. That is the sole source of the entire money supply of the United States Dollar. It does not come from anywhere else. Of course, you get money velocity and money multipliers after that, but this is the origin. Of that $4.4 T, they hold $2.4 T in US Treasury securities. Ok, that's fine. That's the whole point of the federal reserve. They control the money supply through buying / selling (letting mature / redeem) US government securities. But wait, hold up, what the heck happened to the other $2.0 T in assets ... um, where did those go? There are some other assets, but the next largest ... the federal reserve owns $1.7 T in mortgage backed securities. Holy ... effing ... sheeeeeeeet. What in the actual f*** is the central bank doing buying mortgage backed securities? That absolutely, positively, is **NOT** monetary policy. That shit is fiscal policy, which the federal reserved is **NOT** supposed to be engaging in. And now you know why housing prices are even more effed up than tuition prices.",
"title": ""
},
{
"docid": "433806",
"text": "\"1) Are the definitions for capital market from the two sources the same? Yes. They are from two different perspectives. Investopedia is looking at it primarily from the perspective of a trader and they lead-off with the secondary market. This refers to the secondary market: A market in which individuals and institutions trade financial securities. This refers to the primary market: Organizations/institutions in the public and private sectors also often sell securities on the capital markets in order to raise funds. Also, the Investopedia definition leaves much to be desired, but it is supposed to be pithy. So, you are comparing apples and oranges, to some extent. One is an article, as short as it may be, this other one is an entry in a dictionary. 2) What is the opposite of capital market, according to the definition in investopedia? It's not quite about opposites, this is not physics. However, that is not the issue here. The Investopedia definition simply does not mention any other possibilities. The Wikipedia article defines the term more thoroughly. It talks about primary/secondary markets in separate paragraph. 3) According to the Wikipedia's definition, why does stock market belong to capital market, given that stocks can be held less than one year too? If you follow the link in the Wikipedia article to money market: As money became a commodity, the money market is nowadays a component of the financial markets for assets involved in short-term borrowing, lending, buying and selling with original maturities of one year or less. The key here is original maturities of one year or less. Here's my attempt at explaining this: Financial markets are comprised of money markets and capital markets. Money is traded as if it were a commodity on the money markets. Hence, the short-term nature in its definition. They are more focused on the money itself. Capital markets are focused on the money as a means to an end. Companies seek money in these markets for longer terms in order to improve their business in some way. A business may go to the money markets to access money quickly in order to deal with a short-term cash crunch. Meanwhile, a business may go to the capital markets to seek money in order to expand its business. Note that capital markets came first and money markets are a relatively recent development. Also, we are typically speaking about the secondary (capital) market when we are talking about the stock or bond market. In this market, participants are merely trading among themselves. The company that sought money by issuing that stock/bond certificate is out of the picture at that point and has its money. So, Facebook got its money from participants in the primary market: the underwriters. The underwriters then turned around and sold that stock in an IPO to the secondary market. After the IPO, their stock trades on the secondary market where you or I have access to trade it. That money flows between traders. Facebook got its money at the \"\"beginning\"\" of the process.\"",
"title": ""
},
{
"docid": "55443",
"text": "\"I have received a response from SIPC, confirming littleadv's answer: For a brief background, the protections available under the Securities Investor Protection Act (\"\"SIPA\"\"), are only available in the context of a liquidation proceeding of a SIPC member broker-dealer and relate to the \"\"custody\"\" of securities and related cash at the SIPC member broker-dealer. Thus, if a SIPC member broker-dealer were to fail at a time when a customer had securities and/or cash in the custody of the SIPC member broker-dealer, in most instances it would be SIPC's obligation to restore those securities and cash to the customer, within statutory limits. That does not mean, however, that the customer would necessarily receive the original value of his or her purchase. Rather, the customer receives the security itself and/or the value of the customer's account as of the day that the liquidation commenced. SIPC does not protect against the decline in value of any security. In a liquidation proceeding under the SIPA, SIPC may advance up to $500,000 per customer (including a $250,000 limit on cash in the account). Please note that this protection only applies to the extent that you entrust cash or securities to a U.S. SIPC member. Foreign broker dealer subsidiaries are not SIPC members. However, to the extent that any assets, including foreign securities, are being held by the U.S. broker dealer, the assets are protected by SIPC. Stocks listed on the LSE are protected by SIPC to the extent they are held with a SIPC member broker dealer, up to the statutory limit of $500,000 per customer. As I mentioned in the comments, in the case of IB, indeed they have a foreign subsidiary, which is why SIPC does not cover it (rather they are insured by Lloyds of London for such cases).\"",
"title": ""
},
{
"docid": "199237",
"text": "\"This is basically what financial advisers have been saying for years...that you should invest in higher risk securities when you are young and lower risk securities when you get older. However, despite the fact that this is taken as truth by so many financial professionals, financial economists have been unable to formulate a coherent theory that supports it. By changing the preferences of their theoretical investors, they can get solutions like putting all your investments in a super safe asset until you get to a minimum survival level for retirement and then investing aggressively and many other solutions. But for none of the typically assumed preferences does investing aggressively when young and becoming more conservative as you near retirement seem to be the solution. I'm not saying there can be no such preferences, but the difficulty in finding them makes me think maybe this idea is not actually correct. Couple of problems with your intuition that you should think about: It's not clear that things \"\"average out\"\" over time. If you lose a bunch of money in some asset, there's no reason to think that by holding that asset for a while you will make back what you lost--prices are not cyclical. Moreover, doesn't your intuition implicitly suggest that you should transition out of risky securities as you get older...perhaps after having lost money? You can invest in safe assets (or even better, the tangency portfolio from your graph) and then lever up if you do want higher risk/return. You don't need to change your allocation to risky assets (and it is suboptimal to do so--you want to move along the CAL, not the curve). The riskiness of your portfolio should generally coincide (negatively) with your risk-aversion. When you are older and more certain about your life expectancy and your assets, are you exposed to more or less risks? In many cases, less risks. This means you would choose a more risky portfolio (because you are more sure you will have enough to live on until death even if your portfolio takes a dive). Your actual portfolio consists both of your investments and your human capital (the present value of your time and skills). When you are young, the value of this capital changes significantly with market performance so you already have background risk. Buying risky securities adds to that risk. When you are old, your human capital is worth little, so your overall portfolio becomes less risky. You might want to compensate by increasing the risk of your investments. EDIT: Note that this point may depend on how risky your human capital is (how likely it is that your wage or job prospects will change with the economy). Overall the answer to your question is not definitively known, but there is theoretical evidence that investing in risky securities when young isn't optimal. Having said that, most people do seem to invest in riskier securities when young and safer when they are older. I suspect this is because with life experience people become less optimistic as they get older, not because it is optimal to do so. But I can't be sure.\"",
"title": ""
},
{
"docid": "549435",
"text": "An accountant should be able to advise on the tax consequences of different classes of investments/assets/debts (e.g. RRSP, TFSA, mortgage). But I would not ask an accountant which specific securities to hold in these vehicles, or what asset allocation (in terms of geography, capitalization, or class (equity vs fixed income vs derivatives vs structured notes etc). An investment advisor would be better suited to matching your investments to your risk tolerance.",
"title": ""
},
{
"docid": "403701",
"text": "This is really an extended comment on the last paragraph of @BenMiller's answer. When (the manager of) a mutual fund sells securities that the fund holds for a profit, or receives dividends (stock dividends, bond interest, etc.), the fund has the option of paying taxes on that money (at corporate rates) and distributing the rest to shareholders in the fund, or passing on the entire amount (categorized as dividends, qualified dividends, net short-term capital gains, and net long-term capital gains) to the shareholders who then pay taxes on the money that they receive at their own respective tax rates. (If the net gains are negative, i.e. losses, they are not passed on to the shareholders. See the last paragraph below). A shareholder doesn't have to reinvest the distribution amount into the mutual fund: the option of receiving the money as cash always exists, as does the option of investing the distribution into a different mutual fund in the same family, e.g. invest the distributions from Vanguard's S&P 500 Index Fund into Vanguard's Total Bond Index Fund (and/or vice versa). This last can be done without needing a brokerage account, but doing it across fund families will require the money to transit through a brokerage account or a personal account. Such cross-transfers can be helpful in reducing the amounts of money being transferred in re-balancing asset allocations as is recommended be done once or twice a year. Those investing in load funds instead of no-load funds should keep in mind that several load funds waive the load for re-investment of distributions but some funds don't: the sales charge for the reinvestment is pure profit for the fund if the fund was purchased directly or passed on to the brokerage if the fund was purchased through a brokerage account. As Ben points out, a shareholder in a mutual fund must pay taxes (in the appropriate categories) on the distributions from the fund even though no actual cash has been received because the entire distribution has been reinvested. It is worth keeping in mind that when the mutual fund declares a distribution (say $1.22 a share), the Net Asset Value per share drops by the same amount (assuming no change in the prices of the securities that the fund holds) and the new shares issued are at this lower price. That is, there is no change in the value of the investment: if you had $10,000 in the fund the day before the distribution was declared, you still have $10,000 after the distribution is declared but you own more shares in the fund than you had previously. (In actuality, the new shares appear in your account a couple of days later, not immediately when the distribution is declared). In short, a distribution from a mutual fund that is re-invested leads to no change in your net assets, but does increase your tax liability. Ditto for a distribution that is taken as cash or re-invested elsewhere. As a final remark, net capital losses inside a mutual fund are not distributed to shareholders but are retained within the fund to be written off against future capital gains. See also this previous answer or this one.",
"title": ""
},
{
"docid": "193485",
"text": "\"A nondividend distribution is typically a return of capital; in other words, you're getting money back that you've contributed previously (and thus would have been taxed upon in previous years when those funds were first remunerated to you). Nondividend distributions are nontaxable, so they do not represent income from capital gains, but do effect your cost basis when determining the capital gain/loss once that capital gain/loss is realized. As an example, publicly-traded real estate investment trusts (REITs) generally distribute a return of capital back to shareholders throughout the year as a nondividend distribution. This is a return of a portion of the shareholder's original capital investment, not a share of the REITs profits, so it is simply getting a portion of your original investment back, and thus, is not income being received (I like to refer to it as \"\"new income\"\" to differentiate). However, the return of capital does change the cost basis of the original investment, so if one were to then sell the shares of the REIT (in this example), the basis of the original investment has to be adjusted by the nondividend distributions received over the course of ownership (in other words, the cost basis will be reduced when the shares are sold). I'm wondering if the OP could give us some additional information about his/her S-Corp. What type of business is it? In the course of its business and trade activity, does it buy and sell securities (stocks, etc.)? Does it sell assets or business property? Does it own interests in other corporations or partnerships (sales of those interests are one form of capital gain). Long-term capital gains are taxed at rates lower than ordinary income, but the IRS has very specific rules as to what constitutes a capital gain (loss). I hate to answer a question with a question, but we need a little more information before we can weigh-in on whether you have actual capital gains or losses in the course of your S-Corporation trade.\"",
"title": ""
},
{
"docid": "215267",
"text": "It's still an asset because you're keeping it on your books in an interest bearing account. And it's still also a liability because as you note, the money is not technically yours and you owe it to the renter until you settle at the end of the lease/term. Thus, I'd recommend setting the security deposit up in two accounts - an asset account and a liability account. The two will cancel each other out so it won't add to your net worth or equity. If the money is in a bank account that's shared for other purposes, you can create a sub account for the security deposit: Assets->Savings->Bank->Security Deposit: $1500 and the liability can simply be: Liabilities->Security Deposit: $1500 You of course can modify these to best fit your account structure (e.g. organize by property, etc). Finally, instead of transferring the money from an 'Income' account to your savings account, you transfer it directly from the liability account in one go:",
"title": ""
},
{
"docid": "129309",
"text": "\"I was wondering how \"\"future cash flows of the asset\"\" are predicted? Are they also predicted using fundamental and/or technical analysis? There are a many ways to forecast the future cash flows of assets. For example, for companies: It seems like calculating expected/required rate using CAPM does not belong to either fundamental or technical analysis, does it? I would qualify the CAPM as quantitative analysis because it's mathematics and statistics. It's not really fundamental since its does not relies on economical data (except the prices). And as for technical analysis, the term is often used as a synonym for graphical analysis or chartism, but quantitative analysis can also be referred as technical analysis. the present value of future cash flows [...] (called intrinsic price/value, if I am correct?) Yes you are correct. I wonder when deciding whether an asset is over/fair/under-valued, ususally what kind of price is compared to what other kind of price? If it's only to compare with the price, usually, the Net asset value (which is the book value), the Discount Cash flows (the intrinsic value) and the price of comparable companies and the CAPM are used in comparison to current market price of the asset that you are studying. Why is it in the quote to compare the first two kinds of prices, instead of comparing the current real price on the markets to any of the other three kinds? Actually the last line of the quote says that the comparison is done on the observed price which is the market price (the other prices can't really be observed). But, think that the part: an asset is correctly priced when its estimated price is the same as the present value of future cash flows of the asset means that, since the CAPM gives you an expected rate of return, by using this rate to compute the present value of future cash flows of the asset, you should have the same predicted price. I wrote this post explaining some valuation strategies. Maybe you can find some more information by reading it.\"",
"title": ""
},
{
"docid": "283202",
"text": "\"The fact that some asset (in this case corporate bonds) has positive correlation with some other asset (equity) doesn't mean buying both isn't a good idea. Unless they are perfectly correlated, the best risk/reward portfolio will include both assets as they will sometimes move in opposite directions and cancel out each other's risk. So yes, you should buy corporate bonds. Short-term government bonds are essentially the risk-free asset. You will want to include that as well if you are very risk averse, otherwise you may not. Long-term government bonds may be default free but they are not risk free. They will make money if interest rates fall and lose if interest rates rise. Because of that risk, they also pay you a premium, albeit a small one, and should be in your portfolio. So yes, a passive portfolio (actually, any reasonable portfolio) should strive to reduce risk by diversifying into all assets that it reasonably can. If you believe the capital asset pricing model, the weights on portfolio assets should correspond to market weights (more money in bonds than stocks). Otherwise you will need to choose your weights. Unfortunately we are not able to estimate the true expected returns of risky assets, so no one can really agree on what the true optimal weights should be. That's why there are so many rules of thumb and so much disagreement on the subject. But there is little or no disagreement on the fact that the optimal portfolio does include risky bonds including long-term treasuries. To answer your follow-up question about an \"\"anchor,\"\" if by that you mean a risk-free asset then the answer is not really. Any risk-free asset is paying approximately zero right now. Some assets with very little risk will earn a very little bit more than short term treasuries, but overall there's nowhere to hide--the time value of money is extremely low at short horizons. You want expected returns, you must take risk.\"",
"title": ""
},
{
"docid": "452075",
"text": "Here is my perception of the situation, obtained from reading Degiro's Client Agreement. If Degiro shuts down, it will notify you about the fact at least one month in advance, and you will have enough time to order a transfer of your positions to a different broker. If Degiro shuts down unexpectedly, your assets will remain to be held at SPV, a separate legal entity which Degiro uses to hold the financial instruments belonging to the clients. Since SPV does nothing else but holding the assets, it is very unlikely that something bad will happen with it on its own. With some help from Degiro and/or the regulator (AFM) you should be able to transfer your assets from SPV to a different custodian and broker and thus regain control over them. If you have a non-Custody account, you have slightly higher chances of losing your assets, because Degiro can borrow your securities held at SPV. If both the client for whom Degiro borrowed a security and Degiro itself go bankrupt at the same time, the lent security will not be returned to SPV, there will arise a shortage, which will be proportionally distributed among the accounts of the clients holding this particular security. However, then the investor compensation scheme should kick in and help you recover up to 20000 EUR of your losses.",
"title": ""
},
{
"docid": "245867",
"text": "I strongly suggest you go to www.investor.gov as it has excellent information regarding these types of questions. A mutual fund is a company that pools money from many investors and invests the money in securities such as stocks, bonds, and short-term debt. The combined holdings of the mutual fund are known as its portfolio. Investors buy shares in mutual funds. Each share represents an investor’s part ownership in the fund and the income it generates. When you buy shares of a mutual fund you're buying it at NAV, or net asset value. The NAV is the value of the fund’s assets minus its liabilities. SEC rules require funds to calculate the NAV at least once daily. Different funds may own thousands of different stocks. In order to calculate the NAV, the fund company must value every security it owns. Since each security's valuation is changing throughout the day it's difficult to determine the valuation of the mutual fund except for when the market is closed. Once the market has closed (4pm eastern) and securities are no longer trading, the company must get accurate valuations for every security and perform the valuation calculations and distribute the results to the pricing vendors. This has to be done by 6pm eastern. This is a difficult and, more importantly, a time consuming process to get it done right once per day. Having worked for several fund companies I can tell you there are many days where companies are getting this done at the very last minute. When you place a buy or sell order for a mutual fund it doesn't matter what time you placed it as long as you entered it before 4pm ET. Cutoff times may be earlier depending on who you're placing the order with. If companies had to price their funds more frequently, they would undoubtedly raise their fees.",
"title": ""
},
{
"docid": "12481",
"text": "\"After the passage of the Emergency Economic Stabilization Act of 2008 and the implementation of the Troubled Asset Relief Program, the creation of an entirely new Office of Financial Stability in the treasury, the Term Asset-Backed Securities Loan Facility, the Public-Private Investment Program and the Legacy Loans and Legacy Securities Program, the Supervisory Capital Assessment Program, and the Housing and Economic Recovery Act of 2008, I find it remarkable that anyone can seriously think that the US government is not signalling, if not actually doing, *everything* it can short of nationalization to not allow a systemically important bank to collapse. This is to say nothing about the coining of an entirely new institution, the \"\"Too Big To Fail\"\" bank or \"\"Systemically Important Financial Institution\"\" (SIFI). BTW and FYI, [here](http://www.scribd.com/doc/10940608/0116TARP) is the CBO: >This is the first of CBO’s statutory reports on the TARP’s transactions. Through December 31, 2008, those transactions totaled $247 billion. [...][The] CBO estimates that the **subsidy cost** of those transactions (broadly speaking, the difference between what the Treasury paid for the investments or lent to the firms and the market value of those transactions) amounts to **$64 billion**.\"",
"title": ""
},
{
"docid": "63",
"text": "Here are the SEC requirements: The federal securities laws define the term accredited investor in Rule 501 of Regulation D as: a bank, insurance company, registered investment company, business development company, or small business investment company; an employee benefit plan, within the meaning of the Employee Retirement Income Security Act, if a bank, insurance company, or registered investment adviser makes the investment decisions, or if the plan has total assets in excess of $5 million; a charitable organization, corporation, or partnership with assets exceeding $5 million; a director, executive officer, or general partner of the company selling the securities; a business in which all the equity owners are accredited investors; a natural person who has individual net worth, or joint net worth with the person’s spouse, that exceeds $1 million at the time of the purchase, excluding the value of the primary residence of such person; a natural person with income exceeding $200,000 in each of the two most recent years or joint income with a spouse exceeding $300,000 for those years and a reasonable expectation of the same income level in the current year; or a trust with assets in excess of $5 million, not formed to acquire the securities offered, whose purchases a sophisticated person makes. No citizenship/residency requirements.",
"title": ""
},
{
"docid": "275852",
"text": "A Home Equity Line Of Credit (HELOC) is simply a special type of secured credit. Secured credit is credit provided to you, where the lender has some rights to an associated asset in the event that you default. In the case of a HELOC, much like a mortgage, if you default on the payment terms, the bank may be legally able to foreclose on your house, sell the foreclosed property, and take the money owed to it from the proceeds, leaving you with any net remainder. Whether your friend will be able to have a bank offer her credit secured against her business assets would depend on a variety of factors. She should talk to her bank to see whether it would be possible in her case.",
"title": ""
},
{
"docid": "163119",
"text": "\"negotiability is a legal concept that permits free transfer of a security without the requirement of prior consent of the issuer. that means the issuer must pay the current holder of the security, irrespective of who he is. negotiability also protects a good faith buyer of the instrument from adverse ownership claims of purported prior holders of the instrument. it is not related to \"\"negotiating\"\" the price or whatnot. A negotiable security means the current owner does not have to be concerned about acquiring the asset via a bad chain of title b/c he can always assert that he is a \"\"holder in due course\"\" defense against such claims, and have absolute security in his ownership right over the asset. securities and derivatives are different. securities are transferrable instruments representing a direct claim on the issuer for the value of the security, whether debt or equity ownership. derivatives are bilateral contracts, which can only be entered into with the consent of both parties, and can only be transferred by such consent. derivatives represent a claim against the parties of to the derivative that depends on some economic reference which is outside of the financial condition of the two parties to the contract, such as interest rates, FX rates, commodity prices, etc.\"",
"title": ""
},
{
"docid": "125981",
"text": "You can find out the general types of investments by reading the public corporation 10-Q report that is filed with the SEC it can be accessed via the EDGAR system. It will not tell you what securities they have, but it does identify the short term and long term investments categories and their value.",
"title": ""
},
{
"docid": "1472",
"text": "\"From what I've heard in the past, debt can be differentiated between secured debt and unsecured debt. Secured debt is a debt for which something stands good such as a mortgage on your house. You have a debt, but that debt is covered by the value of an asset and if you needed to free yourself of the debt, then you could by selling that asset. This is what is known as \"\"good\"\" debt. Unsecured debt is debt that is incurred where the only thing that is available to pay it back is your income. An example of this is credit card debt where you purchase something that couldn't be sold again to pay off the debt. This is know as \"\"bad\"\" debt. You have to be careful about thinking that house debt is always \"\"good\"\" debt because the house stands good for it though. The problem with that is that the house could go down in value and then suddenly your \"\"good\"\" debt is \"\"bad\"\" debt (or no longer secured). Cars are very risky this way because they go down in value. It is really easy to get a car loan where before long you are upside down. This is the problem with the term \"\"good\"\" debt. The label makes it sound like it is a good idea to have that debt, and the risk associated with having the debt is trivialized and allows yourself to feel good about your financial plan. Perhaps this is why so many houses are in foreclosure right now, people believed the \"\"good\"\" debt myth and thought that it was ok to borrow MORE than the home was worth to get into a house. Thus they turned a secured debt into an unsecured debt and put their residence at risk by levels of debt they couldn't afford. Other advice I've heard and tend to agree with, is that you should only borrow for a house, an education and maybe a car (danger on that last one), being careful to buy a modest house, car etc that is well within your means to repay. So if you do have to borrow for a car, go for basic transportation instead of the $40,000 BMW. Keep you house payment less than 1/4th of your take home pay. Pay off the school loans as quickly as possible. Regardless of the label, \"\"good\"\" \"\"bad\"\" \"\"unsecured\"\" \"\"secured\"\", I think that less debt is better than more debt. There is definitely such a thing as too much \"\"good\"\" debt!\"",
"title": ""
},
{
"docid": "453624",
"text": "\"Historically, Banks are mandated to take relatively safe risks with their money. In exchange, they gain a de-facto permission to invent new money. They have regulations about what mix of assets they are permitted to own. Real estate speculation will be in a different category than a mortgage to someone with good credit. Second, mortgages with a secured asset are pretty safe almost all of the time. That person might stop paying their mortgage, but it is secured; when that happens, the bank gets the secured asset (the right-to-apartment or house or what have you). In a sense, the bank loses only if both the person paying the mortgage is less creditworthy than they look, and the secured asset cannot recoup their losses. In comparison, the person paying the mortgage loses if the secured asset cannot recoup their losses. The bank is buffered from risk two fold. What more, the bank uses the customer to determine what to invest in. Deciding what to do with money is expensive and hard. By both having a customer willing to put their good credit on the line and doing due diligence on the apartment, the Bank in effect uses you as a consultant who decides this may be a solid investment. Much of the risk of failure is on you, so you have lots of incentive to make a good choice. If the Bank was instead deciding which apartment where worth buying, who would decide? A bank employee, whose bonus this year depends on finding a \"\"great apartment to invest in?\"\", but the consequence of a bad choice doesn't show up for many years? The people selling the bank the apartments? Such a business can exist. There are real estate companies that take money, and invest it in real estate. Often the borrow money from Banks secured against their existing real estate and use it to build more real estate. (Notice the bit about it being secured against existing real estate; things go south, Bank gets stuff). The Bank's indirect investment in that apartment in the current system is covered by appraisals, the seller, the mortgage holder, and the system deciding that the mortgage holder is creditworthy. Banks sell risk. They lend you money, you go off and do something risky with it, and they get a the low-risk return on investment of your loan. Multiple such low-risk investments provides them with a relatively dependable stream of money, which they give out to their bondholders, deposit account customers, shareholders or what have you. When you take a mortgage out for that, you are buying risk from the bank. You are more exposed to the failure of the investment than they are. They get less return if things go really well.\"",
"title": ""
},
{
"docid": "403755",
"text": "\"1) When it says \"\"an investment or mutual fund\"\", is a mutual fund not an investment? If no, what is the definition of an investment? A mutual fund is indeed an investment. The article probably mentions mutual funds separately from other investments because it is not uncommon for mutual funds to give you the option to automatically reinvest dividends and capital gains. 2) When it says \"\"In terms of stocks\"\", why does it only mention distribution of dividends but not distribution of capital gains? Since distributions are received as cash deposits they can be used to buy more of the stock. Capital gains, on the other hand, occur when an asset increases in value. These gains are realized when the asset is sold. In the case of stocks, reinvestment of capital gains doesn't make much sense since buying more stock after selling it to realize capital gains results in you owning as much stock as you had before you realized the gains. 3) When it says \"\"In terms of mutual funds\"\", it says about \"\"the reinvestment of distributions and dividends\"\". Does \"\"distributions\"\" not include distributions of \"\"dividends\"\"? why does it mention \"\"distributions\"\" parallel to \"\"dividends\"\"? Used in this setting, dividend and distribution are synonymous, which is highlighted by the way they are used in parallel. 4) Does reinvestment only apply to interest or dividends, but not to capital gain? Reinvestment only applies to dividends in the case of stocks. Mutual funds must distribute capital gains to shareholders, making these distributions essentially cash dividends, usually as a special end of year distribution. If you've requested automatic reinvestment, the fund will buy more shares with these capital gain distributions as well.\"",
"title": ""
},
{
"docid": "345091",
"text": "You should ensure that your broker is a member of the Securities Investor Protection Corporation (SIPC). SIPC protects the cash and securities in your brokerage account much like the Federal Deposit Insurance Corporation (FDIC) protects bank deposits. Securities are protected with a limit of $500,000 USD. Cash is protected with a limit of $250,000 USD. It should be noted that SIPC does not protect investors against loss of value or bad advice. As far as having multiple brokerage accounts for security, I personally don’t think it’s necessary to have multiple accounts for that reason. Depending on account or transaction fees, it might not hurt to have multiple accounts. It can actually be beneficial to have multiple accounts so long as each account serves a purpose in your overall financial plan. For example, I have three brokerage accounts, each of which serves a specific purpose. One provides low cost stock and bond transactions, another provides superior market data, and the third provides low cost mutual fund transactions. If you’re worried about asset security, there are a few things you can do to protect yourself. I would recommend you begin by consulting a qualified financial advisor about your risk profile. You stated that a considerable portion of your total assets are in securities. Depending on your risk profile and the amount of your net worth held in securities, you might be better served by moving your money into lower risk asset classes. I’m not an attorney or a financial advisor. This is not legal advice or financial advice. You can and should consult your own attorney and financial advisor.",
"title": ""
}
] |
PLAIN-1850
|
phosgene
|
[
{
"docid": "MED-3385",
"text": "Diacetyl-containing butter flavor was identified as the cause of an outbreak of bronchiolitis obliterans (BO) and other lung diseases in popcorn-plant workers. Litigation documents show that the outbreak was both predictable and preventable. The industry trade organization was aware of BO cases in workers at butter-flavoring and popcorn-manufacturing plants but often failed to implement industrial hygiene improvements and actively hid pertinent warning information. Due to weaknesses in the organization and mandates of regulatory bodies, organizations such as NIOSH, OSHA, the FDA, particularly the \"generally recognized as safe\" (GRAS) system, and the EPA failed to detect and prevent the outbreak, which highlights the need for systemic changes in food-product regulation, including the need for corporations to act responsibly, for stronger regulations with active enforcement, for a restructuring of the GRAS system, and for criminal penalties against corporations and professionals who knowingly hide information relevant to worker protection.",
"title": "Popcorn-worker lung caused by corporate and regulatory negligence: an avoidable tragedy."
},
{
"docid": "MED-3386",
"text": "Common complications of thoracic radiotherapy include esophagitis and radiation pneumonitis. However, it is important to be aware of uncommon post-radiotherapy complications such as bronchiolitis obliterans organizing pneumonia (BOOP). We report on two patients with carcinoma of the breast who developed an interstitial lung disease consistent with BOOP. BOOP responds to treatment with corticosteroids and the prognosis is generally good despite of the need for long-term administration of corticosteroids as relapses can occur during tapering of steroids. This report provides guidelines for the evaluation and treatment of patients with pulmonary infiltrates after radiotherapy.",
"title": "Bronchiolitis obliterans organizing pneumonia (BOOP) after thoracic radiotherapy for breast carcinoma"
},
{
"docid": "MED-3387",
"text": "Respiratory exposure to diacetyl and diacetyl-containing flavorings used in butter-flavored microwave popcorn (BFMP) causes lung disease, including bronchiolitis obliterans (BO), in flavorings and popcorn manufacturing workers. However, there are no published reports of lung disease among BFMP consumers. We present a case series of three BFMP consumers with biopsy-confirmed BO. We review data relating to consumer exposures, estimate case exposures, and compare them to diacetyl-containing flavoring-exposed manufacturing workers with lung disease. These consumer cases' exposure levels are comparable to those that caused disease in workers. We were unable to identify any other exposures or diseases known or suspected to cause BO in these cases. BFMP poses a significant respiratory risk to consumers. Some manufacturers have substituted diacetyl with other alpha-diketones that are likely to pose a similar risk. Simple consumer practices such as cooling the popcorn bag would eliminate the risk of severe lung disease.",
"title": "Bronchiolitis obliterans and consumer exposure to butter-flavored microwave popcorn: a case series."
}
] |
[
{
"docid": "MED-2712",
"text": "PURPOSE: We reviewed studies from 1990 to 2010 on using aromatherapy for people with anxiety or anxiety symptoms and examined their clinical effects. METHODS: The review was conducted on available electronic databases to extract journal articles that evaluated the anxiolytic effects of aromatherapy for people with anxiety symptoms. RESULTS: The results were based on 16 randomized controlled trials examining the anxiolytic effects of aromatherapy among people with anxiety symptoms. Most of the studies indicated positive effects to quell anxiety. No adverse events were reported. CONCLUSIONS: It is recommended that aromatherapy could be applied as a complementary therapy for people with anxiety symptoms. Further studies with better quality on methodology should be conducted to identify its clinical effects and the underlying biologic mechanisms.",
"title": "A systematic review on the anxiolytic effects of aromatherapy in people with anxiety symptoms."
},
{
"docid": "MED-2173",
"text": "MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes selective destruction of dopaminergic neurons of the nigrostriatal pathway in humans and other primates. It is less specific and much less potent in mice and has only slight effects in rats. Differences in rates and sites of metabolism of MPTP to its active, toxic, highly polar metabolite, MPP+ (1-methyl-4-phenylpyridine), appear to influence species specificity. In rats, type B monoamine oxidase (MAO-B), which mediates the conversion of MPTP to MPP+, may act as an enzymatic barrier at brain microvessels, whereas in primates the enzyme, present mainly in astrocytes, appears important for bioactivation of MPTP into the toxic metabolite. MPP+ is a substrate for catecholamine uptake sites and is concentrated in these neurons. The molecular mechanism of MPP+ toxicity has not been established definitively, but conversion to a free radical or uptake by mitochondria and inhibition of mitochondrial respiratory enzymes, leading to calcium release and cell death have been suggested. The discovery of toxin which causes an animal model of Parkinson's disease has stimulated new research on environmental factors that might contribute to this progressive degenerative disorder and provides a means for assessing new approaches to therapy.",
"title": "MPTP: an industrial chemical and contaminant of illicit narcotics stimulates a new era in research on Parkinson's disease."
},
{
"docid": "MED-2821",
"text": "The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.",
"title": "Turmeric (curcumin) remedies gastroprotective action"
},
{
"docid": "MED-837",
"text": "OBJECTIVE: We performed this study as a pilot experiment to investigate the short term effects of two diets of varying composition on weight loss as the primary outcome in obese women with polycystic ovary syndrome (PCOS) seeking fertility. DESIGN: Randomized clinical trial. SETTING: Academic medical center. PATIENT(S): Thirty-five obese women with PCOS. INTERVENTION(S): We examined the effects of a 1-month dietary intervention on the PCOS phenotype. Participants were randomized to one of two energy-restricted diets; high protein (HP: 30% protein, 40% carbohydrate, and 30% fat) or high carbohydrate (HC: 15% protein, 55% carbohydrate, and 30% fat). The fat content was held constant in both diets. MAIN OUTCOME MEASURE(S): Primary - change in body weight; Secondary - biometric, hormonal, lipid and lipoprotein, and markers of glucose homeostasis and energy metabolism. RESULT(S): Twenty-six women completed the study. Both the HP (-3.7 +/- 1.9 kg) and HC (-4.4 +/- 1.5 kg) diets resulted in significant weight loss, but there was no significant difference in mean weight loss between the two groups. There were also no differences between diets on a variety of measures including circulating androgens, measures of glucose metabolism, and leptin. However, the effects of a hypocaloric diet per se on improving metabolic and reproductive abnormalities in a group of PCOS women were marked by a decline in circulating androgens (P=.03), fasting and area under the curve (AUC) insulins (P<.05) on a 3-hour oral glucose tolerance test (OGTT), and fasting and AUC leptin levels (P<.0001). There was a high prevalence of menstrual bleeding during the trial (14 out of 26 patients). CONCLUSION(S): Those who completed the short-term hypocaloric diet had a significant weight loss and a significant improvement in their reproductive and metabolic abnormalities. There was no increased benefit to a high-protein diet. Future diet studies evaluating the ideal composition of a hypocaloric diet in women with PCOS will require a large study population, and will most likely require a multicenter trial.",
"title": "A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome."
},
{
"docid": "MED-5335",
"text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Does a vegan diet reduce risk for Parkinson's disease?"
},
{
"docid": "MED-3671",
"text": "This study examined the impact of academic stress on salivary cortisol concentrations and lactic acid bacteria activity. Whole, unstimulated saliva samples and faecal samples were collected from 23 healthy undergraduate students (23.0+/-6.8 years; range 18-44) over two 1-week periods: during the beginning of semester (low-stress baseline condition) and during the first week of exams (high-stress condition). Students also completed a series of questionnaires measuring perceived levels of stress, gastrointestinal symptoms, and nutritional intake. Significant findings indicated that faecal lactic acid bacterial levels were lower during the high-stress condition. Paralleling this, students rated perceived levels of stress as being greater during the exam period compared to the baseline condition. The findings from this study have provided further insight into the link between stress and gastrointestinal flora activity in humans.",
"title": "Investigating the role of perceived stress on bacterial flora activity and salivary cortisol secretion: a possible mechanism underlying susceptibil..."
},
{
"docid": "MED-4529",
"text": "Context Lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be present due to the practice of rasa shastra (combining herbs with metals, minerals, and gems). Whether toxic metals are present in both US- and Indian-manufactured Ayurvedic medicines is unknown. Objectives To determine the prevalence of Ayurvedic medicines available via the Internet containing detectable lead, mercury, or arsenic and to compare the prevalence of toxic metals in US- vs Indian-manufactured medicines and between rasa shastra and non–rasa shastra medicines. Design A search using 5 Internet search engines and the search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda, indicated for oral use, and available for sale. From 673 identified products, 230 Ayurvedic medicines were randomly selected for purchase in August–October 2005. Country of manufacturer/Web site supplier, rasa shastra status, and claims of Good Manufacturing Practices were recorded. Metal concentrations were measured using x-ray fluorescence spectroscopy. Main Outcome Measures Prevalence of medicines with detectable toxic metals in the entire sample and stratified by country of manufacture and rasa shastra status. Results One hundred ninety-three of the 230 requested medicines were received and analyzed. The prevalence of metal-containing products was 20.7% (95% confidence interval [CI], 15.2%–27.1%). The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%–30.4%) compared with 19.5% (95% CI, 11.3%–30.1%) in Indian products (P=.86). Rasa shastra compared with non–rasa shastra medicines had a greater prevalence of metals (40.6% vs 17.1%; P=.007) and higher median concentrations of lead (11.5 μg/g vs 7.0 μg/g; P=.03) and mercury (20 800 μg/g vs 34.5 μg/g; P=.04). Among the metal-containing products, 95% were sold by US Web sites and 75% claimed Good Manufacturing Practices. All metal-containing products exceeded 1 or more standards for acceptable daily intake of toxic metals. Conclusion One-fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain detectable lead, mercury, or arsenic.",
"title": "Lead, Mercury, and Arsenic in US- and Indian-Manufactured Ayurvedic Medicines Sold via the Internet"
},
{
"docid": "MED-860",
"text": "Microgreens (seedlings of edible vegetables and herbs) have gained popularity as a new culinary trend over the past few years. Although small in size, microgreens can provide surprisingly intense flavors, vivid colors, and crisp textures and can be served as an edible garnish or a new salad ingredient. However, no scientific data are currently available on the nutritional content of microgreens. The present study was conducted to determine the concentrations of ascorbic acid, carotenoids, phylloquinone, and tocopherols in 25 commercially available microgreens. Results showed that different microgreens provided extremely varying amounts of vitamins and carotenoids. Total ascorbic acid contents ranged from 20.4 to 147.0 mg per 100 g fresh weight (FW), while β-carotene, lutein/zeaxanthin, and violaxanthin concentrations ranged from 0.6 to 12.1, 1.3 to 10.1, and 0.9 to 7.7 mg/100 g FW, respectively. Phylloquinone level varied from 0.6 to 4.1 μg/g FW; meanwhile, α-tocopherol and γ-tocopherol ranged from 4.9 to 87.4 and 3.0 to 39.4 mg/100 g FW, respectively. Among the 25 microgreens assayed, red cabbage, cilantro, garnet amaranth, and green daikon radish had the highest concentrations of ascorbic acids, carotenoids, phylloquinone, and tocopherols, respectively. In comparison with nutritional concentrations in mature leaves (USDA National Nutrient Database), the microgreen cotyledon leaves possessed higher nutritional densities. The phytonutrient data may provide a scientific basis for evaluating nutritional values of microgreens and contribute to food composition database. These data also may be used as a reference for health agencies' recommendations and consumers' choices of fresh vegetables.",
"title": "Assessment of vitamin and carotenoid concentrations of emerging food products: edible microgreens."
},
{
"docid": "MED-4247",
"text": "In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.",
"title": "Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial."
},
{
"docid": "MED-4947",
"text": "The focus of the present study was on the relationship between Hong Kong male subfertility and fish consumption. Mercury concentrations found in the hair of 159 Hong Kong males aged 25-72 (mean age = 37 years) was positively correlated with age and was significantly higher in Hong Kong subjects than in European and Finnish subjects (1.2 and 2.1 ppm, respectively). Mercury in the hair of 117 subfertile Hong Kong males (4.5 ppm, P < 0.05) was significantly higher than mercury levels found in hair collected from 42 fertile Hong Kong males (3.9 ppm). Subfertile males had approx. 40% more mercury in their hair than fertile males of similar age. Although there were only 35 female subjects, they had significantly lower levels of hair mercury than males in similar age groups. Overall, males had mercury levels that were 60% higher than females. Hair samples collected from 16 vegetarians living in Hong Kong (vegans that had consumed no fish, shellfish or meat for at least the last 5 years) had very low levels of mercury. Their mean hair mercury concentration was only 0.38 ppm.",
"title": "Hong Kong male subfertility links to mercury in human hair and fish."
},
{
"docid": "MED-1763",
"text": "The current trends of increasing incidences of testis, breast and prostate cancers are poorly understood, although it is assumed that sex hormones play a role. Disrupted sex hormone action is also believed to be involved in the increased occurrence of genital abnormalities among newborn boys and precocious puberty in girls. In this article, recent literature on sex steroid levels and their physiological roles during childhood is reviewed. It is concluded that (i) circulating levels of estradiol in prepubertal children are lower than originally claimed; (ii) children are extremely sensitive to estradiol and may respond with increased growth and/or breast development even at serum levels below the current detection limits; (iii) no threshold has been established, below which no hormonal effects can be seen in children exposed to exogenous steroids or endocrine disruptors; (iv) changes in hormone levels during fetal and prepubertal development may have severe effects in adult life and (v) the daily production rates of sex steroids in children estimated by the Food and Drug Administration in 1999 and still used in risk assessments are highly overestimated and should be revised. Because no lower threshold for estrogenic action has been established, caution should be taken to avoid unnecessary exposure of fetuses and children to exogenous sex steroids and endocrine disruptors, even at very low levels.",
"title": "The sensitivity of the child to sex steroids: possible impact of exogenous estrogens."
},
{
"docid": "MED-1719",
"text": "OBJECTIVE: Overexpression of IGF-I occurs in tumors diagnosed in childhood (osteosarcoma, Wilms tumor, neuroblastoma, etc.) and in adults (breast, ovaries, colon and prostate cancer). The aim of our study was to establish the prevalence of malignancies in states of congenital IGF-I deficiency. SUBJECTS: We surveyed 222 patients with congenital IGF-I deficiency (Laron syndrome, GH gene deletion, GHRH receptor defects and IGF-I resistance) and 338 first and second-degree relatives. RESULTS: None of the IGF-I deficient patients had cancer, whereas 9-24% of the family members had a history of malignancy. CONCLUSIONS: Congenital IGF-I deficiency acts as a protecting factor for the development of cancer.",
"title": "Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report."
},
{
"docid": "MED-1208",
"text": "The growing macabre fascination with \"last meals\" offers a window into one's true consumption desires when one's value of the future is discounted close to zero. But in contrast to popular anecdotes and individual case studies, we created an empirical catalog of actual last meals - the final food requests of 247 individuals executed in the United States during a recent five-year period. Our content analyses reveal three key findings: (1) the average last meal is calorically rich (2756 calories) and proportionally averages 2.5 times the daily recommended servings of protein and fat, (2) the most frequent requests are also calorie dense: meat (83.9%), fried food (67.9%), desserts (66.3%), and soft drinks (60.0%), and (3) 39.9% requested branded foods or beverages. These findings are respectfully consistent with a model of environmentally contingent temporal discounting, and they are consistent with studies of how food is used to mediate feelings of stress and distress. Given that some people who are warned about the ill effects of obesity might counterintuitively engage in unhealthy overconsumption, the findings also suggest further study relating to the artificial use of mortality salience in campaigns against obesity. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Death row nutrition. Curious conclusions of last meals."
},
{
"docid": "MED-2079",
"text": "Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (-8.78%, -13.72% and -20.80%, respectively; P<.05) compared with baseline period, while high-density lipoprotein cholesterol remained unchanged. Strawberry supplementation also significant decreased serum malondialdehyde, urinary 8-OHdG and isoprostanes levels (-31.40%, -29.67%, -27.90%, respectively; P<.05). All the parameters returned to baseline values after the washout period. A significant increase in plasma total antioxidant capacity measured by both ferric reducing ability of plasma and oxygen radical absorbance capacity assays and vitamin C levels (+24.97%, +41.18%, +41.36%, respectively; P<.05) was observed after strawberry consumption. Moreover, the spontaneous and oxidative hemolysis were significant reduced (-31.7% and -39.03%, respectively; P<.05), compared to the baseline point, which remained stable after the washout period. Finally, strawberry intake significant decrease (P<.05) the number of activated platelets, compared to both baseline and washout values. Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans."
},
{
"docid": "MED-864",
"text": "Hepatotoxic effect related to Ganoderma lucidum (Lingzhi) mushroom powder was first described in a patient from Hong Kong in 2004. In 2005, the authors experienced a case of fatal fulminant hepatitis associated with such a preparation. Both patients had taken other therapeutic agents and traditionally boiled Lingzhi without any toxic effect. After switching to taking Lingzhi in powder form for 1-2 months, the hepatotoxic episode occurred in both patients. The toxic role of Lingzhi powder needs close monitoring in the future, especially in combination with other drugs.",
"title": "Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder."
},
{
"docid": "MED-3842",
"text": "The mammalian lignans enterolactone and enterodiol, which are produced by the microflora in the colon of humans and animals from precursors in foods, have been suggested to have potential anticancer effects. This study determined the production of mammalian lignans from precursors in food bars containing 25 g unground whole flaxseed (FB), sesame seed (SB), or their combination (FSB; 12.5 g each). In a randomized crossover study, healthy postmenopausal women supplemented their diets with the bars for 4 wk each separated by 4-wk washout periods, and urinary mammalian lignan excretion was measured at baseline and after 4 wk as a marker of mammalian lignan production. Results showed an increase with all treatments (65.1-81.0 mumol/day; P < 0.0001), which did not differ among treatments. Lignan excretion with the whole flaxseed was similar to results of other studies using ground flaxseed. An unidentified lignan metabolite was detected after consumption of SB and FSB but not of FB. Thus, we demonstrated for the first time that 1) precursors from unground whole flaxseed and sesame seed are converted by the bacterial flora in the colon to mammalian lignans and 2) sesame seed, alone and in combination with flaxseed, produces mammalian lignans equivalent to those obtained from flaxseed alone.",
"title": "Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed."
},
{
"docid": "MED-1036",
"text": "Much evidence indicates that there is an increased motor activity in the colon from eating in several species of animals. Though some of this effect may be cephalic in origin, the greater part of the response results from the arrival of food in the stomach and proximal intestine. Chemoreceptor stimulation appears to be more important than mechanoreceptor stimulation in bringing about this effect. The means by which this effect comes about could be either hormonal or neural. Several polypeptide hormones released from the proximal gut by eating are candidates. Neural pathways through both parasympathetic and sympathetic systems could be responsible. The exact nature of the change in colonic motility that is produced is unknown. It could involve changes in the pacemakers for colonic contractions (the electrical slow waves of the colon and the migrating spike burst of the colon), changes in the excitability of the colonic musculature or changes in colonic mucosal function.",
"title": "The response of the colon to eating."
},
{
"docid": "MED-861",
"text": "OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.",
"title": "Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica."
},
{
"docid": "MED-4443",
"text": "Flaxseed is one of the most important oilseed crops for industrial as well as food, feed, and fiber purposes. Almost every part of the flaxseed plant is utilized commercially, either directly or after processing. The stem yields good quality fiber having high strength and durability. The seed provides oil rich in omega-3, digestible proteins, and lignans. In addition to being one of the richest sources of α-linolenic acid oil and lignans, flaxseed is an essential source of high quality protein and soluble fiber and has considerable potential as a source of phenolic compounds. Flaxseed is emerging as an important functional food ingredient because of its rich contents of α-linolenic acid (ALA), lignans, and fiber. Lignans appear to be anti-carcinogenic compounds. The omega-3s and lignan phytoestrogens of flaxseed are in focus for their benefits for a wide range of health conditions and may possess chemo-protective properties in animals and humans. This paper presents a review of literature on the nutritional composition of flaxseed, its health benefits, and disease-prevention qualities, utilization of flaxseed for food, feed, and fiber, and processing of flaxseed.",
"title": "Flaxseed: a potential source of food, feed and fiber."
},
{
"docid": "MED-4203",
"text": "Oxygen is vital for most organisms but, paradoxically, damages key biological sites. Oxygenic threat is met by antioxidants that evolved in parallel with our oxygenic atmosphere. Plants employ antioxidants to defend their structures against reactive oxygen species (ROS; oxidants) produced during photosynthesis. The human body is exposed to these same oxidants, and we have also evolved an effective antioxidant system. However, this is not infallible. ROS breach defences, oxidative damage ensues, accumulates with age, and causes a variety of pathological changes. Plant-based, antioxidant-rich foods traditionally formed the major part of the human diet, and plant-based dietary antioxidants are hypothesized to have an important role in maintaining human health. This hypothesis is logical in evolutionary terms, especially when we consider the relatively hypoxic environment in which humans may have evolved. In this paper, the human diet is discussed briefly in terms of its evolutionary development, different strategies of antioxidant defence are outlined, and evolution of dietary antioxidants is discussed from the perspectives of plant need and our current dietary requirements. Finally, possibilities in regard to dietary antioxidants, evolution, and human health are presented, and an evolutionary cost-benefit analysis is presented in relation to why we lost the ability to make ascorbic acid (vitamin C) although we retained an absolute requirement for it.",
"title": "Evolution of dietary antioxidants."
},
{
"docid": "MED-3420",
"text": "Introduction Erectile dysfunction (ED) and cardiovascular disease (CVD) share pathophysiological mechanisms and often co-occur. Yet it is not known whether ED provides an early warning for increased CVD or other causes of mortality. Aim We sought to examine the association of ED with all-cause and cause-specific mortality. Methods Prospective, population-based study of 1,709 men (of 3,258 eligible) aged 40–70 years. ED was measured by self-report. Subjects were followed for a mean of 15 years. Hazard ratios (HR) were calculated using the Cox proportional hazards regression model. Main outcome measures Mortality due to all causes, CVD, malignant neoplasms, and other causes. Results Of 1,709 men, 1,284 survived to the end of 2004 and had complete ED and age data. Of 403 men who died, 371 had complete data. After adjustment for age, body mass index, alcohol consumption, physical activity, cigarette smoking, self-assessed health, and self-reported heart disease, hypertension, and diabetes, ED was associated with HRs of 1.26 [95% confidence interval (CI), 1.01–1.57] for all-cause mortality and 1.43 (95% CI, 1.00–2.05) for CVD mortality. The HR for CVD mortality associated with ED is of comparable magnitude to HRs of some conventional CVD risk factors. Conclusions These findings demonstrate that ED is significantly associated with increased all-cause mortality, primarily through its association with CVD mortality.",
"title": "Erectile Dysfunction and Mortality"
},
{
"docid": "MED-4563",
"text": "BACKGROUND: The use of nasal irrigation for the treatment of nose and sinus complaints has its foundations in yogic and homeopathic traditions. There has been increasing use of saline irrigation, douches, sprays and rinsing as an adjunct to the medical management of chronic rhinosinusitis. Treatment strategies often include the use of topical saline from once to more than four times a day. Considerable patient effort is often involved. Any additional benefit has been difficult to discern from other treatments. OBJECTIVES: To evaluate the effectiveness and safety of topical saline in the management of chronic rhinosinusitis. SEARCH STRATEGY: Our search included the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4 2006), MEDLINE (1950 to 2006) and EMBASE (1974 to 2006). The date of the last search was November 2006. SELECTION CRITERIA: Randomised controlled trials in which saline was evaluated in comparison with either no treatment, a placebo, as an adjunct to other treatments or against treatments. The comparison of hypertonic versus isotonic solutions was also compared. DATA COLLECTION AND ANALYSIS: Trials were graded for methodological quality using the Cochrane approach (modification of Chalmers 1990). Only symptom scores from saline versus no treatment and symptom and radiological scores from the hypertonic versus isotonic group could be pooled for statistical analysis. A narrative overview of the remaining results is presented. MAIN RESULTS: Eight trials were identified that satisfied the inclusion criteria. Three studies compared topical saline against no treatment, one against placebo, one as an adjunct to and one against an intranasal steroid spray. Two studies compared different hypertonic solutions against isotonic saline. There is evidence that saline is beneficial in the treatment of the symptoms of chronic rhinosinusitis when used as the sole modality of treatment. Evidence also exists in favour of saline as a treatment adjunct. No superiority was seen when saline was compared against a reflexology 'placebo'. Saline is not as effective as an intranasal steroid. Some evidence suggests that hypertonic solutions improve objective measures but the impact on symptoms is less clear. AUTHORS' CONCLUSIONS: Saline irrigations are well tolerated. Although minor side effects are common, the beneficial effect of saline appears to outweigh these drawbacks for the majority of patients. The use of topical saline could be included as a treatment adjunct for the symptoms of chronic rhinosinusitis.",
"title": "Nasal saline irrigations for the symptoms of chronic rhinosinusitis."
},
{
"docid": "MED-4374",
"text": "CONTEXT: Despite cancer patients' widespread and growing use of complementary and alternative medicine, minimal attention has been paid to the role of health food stores in the \"supply side\" of this phenomenon. OBJECTIVE: To gain a better understanding of health food store personnel's recommendations for breast cancer patient care. DESIGN: Researcher posing as the daughter of a breast cancer patient and surveying health food store personnel on their product recommendations for cancer care. SETTING: Oahu, Hawaii, summer 1998. PARTICIPANTS: All health food stores (N = 40) offering products for cancer patients. MAIN OUTCOME MEASURES: Recommended products and services, proposed mechanism of action, and costs. RESULTS: Store personnel readily provided information and product recommendations, with shark cartilage being the most frequent. Suggested mechanisms of action drew on traditional healing, scientific, and pseudoscientific rationales. Costs for recommended dosages varied multifold across stores and brands. CONCLUSIONS: Retailers supplying supplements can play an important role in the network of \"authorities\" for patients with breast and other cancers, as they readily provide advice and recommend products. The reasons why patients seek health food store remedies are useful in developing approaches to patient education. Physicians and other providers are in a key position to assist cancer patients in making informed choices when considering health store products.",
"title": "Health food store recommendations for breast cancer patients."
},
{
"docid": "MED-2945",
"text": "BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS: One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.",
"title": "Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men."
},
{
"docid": "MED-1027",
"text": "Current concepts on the aetiology of varicose veins, deep vein thrombosis, and haemorrhoids have been examined and, in the light of epidemiological evidence, found wanting.It is suggested that the fundamental cause of these disorders is faecal arrest which is the result of a low-residue diet.",
"title": "Varicose Veins, Deep Vein Thrombosis, and Haemorrhoids: Epidemiology and Suggested Aetiology"
},
{
"docid": "MED-3399",
"text": "We investigated the effects of Antep pistachio on International Index of Erectile Function (IIEF) scores, penile color Doppler ultrasound (PCDU) parameters and serum lipid levels in patients with ED. A total of 17 married male patients with ED for at least 12 months were included in this prospective study. Patients were put on a 100 g pistachio nuts diet for 3 weeks. IIEF and PCDU were evaluated before and after the pistachio diet. In addition, plasma total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride were measured before and after dietary modifications from all subjects. Mean IIEF-15 score was 36 ± 7.5 before the diet and 54.2 ± 4.9 after the diet (P=0.001). Similarly, an increase in all five domains of IIEF was observed after the diet (P<0.05). Mean peak systolic velocity values before and after the pistachio diet were 35.5 ± 15.2 and 43.3 ± 12.4 cm s(-1), respectively (P=0.018). After the pistachio diet, TC and LDL levels decreased significantly, whereas HDL level increased (P=0.008, 0.007 and 0.001, respectively). We demonstrated that a pistachio diet improved IIEF scores and PCDU parameters without any associated side effects in patients with ED. Furthermore, the lipid parameters showed statistically significant improvements after this diet.",
"title": "Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction."
},
{
"docid": "MED-2488",
"text": "Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.",
"title": "Food prices and blood cholesterol."
},
{
"docid": "MED-3730",
"text": "Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the basis of this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 g/d, did not significantly affect histology or any other measured parameter. The dose of 60 g/d, however, reduced the histologic grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho-nuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present results indicate the potential of freeze-dried strawberry powder for preventing human esophageal cancer, supporting further clinical testing of this natural agent in this setting. ©2011 AACR.",
"title": "Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus."
},
{
"docid": "MED-5142",
"text": "OBJECTIVE: We describe a case of irreversible subacute sclerotic combined degeneration of the spinal cord in a Western vegan subject. METHODS: A 57-y-old man, member of a vegan cult for 13 y, developed weakness, paraplegia, hyper-reflexia, distal symmetric muscular hypotrophy, impairment of superficial sensation in the hands and feet, loss of deep sensation in the lower limbs, and neurogenic bladder and bowel. Magnetic resonance imaging of the cervical and dorsal spine disclosed abnormally increased signal intensity on T(2)-weighted sections in the posterior and lateral columns. Subacute sclerotic combined degeneration of the spinal cord was diagnosed and treatment with cobalamin was started. RESULTS: Despite rehabilitative treatment, the patient developed spastic hypertonia with mild improvement of paresthesias. Six months later, vitamin B12 plasma levels and hematological analysis were normal. One year later, spastic paraplegia was still present and the patient was unable to walk despite improvement on magnetic resonance imaging. CONCLUSION: Irreversible subacute sclerotic combined degeneration of the spinal cord is a rare but possible effect of a strict vegetarian diet.",
"title": "Irreversible subacute sclerotic combined degeneration of the spinal cord in a vegan subject."
},
{
"docid": "MED-4430",
"text": "Guillain-Barré syndrome (GBS) is a classic failure of the immune system with a life-threatening attack upon a critical self-component. The active phase of the disease is short, concordant with the latency of a primary adaptive immune response. Triggers for GBS include infection and (rarely) vaccination; cross-reactivity between infectious and neural epitopes has been well demonstrated, particularly for Campylobacter jejuni and motor axonal forms of GBS in which non-protein gangliosides are antigenic. Most people are probably exposed to a GBS trigger, but only rarely does the disease develop. We propose that GBS illustrates competing determinants of the immune system's decision about whether to mount a response, and that in unlucky affected individuals, co-presentation of cross-reactive antigens with danger signals activating pattern-recognition receptors overcomes normal self-recognition such that a primary response is initiated that attacks the nerve. Then, in most cases of GBS, the response rapidly turns off, and second attacks rarely occur. This suggests active restoration of tolerance, and specific privileged site attributes of nerve and declining danger signals as the trigger wanes may contribute to this restoration. Standard immunosuppression has not been effective in GBS. We suggest this is because immune tolerance is already being restored by the time such therapies are initiated. This in turn suggests that improvements in GBS outcomes are likely to come from better protection of the nerve cells under attack while normal resumption of tolerance is permitted to proceed rather than exploring more aggressive immunosuppressive approaches.",
"title": "Guillain-barré syndrome: modern theories of etiology."
}
] |
4821
|
Financed medical expenses and tax deductions
|
[
{
"docid": "495344",
"text": "You deduct expenses when you incur them (when you pay the hospital, for example). Medical expenses are deducted on Schedule A, subject to 7.5% AGI threshold. Financed or not - doesn't matter. The medical expense is deductible (if it is medically necessary), the loan interest is not.",
"title": ""
}
] |
[
{
"docid": "187448",
"text": "\"The HSA tax deduction comes when you contribute money to the HSA, not when you take money out. So you can contribute up to the max and take your maximum deduction each year, regardless of what medical expenses you have. If you have medical expenses, but no money left in your HSA, you will just have to pay for them out-of-pocket. However, in the future when your HSA has money in it again, you can reimburse yourself for medical expenses you have now. As long as you have an HSA in place (even if there is no money in it currently), there is no time limit to reimburse yourself for those medical expenses. Reimburse yourself for what you can, and keep track of whatever expenses you are unable to reimburse at this time. Hopefully, in a future year your health will improve (or your medical coverage will improve), and you can \"\"catch up\"\" reimbursing yourself for these old expenses. Regarding your question about tax benefit: The HSA acts similar to a traditional IRA when invested, growing tax-deferred. So if you contribute, and choose not to withdraw but instead invest, there are tax advantages, similar to an IRA. However, if you are already investing a sufficient amount in retirement accounts, there is nothing wrong with reimbursing yourself now for the expenses if you need the money. You get the primary tax deduction either way.\"",
"title": ""
},
{
"docid": "462831",
"text": "In the US there's no significant difference between what a business can deduct and what an individual can deduct. However, you can only deduct what is an expense to produce income. Businesses are allowed to write off salaries, but individuals can't write off what they pay their gardener or maid (at least in the US) If you're a sole proprietor in the business of managing properties - you can definitely deduct payments to gardeners or maids. Business paying for a gardener on a private property not related to producing the income (like CEO's daughter's house) cannot deduct that expense for tax purposes (although it is still recorded in the business accounting books as an expense - with no tax benefit). Businesses are allowed to deduct utility expenses as overhead, individuals cannot Same thing exactly. I can deduct utility expenses for my rental property, but not for my primary residence. Food, shelter, clothing and medical care are fundamental human needs, but we still pay for them with after-tax money, and pay additional sales tax. Only interest (and not principal) on a mortgage is deductible in the US, which is great for people who take out mortgages (and helps banks get more business, I'm sure), but you're out of luck if you pay cash for your house, or are renting. Sales taxes are deductible. You can deduct sales taxes you paid during the year if you itemize your deduction. You can chose - you either deduct the sales taxes or the State income taxes, whatever is more beneficial for you. BTW in many states food and medicine are exempt from sales tax. Medical expenses are deductible if they're significant compared to your total income. You can deduct medical expenses in excess of 10% of your AGI. With the ACA kicking in - I don't see how would people even get to that. If your AGI is low you get subsidies for insurance, and the insurance keeps your expenses capped. For self-employed and employed, insurance premiums are pre-tax (i.e.: not even added to your AGI). Principle for mortgage is not deductible because it is not an expense - it is equity. You own an asset, don't you? You do get the standard deduction, even if your itemized (real) deductions are less - business don't get that. You also get an exemption amount (for your basic living needs), which businesses don't get. You can argue about the amounts - but it is there. In some States (like California) renters get tax breaks for renting, depending on the AGI. CA renters credit is phasing out at AGI of about $60K, which is pretty high.",
"title": ""
},
{
"docid": "249228",
"text": "You can use it for medical expenses even if you don't have a high deductible policy. It can cover prescriptions, copays, deductibles, co-insurance, dentist, orthodontics... As long as it is being used for an approved medical expense there is no tax or penalty. Yes it doesn't save you on the monthly service charges but it does allow you to cut your medical expenses for a while.",
"title": ""
},
{
"docid": "41793",
"text": "\"You can deduct what you pay for your own and your family's health insurance regardless of whether it is subsidized by your employer or not, as well as all other medical and dental expenses for your family, as an itemized deduction on Schedule A of Form 1040, but only to the extent that the total exceeds 7.5% of your Adjusted Gross Income (AGI) (10% on tax returns for year 2013 onwards). As pointed out in KeithB's comment, you cannot deduct any health insurance premium (or other medical expense) that was paid for out of pre-tax dollars, nor indeed can you deduct any medical expense to the extent that it was paid for by the insurance company directly to hospital or doctor (or reimbursed to you) for a covered expense; e.g. if the insurance company reimbursed you $72 for a claim for a doctor's visit for which you paid $100 to the doctor, only $28 goes on Schedule A to be added to the amount that you will be comparing to the 7.5% of AGI threshold, and the $72 is not income to you that needs to be reported on Form 1040. Depending on other items on Schedule A, your total itemized deductions might not exceed the standard deduction, in which case you will likely choose to use the standard deduction. In this case, you \"\"lose\"\" the deduction for medical expenses as well as all other expenses deductible on Schedule A. Summary of some of the discussions in the comments Health care insurance premiums cannot be paid for from HSA accounts (IRS Pub 969, page 8, column 2, near the bottom) though there are some exceptions. Nor can health care insurance premiums be paid from an FSA account (IRS Pub 969, page 17, column 1, near the top). If you have a business on the side and file a Schedule C as a self-employed person, you can buy medical insurance for that business's employees (and their families too, if you like) as an employment benefit, and pay for it out of the income of the Schedule C business, (thus saving on taxes). But be aware that if you have employees other than yourself in the side business, they would need to be covered by the same policy too. You can even decide to pay all medical expenses of your employees and their families too (no 7.5% limitation there!) as an employment benefit but again, you cannot discriminate against other employees (if any) of the Schedule C business in this matter. Of course, all this money that reduced your Schedule C income does not go on Schedule A at all. If your employer permits your family to be covered under its health insurance plan (for a cost, of course), check whether you are allowed to pay for the insurance with pre-tax dollars. The private (non-Schedule C) insurance would, of course, be paid for with post-tax dollars. I would doubt that you would be able to save enough money on taxes to make up the difference between $1330/month and $600/month, but it might also be that the private insurance policy covers a lot less than your employer's policy does. As a rule of thumb, group insurance through an employer can be expected to offer better coverage than privately purchased insurance. Whether the added coverage is worth the additional cost is a different matter. But while considering this matter, keep in mind that privately purchased insurance is not always guaranteed to be renewable, and a company might decline to renew a policy if there were a large number of claims. A replacement policy might not cover pre-existing conditions for some time (six months? a year?) or maybe even permanently. So, do consider these aspects as well. Of course, an employer can also change health insurance plans or drop them entirely as an employment benefit (or you might quit and go work for a different company), but as long as the employer's health plan is in existence, you (and continuing members of your family) cannot be discriminated against and denied coverage under the employer's plan.\"",
"title": ""
},
{
"docid": "82874",
"text": "If you know you will have a big bill, like braces. and you fully expect to hit the deductible then it can make sense. The deductible can trip some people up, because if they put too much into the limited purpose FSA and don't hit the deductible for the regular insurance policy, they can't get to all the money in the FSA. Because you have the ability to spend the potential money in the FSA before all the money has been contributed, it can allow you to make that payment for the braces in January. I did this the first year we had the HSA. I knew I needed to pay a dental bill early in the year. But the HSA would only have a few hundred dollars at that time, so I used the limited purpose FSA to be able to make that payment. This could also work if you spent a lot of money in the previous year. Because you have the ability to adjust how much money goes into the HSA each each pay period, this idea does keep the option open to fully fund the HSA if your finances improve. Regarding the deductible. The law limits what you can use the limited purpose FSA for: dental and vision only. There is an exception. If you hit the deductible for the high deductible insurance policy, then you can use the funds in the limited purpose FSA for ANY medical reason. When I did this a few years ago, I needed to send extensive paperwork to the company holding the funds before they would release the funds for dental. Once I sent them proof that I had met the deductible, then any medical expense after that date could use the FSA with minimal paperwork. If you fully fund the FSA beyond the cost of the braces, and then have a light year medical expense wise, you might not be able to spend all money in the FSA by the deadline. Regarding state taxes. I saw no difference in my states (Virginia) treatment of the funds. The state taxable income number was exactly the same as the federal taxable income number. It did not treat the money in the FSA differently than the money in the HSA.",
"title": ""
},
{
"docid": "484424",
"text": "Generally, the HSA is self-reported. The bank/financial provider will allow you to withdraw/spend whatever you want from your HSA. They report to the IRS the total that you withdrew for the year (your gross distributions) on a 1099-SA form. At tax time, you use a form 8889 to report this number of your gross distributions, and how much of it was used for medical expenses. Ideally, all of it was used for medical expenses. If it was not all for medical expenses, there will be extra taxes/penalties due. Different HSAs work differently, but for mine, which is held at a credit union, I can get money out several ways. I have an HSA checkbook and an HSA debit card that I can use anywhere. I can also transfer money out of my HSA into my regular checking account to reimburse myself for an expense, or even stop in at the teller window and take out cash. The credit union doesn't need to see any receipts for any of this. They don't care if I'm spending it at the doctor's office or the casino. It is up to me to make sure I'm spending the money in accordance to the law and that everything is reported correctly on my tax return. Nothing is verified unless you get audited. You definitely should keep documentation on the expenses, because if you are audited, you need to be prepared to account for every withdrawal. Make sure you are very familiar with the rules on eligible medical expenses, so you know what is allowed and what is not. IRS Publication 502 has all the details on what is allowed. As far as how it gets counted towards your deductible, you need to make sure that all of your medical bills get sent to your health insurance, even if you will eventually have to pay for it. For example, let's say you go to the doctor, and the bill is $150. Even if you know that the deductible is not met yet and you will be responsible for the entire $150, make sure the doctor's office submits the bill to your insurance. The insurance company will inform the doctor's office that you are responsible for all of it, but they will apply the amount towards your deductible.",
"title": ""
},
{
"docid": "402982",
"text": "Here are the advantages to the HDHP/HSA option over the PPO option, some of which you've already mentioned: Lower premiums, saving $240 annually. Your employer is contributing $1500 to your HSA. As you mentioned, this covers your deductible if you need it, and if you don't, the $1500 is yours to keep inside your HSA. The ability to contribute more to your HSA. You will be able to contribute additional funds to your HSA and take a tax deduction. Besides the medical expenses applied to your deductible, HSA funds can be spent on medical expenses that are not covered by your insurance, such as dental, vision, chiropractic, etc. Anything left in your HSA at age 65 can be withdrawn just like with a traditional IRA, with tax due (but no penalty) on anything not spent on medical expenses. With the information that you've provided about your two options, I can't think of any scenario where you'd be better off with the PPO. However, you definitely want to look at all the rest of the details to ensure that it is indeed the same coverage between the two options. If you find differences, I wrote an answer on another question that walks you through comparing insurance options under different scenarios.",
"title": ""
},
{
"docid": "441023",
"text": "In addition to the 10%/7.5% limitation mentioned in the answer by mgkrebbs (which means that very few people can take advantage of the deduction), itemized deductions reduce taxes only when the total of all the itemized deductions exceeds the standard deduction available to the taxpayer. People with mortgaged homes have a leg up on this because they can include the mortgage interest and property taxes on Schedule A whereas those who rent their living space cannot. In other words, not having sufficient other itemized deductions can make the really ill person with medical bills large enough to exceed the 10% limitation suffer the double whammy of not getting a tax reduction for any part of the huge medical expense.",
"title": ""
},
{
"docid": "187085",
"text": "During World War II, the United States (US) instituted wage and price controls. To attract better employees, companies would offer benefits to get around salary limits. Health insurance was one of the more successful benefits. At that time, income taxes were newer and there were many ways to evade them. Companies could generally deduct expenses. So at that time, health care was deductible because everything was. And at that time, only wages were taxable compensation from employer to employee. Since that time, many other benefits have become non-deductible for employers, e.g. housing or the reduced deduction for meals and entertainment. But health care is generally regarded as different, as a necessity. While everyone needs to eat, not everyone needs to eat at a $100 a meal restaurant. People who need expensive health care really need it. People who eat expensive food just prefer it. And of course, health care is more intermittent where food is relatively consistent. You don't need ten thousand calories one day and zero the next. But some families have no health care expenses in a year while another might have cancer or a pregnancy. Note that medical care expenses can be deducted for individuals if they are large enough in aggregate and you itemize. And of course both businesses and workers have incentives to maintain the current system with deductibility. Health insurance is a common benefit. Housing is not (although it's worth noting that travel housing and meals are deductible). So there have been few people impacted by making housing taxable while many people would be impacted by taxable health insurance. You can deduct health insurance costs if self-employed. It's also not true that health insurance is the only benefit with preferential tax treatment. Retirement and child care are also deductible. Even meals and housing can be deducted in certain circumstances. The complex rules about what and how much is deductible. There have been rumbles about normalizing the tax treatment of health insurance and medical care, but there is a lot of opposition. Insurance companies oppose making all healthcare expenses deductible, as that reduces their effective benefit. They would prefer only insurance premiums be deductible. Traditionally employed individuals oppose making health insurance taxable, as that would increase their taxes. So the situation persists. There isn't quite enough support to move in either direction, although the current compromise is economically silly.",
"title": ""
},
{
"docid": "156640",
"text": "\"Short answer, yes. But this is not done through the deductions on Schedule A. This can happen if the employer creates a Flexible Spending Account (FSA) for its employees. This can be created for certain approved uses like medical and transportation expenses (a separate account for each category). You can contribute amounts within certain limits to these accounts (e.g. $255 a month for transportation), with pre-tax income, deduct the contributions, and then withdraw these funds to cover your transportation or medical expenses. They work like a (deductible) IRA, except that these are \"\"spending\"\" and not \"\"retirement\"\" accounts. Basically, the employer fulfills the role of \"\"IRA\"\" (FSA, actually) trustee, and does the supporting paperwork.\"",
"title": ""
},
{
"docid": "574417",
"text": "\"When you do your taxes, you have two choices for your deductions. You can take the standard deduction, or you can choose to itemize your deductions. If you itemize your deductions, you use Form 1040 Schedule A. By looking at Schedule A, you can see the list of deductions that are itemized: On Schedule A itself, you only list a total for each of these broad categories. In some cases, this is sufficient detail. However, for certain deductions, finer detail may be required, and you may have to submit additional forms showing this detail. For example, on the medical expense line, you generally only list a total of medical expenses; details are only supplied to the IRS upon request. For noncash gifts to charity, you need to supply more details on Form 8283 if your gifts are worth more than $500. These requirements can be found in the instructions for Schedule A. As noted by @Accumulation in the comments, the above deductions that are a part of your itemized deductions are called \"\"below the line\"\" deductions (because they are subtracted after the adjusted gross income line) and are only able to be deducted if you choose to decline the standard deduction. There are other deductions that are available whether or not you itemize. These \"\"above the line\"\" deductions are found on Form 1040 Lines 23-35. If you look at these lines on the form, you'll see the different types of deductions that are called out here. Some of these deductions require additional details on other forms; for example, the HSA deduction requires details on Form 8889. If you have a business, your business expenses are not part of your itemized deductions at all, and do not appear on Schedule A anywhere. Instead, your business expenses get subtracted from your business's revenue, and the resulting profit (or loss) is what is reported on your Form 1040. Different types of businesses report these expenses differently. If you have a sole proprietorship, the details of your business's expenses are reported on Schedule C. On this schedule, Part II is devoted to deductible business expenses. Take a look at Schedule C, and you'll see that Lines 8-27 are different categories of expenses that get called out on this schedule.\"",
"title": ""
},
{
"docid": "527958",
"text": "It's true that the standard deduction makes the numbers less impressive. I ran your scenario through my favorite, most complete rent vs buy calculator, and your math isn't far off. However, there are a lot of deductions only available if you itemize. Medical expenses, moving expenses, job expenses, charitable contributions, local income/sales taxes, property tax, private mortgage insurance, etc. Property tax on that house alone is going to be nearly equal to the standard deduction, so the point is nearly moot. Anyways, the above linked calculator handles all of those, and more.",
"title": ""
},
{
"docid": "100387",
"text": "IRS Publication 502: Medical expenses are the costs of diagnosis, cure, mitigation, treatment, or prevention of disease, and the costs for treatments affecting any part or function of the body. Loan interest and fees do not meet this definition. Your loan interest and fees are a cost of the payment method you chose (a loan), not a cost of medical treatment. The IRS makes clear where loan interest is deductible. Publication 936 discusses home mortgage interest deductions, and Publication 970 specifically discusses student loan interest deductions. Considering Publication 502's definition of a medical expense, combined with the absence of a publication discussing medical expense loan interest deductions, one must conclude that medical loan interest and fees are not deductible.",
"title": ""
},
{
"docid": "96725",
"text": "If you can afford to max out an HSA and cover out of pocket expenses without withdrawing from it, it makes sense to do so. It might sound initially risky to tie too much money to healthcare expenses, perhaps you'll enjoy exceptional health and not need those funds. However, the annual contribution limit ($3,350/year for an individual) is low enough that it's unlikely you'd overfund your HSA, but even if you didn't need it all for healthcare, after 65 you can withdraw HSA funds without the 20% withdrawal penalty that you're hit with if under 65, so best case it's tax-free, worst-case it's like an IRA. From a tax perspective, your contributions are a tax-deduction like a traditional IRA, there's no tax on the gains, and you withdraw it tax-free as well, so long as you have healthcare expenses. The tricky bit is you can get reimbursed for your expenses at any time. If you pay out of pocket now, in 20 years you can get a reimbursement from your HSA: From HSA Bank's FAQ Can I use my tax-free HSA savings to pay for — or reimburse myself for — IRS-qualified medical expenses from a previous year? Yes, as long as the IRS-qualified medical expenses were incurred after your HSA was established, you can pay them or reimburse yourself with HSA funds at any time. Just be sure to keep sufficient records to show that these expenses were not previously paid for by another source or taken as an itemized deduction in any prior tax year.",
"title": ""
},
{
"docid": "278824",
"text": "\"In the US service animals are treated like durable medical equipment from a tax POV, and some expenses can be deducted. Likewise, expenses associated with working animals are business or hobby expenses than can be deducted to a certain extent. But pets, no. Legally they are \"\"chattels\"\" -- property that can move. Generally speaking, you can't deduct the cost of maintaining your belongings.\"",
"title": ""
},
{
"docid": "65875",
"text": "\"Taxes are a tool for achieving social policy goals. While Americans consider \"\"Socialism\"\" to be a curse, the US is in fact quite socialistic. Mostly towards corporations, but sometimes even the normal people, not only the \"\"Corporation are people, my friend\"\" (M. Romney) get some discounts. The tax deduction on mortgage interest comes as a tool to encourage Americans to own their homes. It is important, socially, for people to own their home to be independent, and in general contributes to the stability of the society. As anything, when taken to the extreme, it in fact achieves exactly the opposite, as we've seen in 2008, but when balanced - works well. Capital gain is taxed in the US, because it is income. Generally, any income is taxed. However, gain sourced from the sale of primary residence is excluded, up to a certain (quite large) amount from this tax (if lived in the residence long enough - 3 of the last 5 years prior to sale). This, again, to encourage Americans to upgrade their houses and make it easier for Americans to relocate when needed (sell one house and buy another without losing cash on taxes). As to \"\"asset producing income\"\" - that is true in the US as well. You cannot deduct your personal expenses, in general. Mortgage interest on primary residence is a notable exception, because it serves a social cause. Similarly, medical expenses are allowed as a deduction, if they're above certain limit, and many other things (for example - if a US person totals his car, and insurance doesn't cover the loss - it is tax deductible, above certain limit, the higher the income - the higher the limit). These are purely social policy breaks. Socialism, something Americans like to have, and love to hate. Many \"\"anti-socialists\"\" in the US are in fact taking advantage of these specific tax breaks the most, because for rich folks these are limited or non-existent (mortgage interest limited up to 1 million, medical expenses are allowed only above certain percentage of income, etc).\"",
"title": ""
},
{
"docid": "381124",
"text": "You can deduct eyesight correction surgery if it is medically necessary, you itemize deductions, and your medical expenses exceed 10% of your AGI. Obviously, the portion you paid with the money from FSA doesn't count, since it is considered reimbursement, but the FSA contributions are pre-tax. Similarly with HSA.",
"title": ""
},
{
"docid": "410226",
"text": "HSA rules are different in some regards than deductions allowable under Pub 502 which deals with medical expenses deductible in Schedule A of your tax return. Pub 969 governs HSA's and similar reimbursement plans, and the guidelines are as follows: Insurance premiums. You can’t treat insurance premiums as qualified medical expenses unless the premiums are for: -Long-term care insurance. -Health care continuation coverage (such as coverage under COBRA). -Health care coverage while receiving unemployment compensation under federal or state law. -Medicare and other health care coverage if you were 65 or older (other than premiums for a Medicare supplemental policy, such as Medigap). Since your wife is still being treated like an employee for health benefits, and you are not on COBRA, thus not eligible for a deduction. You may qualify under the unemployment provision depending on the cause of her disability.",
"title": ""
},
{
"docid": "296163",
"text": "Yes, you will need to deposit the funds into your HSA, then withdraw them to reimburse yourself for the expenses. The tax deduction comes when you contribute (deposit) to your HSA. If you do not deposit the money there, you will not be able to claim the deduction. Your HSA provider reports the amount of your contributions to the IRS, so the amount you say you contribute to your HSA on your tax return has to match what your HSA provider reports. When you deposit the money to your HSA, you need to explicitly tell your provider that the contribution is for tax year 2014. The reason is that you want to make sure that they report the amount of your 2014 contributions to the IRS correctly. After you've deposited the amount into your HSA, you can withdraw it to reimburse yourself for an eligible medical expense. In order to be eligible, it needs to be an expense that was incurred while you had the HSA in place. If you had your HSA account in place before you paid the expense, no problem. But if you set up the HSA account after you paid for the expense, you might be out of luck. The distribution (withdrawal) will be a part of tax year 2015, and you'll see this amount included as part of the gross distributions on your 1099-SA form next year. When I first set up my HSA, I didn't have any extra money to fund the HSA, so I handled it just like you are talking about. I would wait until I had a medical bill, then deposit the amount I needed into my HSA and withdraw it back out to pay the bill.",
"title": ""
},
{
"docid": "387547",
"text": "It is my understanding that the money in the HSA is yours to keep forever, even if you leave the country. When you leave the country and no longer have an HSA-eligible High Deductible Health Plan, you will no longer be able to contribute new money to your HSA. However, you can still spend the money on eligible medical expenses, even if these expenses are outside the U.S. However, there are a few caveats: The HSA money will remain in a U.S. HSA bank account. You won't be able to transfer the entire account to a new account in your home country without paying taxes and penalty. Therefore, you need to have a mechanism for accessing and transferring the money from abroad, so that you can reimburse yourself as you have medical expenses, until the HSA account is empty. Even after you leave the U.S., as long as you have the HSA in place, you will need to file a U.S. tax return (form 1040NR) in any year that you have an HSA distribution. If you decide to take the money out without medical expenses, you will need to pay income tax on the money plus a 20% penalty. See How do I withdraw all money from my HSA account as a non-resident? for more information.",
"title": ""
},
{
"docid": "59000",
"text": "Tax Shield would be known as: A tax shield is a reduction in taxable income for an individual or corporation achieved through claiming allowable deductions such as mortgage interest, medical expenses, charitable donations, amortization and depreciation. These deductions reduce a taxpayer's taxable income for a given year or defer income taxes into future years. Tax shields lower the overall amount of taxes owed by an individual taxpayer or a business. I know of various real estate investors that will use depreciation as noted above to reduce their tax liability though others can use other deductions. Fortune has this on Buffett's taxes in 2015: Here’s the breakdown of Buffett’s income taxes for 2015, according to the statement:",
"title": ""
},
{
"docid": "89157",
"text": "My understanding is that it works as you describe. Is this really a loophole? You could call it that if you want, but let's look at what really is happening. You get the tax deduction when you put money into the HSA, not when you take money out. And you can only put money in when you have the HSA-eligible High Deductible Health Plan (HDHP) in place. While you had the non-HSA eligible plan in place (presumably a more expensive low deductible health plan), you somehow incurred $5000 of out-of-pocket expenses. This is real money that you had to pay out. Finally, you went back to the HDHP and began contributing to the HSA again, taking the tax deduction as you put money in, subject to the contribution limits. The money that is in the HSA is yours, and you had legitimate out-of-pocket medical expenses. Are you really cheating anybody out of anything if you choose to take that money back out? I don't think so.",
"title": ""
},
{
"docid": "420311",
"text": "There is a tax advantage only for medical expenses exceeding 10% of your adjusted gross income (7.5% if over age 65). This limit means only a very few people can take advantage of the deduction. The expenses would be entered on Schedule A (itemized deductions) of form 1040. You don't have to send in the supporting documentation, but you have to keep it in your records to present if audited. Yes, a copay qualifies as an expense, but needs supporting documentation.",
"title": ""
},
{
"docid": "339488",
"text": "Tax regulations vary from country to country - some permitting more deductions, some less - but here are a few guidelines. As regards the home-office: As regards the deductions: Think of it like this: in order to have space for a home-office you needed a bigger home. That leads to increased rates, heating, insurance and so on. Many tax regulators recognise that these are genuine expenses. The alternative is to rent a separate office and incur greater expenses, leading to increased deductions and less overall tax paid (which won't finance the deficit). The usual test for deductions is: was the expense legitimately incurred in the pursuit of revenue? The flexibility permitted will vary by tax authority but you can frequently deduct more than you expected.",
"title": ""
},
{
"docid": "406418",
"text": "\"The piece is a little misguided at best and poor journalism at worst. The problem lies in the difference between what's deductible for individuals and what's deductible for corporations. The short version of the story is that corporations can deduct a hell of a lot more things than individuals can. Individual deductions are spelled out in the Internal Revenue Code. Stuff like medical expenses (above 7.5% of your AGI), certain educational things, etc. For corporations, the basic rule is that they can deduct any \"\"ordinary and necessary\"\" business expenses. That includes operating, travel, interest, employee, etc. I wish that the article had cited specific sections of the Code if this was some kind of loophole or something, but alas, it appears that they didn't. That leads me to believe that these companies are deducting the portion not paid to the government as a business expense. ~~For what it's worth, I don't believe that a company can deduct those expenses for tax purposes unless it's to \"\"protect their business interests.\"\" My assumption (I don't have the time or desire to search case law right now) is that settlements with the US Government are considered to fall under that definition.~~ **EDIT** - See my comment [here](http://www.reddit.com/r/business/comments/11dbzu/federal_regulators_have_lauded_a_series_of/c6ll7ez) for the relevant Treasury Regulation dealing with this.\"",
"title": ""
},
{
"docid": "176908",
"text": "There is a dependent care spending account for child care related expenses. Also Medical and Dental expenses over a certain % of your income maybe deductible on your tax return.",
"title": ""
},
{
"docid": "54400",
"text": "I understand that if I have multiple health insurance policies, I can only make claim from only one of them if ever I incur medical expenses (I'm from the Philippines). In the US, you cannot simultaneously submit a claim for payment of a medical bill, or request reimbursement for a bill already paid, to multiple insurance companies, but if you are covered by more than one policy, then any part of a claim not paid by one company can be submitted to another company that is also covering you. In fact, if you have employer-paid or employer-provided coverage, most insurance companies will want your employer-provided insurance company to be billed first, and will cover whatever is not paid by the employer coverage. For example, if the employer coverage pays 80% of your doctor's bill, the private insurance will pay the remaining 20%. But, the private insurance policies are also quite expensive. Some professional groups in the US offer major medical coverage to their US members, and might be offering this to non-US members as well (though I suspect not). These policies have large deductibles so that coverage kicks in only when the total medical expenses in that year (whether wholly or partially reimbursed, or not reimbursed at all) exceed the large deductible. These types of policies actually pay out to only a few people - if you have more than, say, $20,000 of medical expenses in a year, you have been quite ill, and thus the premiums are usually much smaller than full-fledged coverage insurance policies which pay out much more frequently because of much smaller deductibles.",
"title": ""
},
{
"docid": "388145",
"text": "Yes, absolutely. The HSA, when used for medical expenses, allows you to essentially pay for your medical expenses tax free. Even if you don't have extra room in your budget, you can fund the HSA as you incur medical expenses, then withdraw money to pay the expenses, and you'll see an immediate tax benefit at tax time. However, let's say that you have plenty of room in your budget and you don't have a lot of medical expenses. You already contribute the maximum to your 401(k) or IRA, and you want to do more. The HSA acts like a retirement account in this case, allowing you to contribute before-tax money and let it grow untaxed. The HSA does have a huge benefit that no other retirement account has. If you choose not to reimburse yourself for medical expenses, but you keep track of the unreimbursed expenses you incur, then you can reimburse yourself for these expenses at any point in the future completely tax free. Essentially, your contributions are treated like a traditional IRA, but your withdrawals are treated like a Roth IRA, and can be done at any age. If you don't acquire enough medical expenses, you can still withdraw whatever is left at age 65 and those withdrawals will be taxed like a traditional IRA. The HSA provides for tax-free contributions and growth if used for medical expenses, and tax-deferred growth if withdrawn after age 65 without medical expenses.",
"title": ""
},
{
"docid": "128107",
"text": "\"You can (and definitely should) withdraw any part of the contribution that will put you over the contribution limit. You can (and should if you need to) withdraw to repay any medical payments you made from outside the account. You can (but should avoid at all costs) withdraw (distribute) from the HSA for non-medical reasons. Here's the IRS publication which covers this: https://www.irs.gov/publications/p969 Here's the bit about distributions that covers what you're trying to do: You can receive tax-free distributions from your HSA to pay or be reimbursed for qualified medical expenses you incur after you establish the HSA. If you receive distributions for other reasons, the amount you withdraw will be subject to income tax and may be subject to an additional 20% tax. You don’t have to make distributions from your HSA each year. It is better to pay from your checking and reimburse than to over-fund the HSA. Best route forward is to reduce your contributions for the rest of the year, especially if continuing them will cause excess contributions. Another nasty gotcha: Excess contributions. You will have excess contributions if the contributions to your HSA for the year are greater than the limits discussed earlier. Excess contributions aren’t deductible. Excess contributions made by your employer are included in your gross income. If the excess contribution isn’t included in box 1 of Form W-2, you must report the excess as \"\"Other income\"\" on your tax return. Generally, you must pay a 6% excise tax on excess contributions. See Form 5329, Additional Taxes on Qualified Plans (Including IRAs) and Other Tax-Favored Accounts, to figure the excise tax. The excise tax applies to each tax year the excess contribution remains in the account. You may withdraw some or all of the excess contributions and avoid paying the excise tax on the amount withdrawn if you meet the following conditions. •You withdraw the excess contributions by the due date, including extensions, of your tax return for the year the contributions were made. •You withdraw any income earned on the withdrawn contributions and include the earnings in \"\"Other income\"\" on your tax return for the year you withdraw the contributions and earnings. If you will not be over your maximum contribution, let the contribution ride. Make sure your HSA balance is divided between cash, stock fund, bond fund. Much like your 401k. Because the part that you don't spend on medical expenses this year can be spent in future years' medical expenses, and if you have anything left when you retire you can spend it on whatever you want. And the funds, including growth, are not taxed until you distribute them. Bottom line: if the funds will not cause excess contribution, leave them in. Otherwise, take them out as soon as possible.\"",
"title": ""
},
{
"docid": "527620",
"text": "you wouldn't have to pay income taxes on the portion for health insurance. think of high deductible health plans - the employer puts the deductible into a healthcare savings account which is tax free as long as it's for medical care. right now you can also deduct the portion of your overall expenses that are medical over a portion of your income. 2 issues with your idea, though - 1. right now, there are people who can't get health insurance except through an employer. send them out into the marketplace and they will get turned down. obamacare is supposed to fix this, but if Romney is elected, it will continue. 2. healthcare inflation rises much higher than regular inflation, so if your benefits were included as part of wages and you had to buy it on your own, you would face a continually decreasing amount of money over time to purchase healthcare - a spiral. this is the issue that many have with the voucher system the republicans are proposing for medicare - the voucher will rise at inflation, while healthcare rises much higher than inflation - right now I think it's a difference of 1% versus 8-9% off the top of my head. also, for many industries, it's in the best interest of the company to have a healthy workforce.",
"title": ""
}
] |
8904
|
How is options implied volatility for a stock determined?
|
[
{
"docid": "237499",
"text": "\"There are a few different \"\"kinds\"\" of implied volatility. They are all based on the IVs obtained from the option pricing model you use. (1) Basically, given a few different values (current stock price, time until expiration, right of option, exercise style, strike of the option, interest rates, dividends, etc), you can obtain the IV for a given option price. If you look at the bid of an option, you can calculate the IV for that bid. If you look at the ask, there's a different IV for the ask. You can then look at the mid price, then you have a different IV, and so on and so on. And that's for each strike, in each expiration cycle! So you have a ton of different IVs. (2) In many option trading platforms, you'll see another kind of IV: the IV for each specific expiration cycle. That's calculated based on some of the IVs I mentioned on topic (1). Some kind of aggregation (more on this later). (3) Finally, people often talk about \"\"the IV of stock XYZ\"\". That's, again, an aggregation calculated from many of the IVs mentioned on topic (1). Now, your question seems to be: which IVs, from which options, from which months, with which weight, are part of the expiration cycle IV or for the IV of the stock itself? It really depends on the trading platform you are talking about. But very frequently, people will use a calculation similar to how the CBOE calculates the VIX. Basically, the VIX is just like the IV described on topic (3) above, but specifically for SPX, the S&P 500 index. The very detailed procedure and formulas to calculate the VIX (ie, IV of SPX) is described here: http://cfe.cboe.com/education/vixprimer/about.aspx If you apply the same (or a similar) methodology to other stocks, you'll get what you could call \"\"the IV of stock XYZ\"\".\"",
"title": ""
}
] |
[
{
"docid": "176161",
"text": "\"To understand the VXX ETF, you need to understand VIX futures, to understand VIX futures you need to understand VIX, to understand VIX you need to understand options pricing formulas such as the \"\"Black Scholes\"\" formula Those are your prerequisites. Learn at your own pace. Short Answer: When you buy VXX you are buying the underlying are front month VIX futures. Limited by the supply of the ETF's NAV (Net Asset Value) units. It is assumed that the ETF manager is actually buying and selling more VIX front month futures to back the underlying ETF. Long Answer: Assume nobody knows what an options contract should be worth. Therefore formulas have been devised to standardize how to price an options contract. The Black-Scholes formula is widely used, one of the variables in this formula is \"\"Implied Volatility\"\", which basically accounts for the mispricing of options when the other variables (Intrinsic Value, delta, gamma, theta...) don't completely explain how much the option is worth. People are willing to pay more for options when the perception is that they will be more profitable, \"\"implied volatility\"\" tracks these changes in an option's demand, where the rest of the black-scholes formula creates a price for an option that will always be the same. Each stock in the market that also trades standardized options will have implied volatility which can be computed from the price of those options. The \"\"Volatility Index\"\" (VIX), looks at the implied volatility of MANY STOCK's options contracts. Specifically the \"\"implied volatility of out the money puts on the S&P 500\"\". If you don't know what that quoted part of the sentence means, then you have at least five other individual questions to ask before you re-read this answer and understand the relevance of these followup questions: Why would people buy out-the-money puts on the S&P 500? Why would people pay more for out-the-money puts on the S&P 500 on some days and pay less for them on other days? This is really the key to the whole puzzle. Anyway, now that we have this data, people wanted to speculate on the future value of the VIX. So VIX futures contracts began trading and with it there came a liquid market. There doesn't need to be anything physical to back a financial product anymore. A lot of people don't trade futures, retail investors have practically only heard of \"\"the stock market\"\". So one investment bank decided to make a fund that only holds VIX futures that expire within a month. (front month futures). They split that fund up into shares and listed it on the stock market, like alchemy the VXX was formed. Volatility studies are fascinating, and get way more complex than this now that the VXX ETF also has liquid options contracts trading on it too, and there are leveraged VIX ETF funds that also trade options\"",
"title": ""
},
{
"docid": "393496",
"text": "\"As I understand it, Implied Volatility represents the expected gyrations of an options contract over it's lifetime. No, it represents that expected movement of the underlying stock, not the option itself. Yes, the value of the option will move roughly in the same direction the value of the stock, but that's not what IV is measuring. I even tried staring at the math behind the Options pricing model to see if that could make more sense for me but that didn't help. That formula is correct for the Black-Scholes model - and it is not possible (or at least no one has done it yet) to solve for s to create a closed-form equation for implied volatility. What most systems do to calculate implied volatility is plug in different values of s (standard deviation) until a value for the option is found that matches the quoted market value ($12.00 in this example). That's why it's called \"\"implied\"\" volatility - the value is implied from market prices, not calculated directly. The thing that sticks out to me is that the \"\"last\"\" quoted price of $12 is outside of the bid-ask spread of $9.20 to $10.40, which tells me that the underlying stock has dropped significantly since the last actual trade. If the Implied Vol is calculated based on the last executed trade, then whatever algorithm they used to solve for a volatility that match that price couldn't find a solution, which then choose to show as a 0% volatility. In reality, the volatility is somewhere between the two neighbors of 56% and 97%, but with such a short time until expiry, there should be very little chance of the stock dropping below $27.50, and the value of the option should be somewhere around its intrinsic value (strike - stock price) of $9.18.\"",
"title": ""
},
{
"docid": "577062",
"text": "Historical volatility of a stock is going to be based on past performance, basically its current trend. That can be useful, but really is no indication of how it will perform in the future. Especially with a big swing in the market. Now if you're talking about implied volatility (IV) of an options contract, that's a little different. IV is derived from an option’s price and shows what the market “implies” about the stock’s volatility in the future. Thus it is based on the actions of active traders and market makers. So, it gives you a bit more insight into what's going on, but at times has less to do with fundamentals. I guess a good way to think of IV based on options contracts is as an educated opinion, of the market as a whole, with regards to how much that stock could likely move over a period of time (options expiration). Also note that IV represents the potential for a stock to move, but it does not forecast direction. I don't know of any studies off the top of my head, but I'm sure there have been plenty.",
"title": ""
},
{
"docid": "242663",
"text": "\"Some thoughts on your questions in order, Duration: You might want to look at the longest-dated option (often a \"\"LEAP\"\"), for a couple reasons. One is that transaction costs (spread plus commission, especially spread) are killer on options, so a longer option means fewer transactions, since you don't have to keep rolling the option. Two is that any fundamentals-based views on stocks might tend to require 3-5 years to (relatively) reliably work out, so if you're a fundamental investor, a 3-6 month option isn't great. Over 3-6 months, momentum, short-term news, short squeezes, etc. can often dominate fundamentals in determining the price. One exception is if you just want to hedge a short-term event, such as a pending announcement on drug approval or something, and then you would buy the shortest option that still expires after the event; but options are usually super-expensive when they span an event like this. Strike: Strike price on a long option can be thought of as a tradeoff between the max loss and minimizing \"\"insurance costs.\"\" That is, if you buy a deeply in-the-money put or call, the time value will be minimal and thus you aren't paying so much for \"\"insurance,\"\" but you may have 1/3 or 1/2 of the value of the underlying tied up in the option and subject to loss. If you buy a put or call \"\"at the money,\"\" then you might have only say 10% of the value of the underlying tied up in the option and subject to loss, but almost the whole 10% may be time value (insurance cost), so you are losing 10% if the underlying stock price stays flat. I think of the deep in-the-money options as similar to buying stocks on margin (but the \"\"implied\"\" interest costs may be less than consumer margin borrowing rates, and for long options you can't get a margin call). The at-the-money options are more like buying insurance, and it's expensive. The commissions and spreads add significant cost, on top of the natural time value cost of the option. The annual costs would generally exceed the long-run average return on a diversified stock fund, which is daunting. Undervalued/overvalued options, pt. 1: First thing is to be sure the options prices on a given underlying make sense at all; there are things that \"\"should\"\" hold, for example a synthetic long or short should match up to an actual long or short. These kinds of rules can break, for example on LinkedIn (LNKD) after its IPO, when shorting was not permitted, the synthetic long was quite a bit cheaper than a real long. Usually though this happens because the arbitrage is not practical. For example on LNKD, the shares to short weren't really available, so people doing synthetic shorts with options were driving up the price of the synthetic short and down the price of the synthetic long. If you did actually want to be long the stock, then the synthetic long was a great deal. However, a riskless arbitrage (buy synthetic long, short the stock) was not possible, and that's why the prices were messed up. Another basic relationship that should hold is put-call parity: http://en.wikipedia.org/wiki/Put%E2%80%93call_parity Undervalued/overvalued options, pt. 2: Assuming the relationship to the underlying is sane (synthetic positions equivalent to actual positions) then the valuation of the option could focus on volatility. That is, the time value of the option implies the stock will move a certain amount. If the time value is high and you think the stock won't move much, you might short the option, while if the time value is low and you think the stock will move a lot, you might buy the option. You can get implied volatility from your broker perhaps, or Morningstar.com for example has a bunch of data on option prices and the implied components of the price model. I don't know how useful this really is though. The spreads on options are so wide that making money on predicting volatility better than the market is pretty darn hard. That is, the spread probably exceeds the amount of the mispricing. The price of the underlying is more important to the value of an option than the assumed volatility. How many contracts: Each contract is 100 shares, so you just match that up. If you want to hedge 100 shares, buy one contract. To get the notional value of the underlying multiply by 100. So say you buy a call for $30, and the stock is trading at $100, then you have a call on 100 shares which are currently priced at $10,000 and the option will cost $30*100=3,000. You are leveraged about 3 to 1. (This points to an issue with options for individual investors, which is that one contract is a pretty large notional value relative to most portfolios.)\"",
"title": ""
},
{
"docid": "215596",
"text": "\"Currently, when \"\"implied volatility\"\" is spoken, the Black-Scholes-Merton model is implied. This model has been shown to be deficient, thus the Variance Gamma Model should be used. However, as nearly no one uses VG, it can be assumed that BS is still being implied. The BS formula has multiple variables. Some are external to the underlying in question. The rest are internal. When all but one variable is known or assumed, the last variable can be calculated, so if one has the price of the underlying and all else except the volatility, the volatility can be calculated thus implied. If one selects an implied volatility, and all variables except the underlying price is known, the underlying price can be calculated. For the present, one uses the current price of the underlying to calculate the implied volatility. For future option prices, one assumes an implied volatility at a later date to calculate a possible price. For prices not at the money, the BS model is extremely imprecise. The VG model can better determine a potential future price.\"",
"title": ""
},
{
"docid": "122260",
"text": "\"Their algorithm may be different (and proprietary), but how I would to it is to assume that daily changes in the stock are distributed normally (meaning the probability distribution is a \"\"bell curve\"\" - the green area in your chart). I would then calculate the average and standard deviation (volatility) of historical returns to determine the center and width of the bell curve (calibrating it to expected returns and implied volaility based on option prices), then use standard formulas for lognormal distributions to calculate the probability of the price exceeding the strike price. So there are many assumptions involved, and in the end it's just a probability, so there's no way to know if it's right or wrong - either the stock will cross the strike or it won't.\"",
"title": ""
},
{
"docid": "543312",
"text": "\"Option pricing models used by exchanges to calculate settlement prices (premiums) use a volatility measure usually describes as the current actual volatility. This is a historic volatility measure based on standard deviation across a given time period - usually 30 to 90 days. During a trading session, an investor can use the readily available information for a given option to infer the \"\"implied volatility\"\". Presumably you know the option pricing model (Black-Scholes). It is easy to calculate the other variables used in the pricing model - the time value, the strike price, the spot price, the \"\"risk free\"\" interest rate, and anything else I may have forgotten right now. Plug all of these into the model and solve for volatility. This give the \"\"implied volatility\"\", so named because it has been inferred from the current price (bid or offer). Of course, there is no guarantee that the calculated (implied) volatility will match the volatility used by the exchange in their calculation of fair price at settlement on the day (or on the previous day's settlement). Comparing the implied volatility from the previous day's settlement price to the implied volatility of the current price (bid or offer) may give you some measure of the fairness of the quoted price (if there is no perceived change in future volatility). What such a comparison will do is to give you a measure of the degree to which the current market's perception of future volatility has changed over the course of the trading day. So, specific to your question, you do not want to use an annualised measure. The best you can do is compare the implied volatility in the current price to the implied volatility of the previous day's settlement price while at the same time making a subjective judgement about how you see volatility changing in the future and how this has been reflected in the current price.\"",
"title": ""
},
{
"docid": "125098",
"text": "\"Certainly no one knows in advance how much a stock is going to swing around. However, there are measures of how much it has swung around in the past, and there are people who will estimate the probability. First of all, there's a measure of an individual stock's volatility, commonly referred to as \"\"beta\"\". A stock with a beta of 1 tends to rise and fall about as much as the market at large. A stock with a beta of 2, in the meantime, would rise 10% when the market is up 5%. These are, of course, historical averages. See Wikipedia: http://en.wikipedia.org/wiki/Beta_(finance) Secondly, you can get an implied measure of volatility expectations by looking at options pricing. If a stock is particularly volatile, the chance of a big price move will be baked into the price of the stock options. (Note also that other things affect options pricing, such as the time value of money.) For an options-based measure of the volatility of the whole market, see the Volatility Index aka the \"\"Fear Gauge\"\", VIX. Wikipedia: http://en.wikipedia.org/wiki/VIX Chart: http://finance.yahoo.com/q?s=%5EVIX Looking at individual stocks as a group (and there's an oxymoron for you), individual stocks are definitely much more likely to have big moves than the market. Besides Netflix, consider the BP oil spill, or the Tokyo Electric Power Company's Fukushima incident (yow!). I don't have any detailed statistics on quantitatively how much, mind you, but in application, a standard piece of advice says not to put more than 5% of your portfolio in a single company's stock. Diversification protects you. (Alternatively, if you're trying to play Mr. Sophisticated Stock-Picker instead of just buying an index fund, you can also buy insurance through stock options: hedging your bets. Naturally, this will eat up part of your returns if your pick was a good one).\"",
"title": ""
},
{
"docid": "50726",
"text": "\"people are willing to pay higher premiums for options when stocks go down. Obviously the time value and intrinsic value and interests rates of the option doesn't change because of this so the miscalculation remainder is priced into the implied volatility part of the formula. Basically, anything that suggests the stock price will get volatile (sharp moves in either direction) will increase the implied volatility of the option. For instance, around earnings reports, the IV in both calls and puts in the nearest expiration dates are very high. When stocks go down sharply, the volatility is high because some people are buying puts for protection and others are buying calls because they think there will be a rebound move in the other direction. People (the \"\"sleep-at-night\"\" investors, not the derivatives traders ;) ) tend to be calm when stocks are going up, and fearful when they are going down. The psychology is important to understand and observe and profit from, not to quantitatively prove. The first paragraph should be your qualitative answer\"",
"title": ""
},
{
"docid": "372417",
"text": "\"Here are some things to consider if you want to employ a covered call strategy for consistent returns. The discussion also applies to written puts, as they're functionally equivalent. Write covered calls only on fairly valued stock. If the stock is distinctly undervalued, just buy it. By writing the call, you cap the gains that it will achieve as the stock price gravitates to intrinsic value. If the stock is overvalued, sell it, or just stay away. As the owner of a covered call position, you have full exposure to the downside of the stock. The premium received is normally way too small to protect against much of a drop in price. The ideal candidate doesn't change in price much over the life of the position. Yes, this is low volatility, which brings low option premiums. As a seller you want high premiums. But this can't be judged in a vacuum. No matter how high the volatility in absolute terms, as a seller you're betting the market has overpriced volatility. If volatility is high, so premiums are fat, but the market is correct, then the very real risk of the stock dropping over the life of the position offsets the premium received. One thing to look at is current implied volatility for the at-the-money (ATM), near-month call. Compare it to the two-year historical volatility (Morningstar has this conveniently displayed). Moving away from pure volatility, consider writing calls about three months out, just slightly out of the money. The premium is all time value, and the time value decay accelerates in the final few months. (In theory, a series of one-month options would be higher time value, but there are frictional costs, and no guarantee that today's \"\"good deal\"\" will be repeatable twelve time per year.) When comparing various strikes and expirations, compare time value per day. To compare the same statistic across multiple companies, use time value per day as a percent of capital at risk. CaR is the price of the stock less the premium received. If you already own the stock, track it as if you just bought it for this strategy, so use the price on the day you wrote the call. Along with time value per day, compare the simple annualized percent return, again, on capital at risk, measuring the return if a) the stock is called away, and b) the stock remains unchanged. I usually concentrate more on the second scenario, as we get the capital gain on the stock regardless, without the option strategy. Ideally, you can also calculate the probability (based on implied volatility) of the stock achieving these price points by expiration. Measuring returns at many possible stock prices, you can develop an overall expected return. I won't go into further detail, as it seems outside the scope here. Finally, I usually target a minimum of 25% annualized if the stock remains unchanged. You can, of course, adjust this up or down depending on your risk tolerance. I consider this to be conservative.\"",
"title": ""
},
{
"docid": "136363",
"text": "Since near-term at-the-money (ATM) options are generally the most liquid, the listed implied vol for a stock is usually pretty close to the nearest ATM volatility, but there's not a set convention that I'm aware of. Also note that for most stocks, vol skew (the difference in vol between away-from-the-money and at-the-money options) is relatively small, correct me if I'm wrong, IV is the markets assessment that the stock is about 70% likely (1 Standard Deviation) to move (in either direction) by that percent over the next year. Not exactly. It's an annualized standard deviation of the anticipated movements over the time period of the option that it's implied from. Implied vol for near-term options can be higher or lower than longer-term options, depending on if the market believes that there will be more uncertainty in the short-term. Also, it's the bounds of the expected movement in that time period. so if a stock is at $100 with an implied vol of 30% for 1-year term options, then the market thinks that the stock will be somewhere between $70 and $130 after 1 year. If you look at the implied vol for a 6-month term option, half of that vol is the range of expected movement in 6 months.",
"title": ""
},
{
"docid": "570993",
"text": "\"How accurate is Implied Volatility in predicting future moves? How would you measure this? If the implied volatility says that there's a 1% chance that a stock will double, and it doubles, was it \"\"right\"\"? You could also say that it says there's a 99% change that it doesn't double, so was it \"\"wrong\"\"? What you could measure is the variance of daily returns over a time period, and see how well that compares to implied volatility, but there's no way to compare IV with the absolute price movement. If a stock goes up 0.01 each day, then the variance is 0 (the daily returns are the same each day), but over 250 the stock would go up $2.50.\"",
"title": ""
},
{
"docid": "591229",
"text": "I would make a change to the answer from olchauvin: If you buy a call, that's because you expect that the value of call options will go up. So if you still think that options prices will go up, then a sell-off in the stock may be a good point to buy more calls for cheaper. It would be your call at that point (no pun intended). Here is some theory which may help. An options trader in a bank would say that the value of a call option can go up for two reasons: The VIX index is a measure of the levels of implied volatility, so you could intuitively say that when you trade options you are taking a view on two components: the underlying stock, and the level of the VIX index. Importantly, as you get closer to the expiry date this second effect diminishes: big jumps up in the VIX will produce smaller increases in the value of the call option. Taking this point to its limit, at maturity the value of the call option is only dependent on the price of the underlying stock. An options trader would say that the vega of a call option decreases as it gets closer to expiry. A consequence of this is that if pure options traders are naturally less inclined to buy and hold to expiry (because otherwise they would really just be taking a view on the stock price rather than the stock price & the implied volatility surface). Trading options without thinking too much about implied volatities is of course a valid strategy -- maybe you just use them because you will automatically have a mechanism which limits losses on your positions. But I am just trying to give you an impression of the bigger picture.",
"title": ""
},
{
"docid": "574732",
"text": "\"As JoeTaxpayer says, there's a lot you can do with just the stock price. Exploring that a bit: Stock prices are a combination of market sentiment and company fundamentals. Options are just a layer on top of that. As such, options are mostly formulaic, which is why you have a hard time finding historical option data -- it's just not that \"\"interesting\"\", technically. \"\"Mostly\"\" because there are known issues with the assumptions the Black-Scholes formula makes. It's pretty good, and importantly, the market relies on it to determine fair option pricing. Option prices are determined by: Relationship of stock price to strike. Both distance and \"\"moneyness\"\". Time to expiration. Dividends. Since dividend payments reduce the intrinsic value of a company, the prospect of dividend payments during the life of a call option depresses the price of the option, as all else equal, without the payments, the stock would be more likely to end up in the money. Reverse the logic for puts. Volatility. Interest rates. But this effect is so tiny, it's safe to ignore. #4, Volatility, is the biggie. Everything else is known. That's why option trading is often considered \"\"volatility trading\"\". There are many ways to skin this cat, but the result is that by using quoted historical values for the stock price, and the dividend payments, and if you like, interest rates, you can very closely determine what the price of the option would have been. \"\"Very closely\"\" depending on your volatility assumption. You could calculate then-historical volatility for each time period, by figuring the average price swing (in either direction) for say the past year (year before the date in question, so you'd do this each day, walking forward). Read up on it, and try various volatility approaches, and see if your results are within a reasonable range. Re the Black-Scholes formula, There's a free spreadsheet downloadable from http://optiontradingtips.com. You might find it useful to grab the concept for coding it up yourself. It's VBA, but you can certainly use that info to translate in your language of choice. Or, if you prefer to read Perl, CPAN has a good module, with full source, of course. I find this approach easier than reading a calculus formula, but I'm a better developer than math-geek :)\"",
"title": ""
},
{
"docid": "415281",
"text": "I agree that high volatility just means the underlying stock price fluctuates more, and it does not imply if the stock is going up or down. But a high volatility in the price of an underlying also means that there is a higher chance that the underlying price could reach extreme prices (albeit in either direction). However, if you purchased a call option then if the underlying price reached an extremely high value, then you will be richly rewarded. But if the underlying price reached an extremely low value, you won't lose any more than the initial premium that you paid. There is no additional risk on your side, it's capped to the premium that you paid for the call option. It's this asymmetric outcome (Heads - I win, Tails - I don't lose) combined with high volatility that means that call options will increase in value when the underlying price becomes more volatile. If the optionality wasn't there then the price wouldn't be related to the volatility of the underlying. But that would be called a Future or a Forward :-)",
"title": ""
},
{
"docid": "65900",
"text": "\"With options you pay for a premium which relates to the expected (so-called \"\"implied\"\" volatility). With futures, there is no assumption about the volatility of an underlying stock. In general, when trading options you trade the direction and future expected volatility of an underlying while futures are directional trades only.\"",
"title": ""
},
{
"docid": "118520",
"text": "In short, yes. Implied volatility will capture any expected upcoming material announcements. There is also supply/demand impact bundled in which may inflate an option price, and by extension increase implied volatility. OTM and ITM options are particularly predisposed to this phenomenon -- which is of course at odds with the traditional BS model assumptions -- the result is referred to as the volatility smile. Implied volatility is quoted as an annualised measure but isn't necessarily an annual value -- it will correspond to the option time period.",
"title": ""
},
{
"docid": "46992",
"text": "The options market seems to disagree... While the implied volatility is greater than the historical volatility.. At 23% the implied isn't much higher than the past implied-vol. I'll trust the market over the stock-twits chairman. http://www.cboe.com/framed/IVolframed.aspx?content=http%3a%2f%2fcboe.ivolatility.com%2foptions.j%3fcontract%3dC0F1D96A-D9C7-49D2-8941-45DC1B0E0B0F&sectionName=SEC_TRADING_TOOLS&title=CBOE%20-%20IVolatility%20Services ... that being said -- I (like everyone and their sister) think we break 100 and move hard to 104-105.",
"title": ""
},
{
"docid": "480337",
"text": "\"So, if an out-of-the-money option (all time value) has a price P (say $3.00), and there are N days... The extrinsic value isn't solely determined by time value as your quote suggests. It's also based on volatility and demand. Here is a quote from http://www.tradingmarkets.com/options/trading-lessons/the-mystery-of-option-extrinsic-value-767484.html distinguishing between extrinsic time value and extrinsic non-time value: The time value of an option is entirely predictable. Time value premium declines at an accelerating rate, with most time decay occurring in the last one to two months before expiration. This occurs on a predictable curve. Intrinsic value is also predictable and easily followed. It is worth one point for every point the option is in the money. For example, a call with a strike of 30 has three points of intrinsic value when the current value of the underlying stock is $33 per share; and a 40 put has two points of intrinsic value when the underlying stock is worth $38. The third type of premium, extrinsic value, increases or decreases when the underlying stock changes and when the distance between current value of stock and strike of the option get closer together. As a symptom of volatility, extrinsic value may be greater for highly volatile underlying stock, and lower for less volatile stocks. Extrinsic value is the only classification of option premium that is unpredictable. The SPYs you point out probably had a volatility component affecting value. This portion is a factor of expectations or uncertainty. So an event expected to conclude prior to expiration, but of unknown outcome can cause theta to be higher than p/n. For example, a drug company is being sued and the outcome of a trial will determine whether that company pays out millions or not. The extrinsic will be higher than p/n prior to the outcome of the trial then drops after. Of course, the most common situation where this happens is earnings. After the announcement, it's not unusual to see a dramatic drop in the extrinsic portion of options. This is why sometimes a new option trader gets angry when buying calls prior to earnings. When 'surprise' good earnings are announced as hoped, the rise is stock price is largely offset by a fall in extrinsic value giving call holders little or no gain! As for the reverse situation where theta is lower than p/n would expect? Well you can actually have negative theta meaning the extrinsic portion rises over time. (this statement is a little confusing because theta is usually described as negative, but since you describe it as a positive number, negative here means the opposite of what you'd expect). This is a quote from \"\"Option Volatility & Pricing\"\". Keep in mind that they use 'positive' theta to mean the time value increases up over time: Is it ever possible for an option to have a positive theta such that if nothing changes the option will be worth more tomorrow than it is today? When futures options are subject to stock-type settlement, as they currently are in the United States, the carrying cost on a deeply in-the-money option, either a call or a put, can, under some circumstances, be greater than the volatility component. If this happens, and the option is European (no early exercise permitted), it will have a theoretical value less than parity (less than intrinsic value). As expiration approaches, the value of the option will slowly rise to parity. Hence, the option will have a positive theta. Sheldon Natenberg. Option Volatility & Pricing: Advanced Trading Strategies and Techniques (Kindle Locations 1521-1525). Kindle Edition.\"",
"title": ""
},
{
"docid": "294295",
"text": "I frequently do this on NADEX, selling out-of-the-money binary calls. NADEX is highly illiquid, and the bid/ask is almost always from the market maker. Out-of-the-money binary calls lose value quickly (NADEX daily options exist for only ~21 hours). If I place an above-ask order, it either gets filled quickly (within a few minutes) due to a spike in the underlying, or not at all. I compensate by changing my price hourly. As Joe notes, one of Black-Scholes inputs is volatility, but price determines (implied) volatility, so this is circular. In other words, you can treat the bid/ask prices as bid/ask volatilities. This isn't as far-fetched as it seems: http://www.cmegroup.com/trading/fx/volatility-quoting-fx-options.html",
"title": ""
},
{
"docid": "158717",
"text": "It is a fool's errand to attribute abnormal option volume or volatility to any meaningful move in the stock. One side of the chain is frequently more expensive than the other. The relationship between historical volatility and implied volatility is dubious at best, and also a big area of study.",
"title": ""
},
{
"docid": "328794",
"text": "\"There are two components of option valuation, the value that's \"\"in the money\"\" and the \"\"time value.\"\" In the case of the $395 put, that option was already in the money and it will move less than the stock price by a bit as there will still be some time value there. $22.52 is intrinsic value (the right word for 'in the money') and the rest is time. The $365 strike is still out of the money, but as jldugger implied, the chance of it going through that strike is better as it's $6.66 closer. Looking at the options chain gives you a better perspective on this. If Apple went up $20 Monday, and down $20 Tuesday, these prices would be higher as implied volatility would also go higher. Now, I'd hardly call a drop of under 2% \"\"tanking\"\" but on the otherhand, I'd not call the 25% jump in the option price skyrocketing. Options do this all the time. Curious what prompted the question, are you interested in trading options? This stock in particular?\"",
"title": ""
},
{
"docid": "445771",
"text": "Changes in implied volatility are caused by many things, of course, and it is tough to isolate the effect you are describing, but let's try to generalize for a moment. Implied volatility is generally a measure of how much expect uncertainty there is about the future price of the stock. Uncertainty generally is higher in periods including earnings announcements because it is significant new information about the company's fortunes can make for significant changes in the price. However, you could easily have the case where the earnings are good and for some reason the market is very certain that the earnings will be good and near a certain level. In that case the price would rise, but the implied volatility could well be lower because the market believes that there will be no significant new information in the earnings announcement.",
"title": ""
},
{
"docid": "51218",
"text": "\"There is a white paper on \"\"The weekend effect of equity options\"\" it is a good paper and shows that (for the most part) option values do lose money from Friday to Monday. Which makes sense because it is getting closer to expiration. Of course this not something that can be counted on 100%. If there is some bad news and the stock opens down on a Monday the puts would have increased and the calls decreased in value. Article Summary (from the authors): \"\"We find that returns on options on individual equities display markedly lower returns over weekends (Friday close to Monday close) relative to any other day of the week. These patterns are observed both in unhedged and delta-hedged positions, indicating that the effect is not the result of a weekend effect in the underlying securities. We find even stronger weekend effects in implied volatilities, but only after an adjustment to quote implied volatilities in terms of trading days rather than calendar days.\"\" \"\"Our results hold for puts and calls over a wide range of maturities and strike prices, for both equally weighted portfolios and for portfolios weighted by the market value of open interest, and also for samples that include only the most liquid options in the market. We find no evidence of a weekly seasonal in bid-ask spreads, trading volume, or open interest that could drive the effect. We also find little evidence that weekend returns are driven by higher levels of risk over the weekend. \"\"The effect is particularly strong over expiration weekends, and it is also present to a lesser degree over mid-week holidays. Finally, the effect is stronger when the TED spread and market volatility are high, which we interpret as providing support for a limits to arbitrage explanation for the persistence of the effect.\"\" - Christopher S. Jones & Joshua Shemes You can read more about this at this link for Memphis.edu\"",
"title": ""
},
{
"docid": "488145",
"text": "\"There is only one way to create \"\"stable\"\" income using options: write COVERED calls. This means you must own some stocks which offer an active and liquid option market (FB would be good; T would be useless.) In other words, you need to own some \"\"unstable\"\" stocks, tickers that have sometimes scary volatility, and of course these are not great stocks for a retiree. But, let's assume you own 500 shares of FB, which you bought in June of 2015 for $75. Today, you could have been paid $2,375 for selling five Mar18'16 $105 Calls. Your reasoning is: So, the rule is: ONLY SELL COVERED CALLS AT A PRICE YOU WOULD BE HAPPY TO ACCEPT. If you follow the rule, you'll generate more-or-less \"\"stable\"\" income. Do not venture off this narrow path into the rest of Option Land. There be dragons. You can select strike prices that are far out of the money to minimize the chance of being exercised (and sweeten the deal by collecting an even higher price if the stock flies that high). If you are thinking about doing this, study the subject thoroughly until you know the terminology backwards and forwards. (Don't worry about \"\"the greeks\"\" since market makers manipulate implied volatility so wildly that it overrides everything else.)\"",
"title": ""
},
{
"docid": "458933",
"text": "\"Yes, almost always. I trade some of the most illiquid single stock options, and I would be absolutely murdered if I didn't try to work orders between the bid/ask. When I say illiquid, I mean almost non-existent: ~50 monthly contracts on ALL contracts for a given underlying. Spreads of 30% or more. The only time you shouldn't try to work an order, in my opinion, is when you think you need to trade immediately (rare), if implied volatility (IV) has moved to such a degree that the market makers (MM) won't hit your order while they're offering fair IV (they'll sometimes come down to meet you at their \"\"real\"\" price to get the exchange's liquidity rebate), or if the bid/ask spread is a penny. For illiquid single stock options, you need to be extremely mindful of implied and statistical volatility. You can't just try to always put your order in the middle. The MMs will play with the middle to get you to buy at higher IVs and sell at lower. The only way you can hope that an order working below the bid / above the ask will get filled is if a big player overwhelms the MMs' (who are lined up on the bid and ask) current orders and hits yours with one large order. I've never seen this happen. The only other way is like you said: if the market moves against you, the orders in front of yours disappear, and someone hits your order, but I think that defeats the intent of your question.\"",
"title": ""
},
{
"docid": "501276",
"text": "\"Not cumulative volatility. It's cumulative probability density. Time value isn't linear because PDFs (probability distribution function) aren't linear. It's a type of distribution e.g. \"\"bell-curves\"\") These distributions are based on empirical data i.e. what we observe. BSM i.e. Black-Scholes-Merton includes the factors that influence an option price and include a PDF to represent the uncertainty/probability. Time value is based on historical volatility in the underlying asset price, in this case equity(stock). At the beginning, time value is high since there's time until expiration and the stock is expected to move within a certain range based on historical performance. As it nears expiration, uncertainty over the final value diminishes. This causes probability for a certain price range to become more likely. We can relate that to how people think, which affects the variation in the stock market price. Most people who are hoping for a value increase are optimistic about their chances of winning and will hold out towards the end. They see in the past d days, the stock has moved [-2%,+5%] so as a call buyer, they're looking for that upside. With little time remaining though, their hopes quickly drop to 0 for any significant changes beyond the market price. (Likewise, people keep playing the lottery up until a certain age when they're older and suddenly determine they're never going to win.) We see that reflected in the PDF used to represent options price movements. Thus your time value which is a function of probability decreases in a non-linear fashion. Option price = intrinsic value + time value At expiration, your option price = intrinsic value = stock price - strike price, St >= K, and 0 for St < K.\"",
"title": ""
},
{
"docid": "380427",
"text": "One way is to compare the implied volatility with the realised volatility over a period similar to the time left to expiry. However there are plenty of reasons why the implied may be higher than the historical, for example because the market volatility has increased overall or because the underlying company is going to report their results before the option expires.",
"title": ""
},
{
"docid": "22426",
"text": "Out of the money options often have the biggest changes in value, when the stock moves upward. This person could also gain, by the implied (underlying) volatility of the stock rising if it moves erratically to either side. Still seems to be a very risky game, given only 4 days to expiry.",
"title": ""
},
{
"docid": "228602",
"text": "If we were to observe some call price (e.g., 15), and then derived implied volatilities from the BS formula depending on different strike prices but fixed maturity (i.e, maturity = 1, and strike goes from 80 to 140??), would we then see a smile? Yes. Market prices for various strikes and a given maturity often have higher implied volatilities from the Black-Scholes model away from at-the-money. It is not accounted for in the Black-Scholes model in the fact that volatility is not a function of strike, so volatility is assumed to be constant across strikes, but the market does not price options that way. I don't know that a quantitative theory has ever been proven; I've always just assumed that people are willing to pay slightly more for options deep in or out of the money based on their strategy, but I have no evidence to base that theory on.",
"title": ""
}
] |
11089
|
Using property to achieve financial independence
|
[
{
"docid": "327737",
"text": "Be very careful about buying property because it has been going up quickly in recent years. There are some fundamental factors that limit the amount real-estate can appreciate over time. In a nutshell, the general real-estate market growth is supported by the entry-level property market. That is, when values are appreciating, people can sell and use the capital gains to buy more valuable property. This drives up the prices in higher value properties whose owners can use that to purchase more expensive properties and so on and so forth. At some point in a rising market, the entry-level properties start to become hard for entry-level buyers to afford. The machine of rising prices throughout the market starts grinding to a halt. This price-level can be calculated by looking at average incomes in an area. At some percentage of income, people cannot buy into the market without crazy loans and if those become popular, watch out because things can get really ugly. If you want an example, just look back to the US in 2007-2009 and the nearly apocalyptic financial crisis that ensued. As with most investing, you want to buy low and sell high. Buying into a hot market is generally not very profitable. Buying when the market is abnormally low tends to be a more effective strategy.",
"title": ""
},
{
"docid": "542024",
"text": "Will buying a flat which generates $250 rent per month be a good decision? Whether investing in real estate is a good decision or not depends on many things, including the current and future supply/demand for rental units in your particular area. There are many questions on this site about this topic, and another answer to this question which already addresses many risks associated with owning property (though there are also benefits to consider). I just want to focus on this point you raised: I personally think yes, because rent adjusts with inflation and the rise in the price of the property is another benefit. Could this help me become financially independent in the long run since inflation is getting adjusted in it? In my opinion, the fact that rental income general adjusts with 'inflation' is a hedge against some types of economic risk, not an absolute increase in value. First, consider buying a house to live in, instead of to rent: If you pay off your mortgage before your retire, then you have reduced your cost of accommodations to only utilities, property taxes, and repairs. This gives you a (relatively) known, fixed requirement of cash outflows. If the value of property goes up by the time you retire - it doesn't cost you anything extra, because you already own your house. If the value of property goes down by the time you retire, then you don't save anything, because you already own your house. If you instead rent your whole life, and save money each month (instead of paying off a mortgage), then when you retire, you will have a larger amount of savings which you can use to pay your monthly rental costs each month. By the time you retire, your cost of accommodations will be the market price for rent at that time. If the value of property goes up by the time you retire - you will have to pay more on rent. If the value of property goes down by the time you retire, you will save money on rent. You will have larger savings, but your cash outflow will be a little bit less certain, because you don't know what the market price for rent will be. You can see that, because you need to put a roof over your own head, just by existing you bear risk of the cost of property rising. So, buying your own home can be a hedge against that risk. This is called a 'natural hedge', where two competing risks can mitigate each-other just by existing. This doesn't mean buying a house is always the right thing to do, it is just one piece of the puzzle to comparing the two alternatives [see many other threads on buying vs renting on this site, or on google]. Now, consider buying a house to rent out to other people: In the extreme scenario, assume that you do everything you can to buy as much property as possible. Maybe by the time you retire, you own a small apartment building with 11 units, where you live in one of them (as an example), and you have no other savings. Before, owning your own home was, among other pros and cons, a natural hedge against the risk of your own personal cost of accommodations going up. But now, the risk of your many rental units is far greater than the risk of your own personal accommodations. That is, if rent goes up by $100 after you retire, your rental income goes up by $1,000, and your personal cost of accommodations only goes up by $100. If rent goes down by $50 after you retire, your rental income goes down by $500, and your personal cost of accommodations only goes down by $50. You can see that only investing in rental properties puts you at great risk of fluctuations in the rental market. This risk is larger than if you simply bought your own home, because at least in that case, you are guaranteeing your cost of accommodations, which you know you will need to pay one way or another. This is why most investment advice suggests that you diversify your investment portfolio. That means buying some stocks, some bonds, etc.. If you invest to heavily in a single thing, then you bear huge risks for that particular market. In the case of property, each investment is so large that you are often 'undiversified' if you invest heavily in it (you can't just buy a house $100 at a time, like you could a stock or bond). Of course, my above examples are very simplified. I am only trying to suggest the underlying principle, not the full complexities of the real estate market. Note also that there are many types of investments which typically adjust with inflation / cost of living; real estate is only one of them.",
"title": ""
},
{
"docid": "129149",
"text": "I wrote this in another thread but is also applicable here. In general people make some key mistakes with property: Not factoring in depreciation properly. Houses are perpetually falling down, and if you are renting them perpetually being trashed by the tenants as well - particularly in bad areas. Accurate depreciation costs can often run in the 5-20% range per year depending on the property/area. Add insurance to this as well or be prepared to lose the whole thing in a disaster. Related to 1), they take the index price of house price rises as something they can achieve, when in reality a lot of the house price 'rise' is just everyone having to spend a lot of money keeping them standing up. No investor can actually track a house price graph due to 1) so be careful to make reasonable assumptions about actual achievable future growth (in your example, they could well be lagging inflation/barely growing if you are not pricing in upkeep and depreciation properly). Failure to price in the huge transaction costs (often 5%+ per sale) and capital gains/other taxes (depends on the exact tax structure where you are). These add up very fast if you are buying and selling at all frequently. Costs in either time or fees to real estate rental agents. Having to fill, check, evict, fix and maintain rental properties is a lot more work than most people realise, and you either have to pay this in your own time or someone else’s. Again, has to be factored in. Liquidity issues. Selling houses in down markets is very, very hard. They are not like stocks where they can be moved quickly. Houses can often sit on the market for years before sale if you are not prepared to take low prices. As the bank owns your house if you fail to pay the mortgage (rents collapse, loss of job etc) they can force you to fire sale it leaving you in a whole world of pain depending on the exact legal system (negative equity etc). These factors are generally correlated if you work in the same cities you are buying in so quite a lot of potential long tail risk if the regional economy collapses. Finally, if you’re young they can tie you to areas where your earnings potential is limited. Renting can be immensely beneficial early on in a career as it gives you huge freedom to up sticks and leave fast when new opportunities arise. Locking yourself into 20 yr+ contracts/landlord activities when young can be hugely inhibiting to your earnings potential. Without more details on the exact legal framework, area, house type etc it’s hard to give more specific advise, but in general you need a very large margin of safety with property due to all of the above, so if the numbers you’re running are coming out close (and they are here), it’s probably not worth it, and you’re better of sticking with more hands off investments like stocks and bonds.",
"title": ""
}
] |
[
{
"docid": "1315",
"text": "Set up budget categories. Earmark your income as it is paid, for your budget categories. Pay your bills and expenses. For debts, pay the minimum on everything. There will be an amount left once everything is budgeted. That's the 'extra'. Then focus on, in order of priority, the following: So, when your emergency fund is up to an appropriate level (3-6 months of living expenses as a rule of thumb, adjusted according to your comfort level). Once you have your emergency fund started, budget at least enough toward your 401k to capture any matching offered by your employer. Then use the snowball plan to pay off your debts. (From what your post says, this does not apply to you, but you may have some small credit card debts taht were not discussed). Earmark the 'extra' for the smallest debt first. When that debt is paid, the 'extra' grows by the minimum payment of the smallest. Thus the snowball grows as you pay off debts. Once the debts are gone, reward yourself, within reason (and without going into debt). Now shift your extra into fully funding your retirement savings. Consult a financial advisor to help you plan how to distribute your retirement savings across the available retirement savings types. They can explain why it's good to have some of your retirement savings funded from after tax income. They can help you find the balance between pre- and post-tax funded accounts. Eventually, you may come to the point where you're putting the max allowed into your tax advantaged retirement accounts. At your age, this is a significant achievement. Anything left over after retirement savings is funded can be used for whatever you want. If you choose wealth building, it can lead to financial independence. The first two should be a one time thing. You can/should do more than one at a time. The fourth one is optional, and should not be considered until 1 and 2 are completed, and 3 is maxed out. What you achieve is up to you. Look up FIRE, or Financially independent, retire early. There are groups of folks striving for this. They share advice on frugal living and wealth building strategies. The goal is to save enough capital to live off the passive income of interest and dividends. Most of them seem to have pre-50 target ages. At your age and income, you could hit a pre-40 goal. But it takes commitment and a certain type of personality. Not for me but it might be for you.",
"title": ""
},
{
"docid": "47020",
"text": "\"There's truth to that, although I'm not sure if the ratio is quite 6 to 1. It IS true that they are processing foreclosures much slower now after the robo-signing fiasco, and also that there is some justification for letting a house stay occupied rather than sit empty. I disagree with your assertion that \"\"smart banks\"\" would dump massive amounts of property at a loss. Selling their inventory quickly would slim their balance sheet (which they been trying to do) and let huge losses flow through their income statement. That's a bad way to achieve a good end, even though the changes are purely accounting and not economic. That's not smart for any business, operating in a vacuum and independent of competition, whether a bank or a retailer. Should GM and Ford sell their backlogs of cars at a massive loss now, just to get rid of the property? There's underlying, economic, intrinsic value. Properties in the biggest bust markets, like LV and Phoenix, are down 2/3rds from the prices around 05/06; one would argue that the prices are so low they fail to make economic sense. Florida was a huge bust market, but today's NY Times (http://www.nytimes.com/2011/12/28/us/miami-courts-free-spending-brazilians.html?_r=1&scp=2&sq=brazil&st=cse) talks about a recovery in property values, fueled by Brazilians. Given that cities like Vancouver and throughout the SF Bay Area have seen property prices recover, in part fueled by foreign purchasers (mostly China, etc) why would a bank not want to hold onto the property until it gets a good price?\"",
"title": ""
},
{
"docid": "207815",
"text": "You will find Joe.E, that rents have increased considerably over the last 4 to 5 years in Australia. You can probably achieve rental yields of above 5% more than 20km from major Cities, however closer to cities you might get closer to 5% or under. In Western Sydney, we have been able to achieve rental yields close to 7%. We bought mainly in 2007 and 2008 when no one was buying and we were getting properties for 15% to 20% below market rates. As we bought cheap and rents were on the increase we were able to achieve higher rental yields. An example of one particular deal where we bought for $225K and rented for $300/wk giving us a yield of 6.9%. The rent is now $350/wk giving us a current yield of 8%, and with our interest rate at 6.3% and possibly heading down further, this property is positively geared and pays for itself plus provides us with some additional income. All our properties are yielding between 7.5% to 8.5% and are all positively geared. The capital gains might not be as high as with properties closer to the city, but even if we stopped working we wouldn't have to sell as they all provide us income after paying all expenses on associated with the properties. So in answer to your question I would be aiming for a property with a yield above 5% and preferably above 6%, as this will enable your property/ies to be positively geared at least after a couple of years if not straight away.",
"title": ""
},
{
"docid": "393550",
"text": "Welcome to Get Local Clout, We are an independent news site that has a goal of creating a reliable content for all the business minded folks out there. If it happens that you finally realized that you want to achieve the financial freedom “status,” then visit our site often and try to absorb all the content that you read here, the last thing that you will know is that you are already a financially literate person. We provide an original content about business, money tips, and news. All written by a professional and person that know their stuff really well, and will surely help you and your business.",
"title": ""
},
{
"docid": "386720",
"text": "You remind me a lot of myself as I was thinking about marriage. Luckily for me, my wife was much smarter about all this than I was. Hopefully, I can pass along some of her wisdom. Both of us feel very strongly about being financially independent and if possible we both don't want to take money from each other. In marriage, there is no more financial independence. Do not think in those terms. Life can throw so many curve balls that you will regret it. Imagine sitting down with your new bride and running through the math. She is to contribute $X to the family each month and you are to contribute $Y. Then next thing you know, 6 months later, she has cancer and has to undergo expensive and debilitating treatment. There is no way she can contribute her $X anymore. You tell her that is okay and that you understand, but the pressure weighs down on her every day because she feels like she is not meeting your expectations. Or alternatively, everything goes great with your $X, $Y plan. A few years down the road your wife is pregnant, so you revisit the plan, readjust, etc. Everything seems great. When your child is born, however, the baby has a severe physical or mental handicap. You and your wife decide that she will quit her job to raise your beautiful child. But, the whole time, in the back of her mind she can't get out of her head that she is no longer financially independent and not living up to your expectations. These stresses are not what you want in your marriage. Here is what we do in my family. Hopefully, some of this will be helpful to you. Every year my wife and I sit down and determine what our financial goals are for the year. How much do we want to be putting in retirement? How much do we want to give to charity? Do we want to take any family vacations? We set goals together on what we want to achieve with our money. There is no my money or her money, just ours. Doesn't matter where it comes from. At the beginning of every month, we create a budget in a spreadsheet. It has categories like (food, mortgage or rent, transportation, clothing, utilities) and we put down how much we expect to spend on each of those. It also has categories for entertainment, retirement, charity, cell phones, internet, and so on. Again, we put down how much we expect to spend on each of those. In the spreadsheet, we also track how much income we expect that month and our totals (income minus expenses). If that value is positive, we determine what to do with the remainder. Maybe we save some for a rainy day or for car repairs. Maybe we treat ourselves to an extra fancy dinner. The point is, every dollar should be accounted for. If she wants to go to dinner with some friends, we put that in the budget. If I want a new video game, we put that in the budget. Once a week, we take all our receipts and tally up where we spent our money. We then see how we are doing on our budget. Maybe we were a little high in one category and lower than expected in another. We adjust. We are flexible. But, we go over our finances often to make sure we are achieving our goals. Some specific goals I'd recommend that the two of you consider in your first such yearly meeting: You get out of life what you put into it, and you will get out of your finances what the two of you put into them. By being on the same page, your marriage will be much happier. Money/finances are one of the top causes of divorce. If you two are working together on this, you are much more likely to succeed.",
"title": ""
},
{
"docid": "398206",
"text": "Your question is best asked of a tax expert, not random people on the internet. Such an expert will help you ask the right questions. For example you did not point out the country or state in which you live. That matters. First point is that you will not pay tax on 60K, its expensive to transact real estate, so your net proceeds will be closer to 40K. Also you can probably the deduct the costs of improvements. You implied that you really like this rental property. If that is the case, why would you sell...ever? This home could be a central part of your financial independence plan. So keep it until you die. IIRC when it passes to your heirs, a new cost basis is formed thereby not passing the tax burden onto them. (Assuming the property is located in the US.)",
"title": ""
},
{
"docid": "493075",
"text": "The government gets part of it. The remainder: Borrower relief will be in the form of mortgage modifications, including first-lien principal and forbearance forgiveness and second-lien extinguishments, low- to moderate-income mortgage originations, and community reinvestment and neighborhood stabilization efforts, with initiatives focused on communities experiencing, or at risk of, urban blight. This includes lien releases, uninhabitable and abandoned property demolition, and remediation and property donations. Also, Bank of America will support the expansion of available affordable rental housing. Bank of America has committed to complete delivery of the relief by no later than August 31, 2018. The consumer relief will be subject to oversight by an independent monitor. - See more at: http://newsroom.bankofamerica.com/press-releases/corporate-and-financial-news/bank-america-reaches-comprehensive-settlement-us-departm#sthash.AR7aJl3o.dpuf",
"title": ""
},
{
"docid": "213045",
"text": "It would be worthwhile reading into 'guarantor mortgages' or 'family offset mortgages' to achieve the same outcome. Ideally you are wanting the wealth of your parents to help make a mortgage more accessible to you. The first thought is to merely transfer money physically. However, for the reasons listed in the other posts, this carries potential problems. A guarantor mortgage will mean your parents agree to pay the portion about 75% LTV if you stop paying. You may take out a 95% LTV mortgage and therefore only have to find 5% deposit but benefit from the interest rates of a 75% loan. (Personally the chances of causing a family rift if things go pear-shaped would steer me away from this one. Each to their own though.) A family offset mortgage involves money rather than a guarantee. It will allow for the parents to dedicate some of their money to a third-party (ie. the bank or building society) so that you can achieve a mortgage. In practice, parents deposit money in a dedicated savings account. The bank adds that amount to whatever deposit you may have, and the combined amount is treated as the deposit towards the mortgage. Once your LTV reduces over time (by repayments and house value rises), your parents have their money returned and you carry on as normal. Here's an independent Which article: http://www.which.co.uk/money/mortgages-and-property/guides/first-time-buyer-mortgages/parent-mortgages/ I'd also read a couple of provider's pages to get a feel for the idea: https://www.barclays.co.uk/Mortgages/FamilySpringboardMortgage/P1242627640100 or http://www.scottishbs.co.uk/mortgages/guarantor-mortgage-for-first-time-buyers.html or http://www.mhbs.co.uk/family_deposit_mortgage_1_50_discount_for_term.aspx Not endorsements obviously, just a way to understand the concept and get a feel for the language they use. In short, using the money indirectly is much cleaner than your parents actually just giving you such a large sum and then you having to pay it back.",
"title": ""
},
{
"docid": "137378",
"text": "This is what helped me. - I did my own taxes - get your own job, not from your parents, or parents friends, but entirely by yourself. Complete independence will equate to financial independence - Wikipedia (for specifics and definitions) paired with finance genre movies - audiobook, or YouTube video, 'why an economy grows, and why it doesnt' That's a good start. Good luck! Don't be too gung ho to invest and all that crap, you got lots too learn. Rule 1: don't be too eager, that's how you lose all your money! My best financial investments to date were: 1) my education (engineering) 2) I didn't pay my student loan off, instead, I bought a property, and I made $70,000 in 8 months off of one, and $100,000 off of another one in 2 years, 3) still making minimum payments on my student loan, a dollar today is worth more than a dollar tomorrow 4) pack my own lunches every day, eating out every meal ends up costing more than most mortgage payments. This is in Vancouver BC, Canada.",
"title": ""
},
{
"docid": "18855",
"text": "\"Without knowing what you are trying to achieve - make a bit of pocket money, become financially independent, invest for retirement, learn trading to become a trader - I'll give you a few thoughts ... The difficulty you will have trading with $400-600 is that brokerage will be a high proportion of your \"\"profits\"\". I'm not sure of the US (assuming US rather than AU, NZ, etc) rates for online brokers, but UK online brokers are the order of £6-10 / trade. Having a quick read suggests that the trading is similar $6-10/trade. With doing day trades you will be killed by the brokerage. I'm not sure what percent of profitable trades you have, but if it is 50% (e.g.), you will need to make twice the brokerage fees value on each profitable trade before you are actually making a profit. There can be an emotional effect that trips you up. You will find that trading with your own real money is very different to trading with fake money. Read up about it, this brief blog shows some personal thoughts from someone I read from time to time. With a $10 brokerage, I would suggest the following Another option, which I wouldn't recommend is to leverage your money, by trading CDFs or other derivatives that allow you to trade on a margin. Further to that, learn about trading/investing Plus other investment types I have written about earlier.\"",
"title": ""
},
{
"docid": "343206",
"text": "Look through the related questions. Make sure you fund the max your tax advantaged retirement funds will take this year. Use the 30k to backstop any shortfalls. Invest the rest in a brokerage account. In and out of your tax advantaged accounts, try to invest in index funds. Your feeling that paying someone to manage your investments might not be the best use is shared by many. jlcollinsnh is a financial independence blogger. He, and many others, recommend the Vanguard Total Stock Market Index Admiral Shares. I have not heard of a lower expense ratio (0.05%). Search for financial independence and FIRE (Financial Independence Retire Early). Use your windfall to set yourself on that road, and you will be less likely to sit where I am 25 years from now wishing you had done things differently. Edit: Your attitude should be that the earliest money in your portfolio is in there the longest, and earns the most. Starting with a big windfall puts you years ahead of where you'd normally be. If you set your goal to retire at 40, that money will be worth significantly more in 20 years. (4x what you start with, assuming 7% average yearly return).",
"title": ""
},
{
"docid": "179960",
"text": "\"Right now you are standing at a fork in the road. If I could tell my younger self who blasted past that fork without noticing it what to do, I would say: Research \"\"Financial Independence\"\" and \"\"Early Retirement\"\" and \"\"frugal living\"\". If you do it right you can be financially independent in 5-15 years depending on your comfort level with frugal living. Many people celebrate graduation by financing a new car. It's like a quadruple whammy. New car brings sticker shock. Financing is paying to use someone else's money. Buying a car period is buying into the commuter lifestyle. And the cash flow could have gone to reducing debt or building savings. One blog I read advises that this step adds ten years to the time you have to work before you become financially independent.\"",
"title": ""
},
{
"docid": "187090",
"text": "\"> You said that they were both using the same method, but, in fact, they aren't The same underlying flawed assumptions. >Unless you're arguing an MIT 'academic conspiracy' It's a subconscious bias thing... they all inherently belive that an \"\"inflationary currency\"\" is a good & necessary thing... ergo they do not really TRY to disprove that dogmatic assumption. >BPP is independant, it uses a different methodology, and yet the results confirm those of the BLS. Yup, and that \"\"confirmation\"\" was the entire goal of the project... it is entirely unsurprising that they managed to achieve it.\"",
"title": ""
},
{
"docid": "519296",
"text": "It would be good to know which country you are in? You are basically on the right track with your last point. Usually when you buy your first property you need to come up with a deposit and then borrow the remainder to have enough to purchase the property. In most cases (and most places) the standard percentage of loan to deposit is 80% to 20%. This is expressed as the Loan to Value Ratio (LVR) which in this case would be 80%. (This being the amount of the loan to the value of the property). Some banks and lenders will lend you more than the 80% but this can usually come with extra costs (in Australia the banks charge an extra percentage when you borrow called Loan Mortgage Insurance (LMI) if you borrow over 80% and the LMI gets more expensive the higher LVR you borrow). Also this practice of lending more than 80% LVR has been tightened up since the GFC. So if you are borrowing 80% of the value of the property you will need to come up with the remainder 20% deposit plus the additional closing costs (taxes - in Australia we have to pay Stamp Duty, solicitor or conveyancing fees, loan application fees, building and pest inspection costs, etc.). If you then want to buy a second property you will need to come up with the same deposit and other closing costs again. Most people cannot afford to do this any time soon, especially since the a good majority of the money they used to save before is now going to pay the mortgage and upkeep of your first property (especially if you used to say live with your parents and now live in the property and not rent it out). So what a lot of people do who want to buy more properties is wait until the LVR of the property has dropped to say below 60%. This is achieved by the value of the property going up in value and the mortgage principle being reduced by your mortgage payments. Once you have enough, as you say, collateral or equity in the first property, then you can refinance your mortgage and use this equity in your existing property and the value of the new property you want to buy to basically borrow 100% of the value of the new property plus closing costs. As long as the LVR of the total borrowings versus the value of both properties remains at or below 80% this should be achievable. You can do this in two ways. Firstly you could refinance your first mortgage and borrow up to 80% LVR again and use this additional funds as your deposit and closing costs for the second property, for which you would then get a second mortgage. The second way is to refinance one mortgage over the two properties. The first method is preferred as your mortgages and properties are separated so if something does go wrong you don't have to sell everything up all at once. This process can be quite slow at the start, as you might have to wait a few years to build up equity in one property (especially if you live in it). But as you accumulate more and more properties it becomes easier and quicker to do as your equity will increase quicker with tenants paying a good portion of your costs if not all (if you are positively geared). Of course you do want to be careful if property prices fall (as this may drastically reduce your equity and increase your total LVR or the LVR on individual properties) and have a safety net. For example, I try to keep my LVR to 60% or below, currently they are below 50%.",
"title": ""
},
{
"docid": "269406",
"text": "\"It includes whatever you want to do with your investment. At least initially, it's not so much a matter of calculating numbers as of introspective soul-searching. Identifying your investment objectives means asking yourself, \"\"Why do I want to invest?\"\" Then you gradually ask yourself more and more specific questions to narrow down your goals. (For instance, if your answer is something very general like \"\"To make money\"\", then you may start to ask yourself, \"\"How much money do I want?\"\", \"\"What will I want to use that money for?\"\", \"\"When will I want to use that money?\"\", etc.) Of course, not all objectives are realistic, so identifying objectives can also involve whittling down plans that are too grandiose. One thing that can be helpful is to first identify your financial objectives: that is, money you want to be able to have, and things you want to do with that money. Investment (in the sense of purchasing investment vehicles likes stocks or bonds) is only one way of achieving financial goals; other ways include working for a paycheck, starting your own business, etc. Once you identify your financial goals, you have a number of options for how to get that money, and you should consider how well suited each strategy is for each goal. For instance, for a financial goal like paying relatively small short-term expenses (e.g., your electric bill), investing would probably not be the first choice for how to do that, because: a) there may be easier ways to achieve that goal (e.g., ask for a raise, eat out less); and b) the kinds of investment that could achieve that goal may not be the best use of your money (e.g., because they have lower returns).\"",
"title": ""
},
{
"docid": "569642",
"text": "Hi I am assuming you are doing this in the US? I run a social media / content marketing agency in the UK, Some of our very first clients were real estate agents, the idea we had was to market properties through Facebook using interior and exterior video shots to commercial music, This took off with some estate agents and not so much with others, My biggest piece of advice find a chain and start there that way you will get a hell of a lot of recognition by the smaller firms, You need to find a realistic price point for your clients that is measurable on the ROI and ultimately pays for your lifestyle. I started at £200 which is $257 dollars - arguably very underpriced but it gave me the opportunity to work with a cluster of people, I even went to the extreme of offering free work so I could get work for the portfolio! In terms of who to contact and how to find them.. enter Linkedin.com your new best friend - connect with real estate developers, buyers, owners you name it then informally introduce yourself and ask when they are free for a coffee. Post an article about why video and drone footage is the next big thing for real estate, don't be afraid to ask for the business at the end of the day you are providing cold hard value. I've always tried to get retainer deals with clients in the real estate sector but to achieve this you have to talk to the big boys and not independent firms. I could be wrong though I haven't done business with a lot of people in the states so definitely something to keep in mind. A good lot of this business idea is trial and error but I agree with it 100% just go and do basically, Hope this helps - I am happy to show you some of my work if you want to shoot me over a private message!",
"title": ""
},
{
"docid": "234585",
"text": "RealConnect is a unique independent real estate company which connects residential & commercial property owners & investors to real estate agents and property managers. We operate Australia wide & have registered agents waiting to offer their services from most areas across the country. We have a keen passion to create an easy to use, low cost system to benefit everyone dealing in the real estate industry. We aim to increase profits for property owners as well as real estate agents by lowering the business expenses for the agents and allowing them to offer the same service to property owners for less.",
"title": ""
},
{
"docid": "352613",
"text": "\"I think you have succumbed to a category error. The rational course forward is to classify all property as either his, hers, or family's. Each contributes a portion of wages to the family. Each logs hours spent performing familial duties and is \"\"paid\"\" in virtual dollars into their family account at market rates for that service. At any point actual plus virtual dollars are summed to assess the value of the family and percentages are allocated to each party on this basis. Put this into a pre-nuptual agreement. At the time of the inevitable divorce you leave with yours, she leaves with hers, family's assets are divided as described, and division of children should be as King Solomon suggested. Or you could do what I did: Put all your property (and debts) into one pot. Make sure each partner can competently manage bookkeeping and investments. Accumulate a family net worth sufficient to divide in two and each have financial independence. (I'm working on this last step.)\"",
"title": ""
},
{
"docid": "319307",
"text": "\"how is this new value determined? According to Publication 551: Inherited Property The basis of property inherited from a decedent is generally one of the following. The FMV of the property at the date of the individual's death. The FMV on the alternate valuation date if the personal representative for the estate chooses to use alternate valuation. For information on the alternate valuation date, see the Instructions for Form 706. The value under the special-use valuation method for real property used in farming or a closely held business if chosen for estate tax purposes. This method is discussed later. FMV is Fair Market Value - which is the price that a willing buyer would pay for the property with reasonable knowledge of all the facts of the property. The rest generally apply to farmland or other special-purpose land where the amount of income it generates is not properly reflected in the market value. One or more real estate professionals will run \"\"comps\"\" that show you recent sales in the same area for similar houses to get a rough estimate of fair market value. Does it go off of the tax appraised value? Tax assessment may or may not be accurate depending on tax laws (e.g. limits to tax increases) and consistency with the actual market. Should you, prior to your death, get an independent appraiser to appraise the value of the property and include that assessment of the properties value with the will or something? That should not be necessary - another appraisal will likely be done as part of the estate process after death. One reason you might do one is if you are distributing different assets to different heirs, and you want to make sure that the estate is divided equitably.\"",
"title": ""
},
{
"docid": "91688",
"text": "A budget is a plan for spending money in the future. Tracking spending is only looking at what happened in the past. Many people only track their spending, a proper budget can be key to achieving financial goals. You might earn enough and not spend frivolously enough that you aren't hamstrung by lack of a budget, but if you have specific financial goals, odds are you'll be more successful at achieving them by budgeting rather than only tracking spending. I'm a fan of zero-sum budgets, where every dollar is allocated to a specific bucket ahead of time. Here's a good write-up on zero-sum budgets: How and Why to Use a Zero-Sum Budget",
"title": ""
},
{
"docid": "557820",
"text": "My plan is that one day I can become free of the modern day monetary burdens that most adults carry with them and I can enjoy a short life without these troubles on my mind. If your objective is to achieve financial independence, and to be able to retire early from the workforce, that's a path that has been explored before. So there's plenty of sources that you might want to check. The good news is that you don't need to be an expert on security analysis or go through dozens of text books to invest wisely and enjoy the market returns. This is the Bogleheads philosophy. It's widely accepted by people in academia, and thoroughly tested. Look into it further if you want to see the rationale behind, but, to sum it up: It doesn't matter how expert you are. The idea of beating the market, that an index fund tracks, is about 'outsmarting' the rest of investors. That would be difficult, even if it was a matter of skill, but when it comes to predicting random events we're all equally clueless. *Total Expense Ratio: It gives an idea of how expensive is a given fund in terms of fees. Actively managed funds have higher TER than indexed ones. This doesn't mean there aren't index funds with, unexplainable, high TER out there.",
"title": ""
},
{
"docid": "584304",
"text": "\"You don't state a long term goal for your finances in your message, but I'm going to assume you want to retire early, and retire well. :-) any other ideas I'm missing out on? A fairly common way to reach financial independence is to build one or more passive income streams. The money returned by stock investing (capital gains and dividends) is just one such type of stream. Some others include owning rental properties, being a passive owner of a business, and producing goods that earn long-term royalties instead of just an immediate exchange of time & effort for cash. Of these, rental property is probably one of the most well-known and easiest to learn about, so I'd suggest you start with that as a second type of investment if you feel you need to diversify from stock ownership. Especially given your association with the military, it is likely there is a nearby supply of private housing that isn't too expensive (so easier to get started with) and has a high rental demand (so less risk in many ways.) Also, with our continued current low rate environment, now is the time to lock-in long term mortgage rates. Doing so will reap huge benefits as rates and rents will presumably rise from here (though that isn't guaranteed.) Regarding the idea of being a passive business owner, keep in mind that this doesn't necessarily mean starting a business yourself. Instead, you might look to become a partner by investing money with an existing or startup business, or even buying an existing business or franchise. Sometimes, perfectly good business can be transferred for surprisingly little down with the right deal structure. If you're creative in any way, producing goods to earn long-term royalties might be a useful path to go down. Writing books, articles, etc. is just one example of this. There are other opportunities depending on your interests and skill, but remember, the focus ought to be on passive royalties rather than trading time and effort for immediate money. You only have so many hours in a year. Would you rather spend 100 hours to earn $100 every year for 20 years, or have to spend 100 hours per year for 20 years to earn that same $100 every year? .... All that being said, while you're way ahead of the game for the average person of your age ($30k cash, $20k stocks, unknown TSP balance, low expenses,) I'm not sure I'd recommend trying to diversify quite yet. For one thing, I think you need to keep some amount of your $30k as cash to cover emergency situations. Typically people would say 6 months living expenses for covering employment gaps, but as you are in the military I don't think it's as likely you'll lose your job! So instead, I'd approach it as \"\"How much of this cash do I need over the next 5 years?\"\" That is, sum up $X for the car, $Y for fun & travel, $Z for emergencies, etc. Keep that amount as cash for now. Beyond that, I'd put the balance in your brokerage and get it working hard for you now. (I don't think an average of a 3% div yield is too hard to achieve even when picking a safe, conservative portfolio. Though you do run the risk of capital losses if invested.) Once your total portfolio (TSP + brokerage) is $100k* or more, then consider pulling the trigger on a second passive income stream by splitting off some of your brokerage balance. Until then, keep learning what you can about stock investing and also start the learning process on additional streams. Always keep an eye out for any opportunistic ways to kick additional streams off early if you can find a low cost entry. (*) The $100k number is admittedly a rough guess pulled from the air. I just think splitting your efforts and money prior to this will limit your opportunities to get a good start on any additional streams. Yes, you could do it earlier, but probably only with increased risk (lower capital means less opportunities to pick from, lower knowledge levels -- both stock investing and property rental) also increase risk of making bad choices.\"",
"title": ""
},
{
"docid": "100087",
"text": "CreditKarma review I don't personally use HelloWallet, but I have also heard very good things about it. Independence from financial products is a HUGE thing in the field because so many investment advisers place the firm before the customer (c.f. Too Big To Fail), so having an independent resource is a huge benefit.",
"title": ""
},
{
"docid": "489433",
"text": "\"For allocation, there's rules of thumb. 120-age is the percentage some folks recommend for stock market (high risk) allocation. With the balance in bonds, and a bit of international fund to add some more diversity. However, everyone needs to determine how much risk they're willing to take, and what their horizon is. Once you figure out your allocation, determine how much of your surplus goes into investing, and how much goes into short term savings for your short term financial goals such as purchasing a home. I would highly recommend reading about \"\"Financial Independence, Retire Early\"\" (FIRE). Most of the articles I've seen on it were folks in the US, with the odd Canadian and Brit, but the principles should be able to work in the Netherlands with adjustment. The idea behind FIRE is that you adjust your lifestyle to minimize expenses and save as much of your income as possible. When the growth of your savings is > the amount you spend on a yearly basis, you've reached financial independence and can retire any time you wish. CD ladder is a good idea for your emergency fund, but CDs (at least in the US) usually pay around the same rate as inflation, give or take. A ladder would help you preserve your emergency fund.\"",
"title": ""
},
{
"docid": "521835",
"text": "it depends on the area you want to focus in. to be sure, i will say that pretty much all certificates in finance can be achieved online now. CFP is a pretty ok one. i have it myself. there is quite a bit of material, but isn't too challenging. it focuses on financial planning/personal finance. certainly aids your technical knowledge but is kind of an analog to help boost your sales. most pure planners i know have this but moreover a series of more technical designations. you must have a bachelors to be given the right to use the CFP. CFA is a great one for your resume (and knowledge), but makes the CFP look like a summer vacation. it is for analysis, but has a broad range of potential uses. i know brokers, advisors, planners, and people leaders with these marks. if you are very smart, it will take you a minimum of 2.5 years (really 3yr) to complete due to their testing schedule. they also grade on a very steep curve. from what i understand, the amount of information and level of command you must demonstrate also necessitate this lengthy schedule. beyond that, you can look at getting FINRA licensed in a desired area (e.g. series 7/63 to be a broker). i would caution against this, unless you are very sure of where you want to go or need to meet the requirement for a job. typically jobs with license requirements will permit you 3-6 months to obtain them on company money. you risk spending a good bit of money that won't be reimbursed by getting licensed independently. keep in mind that you cannot actually use your licenses without a firm sponsor. finally, there are a variety of specialized designations like CWS and CMT that i would also caution against unless sure of desired position or meeting job requirements. it is better, in my opinion, to find yourself in a place where getting these will better position you for your current job rather than wasting time on them and finding yourself in a place where they hold no water.",
"title": ""
},
{
"docid": "65875",
"text": "\"Taxes are a tool for achieving social policy goals. While Americans consider \"\"Socialism\"\" to be a curse, the US is in fact quite socialistic. Mostly towards corporations, but sometimes even the normal people, not only the \"\"Corporation are people, my friend\"\" (M. Romney) get some discounts. The tax deduction on mortgage interest comes as a tool to encourage Americans to own their homes. It is important, socially, for people to own their home to be independent, and in general contributes to the stability of the society. As anything, when taken to the extreme, it in fact achieves exactly the opposite, as we've seen in 2008, but when balanced - works well. Capital gain is taxed in the US, because it is income. Generally, any income is taxed. However, gain sourced from the sale of primary residence is excluded, up to a certain (quite large) amount from this tax (if lived in the residence long enough - 3 of the last 5 years prior to sale). This, again, to encourage Americans to upgrade their houses and make it easier for Americans to relocate when needed (sell one house and buy another without losing cash on taxes). As to \"\"asset producing income\"\" - that is true in the US as well. You cannot deduct your personal expenses, in general. Mortgage interest on primary residence is a notable exception, because it serves a social cause. Similarly, medical expenses are allowed as a deduction, if they're above certain limit, and many other things (for example - if a US person totals his car, and insurance doesn't cover the loss - it is tax deductible, above certain limit, the higher the income - the higher the limit). These are purely social policy breaks. Socialism, something Americans like to have, and love to hate. Many \"\"anti-socialists\"\" in the US are in fact taking advantage of these specific tax breaks the most, because for rich folks these are limited or non-existent (mortgage interest limited up to 1 million, medical expenses are allowed only above certain percentage of income, etc).\"",
"title": ""
},
{
"docid": "152478",
"text": "Then: (do these in whatever order) 35 is not mid-life. You're on the tail end of the age to get started on retirement planning. Being single, relatively young, and a great income level, you are ideally situated to consider FIRE'ing yourself. (Financial Independent, Retire Early). The basic idea is to invest a large chunk of your income and establish your comfort level balancing frugality and comfort. There's a table on one of the FIRE websites that shows a graph between % of income saved and the number of years it takes to save enough to be financially independent. If you can go over 50% savings, you can get down to about 10 years. In this case, financially independent is where you can live on a safe percentage of withdrawal from your savings without depleting the savings. At that point, you no longer need to work for a paycheck. You would only do so to extend the savings, increase the safe withdraw rate, or because you want to do something that makes you feel productive.",
"title": ""
},
{
"docid": "518949",
"text": "\"What you need will depend on a number of factors that aren't clear from the question. This coverage is simply called \"\"Vacant home insurance\"\", but not all companies are willing to offer this coverage. Unfortunately, in New York, insurers can also legally drop your standard homeowners' coverage if they become aware that your property has become vacant for 30 days or more. The Insurer's Concerns Typically, a \"\"standard\"\" homeowners policy will have an exclusion clause for vacant homes. The insurance company's concern is that without someone in the home, they will be at risk for break-ins, squatters and vandalism. If you've ever seen \"\"Flip Men\"\" on Spike, you'll know this is a serious concern (great show, by the way). They will use a risk model to calculate an estimated risk for the property (this is why a seasonal vacation home in a sparsely-populated area is often less of a concern than a family home in an urban area). If they estimate the risk to be low, some insurance companies will allow to you buy back that exclusion so that vacant properties are covered. In your case, they have probably decided that either: Your Options First, you need to find a company that is comfortable with taking on the extra risk of a vacant home. This will vary quite a bit by location, but the main ones are Farmer's (they use the Foremost brand name in New York) and Castle Rock. There are lots of insurance agencies that also advertise these products, but most of them are middlemen and use one of these two companies to actually write the coverage. Additionally, since this is a specialty policy, make sure you understand all of the details of the policy, and how they vary from a regular policy including: How to Reduce your Premium costs These are general tips from the Murray Group's website (an independent broker in NY) on how to lower the additional cost of vacant coverage: This may sound expensive, but these steps will all reduce the risk of something really bad happening when you're not there. Additionally, do you know anyone you completely trust (relative, unemployed friend) that might want to live in your old house rent-free for a while? This could work out for you if they are willing to keep the place 100% clean around the clock so that you can show the house at any time. If you have additional/specific questions, you should be able to find an independent insurance broker in your area that would be willing to advise you on your specific situation for a flat fee. Best of luck with getting the home covered and sold quickly!\"",
"title": ""
},
{
"docid": "467878",
"text": "The most important thing to achieve success is to dream. And when you have a dream, the next challenge is how to achieve it. Loan Against Property helps you in fulfilling that dream. So go on, while you make your plans, allow to create certain they reach their heights",
"title": ""
},
{
"docid": "506750",
"text": "In short, if your expenses rise with inflation but your income does not, your expenses will eventually exceed your income. As the article on perpetuities says, a perpetuity is an annuity that pays forever. An annuity is a financial arrangement whereby you are paid a fixed sum every so often for a period of time. Hence, a perpetuity is an arrangement whereby you are paid a fixed sum every so often until you die. Since the sum is fixed in nominal dollars (or other currency units), it will become worth less and less in real dollars as time goes on, which is what will erode your financial independence. To adapt the example from the article that you quote: If you buy an annuity that will pay you $101 per month and your expenses are $100 per month, you may seem to be financially independent. However, if inflation is 2% per year, then next year your expenses will be $102, but the annuity will still only pay you $100. At that point you will no longer be financially independent, since the annuity no longer covers your expenses. There are some senses in which the article's statement is inaccurate in practical terms --- e.g., annuities need not always have fixed payments but may be adjusted for inflation, also there aren't many real perpetuities in existence anyway, and plus it doesn't matter whether the source of the income is an annuity or something else --- but that is the gist of what the article is saying.",
"title": ""
}
] |
379
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Enhanced early production of inflammatory chemokines damages viral control in the lung.
|
[
{
"docid": "19005293",
"text": "Inflammation induced by recognition of pathogen-associated molecular patterns markedly affects subsequent adaptive responses. We asked whether the adaptive immune system can also affect the character and magnitude of innate inflammatory responses. We found that the response of memory, but not naive, CD4+ T cells enhances production of multiple innate inflammatory cytokines and chemokines (IICs) in the lung and that, during influenza infection, this leads to early control of virus. Memory CD4+ T cell–induced IICs and viral control require cognate antigen recognition and are optimal when memory cells are either T helper type 1 (TH1) or TH17 polarized but are independent of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production and do not require activation of conserved pathogen recognition pathways. This represents a previously undescribed mechanism by which memory CD4+ T cells induce an early innate response that enhances immune protection against pathogens.",
"title": "Memory CD4+ T cells induce innate responses independently of pathogen"
}
] |
[
{
"docid": "26068103",
"text": "RSV lower respiratory tract infections (LRTI) are among the most common diseases necessitating hospital admission in children. In addition to causing acute respiratory failure, RSV infections are associated with sequelae such as secondary bacterial infections and reactive airway disease. One characteristic host response observed in severe RSV-induced LRTI and/or subsequent development of asthma is increased expression of interleukin (IL)-10. However, contradictory results have been reported regarding whether IL-10 inhibits asthmatic responses or intensifies the disease. We aimed to reconcile these discordant observations by elucidating the role of IL-10 in regulating the host response to RSV LRTI. In this study, we used a lung-specific, inducible IL-10 over-expression (OE) transgenic mouse model to address this question. Our results showed that the presence of IL-10 at the time of RSV infection not only attenuated acute inflammatory process (i.e. 24 h post-infection), but also late inflammatory changes [characterized by T helper type 2 (Th2) cytokine and chemokine expression]. While this result appears contradictory to some clinical observations where elevated IL-10 levels are observed in asthmatic patients, we also found that delaying IL-10 OE until the late immune response to RSV infection, additive effects rather than inhibitory effects were observed. Importantly, in non-infected, IL-10 OE mice, IL-10 OE alone induced up-regulation of Th2 cytokine (IL-13 and IL-5) and Th2-related chemokine [monocyte chemoattractant protein 1 (MCP-1), chemokine (C-C motif) ligand 3 (CCL3) and regulated upon activation normal T cell expressed and secreted (RANTES)] expression. We identified a subset of CD11b(+)CD11c(+)CD49b(+)F4/80(-)Gr-1(-) myeloid cells as a prinicipal source of IL-10-induced IL-13 production. Therefore, the augmented pathological responses observed in our 'delayed' IL-10 over-expression model could be attributed to IL-10 OE alone. Taken together, our study indicated dual roles of IL-10 on RSV-induced lung inflammation which appear to depend upon the timing of when elevated IL-10 is expressed in the lung.",
"title": "Dual role of interleukin-10 in the regulation of respiratory syncitial virus (RSV)-induced lung inflammation."
},
{
"docid": "15425958",
"text": "Interleukin-10 (IL-10) suppresses the maturation and cytokine production of dendritic cells (DCs), key regulators of adaptive immunity, and prevents the activation and polarization of naïve T cells towards protective gamma interferon-producing effectors. We hypothesized that human cytomegalovirus (HCMV) utilizes its viral IL-10 homolog (cmvIL-10) to attenuate DC functionality, thereby subverting the efficient induction of antiviral immune responses. RNA and protein analyses demonstrated that the cmvIL-10 gene was expressed with late gene kinetics. Treatment of immature DCs (iDCs) with supernatant from HCMV-infected cultures inhibited both the lipopolysaccharide-induced DC maturation and proinflammatory cytokine production. These inhibitory effects were specifically mediated through the IL-10 receptor and were not observed when DCs were treated with supernatant of cells infected with a cmvIL-10-knockout mutant. Incubation of iDCs with recombinant cmvIL-10 recapitulated the inhibition of maturation. Furthermore, cmvIL-10 had pronounced long-term effects on those DCs that could overcome this inhibition of maturation. It enhanced the migration of mature DCs (mDCs) towards the lymph node homing chemokine but greatly reduced their cytokine production. The inability of mDCs to secrete IL-12 was maintained, even when they were restimulated by the activated T-cell signal CD40 ligand in the absence of cmvIL-10. Importantly, cmvIL-10 potentiates these anti-inflammatory effects, at least partially, by inducing endogenous cellular IL-10 expression in DCs. Collectively, we show that cmvIL-10 causes long-term functional alterations at all stages of DC activation.",
"title": "Human Cytomegalovirus-Encoded Interleukin-10 Homolog Inhibits Maturation of Dendritic Cells and Alters Their Functionality"
},
{
"docid": "11328820",
"text": "The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.",
"title": "NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis."
},
{
"docid": "16058322",
"text": "beta-Cell destruction in type 1 diabetes (T1D) is at least in part consequence of a 'dialog' between beta-cells and immune system. This dialog may be affected by the individual's genetic background. We presently evaluated whether modulation of MDA5 and PTPN2, two candidate genes for T1D, affects beta-cell responses to double-stranded RNA (dsRNA), a by-product of viral replication. These genes were selected following comparison between known candidate genes for T1D and genes expressed in pancreatic beta-cells, as identified in previous array analysis. INS-1E cells and primary fluorescence-activated cell sorting-purified rat beta-cells were transfected with small interference RNAs (siRNAs) targeting MDA5 or PTPN2 and subsequently exposed to intracellular synthetic dsRNA (polyinosinic-polycitidilic acid-PIC). Real-time RT-PCR, western blot and viability assays were performed to characterize gene/protein expression and viability. PIC increased MDA5 and PTPN2 mRNA expression, which was inhibited by the specific siRNAs. PIC triggered apoptosis in INS-1E and primary beta-cells and this was augmented by PTPN2 knockdown (KD), although inhibition of MDA5 did not modify PIC-induced apoptosis. In contrast, MDA5 silencing decreased PIC-induced cytokine and chemokine expression, although inhibition of PTPN2 induced minor or no changes in these inflammatory mediators. These findings indicate that changes in MDA5 and PTPN2 expression modify beta-cell responses to dsRNA. MDA5 regulates inflammatory signals, whereas PTPN2 may function as a defence mechanism against pro-apoptotic signals generated by dsRNA. These two candidate genes for T1D may thus modulate beta-cell apoptosis and/or local release of inflammatory mediators in the course of a viral infection by acting, at least in part, at the pancreatic beta-cell level.",
"title": "MDA5 and PTPN2, two candidate genes for type 1 diabetes, modify pancreatic β-cell responses to the viral by-product double-stranded RNA"
},
{
"docid": "6144969",
"text": "Virally induced inflammatory responses, beta cell destruction and release of beta cell autoantigens may lead to autoimmune reactions culminating in type 1 diabetes. Therefore, viral capability to induce beta cell death and the nature of virus-induced immune responses are among key determinants of diabetogenic viruses. We hypothesised that enterovirus infection induces a specific gene expression pattern that results in islet destruction and that such a host response pattern is not shared among all enterovirus infections but varies between virus strains. The changes in global gene expression and secreted cytokine profiles induced by lytic or benign enterovirus infections were studied in primary human pancreatic islet using DNA microarrays and viral strains either isolated at the clinical onset of type 1 diabetes or capable of causing a diabetes-like condition in mice. The expression of pro-inflammatory cytokine genes (IL-1-α, IL-1-β and TNF-α) that also mediate cytokine-induced beta cell dysfunction correlated with the lytic potential of a virus. Temporally increasing gene expression levels of double-stranded RNA recognition receptors, antiviral molecules, cytokines and chemokines were detected for all studied virus strains. Lytic coxsackievirus B5 (CBV-5)-DS infection also downregulated genes involved in glycolysis and insulin secretion. The results suggest a distinct, virus-strain-specific, gene expression pattern leading to pancreatic islet destruction and pro-inflammatory effects after enterovirus infection. However, neither viral replication nor cytotoxic cytokine production alone are sufficient to induce necrotic cell death. More likely the combined effect of these and possibly cellular energy depletion lie behind the enterovirus-induced necrosis of islets.",
"title": "Enterovirus-induced gene expression profile is critical for human pancreatic islet destruction"
},
{
"docid": "21651116",
"text": "Herpesviruses encode membrane-associated G protein-coupled receptors (GPCRs) in their viral genomes that are structurally similar to chemokine receptors. These GPCRs hijack GPCR-mediated cellular signalling networks of the host for survival, replication and pathogenesis. In particular the herpesvirus-encoded chemokine receptors ORF74, BILF1 and US28, which are present at inflammatory sites and tumour cells, provide important virus-specific targets for directed therapies. Given the high druggability of GPCRs in general, these viral GPCRs can be considered promising antiviral drug targets.",
"title": "Herpesvirus-encoded GPCRs: neglected players in inflammatory and proliferative diseases?"
},
{
"docid": "17223891",
"text": "NLRP12 is a member of the intracellular Nod-like receptor (NLR) family that has been suggested to downregulate the production of inflammatory cytokines, but its physiological role in regulating inflammation has not been characterized. We analyzed mice deficient in Nlrp12 to study its role in inflammatory diseases such as colitis and colorectal tumorigenesis. We show that Nlrp12-deficient mice are highly susceptible to colon inflammation and tumorigenesis, which is associated with increased production of inflammatory cytokines, chemokines, and tumorigenic factors. Enhanced colon inflammation and colorectal tumor development in Nlrp12-deficient mice are due to a failure to dampen NF-κB and ERK activation in macrophages. These results reveal a critical role for NLRP12 in maintaining intestinal homeostasis and providing protection against colorectal tumorigenesis.",
"title": "The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis."
},
{
"docid": "17708753",
"text": "Whilst data recognise both myeloid cell accumulation during choroidal neovascularisation (CNV) as well as complement activation, none of the data has presented a clear explanation for the angiogenic drive that promotes pathological angiogenesis. One possibility that is a pre-eminent drive is a specific and early conditioning and activation of the myeloid cell infiltrate. Using a laser-induced CNV murine model, we have identified that disruption of retinal pigment epithelium (RPE) and Bruch's membrane resulted in an early recruitment of macrophages derived from monocytes and microglia, prior to angiogenesis and contemporaneous with lesional complement activation. Early recruited CD11b(+) cells expressed a definitive gene signature of selective inflammatory mediators particularly a pronounced Arg-1 expression. Accumulating macrophages from retina and peripheral blood were activated at the site of injury, displaying enhanced VEGF expression, and notably prior to exaggerated VEGF expression from RPE, or earliest stages of angiogenesis. All of these initial events, including distinct VEGF (+) Arg-1(+) myeloid cells, subsided when CNV was established and at the time RPE-VEGF expression was maximal. Depletion of inflammatory CCR2-positive monocytes confirmed origin of infiltrating monocyte Arg-1 expression, as following depletion Arg-1 signal was lost and CNV suppressed. Furthermore, our in vitro data supported a myeloid cell uptake of damaged RPE or its derivatives as a mechanism generating VEGF (+) Arg-1(+) phenotype in vivo. Our results reveal a potential early driver initiating angiogenesis via myeloid-derived VEGF drive following uptake of damaged RPE and deliver an explanation of why CNV develops during any of the stages of macular degeneration and can be explored further for therapeutic gain.",
"title": "Myeloid Cells Expressing VEGF and Arginase-1 Following Uptake of Damaged Retinal Pigment Epithelium Suggests Potential Mechanism That Drives the Onset of Choroidal Angiogenesis in Mice"
},
{
"docid": "27602752",
"text": "Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.",
"title": "CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS."
},
{
"docid": "23912923",
"text": "V domain-containing Ig suppressor of T-cell activation (VISTA) is a negative checkpoint regulator that suppresses T cell-mediated immune responses. Previous studies using a VISTA-neutralizing monoclonal antibody show that VISTA blockade enhances T-cell activation. The current study describes a comprehensive characterization of mice in which the gene for VISTA has been deleted. Despite the apparent normal hematopoietic development in young mice, VISTA genetic deficiency leads to a gradual accumulation of spontaneously activated T cells, accompanied by the production of a spectrum of inflammatory cytokines and chemokines. Enhanced T-cell responsiveness was also observed upon immunization with neoantigen. Despite the presence of multiorgan chronic inflammation, aged VISTA-deficient mice did not develop systemic or organ-specific autoimmune disease. Interbreeding of the VISTA-deficient mice with 2D2 T-cell receptor transgenic mice, which are predisposed to the development of experimental autoimmune encephalomyelitis, drastically enhanced disease incidence and intensity. Disease development is correlated with the increase in the activation of encephalitogenic T cells in the periphery and enhanced infiltration into the CNS. Taken together, our data suggest that VISTA is a negative checkpoint regulator whose loss of function lowers the threshold for T-cell activation, allowing for an enhanced proinflammatory phenotype and an increase in the frequency and intensity of autoimmunity under susceptible conditions.",
"title": "Disruption of the immune-checkpoint VISTA gene imparts a proinflammatory phenotype with predisposition to the development of autoimmunity."
},
{
"docid": "30398773",
"text": "Alloimmune lung syndromes (allo-LS), including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans organizing pneumonia, are severe complications after hematopoietic stem cell transplantation (HSCT). In our cohort of 110 pediatric patients, 30 had allo-LS (27.3%), 18 with idiopathic pneumonia syndrome and 12 with bronchiolitis obliterans syndrome. Multivariate analysis showed that respiratory viral infection early after HSCT is an important predictor for the development of allo-LS (P <.0001). This was true for all viruses tested. In multivariate analysis, allo-LS was the only predictor for higher mortality (P = .04). Paradoxically, prolonged administration of immunosuppressive agents because of acute graft-versus-host disease had a protective effect on the development of allo-LS (P = .004). We hypothesize that early infection of the respiratory tract with a common cold virus makes the lungs a target for alloimmunity.",
"title": "Strong association between respiratory viral infection early after hematopoietic stem cell transplantation and the development of life-threatening acute and chronic alloimmune lung syndromes."
},
{
"docid": "3083927",
"text": "We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1β, TNF-α, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.",
"title": "Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk."
},
{
"docid": "12058271",
"text": "The bone marrow is the primary site for neutrophil production and release into the circulation. Because the CXC chemokine receptor-4/stromal derived factor-1 (CXCR4/SDF-1) axis plays a central role in the interactions of hematopoietic stem cells, lymphocytes, and developing neutrophils in the marrow, we investigated whether reciprocal CXCR4-dependent mechanisms might be involved in neutrophil release and subsequent return to the marrow following circulation. Neutralizing antibody to CXCR4 reduced marrow retention of infused neutrophils (45.7% +/- 0.5% to 6.9% +/- 0.5%) and was found to mobilize neutrophils from marrow (34.4% +/- 4.4%). Neutrophil CXCR4 expression and SDF-1-induced calcium flux decreased with maturation and activation of the cells, corresponding to the decreased marrow homing associated with these characteristics in vivo. Infusion of the inflammatory mediator and CXCR2 ligand KC led to mobilization of neutrophils from marrow by itself and was augmented 3-fold by low doses of CXCR4-blocking antibody that otherwise had no mobilizing effect. Examination of KC and SDF-1 calcium signaling demonstrated that the effect of KC may, in part, be due to heterologous desensitization to SDF-1. These results suggest that the CXCR4/SDF-1 axis is critical in circulating neutrophil homeostasis and that it may participate in the rapid release of neutrophils from the marrow during inflammation through a novel interaction with inflammatory CXC chemokines.",
"title": "Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis."
},
{
"docid": "22281684",
"text": "Wnt signaling has diverse actions in cardiovascular development and disease processes. Secreted frizzled-related protein 5 (Sfrp5) has been shown to function as an extracellular inhibitor of non-canonical Wnt signaling that is expressed at relatively high levels in white adipose tissue. The aim of this study was to investigate the role of Sfrp5 in the heart under ischemic stress. Sfrp5 KO and WT mice were subjected to ischemia/reperfusion (I/R). Although Sfrp5-KO mice exhibited no detectable phenotype when compared with WT control at baseline, they displayed larger infarct sizes, enhanced cardiac myocyte apoptosis, and diminished cardiac function following I/R. The ischemic lesions of Sfrp5-KO mice had greater infiltration of Wnt5a-positive macrophages and greater inflammatory cytokine and chemokine gene expression when compared with WT mice. In bone marrow-derived macrophages, Wnt5a promoted JNK activation and increased inflammatory gene expression, whereas treatment with Sfrp5 blocked these effects. These results indicate that Sfrp5 functions to antagonize inflammatory responses after I/R in the heart, possibly through a mechanism involving non-canonical Wnt5a/JNK signaling.",
"title": "Secreted Frizzled-related Protein 5 Diminishes Cardiac Inflammation and Protects the Heart from Ischemia/Reperfusion Injury."
},
{
"docid": "35993767",
"text": "Fibroblasts are rich in the surrounding microenvironment of hepatocellular carcinoma (HCC) because most HCCs occur in fibrotic or cirrhotic livers. However, the role of cancer-associated fibroblasts (CAFs) in HCC metastasis remains obscure. Here, we reported that CAFs promote the migration and invasion of HCC cells in vitro and facilitate the HCC metastasis to the bone, brain and lung in NOD/SCID mice. The RayBio human chemokine antibody array revealed that CAFs secret higher levels of CCL2, CCL5, CCL7 and CXCL16 than peri-tumor fibroblasts. CCL2 and CCL5 increase the migration but not the invasion of HCC cells, while CCL7 and CXCL16 promote both migration and invasion of HCC cells. Moreover, CCL2 and CCL5 stimulate the activation of the hedgehog (Hh) pathway, while CCL7 and CXCL16 enhance the activity of the transforming growth factor-β (TGF-β) pathway in HCC cells. The neutralizing antibodies of chemokines notably attenuate the effect of CAFs on HCC metastasis and compromised the activation of Hh and TGF-β pathways in HCC cells. In summary, CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells.",
"title": "Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways."
},
{
"docid": "17438862",
"text": "Postmortem immunohistochemical studies have revealed a state of chronic inflammation limited to lesioned areas of brain in Alzheimer’s disease. Some key actors in this inflammation are activated microglia (brain macrophages), proteins of the classical complement cascade, the pentraxins, cytokines, and chemokines. The inflammation does not involve the adaptive immune system or peripheral organs, but is rather due to the phylogenetically much older innate immune system, which appears to operate in most tissues of the body. Chronic inflammation can damage host tissue and the brain may be particularly vulnerable because of the postmitotic nature of neurons. Many of the inflammatory mediators have been shown to be locally produced and selectively elevated in affected regions of Alzheimer’s brain. Moreover, studies of tissue in such degenerative processes as atherosclerosis and infarcted heart suggest a similar local innate immune reaction may be important in such conditions. Much epidemiological and limited clinical evidence suggests that nonsteroidal anti-inflammatory drugs may impede the onset and slow the progression of Alzheimer’s disease. But these drugs strike at the periphery of the inflammatory reaction. Much better results might be obtained if drugs were found that could inhibit the activation of microglia or the complement system in brain, and combinations of drugs aimed at different inflammatory targets might be much more effective than single agents.",
"title": "Local neuroinflammation and the progression of Alzheimer’s disease"
},
{
"docid": "1574014",
"text": "Open reading frame 74 (ORF74) encoded by human herpesvirus 8 is a highly constitutively active seven transmembrane (7TM) receptor stimulated by angiogenic chemokines, e.g. growth-related oncogene-alpha, and inhibited by angiostatic chemokines e.g. interferon-gamma-inducible protein. Transgenic mice expressing ORF74 under control of the CD2 promoter develop highly vascularized Kaposi's sarcoma-like tumors. Through targeted mutagenesis we here create three distinct phenotypes of ORF74: a receptor with normal, high constitutive signaling through the phospholipase C pathway but deprived of binding and action of chemokines obtained through deletion of 22 amino acids from the N-terminal extension; an ORF74 with high constitutive activity but with selective elimination of stimulatory regulation by angiogenic chemokines obtained through substitution of basic residues at the extracellular ends of TM-V or TM-VI; and an ORF74 lacking constitutive activity but with preserved ability to be stimulated by agonist chemokines obtained through introduction of an Asp residue on the hydrophobic, presumed membrane-exposed face of TM-II. It is concluded that careful molecular dissection can selectively eliminate either agonist or inverse agonist modulation as well as high constitutive activity of the virally encoded oncogene ORF74 and that these mutant forms presumably can be used in transgenic animals to identify the molecular mechanism of its transforming activity.",
"title": "Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74."
},
{
"docid": "16550075",
"text": "BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1alpha and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.",
"title": "BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control."
},
{
"docid": "35395662",
"text": "The virally encoded chemokine receptors US28 from human cytomegalovirus and ORF74 from human herpesvirus 8 are both constitutively active. We show that both receptors constitutively activate the transcription factors nuclear factor of activated T cells (NFAT) and cAMP response element binding protein (CREB) and that both pathways are modulated by their respective endogenous receptor ligands. By addition of specific pathway modulators against the G protein subunit Galphai, phospholipase C, protein kinase C, calcineurin, p38 MAP kinase, and MEK1, we find that the constitutive and ligand-dependent inductions are mediated by multiple yet similar pathways in both receptors. The NFAT and CREB transcription factors and their upstream activators are known inducers of host and virally encoded genes. We propose that the activity of these virally encoded chemokine receptors coordinates host and potentially viral gene expression similarly. As ORF74 is a known inducer of neoplasia, these findings may have important implications for cytomegalovirus-associated pathogenicity.",
"title": "Similar activation of signal transduction pathways by the herpesvirus-encoded chemokine receptors US28 and ORF74."
},
{
"docid": "10906636",
"text": "US28 is one of four 7 transmembrane (7TM) chemokine receptors encoded by human cytomegalovirus and has been shown to both signal and endocytose in a ligand-independent, constitutively active manner. Here we show that the constitutive activity and constitutive endocytosis properties of US28 are separable entities in this viral chemokine receptor. We generated chimeric and mutant US28 proteins that were altered in either their constitutive endocytic (US28 Delta 300, US28 Delta 317, US28-NK1-ctail, and US28-ORF74-ctail) or signaling properties (US28R129A). By using this series of mutants, we show that the cytoplasmic tail domain of US28 per se regulates receptor endocytosis, independent of the signaling ability of the core domain of US28. The constitutive endocytic property of the US28 c-tail was transposable to other 7TM receptors, the herpes virus 8-encoded ORF74 and the tachykinin NK1 receptor (ORF74-US28-ctail and NK1-US28-ctail). Deletion of the US28 C terminus resulted in reduced constitutive endocytosis and consequently enhanced signaling capacity of all receptors tested as assessed by inositol phosphate turnover, NF-kappa B, and cAMP-responsive element-binding protein transcription assays. We further show that the constitutive endocytic property of US28 affects the action of its chemokine ligand fractalkine/CX3CL1 and show that in the absence of the US28 C terminus, fractalkine/CX3CL1 acts as an agonist on US28. This demonstrates for the first time that the endocytic properties of a 7TM receptor can camouflage the agonist properties of a ligand.",
"title": "The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis."
},
{
"docid": "40365566",
"text": "Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b(+) monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b(+) cDCs but not CD103(+) cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l(-/-) mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b(+) cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung.",
"title": "Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen."
},
{
"docid": "45449835",
"text": "Myelin-directed autoimmunity is considered to play a key role in the pathogenesis of multiple sclerosis (MS). Increased production of both pro- and anti-inflammatory cytokines is a common finding in MS. Interleukin-17 (IL-17) is a recently described cytokine produced in humans almost exclusively by activated memory T cells, which can induce the production of proinflammatory cytokines and chemokines from parenchymal cells and macrophages. In situ hybridisation with synthetic oligonucleotide probes was adopted to detect and enumerate IL-17 mRNA expressing mononuclear cells (MNC) in blood and cerebrospinal fluid (CSF) from patients with MS and control individuals. Numbers of IL-17 mRNA expressing blood MNC were higher in patients with MS and acute aseptic meningoencephalitis (AM) compared to healthy individuals. Higher numbers of IL-17 mRNA expressing blood MNC were detected in MS patients examined during clinical exacerbation compared to remission. Patients with MS had higher numbers of IL-17 mRNA expressing MNC in CSF compared to blood. This increase in numbers of IL-17 mRNA expressing MNC in CSF was not observed in patients with AM. Our results thus demonstrate increased numbers of IL-17 mRNA expressing MNC in MS with higher numbers in CSF than blood, and with the highest numbers in blood during clinical exacerbations.",
"title": "Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis."
},
{
"docid": "195683603",
"text": "Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses.",
"title": "Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A."
},
{
"docid": "34016987",
"text": "Monocytes are primary targets for human CMV (HCMV) infection and are proposed to be responsible for hematogenous dissemination of the virus. Monocytes acquire different functional traits during polarization to the classical proinflammatory M1 macrophage or the alternative antiinflammatory M2 macrophage. We hypothesized that HCMV induced a proinflammatory M1 macrophage following infection to promote viral dissemination because, biologically, a proinflammatory state provides the tools to drive infected monocytes from the blood into the tissue. To test this hypothesis of monocyte conversion from a normal quiescent phenotype to an inflammatory phenotype, we used Affymetrix Microarray to acquire a transcriptional profile of infected monocytes at a time point our data emphasized is a key temporal regulatory point following infection. We found that HCMV significantly up-regulated 583 (5.2%) of the total genes and down-regulated 621 (5.5%) of the total genes>or=1.5-fold at 4 h postinfection. Further ontology analysis revealed that genes implicated in classical M1 macrophage activation were stimulated by HCMV infection. We found that 65% of genes strictly associated with M1 polarization were up-regulated, while only 4% of genes solely associated with M2 polarization were up-regulated. Analysis of the monocyte chemokinome at the transcriptional level showed that 44% of M1 and 33% of M2 macrophage chemokines were up-regulated. Proteomic analysis using chemokine Ab arrays confirmed the secretion of these chemotactic proteins from HCMV-infected monocytes. Overall, the results identify that the HCMV-infected monocyte transcriptome displayed a unique M1/M2 polarization signature that was skewed toward the classical M1 activation phenotype.",
"title": "Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage."
},
{
"docid": "219475",
"text": "The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-gamma production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis.",
"title": "Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung."
},
{
"docid": "5172048",
"text": "Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood. One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK). Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading. Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation. We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders. Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis. Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment. These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.",
"title": "Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling"
},
{
"docid": "67045088",
"text": "Post-translational modification of chemokines mediated by the dipeptidyl peptidase DPP4 (CD26) has been shown to negatively regulate lymphocyte trafficking, and its inhibition enhances T cell migration and tumor immunity by preserving functional chemokine CXCL10. By extending those initial findings to pre-clinical models of hepatocellular carcinoma and breast cancer, we discovered a distinct mechanism by which inhibition of DPP4 improves anti-tumor responses. Administration of the DPP4 inhibitor sitagliptin resulted in higher concentrations of the chemokine CCL11 and increased migration of eosinophils into solid tumors. Enhanced tumor control was preserved in mice lacking lymphocytes and was ablated after depletion of eosinophils or treatment with degranulation inhibitors. We further demonstrated that tumor-cell expression of the alarmin IL-33 was necessary and sufficient for eosinophil-mediated anti-tumor responses and that this mechanism contributed to the efficacy of checkpoint-inhibitor therapy. These findings provide insight into IL-33- and eosinophil-mediated tumor control, revealed when endogenous mechanisms of DPP4 immunoregulation are inhibited. Eosinophils have been described mainly in allergy settings but are increasingly appreciated as being involved in other aspects of immunity. Albert and colleagues use a clinically approved inhibitor of the dipeptidyl peptidase DPP4 to facilitate the recruitment of eosinophils to mouse tumors, where they are essential in tumor destruction.",
"title": "Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth"
},
{
"docid": "23985464",
"text": "Wild-type p53 has recently been shown to repress transcription from several cellular and viral promoters. Since p53 mutations are the most frequently reported genetic defects in human cancers, it becomes important to study the effects of mutations of p53 on promoter functions. We, therefore, have studied the effects of wild-type and mutant human p53 on the human proliferating-cell nuclear antigen (PCNA) promoter and on several viral promoters, including the herpes simplex virus type 1 UL9 promoter, the human cytomegalovirus major immediate-early promoter-enhancer, and the long terminal repeat promoters of Rous sarcoma virus and human T-cell lymphotropic virus type I. HeLa cells were cotransfected with a wild-type or mutant p53 expression vector and a plasmid containing a chloramphenicol acetyltransferase reporter gene under viral (or cellular) promoter control. As expected, expression of the wild-type p53 inhibited promoter function. Expression of a p53 with a mutation at any one of the four amino acid positions 175, 248, 273, or 281, however, correlated with a significant increase of the PCNA promoter activity (2- to 11-fold). The viral promoters were also activated, although to a somewhat lesser extent. We also showed that activation by a mutant p53 requires a minimal promoter containing a lone TATA box. A more significant increase (25-fold) in activation occurs when the promoter contains a binding site for the activating transcription factor or cyclic AMP response element-binding protein. Using Saos-2 cells that do not express p53, we showed that activation by a mutant p53 was a direct enhancement. The mutant forms of p53 used in this study are found in various cancer cells. The activation of PCNA by mutant p53s may indicate a way to increase cell proliferation by the mutant p53s. Thus, our data indicate a possible functional role for the mutants of p53 found in cancer cells in activating several important loci, including PCNA.",
"title": "Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells."
},
{
"docid": "15521377",
"text": "Cellular senescence is a stable form of cell-cycle arrest which is thought to limit the proliferative potential of premalignant cells [1]. The senescence phenotype was initially described by Hayflick and Moorhead in 1961 on human fibroblasts undergoing replicative exhaustion in culture [2]. It has been shown that senescence can be triggered in different cell types in response to diverse forms of cellular damage or stress (for review see [1]). Importantly, while senescence was denounced as a tissue culture phenomenon for many years, recent in vivo studies demonstrated that cellular senescence represents a potent failsafe mechanism against tumorigenesis and contributes to the cytotoxicity of certain anticancer agents (see for example [3-7]). Interestingly, senescent cells have also been observed in certain aged or damaged tissues and there is growing evidence that senescence checkpoints can affect the regenerative reserve of tissues and organismal aging [8-11]. However, senescence may also have positive effects on organ maintenance by limiting pathological responses to acute forms of injury such as fibrotic scarring in response to chemical induced liver injury [12]. Over the past years it was also shown that senescent cells can communicate with their environment by secreting a myriad of cytokines and growth factors. Interestingly, this \"senescence associated secretory phenotype (SASP)\" seems to be a double edged sword regarding tumor initiation and maintenance: i) On the one hand, it has been shown that the SASP can have pro-tumorigenic effects. In an experimental system it was shown that senescent mesenchymal cells can enhance the tumorigenicity of surrounding breast cancer cells [13]. ii) Similarly, it is possible that the SASP enhances selection of transformed cell clones in aged organ systems. It has been shown that loss of proliferative competition of non-transformed cells can accelerate leukemogenesis [14]. It remains to be seen whether aberrant secretion of cytokines and growth factors by the SASP can accelerated this process in aged and chronically damage organ systems. iii) In contrast to its pro-tumorigenic aspect, the SASP could also have anti-tumor effects. A recent study showed that in a mosaic liver cancer mouse model the activation of p53 induced senescence, an upregulation of inflammatory cytokines, and activation of innate immune responses leading to tumour cell clearance [15]. iv) In further support that the SASP could have anti-tumor activities, a series of recent papers showed that components of the SASP can stabilize the senescence cell cycle arrest via an autoregulatory feedback loop [16,17] or induces apoptosis of tumor cells [18]. In addition to its effects on tumorigenesis, the SASP could also influence tissue aging. Studies on aging telomere dysfunctional mice have provided direct experimental evidence for an in vivo activation of the SASP in response to telomere dysfunction [19]. Interestingly, this in vivo SASP provoked alterations in stem cell differentiation (skewing of hematopoiesis towards reduction in lymphopoiesis and enhancement of myelopoiesis) that are also characteristic signs of human aging. Figure 1. Different cellular stresses can induce senescence including telomere shortening, DNA damage, and oncogene activation. Senescence of tumor cells ... In light of the many possible roles o the SASP in aging and carcinogenesis, it appears to be of utmost importance to decipher regulatory pathways controlling the SASP. In a current publication, Bhaumik et al. have identified 2 microRNAs (miR-146a/b) that negatively regulate the secretion of IL-6 and IL-8 - two of the SASP [20]. The authors show that these microRNAs are up-regulated at late stages of senescence, many days after a permanent cell cycle arrest has been established. Interestingly, the inhibitory miRs are most strongly up-regulated in senescence of cell lines that show a strong SASP but not in cell lines characterized by a weak SASP. The authors propose a new concept indicating that miRs 146a and b function in a negative feedback loop preventing an over-activation of the SASP in senescent cells. The authors present some initial data suggesting that activation of this negative feedback loop involves IL-1 receptor, IRAK-1, and NFκB signalling leading to an up-regulation of miRs-146a and b. A direct proof that this proposed feedback loop suppresses over-activation of the SASP remains to be demonstrated in future studies. The authors show that blockage of IL-1-receptor signalling prevents both the up-regulation of miRs-146a and b as well as Il-6 secretion. To confirm their new concept, it would be important to show that a selective blockage of miRs-146a and b results in over-activation of the SASP. The work by Bhaumik et al. places mir-146a/b as central players to control IL-6 and IL-8 expression within the SASP. MicroRNAs are emerging therapeutic targets because their expression levels can be effectively modulated via the use of antagomirs (see for example [21]). Also, for increasing microRNA expression, microRNAs can be delivered into cellsin vivo (see for example [22]). Therefore, it will be interesting to functionally test the impact of mir-146 inhibition on tumorigenesis and aging in relevant mouse models. Such studies will be of particular interest, as recent work showed that IL-6 secretion by senescent cells is relevant for initiating and maintaining the senescene response via an autocrine loop [17]. A reduction of miR-146 could increase IL-6 levels in senescent cells, which should stabilize the senescence program and reduce the risk of malignant transformation. Furthermore, it can be speculated that reduction of mir-146 a/b will increase NfκB activation via IRAK1. As NfκB is modulating the expression of various inflammation associated genes, this may also lead to increased clearance of senescent tumor cells by the innate immune system. However, it should be mentioned that Il-6 secreted by senescent cells can also act as a mitogen for surrounding cells, thus potentially increasing the risk of malignant transformation [13,17]. Besides its function in SASP modulation, miR-146 was also reported to target the mRNAs of the BRCA1 and BRCA2 tumor suppressors. In a recent study a G to C polymorphism in miR-146, which leads to an increased processing and release of the mature microRNA, can predict an early onset of breast cancer [23]. Taken together, the study of Bhaumik et al. opens an interesting new research area dealing with the gene regulatory mechanisms that control activation of the SASP. Given the diverse roles of the SASP in modulating tumor progression, immune surveillance of damaged cells, and the stabilization of the senescence arrest itself, it will be of great interest to analyse the influence of SASP regulatory pathways during aging and cancer.",
"title": "Keeping your senescent cells under control"
},
{
"docid": "24917562",
"text": "PURPOSE To determine whether an increased resting energy expenditure (REE) and weight loss in lung cancer patients are related to a systemic inflammatory response. MATERIALS AND METHODS REE was measured by indirect calorimetry using a ventilated hood system. Soluble tumor necrosis factor receptor 55 (sTNF-R55) and sTNF-R75, soluble intercellular adhesion molecule (sICAM)-1, soluble E (sE)-selectin, lipopolysaccharide (LPS)-binding protein (LBP), interleukin (IL)-6, and TNF-alpha were measured using sandwich enzyme-linked immunosorbent assay (ELISA), and C-reactive protein (CRP) was measured by turbidimetry. A cross-sectional study was performed to compare inflammatory mediators between hypermetabolic (REE/Harris Benedict [HB] equation > or = 110%) versus normometabolic (REE/HB < 110%) patients and between patients who lost weight (more than 10% loss of preillness weight) versus those whose weight remained stable. RESULTS Eighty-seven patients with primary non-small-cell lung cancer were consecutively entered onto the study. Mean REE expressed as a percentage of the HB reference values was 118% +/- 12%; 67 patients were considered hypermetabolic. Twenty-six patients had a substantial loss of more than 10% of their preillness weight. Hypermetabolic patients were found to have significantly increased levels of sTNF-R55, sE-selectin, LBP, and CRP compared with normometabolic patients. Weight loss was related with increased levels of the sTNF-Rs, sICAM-1, IL-6, LBP, and CRP. CONCLUSION Hypermetabolism and weight loss are related to the presence of a systemic inflammatory response as reflected by enhanced levels of inflammatory mediators and acute phase proteins in patients with primary non-small-cell lung cancer.",
"title": "Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients."
}
] |
5a8f4837554299458435d599
|
Do both The Portage Canal and Erie Canal allow connection to the Atlantic Ocean ?
|
[
{
"docid": "6921956",
"text": "The Portage Canal was built to connect the Fox River and Wisconsin River at Portage, Wisconsin along the Fox-Wisconsin Waterway. For a time, it completed a route from the north Atlantic Ocean, through the St. Lawrence Seaway and down the Mississippi River to the Gulf of Mexico, and back to the Atlantic.",
"title": ""
},
{
"docid": "10046",
"text": "The Erie Canal is a canal in New York that is part of the east–west, cross-state route of the New York State Canal System (formerly known as the New York State Barge Canal). Originally, it ran 363 mi from Albany, on the Hudson River, to Buffalo, at Lake Erie. It was built to create a navigable water route from New York City and the Atlantic Ocean to the Great Lakes. When completed in 1825, it was the second longest canal in the world (after the Grand Canal in China) and greatly affected the development and economy of New York, New York City, and the United States.",
"title": ""
}
] |
[
{
"docid": "49135530",
"text": "The Saint Lawrence River Divide separates the Great Lakes Basin from the rest of the Atlantic Ocean watershed. Two canals cross the divide: The Chicago Sanitary and Ship Canal crosses the Chicago Portage and connects Lake Michigan to the Mississippi River watershed. The Erie Canal connects Lake Erie to the Hudson River watershed. Historically there were additional canals, e.g., the Ohio and Erie Canal, but most of these are no longer in operation.",
"title": ""
},
{
"docid": "2742812",
"text": "The Chemung Canal is a former canal in New York, United States. The canal connected Seneca Lake at Watkins Glen to the Chemung River at Elmira, New York. It was planned to connect the Finger Lakes region and Pennsylvania's Susquehanna River watershed with New York's Erie Canal system. The latter connected the Great Lakes with the Hudson River and ultimately the Atlantic port of New York City.",
"title": ""
},
{
"docid": "937923",
"text": "The Burgundy Canal (French: \"Canal de Bourgogne\" ) is a canal in Burgundy in central eastern France. It connects the river Yonne at Migennes with the Saône at Saint-Jean-de-Losne. Construction began in 1775 and was completed in 1832. The canal connects the Atlantic Ocean to the Mediterranean Sea via the Seine and the Yonne to the Saône and Rhône.",
"title": ""
},
{
"docid": "24849",
"text": "The Panama Canal (Spanish: \"Canal de Panamá\" ) is an artificial 48 mi waterway in Panama that connects the Atlantic Ocean with the Pacific Ocean. The canal cuts across the Isthmus of Panama and is a key conduit for international maritime trade. There are locks at each end to lift ships up to Gatun Lake, an artificial lake created to reduce the amount of excavation work required for the canal, 85 ft above sea level, and then lower the ships at the other end. The original locks are 110 ft wide. A third, wider lane of locks was constructed between September 2007 and May 2016. The expanded canal began commercial operation on June 26, 2016. The new locks allow transit of larger, Post-Panamax ships, capable of handling more cargo.",
"title": ""
},
{
"docid": "22087",
"text": "The Nicaraguan Canal (Spanish: \"Canal de Nicaragua\" ), formally the Nicaraguan Canal and Development Project (also referred to as the Nicaragua Grand Canal, or the Grand Interoceanic Canal) is a planned shipping route through Nicaragua to connect the Caribbean Sea (and therefore the Atlantic Ocean) with the Pacific Ocean. Its viability has been questioned by shipping experts and engineers. \"Major works\" such as dredging will take place after the finishing of a Pacific Ocean wharf, whose construction was planned to start in late 2016.",
"title": ""
},
{
"docid": "193822",
"text": "The Hay–Pauncefote Treaty is a treaty signed by the United States and the United Kingdom on 18 November 1901, as a preliminary to the creation of the Panama Canal. The Treaty nullified the Clayton–Bulwer Treaty of 1850 and gave the United States the right to create and control a canal across the Central American isthmus to connect the Pacific Ocean and the Atlantic Ocean. In the Clayton–Bulwer Treaty, both nations had renounced building such a canal under the sole control of one nation.",
"title": ""
},
{
"docid": "233684",
"text": "The Delaware and Raritan Canal (D&R Canal) is a canal in central New Jersey, United States, built in the 1830s, that served to connect the Delaware River to the Raritan River. It was intended as an efficient and reliable means of transportation of freight between Philadelphia and New York City, especially coal from the anthracite fields in eastern Pennsylvania. Before the advent of the railroads, the canal allowed shippers to cut many miles off the route from the Pennsylvania coal fields, down the Delaware, around Cape May, and up along the (occasionally treacherous) Atlantic Ocean coast to New York City.",
"title": ""
},
{
"docid": "11580246",
"text": "The Canal de Garonne, formerly known as Canal latéral à la Garonne, is a French canal dating from the mid-19th century which connects Toulouse to Castets-en-Dorthe. The remainder of the route to Bordeaux uses the Garonne River. It is the continuation of the Canal du Midi which connects the Mediterranean with Toulouse. Together they and the Garonne River form the Canal des Deux Mers which connects the Mediterranean Sea to the Atlantic Ocean.",
"title": ""
},
{
"docid": "1516493",
"text": "The Ohio and Erie Canal was a canal constructed during the 1820s and early 1830s in the U.S. state of Ohio. It connected Akron, Summit County, with the Cuyahoga River near its outlet on Lake Erie in Cleveland, Cuyahoga County, and a few years later, with the River Ohio near Portsmouth, Scioto County, and then connections to other canal systems in Pennsylvania.",
"title": ""
},
{
"docid": "6075621",
"text": "The Pennsylvania and Ohio Canal, also known as the P & O Canal, the Cross Cut Canal and the Mahoning Canal was a shipping canal which operated from 1840 until 1877 (though the canal was completely abandoned by 1872). It was unique in that it served to connect canals in two states (the Ohio and Erie Canal in Ohio and the Beaver and Erie Canal in Pennsylvania) and was funded by private interests.",
"title": ""
},
{
"docid": "2290573",
"text": "The Canaveral Barge Canal provides an east-to-west link between the Atlantic Ocean and Indian River Lagoon across northern Merritt Island, Florida, in two segments separated by the Banana River. It is located 15 miles south of Titusville, Florida. The canal is 12 feet deep and has entrances to other water systems including Syke's Creek and various marinas. The canal links Port Canaveral along the Atlantic Ocean to the Intracoastal Waterway running down the center of the Indian River Lagoon. The canal was constructed to allow the transport of crude oil by barge to the two power plants south of Titusville, Florida.",
"title": ""
},
{
"docid": "26908",
"text": "The Saint Lawrence Seaway (French: \"la Voie Maritime du Saint-Laurent\" ) is a system of locks, canals and channels in Canada and the United States that permit ocean-going vessels to travel from the Atlantic Ocean to the Great Lakes of North America, as far inland as the western end of Lake Superior. The Seaway is named for the Saint Lawrence River, which flows from Lake Ontario to the Atlantic Ocean. Legally, the Seaway extends from Montreal, Quebec, to Lake Erie and includes the Welland Canal.",
"title": ""
},
{
"docid": "4551887",
"text": "The Shinnecock Canal (also known as the Shinnecock and Peconic Canal) is a canal that cuts across the South Fork of Long Island at Hampton Bays, New York. At 4700 ft long, it connects Great Peconic Bay and the north fork of Long Island with Shinnecock Bay and the Atlantic Ocean. The canal opened to traffic in 1892.",
"title": ""
},
{
"docid": "466243",
"text": "The Rhine–Main–Danube Canal (German: \"Rhein-Main-Donau-Kanal\"; also called Main-Danube Canal, RMD Canal or Europa Canal), in Bavaria, Germany, connects the Main and the Danube rivers across the European Watershed, running from Bamberg via Nuremberg to Kelheim. The canal connects the North Sea and Atlantic Ocean to the Black Sea, providing a navigable artery between the Rhine delta (at Rotterdam in the Netherlands), and the Danube Delta in south-eastern Romania and south-western Ukraine (or Constanța, through the Danube–Black Sea Canal). The present canal was completed in 1992 and is 171 km long.",
"title": ""
},
{
"docid": "46424651",
"text": "There is a long history of attempts to build a canal across Nicaragua to connect the Atlantic Ocean with the Pacific Ocean. Construction of such a shipping route—using the San Juan River as an access route to Lake Nicaragua—was first proposed in the early colonial era. Napoleon III wrote an article about its feasibility in the middle of the 19th century. The United States abandoned plans to construct a waterway in Nicaragua in the early 20th century after it purchased the French interests in the Panama Canal. The Panama Canal was built and that is now the main connecting route across Central America.",
"title": ""
},
{
"docid": "48127715",
"text": "The St. Lucie Canal (C-44) is a man-made canal built in 1916 in Martin County, Florida to divert floodwaters from Lake Okeechobee via the canal to the South Fork of the St. Lucie River and into the St. Lucie Estuary, a component of the Indian River Lagoon, which connects to the Atlantic Ocean. Resulting from this connection, restoration projects in the St. Lucie River are the northernmost component of the Comprehensive Everglades Restoration Plan.",
"title": ""
},
{
"docid": "3326529",
"text": "The New York State Legislature appointed in 1810 a Commission to Explore a Route for a Canal to Lake Erie, and Report which became known as the Erie Canal Commission. Before 1817, the reports were submitted by the Commissioners Appointed to Provide for the Improvement of the Internal Navigation of the State, from February 1817 on the actual term Canal Commission was used, and its members titled officially Canal Commissioner. Besides, in 1817 a Canal Fund and Commissioners of the Canal Fund, and in 1826 a Canal Board, of which both the Canal Commissioners and the Commissioners of the Canal Fund were members, were created, and the term Canal Commission was applied sometimes to any of these bodies.",
"title": ""
},
{
"docid": "2879036",
"text": "The New York State Canal Corporation is responsible for the oversight, administration and maintenance of the New York State Canal System, which consists of the Erie Canal, Cayuga–Seneca Canal, Oswego Canal and Champlain Canal. It is also involved with the development and maintenance of the New York State Canalway Trail and with the general development and promotion of the Erie Canal Corridor as both a tourist attraction and a working waterway.",
"title": ""
},
{
"docid": "29323",
"text": "The Suez Canal (Arabic: قناة السويس \"qanāt as-suwēs \") is an artificial sea-level waterway in Egypt, connecting the Mediterranean Sea to the Red Sea through the Isthmus of Suez. Constructed by the Suez Canal Company between 1859 and 1869, it was officially opened on November 17, 1869. The canal offers watercraft a shorter journey between the North Atlantic and northern Indian Oceans via the Mediterranean and Red seas by avoiding the South Atlantic and southern Indian oceans, in turn reducing the journey by approximately 7000 km . It extends from the northern terminus of Port Said to the southern terminus of Port Tewfik at the city of Suez. Its length is 193.30 km , including its northern and southern access channels. In 2012, 17,225 vessels traversed the canal (47 per day).",
"title": ""
},
{
"docid": "2076899",
"text": "The St. Peters Canal is a small shipping canal located in eastern Canada on Cape Breton Island. It crosses an isthmus in the village of St. Peter's, Nova Scotia which connects St. Peters Inlet of Bras d'Or Lake to the north with St. Peters Bay of the Atlantic Ocean to the south.",
"title": ""
},
{
"docid": "3197052",
"text": "The Blavet river flows from central Brittany and enters the Atlantic Ocean on the south coast near Lorient. The river is canalised for most of its length, forming one of the links in the Brittany canal system. It connects with the Canal de Nantes à Brest at Pontivy and runs to Hennebont, a distance of 60 km. From the last lock at Polvern, the river is tidal and considered as a maritime waterway, giving access to the seaport of Lorient and the Atlantic Ocean. It became more important when the western half of that system was cut off by the construction of the Guerlédan dam and hydropower plant. Today, boats coming from Nantes via Redon have to take the Canal du Blavet in order to reach the ocean near Lorient.",
"title": ""
},
{
"docid": "2743171",
"text": "The Champlain Canal is a 60 mi canal that connects the south end of Lake Champlain to the Hudson River in New York. It was simultaneously constructed with the Erie Canal and is now part of the New York State Canal System and the Lakes to Locks Passage.",
"title": ""
},
{
"docid": "18073767",
"text": "The New River is a tidal estuary in South Florida, United States. The river is connected to the Everglades through a series of man made canals. After passing through Fort Lauderdale, the river connects to the Atlantic Ocean at Port Everglades cut. The river is entirely within Broward County and is composed from the junction of three main canals which originate in the Everglades, splitting off from the Miami Canal. They are the North New River Canal, which flows on the north side of State Road 84 / Interstate 595; the South New River Canal, which flows on the north side of Griffin Road and the south side of Orange Drive; and a canal which flows south of Sunrise Boulevard.",
"title": ""
},
{
"docid": "36667439",
"text": "Jeremiah's Gutter was a canal located on the border of Orleans and Eastham, Massachusetts, the first canal to cut across the peninsula of Cape Cod. It connected Cape Cod Bay in the west to the Atlantic Ocean in the east. It was active for over 100 years, although it gradually fell out of use and was later replaced by the more widely known Cape Cod Canal.",
"title": ""
},
{
"docid": "1106010",
"text": "The Keweenaw Waterway is a partly natural, partly artificial waterway which cuts across the Keweenaw Peninsula of Michigan; it separates Copper Island from the mainland. Parts of the waterway are variously known as the Keweenaw Waterway, Portage Canal, Portage Lake Canal, Portage River, Lily Pond, Torch Lake, and Portage Lake. The waterway connects to Lake Superior at its north and south entries (upper and lower portage entry lighthouses), with sections known as Portage Lake and Torch Lake in between. The primary tributary to Portage Lake is the Sturgeon River.",
"title": ""
},
{
"docid": "1096823",
"text": "The Cross Florida Barge Canal, now officially the Marjorie Harris Carr Cross Florida Greenway is a protected green belt corridor, one mile (1.6 km) wide in most places. It is named for the leader of opposition to the Cross Florida Barge Canal, a canal project to connect the Gulf of Mexico and the Atlantic Ocean across Florida for barge traffic. Two sections were built but the project was cancelled, mainly for environmental reasons.",
"title": ""
},
{
"docid": "47972096",
"text": "The Erie to Pittsburgh Trail is a rail trail currently in development in Western Pennsylvania and Western New York. When completed the trail will stretch approximately 270 miles from Erie, PA to Pittsburgh, PA. It will connect to the Great Allegheny Passage and the C&O Canal to create 605 miles of continuous off-road trail from Erie, PA to Washington, D.C.. It will also connect to the Erie Canal trail via the flat New York Bike Route 517 along Lake Erie.",
"title": ""
},
{
"docid": "3584593",
"text": "The Black River Canal was a canal built in northern New York in the United States to connect the Erie Canal to the Black River. The canal had 109 locks along its 35 mi length. Remains of several of the canal's former locks are visible along New York State Route 12 near Boonville.",
"title": ""
},
{
"docid": "25081775",
"text": "Erie Canal Lock 52 Complex is a national historic district located at Port Byron and Mentz in Cayuga County, New York. The district includes two contributing buildings (the Erie House and the blacksmith shop / mule barn); three contributing engineering structures (Erie Canal Lock 52, culvert, and canal prism of the enlarged Erie Canal); and archaeological sites associated with the canal operations. Lock 52 was constructed 1849-1853 as part of the Enlarged Erie Canal program. It remained in operation until the rerouting of the canal under the New York State Barge Canal System in 1917. The Erie House was built in 1894 and is a two story frame structure that housed a saloon and hotel.",
"title": ""
},
{
"docid": "2934726",
"text": "Rodrigo de Freitas Lagoon (Portuguese: \"Lagoa Rodrigo de Freitas\") is a lagoon in the district of Lagoa in the Zona Sul (South Zone) area of Rio de Janeiro. The lagoon is connected to the Atlantic Ocean, allowing sea water to enter by a canal along the edge of a park locally known as Jardim de Alah.",
"title": ""
}
] |
3619
|
When do companies typically announce stock splits?
|
[
{
"docid": "500250",
"text": "\"In 2005, Apple announced a split on Feb 11... CUPERTINO, California — February 11, 2005 — Apple® announced today that its Board of Directors has approved a two-for-one split of the Company’s common stock and a proportional increase in the number of Apple common shares authorized from 900 million to 1.8 billion. Each shareholder of record at the close of business on February 18, 2005 will receive one additional share for every outstanding share held on the record date, and trading will begin on a split-adjusted basis on February 28, 2005. ...one month after announcing earnings. CUPERTINO, California—January 12, 2005—Apple® today announced financial results for its fiscal 2005 first quarter ended December 25, 2004. For the quarter, the Company posted a net profit of $295 million, or $.70 per diluted share. These results compare to a net profit of $63 million, or $.17 per diluted share, in the year-ago quarter. Revenue for the quarter was $3.49 billion, up 74 percent from the year-ago quarter. Gross margin was 28.5 percent, up from 26.7 percent in the year-ago quarter. International sales accounted for 41 percent of the quarter’s revenue. I wouldn't expect Apple to offer another split, as it's become somewhat fashionable among tech companies to have high stock prices (see GOOG or NFLX or even BRK-A/BRK-B). Additionally, as a split does nothing to the underlying value of the company, it shouldn't affect your decision to purchase AAPL. (That said, it may change the perception of a stock as \"\"cheap\"\" or \"\"expensive\"\" per human psychology). So, to answer your question: companies will usually announce a stock split after releasing their financial results for the preceding fiscal year. Regardless of results, though, splits happen when the board decides it is advantageous to the company to split its stocks.\"",
"title": ""
}
] |
[
{
"docid": "235779",
"text": "I have had this happen a couple of times because of splits or sales of portions of the company. The general timeline was to announce how the split was to be handled; then the split; then a freeze in purchasing stock in the other company; then a freeze in sales; followed by a short blackout period; then the final transfers to funds/options/cash based on a mapping announced at the start of the process. You need to answer two questions: To determine if the final transactions will make the market move you have to understand how many shares are involved compared to the typical daily volume. There are two caveats: professional investors will be aware of the transaction date and can either ignore the employee transactions or try and take advantage of them; There may also be a mirroring set of transactions if the people left in the old company were awarded shares in your company as part of the sale. If you are happy with the default mapping then you can do nothing, and let the transaction happen based on the announced timeline. It is easy, and you don't have to worry about deadlines. If you don't like the default mapping then you need to know when the blackout period starts, so you don't end up not being able to perform the steps you want when you want. Timing is up to you. If the market doesn't like the acquisition/split it make make sense to make the move now, or wait until the last possible day depending on which part they don't like. Only you can answer that question.",
"title": ""
},
{
"docid": "484778",
"text": "\"There are a few reason why the stock price decreases after a dividend is paid: What's the point of paying a dividend if the stock price automatically decreases? Don't the shareholders just break even? Companies have to do something with their profits. They beholden to their shareholders to make them money either by increasing the share value or paying dividends. So they have the choice between reinvesting their profits into the company to grow the business or just handing the profits directly to the owners of the business (the shareholders). Some companies are as big as they want to be and investing their profits into more capital offers them diminishing returns. These companies are more likely to pay dividends to their shareholders. I assume the price of the stock \"\"naturally\"\" increases over the year to reflect the amount of the dividend payment. This is kind of a vague question but then doesn't it make it difficult to evaluate the fluctuations in stock price (in the way that you would a company that doesn't pay a dividend)? It depends on the company. The price may recover the dividend drop... could take a few days to a week. And that dependings on the company's performance and the overall market performance. With respect to options, I assume nothing special happens? So say I bought $9 call options yesterday that were in the money, all of a sudden they're just not? Is this typically priced into the option price? Is there anything else I need to know about buying options in companies that pay dividends? What if I had an in-the-money option, and all of a sudden out of nowhere a company decides to pay a dividend for the first time. Am I just screwed? One key is that dividends are announced in advance (typically at least, if not always; not sure if it's required by law but I wouldn't be surprised). This is one reason people will sometimes exercise a call option early, because they want to get the actual stock in order to earn the dividend. For \"\"out of the ordinary\"\" large cash dividends (over 10% is the guideline), stock splits, or other situations an option can be adjusted: http://www.888options.com/help/faq/splits.jsp#3 If you have an options account, they probably sent you a \"\"Characteristics and Risks of Standardized Options\"\" booklet. It has a section discussing this topic and the details of what kinds of situations trigger an adjustment. A regular pre-announced <10% dividend does not, while a special large dividend would, is what I roughly get from it. That \"\"Characteristics and Risks of Standardized Options\"\" is worth reading by the way; it's long and complicated, but well, options are complicated. Finally, do all companies reduce their stock price when they pay a dividend? Are they required to? I'm just shocked I've never heard of this before. The company doesn't directly control the stock price, but I do believe this is automatic. I think the market does this automatically because if they didn't, there would be enough people trying to do dividend capture arbitrage that it would ultimately drive down the price.\"",
"title": ""
},
{
"docid": "14133",
"text": "You haven't seen one because you haven't looked for one properly. You can set a google alert for stock split and get information about major issues splitting their stocks quite regularly, as well as a daily dose of recommendations from people without a say in the matter for big companies to split their stock. Stock splits are announced in advance by company management.",
"title": ""
},
{
"docid": "193266",
"text": "Companies do both quite often. They have opposite effects on the share price, but not on the total value to the shareholders. Doing both causes value to shareholders to rise (ie, any un-bought back shares now own a larger percentage of the company and are worth more) and drops the per-share price (so it is easier to buy a share of the stock). To some that's irrelevant, but some might want a share of an otherwise-expensive stock without paying $700 for it. As a specific example of this, Apple (APPL) split its stock in 2014 and also continued a significant buyback program: Apple announces $17B repurchase program, Oct 2014 Apple stock splits 7-to-1 in June 2014. This led to their stock in total being worth more, but costing substantially less per share.",
"title": ""
},
{
"docid": "581848",
"text": "During a stock split the only thing that changes is the number of shares outstanding. Typically a stock splits to lower its price per share. Sometimes if a company's value is falling it will do a reverse split where X shares will be exchanged for Y shares. This is typically done to avoid being de-listed from an exchange if the price per share falls below a certain threshold, usually $1. Again the only thing changing is the number of shares outstanding. A 20 for 1 reverse split means for every 20 shares outstanding the shareholder will be granted one new share. Example X Co. has 1,000,000 shares outstanding for a price of $100 per share. It does a 1 for 10 split. Now there are 10,000,000 shares outstanding for a price of $10 per share. Example Y Co has 1,000,000 shares outstanding for a price of $1 per share. It does a 10 for 1 reverse split. Now there are 100,000 shares outstanding for a price of $10. Quickly looking at the news for ASTI it looks like it underwent a 20 for 1 reverse split. You should probably look at your statements and ask your broker how the arithmetic worked in your case. Investopedia links for Reverse Stock Split and Stock Split",
"title": ""
},
{
"docid": "484190",
"text": "\"What most of these answers here seem to be missing is that a stock \"\"price\"\" is not exactly what we typically expect a price to be--for example, when we go in to the supermarket and see that the price of a gallon of milk is $2.00, we know that when we go to the cash register that is exactly how much we will pay. This is not, however, the case for stocks. For stocks, when most people talk about the price or quote, they are really referring to the last price at which that stock traded--which unlike for a gallon of milk at the supermarket, is no guarantee of what the next stock price will be. Relatively speaking, most stocks are extremely liquid, so they will react to any information which the \"\"market\"\" believes has a bearing on the value of their underlying asset almost (if not) immediately. As an extreme example, if allegations of accounting fraud for a particular company whose stock is trading at $40 come out mid-session, there will not be a gradual decline in the price ($40 -> $39.99 -> $39.97, etc.)-- instead, the price will jump from $40 to say, $20. In the time between the the $40 trade and the $20 trade, even though we may say the price of the stock was $40, that quote was actually a terrible estimate of the stock's current (post-fraud announcement) price. Considering that the \"\"price\"\" of a stock typically does not remain constant even in the span of a few seconds to a few minutes, it should not be hard to believe that this price will not remain constant over the 17.5 hour period from the previous day's close to the current day's open. Don't forget that as Americans go to bed, the Asian markets are just opening, and by the time US markets have opened, it is already past 2PM in London. In addition to the information (and therefore new knowledge) gained from these foreign markets' movements, macro factors can also play an important part in a security's price-- perhaps the ECB makes a morning statement that is interpreted as negative news for the markets or a foreign government before the US markets open. Stock prices on the NYSE, NASDAQ, etc. won't be able to react until 9:30, but the $40 price of the last trade of a broad market ETF at 4PM yesterday probably isn't looking so hot at 6:30 this morning... don't forget either that most individual stocks are correlated with the movement of the broader market, so even news that is not specific to a given security will in all likelihood still have an impact on that security's price. The above are only a few of many examples of things that can impact a stock's valuation between close and open: all sorts of geopolitical events, announcements from large, multi-national companies, macroeconomic stats such as unemployment rates, etc. announced in foreign countries can all play a role in affecting a security's price overnight. As an aside, one of the answers mentioned after hours trading as a reason--in actuality this typically has very little (if any) impact on the next day's prices and is often referred to as \"\"amateur hour\"\", due to the fact that trading during this time typically consists of small-time investors. Prices in AH are very poor predictors of a stock's price at open.\"",
"title": ""
},
{
"docid": "134419",
"text": "\"I can't speak authoritatively to your broader question about stocks in general, but in several years tracking AAPL closely, I can tell you that there's little apparent pattern to when their earnings call will be, or when it will be announced. What little I do know: - AAPL's calls tend to occur on a Tuesday more than any other day of the week - it's announced roughly a month in advance, but has been announced w/ less notice - it has a definite range of dates in which it occurs, typically somewhere in the 3rd week of the new quarter plus or minus a few days More broadly for #1: Given the underlying nature of what an option is, then yes, the day an earnings call date is announced could certainly influence the IV/price of options - but only for options that expire inside the \"\"grey area\"\" (~2 weeks long) window in which the call could potentially occur. Options expiring outside that grey area should experience little to no price change in reaction to the announcement of the date - unless the date was itself surprising, e.g. an earlier date would increase the premium on earlier dated options, a later date would increase the premium for later-dated options. As for #2: The exact date will probably always be a mystery, but the main factors are: - the historical pattern of earnings call dates (and announcements of those dates) which you can look up for any given company - when the company's quarter ends - potentially some influence in how long it takes the company to close out their books for the quarter (some types of businesses would be faster than others) - any special considerations for this particular quarter that affect reporting ability And finally: - a surprise of an earnings call occurring (substantively) later than usual is rarely going to be a good sign for the underlying security, and the expectation of catastrophe - while cratering the underlying - may also cause a disproportionate rise in IVs/prices due to fear\"",
"title": ""
},
{
"docid": "282565",
"text": "A company typically goes public in order to bring in additional capital. In an IPO, the company (through its officials) will typically do so by issuing additional shares, and offering to sell those to investors. If they did not do that, then there would be no net capital gain for the company; if person A sells share in company C to person B, then company C does not benefit directly from the exchange. By issuing and selling additional shares, the total value of all stock in the company can increase. Being publicly traded also greatly increases the confidence in the valuation of the company, as a consequence of the perfect market theory. There is nothing in this that says that initial investors (cofounders, employees, etc.) need to sell their shares in the process. They might choose to do so, or they might not; or they might be prevented from doing so by terms of any agreements that they have signed or by insider trading laws. Compare What happens to internal stock when a company goes public? Depending on specifics, it might be reasonable for the company to perform a share split prior to the initial public offering. That, however, doesn't affect the total value of the shares, only the price per share.",
"title": ""
},
{
"docid": "61103",
"text": "I'm guessing you're conflating bonus share issuance with stock split. That seems very common to me, from a quick search; there's even some issues of terminology between the US and Europe, I think - it seems some Europeans may use Bonus Shares to mean Stock Split, as opposed to the more common meaning in the US of Stock Dividend. Sometimes a bonus share issuance is (incorrectly) called a stock split, like in this public announcement from STADA in 2004. It is a 1:1 bonus share issuance (meaning they issue one bonus share to everyone who has one share now), but it is in essence the same thing as a stock split (a 2:1 stock split, namely). They combined the 1:1 from bonus share with the wording 'split', causing the confusion. Bonus share issuance, also known as a stock dividend, is covered well in this question/answer on this site, or from a search online. It has no obvious effect initially - both involve doubling shares out there and halving the price - but it has a substantially different treatment in terms of accounting, both to the company and to your tax accountant.",
"title": ""
},
{
"docid": "117576",
"text": "\"A stock split can force short sellers of penny stocks to cover their shorts and cauuse the price to appreciate. Example: Someone shorts a worthless pump and dump stock, 10,000 shares at .50. They have to put up $25,000.00 in margin ($2.50 per share for stocks under $2.50). The company announces a 3 to 1 split. Now the short investor must come up with $50,000.00 additional margin or be be \"\"bought in\"\". The short squeeze is on.\"",
"title": ""
},
{
"docid": "533779",
"text": "Stock splits are typically done to increase the liquidity of stock merely by converting every stock of the company into multiple stocks of lower face value. For example, if the initial face value of the stock was $10 and the stock got split 10:1, the new face value of the stock would be $1 each. This has a proportional effect on the market value of the stock also. If the stock was trading at $50, after the split the stock should ideally adjust to $5. This is to ensure that despite the stock split, the market capitalization of the company should remain the same. Number of Shares * Stock Price = Market Capitalization = CONSTANT",
"title": ""
},
{
"docid": "94159",
"text": "\"I don't have anything definitive, but in general positions in a company are not affected materially by what is called a corporate action. \"\"Corp Actions\"\" can really be anything that affects the details of a stock. Common examples are a ticker change, or exchange change, IPO (ie a new ticker), doing a split, or merging with another ticker. All of these events do not change the total value of people's positions. If a stock splits, you might have more shares, but they are worth less per share. A merger is quite similar to a split. The old company's stock is converted two the new companies stock at some ratio (ie 10 shares become 1 share) and then converted 1-to-1 to the new symbol. Shorting a stock that splits is no different. You shorted 10 shares, but after the split those are now 100 shares, when you exit the position you have to deliver back 100 \"\"new\"\" shares, though dollar-for-dollar they are the same total value. I don't see why a merger would affect your short position. The only difference is you are now shorting a different company, so when you exit the position you'll have to deliver shares of the new company back to the brokerage where you \"\"borrowed\"\" the shares you shorted.\"",
"title": ""
},
{
"docid": "309984",
"text": "\"Ordinarily a stock split increases all shareholders' share counts, so that there is no change in anybody's voting power. For example, if you owned 1% of the company before the split, after the split you now have twice as many shares, but there are now twice as many shares outstanding, so you still own 1% of the company. Also, stock splits are not ordinarily \"\"triggered\"\". Usually they happen when the board decides that for one reason or another it's desirable to increase the number of shares in circulation, which causes the price of each share to decrease proportionally. I'm not familiar with the show, and in particular I don't know what the action is that the character being addressed is thinking of taking, but it sounds like they are describing something akin to a \"\"poison pill\"\". In these arrangements, the \"\"pill\"\" is triggered by some predefined condition, say a party acquiring shares in excess of a defined threshold. What typically happens is that shareholders other than the ones who triggered the pill get a chance to buy shares at a substantial discount, thereby diluting the shares of the party that triggered it. Because the other shareholders have to buy their additional shares, albeit at a discount, and because it applies only to certain shares, it's not really a split, but it's close enough that the writers of the show may have felt it was worth using the term that is more familiar to the public.\"",
"title": ""
},
{
"docid": "481169",
"text": "Firstly a stock split is easy, for example each unit of stock is converted into 10 units. So if you owned 1% of the company before the stock split, you will still own 1% after the stock split, but have 10 times the number of shares. The company does not pay out any money when doing this and there is no effect on tax for the company or the share holder. Now onto stock dividend… When a company make a profit, the company gives some of the profit to the share holders as a dividend; this is normally paid in cash. An investor may then wish to buy more shares in the company using the money from the dividend. However buying shares used to have a large cost in broker charges etc. Therefore some companies allowed share holders to choose to have the dividend paid as shares. The company buys enough of their own shares to cover the payout, only having one set of broker charges and then sends the correct number of shares to each share holder that has opted for a stock dividend. (Along with any cash that was not enough to buy a complete share.) This made since when you had paper shares and admin costs where high for stock brokers. It does not make sense these days. A stock dividend is taxed as if you had been paid the dividend in cash and then brought the stock yourself.",
"title": ""
},
{
"docid": "484307",
"text": "\"There's an old adage in the equities business - \"\"buy on rumor, sell on fact\"\". Sometimes the strategy is to buy as soon as the rumor is out about a potential merger and then sell off into the news when it is actually announced, since this is normally when the biggest bounce occurs as part of a merger. The other part of the analysis you should do is to understand which of the companies benefits most (or is hurt the worst) by the merger and then make your play accordingly. Sometimes the company being acquired will see a bounce while the acquiring firm takes a hit, which is an indication the experts think the acquisition will be a drag on the acquiring company (perhaps because it is taking on a great deal of debt to make the acquisition, or because the acquiring firm is paying too much of a premium for what it's getting in return). Other times the exact opposite is true, where the company being acquired takes a hit while the buyer bounces, and again, the reasons for this can vary widely. If you wait until the merger is actually announced then by the time you get in, most of the premium from the announcement will likely have already been realized, and you'll be buying near the top of the market for the stock. The key is to be ahead of the other sellers by seeing the opportunities before they do and then knowing when to get out before everyone else does. Not an easy thing to pull off when you're trying to anticipate the markets, but it can be done if you do the right research and have patience. Good luck!\"",
"title": ""
},
{
"docid": "159439",
"text": "GT BIOPHARMA, INC. ANNOUNCES REVERSE STOCK SPILT AS PART OF OXIS-GEORGETOWN PLANNED MERGER LOS ANGELES, CA / ACCESSWIRE / August 21, 2017 / GT Biopharma Inc. (formerly known as Oxis International, Inc.) announced today a 1-for-300 reverse stock split. Shareholders of GT Biopharma Inc. (OTCQB: OXIS and Euronext Paris: OXI.PA) will be issued 1 share of common stock for every 300 shares common stock that they owned. If you owned fewer than 300 shares, they cashed you out.",
"title": ""
},
{
"docid": "554015",
"text": "What account you put it in depends on why you have those different accounts. First, if you have them due to regulatory requirements, then you of course must follow said regulations. I doubt that's the case here. Otherwise, you might be splitting based on how they trade (ETFs trade as stocks) or you could be splitting based on how you build a portfolio out of them. When you build a non-speculative stock portfolio, you typically want to limit your holdings in a single stock to a fairly small portion of your portfolio (say, 3%) to limit your exposure to bad stuff happening to a single company. That doesn't apply nearly a much to mutual funds, especially index funds. ETFs are much more like mutual funds here. You can also, of course, create an ETF account and put them there. You also say you have a market index account, what is that used for?",
"title": ""
},
{
"docid": "124368",
"text": "You can argue that cash dividend is a kind of split as well by this logic. The stock price on ex-dividend gets a hit coincidental with the dividend to be paid, so one can argue that the investor has the same cash value on the day the dividend was paid as if it wouldn't be paid at all. However, for the company to distribute stocks instead of cash may be advantageous if they have low cash reserves but significant amount of treasury stocks, and the stocks are of high liquidity. It is also a way for the company to release treasury stocks without diluting the current shareholders and creating taxable income to the company, that's an important factor to consider. This is in fact the real answer to your question. The main difference between split and stock dividend is that in split, the stock distributions proportions don't change. With stock dividend - they do. While the outstanding share proportions do not change, total proportions do, because of the treasury stocks being distributed. So company has less stocks in its vaults, but everyone else still has the same proportions of ownership. Compare this to split: company's treasury stocks would be split as well, and it would continue essentially sitting on the same proportion of stocks. That shift of treasury stocks to the outside shareholders - this is what makes it a dividend.",
"title": ""
},
{
"docid": "359734",
"text": "Are you sure you're not just looking at prices that are adjusted for the split, e.g. Yahoo? For example, Gilead Sciences (GILD) split a few months ago, but if you look at a price chart, there isn't an interruption even though the split is clearly marked. (Look in the past six months; it split in January). However, you could also simply be watching companies that happen to not split, for a variety of reasons. This isn't a criticism, but rather just a consequence of whatever stocks you happen to be watching. However, a quick search for information on stock splits yields a few articles (mainly from the Motley Fool) that argue that fewer companies are performing stock splits in recent years; the articles mainly talk about tech companies, and they make the argument that even though the shares in Google and Apple have a high stock price: Google and Apple aren't all that expensive by traditional valuation metrics. Google trades at just 15 times next year's projected profitability. Apple fetches a mere 13 times fiscal 2012's bottom-line estimates. These articles are a bit dated in terms of the stock prices, but the rationale is probably still good. Similar logic could apply for other companies; for example, since May 2009, Panera's stock price has climbed by almost a factor of 4 without splitting. The articles also make the point that stock splits were traditionally seen as bullish signs because: Companies splitting to bring their share prices back down to more accessible levels were optimistic in building those sand castles back up. One could make a fair argument that the overall economic climate isn't as bullish as it used to be, although I would only be convinced that this was affecting stock splits if data could be gathered and tested. A stock split can also raise the price of a stock because if small investors feel the stock is suddenly more accessible to them, they purchase more of it and might therefore drive up the price. (See the Investopedia article on stock splits for more information). Companies might not see the necessity in doing this because their stock price isn't high enough to warrant a split or because the price isn't high enough to outprice smaller investors. One interesting point to make, however, is that even though stock splits can drive small investors to buy more of the stock, this isn't always a gain for the company because professional investors (firms, institutions, etc.) have a tendency to sell after a split. The paper is a bit old, but it's still a very neat read. It's possible that more and more companies no longer see any advantage to splitting because it might not affect their stock price in the long run, and arguably could even hurt it. Considering that large/professional investors likely hold a higher percentage of a company's shares than smaller investors, if a stock split triggers a wave of selling by the former, the increasing propensity to buy of the latter may not be enough to offset the decline in price. Note: My answer only refers to standard stock splits; the reasons above may not apply to a decrease in the number of reverse stock splits (which may not be a phenomenon; I don't know).",
"title": ""
},
{
"docid": "11509",
"text": "The opening price is derived from new information received. It reflects the current state of the market. Opening Price Deviation (from Investopedia): Investor expectation can be changed by corporate announcements or other events that make the news. Corporations typically make news-worthy announcements that may have an effect on the stock price after the market closes. Large-scale natural disasters or man-made disasters such as wars or terrorist attacks that take place in the afterhours may have similar effects on stock prices. When this happens, some investors may attempt to either buy or sell securities during the afterhours. Not all orders are executed during after-hours trading. The lack of liquidity and the resulting wide spreads make market orders unattractive to traders in after-hours trading. This results in a large amount of limit or stop orders being placed at a price that is different from the prior day’s closing price. Consequently, when the market opens the next day, a substantial disparity in supply and demand causes the open to veer away from the prior day’s close in the direction that corresponds to the effect of the announcement, news or event.",
"title": ""
},
{
"docid": "414505",
"text": "\"The key difference I've found between a stock split and a stock dividend – of the exact same stock and class, as opposed to a spin-off – seems to be from the company's own accounting perspective. There doesn't appear to be any actual transfer of value to the shareholder with either kind of transaction; i.e. in theory, each transaction would be immaterial to the value of your holdings. With respect to the company's accounting, a stock split affects the par value of the shares, whereas a stock dividend reduces the retained earnings account in order to increase paid-in or contributed capital. I found a good online source which explains the history behind this accounting difference: McGraw-Hill - Intermediate Accounting eBook, 6/e - Chapter 18 - Stock Dividends and Splits. Small quote: [...] Besides being based on fallacious reasoning, accounting for stock dividends by artificially reclassifying “earned” capital as “invested” capital conflicts with the reporting objective of reporting shareholders' equity by source. Despite these limitations, this outdated accounting standard still applies. Since neither the corporation nor its shareholders apparently benefits from stock dividends, why do companies declare them?23 Occasionally, a company tries to give shareholders the illusion that they are receiving a real dividend. Another reason is merely to enable the corporation to take advantage of the accepted accounting practice of capitalizing retained earnings. Specifically, a company might wish to reduce an existing balance in retained earnings—otherwise available for cash dividends—so it can reinvest the earned assets represented by that balance without carrying a large balance in retained earnings. [...] There's a lot more on that page, before and after, worth reading. From another book: Google Books - Comparative Income Taxation, a Structural Analysis - page 314 - Stock Dividends. Small quote: The distribution of dividends in the form of stock or \"\"bonus\"\" shares to existing shareholders typically involves a transfer for corporate law purposes of retained earnings into stated capital. It can been [sic] viewed as a deemed distribution of a cash dividend to the shareholders followed by a corresponding contribution to capital or as solely as an event at the corporate level which has no effect on the shareholders whose economic interest in the corporation is unchanged by the receipt of additional shares. The systems have taken varied approaches to the stock dividend problem. The treatment is in part a function of the rules dealing with distributions of stated capital. [emphases above are mine] [... continues w/descriptions of different countries' tax treatments of the kinds of stock dividends. Includes U.S., Sweden, Japan, Netherlands, Canada, Australia, U.K., France, Germany. ...] As far as why a corporation might want to capitalize earnings and reduce the equity otherwise available for dividends, I can only imagine that, ignoring taxes for a moment, that it may have something to do with capital ratios that need to be maintained for financing or regulatory purposes? Yet, I remain curious. If I discover more on this then I'll update my answer. Additional resources:\"",
"title": ""
},
{
"docid": "453582",
"text": "\"Investopedia explains how a stock split impacts the stock's options: Each option contract is typically in control of 100 shares of an underlying security at a predetermined strike price. To find the new coverage of the option, take the split ratio and multiply by the old coverage (normally 100 shares). To find the new strike price, take the old strike price and divide by the split ratio. Say, for example, you own a call for 100 shares of XYZ with a strike price of $75. Now, if XYZ had a stock split of 2 for 1, then the option would now be for 200 shares with a strike price of $37.50. If, on the other hand, the stock split was 3 for 2, then the option would be for 150 shares with a strike price of $50. So, yes, a 2 for 1 stock split would halve the option strike prices. Also, in case the Investopedia article isn't clear, after a split the options still control 100 shares per contract. Regarding how a dividend affects option prices, I found an article with a good explanation: As mentioned above, dividends payment could reduce the price of a stock due to reduction of the company's assets. It becomes intuitive to know that if a stock is expected to go down, its call options will drop in extrinsic value while its put options will gain in extrinsic value before it happens. Indeed, dividends deflate the extrinsic value of call options and inflate the extrinsic value of put options weeks or even months before an expected dividend payment. Extrinsic value of Call Options are deflated due to dividends not only because of an expected reduction in the price of the stock but also due to the fact that call options buyers do not get paid the dividends that the stock buyers do. This makes call options of dividend paying stocks less attractive to own than the stocks itself, thereby depressing its extrinsic value. How much the value of call options drop due to dividends is really a function of its moneyness. In the money call options with high delta would be expected to drop the most on ex-date while out of the money call options with lower delta would be least affected. If a stock is expected to drop by a certain amount, that drop would already have been priced into the extrinsic value of its put options way beforehand. This is what happens to put options of dividend paying stocks. This effect is again a function of options moneyness but this time, in the money put options raise in extrinsic value more than out of the money put options. This is because in the money put options with delta of close to -1 would gain almost dollar or dollar on the drop of a stock. As such, in the money put options would rise in extrinsic value almost as much as the dividend rate itself while out of the money put options may not experience any changes since the dividend effect may not be strong enough to bring the stock down to take those out of the money put options in the money. So, no, a dividend of $1 will not necessarily decrease an option's price by $1 on the ex-dividend date. It depends on whether it's a call or put option, and whether the option is \"\"in the money\"\" or \"\"out of the money\"\" and by how much.\"",
"title": ""
},
{
"docid": "72372",
"text": "Stock values are generally reflective of a company's overall potential; and to some extent investor confidence in the prospect of a continued growth of that potential. Sales over such a short period of time such as a single weekend do not noticeably impact a stock's valuation. A stock's value has more to do with whether or not they meet market expectations for sales over a certain period of time (generally 1 quarter of a year) than it does that they actually had sales (or profits) on any given day. Of course, catastrophic events, major announcements, or new product releases do sometimes cause significant changes in a stock's value. For this reason you will often see stocks have significant volatility in periods around earnings announcements, merger rumors, or when anything unexpected happens in the world that might benefit or hurt their potential sales and growth. But overall a normal, average weekend of sales is already built into the price of a stock during normal trading.",
"title": ""
},
{
"docid": "238215",
"text": "You'd likely be subject to a lock-up period before you could sell the shares along with possibly having other rules about how you could sell your shares as you'd likely be seen as an insider that may have information that gives you an unfair advantage for selling the stock possibly. Depending on how far in advance you hold the shares, you may or may not have adjustments in the valuation and number of shares as some companies may do a split or reverse split when preparing for an IPO. A company I worked for in the late 1990s had an IPO and my stock options had a revised strike price because of a reverse stock split that was done prior to the IPO.",
"title": ""
},
{
"docid": "231781",
"text": "From Investopedia, A stock split is usually done by companies that have seen their share price increase to levels that are either too high or are beyond the price levels of similar companies in their sector. The primary motive is to make shares seem more affordable to small investors even though the underlying value of the company has not changed. From Wikipedia, It is often claimed that stock splits, in and of themselves, lead to higher stock prices; research, however, does not bear this out. What is true is that stock splits are usually initiated after a large run up in share price...stock splits do increase the liquidity of a stock; there are more buyers and sellers for 10 shares at $10 than 1 share at $100. Some companies have the opposite strategy: by refusing to split the stock and keeping the price high, they reduce trading volume. Berkshire Hathaway is a notable example of this. Something more to munch on, Why Warren Buffett Is Against Stock Splits.",
"title": ""
},
{
"docid": "129481",
"text": "I'm going to guess that you found this because of a stock screener. This company went through a 1:20 reverse split on June 30, so every 20 shares outstanding became a single share. Where before you had 20 shares worth $100 you now have 1 share worth $100, the value of the company doesn't change because of a split. This company was never trading for $30+ per share. Reverse splits are typical of a floundering company trading on an exchange that has a minimum share price requirement. While reverse splits don't change the value of the company, just the number of shares outstanding and the price per share, no healthy company performs a reverse split. Reverse splits are generally a massive signal to jump ship... The company seems to be trading for $1 right now, why the value fell from a pre-split $1.65 ($33/20) to $1 is anyone's guess; how the company ever got to $1.65 is also anyone's guess. But looking at the most recent 10-Q there are numerous causes for concern: Note 2. Capital Stock On March 6, 2017, the Company issued as compensation for services provided a total of 650,000 common shares with a fair value of $390,000 to a third party. The fair value of the shares was based on the price quoted on the OTC pink sheets on the grant date. this indicates a share price of $0.60 ($390,000/650,000) as of 3/6/2017, just to reinforce that the google price chart doesn't show the true past but a past adjusted for the split Results of Operations The three months ended March 31, 2017 compared to the three months ended March 31, 2016 For the three months ended March 31, 2017 compared to the three months ended March 31, 2016, total revenues were $0 and $0, respectively, and net losses from operations were $414,663 and $26,260, respectively. The net losses were attributable to costs attributable to operating as a public company, in particular, common stock with a valuation of $390,000 that was issued to an investor relations firm in the first quarter of 2017. Going Concern As of March 31, 2017, there is substantial doubt regarding our ability to continue as a going concern as we have not generated sufficient cash flow to fund our proposed business. We have suffered recurring losses from operations since our inception. In addition, we have yet to generate an internal cash flow from our business operations or successfully raised the financing required to develop our proposed business. As a result of these and other factors, our independent auditor has expressed substantial doubt about our ability to continue as a going concern. Liquidity and Capital Resources We had no cash as of the date of March 31, 2017. Additionally, since there is no balance sheet in the last 10-Q (another bad sign), the last annual report 10-K has this balance sheet: So the company: So why did the stock value plummet? It's anyones' guess but there is no shortage of ways to justify it. In fact, it's reasonable to ask how is this company still worth $3mm ($1 * 3mm shares outstanding)...",
"title": ""
},
{
"docid": "50141",
"text": "Prices can go up or down for a variety of reasons. If interest rates decline typically every stock goes up, and vice versa. Ultimately, there are two main value-related factors to a price of a stock: the dividends the company may issue or the payoff in the event the company is bought by someone else. Any dividend paid will give concrete value to a stock. For example, imagine a company has shares selling at $1.00 and they announce that they will pay a dividend at the end of the year of $1.00 per share. If their claim is believable then the stock is practically FREE at $1.00 a share, so in all likelihood the stock will go up a lot, just on the basis of the dividend alone. If a company is bought by another, they need to buy at least a majority of the shares, and in some cases all the shares. Since the price the buyer will be willing to pay for the company is related to its potential future income for the buyer, the more profitable the company is, the more a buyer will be willing to pay and hence the greater the value of the stock.",
"title": ""
},
{
"docid": "399345",
"text": "A stock dividend isn't exactly a split. Example: You have 100 shares of stock worth $5 a share (total value $500). The company wants to distribute a dividend worth 1%. You could expect a check for $5. But If they wanted to do a stock dividend they could send you 0.01 shares for every share you own, in your case you will be given a single share worth $5. Now you own 101 shares. Why a share dividend? It doesn't take cash to give the dividend. It keeps the money invested in the company. Some investors re-invest a cash dividend, some don't. A cash dividend is generally taxable income for the investor; a stock dividend isn't. Some investors prefer one over the other, but it depends on their specific financial picture. Neither a stock dividend, a cash dividend or split changes anything. The split changes the price to meet a goal. The cash dividend lowers the price by sending excess cash to the investors. The stock dividend lowers the price by creating new shares and retaining cash. It company picks the message and the method. depending on their goals and situation. Remember that a company may want to give a dividend because they have a history of doing so, but not have the cash to do so. It is like a split because the number of shares you own will go up, and the price per share will go down. But a split is generally done to bring the price of a share to within a specific range. The company sees a benefit to having a stock mid priced, instead of very high or very low.",
"title": ""
},
{
"docid": "549528",
"text": "\"Dividends are declared by the board of directors of a corporation on date A, to stock holders of record on date B (a later date). These stockholders then receive the declared dividend on date C, the so-called payment date. All of these dates are announced on the first (declaration) date. If there is no announcement, no dividend will be paid. The stock typically goes down in price by approximately the amount of the dividend on the date it \"\"goes ex,\"\" but then moves in price to reflect other developments, including the possibility of another declaration/payment, three months hence. Dividends are important to some investors, especially those who live on the income. They are less important to investors who are out for capital gains (and who may prefer that the company reinvest its money to seek such gains instead of paying dividends). In actual fact, dividends are one component of \"\"total\"\" or overall return. The other component is capital gains, and the sum of the two represents your return.\"",
"title": ""
},
{
"docid": "144005",
"text": "As I write this, the NASDAQ Composite is at 2790.00, down 6.14 points from yesterday. To calculate the percentage, you take 6.14 and divide by yesterday's close of 2796.14 to yield 0.22%. In your example, if SPY drops from 133.68 to 133.32, you use the difference of -0.36 and divide by the original, i.e. -0.36/133.68 = -0.27%. SPY is an ETF which you can invest in that tracks the S&P 500 index. Ideally, the index would have dropped the same percentage as SPY, but the points would be different (~10x higher). To answer your question about how one qualifies a point, it completely depends on the index being discussed. For example, the S&P 500 is a market-capitalization weighted index of the common stock of 500 large-cap US public companies. It is as if you owned every share of each of the 500 companies, then divide by some large constant to create a number that's easily understood mentally (i.e. 1330). The NASDAQ Composite used the same methodology but includes practically all stocks listed on the NASDAQ. Meanwhile, the Dow Jones Industrial Average is a price-weighted index of 30 large-cap companies. It's final value is modified using a divisor known as the Dow Divisor, which accounts for stock splits and similar events that have occurred since a stock has joined the index. Thus, points when referring to an index do not typically represent dollars. Rather, they serve as a quantitative measure of how the market is doing based on the performance of the index constituents. ETFs like SPY add a layer of abstraction by creating an investible vehicle that ideally tracks the value of the underlying index directly. Finally, neither price nor index value is related to volume. Volume is a raw measurement of the total number of shares traded for a given stock or the aggregate for a given exchange. Hope this helps!",
"title": ""
}
] |
1654
|
What should I consider when factoring fluctuating exchange rates into risk/return of overseas stock trading?
|
[
{
"docid": "378390",
"text": "Which of these two factors is likely to be more significant? There is long term trend that puts one favourable with other. .... I realise that I could just as easily have lost 5% on the LSE and made 5% back on the currency, leaving me with my original investment minus various fees; or to have lost 5% on both. Yes that is true. Either of the 3 scenarios are possible. Those issues aside, am I looking at this in remotely the right way? Yes. You are looking at it the right way. Generally one invests in Foreign markets for;",
"title": ""
}
] |
[
{
"docid": "1577",
"text": "If I buy VUSA from one exchange, can I sell it in a different exchange, assuming my brokerage account lets me trade in both exchanges? Or is it somehow tied to the exchange I bought it from? This doesn't happen for all securities and between all stock exchanges. So that is dependent on broker and country. I checked for VUSA with Selftrade. They categorically refused allowing me to trade in VUSA in different exchanges. I can only buy and sell in same currency only, albeit sell(buy) in the same exchange where I buy(sell) from. Should be the same behaviour for all brokers for us mere mortals, if you are a bank or a millionaire than that might be a different question. The VUSA you quote is quoted in GBP in LSE and in EUR in AEX, and the ETF has been created by an Irish entity and has an Irish ISIN. As Chris mentioned below, happens between US and Canadian exchanges, but not sure it happens across all exchanges. You cannot deal in inter-listed stocks in LSE and NYSE. Since it's the same asset, its value should not vary across exchanges once you compensate for exchange rates, right? Yes, else it opens up itself for arbitrage (profit without any risk) which everybody wants. So even if any such instance occurs, either people will exploit it to make the arbitrage profit zero (security reflects the equilibrium price) or the profit from such transaction is so less, compared with the effort involved, that people will tend to ignore it. Anyways arbitrage profit is very difficult to garner nowadays, considering the super computers at work in the market who exploit these discrepancies, the moment they see them and bring the security right to the zero arbitrage profit point. If there's no currency risk because of #2, what other factors should I consider when choosing an exchange to trade in? Liquidity? Something else? Time difference, by the time you wake up to trade in Japan, the Japanese markets would have closed. Tax implications across multiple continents. Law of the land, providing protection to investors. Finding a broker dealing in markets you want to explore or dealing with multiple brokers. Regulatory headaches.",
"title": ""
},
{
"docid": "490587",
"text": "\"Theoretically, it shouldn't matter which one you use. Your return should only depend on the stock returns in SGD and the ATS/SGD exchange rate (Austrian Schillings? is this an question from a textbook?). Whether you do the purchase \"\"through\"\" EUR or USD shouldn't matter as the fluctuations in either currency \"\"cancel\"\" when you do the two part exchange SGD/XXX then XXX/ATS. Now, in practice, the cost of exchanging currencies might be higher in one currency or the other. Likely a tiny, tiny amount higher in EUR. There is some risk as well as you will likely have to exchange the money and then wait a day or two to buy the stock, but the risk should be broadly similar between USD and EUR.\"",
"title": ""
},
{
"docid": "14781",
"text": "\"Yes, you're still exposed to currency risk when you purchase the stock on company B's exchange. I'm assuming you're buying the shares on B's stock exchange through an ADR, GDR, or similar instrument. The risk occurs as a result of the process through which the ADR is created. In its simplest form, the process works like this: I'll illustrate this with an example. I've separated the conversion rate into the exchange rate and a generic \"\"ADR conversion rate\"\" which includes all other factors the bank takes into account when deciding how many ADR shares to sell. The fact that the units line up is a nice check to make sure the calculation is logically correct. My example starts with these assumptions: I made up the generic ADR conversion rate; it will remain constant throughout this example. This is the simplified version of the calculation of the ADR share price from the European share price: Let's assume that the euro appreciates against the US dollar, and is now worth 1.4 USD (this is a major appreciation, but it makes a good example): The currency appreciation alone raised the share price of the ADR, even though the price of the share on the European exchange was unchanged. Now let's look at what happens if the euro appreciates further to 1.5 USD/EUR, but the company's share price on the European exchange falls: Even though the euro appreciated, the decline in the share price on the European exchange offset the currency risk in this case, leaving the ADR's share price on the US exchange unchanged. Finally, what happens if the euro experiences a major depreciation and the company's share price decreases significantly in the European market? This is a realistic situation that has occurred several times during the European sovereign debt crisis. Assuming this occurred immediately after the first example, European shareholders in the company experienced a (43.50 - 50) / 50 = -13% return, but American holders of the ADR experienced a (15.95 - 21.5093) / 21.5093 = -25.9% return. The currency shock was the primary cause of this magnified loss. Another point to keep in mind is that the foreign company itself may be exposed to currency risk if it conducts a lot of business in market with different currencies. Ideally the company has hedged against this, but if you invest in a foreign company through an ADR (or a GDR or another similar instrument), you may take on whatever risk the company hasn't hedged in addition to the currency risk that's present in the ADR/GDR conversion process. Here are a few articles that discuss currency risk specifically in the context of ADR's: (1), (2). Nestle, a Swiss company that is traded on US exchanges through an ADR, even addresses this issue in their FAQ for investors. There are other risks associated with instruments like ADR's and cross-listed companies, but normally arbitrageurs will remove these discontinuities quickly. Especially for cross-listed companies, this should keep the prices of highly liquid securities relatively synchronized.\"",
"title": ""
},
{
"docid": "115115",
"text": "Firstly, I think you need to separate your question into two parts: If you are Chinese, live in China and intend to stay in China for most of your life then the default answer to question 1 should be Renminbi. Question 2 is not as important, you can hold USD in almost any country in the world. Any investment you hold has risk, which may include market risk, credit risk, liquidity risk, inflation risk etc. Holding USD will expose you to exchange rate fluctuations as well. If the Renminbi rises in value against the dollar your returns in USD will be reduced by the same amount (remember that for currency fluctuations you have to multiply the percentages, see here for a good explanation). The first thing you probably want to do is find out exactly what the assets are in the 理财 you have invested in. The fact that there is a 'risk level' (even if it is only 2) would suggest to me that the fund is investing in some combination of bonds and stocks which means that your returns are not guaranteed and could make a loss. Interest rates on deposit accounts are mandated by the government in China, and the current 12 month deposit rate on RMB is 3%. To earn over 3%, GEB must be investing your assets in something else (I'm guessing bonds). Bear in mind that 1.5 years is a very short amount of time in investments, so don't assume this return will continue! I'm afraid I've only been studying Chinese for a year, so I can't really help you much with the link you've sent through - you may want to check if there is any guaranteed minimum return, which can be the case in more complex structured products. Ultimately you will need to pick an investment which you feel gives you the best combination of risk and return for your situation, there are a huge amount of options to choose between. The 4-5% you are earning right now is not a huge risk premium on the 3% you could earn in China from a time deposit, but in the current environment you may struggle to beat it without taking on more risk. Before considering that though - understand how much risk you already have with GEB.",
"title": ""
},
{
"docid": "391605",
"text": "\"Should I invest the money I don't need immediately and only withdraw it next year when I need it for living expenses or should I simply leave it in my current account? This might come as a bit of a surprise, but your money is already invested. We talk of investment vehicles. An investment vehicle is basically a place where you can put money and have it either earn a return, or be able to get it back later, or both. (The neither case is generally called \"\"spending\"\".) There are also investment classes which are things like cash, stocks, bonds, precious metals, etc.: different things that you can buy within an investment vehicle. You currently have the money in a bank account. Bank accounts currently earn very low interest rates, but they are also very liquid and very secure (in the sense of being certain that you will get the principal back). Now, when you talk about \"\"investing the money\"\", you are probably thinking of moving it from where it is currently sitting earning next to no return, to somewhere it can earn a somewhat higher return. And that's fine, but you should keep in mind that you aren't really investing it in that case, only moving it. The key to deciding about an asset allocation (how much of your money to put into what investment classes) is your investment horizon. The investment horizon is simply for how long you plan on letting the money remain where you put it. For money that you do not expect to touch for more than five years, common advice is to put it in the stock market. This is simply because in the long term, historically, the stock market has outperformed most other investment classes when looking at return versus risk (volatility). However, money that you expect to need sooner than that is often recommended against putting it in the stock market. The reason for this is that the stock market is volatile -- the value of your investment can fluctuate, and there's always the risk that it will be down when you need the money. If you don't need the money within several years, you can ride that out; but if you need the money within the next year, you might not have time to ride out the dip in the stock market! So, for money that you are going to need soon, you should be looking for less volatile investment classes. Bonds are generally less volatile than stocks, with government bonds generally being less volatile than corporate bonds. Bank accounts are even less volatile, coming in at practically zero volatility, but also have much lower expected rates of return. For the money that you need within a year, I would recommend against any volatile investment class. In other words, you might take whichever part you don't need within a year and put in bonds (except for what you don't foresee needing within the next half decade or more, which you can put in stocks), then put the remainder in a simple high-yield deposit-insured savings account. It won't earn much, but you will be basically guaranteed that the money will still be there when you want it in a year. For the money you put into bonds and stocks, find low-cost index mutual funds or exchange-traded funds to do so. You cannot predict the future rate of return of any investment, but you can predict the cost of the investment with a high degree of accuracy. Hence, for any given investment class, strive to minimize cost, as doing so is likely to lead to better return on investment over time. It's extremely rare to find higher-cost alternatives that are actually worth it in the long term.\"",
"title": ""
},
{
"docid": "79777",
"text": "\"It's simply supply and demand. First, demand: If you're an importer trying to buy from overseas, you'll need foreign currency, maybe Euros. Or if you want to make a trip to Europe you'll need to buy Euros. Or if you're a speculator and think the USD will fall in value, you'll probably buy Euros. Unless there's someone willing to sell you Euros for dollars, you can't get any. There are millions of people trying to exchange currency all over the world. If more want to buy USD, than that demand will positively influence the price of the USD (as measured in Euros). If more people want to buy Euros, well, vice versa. There are so many of these transactions globally, and the number of people and the nature of these transactions change so continuously, that the prices (exchange rates) for these currencies fluctuate continuously and smoothly. Demand is also impacted by what people want to buy and how much they want to buy it. If people generally want to invest their savings in stocks instead of dollars, i.e., if lots of people are attempting to buy stocks (by exchanging their dollars for stock), then the demand for the dollar is lower and the demand for stocks is higher. When the stock market crashes, you'll often see a spike in the exchange rate for the dollar, because people are trying to exchange stocks for dollars (this represents a lot of demand for dollars). Then there's \"\"Supply:\"\" It may seem like there are a fixed number of bills out there, or that supply only changes when Bernanke prints money, but there's actually a lot more to it than that. If you're coming from Europe and want to buy some USD from the bank, well, how much USD does the bank \"\"have\"\" and what does it mean for them to have money? The bank gets money from depositors, or from lenders. If one person puts money in a deposit account, and then the bank borrows that money from the account and lends it to a home buyer in the form of a mortgage, the same dollar is being used by two people. The home buyer might use that money to hire a carpenter, and the carpenter might put the dollar back into a bank account, and the same dollar might get lent out again. In economics this is called the \"\"multiplier effect.\"\" The full supply of money being used ends up becoming harder to calculate with this kind of debt and re-lending. Since money is something used and needed for conducting of transactions, the number of transactions being conducted (sometimes on credit) affects the \"\"supply\"\" of money. Demand and supply blur a bit when you consider people who hoard cash. If I fear the stock market, I might keep all my money in dollars. This takes cash away from companies who could invest it, takes the cash out of the pool of money being used for transactions, and leaves it waiting under my mattress. You could think of my hoarding as a type of demand for currency, or you could think of it as a reduction in the supply of currency available to conduct transactions. The full picture can be a bit more complicated, if you look at every way currencies are used globally, with swaps and various exchange contracts and futures, but this gives the basic story of where prices come from, that they are not set by some price fixer but are driven by market forces. The bank just facilitates transactions. If the last price (exchange rate) is 1.2 Dollars per Euro, and the bank gets more requests to buy USD for Euros than Euros for USD, it adjusts the rate downwards until the buying pressure is even. If the USD gets more expensive, at some point fewer people will want to buy it (or want to buy products from the US that cost USD). The bank maintains a spread (like buy for 1.19 and sell for 1.21) so it can take a profit. You should think of currency like any other commodity, and consider purchases for currency as a form of barter. The value of currency is merely a convention, but it works. The currency is needed in transactions, so it maintains value in this global market of bartering goods/services and other currencies. As supply and demand for this and other commodities/goods/services fluctuate, so does the quantity of any particular currency necessary to conduct any of these transactions. A official \"\"basket of goods\"\" and the price of those goods is used to determine consumer price indexes / inflation etc. The official price of this particular basket of goods is not a fundamental driver of exchange rates on a day to day basis.\"",
"title": ""
},
{
"docid": "580757",
"text": "If you do not understand the volatility of the fx market, you need to stop trading it, immediately. There are many reasons that fx is riskier than other types of investing, and you bear those risks whether you understand them or not. Below are a number of reasons why fx trading has high levels of risk: 1) FX trades on the relative exchange rate between currencies. That means it is a zero-sum game. Over time, the global fx market cannot 'grow'. If the US economy doubles in size, and the European economy doubles in size, then the exchange rate between the USD and the EUR will be the same as it is today (in an extreme example, all else being equal, yes I know that value of currency /= value of total economy, but the general point stands). Compare that with the stock market - if the US economy doubles in size, then effectively the value of your stock investments will double in size. That means that stocks, bonds, etc. tied to real world economies generally increase when the global economy increases - it is a positive sum game, where many players can be winners. On the long term, on average, most people earn value, without needing to get into 'timing' of trades. This allows many people to consider long-term equity investing to be lower risk than 'day-trading'. With FX, because the value of a currency is in its relative position compared with another currency, 1 player is a winner, 1 player is a loser. By this token, most fx trading is necessarily short-term 'day-trading', which by itself carries inherent risk. 2) Fx markets are insanely efficient (I will lightly state that this is my opinion, but one that I am not alone in holding firmly). This means that public information about a currency [ie: economic news, political news, etc.] is nearly immediately acted upon by many, many people, so that the revised fx price of that currency will quickly adjust. The more efficient a market is, the harder it is to 'time a trade'. As an example, if you see on a news feed that the head of a central bank authority made an announcement about interest rates in that country [a common driver of fx prices], you have only moments to make a trade before the large institutional investors already factor it into their bid/ask prices. Keep in mind that the large fx players are dealing with millions and billions of dollars; markets can move very quickly because of this. Note that some currencies trade more frequently than others. The main currency 'pairs' are typically between USD and / or other G10 country-currencies [JPY, EUR, etc.]. As you get into currencies of smaller countries, trading of those currencies happens less frequently. This means that there may be some additional time before public information is 'priced in' to the market value of that currency, making that currency 'less efficient'. On the flip side, if something is infrequently traded, pricing can be more volatile, as a few relatively smaller trades can have a big impact on the market. 3) Uncertainty of political news. If you make an fx trade based on what you believe will happen after an expected political event, you are taking risk that the event actually happens. Politics and world events can be very hard to predict, and there is a high element of chance involved [see recent 'expected' election results across the world for evidence of this]. For something like the stock market, a particular industry may get hit every once in a while with unexpected news, but the fx market is inherently tied to politics in a way that may impact exchange rates multiple times a day. 4) Leveraging. It is very common for fx traders to borrow money to invest in fx. This creates additional risk because it amplifies the impact of your (positive or negative) returns. This applies to other investments as well, but I mention it because high degrees of debt leveraging is extremely common in FX. To answer your direct question: There are no single individual traders who spike fx prices - that is the impact you see of a very efficient market, with large value traders, reacting to frequent, surprising news. I reiterate: If you do not understand the risks associated with fx trade, I recommend that you stop this activity immediately, at least until you understand it better [and I would recommend personally that any amateur investor never get involved in fx at all, regardless of how informed you believe you are].",
"title": ""
},
{
"docid": "575046",
"text": "why should I have any bias in favour of my local economy? The main reason is because your expenses are in the local currency. If you are planning on spending most of your money on foreign travel, that's one thing. But for most of us, the bulk of our expenses are incurred locally. So it makes sense for us to invest in things where the investment return is local. You might argue that you can always exchange foreign results into local currency, and that's true. But then you have two risks. One risk you'll have anywhere: your investments may go down. The other risk with a foreign investment is that the currency may lose value relative to your currency. If that happens, even a good performing investment can go down in terms of what it can return to you. That fund denominated in your currency is really doing these conversions behind the scenes. Unless the bulk of your purchases are from imports and have prices that fluctuate with your currency, you will probably be better off in local investments. As a rough rule of thumb, your country's import percentage is a good estimate of how much you should invest globally. That looks to be about 20% for Australia. So consider something like 50% local stocks, 20% local bonds, 15% foreign stocks, 5% foreign bonds, and 10% local cash. That will insulate you a bit from a weak local currency while not leaving you out to dry with a strong local currency. It's possible that your particular expenses might be more (or less) vulnerable to foreign price fluctuations than the typical. But hopefully this gives you a starting point until you can come up with a way of estimating your personal vulnerability.",
"title": ""
},
{
"docid": "104480",
"text": "The exchange rate between two currencies is simply the price that the most recent market participants were able to agree on, when trading. ie: if the USDCAD is 1.36, it's because the last trade that happened where someone bought 1 USD cost 1.36 CAD. There is no one person/organization which 'decides' the rate between two currencies. The rate moves you see is just the reality of money changing hands as people in various situations trade currencies for various reasons. Just like with stocks or any other market product, foreign exchange rates can fluctuate wildly based on many things. It is very difficult to forecast where rates will go, because the biggest changes in rates can often be unpredictable news events. For example, when Brexit happened, the value of the GBP plummeted relative to other currencies, because the market traders had less faith in the UK economy, and therefore weren't willing to pay as much to buy GBP. See more here: https://money.stackexchange.com/a/76482/44232. There is a very high level of risk in the foreign exchange market; for your sake, don't get involved in any trading that you do not well understand, first.",
"title": ""
},
{
"docid": "145140",
"text": "That is absolute rubbish. Warren Buffet follows simple value and GARP tenants that literally anyone could follow if they had the discipline to do so. I have never once heard of an investment made by Warren Buffet that wasn't rooted in fundamentals and easy to understand. The concept is fairly simple as is the math, buying great companies trading at discounts to what they are worth due to market fluctuations, emotionality, or overreactions to key sectors etc. If I buy ABC corp at $10 knowing it is worth $20, it could go down or trade sideways for FIVE YEARS doing seemingly nothing and then one day catch up with its worth due to any number of factors. In that case, my 100% return which took five years to actualize accounts for an average 20% return per year. Also (and this should be obvious), but diversification is a double edged sword. Every year, hundreds of stocks individually beat the market return. Owning any one of these stocks as your only holding would mean that YOU beat the market. As you buy more stocks and diversify your return will get closer and closer to that of an index or mutual fund. My advice is to stick to fundamentals like value and GARP investing, learn to separate when the market is being silly from when it is responding to a genuine concern, do your own homework and analysis on the stocks you buy, BE PATIENT after buying stock that your analysis gives you confidence in, and don't over diversify. If you do these things, congrats. YOU ARE Warren Buffet.",
"title": ""
},
{
"docid": "426703",
"text": "\"In addition to @MD-tech's answer: I'd distinguish between stock of a foreign company traded in local currency at a local exchange from the same stock traded in the foreign currency at a foreign exchange (and maybe with a foreign bank holding your accounts). The latter option will typically have higher variation because of exchange rate, and (usually) higher risks associated with possibility of recovery, (double) taxation and the possible legal difficulties @MD-tech mentions. Trading the foreign stock at a local exchange may mean that the transaction volume is far lower than at their \"\"home\"\" exchange. Holding stock of companies working in foreign markets OTOH can be seen as diversification and may lower your risk. If you only invest in the local market, your investments may be subject to the same economic fluctuations that your wage/employment/pension situation is subject to - it may be good to try de-correlating this a bit. Of course, depending on political circumstances in your home country, foreign investments may be less risky (though I'd suspect these home countries also come with a high risk of seizing foreign investments...)\"",
"title": ""
},
{
"docid": "195967",
"text": "\"Wikipedia has a solid article on Money Market Funds which includes a section on \"\"Breaking the Buck\"\" when the money market fund fails to return its full dollar. Money market funds smoothing out the daily (generally small) fluctuations of investing in short-term treasuries directly but have similar risk over longer periods. Some funds can and have lost money in market crashes, though even the worst performers still returned 95+ cents on the dollar. While few investments are guaranteed and likely none in your retirement account, money-market funds are likely the choice you have with the least fluctuation and similar minimal risk to short term treasuries. However, a second important risk to consider is inflation. Money market funds generally have returns similar or less than the inflation rate. While money markets funds help you avoid the fluctuations of the stock market the value of your retirement account falls behind the cost of goods over time. Unless the investor is fairly old most financial professionals would recommend only a small portion of a retirement account be in money market instruments. Vanguard also has a set of target retirement investment funds that are close to what many professionals would recommend. Consulting a financial professional to discuss your particular needs is a good option as well.\"",
"title": ""
},
{
"docid": "128048",
"text": "\"When you invest in an S&P500 index fund that is priced in USD, the only major risk you bear is the risk associated with the equity that comprises the index, since both the equities and the index fund are priced in USD. The fund in your question, however, is priced in EUR. For a fund like this to match the performance of the S&P500, which is priced in USD, as closely as possible, it needs to hedge against fluctuations in the EUR/USD exchange rate. If the fund simply converted EUR to USD then invested in an S&P500 index fund priced in USD, the EUR-priced fund may fail to match the USD-priced fund because of exchange rate fluctuations. Here is a simple example demonstrating why hedging is necessary. I assumed the current value of the USD-priced S&P500 index fund is 1,600 USD/share. The exchange rate is 1.3 USD/EUR. If you purchase one share of this index using EUR, you would pay 1230.77 EUR/share: If the S&P500 increases 10% to 1760 USD/share and the exchange rate remains unchanged, the value of the your investment in the EUR fund also increases by 10% (both sides of the equation are multiplied by 1.1): However, the currency risk comes into play when the EUR/USD exchange rate changes. Take the 10% increase in the price of the USD index occurring in tandem with an appreciation of the EUR to 1.4 USD/EUR: Although the USD-priced index gained 10%, the appreciation of the EUR means that the EUR value of your investment is almost unchanged from the first equation. For investments priced in EUR that invest in securities priced in USD, the presence of this additional currency risk mandates the use of a hedge if the indexes are going to track. The fund you linked to uses swap contracts, which I discuss in detail below, to hedge against fluctuations in the EUR/USD exchange rate. Since these derivatives aren't free, the cost of the hedge is included in the expenses of the fund and may result in differences between the S&P500 Index and the S&P 500 Euro Hedged Index. Also, it's important to realize that any time you invest in securities that are priced in a different currency than your own, you take on currency risk whether or not the investments aim to track indexes. This holds true even for securities that trade on an exchange in your local currency, like ADR's or GDR's. I wrote an answer that goes through a simple example in a similar fashion to the one above in that context, so you can read that for more information on currency risk in that context. There are several ways to investors, be they institutional or individual, can hedge against currency risk. iShares offers an ETF that tracks the S&P500 Euro Hedged Index and uses a over-the-counter currency swap contract called a month forward FX contract to hedge against the associated currency risk. In these contracts, two parties agree to swap some amount of one currency for another amount of another currency, at some time in the future. This allows both parties to effectively lock in an exchange rate for a given time period (a month in the case of the iShares ETF) and therefore protect themselves against exchange rate fluctuations in that period. There are other forms of currency swaps, equity swaps, etc. that could be used to hedge against currency risk. In general, two parties agree to swap one quantity, like a EUR cash flow, payments of a fixed interest rate, etc. for another quantity, like a USD cash flow, payments based on a floating interest rate, etc. In many cases these are over-the-counter transactions, there isn't necessarily a standardized definition. For example, if the European manager of a fund that tracks the S&P500 Euro Hedged Index is holding euros and wants to lock in an effective exchange rate of 1.4 USD/EUR (above the current exchange rate), he may find another party that is holding USD and wants to lock in the respective exchange rate of 0.71 EUR/USD. The other party could be an American fund manager that manages a USD-price fund that tracks the FTSE. By swapping USD and EUR, both parties can, at a price, lock in their desired exchange rates. I want to clear up something else in your question too. It's not correct that the \"\"S&P 500 is completely unrelated to the Euro.\"\" Far from it. There are many cases in which the EUR/USD exchange rate and the level of the S&P500 index could be related. For example: Troublesome economic news in Europe could cause the euro to depreciate against the dollar as European investors flee to safety, e.g. invest in Treasury bills. However, this economic news could also cause US investors to feel that the global economy won't recover as soon as hoped, which could affect the S&P500. If the euro appreciated against the dollar, for whatever reason, this could increase profits for US businesses that earn part of their profits in Europe. If a US company earns 1 million EUR and the exchange rate is 1.3 USD/EUR, the company earns 1.3 million USD. If the euro appreciates against the dollar to 1.4 USD/EUR in the next quarter and the company still earns 1 million EUR, they now earn 1.4 million USD. Even without additional sales, the US company earned a higher USD profit, which is reflected on their financial statements and could increase their share price (thus affecting the S&P500). Combining examples 1 and 2, if a US company earns some of its profits in Europe and a recession hits in the EU, two things could happen simultaneously. A) The company's sales decline as European consumers scale back their spending, and B) the euro depreciates against the dollar as European investors sell euros and invest in safer securities denominated in other currencies (USD or not). The company suffers a loss in profits both from decreased sales and the depreciation of the EUR. There are many more factors that could lead to correlation between the euro and the S&P500, or more generally, the European and American economies. The balance of trade, investor and consumer confidence, exposure of banks in one region to sovereign debt in another, the spread of asset/mortgage-backed securities from US financial firms to European banks, companies, municipalities, etc. all play a role. One example of this last point comes from this article, which includes an interesting line: Among the victims of America’s subprime crisis are eight municipalities in Norway, which lost a total of $125 million through subprime mortgage-related investments. Long story short, these municipalities had mortgage-backed securities in their investment portfolios that were derived from, far down the line, subprime mortgages on US homes. I don't know the specific cities, but it really demonstrates how interconnected the world's economies are when an American family's payment on their subprime mortgage in, say, Chicago, can end up backing a derivative investment in the investment portfolio of, say, Hammerfest, Norway.\"",
"title": ""
},
{
"docid": "30774",
"text": "The biggest challenge with owning any individual stock is price fluctuation, which is called risk. The scenarios you describe assume that the stock behaves exactly as you predict (price/portfolio doubles) and you need to consider risk. One way to measure risk in a stock or in a portfolio is Sharpe Ratio (risk adjusted return), or the related Sortino ratio. One piece of advice that is often offered to individual investors is to diversify, and the stated reason for diversification is to reduce risk. But that is not telling the whole story. When you are able to identify stocks that are not price correlated, you can construct a portfolio that reduces risk. You are trying to avoid 10% tax on the stock grant (25%-15%), but need to accept significant risk to avoid the 10% differential tax ($1000). An alternative to a single stock is to invest in an ETF (much lower risk), which you can buy and hold for a long time, and the price/growth of an ETF (ex. SPY) can be charted versus your stock to visualize the difference in growth/fluctuation. Look up the beta (volatility) of your stock compared to SPY (for example, IBM). Compare the beta of IBM and TSLA and note that you may accept higher volatility when you invest in a stock like Tesla over IBM. What is the beta of your stock? And how willing are you to accept that risk? When you can identify stocks that move in opposite directions, and mix your portfolio (look up beta balanced portolio), you can smooth out the variability (reduce the risk), although you may reduce your absolute return. This cannot be done with a single stock, but if you have more money to invest you could compose the rest of your portfolio to balance the risk for this stock grant, keep the grant shares, and still effectively manage risk. Some years ago I had accumulated over 10,000 shares (grants, options) in a company where I worked. During the time I worked there, their price varied between $30/share and < $1/share. I was able to liquidate at $3/share.",
"title": ""
},
{
"docid": "382505",
"text": "You can calculate your exposure intuitively, by calculating your 'fx sensitivity'. Take your total USD assets, let's assume $50k. Convert to EUR at the current rate, let's assume 1 EUR : 1.1 USD, resulting in 45.5k EUR . If the USD strengthens by 1%, this moves to a rate of ~1.09, resulting in 46k EUR value for the same 50k of USD investments. From this you can see that for every 1% the USD strengthens, you gain 500 EUR. For every 1% the USD weakens, you lose 500 EUR. The simplest way to reduce your exchange rate risk exposure, is to simply eliminate your foreign currency investments. ie: if you do not want to be exposed to fluctuations in the USD, invest in EUR only. This will align your assets with the currency of your future expenses [assuming you intend to continue living in Europe].This is not possible of course, if you would like to maintain investments in US assets. One relatively simple method available to invest in the US, without gaining an exposure to the USD, is to invest in USD assets only with money borrowed in USD. ie: if you borrow $50k USD, and invest $50k in the US stock market, then your new investments will be in the same currency as your debt. Therefore if the USD strengthens, your assets increase in relative EUR value, and your debt becomes more expensive. These two impacts wash out, leaving you with no net exposure to the value of the USD. There is a risk to this option - you are investing with a higher 'financial leverage' ratio. Using borrowed money to invest increases your risk; if your investments fall in value, you still need to make the periodic interest payments. Many people view this increased risk as a reason to never invest with borrowed money. You are compensated for that risk, by increased returns [because you have the ability to earn investment income without contributing any additional money of your own]. Whether the risk is worth it to you will depend on many factors - you should search this site and others on the topic to learn more about what those risks mean.",
"title": ""
},
{
"docid": "590364",
"text": "Bonds released at the same time have different interest rates because they have different levels of risks and liquidity associated. Risk will depend on the company / country / municipality that offers the bond: their financial position, and their resulting ability to make future payments & avoid default. Riskier organizations must offer higher interest rates to ensure that investors remain willing to loan them money. Liquidity depends on the terms of the loan - principal-only bonds give you minimal liquidity, as there are no ongoing interest payments, and nothing received until the bond's maturity date. All bonds provide lower liquidity if they have longer maturity dates. Bonds with lower liquidity must have higher returns to compensate for the fact that you will have to give up your cash for a longer period of time. Bonds released at different times will have different interest rates because of what the general 'market rate' for interest was in those periods. ie: if a bond is released in 2016 with interest rates approaching 0%, even a high risk bond would have a lower interest rate than a bond released in the 1980s, when market rates were approaching 20%. Some bonds offer variable interest tied to some market indicator - those will typically have higher interest at the time of issuance, because the bondholder bears some risk that the prevailing market rate will drop. Note regarding sale of bonds after market rates have changed: The value of your bonds will fluctuate with the market. If a bond was offered with 1% interest, and next year interest rates go up and a new identical bond is offered for 2% interest, when you sell your old bond you will take a loss, because the market won't want to pay full price for it anymore. Whether you should sell lower-interest rate bonds depends on how you feel about the factors above - do you want junk bonds that have stock-like levels of returns but high risks of default, maturing in 30 years? Or do you want AAA+ Bonds that have essentially 0% returns maturing in 30 days? If you are paying interest on debt, it is quite likely that you could achieve a net income benefit by selling the bonds, and paying off debt [assuming your debt has a higher interest rate than your low-rate bonds]. Paying off debt is sometimes referred to as a 'zero risk return', because essentially there is no real risk that your lender would otherwise go bankrupt. That is, you will owe your bank the car loan until you pay it, and paying it is the only thing you can do to reduce it. However, some schools of thought suggest that maintaining savings + liquid investments makes sense even if you have some debt, because cash + liquid investments can cover you in some emergencies that credit cards can't help you with. ie: if you lose your job, perhaps your credit could be pulled and you would have nothing except for your liquid savings to tide you over. How much you should save in this way is a matter of opinion, but often repeated numbers are either 3 months or 6 months worth [which is sometimes taken as x months of expenses, and sometimes as x months of after-tax income]. You should look into this issue further; there are many questions on this site that discuss it, I'm sure.",
"title": ""
},
{
"docid": "121595",
"text": "In less than two decades, more than half of all publicly traded companies have disappeared. There were 7,355 U.S. stocks in November 1997, according to the Center for Research in Security Prices at the University of Chicago’s Booth School of Business. Nowadays, there are fewer than 3,600. A close look at the data helps explain why stock pickers have been underperforming. And the shrinking number of companies should make all investors more skeptical about the market-beating claims of recently trendy strategies. Back in November 1997, there were more than 2,500 small stocks and nearly 4,000 tiny “microcap” stocks, according to CRSP. At the end of 2016, fewer than 1,200 small and just under 1,900 microcap stocks were left. Most of those companies melted away between 2000 and 2012, but the numbers so far show no signs of recovering. Several factors explain the shrinking number of stocks, analysts say, including the regulatory red tape that discourages smaller companies from going and staying public; the flood of venture-capital funding that enables young companies to stay private longer; and the rise of private-equity funds, whose buyouts take shares off the public market. For stock pickers, differentiating among the remaining choices is “an even harder game” than it was when the market consisted of twice as many companies, says Michael Mauboussin, an investment strategist at Credit Suisse in New York who wrote a report this spring titled “The Incredible Shrinking Universe of Stocks.” That’s because the surviving companies tend to be “fewer, bigger, older, more profitable and easier to analyze,” he says — making stock picking much more competitive. Consider small-stock funds. Often, they compare themselves to the Russell 2000, an index of the U.S. stocks ranked 1,001 through 3,000 by total market value. “Twenty years ago, there were over 4,000 stocks smaller” than the inclusion cutoff for the Russell 2000, says Lubos Pastor, a finance professor at the University of Chicago. “That number is down to less than 1,000 today.” So fund managers have far fewer stocks to choose from if they venture outside the index — the very area where the best bargains might be found. More money chasing fewer stocks could lead some fund managers to buy indiscriminately, regardless of value. Eric Cinnamond is a veteran portfolio manager with a solid record of investing in small stocks. Last year, he took the drastic step of shutting down his roughly $400 million mutual fund, Aston/River Road Independent Value, and giving his investors their money back. “Prices got so crazy in small caps, I fired myself,” he says. “My portfolio was 90% in cash at the end, because I couldn’t find anything to buy. If I’d kept investing, I was sure I’d lose people their money.” He adds, “It was the hardest thing I’ve ever done professionally, but I didn’t feel I had a choice. I knew my companies were overvalued.” Mr. Cinnamond hopes to return to the market when, in his view, values become attractive again. He doesn’t expect recent conditions to be permanent. The evaporation of thousands of companies may have one enduring result, however — and it could catch many investors by surprise. Most research on historical returns, points out Mr. Mauboussin, is based on the days when the stock market had twice as many companies as it does today. “Was the population of companies so different then,” he asks, “that the inferences we draw from it might no longer be valid?” So-called factor investing, also known as systematic or smart-beta investing, picks hundreds or thousands of stocks at a time based on common sources of risk and return. Among them: how big companies are, how much their shares fluctuate, how expensive their shares are relative to asset value and so on. But the historical outperformance of many such factors may have been driven largely by the tiniest companies — exactly those that have disappeared from the market in droves. Before concluding that small stocks or cheap “value” stocks will outrace the market as impressively as they did in the past, you should pause to consider how they will perform without the tailwinds from thousands of tiny stocks that no longer exist. The stock market has more than tripled in the past eight years, so the eclipse of so many companies hasn’t been a catastrophe. But it does imply that investing in some of the market’s trendiest strategies might be less profitable in the future than they looked in the past.",
"title": ""
},
{
"docid": "269646",
"text": "I find that there are two violation of law , prima facie , if someone earns money by depositing in the online account and then not reporting it ( including in his total income for the year ) and not bringing in India. Income Tax Act violation 1. It is simply comcealment liable for penalty & prosecution under I.T.Act. 2. You should know that anyone who is resident of India as per income Tax Act and having taxable income ( gross total income exceeding exemption limit) will have to fill up the column in his/her income tax return whether Previously these column were not in the Income Tax Return. So , now anyone who is liable to file return of Income can be tried for false return if he has hiddne assets aborad. 2. FEMA violation RBI permits remittance under Liberalized Remittance Scheme. However this scheme can not be used for certain purpose . It is important to examine whether RBI prohibits use of remittance for any entity or business you have described. You can read following FAQ on RBI site Q. 30. What are the prohibited items under the Scheme? Ans. The remittance facility under the Scheme is not available for the following: i) Remittance for any purpose specifically prohibited under Schedule-I (like purchase of lottery tickets/sweep stakes, proscribed magazines, etc.) or any item restricted under Schedule II of Foreign Exchange Management (Current Account Transactions) Rules, 2000; ii) Remittance from India for margins or margin calls to overseas exchanges / overseas counter-party; iii) Remittances for purchase of FCCBs issued by Indian companies in the overseas secondary market; iv) Remittance for trading in foreign exchange abroad; v) Remittance by a resident individual for setting up a company abroad; vi) Remittances directly or indirectly to Bhutan, Nepal, Mauritius and Pakistan; vii) Remittances directly or indirectly to countries identified by the Financial Action Task Force (FATF) as “non co-operative countries and territories”, from time to time; and viii) Remittances directly or indirectly to those individuals and entities identified as posing significant risk of committing acts of terrorism as advised separately by the Reserve Bank to the banks. You will have to examine , if the remittance was NOT done for purpose not allowed by RBI under LRS . If you clear this , you can say there is no violation and your violation is restricted to I.T.Act only.",
"title": ""
},
{
"docid": "483123",
"text": "\"The question is: how do you quantify investment risk? As Michael S says, one approach is to treat investment returns as a random variable. Bill Goetzmann (Yale finance professor) told me that if you accept that markets are efficient or that the price of an asset reflects it's underlying value, then changes in price represent changes in value, so standard deviation naturally becomes the appropriate measure for riskiness of an asset. Essentially, the more volatile an asset, the riskier it is. There is another school of thought that comes from Ben Graham and Warren Buffett, which says that volatility is not inherently risky. Rather, risk should be defined as the permanent loss of capital, so the riskiness of an asset is the probability of a permanent loss of capital invested. This is easy to do in casino games, based on basic probability such as roulette or slots. But what has been done with the various kinds of investment risks? My point is saying that certain bonds are \"\"low risk\"\" isn't good enough; I'd like some numbers--or at least a range of numbers--and therefore one could calculate expected payoff (in the statistics sense). Or can it not be done--and if not, why not? Investing is more art than science. In theory, a Triple-A bond rating means the asset is riskless or nearly riskless, but we saw that this was obviously wrong since several of the AAA mortgage backed securities (MBS) went under prior to the recent US recession. More recently, the current threat of default suggests that bond ratings are not entirely accurate, since US Treasuries are considered riskless assets. Investors often use bond ratings to evaluate investments - a bond is considered investment grade if it's BBB- or higher. To adequately price bonds and evaluate risk, there are too many factors to simply refer to a chart because things like the issuer, credit quality, liquidity risk, systematic risk, and unsystematic risk all play a factor. Another factor you have to consider is the overall portfolio. Markowitz showed that adding a riskier asset can actually lower the overall risk of a portfolio because of diversification. This is all under the assumption that risk = variance, which I think is bunk. I'm aware that Wall Street is nothing like roulette, but then again there must be some math and heavy economics behind calculating risk for individual investors. This is, after all, what \"\"quants\"\" are paid to do, in part. Is it all voodoo? I suspect some of it is, but not all of it. Quants are often involved in high frequency trading as well, but that's another note. There are complicated risk management products, such as the Aladdin system by BlackRock, which incorporate modern portfolio theory (Markowitz, Fama, Sharpe, Samuelson, etc) and financial formulas to manage risk. Crouhy's Risk Management covers some of the concepts applied. I also tend to think that when people point to the last x number of years of stock market performance, that is of less value than they expect. Even going back to 1900 provides \"\"only\"\" 110 years of data, and in my view, complex systems need more data than those 40,500 data points. 10,000 years' worth of data, ok, but not 110. Any books or articles that address these issues, or your own informed views, would be helfpul. I fully agree with you here. A lot of work is done in the Santa Fe Institute to study \"\"complex adaptive systems,\"\" and we don't have any big, clear theory as of yet. Conventional risk management is based on the ideas of modern portfolio theory, but a lot of that is seen to be wrong. Behavioral finance is introducing new ideas on how investors behave and why the old models are wrong, which is why I cannot suggest you study risk management and risk models because I and many skilled investors consider them to be largely wrong. There are many good books on investing, the best of which is Benjamin Graham's The Intelligent Investor. Although not a book on risk solely, it provides a different viewpoint on how to invest and covers how to protect investments via a \"\"Margin of Safety.\"\" Lastly, I'd recommend Against the Gods by Peter Bernstein, which covers the history of risk and risk analysis. It's not solely a finance book but rather a fascinating historical view of risk, and it helps but many things in context. Hope it helps!\"",
"title": ""
},
{
"docid": "585494",
"text": "\"Pay off the credit cards. From now on, pay off the credit cards monthly. Under no circumstances should you borrow money. You have net worth but no external income. Borrowing is useless to you. $200,000 in two bank accounts, because if one bank collapses, you want to have a spare while you wait for the government to pay off the guarantee. Keep $50,000 in checking and another $50k in savings. The remainder put into CDs. Don't expect interest income beyond inflation. Real interest rates (after inflation) are often slightly negative. People ask why you might keep money in the bank rather than stocks/bonds. The problem is that stocks/bonds don't always maintain their value, much less go up. The bank money won't gain, but it won't suddenly lose half its value either. It can easily take five years after a stock market crash for the market to recover. You don't want to be withdrawing from losses. Some people have suggested more bonds and fewer stocks. But putting some of the money in the bank is better than bonds. Bonds sometimes lose money, like stocks. Instead, park some of the money in the bank and pick a more aggressive stock/bond mixture. That way you're never desperate for money, and you can survive market dips. And the stock/bond part of the investment will return more at 70/30 than 60/40. $700,000 in stock mutual funds. $300,000 in bond mutual funds. Look for broad indexes rather than high returns. You need this to grow by the inflation rate just to keep even. That's $20,000 to $30,000 a year. Keep the balance between 70/30 and 75/25. You can move half the excess beyond inflation to your bank accounts. That's the money you have to spend each year. Don't withdraw money if you aren't keeping up with inflation. Don't try to time the market. Much better informed people with better resources will be trying to do that and failing. Play the odds instead. Keep to a consistent strategy and let the market come back to you. If you chase it, you are likely to lose money. If you don't spend money this year, you can save it for next year. Anything beyond $200,000 in the bank accounts is available for spending. In an emergency you may have to draw down the $200,000. Be careful. It's not as big a cushion as it seems, because you don't have an external income to replace it. I live in southern California but would like to move overseas after establishing stable investments. I am not the type of person that would invest in McDonald's, but would consider other less evil franchises (maybe?). These are contradictory goals, as stated. A franchise (meaning a local business of a national brand) is not a \"\"stable investment\"\". A franchise is something that you actively manage. At minimum, you have to hire someone to run the franchise. And as a general rule, they aren't as turnkey as they promise. How do you pick a good manager? How will you tell if they know how the business works? Particularly if you don't know. How will you tell that they are honest and won't just embezzle your money? Or more honestly, give you too much of the business revenues such that the business is not sustainable? Or spend so much on the business that you can't recover it as revenue? Some have suggested that you meant brand or stock rather than franchise. If so, you can ignore the last few paragraphs. I would be careful about making moral judgments about companies. McDonald's pays its workers too little. Google invades privacy. Exxon is bad for the environment. Chase collects fees from people desperate for money. Tesla relies on government subsidies. Every successful company has some way in which it can be considered \"\"evil\"\". And unsuccessful companies are evil in that they go out of business, leaving workers, customers, and investors (i.e. you!) in the lurch. Regardless, you should invest in broad index funds rather than individual stocks. If college is out of the question, then so should be stock investing. It's at least as much work and needs to be maintained. In terms of living overseas, dip your toe in first. Rent a small place for a few months. Find out how much it costs to live there. Remember to leave money for bigger expenses. You should be able to live on $20,000 or $25,000 a year now. Then you can plan on spending $35,000 a year to do it for real (including odd expenses that don't happen every month). Make sure that you have health insurance arranged. Eventually you may buy a place. If you can find one that you can afford for something like $100,000. Note that $100,000 would be low in California but sufficient even in many places in the US. Think rural, like the South or Midwest. And of course that would be more money in many countries in South America, Africa, or southern Asia. Even southern and eastern Europe might be possible. You might even pay a bit more and rent part of the property. In the US, this would be a duplex or a bed and breakfast. They may use different terms elsewhere. Given your health, do you need a maid/cook? That would lean towards something like a bed and breakfast, where the same person can clean for both you and the guests. Same with cooking, although that might be a second person (or more). Hire a bookkeeper/accountant first, as you'll want help evaluating potential purchases. Keep the business small enough that you can actively monitor it. Part of the problem here is that a million dollars sounds like a lot of money but isn't. You aren't rich. This is about bare minimum for surviving with a middle class lifestyle in the United States and other first world countries. You can't live like a tourist. It's true that many places overseas are cheaper. But many aren't (including much of Europe, Japan, Australia, New Zealand, etc.). And the ones that aren't may surprise you. And you also may find that some of the things that you personally want or need to buy are expensive elsewhere. Dabble first and commit slowly; be sure first. Include rarer things like travel in your expenses. Long term, there will be currency rate worries overseas. If you move permanently, you should certainly move your bank accounts there relatively soon (perhaps keep part of one in the US for emergencies that may bring you back). And move your investments as well. Your return may actually improve, although some of that is likely to be eaten up by inflation. A 10% return in a country with 12% inflation is a negative real return. Try to balance your investments by where your money gets spent. If you are eating imported food, put some of the investment in the place from which you are importing. That way, if exchange rates push your food costs up, they will likely increase your investments at the same time. If you are buying stuff online from US vendors and having it shipped to you, keep some of your investments in the US for the same reason. Make currency fluctuations work with you rather than against you. I don't know what your circumstances are in terms of health. If you can work, you probably should. Given twenty years, your million could grow to enough to live off securely. As is, you would be in trouble with another stock market crash. You'd have to live off the bank account money while you waited for your stocks and bonds to recover.\"",
"title": ""
},
{
"docid": "317399",
"text": "The major drawback to borrowing to invest (i.e. using leverage) is that your return on investment must be high enough to overcome the cost of finance. The average return on the S&P 500 is about 9.8% (from CNBC) a typical unsecured personal loan will have an interest rate of around 18-36% APR (from NerdWallet). This means that on average you will be paying more interest than you are receiving in returns so are losing money on the margin investment. Sometimes the S&P falls and over those periods you would be paying out interest having lost money so will have a negative return! You may have better credit and so be able to get a lower rate but I don't know your loan terms currently. Secured loans, such as remortgaging your house, will have lower costs but come with more life changing risks. The above assumes that you are getting financing by directly borrowing money, however, it is also possible to trade on margin. This is where you post a proportion of the value that you wish to trade with as collateral against a loan to buy the security. This form of finance is normally used by day traders and other short term holders of stocks. Although the financing costs here are low (I am not charged an interest rate on intraday margin trading) there are very high costs if you exceed the term of the loan. An example is that I am charged a fee if I hold a position overnight and my profits and losses are crystallised at that time. If I am in a losing position at that time the crystallisation process and fee can result in not having enough margin to recover the position and the loss of a potentially profit making position. Additionally if the amount of collateral cash (margin) posted is insufficient to cover the expected losses as calculated by your broker they will initiate a margin call asking for more collateral money. If you do not (or cannot) post this extra margin your losing position will be cashed out and you will take as a loss the total loss at that time. Since the market can change very rapidly, such as in a flash crash, this can result in your losing more money than you had in the first place. As this is essentially a loan you can be bankrupted by this. Overall using leverage to invest magnifies your potential profits but it also magnifies your potential losses. In many cases this magnification could be sufficient to lose you more money than you had originally invested. In addition to magnification you need to consider the cost of finance and that your return over the course of the loan needs to be higher than your cost of finance as well as inflation and other opportunity costs of capital. The S&P 500 is a relatively low volatility market in general so is unlikely to return losses in any given period that will mean that leverage of 1.25 times will take you into losses beyond your own capital investment but it is not impossible. The low level of risk automatically means that your returns are lower and so your cost of capital is likely to be a large proportion of your returns and your returns may not completely cover the cost of capital even when you are making money. The key thing if you are going to trade or invest on leverage is to understand the terms and costs of your leverage and discount them from any returns that you receive before declaring to yourself that you are profitable. It is even more important than usual to know how your positions are doing and whether you are covering your cost of capital when using leverage. It is also very important to know the terms of your leverage in detail, especially what will happen when and if your credit runs out for whatever reason be it the end of the financing period (the length of the loan) or your leverage ratio gets too high. You should also be aware of the costs of closing out the loan early should you need to do so and how to factor that into your investing decisions.",
"title": ""
},
{
"docid": "255789",
"text": "As mentioned in the comments, the problem stems with converting your U.S. Dollars to Indian Rupees so as to be able to purchase an Indian fixed deposit. At the time of writing this, 1 U.S. Dollar = 64 Indian Rupees. Consider the following economic factors: Both of the above factors are not definitive but are worth considering. You might be thinking- what if I never intend to convert my rupees back to dollars? If it is the case that money converted to rupees would stay that way, that then eliminates the risk of foreign exchange losses mentioned above. However, you must still keep in mind that part of the reason interest rates on fixed deposits is as high in India is because inflation is high. A 9% return must be looked at after adjusting for inflation. Inflation is somewhere between 5%-6% at the time of writing which then reduces your real return to about 4% (pre-tax).",
"title": ""
},
{
"docid": "469652",
"text": "HSBC exchange spread between HKD and USD was 483 bps (1 bps is 0.0001) on their 24 hours exchange network a few weeks ago when I checked. It is very high for a pair of linked currencies which has very little fluctuation. One should expect less than 5 bps or even 1 bps. I did my currency conversion at a US brokerage which can take HKD currency and then I was able to pick the time/rate and amount I like to make the conversion. Basically, the currency pair runs within a tight band and you just need to buy USD with HKD at the time when it is near the edge of the band to your advantage. There is usually no fee on currency conversion. They make money through the spread. HSBC premier allows you to wire free among countries. I forget whether they offer tighter spread or not. Rob was right on about the cost of transferring money overseas. The majority of the cost is in the conversion, not the wiring.",
"title": ""
},
{
"docid": "115134",
"text": "How I understand it is: supply/demand affect price of stock negatively/positively, respectively. Correct. Volume is the amount of buying/selling activity in these stocks (more volume = more fluctuation, right?). Sort of. Higher volume means higher liquidity. That is, a stock that is traded more is easier to trade. It doesn't necessarily mean more fluctuation and in the real world, it often means that these are well-understood stocks with a high amount of analyst coverage. This tends towards these stocks not being as volatile as smaller stocks with less liquidity. Company revenue (and profit) will help an investor predict company growth. That is one factor in a stock price. There are certain stocks that you would buy without them making a profit because their future revenue looks potentially explosive. However, these stocks are very risky and are bubble-prone. If you're starting out in the share market, it's generally a good idea to invest in index funds (I am not a broker, my advice should not be taken as financial advice). These funds aggregate risk by holding a lot of different companies. Also, statistics have shown that over time, buying and holding index funds long term tends to dramatically outperform other investment strategies, particularly for people with low amounts of capital.",
"title": ""
},
{
"docid": "280779",
"text": "Other than the exchange risk, one more thing to consider is interest rate risk and the returns you are generating from your money. If it is lying around in a current account with no interest then it is rational to keep it where you intend to stay(US or AUS). Now if your money is working for you, earning interest or has been invested in the market then it seems reasonable that you should put it where it earns the maximum for you. But that comes with a rider, the exchange risk you may have to bear if you are converting between the currencies. Do the returns earned by your money cancel out the FX rates moving up and down and still leave you with a positive return, compared with what you would earn if your money was where you stayed. Consider the below scenarios Do evaluate all your options before you transfer your money.",
"title": ""
},
{
"docid": "163197",
"text": "If you want to invest in stocks, bonds and mutual funds I would suggest you take a portion of your inheritance and use it to learn how to invest in this asset class wisely. Take courses on investing and trading (two different things) in paper assets and start trading on a fantasy exchange to test and hone your investment skills before risking any of your money. Personally I don't find bonds to have a meaningful rate of return and I prefer stocks that have a dividend over those that don't. Parking some of your money in an IRA is a good strategy for when you do not see opportunities to purchase cashflow-positive assets right away; this allows you to wait and deploy your capital when the opportunity presents itself and to educate yourself on what a good opportunity looks like.",
"title": ""
},
{
"docid": "495600",
"text": "\"Question 1: How do I start? or \"\"the broker\"\" problem Get an online broker. You can do a wire transfer to fund the account from your bank. Question 2: What criticism do you have for my plan? Dividend investing is smart. The only problem is that everyone's currently doing it. There is an insatiable demand for yield, not just individual investors but investment firms and pension funds that need to generate income to fund retirements for their clients. As more investors purchase the shares of dividend paying securities, the share price goes up. As the share price goes up, the dividend yield goes down. Same for bonds. For example, if a stock pays $1 per year in dividends, and you purchase the shares at $20/each, then your yearly return (not including share price fluctuations) would be 1/20 = 5%. But if you end up having to pay $30 per share, then your yearly return would be 1/30 or 3.3% yield. The more money you invest, the bigger this difference becomes; with $100K invested you'd make about $1.6K more at 5%. (BTW, don't put all your money in any small group of stocks, you want to diversify). ETFs work the same way, where new investors buying the shares cause the custodian to purchase more shares of the underlying securities, thus driving up the price up and yield down. Instead of ETFs, I'd have a look at something called closed end funds, or CEFs which also hold an underlying basket of securities but often trade at a discount to their net asset value, unlike ETFs. CEFs usually have higher yields than their ETF counterparts. I can't fully describe the ins and outs here in this space, but you'll definately want to do some research on them to better understand what you're buying, and HOW to successfully buy (ie make sure you're buying at a historically steep discount to NAV [https://seekingalpha.com/article/1116411-the-closed-end-fund-trifecta-how-to-analyze-a-cef] and where to screen [https://www.cefconnect.com/closed-end-funds-screener] Regardless of whether you decide to buy stocks, bonds, ETFs, CEFs, sell puts, or some mix, the best advice I can give is to a) diversify (personally, with a single RARE exception, I never let any one holding account for more than 2% of my total portfolio value), and b) space out your purchases over time. b) is important because we've been in a low interest rate environment since about 2009, and when the risk free rate of return is very low, investors purchase stocks and bonds which results in lower yields. As the risk free rate of return is expected to finally start slowly rising in 2017 and gradually over time, there should be gradual downward pressure (ie selling) on the prices of dividend stocks and especially bonds meaning you'll get better yields if you wait. Then again, we could hit a recession and the central banks actually lower rates which is why I say you want to space your purchases out.\"",
"title": ""
},
{
"docid": "557550",
"text": "First, currencies are not an investment; they are a medium of exchange; that is, you use currency to buy goods and services and/or investments. The goods and services you intend to buy in your retirement are presumably going to be bought in your country; to buy these you will need your country's currency. The investments you intend to buy now require the currency of whatever country they are located in. If you want to buy shares in Microsoft you need USD; if you want shares in BHP-Billiton you need AUD or GBP (It is traded on two exchanges), if you want property in Kuwait you need KWD and if you want bonds in your country you need IDR. When you sell these later to buy the goods and services you were saving for you need to convert from whatever currency you get for selling them into whatever currency you need to buy. When you invest you are taking on risk for which you expect to be compensated for - the higher the risk you take the better the returns had better be because there is always the chance that they will be negative, right down to losing it all if you are unlucky. There is no 100% safe investment; if you want to make sure you get full value for your money spend it all right now! If you invest overseas then, in addition to all the other investment risks, you are adding currency risk as well. That is, the risk that when you redeem your investments the overseas currency will have fallen relative you your currency. One of the best ways of mitigating risk is diversification; which allows the same return at a lower risk (or a higher return at the same risk). A pure equity portfolio is not diversified across asset classes (hopefully it is diversified across the equities). Equities are a high risk-high yield class; particularly in a developing economy like Indonesia. If you are very young with a decades long investment horizon this may be OK but even then, a diversified portfolio will probably offer better rewards at the same risk. Diversifying into local cash, bonds and property with a little foreign equities, bonds and property will serve you better than worrying about the strength of the IDR. Oh, and pay a professional for some real advice rather than listening to strangers on the internet.",
"title": ""
},
{
"docid": "158520",
"text": "There are different perspectives from which to calculate the gain, but the way I think it should be done is with respect to the risk you've assumed in the original position, which the simplistic calculation doesn't factor in. There's a good explanation about calculating the return from a short sale at Investopedia. Here's the part that I consider most relevant: [...] When calculating the return of a short sale, you need to compare the amount the trader gets to keep to the initial amount of the liability. Had the trade in our example turned against you, you (as the short seller) would owe not only the initial proceeds amount but also the excess amount, and this would come out of your pocket. [...] Refer to the source link for the full explanation. Update: As you can see from the other answers and comments, it is a more complex a Q&A than it may first appear. I subsequently found this interesting paper which discusses the difficulty of rate of return with respect to short sales and other atypical trades: Excerpt: [...] The problem causing this almost uniform omission of a percentage return on short sales, options (especially writing), and futures, it may be speculated, is that the nigh-well universal and conventional definition of rate of return involving an initial cash outflow followed by a later cash inflow does not appear to fit these investment situations. None of the investment finance texts nor general finance texts, undergraduate or graduate, have formally or explicitly shown how to resolve this predicament or how to justify the calculations they actually use. [...]",
"title": ""
},
{
"docid": "121100",
"text": "Some qualitative factors to consider when deciding whether to finance with equity vs debt (for a publicly traded company): 1) The case for equity: Is the stock trading high relative to what management believes is its intrinsic value? If so, raising equity may be attractive since management would be raising a lot of $$$, but the downside is you give up future earnings since you are diluting current ownership 2) The case for debt: What is the expected return for the project in which the raised capital will be utilized for? Is its expected return higher than the interest payments (in % terms)? If so raising debt would be more attractive than raising equity since current ownership would not be diluted That's all I can think of off the top of my head right now, I'm sure there are a few more qualitative factors to consider but I think these two are the most intuitive",
"title": ""
}
] |
PLAIN-1114
|
endothelium
|
[
{
"docid": "MED-1509",
"text": "AIMS/HYPOTHESIS: Sedentary (sitting) behaviours are ubiquitous in modern society. We conducted a systematic review and meta-analysis to examine the association of sedentary time with diabetes, cardiovascular disease and cardiovascular and all-cause mortality. METHODS: Medline, Embase and the Cochrane Library databases were searched for terms related to sedentary time and health outcomes. Cross-sectional and prospective studies were included. RR/HR and 95% CIs were extracted by two independent reviewers. Data were adjusted for baseline event rate and pooled using a random-effects model. Bayesian predictive effects and intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future. RESULTS: Eighteen studies (16 prospective, two cross-sectional) were included, with 794,577 participants. Fifteen of these studies were moderate to high quality. The greatest sedentary time compared with the lowest was associated with a 112% increase in the RR of diabetes (RR 2.12; 95% credible interval [CrI] 1.61, 2.78), a 147% increase in the RR of cardiovascular events (RR 2.47; 95% CI 1.44, 4.24), a 90% increase in the risk of cardiovascular mortality (HR 1.90; 95% CrI 1.36, 2.66) and a 49% increase in the risk of all-cause mortality (HR 1.49; 95% CrI 1.14, 2.03). The predictive effects and intervals were only significant for diabetes. CONCLUSIONS/INTERPRETATION: Sedentary time is associated with an increased risk of diabetes, cardiovascular disease and cardiovascular and all-cause mortality; the strength of the association is most consistent for diabetes.",
"title": "Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis."
},
{
"docid": "MED-1507",
"text": "Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women."
},
{
"docid": "MED-1513",
"text": "Even when adults meet physical activity guidelines, sitting for prolonged periods can compromise metabolic health. TV time and objective-measurement studies show deleterious associations, and breaking up sedentary time is beneficial. Sitting time, TV time, and time sitting in automobiles increase premature mortality risk. Further evidence from prospective studies, intervention trials, and population-based behavioral studies is required.",
"title": "Too Much Sitting: The Population-Health Science of Sedentary Behavior"
},
{
"docid": "MED-1512",
"text": "BACKGROUND: Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. METHODS: Forty-five women were randomly assigned to four interventions: \"placebo ingestion\" (n = 11), \"curcumin ingestion\" (n = 11), \"exercise training with placebo ingestion\" (n = 11), or \"exercise training with curcumin ingestion\" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. RESULTS: There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. CONCLUSIONS: These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.",
"title": "Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study."
},
{
"docid": "MED-1517",
"text": "BACKGROUND: Sedentary behavior is a risk factor for cardiometabolic disease. Regularly interrupting sedentary behavior with activity breaks may lower this risk. OBJECTIVE: We compared the effects of prolonged sitting, continuous physical activity combined with prolonged sitting, and regular activity breaks on postprandial metabolism. DESIGN: Seventy adults participated in a randomized crossover study. The prolonged sitting intervention involved sitting for 9 h, the physical activity intervention involved walking for 30 min and then sitting, and the regular-activity-break intervention involved walking for 1 min 40 s every 30 min. Participants consumed a meal-replacement beverage at 60, 240, and 420 min. RESULTS: The plasma incremental area under the curve (iAUC) for insulin differed between interventions (overall P < 0.001). Regular activity breaks lowered values by 866.7 IU · L(-1) · 9 h(-1) (95% CI: 506.0, 1227.5 IU · L(-1) · 9 h(-1); P < 0.001) when compared with prolonged sitting and by 542.0 IU · L(-1) · 9 h(-1) (95% CI: 179.9, 904.2 IU · L(-1) · 9 h(-1); P = 0.003) when compared with physical activity. Plasma glucose iAUC also differed between interventions (overall P < 0.001). Regular activity breaks lowered values by 18.9 mmol · L(-1) · 9 h(-1) (95% CI: 10.0, 28.0 mmol · L(-1) · 9 h(-1); P < 0.001) when compared with prolonged sitting and by 17.4 mmol · L(-1) · 9 h(-1) (95% CI: 8.4, 26.3 mmol · L(-1) · 9 h(-1); P < 0.001) when compared with physical activity. Plasma triglyceride iAUC differed between interventions (overall P = 0.023). Physical activity lowered values by 6.3 mmol · L(-1) · 9 h(-1) (95% CI: 1.8, 10.7 mmol · L(-1) · 9 h(-1); P = 0.006) when compared with regular activity breaks. CONCLUSION: Regular activity breaks were more effective than continuous physical activity at decreasing postprandial glycemia and insulinemia in healthy, normal-weight adults. This trial was registered with the Australian New Zealand Clinical Trials registry as ACTRN12610000953033.",
"title": "Breaking prolonged sitting reduces postprandial glycemia in healthy, normal-weight adults: a randomized crossover trial."
},
{
"docid": "MED-1514",
"text": "OBJECTIVE: Total sedentary (absence of whole-body movement) time is associated with obesity, abnormal glucose metabolism, and the metabolic syndrome. In addition to the effects of total sedentary time, the manner in which it is accumulated may also be important. We examined the association of breaks in objectively measured sedentary time with biological markers of metabolic risk. RESEARCH DESIGN AND METHODS: Participants (n = 168, mean age 53.4 years) for this cross-sectional study were recruited from the 2004-2005 Australian Diabetes, Obesity and Lifestyle study. Sedentary time was measured by an accelerometer (counts/minute(-1) < 100) worn during waking hours for seven consecutive days. Each interruption in sedentary time (counts/min > or = 100) was considered a break. Fasting plasma glucose, 2-h plasma glucose, serum triglycerides, HDL cholesterol, weight, height, waist circumference, and resting blood pressure were measured. MatLab was used to derive the breaks variable; SPSS was used for the statistical analysis. RESULTS: Independent of total sedentary time and moderate-to-vigorous intensity activity time, increased breaks in sedentary time were beneficially associated with waist circumference (standardized beta = -0.16, 95% CI -0.31 to -0.02, P = 0.026), BMI (beta = -0.19, -0.35 to -0.02, P = 0.026), triglycerides (beta = -0.18, -0.34 to -0.02, P = 0.029), and 2-h plasma glucose (beta = -0.18, -0.34 to -0.02, P = 0.025). CONCLUSIONS: This study provides evidence of the importance of avoiding prolonged uninterrupted periods of sedentary (primarily sitting) time. These findings suggest new public health recommendations regarding breaking up sedentary time that are complementary to those for physical activity.",
"title": "Breaks in sedentary time: beneficial associations with metabolic risk."
},
{
"docid": "MED-1510",
"text": "Eight young men (group A) underwent 5 h of quiet sitting, preceded by 30 min of recumbency, 20 min of standing, and 20 s of walking, and five other young men (group B) underwent 70 min of sitting, preceded by recumbency only, to determine the effects of prolonged sitting and previous posture on hemodynamic responses (measured by impedance plethysmography). Group A showed more calf blood pooling and a decrease in thigh blood flow during sitting in comparison with the control group, but after 1 h of sitting hemodynamic responses of the two groups were similar. Sitting for 5 h (1st vs. 5th h) resulted in an increase in calf venous pooling (17%) and a decrease in calf BF (13%), a reduction in gravitational pooling in the thigh (corresponding to increased pooling in the calf), increases in diastolic and mean arterial pressures (6 and 7.3 mmHg, respectively), and minor changes in heart rate, stroke volume, and cardiac output. The results show that it is necessary to sit for 1 h before hemodynamic responses can be assessed in this position, regardless of the posture maintained previously. The main effect of prolonged sitting is pooling in the calf, which is compensated for by an increase in peripheral resistance.",
"title": "Hemodynamic responses during prolonged sitting."
},
{
"docid": "MED-1516",
"text": "Summary Sedentary activity is a modifiable life-style behavior and a key component in the etiology of atherosclerotic cardiovascular disease (ACVD). US adults and children spend more than half their waking time in sedentary pursuits. Sedentary activity has been shown to result in impaired insulin sensitivity, impaired metabolic function and attenuated endothelial function, which are classic markers of ACVD. Sedentary activity is defined as ‘sitting without otherwise being active.’ This behavior promotes reduced muscular activity of the lower extremities which decreases leg blood flow, increases blood pooling in the calf, augments mean arterial pressure, and deforms arterial segments resulting in low mean shear stress (SS). SS activates distinct physiological mechanisms which have been proposed to be protective against ACVD; specifically through a SS-induced endothelium-derived nitric oxide mechanism. Reduced bioavailability of nitric oxide creates a pro-oxidant milieu resulting in increased oxidative stress. There is sufficient evidence which demonstrates that endothelial function is attenuated in the presence of oxidative stress. Sedentary activity results in low SS in the lower extremities which may result in increased oxidative stress and impaired endothelial function. This review furthers the use of sitting as model to study the effects of inactivity, discusses possible physiological mechanisms and suggests future directions.",
"title": "Sitting and endothelial dysfunction: The role of shear stress"
},
{
"docid": "MED-1518",
"text": "OBJECTIVE: Sedentariness is associated with weight gain and obesity. A treadmill desk is the combination of a standing desk and a treadmill that allow employees to work while walking at low speed. DESIGN AND METHODS: The hypothesis was that a 1-year intervention with treadmill desks is associated with an increase in employee daily physical activity (summation of all activity per minute) and a decrease in daily sedentary time (zero activity). Employees (n = 36; 25 women, 11 men) with sedentary jobs (87 ± 27 kg, BMI 29 ± 7 kg/m(2) , n = 10 Lean BMI < 25 kg/m(2) , n = 15 Overweight 25 < BMI < 30 kg/m(2) , n = 11 Obese BMI > 30 kg/m(2) ) volunteered to have their traditional desk replaced with a treadmill desk to promote physical activity for 1 year. RESULTS: Daily physical activity (using accelerometers), work performance, body composition, and blood variables were measured at Baseline and 6 and 12 months after the treadmill desk intervention. Subjects who used the treadmill desk increased daily physical activity from baseline 3,353 ± 1,802 activity units (AU)/day to, at 6 months, 4,460 ± 2,376 AU/day (P < 0.001), and at 12 months, 4,205 ± 2,238 AU/day (P < 0.001). Access to the treadmill desks was associated with significant decreases in daily sedentary time (zero activity) from at baseline 1,020 ± 75 min/day to, at 6 months, 929 ± 84 min/day (P < 0.001), and at 12 months, 978 ± 95 min/day (P < 0.001). For the whole group, weight loss averaged 1.4 ± 3.3 kg (P < 0.05). Weight loss for obese subjects was 2.3 ± 3.5 kg (P < 0.03). Access to the treadmill desks was associated with increased daily physical activity compared to traditional chair-based desks; their deployment was not associated with altered performance. For the 36 participants, fat mass did not change significantly, however, those who lost weight (n = 22) lost 3.4 ± 5.4 kg (P < 0.001) of fat mass. Weight loss was greatest in people with obesity. CONCLUSIONS: Access to treadmill desks may improve the health of office workers without affecting work performance. Copyright © 2012 The Obesity Society.",
"title": "Treadmill desks: A 1-year prospective trial."
},
{
"docid": "MED-1515",
"text": "Long periods of sedentary behaviour may adversely affect health irrespective of overall physical activity levels. This study compared the effects of sitting, standing and walking on postprandial lipaemia in healthy normolipidaemic Japanese men. 15 participants, aged 26.8±2.0 years (mean±SD), completed 3, 2-day trials in a random order: 1) sitting (control), 2) standing, and 3) walking. On day 1 of the sitting trial, participants rested. On day 1 of the standing trial, participants stood for six, 45-min periods. On day 1 of the walking trial, participants walked briskly for 30 min at approximately 60% of maximum heart rate. On day 2 of each trial, participants rested and consumed test meals for breakfast and lunch. Venous blood samples were collected in the morning and afternoon on day 1, and in the fasted state (0 h) and at 2, 4 and 6 h postprandially on day 2. On day 2 area under the serum triacylglycerol concentration vs. time curve was 18% lower on the walking trial than the sitting and standing trials (1-factor ANOVA, P=0.015). Hence postprandial lipaemia was not reduced after standing but was reduced after low-volume walking compared with sitting in healthy normolipidaemic Japanese men. © Georg Thieme Verlag KG Stuttgart · New York.",
"title": "Postprandial lipaemia: effects of sitting, standing and walking in healthy normolipidaemic humans."
},
{
"docid": "MED-1511",
"text": "Aims Prolonged sedentary time is ubiquitous in developed economies and is associated with an adverse cardio-metabolic risk profile and premature mortality. This study examined the associations of objectively assessed sedentary time and breaks (interruptions) in sedentary time with continuous cardio-metabolic and inflammatory risk biomarkers, and whether these associations varied by sex, age, and/or race/ethnicity. Methods and results Cross-sectional analyses with 4757 participants (≥20 years) from the 2003/04 and 2005/06 US National Health and Nutrition Examination Survey (NHANES). An Actigraph accelerometer was used to derive sedentary time [<100 counts per minute (cpm)] and breaks in sedentary time. Independent of potential confounders, including moderate-to-vigorous exercise, detrimental linear associations (P for trends <0.05) of sedentary time with waist circumference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, HOMA-%B, and HOMA-%S were observed. Independent of potential confounders and sedentary time, breaks were beneficially associated with waist circumference and C-reactive protein (P for trends <0.05). There was limited evidence of meaningful differences in associations with biomarkers by age, sex, or race/ethnicity. Notable exceptions were sex-differences in the associations of sedentary time and breaks with HDL-cholesterol, and race/ethnicity differences in the association of sedentary time with waist circumference with associations detrimental in non-Hispanic whites, null in Mexican Americans, and beneficial in non-Hispanic blacks. Conclusion These are the first population-representative findings on the deleterious associations of prolonged sedentary time with cardio-metabolic and inflammatory biomarkers. The findings suggest that clinical communications and preventive health messages on reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk.",
"title": "Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003–06"
},
{
"docid": "MED-1508",
"text": "The obesity epidemic is attributed in part to reduced physical activity. Evidence supports that reducing time spent sitting, regardless of activity, may improve the metabolic consequences of obesity. Analyses were conducted in a large prospective study of US adults enrolled by the American Cancer Society to examine leisure time spent sitting and physical activity in relation to mortality. Time spent sitting and physical activity were queried by questionnaire on 53,440 men and 69,776 women who were disease free at enrollment. The authors identified 11,307 deaths in men and 7,923 deaths in women during the 14-year follow-up. After adjustment for smoking, body mass index, and other factors, time spent sitting (≥6 vs. <3 hours/day) was associated with mortality in both women (relative risk = 1.34, 95% confidence interval (CI): 1.25, 1.44) and men (relative risk = 1.17, 95% CI: 1.11, 1.24). Relative risks for sitting (≥6 hours/day) and physical activity (<24.5 metabolic equivalent (MET)-hours/week) combined were 1.94 (95% CI: 1.70, 2.20) for women and 1.48 (95% CI: 1.33, 1.65) for men, compared with those with the least time sitting and most activity. Associations were strongest for cardiovascular disease mortality. The time spent sitting was independently associated with total mortality, regardless of physical activity level. Public health messages should include both being physically active and reducing time spent sitting.",
"title": "Leisure Time Spent Sitting in Relation to Total Mortality in a Prospective Cohort of US Adults"
}
] |
[
{
"docid": "MED-5270",
"text": "Abnormalities in endothelial function may be associated with increased cardiovascular risk in diabetic patients. We examined the effect of an oleic-acid-rich diet on insulin resistance and endothelium-dependent vasoreactivity in type 2 diabetes. Eleven type 2 diabetic patients were changed from their usual linoleic-acid-rich diet and treated for 2 months with an oleic-acid-rich diet. Insulin-mediated glucose transport was measured in isolated adipocytes. Fatty acid composition of the adipocyte membranes was determined by gas-liquid chromatography and flow-mediated endothelium-dependent and -independent vasodilatation were measured in the superficial femoral artery at the end of each dietary period. There was a significant increase in oleic acid and a decrease in linoleic acid on the oleic-acid-rich diet (p<0.0001). Diabetic control was not different between the diets, but there was a small but significant decrease in fasting glucose/insulin on the oleic-acid-rich diet. Insulin-stimulated (1 ng/ml) glucose transport was significantly greater on the oleic- acid-rich diet (0.56+/-0.17 vs. 0.29+/-0.14 nmol/10(5) cells/3 min, p<0.0001). Endothelium-dependent flow-mediated vasodilatation (FMD) was significantly greater on the oleic-acid-rich diet (3.90+/-0.97% vs. 6.12+/-1.36% p<0.0001). There was a significant correlation between adipocyte membrane oleic/linoleic acid and insulin-mediated glucose transport (p<0.001) but no relationship between insulin-stimulated glucose transport and change in endothelium-dependent FMD. There was a significant positive correlation between adipocyte membrane oleic/linoleic acid and endothelium-dependent FMD (r=0.61, p<0.001). Change from polyunsaturated to monounsaturated diet in type 2 diabetes reduced insulin resistance and restored endothelium-dependent vasodilatation, suggesting an explanation for the anti-atherogenic benefits of a Mediterranean-type diet.",
"title": "Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependen..."
},
{
"docid": "MED-5281",
"text": "Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.",
"title": "The Vascular Endothelium and Human Diseases"
},
{
"docid": "MED-2697",
"text": "OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.",
"title": "Impaired endothelial function following a meal rich in used cooking fat."
},
{
"docid": "MED-3250",
"text": "The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.",
"title": "Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia."
},
{
"docid": "MED-5013",
"text": "INTRODUCTION: Endothelial dysfunction is known to occur in patients with coronary artery disease. Flow-mediated dilation of the brachial artery using Doppler ultrasound is a non-invasive technique for the assessment of endothelial function. The objective of the study was to use the above method to evaluate the pathophysiology of high-fat (HF) intake on endothelial function in a local population. A popular local dish \"nasi-lemak\", a source of high saturated fat content from coconut milk, was chosen to represent a local high-fat meal (LHF). In addition, the effects of a Western high-fat (WHF) (\"McDonald's\") meal and a low-fat (LF) meal control on endothelial function were studied. MATERIALS AND METHODS: The study population consisted of 10 healthy male non-smoker (mean age 22 +/- 2 years) with normal body mass index, normal fasting sugar and lipid profiles. Nitric oxide dependent flow-mediated dilation and nitric oxide independent (GTN) dilation was assessed by Doppler flow in the brachial artery before and 4 hours after each meal on separate occasions by 2 experienced sonographers blinded to the type of meals. RESULTS: The baseline brachial artery size, baseline vessel flow and increase in flow after cuff deflation were similar for each of the six arterial studies. In response to reactive hyperaemia after cuff deflation, the endothelium-dependent dilation was significantly different between the meals. There was a marked decrease in endothelium-dependent dilation after the WHF meal compared to the LF meal (8.6 +/- 2.2% vs. -0.8 +/- 1.1%, P < 0.006). There was also a marked decrease in endothelium-dependent dilation after the LHF meal compared to the LF meal (7.7 +/- 2.1% vs. -0.8 +/- 1.1%, P < 0.001). When comparing between the two HF meals, the change in endothelium-dependent dilation was not significant (7.7 vs. 8.6%, P = 0.678). GTN-induced dilation was not significantly different before and after the LF, WHF or LHF (0.1 +/- 0.5% vs. 0.2 +/- 0.9% vs. 1.3 +/- 0.5%, P = 0.094). CONCLUSION: The results suggest that in a local population, impairment of endothelial function is a possible mechanism in the pathophysiology of atherosclerosis from HF intake, beyond just affecting lipid levels. This effect is observed after both a LHF and a WHF meal intake. This technique to study endothelial function may be a useful non-invasive screening tool in the study of other HF diet choices and provides further information for the education of the influence of dietary choices on atherosclerosis.",
"title": "Impairment of endothelial function--a possible mechanism for atherosclerosis of a high-fat meal intake."
},
{
"docid": "MED-3255",
"text": "BACKGROUND: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention reduces children's serum total cholesterol concentration, but its effect on vascular endothelial function is unknown. METHODS AND RESULTS: Between 1990 and 1992, we randomized healthy 7-month-old infants (n=1062) to intervention (low-saturated-fat diet) and control (unrestricted diet) groups. At the age of 11 years, endothelium-dependent (flow-mediated) and endothelium-independent (nitrate-mediated) vasodilatory responses of the brachial artery were measured with high-resolution ultrasound in 179 intervention and 190 control children. The effect of intervention on endothelial function was significant in boys (P=0.0034) but not in girls (P=0.69). The maximum endothelium-dependent dilation response (mean+/-SD) was 9.62+/-3.53% and 8.36+/-3.85% in intervention boys and control boys and 8.84+/-4.00% and 8.44+/-3.60% in intervention girls and control girls, respectively. Intervention had no effect on nitrate-mediated dilation. The difference in endothelial function in boys remained significant after adjustment for current serum total or LDL cholesterol but became nonsignificant after adjustment for mean cholesterol measured under 3 years of age (adjusted means: 9.46% [CI 8.68% to 10.24%] versus 8.54% [CI 7.75% to 9.32%], P=0.11). CONCLUSIONS: A low-saturated-fat diet introduced in infancy and maintained during the first decade of life is associated with enhanced endothelial function in boys. The effect is explained in part by the diet-induced reduction in serum cholesterol concentration.",
"title": "Endothelial function in healthy 11-year-old children after dietary intervention with onset in infancy: the Special Turku Coronary Risk Factor Inter..."
},
{
"docid": "MED-880",
"text": "Caffeine is the most widely used pharmacologic substance in the world. It is found in common nonessential grocery items (e.g., coffee, tea, cocoa, and chocolate). The effects of caffeine on cardiovascular diseases, including hypertension, remain controversial, and there is little information on its direct effect on vascular function. The purpose of this study was to determine the effect of caffeine on endothelial function in humans. This study was a double-blind, randomized placebo and active drug study. Forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside, an endothelium-independent vasodilator, were evaluated in healthy young men before and after the oral administration of caffeine 300 mg (n = 10) or placebo (n = 10). FBF was measured by using a strain-gauge plethysmograph. Caffeine significantly increased systolic and diastolic blood pressures by 6.0 +/- 6.0 and 2.6 +/- 3.1 mm Hg (p <0.05), respectively, but did not alter heart rate or baseline FBF. Caffeine augmented the FBF responses to ACh from 21.2 +/- 7.1 to 26.6 +/- 8.1 ml/min/100 ml tissue (p <0.05), whereas sodium nitroprusside-stimulated vasodilation was not altered by caffeine administration. The intra-arterial infusion of N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished the caffeine-induced augmentation of FBF response to ACh. In the placebo group, the ACh- and sodium nitroprusside-stimulated vasodilation was similar before and after the follow-up period. In conclusion, these findings suggest that the acute administration of caffeine augments endothelium-dependent vasodilation in healthy young men through an increase in nitric oxide production.",
"title": "Effects of acute administration of caffeine on vascular function."
},
{
"docid": "MED-967",
"text": "BACKGROUND: Observational evidence has consistently linked increased fruit and vegetable consumption with reduced cardiovascular morbidity; however, there is little direct trial evidence to support the concept that fruit and vegetable consumption improves vascular function. This study assessed the dose-dependent effects of a fruit and vegetable intervention on arterial health in subjects with hypertension. METHODS AND RESULTS: After a 4-week run-in period during which fruit and vegetable intake was limited to 1 portion per day, participants were randomized to consume either 1, 3, or 6 portions daily for the next 8 weeks. Endothelium-dependent and -independent arterial vasodilator responses were assessed by venous occlusion plethysmography in the brachial circulation before and after intervention. Compliance was monitored with serial contemporaneous 4-day food records and by measuring concentrations of circulating dietary biomarkers. A total of 117 volunteers completed the 12-week study. Participants in the 1-, 3-, and 6-portions/d groups reported consuming on average 1.1, 3.2, and 5.6 portions of fruit and vegetables, respectively, and serum concentrations of lutein and beta-cryptoxanthin increased across the groups in a dose-dependent manner. For each 1-portion increase in reported fruit and vegetable consumption, there was a 6.2% improvement in forearm blood flow responses to intra-arterial administration of the endothelium-dependent vasodilator acetylcholine (P=0.03). There was no association between increased fruit and vegetable consumption and vasodilator responses to sodium nitroprusside, an endothelium-independent vasodilator. CONCLUSIONS: The present study illustrates that among hypertensive volunteers, increased fruit and vegetable consumption produces significant improvements in an established marker of endothelial function and cardiovascular prognosis.",
"title": "Dietary intake of fruits and vegetables improves microvascular function in hypertensive subjects in a dose-dependent manner."
},
{
"docid": "MED-969",
"text": "The endothelium is a highly metabolically active organ that is involved in many physiological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion and trafficking, inflammation, and hemostasis. Endothelial cell phenotypes are differentially regulated in space and time. Endothelial cell heterogeneity has important implications for developing strategies in basic research, diagnostics and therapeutics. The goals of this review are to: (i) consider mechanisms of endothelial cell heterogeneity; (ii) discuss the bench-to-bedside gap in endothelial biomedicine; (iii) revisit definitions for endothelial cell activation and dysfunction; and (iv) propose new goals in diagnosis and therapy. Finally, these themes will be applied to an understanding of vascular bed-specific hemostasis.",
"title": "Spatial and temporal dynamics of the endothelium."
},
{
"docid": "MED-5280",
"text": "BACKGROUND: Hypertriglyceridemia is now accepted as a risk factor for coronary heart disease, although the mechanism behind the increased risk is not well understood. The present study was undertaken to investigate the effects of triglyceridemia on endothelial function, because impaired endothelial function is considered a marker of atherogenesis. METHODS AND RESULTS: Flow- and nitroglycerin-induced dilatation of the brachial artery was investigated noninvasively by high-resolution ultrasound technique in seven young, healthy men without risk factors for coronary heart disease. Transient triglyceridemia was induced by infusion of a triglyceride emulsion, Intralipid, which raised free fatty acid concentrations twofold and triglyceride levels fourfold. Flow-induced vasodilatation decreased from 7.1+/-3.0% to 1.6+/-2.6% (P<.0002), whereas nitroglycerin-induced vasodilatation decreased from 20.5+/-5.8% to 11.5+/-3.2% (P<.002) before and after 1 hour of infusion of Intralipid, respectively. CONCLUSIONS: Transient triglyceridemia decreases vascular reactivity, presumably by both endothelium-dependent and endothelium-independent mechanisms.",
"title": "Transient triglyceridemia decreases vascular reactivity in young, healthy men without risk factors for coronary heart disease."
},
{
"docid": "MED-2222",
"text": "Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans."
},
{
"docid": "MED-1647",
"text": "BACKGROUND: Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA). Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. CONCLUSIONS: Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.",
"title": "Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease."
},
{
"docid": "MED-3477",
"text": "BACKGROUND: Although numerous human studies have shown consistent effects of some polyphenol-rich foods on several intermediate markers for cardiovascular diseases, it is still unknown whether their action could be specifically related to polyphenols. OBJECTIVE: We investigated the effect of orange juice and its major flavonoid, hesperidin, on microvascular reactivity, blood pressure, and cardiovascular risk biomarkers through both postprandial and chronic intervention studies. DESIGN: Twenty-four healthy, overweight men (age 50-65 y) were included in a randomized, controlled, crossover study. Throughout the three 4-wk periods, volunteers daily consumed 500 mL orange juice, 500 mL control drink plus hesperidin (CDH), or 500 mL control drink plus placebo (CDP). All measurements and blood collections were performed in overnight-fasted subjects before and after the 4-wk treatment periods. The postprandial study was conducted at the beginning of each experimental period. RESULTS: Diastolic blood pressure (DBP) was significantly lower after 4 wk consumption of orange juice or CDH than after consumption of CDP (P = 0.02), whereas microvascular endothelium-related reactivity was not significantly affected when measured after an overnight fast. However, both orange juice and CDH ingestion significantly improved postprandial microvascular endothelial reactivity compared with CDP (P < 0.05) when measured at the peak of plasma hesperetin concentration. CONCLUSIONS: In healthy, middle-aged, moderately overweight men, orange juice decreases DBP when regularly consumed and postprandially increases endothelium-dependent microvascular reactivity. Our study suggests that hesperidin could be causally linked to the beneficial effect of orange juice. This trial is registered at clinicaltrials.gov as NCT00983086.",
"title": "Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers."
},
{
"docid": "MED-5272",
"text": "Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.",
"title": "Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial..."
},
{
"docid": "MED-953",
"text": "Epidemiological studies indicate that diets rich in fruits and vegetables (F&V) are protective against CVD. Puréed F&V products retain many beneficial components, including flavonoids, carotenoids, vitamin C and dietary fibres. The present study aimed to establish the physiological effects of acute ingestion of a F&V purée-based drink (FVPD) on vasodilation, antioxidant status, phytochemical bioavailability and other CVD risk factors. A total of twenty-four subjects, aged 30-70 years, completed the randomised, single-blind, controlled, crossover test meal study. Subjects consumed 400 ml of the FVPD, or a fruit-flavoured sugar-matched control, after following a low-flavonoid diet for 5 d. Blood and urine samples were collected throughout the study day, and vascular reactivity was assessed at 90 min intervals using laser Doppler iontophoresis. The FVPD significantly increased plasma vitamin C (P= 0·002) and total nitrate/nitrite (P= 0·001) concentrations. There was a near significant time by treatment effect on ex vivo LDL oxidation (P= 0·068), with a longer lag phase after consuming the FVPD. During the 6 h after juice consumption, the antioxidant capacity of plasma increased significantly (P= 0·003) and there was a simultaneous increase in plasma and urinary phenolic metabolites (P< 0·05). There were significantly lower glucose and insulin peaks after ingestion of the FVPD compared with control (P= 0·019 and 0·003) and a trend towards increased endothelium-dependent vasodilation following FVPD consumption (P= 0·061). Overall, FVPD consumption significantly increased plasma vitamin C and total nitrate/nitrite concentrations, with a trend towards increased endothelium-dependent vasodilation. Puréed F&V products are useful vehicles for increasing micronutrient status, plasma antioxidant capacity and in vivo NO generation, which may contribute to CVD risk reduction.",
"title": "Effects of acute consumption of a fruit and vegetable purée-based drink on vasodilation and oxidative status."
},
{
"docid": "MED-1866",
"text": "Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti-inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I-converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti-inflammatory, and endothelium-dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks. © 2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function."
},
{
"docid": "MED-965",
"text": "Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive endothelium-derived relaxing factor, it has become evident that NO is not only a major cardiovascular signalling molecule, but that changes in its bioavailability are crucial in determining whether atherosclerosis will develop or not. Sustained high levels of harmful circulating stimuli associated with cardiovascular risk factors such as diabetes mellitus elicit responses in endothelial cells that appear sequentially, namely endothelial cell activation and endothelial dysfunction (ED). ED, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis. The pathogenesis of ED is multifactorial; however, oxidative stress appears to be the common underlying cellular mechanism in the ensuing loss of vaso-active, inflammatory, haemostatic and redox homeostasis in the body’s vascular system. The role of ED as a pathophysiological link between early endothelial cell changes associated with cardiovascular risk factors and the development of ischaemic heart disease is of importance to basic scientists and clinicians alike.",
"title": "Endothelial dysfunction: the early predictor of atherosclerosis"
},
{
"docid": "MED-5261",
"text": "OBJECTIVE—To examine the acute effects of consumption of monounsaturated (MUFAs) and saturated fatty acids (SAFAs) on endothelial function in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 33 participants were examined after consumption of two different isocaloric meals: one rich in MUFA and one rich in SAFA, in the form of extra-virgin olive oil and butter, respectively. Endothelial function was assessed by determination of flow-mediated dilatation (FMD). RESULTS—FMD did not change significantly after the MUFA-rich meal but declined after the SAFA-rich meal. The FMD during the experiment, expressed as incremental area under the curve, increased after the MUFA-rich meal by 5.2 ± 2.5% and decreased after the SAFA-rich meal by 16.7 ± 6.0% (Δ = −11.5 ± 6.4%; P = 0.008). CONCLUSIONS—Consumption of an SAFA-rich meal is harmful for the endothelium, while a MUFA-rich meal does not impair endothelial function in subjects with type 2 diabetes.",
"title": "Differential Effects of Two Isoenergetic Meals Rich in Saturated or Monounsaturated Fat on Endothelial Function in Subjects With Type 2 Diabetes"
},
{
"docid": "MED-1683",
"text": "In recent years, it has been shown that platelets are not only involved in the arterial thrombotic process, but also that they play an active role in the inflammatory process of atherogenesis from the beginning. The interaction between platelets and endothelial cells occurs in two manners: activated platelets unite with intact endothelial cells, or platelets in resting adhere to activated endothelium. In this context, inhibition of the platelet function (adhesion/aggregation) could contribute to the prevention of atherothrombosis, the leading cause of cardiovascular morbidity. This can be achieved with antiplatelet agents. However, at the public health level, the level of primary prevention, a healthy diet has also been shown to exert beneficial effects. Among those elements of a healthy diet, the consumption of tomatoes (Solanum lycopersicum L.) stands out for its effect on platelet anti-aggregation activity and endothelial protection, which may be beneficial for cardiovascular health. This article briefly discusses the involvement of platelets in atherogenesis and the possible mechanisms of action provided by tomatoes for platelet anti-aggregation activity and endothelial protection.",
"title": "Platelets and atherogenesis: Platelet anti-aggregation activity and endothelial protection from tomatoes (Solanum lycopersicum L.)"
},
{
"docid": "MED-5295",
"text": "The plasma sodium concentration has a direct effect on blood pressure in addition to its effects on extracellular volume regulated through changes in the endothelium. The mechanism for elevated blood pressure seen with habitually increased salt intake is unclear, especially the effect of salt in a single meal on plasma sodium concentration and blood pressure. To resolve this we compared the effect of soup with or without 6 g of salt (an amount similar to that in a single meal) on the plasma sodium concentration and blood pressure in 10 normotensive volunteers using a randomized, crossover design. The plasma sodium concentration was significantly increased by 3.13±0.75 mmol/l with salted compared with unsalted soup. Blood pressure increased in volunteers ingesting soup with added salt, and there was a significant positive correlation between plasma sodium concentration and systolic blood pressure. A 1-mmol/l increase in plasma sodium was associated with a 1.91-mm Hg increase in systolic blood pressure by linear regression. Thus, changes in plasma sodium concentration occur each time a meal containing salt is consumed. A potential mechanism for the changes in blood pressure seen with salt intake may be through its effects on plasma sodium concentration.",
"title": "Dietary salt influences postprandial plasma sodium concentration and systolic blood pressure."
},
{
"docid": "MED-1373",
"text": "The endothelium is involved in many of the processes related to the development of atherosclerosis, which is considered an inflammatory disease. Actually, traditional risk factors for atherosclerosis predispose to endothelial dysfunction, which is manifested as an increase in the expression of specific cytokines and adhesion molecules. There are firm evidence supporting the beneficial effects of olive oil, the most genuine component of the Mediterranean diet. Although the effects of olive oil and other oleic acid-rich dietary oils on atherosclerosis and plasma lipids are well known, the roles of minor components have been less investigated. Minor components constitute only 1-2% of virgin olive oil (VOO) and are composed of hydrocarbons, polyphenols, tocopherols, sterols, triterpenoids and other components usually found in traces. Despite their low concentration, non-fatty acid constituents may be of importance because studies comparing monounsaturated dietary oils have reported different effects on cardiovascular disease. Most of these compounds have demonstrated antioxidant, anti-inflammatory and hypolipidemic properties. In this review, we summarize current knowledge on the effects of these compounds contained in VOO on vascular dysfunction and the mechanisms by which they modulate endothelial activity. Such mechanisms involve the release of nitric oxide, eicosanoids (prostaglandins and leukotrienes) and adhesion molecules, in most cases by activation of nuclear factor kappaB by reactive oxygen species.",
"title": "The role of virgin olive oil components in the modulation of endothelial function."
},
{
"docid": "MED-1649",
"text": "OBJECTIVE: The association of coffee consumption with cardiovascular disease remains controversial. Endothelial function is associated with cardiovascular risk. We examined the association between chronic coffee consumption and endothelium function in elderly inhabitants of the island of Ikaria. METHODS: The analysis was conducted on 142 elderly subjects (aged 66-91 years) of the Ikaria Study. Endothelial function was evaluated by ultrasound measurement of flow-mediated dilation (FMD). Coffee consumption was evaluated based on a food frequency questionnaire and was categorized as 'low' (< 200 ml/day), 'moderate' (200-450 ml/day), or 'high' (> 450 ml/day). RESULTS: From the subjects included in the study, 87% consumed a boiled Greek type of coffee. Moreover, 40% had a 'low', 48% a 'moderate' and 13% a 'high' daily coffee consumption. There was a linear increase in FMD according to coffee consumption ('low': 4.33 ± 2.51% vs 'moderate': 5.39 ± 3.09% vs 'high': 6.47 ± 2.72%; p = 0.032). Moreover, subjects consuming mainly a boiled Greek type of coffee had a significantly higher FMD compared with those consuming other types of coffee beverages (p = 0.035). CONCLUSIONS: Chronic coffee consumption is associated with improved endothelial function in elderly subjects, providing a new connection between nutrition and vascular health.",
"title": "Consumption of a boiled Greek type of coffee is associated with improved endothelial function: the Ikaria study."
},
{
"docid": "MED-330",
"text": "Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.",
"title": "Dietary Phosphorus Acutely Impairs Endothelial Function"
},
{
"docid": "MED-3438",
"text": "Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection satisfactory for sexual performance. Evidence is accumulating to consider ED as a vascular disorder. Common risk factors for atherosclerosis are frequently found in association with ED, and ED is frequently reported in vascular syndromes, such as coronary artery disease (CAD), hypertension, cerebrovascular disease, peripheral arterial disease, and diabetes mellitus. Finally, similar early impairment of endothelium-dependent vasodilatation and late obstructive vascular changes has been reported in both ED and other vascular syndromes. Recently, we proposed a pathophysiologic mechanism to explain the link between ED and CAD called the artery size hypothesis. Given the systemic nature of atherosclerosis, all major vascular beds should be affected to the same extent. However, symptoms rarely become evident at the same time. This difference in rate of occurrence of different symptoms is proposed to be caused by the different size of the arteries supplying different vascular beds that allow a larger vessel to better tolerate the same amount of plaque compared with a smaller one. According to this hypothesis, because penile arteries are smaller in diameter than coronary arteries, patients with ED will seldom have concomitant symptoms of CAD, whereas patients with CAD will frequently complain of ED. Available clinical evidence appears to support this hypothesis.",
"title": "The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease."
},
{
"docid": "MED-4124",
"text": "OBJECTIVE: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.g., by the diet. Erythritol, a simple polyol, could be such a compound. It is orally available, well tolerated, and its chemical structure resembles that of mannitol, a well-known hydroxyl radical (HO*) scavenger. METHODS: We studied the antioxidant properties of erythritol in vitro and subsequently determined its antioxidant activity and its vasoprotective effect in the streptozotocin diabetic rat. RESULTS: Erythritol was shown to be an excellent HO* radical scavenger and an inhibitor of 2,2'-azobis-2-amidinopropane dihydrochloride-induced hemolysis but inert toward superoxide radicals. High-performance liquid chromatographic and electron spin resonance spectroscopy studies showed that the reaction of erythritol with hydroxyl radicals resulted in the formation of erythrose and erythrulose by abstraction of a carbon-bound hydrogen atom. In the streptozotocin diabetic rat, erythritol displayed an endothelium-protective effect and, in accordance with the in vitro experiments, erythrose was found in the urine of erythritol-consuming rats. CONCLUSION: Erythritol acts as an antioxidant in vivo and may help protect against hyperglycemia-induced vascular damage. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Erythritol is a sweet antioxidant."
},
{
"docid": "MED-5267",
"text": "BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.",
"title": "Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men."
},
{
"docid": "MED-5285",
"text": "High blood pressure is an important risk factor for cardiovascular disease and cardiovascular events worldwide. Clinical and epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. According to this, cocoa has a high content in polyphenols, especially flavanols. Flavanols have been described to exert favorable effects on endothelium-derived vasodilation via the stimulation of nitric oxide-synthase, the increased availability of l-arginine, and the decreased degradation of NO. Cocoa may also have a beneficial effect by protecting against oxidative stress alterations and via decreased platelet aggregation, decreased lipid oxidation, and insulin resistance. These effects are associated with a decrease of blood pressure and a favorable trend toward a reduction in cardiovascular events and strokes. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events. A 3 mmHg systolic blood pressure reduction has been estimated to decrease the risk of cardiovascular and all-cause mortality. This paper summarizes new findings concerning cocoa effects on blood pressure and cardiovascular health, focusing on putative mechanisms of action and \"nutraceutical \" viewpoints.",
"title": "Cocoa, Blood Pressure, and Cardiovascular Health."
},
{
"docid": "MED-1640",
"text": "Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.",
"title": "Effect of coffee on endothelial function in healthy subjects: the role of caffeine."
},
{
"docid": "MED-2224",
"text": "BACKGROUND: Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. METHODS AND RESULTS: We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36+/-0.51 to 2.51+/-0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5+/-11.4% versus -4.3+/-11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) in the dark chocolate group but remained unchanged in the control group. CONCLUSIONS: Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.",
"title": "Dark chocolate improves coronary vasomotion and reduces platelet reactivity."
},
{
"docid": "MED-5266",
"text": "Current National Cholesterol Education Program guidelines consider desirable total and low-density lipoprotein cholesterol levels to be < 200 and < 160 mg/dl, respectively, for healthy individuals without multiple coronary risk factors. To determine the extent to which these levels affect vascular function, we assessed flow-mediated (endothelium-dependent) brachial artery vasoactivity noninvasively before, during, and after cholesterol lowering (simvastatin 10 mg/day) in 7 healthy middle-aged men with cholesterol levels meeting current recommendations. Flow-mediated brachial artery vasoactivity was measured using 7.5 MHz ultrasound and expressed as percent diameter change from baseline to hyperemic conditions (1 minute following 5 minutes of blood pressure cuff arterial occlusion). Flow-mediated vasoactivity rose from 5.0 +/- 3.6% at baseline to 10.5 +/- 5.6%, 13.3 +/- 4.3%, and 15.7 +/- 4.9% (all p < 0.05) as cholesterol fell from 200 +/- 12 to 161 +/- 18, 169 +/- 16, and 153 +/- 11 mg/dl after 2, 4, and 12 weeks, respectively, of cholesterol-lowering therapy. Vasoactivity and cholesterol returned to baseline levels 12 weeks after simvastatin discontinuation. Overall, vasoactivity was found to correlate inversely with cholesterol levels (r = -0.47, p = 0.004). These data suggest that flow-mediated brachial artery vasoactivity responds rapidly to changes in cholesterol levels and that endothelial function improves by lowering cholesterol levels below recommendations of current guidelines.",
"title": "Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men."
}
] |
5ac15db05542994d76dccdec
|
When was the artist who did the art of Batman: In Darkest Knight born?
|
[
{
"docid": "7467697",
"text": "Batman: In Darkest Knight is a one-shot comic book, published in 1994 and written by Mike W. Barr with art by Jerry Bingham. The comic is an \"Elseworlds\" story in which Bruce Wayne becomes the Green Lantern instead of Hal Jordan. This one change creates a domino effect which alters many events and characters in the DC Universe. The story draws heavily from related \"Batman\" comics, including \"\" and \"\".",
"title": ""
},
{
"docid": "21360634",
"text": "Gerald \"Jerry\" Joseph Bingham, Jr. (born June 25, 1953, in Chicago, Illinois) is an American artist who has worked in the fields of comic books, commercial illustration, and design. He is best known for his artwork on \"Marvel Team-Up\" and the DC Comics graphic novel \"\".",
"title": ""
}
] |
[
{
"docid": "36906344",
"text": "Batman: The Dark Knight Returns is a two-part direct-to-video animated superhero film, an adaptation of the 1986 comic book \"The Dark Knight Returns\" by Frank Miller. It was directed by Jay Oliva, who worked as a storyboard artist on \"Man of Steel\", \"\", \"\" and \"\". Several other \"Batman\" veterans were also involved in the film. Part 1 was released September 25, 2012, and Part 2 was released January 29, 2013. A deluxe edition combining both films was released on October 8, 2013. It is the 15th film in the DC Universe Animated Original Movies series.",
"title": ""
},
{
"docid": "2201378",
"text": "Caroline Keene \"Carrie\" Kelley is a fictional character from Frank Miller's graphic novels \"Batman: The Dark Knight Returns\" (1986) and its sequels \"Batman: The Dark Knight Strikes Again\" (2001) and \"Batman: The Dark Night: The Master Race (2015-2017).\" She becomes the new Robin in \"The Dark Knight Returns\" when she saves Batman's life. Later in \"The Dark Knight Strikes Again\", she adopts the identity Catgirl. She was the first full-time female Robin in the history of the Batman franchise, though Julie Madison had passed off as Robin for a brief time in a Bob Kane story published in \"Detective Comics\" #49 in March 1941.",
"title": ""
},
{
"docid": "39851373",
"text": "The Dark Knight is the nickname of the superhero Batman who appears in American comic books published by DC Comics. Batman was first referred to by the nickname in \"Batman\" #1 (Spring 1940), in a story written by Bill Finger.",
"title": ""
},
{
"docid": "33417500",
"text": "Tom Wu is a Chinese British actor. He was born in Hong Kong and grew up in Chinatown, London. He is a martial arts expert who has appeared in films such as \"Revolver\", \"Shanghai Knights\", \"Batman Begins\" and the Bollywood sci-fi movie \"Ra.One\".",
"title": ""
},
{
"docid": "22914208",
"text": "Batman: Haunted Knight is an anthology trade paperback published by DC Comics in 1996. It reprinted three one shot specials from the previous three years (three \"\"). Each of the stories were written by Jeph Loeb and featured art by Tim Sale. The popularity of these led to the limited series \"\".",
"title": ""
},
{
"docid": "73243",
"text": "The Dark Knight Returns (alternatively titled Batman: The Dark Knight Returns) is a 1986 four-issue comic book miniseries starring Batman, written by Frank Miller, illustrated by Miller and Klaus Janson, and published by DC Comics. When the series was collected into a single volume later that year, the story title for the first issue was applied to the entire series. \"The Dark Knight Returns\" tells an alternative story of Bruce Wayne, who at 55 years old returns from retirement to fight crime and faces opposition from the Gotham City police force and the United States government. The story introduces Carrie Kelley as the new Robin and culminates with a confrontation against Superman.",
"title": ""
},
{
"docid": "29075630",
"text": "The Dark Knight Rises is a 2012 superhero film directed by Christopher Nolan, who co-wrote the screenplay with his brother Jonathan Nolan, and the story with David S. Goyer. Featuring the DC Comics character Batman, the film is the final installment in Nolan's \"Batman\" film trilogy, and the sequel to \"Batman Begins\" (2005) and \"The Dark Knight\" (2008). Christian Bale reprises the lead role of Bruce Wayne/Batman, with a returning cast of allies: Michael Caine as Alfred Pennyworth, Gary Oldman as James Gordon, and Morgan Freeman as Lucius Fox. The film introduces Selina Kyle (Anne Hathaway), and Bane (Tom Hardy). Eight years after the events of \"The Dark Knight\", merciless revolutionary Bane forces an older Bruce Wayne to resume his role as Batman and save Gotham City from nuclear destruction.",
"title": ""
},
{
"docid": "2237648",
"text": "All Star Batman & Robin, the Boy Wonder is an American comic book series written by Frank Miller and penciled by Jim Lee. It was published by DC Comics, with a sporadic schedule, between 2005 and 2008. The series was to be rebooted under the title \"Dark Knight: Boy Wonder\" in 2011, when both Miller and Lee were to finish the last six issues. The series retells the origin story of Dick Grayson, who became Batman's sidekick Robin.",
"title": ""
},
{
"docid": "1362720",
"text": "Batman: Knight Gallery is an American comic book published in 1995 by the DC Comics imprint \"Elseworlds\". Written by Doug Moench, and features the art of Thomas Grummett, Michael Manley, Vincent Giarrano, James Balent, Bret Blevins, Graham Nolan, Norm Breyfogle, Neal Adams, George Pérez, Stephen De Stefano, Tom Lyle, Gary Frank, David Taylor, Anton Furst.",
"title": ""
},
{
"docid": "37306091",
"text": "Knight's Spider Web Farm is an art studio, retail outlet and residence owned by Will Knight, an artist who uses spider webs to produce art. It is located in Williamstown, Vermont. Knight calls his farm \"The Original Web Site\". The finished artwork uses whole spider webs as a form of textile art over painted or stained wood.",
"title": ""
},
{
"docid": "14666638",
"text": "Batman (Bruce Wayne) is a fictional character, a superhero and an alternative version of the DC Comics character of the same name. This version of Batman was created by Frank Miller and first appeared in \"The Dark Knight Returns\" #1 (February 1986). This satirical version of the character is regarded as an older, darker interpretation of the character who, after years of retirement, resumes his role of a vigilante and, eventually, a revolutionary freedom fighter.",
"title": ""
},
{
"docid": "4276475",
"text": "The Dark Knight is a 2008 superhero film directed, co-produced, and co-written by Christopher Nolan. Featuring the DC Comics character Batman, the film is the second part of Nolan's \"The Dark Knight Trilogy\" and a sequel to 2005's \"Batman Begins\", starring an ensemble cast including Christian Bale, Michael Caine, Heath Ledger, Gary Oldman, Aaron Eckhart, Maggie Gyllenhaal and Morgan Freeman. In the film, Bruce Wayne/Batman (Bale), Police Lieutenant James Gordon (Oldman) and District Attorney Harvey Dent (Eckhart) form an alliance to dismantle organized crime in Gotham City, but are menaced by a criminal mastermind known as the Joker (Ledger) who seeks to undermine Batman's influence and create chaos.",
"title": ""
},
{
"docid": "38766047",
"text": "Nathan Crowley (born 1966) is an English production designer and a former art director. He was nominated for an Academy Award for Best Production Design for \"The Prestige\" (2006), \"The Dark Knight\" (2008), and \"Interstellar\" (2014). For \"The Prestige\", he was nominated with set decorator Julie Ochipinti, for \"The Dark Knight\", he was nominated with set decorator Peter Lando, and for \"Interstellar\", he was nominated with set decorator Gary Fettis. Crowley was also nominated for the BAFTA Award for Best Production Design for \"Batman Begins\" (2005) and \"The Dark Knight\" (2008).",
"title": ""
},
{
"docid": "52130621",
"text": "\"The DArkest Knight\" is tenth episode of the seventh season of the American mystery–thriller television series \"Pretty Little Liars\". The installment was directed by Arlene Sanford and written by showrunner I. Marlene King and executive producer Maya Goldsmith. It premiered on August 23, 2016, on the cable network Freeform.",
"title": ""
},
{
"docid": "14579825",
"text": "Batman: Gotham Knight (バットマン ゴッサムナイト , Battoman Gossamunaito )",
"title": ""
},
{
"docid": "852807",
"text": "Batman: Legends of the Dark Knight, commonly referred to as simply Legends of the Dark Knight is a DC comic book featuring Batman. It was launched in 1989 with the popularity of the \"Batman\" movie, following on from Frank Miller's \"\". It differs from other Batman titles in that it has constantly rotating creative teams, and the stories are not necessarily part of the current events of the other Batman comics. Initially the title was promoted as running only stand alone self-contained five issue stories of graphic novel quality. However, after issue 20, stories of different lengths started to appear. While some stories have tied in with the other titles, generally this has not been the case.",
"title": ""
},
{
"docid": "29847253",
"text": "\"Prey\" is a Batman comic book story arc written by Doug Moench, with art by Paul Gulacy and Terry Austin. It was originally published in five parts by DC Comics from September 1990 through February 1991 for \"Legends of the Dark Knight\", issues 11 through 15, and later compiled as a trade paperback.",
"title": ""
},
{
"docid": "11368350",
"text": "Batman: The Dark Knight was an American comic book ongoing series, written and penciled by David Finch and featuring Batman. One of two new ongoing titles to feature Bruce Wayne after the \"\" storyline, \"The Dark Knight\" depicts Bruce Wayne's life in Gotham City following his new global commitment to the newly established \"Batman Incorporated\". In Finch's words, \"The stories I'm telling are all about relationships and connections he has in Gotham City that he can't walk away from.\"",
"title": ""
},
{
"docid": "42106513",
"text": "Batman: Arkham Knight is a 2015 action-adventure video game developed by Rocksteady Studios and published by Warner Bros. Interactive Entertainment. Based on the DC Comics superhero Batman, it is the successor to the 2013 video game \"\", and the fourth main installment in the \"\" series. \"Arkham Knight\" was released worldwide on June 23, 2015 for PlayStation 4, Xbox One and Microsoft Windows.",
"title": ""
},
{
"docid": "53455408",
"text": "Katherine Knight is a Canadian artist and documentary filmmaker whose artistic practice considers the relationships between landscape and personal experiences of time and place. Her works are included in many public collections, including the National Gallery of Canada, the Canadian Museum of Contemporary Photography, Banff Centre for the Arts and The Canada Council Art Bank. In addition to her artistic practice, Katherine Knight teaches in the Visual Art Department at York University.",
"title": ""
},
{
"docid": "4335",
"text": "Batman is a fictional superhero appearing in American comic books published by DC Comics. The character was created by artist Bob Kane and writer Bill Finger, and first appeared in \"Detective Comics\" #27 (1939). Originally named the \"Bat-Man\", the character is also referred to by such epithets as the Caped Crusader, the Dark Knight, and the World's Greatest Detective.",
"title": ""
},
{
"docid": "5250471",
"text": "Batman: The Dark Knight (formerly known as Batman: The Ride) is a steel floorless roller coaster designed by Bolliger & Mabillard located in the south end of Six Flags New England. The roller coaster has 2600 ft of track, reaches a maximum height of 117.8 ft , and features five inversions. The coaster was announced on February 6, 2002 and opened to the public on April 20, 2002. In 2008, the ride's name was changed to \"Batman: The Ride\" to avoid confusion with The Dark Knight Coaster that was planned to be built at the park; after the project was cancelled, the ride's name reverted to its original.",
"title": ""
},
{
"docid": "4967970",
"text": "\"Mutual Feeling\" is the fifth single released by the British R&B recording artist Beverley Knight from her debut album \"The B-Funk\" (1995). The track, which peaked at #124 on the UK Singles Chart when it was released in 1996, did not have a promotional video made to accompany it and remains Knight's second lowest charting single to date in the UK, after \"After You\".",
"title": ""
},
{
"docid": "42114042",
"text": "The Arkham Knight is a fictional supervillain appearing in American comic books published by DC Comics, and is the titular character in Rocksteady Studios' video game \"\". The persona first appeared in \"Batman: Arkham Knight\" #1 (February 2015). He later received his own 6-issue miniseries \"Batman: Arkham Knight GENESIS\", with #1 released on August 26, 2015.",
"title": ""
},
{
"docid": "49515168",
"text": "Loui Jover (born April 1967) is an Australian painter and artist. He is known for his artwork in ink wash paintings on vintage book pages. Jover started his work on art in his childhood, but did not start public art until 1989, when he joined the Australian army as an illustrator and photographer.",
"title": ""
},
{
"docid": "8802309",
"text": "Batman Castle of the Bat is a DC Comics \"Elseworlds\" special published in 1994. Written by Jack C. Harris with art by Bo Hampton as the artist and Tracy Hampton-Munsey as the letterer.",
"title": ""
},
{
"docid": "10077082",
"text": "Batman/Houdini: The Devil's Workshop is a 1993 \"Elseworlds\" one-shot, written by Howard Chaykin and John Francis Moore, with full-painted art by Mark Chiarello. The story recounts a fictional encounter between the superhero Batman and famous escape artist Harry Houdini in early 20th century Gotham.",
"title": ""
},
{
"docid": "22691744",
"text": "Lu Shengzhong(Chinese:吕胜中) (born 1952) is a Chinese artist who specializes in the ancient Chinese art of paper cutting. He grew up during the turbulent Cultural Revolution, did not follow the pack of Chinese contemporary artists who embraced the international vogue for installation art as his country began opening up to the West in the 1980s. \"I walked away from the cultural confusion of the time and turned back to traditional folk art,\" he says.",
"title": ""
},
{
"docid": "562765",
"text": "Batman: Gotham Knights was a monthly American comic book series published by DC Comics. The original intent of this book was to feature the exploits of Batman and his extended family, such as Alfred Pennyworth, Batgirl, Nightwing, Robin, Oracle, and Catwoman, among others. The latter section of the run, however, came to focus much more upon his enemies.",
"title": ""
},
{
"docid": "3473759",
"text": "Matt Haley (born June 10, 1970 in Houston, Texas) is an American film director, art director and book illustrator artist. He was the art director of Morgan Spurlock's \"Comic-Con Episode IV: A Fan's Hope\" feature documentary, which debuted at the 2010 Toronto International Film Festival. He was the artist and creative consultant for both seasons of Stan Lee's TV series \"Who Wants To Be A Superhero\". Notable comic book works include \"GHOST\" (Dark Horse Comics), \"Elseworld's Finest: Supergirl and Batgirl\", \"Batman: Batgirl\", the \"Superman Returns\" movie adaptation (DC Comics), and \"THE ORDER\" (Marvel).",
"title": ""
}
] |
5765
|
When does it make sense for the money paid for equity to go to the corporation?
|
[
{
"docid": "289656",
"text": "If Jack owns all of the one million founding shares (which I assume you meant), and wants to transfer 250,000 shares to Venturo, then he is just personally selling shares to Venturo and the corporation gains nothing. If Jack does not own all of the founding shares, and the corporation had retained some, then the corporate shares could be sold to raise cash for the corporation. Usually in situations like this, the corporation will create more shares, diluting existing shareholders, and then sell the new shares on the open market to raise cash.",
"title": ""
},
{
"docid": "2205",
"text": "If the check is written as a check to BigCo, it is less clear how Jack can compensate himself for the equity sale. It is as if the equity was owned by the corporation, not by Jack. This is correct. If the check is written to BigCo, then it is BigCo issuing new shares. Jack doesn't compensate himself for the equity sale, as he didn't sell anything. The company traded shares for money which it uses for expansion. In the long term, the capital gain from expansion may exceed the value of a $200,000 no-interest loan to the company. If the value of the company before investing $250,000 is $1 million, then the value after investing is $1.25 million. So $250,000 is 20% of the value of the company. BigCo should not give the buyer 25% of BigCo but only 20% in that example. If it does give 25%, the buyer is getting a $312,500 stake for only $250,000. With the other example, Jack sells 25% of the company for $250,000 from his personal shares. This doesn't change the assessed value of the company, just Jack's stake. Jack then loans the company $200,000. This also doesn't change the assessed value of the company (at least in theory). It gains $200,000 but has an offsetting debt of $200,000. In net, that's no change. Assets and liabilities balance the same. So if you know that the assessed value of the company is $1 million and that the buyer is paying $250,000 for a 25% stake at that same valuation, then you know that the check is being written to Jack. If the check is written to BigCo, then one or more of those numbers is incorrect. The buyer could be getting a 20% stake. The new value of the company after the investment is $1.25 million. Or paying $333,333.33. The new value of the company after the investment is $1,333,333.33. Or BigCo could only be worth $750,000 before the investment. The new value of the company after the investment is $1 million. Or Jack is getting screwed, selling $312,500 in stock (25%) for only $250,000. Jack's shares drop from being worth $1 million to only $937,500. The value of the company is $1.25 million. Or some combination of smaller changes that balances.",
"title": ""
},
{
"docid": "303810",
"text": "The check is written to BigCo. Jack is being diluted, corporation issues more shares. There's no gain, no change in Jack's equity value. Jack didn't lose or win anything. BigCo was worth $1M before the additional money, it is worth $1.25M after the additional money, with Jack owning the same $1M, but the cake is now bigger (obviously the numbers are wrong in your example, but you get the point).",
"title": ""
},
{
"docid": "121622",
"text": "\"BigCo is selling new shares and receives the money from Venturo. If Venturo is offering $250k for 25% of the company, then the valuation that they are agreeing on is a value of $1m for the company after the new investment is made. If Jack is the sole owner of one million shares before the new investment, then BigCo sells 333,333 shares to Venturo for $250k. The new total number of shares of BigCo is 1,333,333; Venturo holds 25%, and Jack holds 75%. The amount that Jack originally invested in the company is irrelevant. At the moment of the sale, the Venturo and Jack agree that Jack's stake is worth $750k. The value of Jack's stake may have gone up, but he owes no capital gains tax, because he hasn't realized any of his gains yet. Jack hasn't sold any of his stake. You might think that he has, because he used to hold 100% and now he holds 75%. However, the difference is that the company is worth more than was before the sale. So the value of his stake was unchanged immediately before and after the sale. Jack agrees to this because the company needs this additional capital in order to meet its potential. (See \"\"Why is stock dilution legal?\"\") For further explanation and another example of this, see the question \"\"If a startup receives investment money, does the startup founder/owner actually gain anything?\"\" Your other scenario, where Venturo purchases existing shares directly from Jack, is not practical in this situation. If Jack sells his existing shares, you are correct that the company does not gain any additional capital. An investor would not want to invest in the company this way, because the company is struggling and needs new capital.\"",
"title": ""
}
] |
[
{
"docid": "115814",
"text": "Does it make sense for stocks to earn a premium indefinitely? Yes. There is good reason to think that the stock market will make money indefinitely: the stock market is the primary mechanism through which investors bear market risk, which requires compensation. If you think of all the owners of firms (stockholders and bondholders, generally) the risk premium that stocks earn stocks is the way bondholders pay equityholders to bear the risk that they do not wish to. Will stock prices always go up in the long run? As long as companies pay out less in dividends than their profit, prices will go up. That could change if we were to change our corporate culture and/or tax practices so that firms paid out more in dividends. However, for the purposes of your question, I think it doesn't matter much whether the investor makes money as dividends or capital gains. Does the 5-7% guess apply only to the US market? I didn't write (nor read) the books in question, but most likely that is a global number. The US dominates the global equity market, so it's often a good proxy. However, international returns taken together have no less risk and earn no less over long horizons in general. The particular examples you have pointed out are special cases that only apply to a part of the global economy and a particular time period. There are plenty of examples of stock markets and time periods that did much better than the US market to offset your examples. Is 5-7% a reasonable long-term estimate of equity returns? Equity will always earn more in expectation than risk-free securities will. How much more depends on major economic factors. 5-7% has been a good estimate for the market risk premium for many, many decades (stocks should earn this plus whatever the risk-free rate is). However, that is just an empirical observation, not a rule. It can change. Some day technological progress could slow down or stop, we could run out of important resources in a way that we can't compensate for, our population permanently could stop growing, aliens could invade, etc. Down the road it is certainly possible for expected equity returns to go down and never go back up again. This would result from a permanent, global, economic shift that I think would be pretty obvious. That is, you wouldn't have to look at stock prices to know it was happening.",
"title": ""
},
{
"docid": "235484",
"text": "\"Is all interest on a first time home deductible on taxes? What does that even mean? If I pay $14,000 in taxes will My taxes be $14,000 less. Will my taxable income by that much less? If you use the standard deduction in the US (assuming United States), you will have 0 benefit from a mortgage. If you itemize deductions, then your interest paid (not principal) and your property tax paid is deductible and reduces your income for tax purposes. If your marginal tax rate is 25% and you pay $10000 in interest and property tax, then when you file your taxes, you'll owe (or get a refund) of $2500 (marginal tax rate * (amount of interest + property tax)). I have heard the term \"\"The equity on your home is like a bank\"\". What does that mean? I suppose I could borrow using the equity in my home as collateral? If you pay an extra $500 to your mortgage, then your equity in your house goes up by $500 as well. When you pay down the principal by $500 on a car loan (depreciating asset) you end up with less than $500 in value in the car because the car's value is going down. When you do the same in an appreciating asset, you still have that money available to you though you either need to sell or get a loan to use that money. Are there any other general benefits that would drive me from paying $800 in rent, to owning a house? There are several other benefits. These are a few of the positives, but know that there are many negatives to home ownership and the cost of real estate transactions usually dictate that buying doesn't make sense until you want to stay put for 5-7 years. A shorter duration than that usually are better served by renting. The amount of maintenance on a house you own is almost always under estimated by new home owners.\"",
"title": ""
},
{
"docid": "538490",
"text": "An equity tax does seem to make some sense. It would probably help to stave off deflation as well because it would encourage growth and investment where people would otherwise choose to sit on their money or worse. An equity tax on currency or liquid investments of even .5% APR would have a huge effect on the behavior of corporations. Sadly the largest of them would have the resources to avoid the tax by keeping all of their money out of the country.",
"title": ""
},
{
"docid": "42625",
"text": "\"This question drives at what value a shareholder actually provides to a corporation, and by extent, to the economy. If you subscribe for new shares (like in an Initial Public Offering), it is very straightforward to say \"\"I have provided capital to the corporation, which it is using to advance its business.\"\" If you buy shares that already exist (like in a typical share purchase on a public exchange), your money doesn't go to the company. Instead, it goes to someone who paid someone who paid someone who paid someone (etc.) who originally contributed money to the corporation. In theory, the value of a share price does not directly impact the operation of the company itself, apart from what @DanielCarson aptly noted (employee stock options are affected by share price, impacting morale, etc.). This is because in theory, the true value of a company (and thus, the value of a share) is the present value of all future cashflows (dividends + final liquidation). This means that in a technical sense, a company's share price should result from the company's value. The company's true value does not result from the share price. But what you are doing as a shareholder is impacting the liquidity available to other potential investors (also as mentioned by @DanielCarson, in reference to the desirability for future financing). The more people who invest their money in the stock market, the more liquid those stocks become. This is the true value you add to the economy by investing in stocks - you add liquidity to the market, decreasing the risk of capital investment generally. The fewer people there are who are willing to invest in a particular company, the harder it is for an investor to buy or sell shares at will. If it is difficult to sell shares in a company, the risk of holding shares in that company is higher, because you can't \"\"cash out\"\" as easily. This increased risk then does change the value of the shares - because even though the corporation's internal value is the same, the projected cashflows of the shares themselves now has a question mark around the ability to sell when desired. Whether this actually has an impact on anything depends on how many people join you in your declaration of ethical investing. Like many other forms of social activism, success relies on joint effort. This goes beyond the direct and indirect impacts mentioned above; if 'ethical investing' becomes more pronounced, it may begin to stigmatize the target companies (fewer people wanting to work for 'blacklist' corporations, fewer people buying their products, etc.).\"",
"title": ""
},
{
"docid": "345681",
"text": "\"Equity does not represent production divisions in a company (i.e. chocolate, strawberry, and vanilla does not make sense). In Sole proprietorship, equity represents 1 owner. In Partnership, equity has at least two sub-accounts, namely Partner 1 and Partner 2. In Corporations, equity may have Common Stockholders and Preferred Stockholders, or even different class of shares for insiders and angel investors. As you can see, equity represents who owns the company. It is not what the company does or manufactures. First and foremost, define the boundary of the firm. Are your books titled \"\"The books of the family of Doe\"\", \"\"The books of Mr & Mrs Doe\"\", or \"\"The books of Mr & Mrs Doe & Sons\"\". Ask yourself, who \"\"owns\"\" this family. If you believe that a marriage is perpetual until further notice then it does not make any sense to constantly calculate which parent owns the family more. In partnership, firm profits are attributed to partner's accounts using previously agreed ratio. For example, (60%/40% because Partner 1 is more hard working and valuable to the firm. Does your child own this family? Does he/she have any rights to use the assets, to earn income from the assets, to transfer the assets to others, or to enforce private property rights? If they don't have a part of these rights, they are certainly NOT part of Equity. So what happens to the expenses of children if you follow the \"\"partnership\"\" model? There are two ways. The first way is to attribute the Loss to the parents/family since you do not expect the children to repay. It is an unrecoverable loss written off. The second way is to create a Debtor(Asset) account to aggregate all child expense, then create a separate book called \"\"The books Children 1\"\", and classify the expense in that separate book. I advise using \"\"The family of Doe\"\" as the firm's boundary, and having 1 Equity account to simplify everything. It is ultimately up to you to decide the boundaries.\"",
"title": ""
},
{
"docid": "3750",
"text": "\"The implication is market irrationality is stronger than market rationality. Aka nothing makes sense when TSLA climbs to $400 or when CMG rises to $750. I wouldn't say there is a systematic flaw in valuation. I think there is just a lot of ignorance. Markets are more open to household investors than ever before. You used to go to your broker and ask him what's up and he'd give you the inside scoop since you pay them money. Now you go onto marketwatch and get some random nobody's opinion on everything and make stock selections based on that. But eventually the chickens come home to roost and things will correct itself. Big players will jump ship and cause signals to other traders to jump ship. The public can pump stocks up pretty high but it doesn't just go to infinity. Eventually someone will stop and say, \"\"wtf is going on\"\" and start selling. Stocks are sold on a basis of a limit order book so it's real prices that people are paying. People don't care about prices currently because most don't have any finance knowledge but want to invest their own money. They just hear about Tesla doing something amazing (from some clickbait article or news outlet) and can't stop thinking about buying Tesla. They go to Chipotle and think \"\"wow this place is so good and hip, they must be a great investment\"\". The markets have been filled with more subjective analysis than ever before especially with so much low quality information at your fingertips. Equally ignorant people startin blogs about investment and personal finance being shepherds for other ignorant people. In the end they all lose. People who exclaim \"\"this stock is going up to $250 easily\"\" with literally zero quantitative analysis or even a baseline reference point to back it up are prime examples of this. Ignorance of markets and cheap money almost always lead to market runs that end catastrophically. Dot com bubble, 1929 market crash, 2008, it's always the same. People who have no business taking loans out or buying on margin or leveraging positions with debt only to get fucked over once things are brought back down to Earth. After 2 runs of QE, we now have cheap money and with everyone being a crier for their personal investment strategy, we now also have rampant ignorance. I don't expect things to last but no one can call the bottom or the top, or else you'd be very very rich. Have a safe portfolio, don't try to time the markets. Have a strategy that hedges against unexpected change, don't try to gamble on this change. Because it's ultimately impossible to predict the movement of every single person on this earth that invests their money into markets. So don't try. Just be prepared. ---- To expand further into valuation theory: at the end of the day, people invest their money to make more money. It's as simple as that. If your money doesn't grow in an investment vehicle, it's ultimately a shit investment. But no one values intrinsic value of a company's equity before they decide whether or not $380 for TSLA is a good/bad deal. As a result, stocks can be pumped up way higher and people still see the gains on their stocks through capital gains fueled by other optimistic investors. Non-zero sum goes both ways. People can make shitloads of money on stock without an equitable loser--people can also lose shitloads on stock without any real winner emerging from the rubble. When this bubble bursts, lots and lots of people will lose money on TSLA when people's expectations become rational and they stop paying $300 a share for a negative or 70 PE ratio. It's insane what multipliers people will pay for these companies without even realizing the implication--if you buy a share of a company with a PE ratio of 70, you just paid 70 times their earnings for a share. In an ideal world where they released every single penny of earnings as dividends, it would take you 70 periods to reclaim your money on that share. This obviously doesn't take into account capital gains, but capital gains aren't supposed to be this irrational to where a stock can be pumped up into 70x PE ratio in the first place. It's a whole messed up web of confusion and irrationality and eventually something will catalyze a reaction. Imagine a market where everyone just agreed to pump up a single stock to infinity and everyone just rakes in shitloads of money. Would this work? Of course not. It's literally a pyramid scheme that relies on future generations to constantly inject capital--no real value is being created by this scheme. It requires constantly more future generations to continue adding money into the scheme and will crash once people stop pumping money into it. The same thing will happen here. Everyone \"\"agreed\"\" to pump up TSLA (in a sense) but eventually people will realize this is stupid as shit and the pyramid will come tumbling down because there is nothing they receive from this scheme other than the money from other people. It's essentially moving money around, making 0 use of it, until people stop pumping money into the system and everyone realizes that nothing of real value had been produced through the use of this money. Ultimately the only thing that creates real value is the money that is returned to shareholders from an outside party--the company you're invested in. Real value is not created when people exchange stock and money. So why do these transactions create higher values in equity? The basis of equity valuation states that dividends are the only way for companies to raise the price of their stock, going off the traditional Dividend Discount Model. And theoretically, that's the only logical explanation. Buying and trading stock does nothing for the company, minus T Stock they might own. Ultimately the only party creating real value is the underlying company. If they aren't creating real value, then their stock should not be increasing, period. The way they create value is by efficiently utilizing assets to generate returns on investment which can be returned to investors through dividends. Dividends can only be increased (while maintaining an equitable payout ratio) by generating more net income that can increase the actual pool of money that can be allocated back to investors. TSLA does not do this. TSLA regularly loses money and overpromises. There is no logical explanation for any of this except that everyone is irrational. Obviously theory is not the same as in practice but the theory is important here because it's really the basis for any investment at all. At the end of the day, a share of stock is the right to a share of the company's equity. People own equity in companies because companies generate money that it returns back to its owners. That's what a company does. That's what an owner does. If you own shares of a company, you're an owner. And if your company does not return more money back to you YoY, then why are you invested in them? Ultimately, you're riding a capital gains wave that will eventually subside once market irrationality succumbs to rationality. And it always does because the real value always catches up to the fake value that is caused by pumping and dumping stocks.\"",
"title": ""
},
{
"docid": "149493",
"text": "\"For this to work, those who control the dilution must also control their salaries because the only way for them to be paid off when it's the corporation itself selling is to gain access to the proceeds. When a corporation sells newly issued equity, the corporation itself owns the money. To at least have the appearance of propriety, the scammers must be paid those proceeds. Both actions imply that the board is captured by the scammers. There are many corporations that seem to do this even with persistently large market capitalizations. The key difference between this and pump-and-dump is that its a fraudulent group of investors selling in this case instead of the corporation itself. A detailed simple example Corporations are mandated by law to be little oligarchies; although, \"\"republic\"\" is now becoming more appropriate with all of the new shareholder rights. A corporation is controlled at root by the board of directors who are elected by the shareholders. The board has no direct operational control, as that is left to the \"\"king\"\", the CEO; however, the board does control what everyone wants access to: the money. Board members have all sorts of legal qualitative mandates on how to behave, and they've functioned fairly decently efficiently over the long run, but there are definitely some bad apples. Boards are somewhat intransigent since it's difficult to hold board elections, and usually only specific board members are put up for election by a shareholder vote, so a bad one has the potential to really get stuck in there. Once a bad one is in there, they don't care because they know it will be tough to get them out, so they run roughshod over the company's purse. Only the board can take action on major funding such as the CEO's operating budget, board compensation, financing, investment, etc, some with shareholder approval, some without. The corporation itself owns all of those assets, but the board controls them. In this example, they scheme with most likely the top executive, but a rubber stamp top executive could allow a lower rung to scheme with the board, but the board is always constant until the law is changed. Because there's no honor amongst thieves, the board votes which can require some combination of executive and shareholder approval are taken very close together: sell shares, increase salaries to key executive schemers, increase board compensation. The trusting shareholders believe this is in the best interests of the company at large so go along. So the money flows from existing & new shareholders to the corporation now controlled by a malicious board and then finally to the necessary malicious executive and the vital malicious board.\"",
"title": ""
},
{
"docid": "512429",
"text": "\"So some background here - when corporations, large ones have to deal with tax, they generally try to avoid as much tax as possible. Since there are places that are \"\"tax havens\"\" where there is less to even no tax on profit, a lot of money gets routed there to avoid taxes in other places (US or other unfavorable countries). The problem with this from an IRS/government view is that they keep losing millions/billions of dollars in money because of this. I think the corporate federal tax rate is around 35% and that is without state taxes. Unfortunately when you have less and less money at home - less investment at home happens. Corporations stop doing business at home because they have more money somewhere else - and it makes sense to move more of the company to where the money is or to more favorable tax locations. Even worse - the corporation might just \"\"save\"\" its money somewhere else and kill all reinvestment - thus the money is effectively dead to the rest of the economy. There is a lot of talk about a 'one-time' repatriation tax to allow companies that have dodged their tax burdens to have their money come back to the US (and thus can be used locally) at 10% instead of 35% since there is theroretically a vast amount of cash that would be injected into the US economy. The government is hoping this stimulation will help GDP grow, taxes grow, and help the economy as a whole. In reality, it will reward corporations that broke the law (even though everyone does it), and probably just go into savings accounts here in the US - and not be the \"\"silver bullet\"\" to the economy on verge of collapse again.\"",
"title": ""
},
{
"docid": "399191",
"text": "\"what does negative Total Equity means in McDonald's balance sheet? It means that their liabilities exceed their total assets. Usually is means that a company has accumulated losses over time, but that's just one explanation. But, isn't McDonald a very healthy company, and never lost money? Just because a company has \"\"always\"\" money does not mean it's a healthy company. It may have borrowed a lot of money in order to operate, and now the growth is not able to keep up with the debt load. In McDonald's case, the major driver in the equity change is the fact that they have bought back over $20 Billion in stock over the past few years, which reduces assets and equity. If they had instead paid off debt, their equity would not be negative, but their debt may be so cheap (in terms of interest rate) that it made more financial sense to buy back stock instead of paying off debt. There are too many variables to assess that in this forum.\"",
"title": ""
},
{
"docid": "333755",
"text": "\"There are many different methods for a corporation to get money, but they mostly fall into three categories: earnings, debt and equity. Earnings would be just the corporation's accumulation of cash due to the operation of its business. Perhaps if cash was needed for a particular reason immediately, a business may consider selling a division or group of assets to another party, and using the proceeds for a different part of the business. Debt is money that (to put it simply) the corporation legally must repay to the lender, likely with periodic interest payments. Apart from the interest payments (if any) and the principal (original amount leant), the lender has no additional rights to the value of the company. There are, basically, 2 types of corporate debt: bank debt, and bonds. Bank debt is just the corporation taking on a loan from a bank. Bonds are offered to the public - ie: you could potentially buy a \"\"Tesla Bond\"\", where you give Tesla $1k, and they give you a stated interest rate over time, and principal repayments according to a schedule. Which type of debt a corporation uses will depend mostly on the high cost of offering a public bond, the relationships with current banks, and the interest rates the corporation thinks it can get from either method. Equity [or, shares] is money that the corporation (to put it simply) likely does not have a legal obligation to repay, until the corporation is liquidated (sold at the end of its life) and all debt has already been repaid. But when the corporation is liquidated, the shareholders have a legal right to the entire value of the company, after those debts have been paid. So equity holders have higher risk than debt holders, but they also can share in higher reward. That is why stock prices are so volatile - the value of each share fluctuates based on the perceived value of the entire company. Some equity may be offered with specific rules about dividend payments - maybe they are required [a 'preferred' share likely has a stated dividend rate almost like a bond, but also likely has a limited value it can ever receive back from the corporation], maybe they are at the discretion of the board of directors, maybe they will never happen. There are 2 broad ways for a corporation to get money from equity: a private offering, or a public offering. A private offering could be a small mom and pop store asking their neighbors to invest 5k so they can repair their business's roof, or it could be an 'Angel Investor' [think Shark Tank] contributing significant value and maybe even taking control of the company. Perhaps shares would be offered to all current shareholders first. A public offering would be one where shares would be offered up to the public on the stock exchange, so that anyone could subscribe to them. Why a corporation would use any of these different methods depends on the price it feels it could get from them, and also perhaps whether there are benefits to having different shareholders involved in the business [ie: an Angel investor would likely be involved in the business to protect his/her investment, and that leadership may be what the corporation actually needs, as much or more than money]. Whether a corporation chooses to gain cash from earnings, debt, or equity depends on many factors, including but not limited to: (1) what assets / earnings potential it currently has; (2) the cost of acquiring the cash [ie: the high cost of undergoing a public offering vs the lower cost of increasing a bank loan]; and (3) the ongoing costs of that cash to both the corporation and ultimately the other shareholders - ie: a 3% interest rate on debt vs a 6% dividend rate on preferred shares vs a 5% dividend rate on common shares [which would also share in the net value of the company with the other current shareholders]. In summary: Earnings would be generally preferred, but if the company needs cash immediately, that may not be suitable. Debt is generally cheap to acquire and interest rates are generally lower than required dividend rates. Equity is often expensive to acquire and maintain [either through dividend payments or by reduction of net value attributable to other current shareholders], but may be required if a new venture is risky. ie: a bank/bondholder may not want to lend money for a new tech idea because it is too risky to just get interest from - they want access to the potential earnings as well, through equity.\"",
"title": ""
},
{
"docid": "108770",
"text": "\"A bit strange but okay. The way I would think about this is again that you need to determine for what purpose you're computing this, in much the same way you would if you were to build out the model. The IPO valuation is not going to be relevant to the accretion/dilution analysis unless you're trying to determine whether the transaction was net accretive at exit. But that's a weird analysis to do. For longer holding periods like that you're more likely to look at IRR, not EPS. EPS is something investors look at over the short to medium term to get a sense of whether the company is making good acquisition decisions. And to do that short-to-medium term analysis, they look at earnings. Damodaran would say this is a shitty way of looking at things and that you should probably be looking at some measure of ROIC instead, and I tend to agree, but I don't get paid to think like an investor, I get paid to sell shit to them (if only in indirect fashion). The short answer to your question is that no, you should not incorporate what you are calling liquidation value when determining accretion/dilution, but only because the market typically computes accretion/dilution on a 3-year basis tops. I've never put together a book or seen a press release in my admittedly short time in finance that says \"\"the transaction is estimated to be X% accretive within 4 years\"\" - that just seems like an absurd timeline. Final point is just that from an accounting perspective, a gain on a sale of an asset is not going to get booked in either EBITDA or OCF, so just mechanically there's no way for the IPO value to flow into your accretion/dilution analysis there, even if you are looking at EBITDA/shares. You could figure the gain on sale into some kind of adjusted EBITDA/shares version of EPS, but this is neither something I've ever seen nor something that really makes sense in the context of using EPS as a standardized metric across the market. Typically we take OUT non-recurring shit in EPS, we don't add it in. Adding something like this in would be much more appropriate to measuring the success of an acquisition/investing vehicle like a private equity fund, not a standalone operating company that reports operational earnings in addition to cash flow from investing. And as I suggest above, that's an analysis for which the IRR metric is more ideally situated. And just a semantic thing - we typically wouldn't call the exit value a \"\"liquidation value\"\". That term is usually reserved for dissolution of a corporate entity and selling off its physical or intangible assets in piecemeal fashion (i.e. not accounting for operational synergies across the business). IPO value is actually just going to be a measure of market value of equity.\"",
"title": ""
},
{
"docid": "79411",
"text": "\"This is not an end-all answer but it'll get you started I have been through accounting courses in college as well as worked as a contractor (files as sole proprietor) for a few years but IANAA (I am not an accountant). Following @MasonWheeler's answer, if you're making that much money you should hire a bean counter to at least overlook your bookkeeping. What type of business? First, if you're the sole owner of the business you will most likely file as a sole proprietorship. If you don't have an official business entity, you should get it registered officially asap, and file under that name. The problem with sole proprietorships is liability. If you get sued, not only are your business' assets vulnerable but they can go after your personal assets too (including house/cars/etc). Legally, you and your business are considered one and the same. To avoid liability issues, you could setup a S corporation. Basically, the business is considered it's own entity and legal matters can only take as much as the business owns. You gain more protection but if you don't explicitly keep your business finances separate from your personal finances, you can get into a lot of trouble. Also, corporations generally pay out more in taxes. Technically, since the business is it's own entity you'll need to pay yourself a 'reasonable salary'. If you skip the salary and pay yourself the profits directly (ie evade being taxed on income/salary) the IRS will shut you down (that's one of the leading causes of corporations being shut down). You can also pay distribute bonuses on top of that but it would be wise to burn the words 'within reason' into your memory first. The tax man gets mad if you short him on payroll taxes. S corporations are complicated, if you go that route definitely seek help from an accountant. Bookkeeping If you're not willing to pay a full time accountant you'll need to do a lot of studying about how this works. Generally, even if you have a sole proprietorship it's best to have a separate bank account for all of your business transactions. Every source/drain of money will fall into one of 3 categories... Assets - What your business owns: Assets can be categorized by liquidity. Meaning how fast you can transform them directly into cash. Just because a company is worth a lot doesn't necessarily mean it has a lot of cash. Some assets depreciate (lose value over time) whereas some are very hard to transform back into cash based on the value and/or market fluctuations (like property). Liabilities - What you owe others and what others owe you: Everything you owe and everything that is owed to you gets tracked. Just like credit cards, it's completely possible to owe more than you own as long as you can pay the interest to maintain the loans. Equity - the net worth of the company: The approach they commonly teach in schools is called double-entry bookkeeping where they use the equation: In practice I prefer the following because it makes more sense: Basically, if you account for everything correctly both sides of the equation should match up. If you choose to go the sole proprietorship route, it's smart to track everything I've mentioned above but you can choose to keep things simple by just looking at your Equity. Equity, the heart of your business... Basically, every transaction you make having to do with your business can be simplified down to debits (money/value) increasing and credits (money/value) decreasing. For a very simple company you can assess this by looking at net profits. Which can be calculated with: Revenues, are made up of money earned by services performed and goods sold. Expenses are made up of operating costs, materials, payroll, consumables, interest on liabilities, etc. Basically, if you brought in 250K but it cost you 100K to make that happen, you've made 150K for the year in profit. So, for your taxes you can count up all the money you've made (Revenues), subtract all of the money you've paid out (Expenses) and you'll know how much profit you've made. The profit is what you pay taxes on. The kicker is, there are gray areas when it comes to deducting expenses. For instance, you can deduct the expense of using your car for business but you need to keep a log and can only expense the miles you traveled explicitly for business. Same goes for deducting dedicated workspaces in your house. Basically, do the research if you're not 100% sure about a deduction. If you don't keep detailed books and try to expense stuff without proof, you can get in trouble if the IRS comes knocking. There are always mythical stories about 'that one guy' who wrote off his boat on his taxes but in reality, you can go to jail for tax fraud if you do that. It comes down to this. At the end of the year, if your business took in a ton of money you'll owe a lot in taxes. The better you can justify your expenses, the more you can reduce that debt. One last thing. You'll also have to pay your personal federal/state taxes (including self-employment tax). That means medicare/social security, etc. If this is your first foray into self-employment you're probably not familiar with the fact that 1099 employers pick up 1/2 of the 15% medicare/social security bill. Typically, if you have an idea of what you make annually, you should be paying this out throughout the year. My pay as a contractor was always erratic so I usually paid it out once/twice a year. It's better to pay too much than too little because the gov't will give you back the money you overpaid. At the end of the day, paying taxed sucks more if you're self-employed but it balances out because you can make a lot more money. If as you said, you've broken six figures, hire a damn accountant/adviser to help you out and start reading. When people say, \"\"a business degree will help you advance in any field,\"\" it's subjects like accounting are core requirements to become a business undergrad. If you don't have time for more school and don't want to pay somebody else to take care of it, there's plenty of written material to learn it on your own. It's not rocket surgery, just basic arithmetic and a lot of business jargon (ie almost as much as technology).\"",
"title": ""
},
{
"docid": "410874",
"text": "\"all the other answers are spot on, but look at it this way. really all you mean when you say \"\"building equity\"\" is \"\"accumulating wealth\"\". if that is the goal, then having her invest the money in a brokerage (e.g. ira) account makes a lot more sense. if you can't afford the apartment without her, then you can't afford to pay out her portion of the equity in the future. which means she is not building equity, you are just borrowing money from her. the safest and simplest thing for you to do is to agree on a number that does not include \"\"equity\"\". to be really safe, you might want to both sign something in writing that says she will never have an equity stake unless you agree to it in writing. it doesn't have to be anything fancy. in fact, the shorter the better. i am thinking about 3 sentences should do the trick. if you feel you absolutely have to borrow money from her on a monthly basis to afford your mortgage, then i recommend you make it an unsecured loan. just be sure to specify the interest rate (even if it is zero), and the repayment terms (and ideally, late payment penalties). again, nothing fancy, 10 sentences maybe. e.g. \"\"john doe will borrow x$ per month, until jane doe vacates the apartment. after such time, john doe will begin repaying the loan at y$ per month....\"\" that said, borrowing money from friends and family almost never turns out well. at the very least, you need to save up a few months of rent so that if you do break up, you have time to find another roommate. disclaimer: i do not have any state-issued professional licenses.\"",
"title": ""
},
{
"docid": "159590",
"text": "Is she entitled to more of the equity because she made more? No. Equity should be determined by how much each paid. But she is entitled to more of the equity if she paid more. And that may be what she is saying. That she contributed more to the household's finances than you did. If you always paid the mortgage out of the joint account, you could presumably go back and look at the account to find out how much each of you contributed to it. That would give you a reasonable split for the remainder of the equity after your initial investment. If you both put your entire paychecks into the joint account every time, then it will be the same as the ratio of what you each made. That would also make sense for splitting up whatever remains in that account. While you're doing that, you may want to ask for more for your original $65,000. By my calculation, if your mortgage was 3.5%, that $65,000 saved the household more than $12,000 in interest that became equity instead. So you could reasonably bump your return on the initial investment up to $77,000 while making the concession on the rest of the equity. This is just a suggestion for a framework for splitting the equity. If you can agree on a split, it will almost certainly be easier than going to a mediator or court.",
"title": ""
},
{
"docid": "306149",
"text": "Fully Paid up Partly Paid up: A company may issue stock to you which is only partly paid up, for example, a company may issue a stock of face value 10 to you and ask you to pay 5 now and other 5 will be adjusted later by some other mechanism. This stock shall be partly paid up. Usually, these stocks are issued in different circumstances, for example as part payment for debentures, preference shares or other capital structuring. On the other hand for a fully paid up share no more money needs to be paid by you or no other adjustments need to be made. So, above, the company is issuing you with stocks for which you will need to pay no further money, they are fully paid for. Authorized Capital: Authorized capital of a company is the amount of money a company can raise by selling stock (not debt, equity). This number is registered when the company is incorporated, subsequently, this number can be revised upward by applying to the registrar of companies. Now, this means that at max. the company is authorized to raise this much capital and no more. However, a company may raise less than this, which is called Issued Capital. In your case, the company is raising its authorized capital by applying to the registrar of companies, though in this case they are looking at their full authorized capital to be issued capital, it was not necessary to do so. Increase of Authorized capital: The main benefit is that the company can get more money in form of equity and utilize the same, perhaps, for expansion of business etc., that is the primary benefit. Bonus Share: Usually, companies keep some surplus as reserve, this money comes out of the profit the company makes and is essentially money of the shareholders. This reserve surplus is maintained for situations, when the money may be required for exigencies. However, this surplus grows over a few years and the company usually the company plans for an expansion of business. However, this money cannot be just taken, as it belongs to the shareholder, so shareholders are issued extra equity in proportion to their current holding and this surplus is capitalized i.e. used as part of the company's equity capital. Bonus declaration does not add t o the value of the company and the share prices fall in proportion (but not quite) to the bonus.",
"title": ""
},
{
"docid": "314056",
"text": "This question is indeed rather complicated. Let's simplify it a little bit. Paying down your mortgage makes sense if your expected return in the rest of your portfolio is less than the cost of the mortgage. In many cases, people may also decide to pay down their mortgage because they are risk-averse and do not like carrying debt. There's no tax benefit to doing so, though; Canada doesn't generally allow you to write off mortgage interest, unlike the U.S. As to keeping money in the corporation or not, I'm not going to address that. I don't have a firm enough understanding of corporate taxation. Canadian Couch Potato advises treating all of your investment assets as one large portfolio. That is what you are trying to do here. However, let's consider a different approach. If you do not have enough money to max out your RRSP or TFSA, you may choose to keep your TFSA for an emergency fund, where the money is kept highly liquid. Keep your cash in an interest-bearing TFSA, or perhaps invest it in the money market, inside your TFSA. Then, use your RRSP for the rest of your investment money, split according to your investment goals. This is not the most tax-efficient approach, but it is nice and simple. But you are looking for the most tax-efficient approach. So, let's assume you have enough to more than max out your TFSA and RRSP contributions, and all of your investments are going toward your retirement, which is at least a decade away. Because you are not taxed on your investment income from RRSPs (until you withdraw the money) or TFSA, it makes sense to hold the least tax-efficient investments there. Tax-advantaged investments such as Canadian equities should be held in your investment accounts outside of TFSA and RRSPs. Again, the Canadian Couch Potato has a great article on where to put your investment assets. That article covers interest, dividends, foreign dividends, and capital gains, as well as RRSPs, RESPs, and TFSAs. That article recommends holding Canadian equities in a taxable account, REITs in a tax-sheltered account (TFSA or RRSP), bonds, GICs, and money-market funds in a tax-sheltered account (as these count as interest). The article goes into rather more detail than this, and is worth checking out. It mentions the 15% withholding tax on US-listed ETFs, for example. In addition to that website, I recommend the following three books: The above three resources strongly advocate passive indexed investments, which I like but not everyone agrees with. All three specifically discuss tax implications, which is why I include them here.",
"title": ""
},
{
"docid": "80913",
"text": "\"It should be pretty obvious that without knowing what sort of assets the company owns, and what sort of net earnings are being generated it's impossible to say what a $20k equity investment should get you in terms of ownership percentage. With that said, you want to look at a few to several years of books, look for trends. Some things to understand that might be subtle red flags: It's extremely common for early stage investors to essentially make loans rather than strictly buying shares. In the worst case scenario creditors get to participate in liquidation proceedings before shareholders do. You may be better off investing in this business via a loan that's convertible to equity at your discretion. Single owner service companies are difficult because all of the net earnings go to the proprietor and that person maintains all of the relationships. So taking something like 5 years of net earnings as the value of the company doesn't make much sense because you (or someone else) couldn't just step in and replace the owner. Granted, you aren't contemplating taking over the business, but it negates using an X years of net earnings valuation method. When you read about valuation there is a sort of overriding assumption that no single person could topple the operation which couldn't be farther from the truth in single employee service companies. Additionally, understand that your investment in a single owner company hinges completely on one person's ability and willingness to work. It's really vital to understand the purpose of the funds. Someone will be hired? $20,000 couldn't be even six months of wages... Put things in to perspective with a pad, pen and calculator. Don't invest in the pipe dream of a friend of yours, and DEFINITELY don't hand this person the downpayment for their new house. The first rule of investing is \"\"don't lose money,\"\" this isn't emotional, this is a dollars and cents pragmatic process. Why does the business need this money? How will you be paid back? Personally, I think it would be more gratifying to put $20k in a blender and watch it blend, this is probably a horrible investment. The risk should just be left to credit card companies.\"",
"title": ""
},
{
"docid": "117509",
"text": "What kind of financial analysis would make you comfortable about this decision? The HELOC and ARM are the biggest red flags to me in your current situation. While I don't expect interest rates to skyrocket in the near future, they introduce an interest rate risk that is easy to get rid of. Getting rid of the HELOC and converting to a fixed mortgage would be my first priority. If you also want to upgrade to a new home at the same time (meaning buy a new home contingent on the sale of your first, paying off the HELOC and mortgage), that's fine, but make sure that you can comfortably afford the payment on a fixed-rate mortgage with at least 20% down. I would not take additional cash out of your equity just to save it. You're going to pay more in interest that you're going to get in savings. From there things get trickier. While many people would keep the first property on a mortgage and rent it out, I am not willing to be a landlord for a part-time job, especially when the interest on the mortgage gouges my return on the rent. PLus leverage increases the risks as well - all it takes is to go one or two months without rent and you can find yourself unable to make a mortgage payment, wrecking your credit and possibly risking foreclosure. So my options in order of precedence would be: At what point does it make sense to become a landlord? The complicated answer is when the benefits (rent, appreciation) relative to the costs (maintenance, interest, taxes, etc.) and risks (lost rent, bad renters, home value variance) give you a better return that you could find in investments of similar risk. The simple answer is when you can pay cash for it. That takes interest and lost rent out of the equation. Again, some are willing to take those risks and pay 20% down on rental property. Some are able to make it work. Some of those go broke or lose their properties. when calculating the 20% down of a new property, does that need to be liquid funds, or can that be based on the value of the home you are selling You can make the purchase of the new home contingent on the sale of the first if you need to get the equity out of it to make the 20%. Do NOT refinance the first just to pull out the equity to make a down payment. It's not worth the fees of a refinance.",
"title": ""
},
{
"docid": "48569",
"text": "Most businesses want to grow, and there are a variety of ways to raise the money needed to hire new employees and otherwise invest in the business to increase the rate of that growth. You as a stock holder should hope that management is choosing the least expensive option for growth. Some of the options are debt, selling equity to venture capitalists, or selling equity on the open market (going public). If they choose debt, they pay interest on that debt. If they choose to sell equity to venture capitalists, then your shares get diluted, but hopefully the growth makes up for some of that dilution. If they choose to go public, dilution is still a concern, but the terms are usually a little more favorable for the company selling because the market is so liquid. In the US, current regulations for publicly traded companies cost somewhere in the neighborhood of $1M/year, so that's the rule of thumb for considering whether going public makes sense when calculating the cost of fundraising, but as mentioned, regulations make it less advantageous for executives who choose to sell their shares after the company goes public. (They can't sell when good spot prices appear.) Going public is often considered the next step for a company that has grown past the initial venture funding phase, but if cash-flow is good, plenty of companies decide to just reinvest profits and skip the equity markets altogether.",
"title": ""
},
{
"docid": "538518",
"text": "\"I am not familiar with this broker, but I believe this is what is going on: When entering combination orders (in this case the purchase of stocks and the writing of a call), it does not make sense to set a limit price on the two \"\"legs\"\" of the order separately. In that case it may be possible that one order gets executed, but the other not, for example. Instead you can specify the total amount you are willing to pay (net debit) or receive (net credit) per item. For this particular choice of a \"\"buy and write\"\" strategy, a net credit does not make sense as JoeTaxpayer has explained. Hence if you would choose this option, the order would never get executed. For some combinations of options it does make sense however. It is perhaps also good to see where the max gain numbers come from. In the first case, the gain would be maximal if the stock rises to the strike of the call or higher. In that case you would be payed out $2,50 * 100 = $250, but you have paid $1,41*100 for the combination, hence this leaves a profit of $109 (disregarding transaction fees). In the other case you would have been paid $1,41 for the position. Hence in that case the total profit would be ($1,41+$2,50)*100 = $391. But as said, such an order would not be executed. By the way, note that in your screenshot the bid is at 0, so writing a call would not earn you anything at all.\"",
"title": ""
},
{
"docid": "177528",
"text": "Founder makes available 100% equity, but uses a reasonable amount of the proceeds to pay him/herself a salary (or wage) and from that salary invests in the same initial offering to acquire shares for him/herself. I see several problems. What is a reasonable salary? Also, this leaves the door open to the following scam: Founders say that they are going to follow this plan. However, instead of buying shares, they simply quit after being paid the salary. They use knowledge gained from this business to start a competitor. Investors are left holding an empty company. Tax consequences. The founder would pay income tax on the salary. By contrast, if the founder instead sells shares, that would be capital gains tax, which is lower in many countries (e.g. the United States). Why would I want to invest in a business where the founders don't believe in it enough to take a significant equity stake? Consider the Amazon.com example. Jeff Bezos makes a minimal salary, around $80,000 a year, less than many of his employees. But he has a substantial ownership position. If the company doesn't make money, he won't. Would investors really value the stocks with a P/E of 232.10 in 2016 if they didn't trust him to make the right long term decisions? It's also worth noting that most initial public offerings (IPOs) are not made when the founder is the only employee. A single employee company instead looks for private investors, often called angel investors. Companies generally don't go public until they are established in some way, often making money. Negotiating with angel investors is different from negotiating with the public. They can personally review the books and once invested tend to have input on how the money is spent. In other words, this is mostly solving the wrong problem if you talk about IPOs. This might make more sense with a crowdfunded venture, as that replaces a few angel investors with many individuals. But most crowdfunded ventures tend to approach things from the opposite direction. Instead of looking for investors, they look for customers. If they offer a useful product, they will get customers. If not, they never get the money. Beyond all this, if a founder is only going to get a fair salary some of the time, then why put in any sweat equity? This works fine if the company looks valuable after a year. What if it doesn't? The founder is out a year of sweat equity and has nothing in return. That happens now too, but the possibility of the big return offsets it. You're taking out the big return. I don't think that this is good for either founders or investors. The founder trades a potentially good or even great return for a mediocre return. The investors trade a situation where both they and the founder benefit from a successful company to one where they benefit a lot more than the founder. That's not good for either side.",
"title": ""
},
{
"docid": "288701",
"text": "Yes, there are times when co-signing is the right choice. One is when you know more about the person than the loan issuer does. Consider a young person who has just started working in a volatile field, the kind of job where you can be told on Friday that you only get one shift next week but things might pick up the week after, and who makes maybe $12 an hour in that job. You've done the math and with 40 hour weeks they can easily afford the loan. Furthermore, you know this person well and you know that after a few weeks of not enough shifts, they've got the gumption to go out and find a second job or a different job that will give them 40 hours or more a week. And you know that they have some savings they could use to ensure that no payments will be missed even on low-wage weeks. You can cosign for this person, say for a car loan to get them a car they can drive to that job, knowing that they aren't going to walk away and just stop making the payments. The loan issuer doesn't know any of that. Or consider a young person with poor credit but good income who has recently decided to get smart about money, has written out a budget and a plan to rehabilitate their credit, and who you know will work passionately to make every payment and get the credit score up to a place where they can buy a house or whatever their goal is. Again, you can cosign for this person to make that happen, because you know something the lender doesn't. Or consider a middle aged person who's had some very hard knocks: laid off in a plant closing perhaps, marriage failure, lost all their house equity when the market collapsed, that sort of thing. They have a chance to start over again somewhere else and you have a chance to help. Again you know this isn't someone who is going to mismanage their money and walk away from the payments and leave you holding the bag. If you would give the person the money anyway (say, a car for your newly graduated child) then cosigning instead gives them more of a sense of accomplishment, since they paid for it, and gives them a great credit rating too. If you would not give the person the entire loan amount, but would make their payments for many months or even a year (say, your brother's mortgage for the house where he lives with a sick wife and 3 small children), then cosigning is only making official what you would have done anyway. Arrange with the borrower that if they can't make their payments any more, you will backstop them AND the item (car, house, whatever) is going up for sale to cover your losses. If you don't think you could enforce that just from the strength of the relationship, reconsider co-signing. Then sign what you need to sign and step away from it. It's their loan, not yours. You want them to pay it and to manage it and to leave you out of it until it's all paid off and they thank you for your help. If things go south, you will have to pay, and it may take a while for you to sell the item or otherwise stop the paying, so you do need to be very confident that the borrower is going to make every single payment on time. My point is just that you can have that confidence, based on personal knowledge of character, employment situation, savings and other resources, in a way that a lender really cannot.",
"title": ""
},
{
"docid": "273187",
"text": "why does it make sense financially to buy property and become a landlord? Because then your investment generates cash instead of just sitting idle. All taxes, fees and repairs aside it would take almost 21 years before I start making profits. No - your profit will be the rents that you collect (minus expenses). You still have an asset that is worth roughly what you paid for it (and might go up in value), so you don't need to recoup the entire cost of the property before making a profit. Compared to investing the same 150k in an ETF portfolio with conservative 4% in annual returns I would have made around 140k € after taxes in the same 21 years i.e. almost doubled the money. If you charge 600 € / month (and never miss a month of rental income), after 21 years you have made 151k € in rents plus you still have a property. That property is most likely going to be worth more than you paid for it, so you should have at least 300k € in assets. Having said all that, it does NOT always make sense to invest in rental property. Being a landlord can be a hard job, and there are many risks involved that are different that risks in financial investments.",
"title": ""
},
{
"docid": "446652",
"text": "I think I understand what I am doing wrong. To provide some clarity, I am trying to determine what the value of a project is to a firm. To do this I am taking FCF, not including interest or principal payments, and discounting back to get an NPV enterprise value. I then back off net debt to get to equity value. I believe what I am doing wrong is that I show that initial $50M as a cash outflow in period 0 and then back it off again when I go from enterprise value to equity value. Does this make any sense? Thanks for your help.",
"title": ""
},
{
"docid": "392741",
"text": "\"Someone's (or, a bank's) \"\"exposure to equities\"\" refers to the amount of value which has a risk that fluctuates with the equities market (ie: the stock market). In very broad terms, I think it might make sense to say that exposure to equities could mean, for example, owning many rental properties, if the rental market was \"\"highly correlated\"\" with the equities market. That is - if house prices go down when the equities market goes down, and if that relationship is very strong, then owning a house means you are exposed to the equities market. However, in the sense it is used there, it seems to mean direct exposure to equities - ie: owning stocks and stock-based funds.\"",
"title": ""
},
{
"docid": "569490",
"text": "> K-12 teachers never make six figure sums. In the U.S. that seems true. I found [this from 2012](http://money.usnews.com/careers/best-jobs/high-school-teacher/salary) that puts the median high-school teacher's salary at $55,050, with the top ten percent making about $85k. (By the way, this [OECD chart from 2013](http://educationbythenumbers.org/content/us-teachers-6th-highest-paid-world_982/) shows that the U.S. ranks 6th in the world in pay for primary-school teachers. I was surprised when I found this out.) > Professors in universities sometimes do, but for every professor that makes a lot of money there are probably dozens of untenured faculty who are barely making enough to feed themselves and put gas in their cars. You may be interested in [this chart from 2011](http://chronicle.com/article/Average-Faculty-Salaries-by/126586/) that gives salaries for professors, associate professors, assistant professors, new assistant professors, and instructors--all broken down by field. The data are only for four-year colleges and universities, though; that excludes community colleges, but I'm not sure whether it includes business schools, medical schools, or other graduate institutions. Not surprisingly, law and engineering are the most lucrative fields. > The real reason the big corporate interests want to privatize US education is to use all those jobs as bargaining chips in globalization. Interesting. Can you explain how this is intended to work? And if it would make sense for American corporations to do this, would it make sense for corporations from other countries to do it too? Are they doing it? I don't know anything about GATS or TiSA. Edit: grammar",
"title": ""
},
{
"docid": "104485",
"text": "If you have a new company and you want to attract investors, such as venture capitalists and private equity, incorporating in Delaware LLC probably makes sense. There are actually many investors who will only invest in a Delaware Online incorporation, so starting off by creating a Delaware corporation from the beginning may save a lot of money and stress down the road. You can also choose to form an LLC in Delaware, to begin with, then convert it to a C corporation later.",
"title": ""
},
{
"docid": "23569",
"text": "Does this make sense? Some corporate behemoth was making tons of money by selling disgusting sludge which I would not feed to a fucking dog, and because the true nature of this shit came to light, they lost a lot of business. They only had the business in the first place because people were unaware of what they were doing, and when the people learned, they were disgusted and tended to avoid it.",
"title": ""
},
{
"docid": "65040",
"text": "As the owner of the S-corp, it is far easier for you to move money in/out of the company as contributions and distributions rather than making loans to the company. Loans require interest payments, 1099-INT forms, and have tax consequences, whereas the distributions don't need to be reported because you pay taxes on net profits regardless of whether the money was distributed. If you were paid interest, disregard this answer. I don't know if or how you could re-categorize the loan once there's a 1099-INT involved. If no interest was ever paid, you just need to account for it properly: If the company didn't pay you any interest and never issued you a 1099-INT form (i.e. you wrote a check to the company, no promissory note, no tax forms, no payments, no interest, etc.) then you can categorize that money as a capital contribution. You can likewise take that money back out of the company as a capital distribution and neither of these events are taxable nor do they need to be reported to the IRS. In Quickbooks, create the following Equity accounts -- one for each shareholder making capital contributions and distributions: When putting money into the company, deposit into your corporate bank account and use the Capital Contribution equity account. When taking money out of the company, write yourself a check and use the Distributions account. At the end of every tax year, you can close out your Contributions and Distributions to Retained Earnings by making a general journal entry. For example, debit retained earnings and credit distributions on Dec 31 every year to zero-out the distributions account. For contributions, do the reverse and credit retained earnings. There are other ways of recording these transactions -- for example I think some people just use a Member Capital equity account instead of separate accounts for contributions and distributions -- and QB might warn you about posting journal entries to the special Retained Earnings account at the end of the year. In any case, this is how my CPA set up my books and it's been working well enough for many years. Still, never a bad idea to get a second opinion from your CPA. Be sure to pay yourself a reasonable salary, you can't get out of payroll taxes and just distribute profits -- that's a big red flag that can trigger an audit. If you're simply distributing back the money you already put into the company, that should be fine.",
"title": ""
},
{
"docid": "475560",
"text": "\"Recently, I asked about what the company valuation is and how many shares does my 4% represent.CFO told me that there is no point to talk about \"\"shares\"\" or \"\"stock\"\" since the company is not public. Is it right? No, it is wrong. Shares and stocks exist regardless of how they can be traded. Once a company is formed, there are stocks that belong to the owners in the proportion of the ownership. They may not exist physically, but they do exist on paper. As an owner of 5% of the company, you own 5% of the company stocks. I asked if my investor portion equity will be subjected under a vesting schedule, CFO said yes. That doesn't make sense to me, because I bought those 4%? Aren't those supposed to be fully vested? I agree to my employee equity to be vested. Doesn't make sense to me either, since your money is already in their pocket. But I'm not sure if its illegal. If that's what is written in the signed contract - then may be its possible to have that situation. But it doesn't make much sense, because these shares are granted to you in return to your money, not some potential future work (as the 1% employee's portion). You already gave the money, so why wouldn't they be vested? Best to read the contract upon which you gave them your money, I really hope you have at least that and not just gave them a check....\"",
"title": ""
}
] |
5a8a4aa955429930ff3c0d7c
|
Are The Gaslight Anthem and No Devotion both from the United States?
|
[
{
"docid": "43190994",
"text": "No Devotion are a Welsh/American alternative rock band formed in 2014. They are composed of American vocalist Geoff Rickly (of the band Thursday) from New Jersey, and former band members of the Welsh band Lostprophets. The band formed in the wake of Lostprophets' dissolution in 2013.",
"title": ""
},
{
"docid": "14111532",
"text": "The Gaslight Anthem is an American rock band from New Brunswick, New Jersey, formed in 2006. The band consists of Brian Fallon (lead vocals, rhythm guitar), Alex Rosamilia (lead guitar, backing vocals), Alex Levine (bass guitar, backing vocals), and Benny Horowitz (drums, percussion, backing vocals).",
"title": ""
}
] |
[
{
"docid": "36513489",
"text": "\"45\" is a song by American rock band The Gaslight Anthem, released on May 8, 2012 as the lead single from their fourth studio album, \"Handwritten\" (2012).",
"title": ""
},
{
"docid": "41270557",
"text": "The B-Sides is a compilation album by American rock band the Gaslight Anthem, released on January 28, 2014, on SideOneDummy Records. The album compiles various b-sides and outtakes, many in acoustic form, from the band's singles from 2008 and 2011.",
"title": ""
},
{
"docid": "12680584",
"text": "Sink or Swim is the debut studio album by The Gaslight Anthem, released May 29, 2007 through XOXO Records.",
"title": ""
},
{
"docid": "34010535",
"text": "Elsie is the debut studio album by The Horrible Crowes, a Gaslight Anthem side-project made up of Ian Perkins and Gaslight Anthem founder Brian Fallon. It was released on September 6, 2011, through SideOneDummy Records.",
"title": ""
},
{
"docid": "41270973",
"text": "Live in London is the first live DVD by American rock band The Gaslight Anthem which will be released on December 17, 2013 through Mercury Records. Most of the DVD's ten songs are from the band's 2012 album, \"Handwritten\" and were recorded during two shows at the Troxy in London on March 29 and 30, 2013. The cover forms a homage to the album art of The Clash's \"London Calling\"",
"title": ""
},
{
"docid": "34857046",
"text": "Handwritten is the fourth studio album by American rock band The Gaslight Anthem, released on July 20, 2012, through Mercury Records. Produced by Brendan O'Brien, the album was preceded by its lead single, \"45\", and features liner notes by Nick Hornby.",
"title": ""
},
{
"docid": "30133375",
"text": "The discography of The Gaslight Anthem, an American rock band formed in 2005, consists of five studio albums, two extended plays, and eight singles. The members are Brian Fallon (vocals and guitar), Alex Rosamilia (guitar), Alex Levine (bass), and Benny Horowitz (drums/percussion).",
"title": ""
},
{
"docid": "12207865",
"text": "Broadway Calls is an American punk rock band from Rainier, Oregon. The band has released three records and toured the United States and Canada extensively and often. More recently the band has completed tours in Europe. Broadway Calls have toured with such bands as Alkaline Trio, The Gaslight Anthem, Rancid, The Bouncing Souls, and Bad Religion.",
"title": ""
},
{
"docid": "29836065",
"text": "Brian Fallon (born January 28, 1980) is an American singer, songwriter, and guitarist. He is best known as the lead vocalist, guitarist, and songwriter of the rock band The Gaslight Anthem, with whom he has recorded five studio albums. He is also a member of the duo The Horrible Crowes, alongside The Gaslight Anthem's guitar technician and touring guitarist Ian Perkins.",
"title": ""
},
{
"docid": "18518098",
"text": "The oldest national anthem, defined as \"a song, as of praise, devotion, or patriotism\", is the Dutch national anthem \"Het Wilhelmus\", which was written between 1568 and 1572, but not then given any official status. The first anthem to be officially proclaimed as such was \"God Save The Queen\", adopted by Great Britain in 1745. \"Het Wilhelmus\" was declared the national anthem of the Netherlands in 1932; both of these anthems remain in use today. A royal or imperial anthem is a song that is similar in patriotic character to a national anthem, but which specifically praises a monarch, or royal dynasty. Some states have doubled their royal or imperial anthem as their national anthem.",
"title": ""
},
{
"docid": "38537237",
"text": "Covering Ground is the third studio album by Chuck Ragan, which was recorded in 2011 and produced by Christopher Thorn. The album was recorded during Hot Water Music's hiatus and features a strong folk influence with themes surrounding the life on the road away from loved ones. Brian Fallon of The Gaslight Anthem and Frank Turner are both featured as guest vocalists on selected tracks.",
"title": ""
},
{
"docid": "43068840",
"text": "Get Hurt is the fifth studio album by American rock band The Gaslight Anthem, released in the UK on August 11, 2014, through Virgin EMI, and in the United States on August 12, 2014, through Island Records. It marks their first album on Island Records, which absorbed the band and its previous label, Mercury Records.",
"title": ""
},
{
"docid": "21470",
"text": "Most nation-states have anthems, defined as \"a song, as of praise, devotion, or patriotism\"; most anthems are either marches or hymns in style. A hymn can become a national anthem by a provision in the state's constitution, by a law enacted by its legislature, or simply by tradition. A royal anthem is a patriotic song similar to a national anthem, but it specifically praises or prays for a monarch or royal dynasty. Such anthems are usually performed at public appearances by the monarch or during other events of royal importance. Some states use the royal anthem as the national anthem, such as the anthem of Jordan.",
"title": ""
},
{
"docid": "24333102",
"text": "Live at Park Ave. is a live album by The Gaslight Anthem, released exclusively on vinyl on April 19, 2009.",
"title": ""
},
{
"docid": "17884948",
"text": "The '59 Sound is the second studio album by American rock band The Gaslight Anthem, released on August 19, 2008 by record label SideOneDummy.",
"title": ""
},
{
"docid": "1942791",
"text": "Derek R Grant is the drummer for punk band Alkaline Trio, where he replaced Mike Felumlee. He is also a member of Chicago \"supergroup\" Dead Ending. He was previously a member of The Suicide Machines, Telegraph, Gyga, Thoughts of Ionesco, Remainder, Walls of Jericho, The Exceptions and Broken Spoke. Besides playing the drums, Grant is an accomplished guitarist and singer, and has filled in as guitarist for both Face to Face (1998) and The Gaslight Anthem (October 2008).",
"title": ""
},
{
"docid": "13814965",
"text": "During his time at the Moscow Conservatoire, around September 1866 the school's principal, Nikolay Rubinstein commissioned Pyotr Ilyich Tchaikovsky to compose a Festival Overture on the Danish National Anthem to be played for the visit of the Tsarevich (heir to the throne) to Moscow, accompanied by his new Danish bride, Princess Dagmar of Denmark. The Tsarrevich would eventually be crowned Tsar Alexander III of Russia and remain a devoted follower of Tchaikovsky's music, awarding the composer both the Order of St. Vladimir (Fourth Class) in 1884 and a state pension in 1885.",
"title": ""
},
{
"docid": "30001320",
"text": "Alex Rosamilia (born 1982) is an American musician. Rosamilia is one of the founding members of the band The Gaslight Anthem. He plays lead guitar and provides backing vocals for the band.",
"title": ""
},
{
"docid": "48809920",
"text": "Painkillers is the debut studio album by Brian Fallon, singer/guitarist of American rock band The Gaslight Anthem, released on March 11, 2016, through Island Records.",
"title": ""
},
{
"docid": "39475370",
"text": "Here Comes My Man is an EP by The Gaslight Anthem. The EP features performances of 3 original songs, and one cover. It was released on November 28, 2012 exclusively in the UK.",
"title": ""
},
{
"docid": "42285511",
"text": "Territories of the United States on stamps discusses commemorative postal issues devoted to lands that have been ceded to the nation or purchased by treaty in conjunction with both war and peace. Thirteen states have been created from colonial territories, two from independent republics, four from previous states in the Union, and an additional thirty-one from United States territories.",
"title": ""
},
{
"docid": "39247799",
"text": "Mindflux is the name of a rave song by the British dance outfit N-Joi, released in 1991 from their \"Adrenalin EP\". The single, despite being released in the United Kingdom, only charted in the United States on Billboards Hot Dance Club Play Chart, reaching number 1 in 1992, giving the act its first of two number ones on this chart, the other coming from the act's first hit, 1990's \"Anthem\", which was re-released in 1996 as \"The New Anthem\". The video for the single, in which the duo are performing in a concert, featured singer/actress Saffron and a male both dancing on stage.",
"title": ""
},
{
"docid": "16462123",
"text": "Señor and the Queen is an EP by The Gaslight Anthem. It consists of 4 songs and was released in early 2008 by Sabot Productions. It was released simultaneously on vinyl, with the double-7\" white (100 copies) and double-7\" red editions (500 copies) being the most sought after.",
"title": ""
},
{
"docid": "26603433",
"text": "American Slang is the third studio album by New Jersey–based rock group The Gaslight Anthem. It was released on June 15, 2010 on SideOneDummy Records, which released their previous album, \"The '59 Sound\". The album was produced by \"'The '59 Sound\" producer Ted Hutt.",
"title": ""
},
{
"docid": "50172260",
"text": "Georgia is a three song EP by Brian Fallon, singer/guitarist of American rock band The Gaslight Anthem, released on April 16, 2016, through Island Records. It is a Record Store Day 2016 exclusive, limited to 2,000 pressings on 10\" vinyl.",
"title": ""
},
{
"docid": "41270803",
"text": "Singles Collection: 2008–2011 is a box set by American rock band The Gaslight Anthem which was released on June 18, 2013. The box set contains nine black vinyl 7\" singles packaged in a wooden box and feature the band's singles from 2008–2011 along with live recordings, acoustic sessions and B-sides. The box set was limited to only 2,500 copies.",
"title": ""
},
{
"docid": "39468835",
"text": "Hold You Up is a vinyl only EP by The Gaslight Anthem released on 10\" red vinyl. It was released on November 23, 2012 for Black Friday Record Store Day (limited to 3000 copies). The EP features two original acoustic performances and one cover song.",
"title": ""
},
{
"docid": "11021753",
"text": "The Gaslight was an automobile manufactured in Detroit, Michigan by the Gaslight Motors Company from 1960-c.1961. The Gaslight was a venture that built a replica-style veteran car, based on the 1902 Rambler. It was built with a modern air-cooled single-cylinder engine of 4 hp . The vehicle had a 77 in wheelbase, and weighed 640 lb . It sold for $1,495.",
"title": ""
},
{
"docid": "765082",
"text": "In American and Canadian sports, a fight song is a song associated with a team. In both professional and amateur sports, fight songs are a popular way for fans to cheer for their team. Fight songs are laden with history; in singing a fight song, fans feel part of a large, time-honored tradition. Although the term \"fight song\" is primarily used in the United States, the use of fight songs is commonplace around the world, but they may also be referred to as team anthems, team songs or games songs in other countries, even such as Australia, Mexico and New Zealand. Fight songs differ from stadium anthems, used for similar purposes, in that they are usually written specifically for the purposes of the team, whereas stadium anthems are not.",
"title": ""
},
{
"docid": "24719789",
"text": "Pin Points and Gin Joints is the eighth studio album by The Mighty Mighty Bosstones, which was released on December 8, 2009. It is their first album of all new material since the release of \"A Jackknife to a Swan\" in 2002. \"Pin Points and Gin Joints\" was produced by Ted Hutt, notable for working with other bands such as The Bouncing Souls, Flogging Molly, and The Gaslight Anthem. Recording and writing sessions for the album lasted from November 2008 to July 2009.",
"title": ""
}
] |
574
|
In domesticated populations of Saccharomyces cerevisiae, segmental aneuploidy occurs infrequently.
|
[
{
"docid": "10300888",
"text": "Whereas domestication of livestock, pets, and crops is well documented, it is still unclear to what extent microbes associated with the production of food have also undergone human selection and where the plethora of industrial strains originates from. Here, we present the genomes and phenomes of 157 industrial Saccharomyces cerevisiae yeasts. Our analyses reveal that today's industrial yeasts can be divided into five sublineages that are genetically and phenotypically separated from wild strains and originate from only a few ancestors through complex patterns of domestication and local divergence. Large-scale phenotyping and genome analysis further show strong industry-specific selection for stress tolerance, sugar utilization, and flavor production, while the sexual cycle and other phenotypes related to survival in nature show decay, particularly in beer yeasts. Together, these results shed light on the origins, evolutionary history, and phenotypic diversity of industrial yeasts and provide a resource for further selection of superior strains. PAPERCLIP.",
"title": "Domestication and Divergence of Saccharomyces cerevisiae Beer Yeasts"
}
] |
[
{
"docid": "7643848",
"text": "We have characterized the membrane topology of a 60-kDa inner membrane protein from Escherichia coli that is homologous to the recently identified Oxa1p protein in Saccharomyces cerevisiae mitochondria implicated in the assembly of mitochondrial inner membrane proteins. Hydrophobicity and alkaline phosphatase fusion analyses suggest a membrane topology with six transmembrane segments, including an N-terminal signal-anchor sequence not present in mitochondrial Oxa1p. In contrast to partial N-terminal fusion protein constructs, the full-length protein folds into a protease-resistant conformation, suggesting that important folding determinants are present in the C-terminal part of the molecule.",
"title": "Membrane topology of the 60-kDa Oxa1p homologue from Escherichia coli."
},
{
"docid": "2817000",
"text": "In S. cerevisiae, histone variant H2A.Z is deposited in euchromatin at the flanks of silent heterochromatin to prevent its ectopic spread. We show that H2A.Z nucleosomes are found at promoter regions of nearly all genes in euchromatin. They generally occur as two positioned nucleosomes that flank a nucleosome-free region (NFR) that contains the transcription start site. Astonishingly, enrichment at 5' ends is observed not only at actively transcribed genes but also at inactive loci. Mutagenesis of a typical promoter revealed a 22 bp segment of DNA sufficient to program formation of a NFR flanked by two H2A.Z nucleosomes. This segment contains a binding site of the Myb-related protein Reb1 and an adjacent dT:dA tract. Efficient deposition of H2A.Z is further promoted by a specific pattern of histone H3 and H4 tail acetylation and the bromodomain protein Bdf1, a component of the Swr1 remodeling complex that deposits H2A.Z.",
"title": "Histone Variant H2A.Z Marks the 5′ Ends of Both Active and Inactive Genes in Euchromatin"
},
{
"docid": "86231298",
"text": "Protein modification by the ubiquitin-like SUMO protein contributes to many cellular regulatory mechanisms. In Saccharomyces cerevisiae, both sumoylating and desumoylating activities are essential for viability. Of its two known desumoylating enzymes, Ubl-specific protease (Ulp)1 and Ulp2/Smt4, Ulp1 is specifically required for cell cycle progression. A ∼200-residue segment, the Ulp domain (UD), is conserved among Ulps and includes a core cysteine protease domain that is even more widespread. Here we demonstrate that the Ulp1 UD by itself can support wild-type growth rates and in vitro can cleave SUMO from substrates. However, in cells expressing only the UD of Ulp1, many SUMO conjugates accumulate to high levels, indicating that the nonessential Ulp1 NH2-terminal domain is important for activity against a substantial fraction of sumoylated targets. The NH2-terminal domain also includes sequences necessary and sufficient to concentrate Ulp1 at nuclear envelope sites. Remarkably, NH2-terminally deleted Ulp1 variants are able, unlike full-length Ulp1, to suppress defects of cells lacking the divergent Ulp2 isopeptidase. Thus, the NH2-terminal regulatory domain of Ulp1 restricts Ulp1 activity toward certain sumoylated proteins while enabling the cleavage of others. These data define key functional elements of Ulp1 and strongly suggest that subcellular localization is a physiologically significant constraint on SUMO isopeptidase specificity.",
"title": "The Ulp1 SUMO isopeptidase distinct domains required for viability, nuclear envelope localization, and substrate specificity"
},
{
"docid": "32638085",
"text": "Histone acetylation and deacetylation in the yeast Saccharomyces cerevisiae occur by targeting acetyltransferase and deacetylase enzymes to gene promoters and, in an untargeted and global manner, by affecting most nucleosomes. Recently, new roles for histone acetylation have been uncovered, not only in transcription but also in DNA replication, repair and heterochromatin formation. Interestingly, specific acetylatable lysines can function as binding sites for regulatory factors. Moreover, histone deacetylation is not only repressive but can be required for gene activity.",
"title": "Histone acetylation and deacetylation in yeast"
},
{
"docid": "39462488",
"text": "Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Saccharomyces cerevisiae proteins Tof1 and Mrc1 facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint.",
"title": "Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility"
},
{
"docid": "145335387",
"text": "As in other countries, suburbanization in China occurred after the cities had experienced a period of sustained industrial and population growth. This study examines suburbanization in Beijing, Shanghai, Shenyang, and Dalian. As a result of economic restructuring, the urban core registered net population loss from 1982 to 1990 because of decentralization while the inner suburbs gained population. Among the forces driving suburbanization were marketization of urban land, the shift of industrial land to tertiary use, transportation improvement, the availability of foreign and domestic capital, housing rehabilitation in the city, and new housing construction in the suburbs. There were certain similarities but major differences between American and Chinese suburbanization. Unlike the current metropolitan landscape in the United States where suburban growth has given rise to a polycentric spatial structure, suburbanization in China is still at the incipient stage of development with suburbs dominated by centra...",
"title": "ECONOMIC RESTRUCTURING AND SUBURBANIZATION IN CHINA"
},
{
"docid": "13613916",
"text": "Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief of glucose repression.",
"title": "Glucose repression in Saccharomyces cerevisiae"
},
{
"docid": "9704467",
"text": "We developed the Yeast Gene Order Browser (YGOB; http://wolfe.gen.tcd.ie/ygob) to facilitate visual comparisons and computational analysis of synteny relationships in yeasts. The data presented in YGOB, currently covering seven species, are based on sets of homologous genes that have been intensively manually curated based on both sequence similarity and genomic context (synteny). We reconciled different laboratories' lists of paralogous Saccharomyces cerevisiae gene pairs formed by genome duplication (ohnologs), and present near-exhaustive lists of the ohnolog pairs retained in S. cerevisiae (551, including 22 previously unidentified), Saccharomyces castellii (599), and Candida glabrata (404).",
"title": "in polyploid species"
},
{
"docid": "4414481",
"text": "Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals. We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide). In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals.",
"title": "Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration"
},
{
"docid": "34074902",
"text": "Abstract Feline leukemia virus (FeLV), Gammaretrovirus, and feline immunodeficiency virus, a Lentivirus, are members of the family Retroviridae, and may establish persistent infections in the domestic cat (Felis catus). Cytoproliferative and cytosuppressive disorders may result from infection with these viruses. Morbidity and mortality rates are high in domestic cats worldwide. Infection of endangered neotropic small felids with these viruses could be devastating. To investigate the prevalence of FeLV and feline lentiviruses in neotropic small felids kept in captivity in São Paulo state, Brazil, serum samples from 104 animals belonging to the species Leopardus pardalis, Leopardus tigrinus, Leopardus wiedii, Herpailurus yaguarondi, and Oncifelis geoffroyi were tested for FeLV and feline lentiviruses by commercially available immunoassays. All results were negative, suggesting that retrovirus infection is not an important clinical problem in these populations. Because domestic cats in São Paulo city are naturally infected with these pathogens, and feral cats are commonly found in zoologic facilities in Brazil, preventive measures should be taken to avoid transmission of retroviruses to naive populations of wild and captive neotropic felids in Brazil.",
"title": "SEROSURVEY FOR FELINE LEUKEMIA VIRUS AND LENTIVIRUSES IN CAPTIVE SMALL NEOTROPIC FELIDS IN SÃO PAULO STATE, BRAZIL"
},
{
"docid": "14145440",
"text": "BACKGROUND DNA replication and mitosis are triggered by activation of kinase complexes, each made up of a cyclin and a cyclin-dependent kinase (Cdk). It had seemed possible that the association of Cdks with different classes of cyclins specifies whether S phase (replication) or M phase (mitosis) will occur. The recent finding that individual B-type cyclins (encoded by the genes CLB1-CLB6) can have functions in both processes in the budding yeast Saccharomyces cerevisiae casts doubt on this notion. RESULTS S. cerevisiae strains lacking C1b1-C1b4 undergo DNA replication once but fail to enter mitosis. We have isolated mutations in two genes, SIM1 and SIM2 (SIM2 is identical to SEC72), which allow such cells to undergo an extra round of DNA replication without mitosis. The Clb5 kinase, which promotes S phase, remains active during the G2-phase arrest of cells of the parental strain, but its activity declines rapidly in sim mutants. Increased expression of the CLB5 gene prevents re-replication. Thus, a cyclin B-kinase that promotes DNA replication in G1-phase cells can prevent re-replication in G2-phase cells. Inactivation of C1b kinases by expression of the specific C1b-Cdk1 inhibitor p40SIC1 is sufficient to induce a prereplicative state at origins of replication in cells blocked in G2/M phase by nocodazole. Re-activation of C1b-Cdk1 kinases induces a second round of DNA replication. CONCLUSIONS We propose that S-phase-promoting cyclin B--Cdk complexes prevent re-replication during S, G2 and M phases by inhibiting the transition of replication origins to a pre-replicative state. This model can explain both why origins 'fire' only once per S phase and why S phase is dependent on completion of the preceding M phase.",
"title": "S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state"
},
{
"docid": "365896",
"text": "We describe methods for obtaining a quantitative description of RNA processing at high resolution in budding yeast. As a model gene expression system, we constructed tetON (for induction studies) and tetOFF (for repression, derepression, and RNA degradation studies) yeast strains with a series of reporter genes integrated in the genome under the control of a tetO7 promoter. Reverse transcription and quantitative real-time-PCR (RT-qPCR) methods were adapted to allow the determination of mRNA abundance as the average number of copies per cell in a population. Fluorescence in situ hybridization (FISH) measurements of transcript numbers in individual cells validated the RT-qPCR approach for the average copy-number determination despite the broad distribution of transcript levels within a population of cells. In addition, RT-qPCR was used to distinguish the products of the different steps in splicing of the reporter transcripts, and methods were developed to map and quantify 3'-end cleavage and polyadenylation. This system permits pre-mRNA production, splicing, 3'-end maturation and degradation to be quantitatively monitored with unprecedented kinetic detail, suitable for mathematical modeling. Using this approach, we demonstrate that reporter transcripts are spliced prior to their 3'-end cleavage and polyadenylation, that is, cotranscriptionally.",
"title": "RiboSys, a high-resolution, quantitative approach to measure the in vivo kinetics of pre-mRNA splicing and 3'-end processing in Saccharomyces cerevisiae."
},
{
"docid": "25462689",
"text": "We have investigated HO endonuclease-induced double-strand break (DSB) recombination and repair in a LACZ duplication plasmid in yeast. A 117-bp MATa fragment, embedded in one copy of LACZ, served as a site for initiation of a DSB when HO endonuclease was expressed. The DSB could be repaired using wild-type sequences located on a second, promoterless, copy of LACZ on the same plasmid. In contrast to normal mating-type switching, crossing-over associated with gene conversion occurred at least 50% of the time. The proportion of conversion events accompanied by exchange was greater when the two copies of LACZ were in direct orientation (80%), than when inverted (50%). In addition, the fraction of plasmids lost was significantly greater in the inverted orientation. The kinetics of appearance of intermediates and final products were also monitored. The repair of the DSB is slow, requiring at least an hour from the detection of the HO-cut fragments to completion of repair. Surprisingly, the appearance of the two reciprocal products of crossing over did not occur with the same kinetics. For example, when the two LACZ sequences were in the direct orientation, the HO-induced formation of a large circular deletion product was not accompanied by the appearance of a small circular reciprocal product. We suggest that these differences may reflect two kinetically separable processes, one involving only one cut end and the other resulting from the concerted participation of both ends of the DSB.",
"title": "Genetic and physical analysis of double-strand break repair and recombination in Saccharomyces cerevisiae."
},
{
"docid": "984825",
"text": "Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs, enhances the function of transfer RNA and ribosomal RNA by stabilizing the RNA structure. Messenger RNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function--it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding centre. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological relevance was unclear. Here we present a comprehensive analysis of pseudouridylation in Saccharomyces cerevisiae and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as many novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1-4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease.",
"title": "Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells"
},
{
"docid": "23604601",
"text": "The IME1 gene of Saccharomyces cerevisiae is required for initiation of meiosis. Transcription of IME1 is detected under conditions which are known to induce initiation of meiosis, namely starvation for nitrogen and glucose, and the presence of MATa1 and MAT alpha 2 gene products. In this paper we show that IME1 is also subject to translational regulation. Translation of IME1 mRNA is achieved either upon nitrogen starvation, or upon G1 arrest. In the presence of nutrients, constitutively elevated transcription of IME1 is also sufficient for the translation of IME1 RNA. Four different conditions were found to cause expression of Ime1 protein in vegetative cultures: elevated transcription levels due to the presence of IME1 on a multicopy plasmid; elevated transcription provided by a Gal-IME1 construct; G1 arrest due to alpha-factor treatment; G1 arrest following mild heat-shock treatment of cdc28 diploids. Using these conditions, we obtained evidence that starvation is required not only for transcription and efficient translation of IME1, but also for either the activation of Ime1 protein or for the induction/activation of another factor that, either alone or in combination with Ime1, induces meiosis.",
"title": "Post-transcriptional regulation of IME1 determines initiation of meiosis in Saccharomyces cerevisiae."
},
{
"docid": "9548440",
"text": "Trisomic and monosomic (aneuploid) embryos account for at least 10% of human pregnancies and, for women nearing the end of their reproductive lifespan, the incidence may exceed 50%. The errors that lead to aneuploidy almost always occur in the oocyte but, despite intensive investigation, the underlying molecular basis has remained elusive. Recent studies of humans and model organisms have shed new light on the complexity of meiotic defects, providing evidence that the age-related increase in errors in the human female is not attributable to a single factor but to an interplay between unique features of oogenesis and a host of endogenous and exogenous factors.",
"title": "Human aneuploidy: mechanisms and new insights into an age-old problem"
},
{
"docid": "14446279",
"text": "In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.",
"title": "Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region"
},
{
"docid": "43752562",
"text": "Subcellular membranes of Saccharomyces cerevisiae, including mitochondria, microsomes, plasma membranes, secretory vesicles, vacuoles, nuclear membranes, peroxisomes, and lipid particles, were isolated by improved procedures and analyzed for their lipid composition and their capacity to synthesize phospholipids and to catalyze sterol delta 24-methylation. The microsomal fraction is heterogeneous in terms of density and classical microsomal marker proteins and also with respect to the distribution of phospholipid-synthesizing enzymes. The specific activity of phosphatidylserine synthase was highest in a microsomal subfraction which was distinct from heavier microsomes harboring phosphatidylinositol synthase and the phospholipid N-methyltransferases. The exclusive location of phosphatidylserine decarboxylase in mitochondria was confirmed. CDO-diacylglycerol synthase activity was found both in mitochondria and in microsomal membranes. Highest specific activities of glycerol-3-phosphate acyltransferase and sterol delta 24-methyltransferase were observed in the lipid particle fraction. Nuclear and plasma membranes, vacuoles, and peroxisomes contain only marginal activities of the lipid-synthesizing enzymes analyzed. The plasma membrane and secretory vesicles are enriched in ergosterol and in phosphatidylserine. Lipid particles are characterized by their high content of ergosteryl esters. The rigidity of the plasma membrane and of secretory vesicles, determined by measuring fluorescence anisotropy by using trimethylammonium diphenylhexatriene as a probe, can be attributed to the high content of ergosterol.",
"title": "Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae."
},
{
"docid": "9451052",
"text": "Histone variant H2A.Z-containing nucleosomes are incorporated at most eukaryotic promoters. This incorporation is mediated by the conserved SWR1 complex, which replaces histone H2A in canonical nucleosomes with H2A.Z in an ATP-dependent manner. Here, we show that promoter-proximal nucleosomes are highly heterogeneous for H2A.Z in Saccharomyces cerevisiae, with substantial representation of nucleosomes containing one, two, or zero H2A.Z molecules. SWR1-catalyzed H2A.Z replacement in vitro occurs in a stepwise and unidirectional fashion, one H2A.Z-H2B dimer at a time, producing heterotypic nucleosomes as intermediates and homotypic H2A.Z nucleosomes as end products. The ATPase activity of SWR1 is specifically stimulated by H2A-containing nucleosomes without ensuing histone H2A eviction. Remarkably, further addition of free H2A.Z-H2B dimer leads to hyperstimulation of ATPase activity, eviction of nucleosomal H2A-H2B, and deposition of H2A.Z-H2B. These results suggest that the combination of H2A-containing nucleosome and free H2A.Z-H2B dimer acting as both effector and substrate for SWR1 governs the specificity and outcome of the replacement reaction.",
"title": "Stepwise Histone Replacement by SWR1 Requires Dual Activation with Histone H2A.Z and Canonical Nucleosome"
},
{
"docid": "16686383",
"text": "The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We identify posttranslational modifications of Saccharomyces cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants shows growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody, we show that the association of phosphorylated Cse4 with centromeres increases in response to defective microtubule attachment or reduced cohesion. We determine that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 are reduced at centromeres in ipl1 strains in vivo, and in vitro assays show phosphorylation of Cse4 by Ipl1. Consistent with these results, we observe that a phosphomimetic cse4-4SD mutant suppresses the temperature-sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80, which are defective for chromosome biorientation. Furthermore, cell biology approaches using a green fluorescent protein-labeled chromosome show that cse4-4SD suppresses chromosome segregation defects in dam1 spc34 strains. On the basis of these results, we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our results provide a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation.",
"title": "Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in Saccharomyces cerevisiae"
},
{
"docid": "23664875",
"text": "Termination of replication forks at the natural termini of the rDNA of Saccharomyces cerevisiae is controlled in a sequence-specific and polar mode by the interaction of the Fob1p replication terminator protein with the tandem Ter sites located in the nontranscribed spacers. Here we show, by both 2D gel analyses and chromatin immunoprecipitations (ChIP), that there exists a second level of global control mediated by the intra-S-phase checkpoint protein complex of Tof1p and Csm3p that protect stalled forks at Ter sites against the activity of the Rrm3p helicase (\"sweepase\"). The sweepase tends to release arrested forks presumably by the transient displacement of the Ter-bound Fob1p. Consistent with this mechanism, very few replication forks were arrested at the natural replication termini in the absence of the two checkpoint proteins. In the absence of the Rrm3p helicase, there was a slight enhancement of fork arrest at the Ter sites. Simultaneous deletions of the TOF1 (or CSM3), and the RRM3 genes restored fork arrest by removing both the fork-releasing and fork-protection activities. Other genes such as MRC1, WSS1, and PSY2 that are also involved in the MRC1 checkpoint pathway were not involved in this global control. This observation suggests that Tof1p-Csm3p function differently from MRC1 and the other above-mentioned genes. This mechanism is not restricted to the natural Ter sites but was also observed at fork arrest caused by the meeting of a replication fork with transcription approaching from the opposite direction.",
"title": "The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae."
},
{
"docid": "42267740",
"text": "Various proteins have been found to play roles in both the repair of UV damaged DNA and heterochromatin-mediated silencing in the yeast Saccharomyces cerevisiae. In particular, factors that are involved in the methylation of lysine-79 of histone H3 by Dot1p have been implicated in both processes, suggesting a bipartite function for this modification. We find that a dot1 null mutation and a histone H3 point mutation at lysine-79 cause increased sensitivity to UV radiation, suggesting that lysine-79 methylation is important for efficient repair of UV damage. Epistasis analysis between dot1 and various UV repair genes indicates that lysine-79 methylation plays overlapping roles within the nucleotide excision, post-replication and recombination repair pathways, as well as RAD9-mediated checkpoint function. In contrast, epistasis analysis with the H3 lysine-79 point mutation indicates that the lysine-to-glutamic acid substitution exerts specific effects within the nucleotide excision repair and post-replication repair pathways, suggesting that this allele only disrupts a subset of the functions of lysine-79 methylation. The overall results indicate the existence of distinct and separable roles of histone H3 lysine-79 methylation in the response to UV damage, potentially serving to coordinate the various repair processes.",
"title": "Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae."
},
{
"docid": "4319844",
"text": "Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that occurs in a subset of cancers. By analyzing telomerase-positive cells and their human TERC knockout-derived ALT human cell lines, we show that ALT cells harbor more fragile telomeres representing telomere replication problems. ALT-associated replication defects trigger mitotic DNA synthesis (MiDAS) at telomeres in a RAD52-dependent, but RAD51-independent, manner. Telomeric MiDAS is a conservative DNA synthesis process, potentially mediated by break-induced replication, similar to type II ALT survivors in Saccharomyces cerevisiae Replication stresses induced by ectopic oncogenic expression of cyclin E, G-quadruplexes, or R-loop formation facilitate the ALT pathway and lead to telomere clustering, a hallmark of ALT cancers. The TIMELESS/TIPIN complex suppresses telomere clustering and telomeric MiDAS, whereas the SMC5/6 complex promotes them. In summary, ALT cells exhibit more telomere replication defects that result in persistent DNA damage responses at telomeres, leading to the engagement of telomeric MiDAS (spontaneous mitotic telomere synthesis) that is triggered by DNA replication stress, a potential driver of genomic duplications in cancer.",
"title": "Alternative Lengthening of Telomeres Mediated by Mitotic DNA Synthesis Engages Break-Induced Replication Processes."
},
{
"docid": "1256116",
"text": "The YEAst Search for Transcriptional Regulators And Consensus Tracking (YEASTRACT) information system (http://www.yeastract.com) was developed to support the analysis of transcription regulatory associations in Saccharomyces cerevisiae. Last updated in June 2010, this database contains over 48,200 regulatory associations between transcription factors (TFs) and target genes, including 298 specific DNA-binding sites for 110 characterized TFs. All regulatory associations stored in the database were revisited and detailed information on the experimental evidences that sustain those associations was added and classified as direct or indirect evidences. The inclusion of this new data, gathered in response to the requests of YEASTRACT users, allows the user to restrict its queries to subsets of the data based on the existence or not of experimental evidences for the direct action of the TFs in the promoter region of their target genes. Another new feature of this release is the availability of all data through a machine readable web-service interface. Users are no longer restricted to the set of available queries made available through the existing web interface, and can use the web service interface to query, retrieve and exploit the YEASTRACT data using their own implementation of additional functionalities. The YEASTRACT information system is further complemented with several computational tools that facilitate the use of the curated data when answering a number of important biological questions. Since its first release in 2006, YEASTRACT has been extensively used by hundreds of researchers from all over the world. We expect that by making the new data and services available, the system will continue to be instrumental for yeast biologists and systems biology researchers.",
"title": "YEASTRACT: providing a programmatic access to curated transcriptional regulatory associations in Saccharomyces cerevisiae through a web services interface"
},
{
"docid": "10874408",
"text": "DNA double-strand breaks (DSBs), which are formed by the Spo11 protein, initiate meiotic recombination. Previous DSB-mapping studies have used rad50S or sae2Δ mutants, which are defective in break processing, to accumulate Spo11-linked DSBs, and report large (≥ 50 kb) “DSB-hot” regions that are separated by “DSB-cold” domains of similar size. Substantial recombination occurs in some DSB-cold regions, suggesting that DSB patterns are not normal in rad50S or sae2Δ mutants. We therefore developed a novel method to map genome-wide, single-strand DNA (ssDNA)–associated DSBs that accumulate in processing-capable, repair-defective dmc1Δ and dmc1Δ rad51Δ mutants. DSBs were observed at known hot spots, but also in most previously identified “DSB-cold” regions, including near centromeres and telomeres. Although approximately 40% of the genome is DSB-cold in rad50S mutants, analysis of meiotic ssDNA from dmc1Δ shows that most of these regions have substantial DSB activity. Southern blot assays of DSBs in selected regions in dmc1Δ, rad50S, and wild-type cells confirm these findings. Thus, DSBs are distributed much more uniformly than was previously believed. Comparisons of DSB signals in dmc1, dmc1 rad51, and dmc1 spo11 mutant strains identify Dmc1 as a critical strand-exchange activity genome-wide, and confirm previous conclusions that Spo11-induced lesions initiate all meiotic recombination.",
"title": "Mapping Meiotic Single-Strand DNA Reveals a New Landscape of DNA Double-Strand Breaks in Saccharomyces cerevisiae"
},
{
"docid": "36904081",
"text": "The yeast ribosomal protein gene RPL32 of Saccharomyces cerevisiae is of particular interest for two reasons: 1) it is adjacent to another ribosomal protein gene, RP29, whose divergent transcription may be driven from the same control sequences, and 2) it appears that the splicing of its transcript is regulated by the product of the gene, ribosomal protein in L32. RPL32 has been analyzed in detail. It is essential for cell growth. Its sequence predicts L32 to be a protein of 105 amino acids, somewhat basic near the NH2 terminus, rather acidic near the COOH terminus, and homologous to ribosomal protein L30 of mammals. The reading frame has been confirmed by partial NH2-terminal analysis of L32. The nucleotide sequence also predicts an intron of 230 nucleotides, which begins with the unusual sequence GTCAGT and ends 40 nucleotides downstream of the consensus sequence TAC-TAAC. The intron has been confirmed by determination of the sequence of a cDNA clone. Transcription initiates 58 nucleotides upstream of the AUG initiation codon, and the polyadenylation site occurs 100 nucleotides downstream of the termination codon. Regulation of the transcription of ribosomal protein genes has been linked to two related consensus sequences. Analysis of the intergenic region between RP29 and RPL32 reveals three copies of these sequences. A deletion removing all three sequences reduces synthesis of a L32-LacZ fusion protein by more than 90%. Some residual activity, however, remains.",
"title": "The yeast ribosomal protein L32 and its gene."
},
{
"docid": "516867",
"text": "The unicellular eukaryotic organisms represent the popular model systems to understand aging in eukaryotes. Candida albicans, a polymorphic fungus, appears to be another distinctive unicellular aging model in addition to the budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe. The two types of Candida cells, yeast (blastospore) form and hyphal (filamentous) form, have similar replicative lifespan. Taking the advantage of morphologic changes, we are able to obtain cells of different ages. Old Candida cells tend to accumulate glycogen and oxidatively damaged proteins. Deletion of the SIR2 gene causes a decrease of lifespan, while insertion of an extra copy of SIR2 extends lifespan, indicating that like in S. cerevisiae, Sir2 regulates cellular aging in C. albicans. Interestingly, Sir2 deletion does not result in the accumulation of extra-chromosomal rDNA molecules, but influences the retention of oxidized proteins in mother cells, suggesting that the extra-chromosomal rDNA molecules may not be associated with cellular aging in C. albicans. This novel aging model, which allows efficient large-scale isolation of old cells, may facilitate biochemical characterizations and genomics/proteomics studies of cellular aging, and help to verify the aging pathways observed in other organisms including S. cerevisiae.",
"title": "Candida albicans, a distinctive fungal model for cellular aging study"
},
{
"docid": "21425864",
"text": "Glycosyl phosphatidylinositols (GPIs) anchor many proteins to the surface of eukaryotic cells and may also serve as sorting signals on proteins and participate in signal transduction. We have isolated a Saccharomyces cerevisiae GPI anchoring mutant, gpi1, using a colony screen for cells blocked in [3H]inositol incorporation into protein. The gpi1 mutant is defective in vitro in the synthesis of N-acetylglucosaminyl phosphatidylinositol, the first intermediate in GPI synthesis, and is also temperature-sensitive for growth. Completion of the first step in GPI assembly is therefore required for growth of the unicellular eukaryote S. cerevisiae. GPI synthesis could therefore be exploited as a target for antifungal or antiparasitic agents.",
"title": "A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis."
},
{
"docid": "26083387",
"text": "The Saccharomyces cerevisiae DNA helicase Rrm3p is needed for normal fork progression through >1000 discrete sites scattered throughout the genome. Here we show that replication of all yeast chromosomes was markedly delayed in rrm3 cells. Delayed replication was seen even in a region that lacks any predicted Rrm3p-dependent sites. Based on the pattern of replication intermediates in two-dimensional gels, the rate of fork movement in rrm3 cells appeared similar to wild-type except at known Rrm3p-dependent sites. These data suggest that although Rrm3p has a global role in DNA replication, its activity is needed only or primarily at specific, difficult-to-replicate sites. By the criterion of chromatin immunoprecipitation, Rrm3p was associated with both Rrm3p-dependent and -independent sites, and moved with the replication fork through both. In addition, Rrm3p interacted with Pol2p, the catalytic subunit of DNA polymerase epsilon, in vivo. Thus, rather than being recruited to its sites of action when replication forks stall at these sites, Rrm3p is likely a component of the replication fork apparatus.",
"title": "The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes."
},
{
"docid": "6106004",
"text": "Publisher Summary The budding yeast Saccharomyces cerevisiae ( S. cerevisiae ) divides asymmetrically. In vegetative growth, yeast cells reproduce by budding, and the position where the bud forms ultimately determines the plane of cell division. This chapter describes the detailed procedures for the separation and isolation of mothers and daughters. These protocols have been used by investigators studying aging, bud site selection, and other aspects of asymmetric cell division. The chapter describes the procedures for performing life span analysis by micromanipulation and the steps for the large-scale collection of old cells. At the beginning and the end of a life span, it can be difficult to distinguish mothers from daughters. At most points in the life span, daughter cells are smaller than the mothers that produced them. In addition, mother cells will generally bud a second time before their daughter cells form their first bud. One method for effective isolation of virgin daughter cells from mother cells, but not for recovery of old mothers, is called a “baby machine. ” Mother cells are attached to a membrane and allowed to divide. Daughter cells from these attached cells are eluted continuously by washing the membrane.",
"title": "Separation of mother and daughter cells."
}
] |
917
|
If I helped my friend to file taxes; can I represent her on a phone call with FTB?
|
[
{
"docid": "379233",
"text": "In order for you to be able to talk to the FTB on someone's behalf, that someone has to submit form 3520. Note that since you're not a professional, this form must be paper-filed (CRTP, EA, CPA or attorneys can have this filed on-line). Once the form is accepted by the FTB, you can contact the FTB on behalf of your friend. Pay attention: you're going to represent the partnership, not the individual.",
"title": ""
}
] |
[
{
"docid": "366761",
"text": "I called the IRS (click here for IRS contact info) and they said I do not need to get a new EIN. I could have just filed the appropriate employer federal tax return (940/941) and then the filing requirements would have been updated. But while I was on the phone, they just updated the filing requirements for my LLC so I am all good now (I still need to file the correct form and make the correct payments, etc. but I can use this same EIN going forward). Disclaimer: Don't trust me (or this answer) for tax advice (your situation may be different). The IRS person on the phone was very helpful so I recommend calling them if you are in a similar situation. FYI, I have found calling the IRS to always be very helpful.",
"title": ""
},
{
"docid": "222726",
"text": "\"What is the right way to handle this? Did you check the forms? Did the form state $0 tax due on the FTB LLC/Corp form (I'm guessing you operate as LLC/Corp, since you're dealing with the Franchise Tax)? The responsibility is ultimately yours. You should cross check all the numbers and verify that they're correct. That said, if the CPA filled the forms incorrectly based on your correct data - then she made a mistake and can be held liable. CPA filing forms from a jurisdiction on the other end of the country without proper research and knowledge may be held negligent if she made a grave mistake. You can file a law suit against the CPA (which will probably trigger her E&O insurance carrier who'll try to settle if there's a good chance for your lawsuit to not be thrown away outright), or complain to the State regulatory agency overseeing CPAs in the State of her license. Or both. Am I wrong for expecting the CPA should have properly filled out and filed my taxes? No, but it doesn't shift the responsibility from you. How can I find out if the CPA has missed anything else? Same as with doctors and lawyers - get a second opinion. Preferably from a CPA licensed in California. You and only you are responsible for your taxes. You may try to pin the penalties and interest on the CPA if she really made a mistake. California is notorious for very high LLC/Corp franchise tax (cost of registering to do business in the State). It's $800 a year. You should have read the forms and the instructions carefully, it is very prominent. It is also very well discussed all over the Internet, any search engine would pop it up for you with a simple \"\"California Franchise Tax for LLC/Corp\"\" search. CA FTB is also very aggressive in assessing and collecting the fee, and the rules of establishing nexus in CA are very broad. From your description it sounds like you were liable for the Franchise tax in CA, since you had a storage facility in CA. You may also be liable for sales taxes for that period.\"",
"title": ""
},
{
"docid": "105158",
"text": "\"Does location of EA or CPA matter? Not in particular. The FTB has field offices all over the State, so if a meeting needs to be arranged - it will be in the nearest office. When you interview the potential candidates, you can ask them how they would deal the case if there's a need of an in-person visit to the FTB, and if it is even an option you should be worrying about. Likely not, since as you mentioned before you're in a mail audit process. Are there websites that rate EAs or CPAs, for example, on how many audits they have won? Or should I simply rely on yelp.com ratings. There's no \"\"winning\"\" in audits. Ideally, given the same data, any EA or CPA would reach the same result in the discussion re audits with the FTB. Obviously, some are more experienced and some are less, and some are specializing on specific types of audits/entities, etc. Yelp is a place to start, but take the reviews there with a grain of salt since most reviewers are probably there to rant. If you see a repetitive pattern in the reviews - take that into consideration. For example, you probably don't want to hire someone who's been repeatedly unresponsive to their clients, not returning calls, not answering questions, being late, etc. Are all EAs and CPAs equal No. Some are generalists, some specialize in a specific area. Some build practice elusively on representation (IRS or FTB, or both), some provide a wide range of services from bookkeeping to Tax Court representation. I suggest looking for those who prominently advertise themselves as specializing in your area (whatever your type of business is), and representation in front of the FTB. Specialists, especially experienced, cost much more. Keep in mind - you'll be getting what you paid for. Also, when you hire a \"\"big shot\"\" EA/CPA - check who's actually going to do the work, and how much oversight the \"\"big shot\"\" is going to provide. Anything else that I potentially missed? Any specific questions that I should ask EA or CPA on initial interview? For example, if my EA/CPA could also talk with auditor in case FTB would want to talk directly with taxpayer, if possible? Well, that's the point of representation - to represent. They should be talking to the FTB in your name. You should verify credentials (IRS for EAs, CA CBA for CPAs), make sure their license is current. You can ask them about their continued education and how much of it is dedicated to the CA State law and FTB regulations. Ask them about their experience with similar cases. Overall, a decently qualified tax professional should be able to handle a mail audit without an issue, in-person representation may be harder since it does not only require being competent in the tax law, but also have some people skills.\"",
"title": ""
},
{
"docid": "467390",
"text": "For Federal Return, Schedule H and its Instructions are a great start. You are the nanny's employer, and are responsible for FICA (social security and medicare) withholding, and also paying the employer portion. You will offer her a W4 so she can tell you how much federal and state tax to withhold. You'll use Circular E the employer's tax guide to calculate withholding. In January, you'll give her a W-2, and file the information with your own tax return. For State, some of the above applies, but as I recall, in my state, I had to submit withholding quarterly separate from my return. As compared to Federal, where I adjusted my own withholding so at year end the tax paid was correct. Unemployment insurance also needs to be paid, I believe this is state. This issue is non-political - I told my friends at the IRS that (a) the disparity between state and federal to handle the nanny tax was confusing for those of us trying to comply, and (b) even though we are treated as an employer, a 'guide to the nanny tax' would be helpful, a single IRS doc that doesn't mix non-nanny type issues into the mix. In the end, if a service is cost effective, go for it, your time is valuable, and thi is something that only lasts a few years.",
"title": ""
},
{
"docid": "237331",
"text": "If you're under audit - you should get a proper representation. I.e.: EA or CPA licensed in California and experienced with the FTB audit representation. There's a penalty on failure to file form 1099, but it is with the IRS, not the FTB. If I remember correctly, it's something like $50 or $100 per instance. Technically they can disqualify deductions claiming you paid under the table and no taxes were paid on the other side, however I doubt they'd do it in a case of simple omission of filing 1099 forms. Check with your licensed tax adviser. Keep in mind that for the IRS 2011 is now closed, since the 3-year statute of limitations has passed. For California the statute is 4 years, and you're almost at the end of it. However since you're already under audit they may ask you to agree to extend it.",
"title": ""
},
{
"docid": "204703",
"text": "The request for your parent's income comes from Form 8615, Tax for Certain Children Who Have Unearned Income. I typically see this form appear as I'm doing my daughter's taxes and start to enter data from stock transactions. In other words, your earned income is your's. But if you are a dependent, or 'can be,' the flow avoids the potentially lucrative results from gifting children appreciated stock, and have them take the gain at their lower, potentially zero cap gain rate. I suggest you grab a coffee and thumb through Pub 929 Tax Rules for Children and Dependents to understand this better. From page 14 of the linked doc - Parent's return information not available. If a child can’t get the required information about his or her parent's tax return, the child (or the child's legal representative) can request the necessary information from the Internal Revenue Service (IRS). How to request. After the end of the tax year, send a signed, written request for the information to the Internal Revenue Service Center where the parent's return will be filed. (The IRS can’t process a request received before the end of the tax year.) It also suggests that you file for an extension for the due date of your return. Include payment for the tax you expect to pay, say by plugging in $200K for parent income as an estimate. My parents' accountant tells them I do not need it. Well, a piece of software told you that you do, and 3 people on line who collectively qualify as experts documented why. (Note, I am not full of myself. This board operates via the wisdom of crowds. Members DStanley, and Ben Miller, commented and edited to help me form a well documented response that would be tough to argue against.)",
"title": ""
},
{
"docid": "357481",
"text": "\"Sue the debt collectors in small claims court. There are several example stories around the internet, but this is a well written one from the consumerist. If your phone is a cell phone: \"\"it is against the law for a company to leave a pre-recorded message on your cell phone.\"\" In fact, the call frequency increased once they realized they had reached a live person. I called each of these companies multiple times, and though I was given assurances each time that my number would be taken off of their lists, the calls continued, morning, noon and night. At my wits end, I decided the only way to have the harassing calls stop was to file suits against the collection companies. It's very important to understand that it is against the law for a company to leave a pre-recorded message on your cell phone. Armed with this knowledge, I filed suit against several of the collection companies. I filed in small claims court so I did not need to hire an attorney, and the process was as simple as completing a paragraph on a complaint form. For evidence, I had over a hundred Google Voicemail transcripts showing the times the companies called and the text of the pre-recorded messages. Mysteriously, the calls all stopped immediately on the same date the collection companies received the certified letters stating they were being sued. Then a new flurry of calls began pouring in. This time it was their attorneys. The attorneys representing these out of state collection companies were all desperate to settle out of court. hey did not want to incur the expense of traveling for court or hiring a local law firm who wasn't on retainer. They also understood they had no justifiable defense for the calls. To make a long story short, so far I have successfully sued 3 of these collection companies and settled for more than $5,000 out of court. All it cost me was $35 and 20 minutes per suit. Making these companies pay is the only incentive for them to stop their illegal and harassing practices. If more consumers knew their rights and actually took a few minutes to stand up for them, it would become less profitable for these companies to conduct business the way they do now. -Source And whether you have a cell phone or land line, It is illegal for the debt collectors to tell you they are calling to collect a debt for someone else under the Fair Debt Collection Practices Act (wikipedia, ftc docs). What Remedies Are Available If The Debt Collector Violates The Law Under the Fair Debt Collection Practices Act, you have the right to sue a debt collector in state or federal court within one year from the date of the violation. If you win, you may recover damages in the amount of any losses you suffered as a result of the violation, plus an additional amount of up to $1,000.00. You may also be able to recover court costs and attorney fees. If the same debt collector has engaged in unlawful conduct with a number of consumers, it may be possible to find a lawyer who will file a class action lawsuit. -Source With regard to whether you can sue under FDCPA if you are not the debtor, one FDCPA lawyer (take with grain of salt) says yes: Did you know that it doesn't matter if you owe the account the debt collector is calling you about or not? If a debt collector violates the FDCPA (the federal Fair Debt Collection Practices Act, 15 USC 1692 et. seq.) that debt collector could be liable to pay you statutory damages, actual damages, attorney's fees, and court costs. -Source\"",
"title": ""
},
{
"docid": "382712",
"text": "\"The seriousness of your situation depends on whether your girlfriend was owed a refund for each tax return she failed to file, or whether she owed additional money. If she owed money on one or more of the tax returns she failed to file, stop! It is time to consult a lawyer. At the very least, you need to contact an accountant who specialises in this sort of thing. She will owe interest and penalties, and may be liable for criminal prosecution. There are options available and lawyers who specialise in this sort of thing (e.g. this one, from a simple google search). If she is in this position, you need professional help and you need it soon, so you can make a voluntary disclosure and head off criminal prosecution. Assuming the taxes are fairly simple, you are likely looking at a few thousand dollars, but probably less than $7,500, for professional help. There will be substantial penalties assessed as well, for any taxes owing. If you wait until the CRA starts proceedings, you are most likely looking at $10,000 to $50,000, assuming the matter is not too complicated, and would be facing the possibility of a jail term not exceeding five years. If she was due a refund on every single one of the tax returns she failed to file, or at least if she did not owe additional money, you are probably in a situation you can deal with yourself. She will want to file all of the tax returns as soon as possible, but will not be assessed a penalty. I have personally filed taxes several months late a number of times, when I was owed a refund. You may still want to consider professional help, but it is probably not necessary. Under no circumstances should she allow her father near her finances again, ever. You should also be careful to trust any responses to this question, including my response, because we are unlikely to be professional accountants (I certainly am not). You are well outside the abilities of an H&R Block \"\"accountant\"\" in this matter and need a real certified accountant and/or a lawyer who specialises in Failure To File cases.\"",
"title": ""
},
{
"docid": "37327",
"text": "I was in a similar (but not quite as bad situation) a couple years ago, and I had a stroke of luck that helped me, but your friend might be able to force a similar situation. My parents refused to take out the huge parent loan (understandably so), but my dad made enough money that I wasn't eligible for much aid. My stroke of luck came when they got divorced; I could refile my FAFSA with only one parent (using my mom with very little income), my aid shot through the roof and nearly covered my undergrad (this happened in California, I don't know if this works in other states). My advice for your friend would be to take the 6 units/part time job option, but do what she can to earn enough to pay her own rent/food/other bills. I think the requirement for filing as an independent is that you supply >50% of your own income. It won't kick in right away, but for next school year this would end up getting her a lot more money from the state/federal governments. For me it was enough to cover my school, food, rent, gas, car payment, and still have a little left over. (I don't know if this is still possible, and I know it doesn't work for graduate school, or if it applies to every state. It might be an option worth pursuing though)",
"title": ""
},
{
"docid": "166522",
"text": "\"I had about $16k in student loans. I defaulted on the loans, and they got > passed to a collection type agency (OSCEOLA). These guys are as legitimate as a collection agency can be. One thing that I feel is very sketchy is when they were verifying my identity they said \"\"Does your Social Security Number end in ####. Is your Birthday Month/Day/Year.\"\" That is not sketchy. It would be sketchy for a caller to ask you to give that information; that's a common scheme for identity theft. OSCEOLA are following the rules on this one. My mom suggested I should consider applying for bankruptcy Won't help. Student loans can't be discharged in bankruptcy. You have the bankruptcy \"\"reform\"\" act passed during the Bush 43 regime for that. The loan itself is from school. What school? Contact them and ask for help. They may have washed their hands of your case when they turned over your file to OSCEOLA. Then again, they may not. It's worth finding out. Also, name and shame the school. Future applicants should be warned that they will do this. What can I do to aid in my negotiations with this company? Don't negotiate on the phone. You've discovered that they won't honor such negotiations. Ask for written communications sent by postal mail. Keep copies of everything, including both sides of the canceled checks you use to make payments (during the six months and in the future). Keep making the payments you agreed to in the conversation six months ago. Do not, EVER, ignore a letter from them. Do not, EVER, skip going to court if they send you a summons to appear. They count on people doing this. They can get a default judgement if you don't show up. Then you're well and truly screwed. What do you want? You want the $4K fee removed. If you want something else, figure out what it is. Here's what to do: Write them a polite letter explaining what you said here. Recount the conversation you had with their telephone agent where they said they would remove the $4K fee if you made payments. Recount the later conversation. If possible give the dates of both conversations and the names of the both agents. Explain the situation completely. Don't assume the recipient of your letter knows anything about your case. Include evidence that you made payments as agreed during the six months. If you were late or something, don't withhold that. Ask them to remove the extra $4K from your account, and ask for whatever else you want. Send the letter to them with a return receipt requested, or even registered mail. That will prevent them from claiming they didn't get it. And it will show them you're serious. Write a cover letter admitting your default, saying you relied on their negotiation to set things straight, and saying you're dismayed they aren't sticking to their word. The cover letter should ask for help sorting this out. Send copies of the letter with the cover letter to: Be sure to mark your letter to OSCEOLA \"\"cc\"\" all these folks, so they know you are asking for help. It can't hurt to call your congressional representative's office and ask to whom you should send the letter, and then address it by name. This is called Constituent Service, and they take pride in it. If you send this letter with copies you're letting them know you intend to fight. The collection agency may decide it's not worth the fight to get the $4K and decide to let it go. Again, if they call to pressure you, say you'd rather communicate in writing, and that they are not to call you by telephone. Then hang up. Should I hire a lawyer? Yes, but only if you get a court summons or if you don't get anywhere with this. You can give the lawyer all this paperwork I've suggested here, and it will help her come up to speed on your case. This is the kind of stuff the lawyer would do for you at well over $100 per hour. Is bankruptcy really an option Certainly not, unfortunately. Never forget that student lenders and their collection agencies are dangerous and clever predators. You are their lawful prey. They look at you, lick their chops, and think, \"\"food.\"\" Watch John Oliver's takedown of that industry. https://www.youtube.com/watch?v=hxUAntt1z2c Good luck and stay safe.\"",
"title": ""
},
{
"docid": "15319",
"text": "\"3) NOT to claim her as my dependent. No additional tax return (since she is NOT my dependent), but also no penalty. My end of year balance would be $0 No. Not claiming her as a dependent does not save you from being responsible for her penalty. You are responsible for her penalty if she is your dependent (i.e. she meets the conditions for being your dependent), regardless of whether you claim her on your tax return or not. If you have the option of claiming her or not, then she is your dependent, and you are responsible for her penalty. 26 CFR 1.5000A-1(c)(2)(i): For a month when a nonexempt individual does not have minimum essential coverage, if the nonexempt individual is a dependent (as defined in section 152) of another individual for the other individual's taxable year including that month, the other individual is liable for the shared responsibility payment attributable to the dependent's lack of coverage. An individual is a dependent of a taxpayer for a taxable year if the individual satisfies the definition of dependent under section 152, regardless of whether the taxpayer claims the individual as a dependent on a Federal income tax return for the taxable year. [...] Form 1040 instructions, Line 61: [...] If you had qualifying health care coverage (called minimum essential coverage) for every month of 2015 for yourself, your spouse (if filing jointly), and anyone you can or do claim as a dependent, check the box on this line and leave the entry space blank. Otherwise, do not check the box on this line. If you, your spouse (if filing jointly), or someone you can or do claim as a dependent didn’t have coverage for each month of 2015 you must either claim a coverage exemption on Form 8965 or report a shared responsibility payment on line 61. [...] So you cannot check the box and must report exemptions for your sister, or report a shared responsibility payment. Form 8965 instructions, Definitions, \"\"Tax household\"\": For purposes of Form 8965, your tax household generally includes you, your spouse (if filing a joint return), and any individual you claim as a dependent on your tax return. It also generally includes each individual you can, but don't, claim as a dependent on your tax return. [...] Your sister is part of your tax household regardless of whether you claim her, and you must compute her shared responsibility payment for any months she did not have insurance and did not qualify for an exemption.\"",
"title": ""
},
{
"docid": "162405",
"text": "I hate apples business practice down to the core, but whenever a not-so-tech-savvy friend or older gentleman/lady asks me what I think about Apple,...I cite their customer service. A lot of the other companies out there either require a million dollar service package, or you are on the phone with a call center in India. I don't mind this myself as I love the freedom it gives me over Apple (Hell, none of my software/hardware (except my laptop) is an OEM package)...but for an older lady who just cant seem to figure out how to get her email open...an apple care center (or whatever they call them, genius bars?) down the road is a fantastic option.",
"title": ""
},
{
"docid": "446628",
"text": "Does this technically mean that she has to pay AMT on $400,000? Yes. Well, not exactly 400,000. She paid $1 per share, so 390,000. And if so, is %28 the AMT for this sum? (0.28 * $400,000 = $112,000)? Or does she have to include her salary on top of that before calculating AMT? (Suppose in the fake example that her salary is $100,000 after 401k). All her income is included in calculating the AMT, minus the AMT exemption amount. The difference between the regular calculated tax and the calculated AMT is then added to the regular tax. Note that some deductions allowed for the regular calculation are not allowed for the AMT calculation. How does California state tax come into play for this? California has its own AMT rules, and in California any stock option exercise is subject to AMT, unless you sell the stock in the same year. Here's a nice and easy to understand write up on the issue from the FTB. When would she have to pay the taxes for this huge AMT? Tax is due when income is received (i.e.: when you exercise the options). However, most people don't actually pay the tax then, but rather discover the huge tax liability when they prepare to submit their tax return on April 15th. To avoid that, I'd suggest trying to estimate the tax and adjust your withholding using form W4 so that by the end of the year you have enough withheld. Suppose in the worst case, the company goes completely under. Does she get her massive amounts of tax back? Or if it's tax credit, where can I find more info on this? That would be capital loss, and only up to $3K a year of capital loss can be deducted from the general income. So it will continue offsetting other capital gains or being deducted $3K a year until it all clears out. Is there any way to avoid this tax? (Can she file an 83b election?) You asked and answered. Yes, filing 83(b) election is the way to go to avoid this situation. This should be done within 30 days of the grant, and submitted to the IRS, and a copy attached to the tax return of the grant year. However, if you're considering exercise - that ship has likely sailed a long time ago. Any advice for Little Susie on how she can even afford to pay that much tax on something she can't even sell anytime soon? Don't exercise the options? Should she take out a loan? (e.g. I've heard that in the extreme case, you can find angel investors who are willing to pay all your taxes/strike price, but want 50% of your equity? I've also heard that you can sell your illiquid shares on SecondMarket?) Is she likely to get audited by IRS for pulling something like this? You can take a loan secured by shares you own, there's nothing illegal in it. If you transfer your shares - the IRS only cares about the taxes being paid, however that may be illegal depending on the terms and the conditions of the grant. You'll need to talk to a lawyer about your situation. I suggest talking to a licensed tax adviser (EA/CPA licensed in your State) about the specifics concerning your situation.",
"title": ""
},
{
"docid": "324417",
"text": "\"**Reposted so you don't have to look at silly GIFs for 50% of the article.** Sophie is a physical penetration tester and information security consultant. She specializes in social engineering security assessments including physical, voice (vishing) and text (phishing). She consults in remediation and prevention of security incidents through creation of policy and procedures, as well as customized training for your individual office culture. Prior to working in infosec, Sophie was a journalist, photographer, and a mom. Hello! My name is Sophie and I break into buildings. I get paid to think like a criminal. Organizations hire me to evaluate their security, which I do by seeing if I can bypass it. During tests I get to do some lockpicking, climb over walls or hop barbed wire fences. I get to go dumpster diving and play with all sorts of cool gadgets that Q would be proud of. But usually, I use what is called social engineering to convince the employees to let me in. Sometimes I use email or phone calls to pretend to be someone I am not. Most often I get to approach people in-person and give them the confidence to let me in. My frequently asked questions include: What break-in are you most proud of? What have you done for a test that you were the most ashamed of? What follows is the answer to both of these questions. A few months ago, a client had hired me to test two of their facilities. A manufacturing plant, plus data center and office building nearby. First step: open source intelligence, or OSINT. I look at maps, satellite images, study what I can of their delivery and supply schedules, and so on. The manufacturing facility looked like a prison. No windows, heavy iron gates, no landscaping. Generally a monstrosity of architecture. This facility had armed guards, badge readers, biometric security controls and turnstiles at every entrance. I remember thinking, \"\"It's got to be hell to work in there. I wonder if I can use that…\"\" One thing was for sure… The chances of tailgating (following behind an employee with valid credentials) into this building were next to non-existent. I was going to have to get down and dirty with my social engineering. First stop: LinkedIn. Your LinkedIn is my best friend. The more information you have on your LinkedIn, the more options I have. I have several fake LinkedIn profiles that you are probably connected to. I scour profiles of employees who work at these facilities, and cross-reference them to other social media sites. And I find a lovely young woman who I'm going to call Mary. Mary was a brand-new hire working as an assistant at the manufacturing facility. Mary had a public Facebook account too. On Mary's public Facebook account, she documented all of her family's adventures. Side note: Now I know where Mary went to high school, her mother's maiden name, the names of her pets, etc. Answers to those \"\"security questions\"\" you use to reset your passwords are very easy to find if you aren't careful with that information. Not to mention that now I know where Mary works, where her kids go to school, where they vacation…I could go on. Scary stuff. This is not an advanced investigation. I'm not a private investigator and I don't have the resources of the NSA. But I can do a lot of damage with simple methods. Most notably to me, there were photos Mary posted of her time volunteering with a certain maternity support center. Her passion for children and caring new moms was very plain. So of course, I took advantage of it. For this assessment I played two roles. For the first, I spoofed my phone number to make it look like it was coming from the company's headquarters. I called the front desk of the manufacturing facility and was transferred to Mary. \"\"Hi Mary!\"\" I said, \"\"My name is Barbara.\"\" \"\"I am a project coordinator with facilities management. We are renovating a few of our facilities. We are sending an interior designer out to you tomorrow so she can put together proposals to update your space!\"\" Mary replied, \"\"Well that's great! But why the short notice?\"\" I could feel her getting suspicious, so I pulled out my trump card… *Sigh* \"\"Well Mary… You really should have heard from me sooner. I've just been so overloaded at work…I feel like I can't catch up, and to top it off the baby is due in 6 weeks. If my boss finds out I messed this up he's going to flip.\"\" I was really getting into this, voice shaking. (Yes, I know, I'm a terrible human being.) She cut me off, \"\"Oh hunny, hunny it's ok. We will work this out! Tell me about the baby! Is it your first? Boy or girl?!\"\" Our Mary was committed at this point. Not because she is stupid, but because she is a good person. She wanted to help me. We talked babies and birth plans for a while (never pick a pretext you can't speak about at length.) Mary took down the name of the \"\"designer\"\" who was coming by the next day and we said our goodbyes. Mary could have saved her company a lot of heartache by simply verifying that I was who I claimed to be. (Just to be clear here, I would never give out Mary's real identity. I'm not totally heartless. This could have happened to anyone. She has not been fired.) I showed up the next day as \"\"Claire\"\" with a fictional architecture firm that I had made business cards and a website for. My alter-ego Barb had done most of the leg work for me. When I arrived, Mary and her boss were waiting for me with smiles. I shook hands all around and handed them the business card I printed out the night before. I was given a visitor badge and the red carpet was rolled out. I gained rapport with the staff there by asking them to tell me what they wanted in an office space. They were so excited. I might have claimed to be on the team that put together the Google offices…(Yes, I am HORRIBLE. This is my inner demon child.) \"\"You want a standing desk? New chairs over here?! Ergonomic keyboards for everyone! Let's look at swatches!\"\" We became best buds. I was given complete and unaccompanied access to the facility where I stayed for several hours. I gained network access and stole several thousands of dollars in physical primitives by picking my way through cheap locks (credit to Deviant Ollam for the rad lockpicking animations.) This client had been pretty confident that I wouldn't get into either facility, much less be able to hit both in a short time span. So the timeline was left to my discretion, but it was assumed that I would need to fly to the area twice. I didn't see the need in burdening them with two round-trip expenses. I went back to Mary's office and said, \"\"Well I think I have what I need from here. How do I get to the office center?\"\" She looked at her watch and said, \"\"It's almost lunch time. I'll take you there!\"\" A whole group of us piled into the parking lot, and they took me to a nearby taco shop. That's right. My Marks took me to get tacos… I love my job. After lunch they drove me to the offices and a few of them came in with me to show me around. I took FOREVER looking around this office space, and eventually they said their goodbyes because they had to go back to work. They had a strict policy of escorting visitors. But I had been seen walking around with trusted insiders so no one questioned me. I was free to take my time. I made myself at home. My main objective at this site was to weasel my way into private corner offices. When I accomplished my goals, I tracked down my point of contact's office. This is the man who hired me in the first place. This is the best part of every job. Steve was there, hard at work when I disturbed his groove by knocking on the door. He glanced up, \"\"Hi there, can I help you?\"\" I smiled. \"\"Hi Steve! I'm Sophie from Sincerely Security. It's nice to meet you in-person!\"\" I will never forget the look on his face… Pure gold. \"\"Who?.... Wait, what? How? How did you get in here?!\"\" We stayed in his office and talked for a long time. I went over exactly the steps that could have prevented my success. First of all, the desire to help others is human and natural. We don't want to discourage that. Second, I'm sure they did have some sort of policy that required visitors to check in showing government issued identification, but they weren't following it. We also need to post by every computer, phone and door: \"\"TRUST, BUT VERIFY.\"\" An employee who does their homework can ruin my day. Third, if it seems too good to be true, it probably is. Is your company going to hire the team who designed Google's offices? Magic 8 ball says no. Lastly, the team who took me to the second location should have found someone else to escort me through the building. I've been doing this job for a couple years now, and almost every job is a variant of this story. Very rarely do I go through an entire assessment without some sort of social engineering. There are ways to protect yourself and your company from attacks like this. I think it starts by sharing stories like these, and educating and empowering each other to be vigilant.\"",
"title": ""
},
{
"docid": "34338",
"text": "\"If you live outside the US, then you probably need to deal with foreign tax credits, foreign income exclusions, FBAR forms (you probably have bank account balances enough for the 10K threshold) , various monsters the Congress enacted against you like form 8939 (if you have enough banking and investment accounts), form 3520 (if you have a IRA-like local pension), form 5471 (if you have a stake in a foreign business), form 8833 (if you have treaty claims) etc ect - that's just what I had the pleasure of coming across, there's more. TurboTax/H&R Block At Home/etc/etc are not for you. These programs are developed for a \"\"mainstream\"\" American citizen and resident who has nothing, or practically nothing, abroad. They may support the FBAR/FATCA forms (IIRC H&R Block has a problem with Fatca, didn't check if they fixed it for 2013. Heard reports that TurboTax support is not perfect as well), but nothing more than that. If you know the stuff well enough to fill the forms manually - go for it (I'm not sure they even provide all these forms in the software though). Now, specifically to your questions: Turbo tax doesn't seem to like the fact that my wife is a foreigner and doesn't have a social security number. It keeps bugging me to input a valid Ssn for her. I input all zeros for now. Not sure what to do. No, you cannot do that. You need to think whether you even want to include your wife in the return. Does she have income? Do you want to pay US taxes on her income? If she's not a US citizen/green card holder, why would you want that? Consider it again. If you decide to include here after all - you have to get an ITIN for her (instead of SSN). If you hire a professional to do your taxes, that professional will also guide you through the ITIN process. Turbo tax forces me to fill out a 29something form that establishes bonafide residency. Is this really necessary? Again in here it bugs me about wife's Ssn Form 2555 probably. Yes, it is, and yes, you have to have a ITIN for your wife if she's included. My previous state is California, and for my present state I input Foreign. When I get to the state tax portion turbo doesn't seem to realize that I have input foreign and it wants me to choose a valid state. However I think my first question is do i have to file a California tax now that I am not it's resident anymore? I do not have any assets in California. No house, no phone bill etc If you're not a resident in California, then why would you file? But you might be a partial resident, if you lived in CA part of the year. If so, you need to file 540NR for the part of the year you were a resident. If you have a better way to file tax based on this situation could you please share with me? As I said - hire a professional, preferably one that practices in your country of residence and knows the provisions of that country's tax treaty with the US. You can also hire a professional in the US, but get a good one, that specializes on expats.\"",
"title": ""
},
{
"docid": "520395",
"text": "\"I've received letters notifying me of data breaches in the past. In the end, I've never signed up for the offered protection service, figuring if \"\"they\"\" can hack Target or ADP or the IRS, they can hack anybody, like... Equifax. And now Equifax has been hacked. My family's Social Security Numbers were stolen from a hospital database. I think that information, plus public information was used to gain further data from the IRS FAFSA tool. (we got a letter from the IRS). Ultimately, fraudsters used whatever data they had to file a tax return with the IRS and with the Cali FTB (we don't and never have lived in California). We got letters from both, and managed to stop the fraud before it really impacted us...other than having to file a paper tax form this past tax season. Anyway... in a world where Equifax gets hacked: the only solution is: I don't bother with the crazy password schemes you talk about... I have a few different passwords I use, but most my investment accounts use the same username and password. It's all about risk. Bruce Schneier says the same thing. The amount to spend on security should depend on what you're trying to protect. I don't care much if somebody gets into my google account, because I have a google account just because I have to. I barely use it at all. Similarly my yahoo account. My yahoo account uses my \"\"insecure password\"\", and my investment accounts use my \"\"secure password\"\". Credit Card info? Meh. Unless they get into the credit card company database, which undoubtedly has my Social Security Number, it's not that big of a deal. Yeah, they can make fraudulent charges, but there are legal protections, so in theory I can't be out any money. So think this way: what's the risk, and what's the appropriate level of effort to take to mitigate that risk.\"",
"title": ""
},
{
"docid": "342400",
"text": "Look I'm up for a dialogue, but I'd appreciate civility. If you look back at my responses on this post I've said multiple times that I'm willing to help people who help themselves. I'm also pointing out that 1.) this article 'slavery' aspect is off and 2.) I'm not 100% convinced she is doing all she can to further better herself (maybe she is but the article didn't convince me). I've said before I give her props for getting her ass off, good on her. And I'm all for helping out people (for a limited time) who actually deserve it and have actually worked hard for it. In the lead featured in the article sounds like she would be a very very good candidate. I am a generous person, I want to help people and I'm willing to do so. They just need to want help. My generosity ends when it becomes mandatory to support anyone who has made any number of bad decisions and is not deserving of my help (we can talk about who deserves help in more detail anytime). Should I support a family of people in which the parents keep pumping out kids, and the mom is a stat at home mom and the dad works at a slightly above minimum wage? No! Should I support single mom who chooses not to work, and mooches off friends and family? No Both of these cases may seem cherry picked, and while they are to an extent they are both real cases that I've/a personal friend have witnessed.",
"title": ""
},
{
"docid": "133235",
"text": "\"Do I understand correctly, that we still can file as \"\"Married filing jointly\"\", just add Schedule C and Schedule SE for her? Yes. Business registration information letter she got once registered mentions that her due date for filing tax return is January 31, 2016. Does this prevent us from filing jointly (as far as I understand, I can't file my income before that date)? IRS sends no such letters. IRS also doesn't require any registration. Be careful, you might be a victim to a phishing attack here. In any case, sole proprietor files a regular individual tax return with the regular April 15th deadline. Do I understand correctly that we do not qualify as \"\"Family partnership\"\" (I do not participate in her business in any way other than giving her money for initial tools/materials purchase)? Yes. Do I understand correctly that she did not have to do regular estimated tax payments as business was not expected to generate income this year? You're asking or saying? How would we know what she expected? In any case, you can use your withholding (adjust the W4) to compensate.\"",
"title": ""
},
{
"docid": "169723",
"text": "I agree with mhoran_psprep's answer, but would like to add a few additional points to consider. TurboTax and the professional it will send to represent you in case of a tax audit have no more information about your tax return than what you entered into the program. Now, there are three (or four) different kinds of audits. The correspondence audit is the most common kind where IRS sends a letter requesting copies of documents supporting a deduction or tax credit that you have claimed. Representation is hardly necessary in this case. The office audit is more serious where you have to make an appointment and go to the local IRS office with paperwork that the examining agent needs to see physically, and to answer questions, etc. It would be better to be accompanied by a representative at these meetings. But, office audits are not as common as correspondence audits, and, because they are expensive for the IRS, usually occur when the IRS is fairly sure of recovering a substantial sum of money. If you have been cutting corners and pushing the envelope in taking large enough deductions to make it worthwhile for the IRS to go after you, you probably should not have been using TurboTax to file your income tax return but should have been using an accountant or tax preparer, who would be representing you in case of an audit. If the reason that you used TurboTax is that no accountant was willing to prepare a tax return with the deductions that you wished to claim, I doubt that having TurboTax's representative with you when you go to the IRS office will help you all that much. An example of a field audit is when the IRS agent comes to your home to see if you actually have a space set aside to use exclusively as your home office as you claimed you did etc. A Taxpayer Compliance Measurement Program (TCMP) audit is where the IRS randomly chooses returns for statistical checks that taxpayers are complying with the regulations. The taxpayer has to prove every line of the return. You claim to be filing as Married Filing Jointly? Bring in your marriage certificate. Submit birth certificates and Social Security cards of your dependent children. And so on. Yes, having TurboTax represent you for only $49.95 will help, but not if you are not married and cannot provide the IRS with a marriage certificate etc. So, pay the fee for peace of mind if you like, and as insurance as littleadv suggests. But be sure you understand what you might be getting for the money. Most tax returns selected for audit are selected for what the IRS believes are good reasons, not at random. If what you said If my tax return is randomly selected for audit they will represent me. is interpreted literally, TurboTax will represent you only if your return is selected for examination under the TCMP program, not if it is selected for audit because the IRS believes that something is fishy about your return. And as always, you get what you pay for.",
"title": ""
},
{
"docid": "350972",
"text": "\"I'm working from 6am-2pm today (from home, since it's Saturday) and I'm on call from 2pm-4am tomorrow. If the phone rings at our company help desk at any time from 2pm-4am, I am expected to answer it or return the call promptly. I'm not paid for the entire time of 2pm-4am, but only for the time I'm \"\"on a call\"\" essentially. It was a shock when I found out that was the terms of the job (3 months in, there were dramatic changes in my schedule) and most of my friends seem to agree with me. Am I off base?\"",
"title": ""
},
{
"docid": "131926",
"text": "\"I agree about not wanting to get into your friend's personal business, and it's a scummy bill collector that repeatedly calls friends or family to track down a debtor. On the other hand, at least he's made it obvious he's calling about a debt as opposed to pretending to be tracking down your friend with some other pretext. Nevertheless, you want the calls to stop. Here are two suggestions: Perhaps, a small fib: \"\"The creep owes me money too! Grrr! Let me know when you find him!\"\" The bill collector probably won't call you again :-) Or, if you're like me and uncomfortable fibbing – even to a scummy bill collector! – then here's a more truthful yet direct approach: \"\"I told you already it's not my debt, it's none of my business, and that I want you to stop calling me. You have no right to harass me and if you call again I will involve the police. There will be no other warning.\"\" Then have the phone company block the bill collector's phone number from calling you.\"",
"title": ""
},
{
"docid": "521061",
"text": "\"This is exactly what I feel. Having doing tech support for offices, friends and family, it dawned on me that they had no one else to call. If Grandma calls \"\"Sony\"\" because she can't find her email, well then they tell her to call Microsoft. Then she calls Microsoft and it seems it's a hardware issue, they send her back to Sony. In the end, the customer doesn't fully understand why they are being sent back and forth, they just want it fixed, or a reason. Apple is almost completely vertically integrated, they can solve most of the problems or at least provide the illusion that the customer is being helped.\"",
"title": ""
},
{
"docid": "218986",
"text": "\"You don't have to hire a tax consultant, there is a number of companies who sell software (installable or web-based) that helps you do it by asking for all relevant data interview-style. These typically cost between 15 and 25 EUR. I'm not sure whether any of them are available in English, but if you can read German well, you should be OK. taxback.com is in English, but to be honest it looks a bit dodgy to me. Now for your questions: are there some tricky fields (lines) that after filling in my taxes will be counted higher? This is rare, at least for employees you nearly always get something back. are there some tricky fields (lines) that after filling in my taxes could be counted lower? Not in general. Marriage is mentioned below, and otherwise it's all about individual deductibles. Ah, one important factor: if you have investment income and have not filed a Freistellungsauftrag with your bank, you can get some of the taxes by filling out the \"\"Anlage KAP\"\" form with data you got in the Jahressteuerbescheinigung from your bank. are there some flat-rates (Pauschals) that I could get advantage from? Absolutely. As an employee, the biggest factor is the Werbungskostenpauschale of (I think currently) 1000 EUR for general work-related expenses, which will be accepted without proof. If your expenses are higher than that and you file individual expenses, there are flat rates for work-related moving and for commuting distance. is it better to give a tax return together with my wife (who was only a girlfriend in 2013 living with me in one household) or to give it separately? It's not possible to do a joint tax filing for the time before your marriage. What you should consider is to apply for a different tax class from now on, if one of you earns significantly more than the other. when separately, do I have to fill her information in my tax return or can I just pretend there is nobody else in my apartment? As far as taxes are concerned, unmarried roommates are treated completely separately with one exception: only one of you can deduct service charges included in your rent. You have to get a Nebenkostenabrechnung from your landlord, and service charges, i.e. janitor, gardener, etc. should be marked separately. But this may not be worth bothering with, usually it results in a tax return of maybe 15 EUR. is there any guide in English that could be of help with filling in the tax return form? I couldn't find anything that looked really useful in a short search.\"",
"title": ""
},
{
"docid": "23675",
"text": "I asked my realtor, but she recommends to go with just one banker (her friend), and not to do any rate shopping. You need a new realtor. Anyone who would offer such advice is explicitly stating they are not advocating on your behalf. I'd do the rate shopping first. When you make an offer, once it's accepted, time becomes critical. The seller expects you to go to closing in so many days after signing the P&S. The realtor is specifically prohibited from pushing a particular lender on you. She should know better. In response to comment - Rate Shopping can be as simple as making a phone call, and having a detailed conversation. Jasper's list can be conveyed verbally. Prequalification is the next step, where a bank actually writes a letter indicating they have a high confidence you will qualify for the loan.",
"title": ""
},
{
"docid": "544663",
"text": "\"This is more of a long comment but may answer user's situation too. I have dealt with joint mortgages before in 3 states in the US. Basically in all three states if one party wants to sell, the home goes up for sale. This can be voluntary or it can go up via auction (not a great choice). In 2 of the 3 states the first person to respond to the court about the property, the other party pays all legal fees. Yes you read this right. In one case I had an ex who was on my mortgage, she had no money invested in the house ($0 down and still in college with no job). [If she wasn't on the mortgage I wouldn't have gotten loan - old days of dumb rules] When we split her lawyer was using the house as a way to extort other money from me. Knowing the state's laws I already filed a petition for the property but put it on hold with the clerk. Meaning that no one else could file but if someone tried mine would no longer be on hold. My ex literally spent thousands of dollars on this attorney and they wanted to sell the house and get half the money from the house. So sale price minus loan amount divided between us. This is the law in almost every state if there is no formal contract. I was laughing because she wanted what would be maybe 50-75K for paying no rent, no money down, and me paying for her college. Finally I broke her attorney down (I didn't lawyer up but had many friends who were lawyers advising). After I told her lawyer she wasn't getting anything - might have said it in not a nice way - her lawyer gave me her break down. To paraphrase she said, \"\"We are going to file now. My assistant is in the court clerk's office. You can tell the court whatever you want. Maybe they will give you a greater percentage since you put the money down and paid for everything but you are taking that chance. But you will pay for your lawyer and you will need one. And you will pay for me the entire time. And this will be a lengthy process. You would be better served to pay my client half now.\"\" Her office was about 2 blocks from court. I laughed at her and simply told her to have her assistant do whatever she wanted. I then left to go to clerk's office to take the hold off. She had beat me to the office (I moved my car out of her garage). By the time I got there she was outside yelling at her assistant, throwing a hissy fit, and papers were flying everywhere. We \"\"settled\"\" the next day. She got nothing other than the things she had already stolen from me. If I wouldn't have known about this loophole my ex would have gotten or cost me through attorney's fees around 40-50K for basically hiring a lawyer. My ex didn't really have any money so I am pretty sure lawyer was getting a percent. Moral of the story: In any contract like this you always want to be the one bringing in the least amount of money. There are no laws that I know of in any country where the person with the least amount on a contract will come out worse (%-wise). Like I said in the US the best case scenario that I know of for joint property is that the court pays out the stakeholder all of their contributions then it splits things 50/50. This is given no formal contract that the court upholds. Don't even get me started with hiring attorneys because I have seen the courts throw out so many property contracts it isn't even funny. One piece of advice on a contract if you do one. Make it open and about percentages. Party A contributes 50K, Party B 10K, Party A will pay this % of mortgage and maintenance and will get this % when home is sold. I have found the more specific things are the more loopholes for getting out of them. There are goofy ass laws everywhere that make no sense. Why would the person first filing get their lawyers paid for??? The court systems in almost all countries can have their comical corners. You will never be able to write a contract that covers everything. If the shower handle breaks, who pays for it? There is just too many one-off things with a house. You are in essence getting in a relationship with this person. I hear others say it is a business transaction. NO. You are living with this person. There is no way to make it purely business. For you to be happy with this outcome both of you must remain somewhat friends and at the very least civil with each other. To add on to the previous point, the biggest risk is this other person's character and state of mind. They are putting in the most money so you don't exactly have a huge money risk. You do have a time and a time-cost risk. Your time or the money you do have in this may be tied up in trying to get your money out or house sold. A jerk could basically say that you get nothing, and make you traverse the court system for a couple years to get a few thousand back. And that isn't the worst case scenario. Always know your worst case scenario. Yours is this dude is in love with you. When he figures out 2-3 years later after making you feel uncomfortable the entire time that you are not in love with him, he starts going nuts. So he systematically destroys your house. Your house worth plummets, you want out, you can't sell the house for price of loan, lenders foreclose or look to sue you, you pay \"\"double rent\"\" because you can't live with the guy, and you have to push a scooter to get to work. That is just the worst case scenario. Would I do this if I were 25 and had no family? Yea, why not if I trusted the other person and was friends with them? If it were just a co-worker? That is really iffy with me. Edit: Author said he will not be living with the person. So wording can be changed to say \"\"potentially\"\" in front of living with him in my examples.\"",
"title": ""
},
{
"docid": "115172",
"text": "I have been in a similar position for quite a while now and the only thing that seems to help is screening phone calls. I have a long list of collector numbers set to not ring on my phone. They can still leave a voice mail but they never do. As far as I know there aren't any laws that protect you from nuisance phone calls. FDCPA letters only apply to the debtor and the collector it is sent to it doesn't protect an unrelated third party from getting annoying phone calls. I have a feeling that sending FDCPA letters is just confirming that you probably are the debtor and prolong the collection calls.",
"title": ""
},
{
"docid": "324445",
"text": "\"Having worked in insurance, I can give you a few pointers. Firstly, state that you \"\"may have to complain\"\". Insurers hate complaints because they really complicate matters, are loads of work and must be tracked. I would advise not actually escalating it to a complaint until later as this may cause a delay as the actual process is quite convoluted. Mentioning the possibility of complaint sometimes makes people a bit more active. Try and resolve the issue, and if you aren't getting anywhere then make a complaint. Maintain a friendly, assertive, polite demeanor. If you get angry and aggressive you'll not likely get far. Remember that the people on the end of the phone are both human and more knowledgeable about insurance than you. You want them on your side, not against you. Make copious notes. If you can, record calls. If you are recording calls you will likely legally need to give them the option of not being recorded, so make sure you mention that you're recording each individual call as soon as you start speaking to the handler. Refer to your notes and make sure you carry out actions you say you will. If you spend a few days sending something you said you'd email over that day, and you then chase them a few days after that they may not have had the document through their workflow yet. It also engenders urgency if you're acting promptly, and suggests that you don't really care if you're taking your time. Get Names. This is an important step, as this gives the handler someone to talk to who may be familiar with your case. You may end up speaking to the same people more than once, so try and build a rapport if you do. \"\"I like this guy\"\" may lead to a bit more effort being put in, and a potentially better outcome. In my experience, GoSkippy can be a bit slow to respond to things, so you'll likely have to chase them up. If you chase them up and say \"\"I called on X date, discussing Y with Z and Z said they would do A, B and C. Has this been done yet?\"\" it looks better than saying \"\"I called about a week ago and spoke to one of your colleagues who said he'd do something for me. He's not done it, what's going on?\"\", As to a plan of action, I would split this into two points: Mis-sold policy and definition of commuting. Mis-sold policy - If they truly gave your wife two options, then they messed up. The standard 3 offered by goskippy are Social Domestic and Pleasure (SDP), SDP+Commuting, and SDP+C and Business use. Other companies sometimes roll commuting into SDP as standard. On the comparison sites however, there are usually the three separate options, and if you used one to set the policy up and clicked \"\"SDP Only\"\" then you may be in trouble. Social domestic and pleasure only DOES NOT include commuting. Whilst it is your responsibility to thoroughly check any documentation that comes through, it could be argued that if given two options between Business Use and SDP, then a reasonable person could be considered to assume that Goskippies definition of SDP did include commuting. Therefore, they need to prove to you that there were three options offered and that your wife specifically excluded commuting. IF they can't, then you should be able to argue that only two were offered and that commuting could have reasonably been assumed to be included. Use that term \"\"reasonable person\"\" btw, it's used in a lot of internal literature - at least at the insurer, I worked at. not commuting - Firstly, clarify their definition of \"\"commuting\"\". If your wife was on her way to work afterwards, then they may well consider she was commuting. For instance, at present, I drive from my house to my son's childminders, then to my wife's work and finally to mine. My commute could be argued to be 1 minute (my workplace is probably a minutes drive from my wife's, but I can't park in her car-park), but if I were to have an accident between my house and my son's childminder (~15 mins drive) the insurers would probably consider that commuting. If she was not on her way to work afterwards, and assuming your wife arranged her visit via text (or whatsapp, fb messenger or similar) you should easily be able to show that your wife had driven from a friends house to the childminder. If she was on a holiday day or was not working on that day, then that's also something you should be able to prove either with proof of her working pattern or proof of her holiday. If she doesn't have a job at all, then again, that's something that's provable. Proof reigns king in claims, so if you can prove certain key facts then you should be on to a winner.\"",
"title": ""
},
{
"docid": "221502",
"text": "I was in that same situation years ago with my parents. One way she could apply for a loan in her name without her parents is if she is not currently living with them she shouldn't need them to cosign if she doesn't have bad credit. But if she isn't living with them and they aren't financing her room and board they can't claim her as a dependent so if she really wants to stick it to them she can go and try to politely explain how the loans work and tell them if they don't cosign for her then she will apply on her own (which she can only do while not living with them I believe but not sure) and they will HAVE to STOP claiming her as a dependent on their taxes. If they don't agree she can put her foot down and force them to stop claiming her and tell them she will file her own application anyway and if they continue claiming her and get in trouble for it it's their own fault cause she warned them to stop first. They may agree to cosign rather than lose her as a dependent if it makes that big of a difference on their taxes, if they don't then she can forcefully punish them financially and their taxes will go up. Those were my choices when my parents refused to cosign for me to live at school but that was back in 1999-2000 and things may have changed since then, things also change state by state and I live in PA.",
"title": ""
},
{
"docid": "396792",
"text": "\"Paypal linked with my bank account. 1.Can I use my Saving bank account to receive payments from my clients? Or is it necessary to open a current account? Yes you can get funds into your savings account. However it is advisable to keep a seperate account as it would help with your IT Returns. 2.I will be paying a certain % as commission on every sales to a couple of sales guys (who are not my employees but only working on commission). Can I show this as an expense in my IT returns? As you are earning as freelancer, you are eligible for certain deductions like Phone calls, Laptop, other hardware, payments to partners. It is important that you maintain a book of records. An accountant for a small fee of Rs 5 K should be able to help you. In the Returns you have to show Net income after all these deductions, there is no place to enter expenses. 3.Since I will be receiving all the payments in Euros so am I falling under a category of \"\"Exporter of services\"\"? The work you are doing can be Free Lancing. 4.Do I need an Import Export Code (IEC) for smoothly running this small business? You can run this without one as Free lancing. IEC would be when you grow big and are looking for various benefits under tax and pay different taxes and are incorporated as a company.\"",
"title": ""
},
{
"docid": "520026",
"text": "You could do a voluntary repossession. While a repossession never looks good on your credit a voluntary repossession is slightly better. A good friend of mine had a situation like this about 11 years ago. She was in an accident didn't have replacement coverage insurance and was left with a large chunk of debt on a wrecked vehicle that she then rolled into a new car. In the end it came down to the simple fact that she could not afford a car loan on a vehicle that never was worth as much as she owed. Since the car was worth less than the loan she really couldn't sell it to fix the problem. She called and arranged a voluntary repossession. She stopped making payments, and parked the car till they came and picked it up. (Took about 4 months and 20 phone calls from her for them to come get it.) In the mean time, I purchased her a much older used but decent car for a couple thousand and she paid me back over the next year. The total she paid me back was less than the money she would have paid in the 4 months it took them to come get the car. In fact by the time they picked up the car she had paid back over half on the car I bought her. Yes the repossession did stay on her credit for seven years but during that time she was approved for a mortgage, cellphone plans, and credit cards etc. Therefore I don't know that it did that much damage to her credit. When her car was sold at auction by the repo company it sold for much less than the loan amount. Technically she was on the hook for the remaining amount. The outstanding balance on the loan was then sold several times to several different collection agencies. Over the years since then she has gotten letters every now and then demanding she pay the amount off, she ignores these. Most of these letters even included very favorable terms (full forgiveness for 20% of the amount) At this point the statute time has run out on the debt so there is no recourse for anyone to collect from her. The statute time limit varies from state to state. Some states it is as long as 10 years in others it is as short as 3 years. What this means is that counting from the date of the repossession, incurrance of debt, last payment, or agreement to pay whichever is later if the statute period has elapsed and the lender/collector has not filed a suit against you by the end of the period then they have effectively abandoned the debt and cannot collect. Find out what that period of time is in your state. If you can avoid the collection agencies till that period runs out you are scott free. You just have to make sure that you do not ever send them any money, or agree to pay them anything as this resets the calendar. If you do not want to wait for the calendar to run out if you wait long enough you will probably be offered favorable terms to pay only a fraction of the remaining amount, you just have to wait it out. Note, I normally would not endorse anyone not paying off their debts. However sometimes it is necessary and it is for this type of situation that we have things like this and bankruptcy.",
"title": ""
}
] |
815
|
Mutations in RIM1 decrease levels of IME1 RNA.
|
[
{
"docid": "8148304",
"text": "In the yeast Saccharomyces cerevisiae, genetic studies suggest that the RIM1 gene encodes a positive regulator of meiosis. rim1 mutations cause reduced expression of IME1, which is required for expression of many meiotic genes, and thus lead to a partial defect in meiosis and spore formation. We report the sequence of RIM1 and functional analysis of its coding region. The RIM1 gene product (RIM1) contains three regions similar to C2H2 zinc fingers. Serine substitutions for cysteine in each of the putative zinc fingers abolish RIM1 function. The carboxyl-terminus of RIM1 is enriched in acidic amino acids and is required for full RIM1 activity. RIM1 also contains two putative cAMP-dependent protein kinase (cAPK) phosphorylation sites. At one site, substitution of alanine for serine does not affect RIM1 activity; at the other site, this substitution impairs activity. This analysis of RIM1 suggests that the protein may function as a transcriptional activator. We have used the cloned RIM1 gene to create a complete rim1 deletion. This null allele, like previously isolated rim1 mutations, causes a partial meiotic defect. In addition to RIM1, maximum IME1 expression requires the MCK1 and IME4 gene products. Defects associated with rim1, mck1, and ime4 mutations in expression of a meiotic reporter gene (ime2-lacZ) and in sporulation are additive. These findings suggest that RIM1 acts independently of MCK1 and IME4 to stimulate IME1 expression.",
"title": "Molecular characterization of the yeast meiotic regulatory gene RIM1."
}
] |
[
{
"docid": "23604601",
"text": "The IME1 gene of Saccharomyces cerevisiae is required for initiation of meiosis. Transcription of IME1 is detected under conditions which are known to induce initiation of meiosis, namely starvation for nitrogen and glucose, and the presence of MATa1 and MAT alpha 2 gene products. In this paper we show that IME1 is also subject to translational regulation. Translation of IME1 mRNA is achieved either upon nitrogen starvation, or upon G1 arrest. In the presence of nutrients, constitutively elevated transcription of IME1 is also sufficient for the translation of IME1 RNA. Four different conditions were found to cause expression of Ime1 protein in vegetative cultures: elevated transcription levels due to the presence of IME1 on a multicopy plasmid; elevated transcription provided by a Gal-IME1 construct; G1 arrest due to alpha-factor treatment; G1 arrest following mild heat-shock treatment of cdc28 diploids. Using these conditions, we obtained evidence that starvation is required not only for transcription and efficient translation of IME1, but also for either the activation of Ime1 protein or for the induction/activation of another factor that, either alone or in combination with Ime1, induces meiosis.",
"title": "Post-transcriptional regulation of IME1 determines initiation of meiosis in Saccharomyces cerevisiae."
},
{
"docid": "19255949",
"text": "Mutations in the PARN gene (encoding poly(A)-specific ribonuclease) cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita, but how PARN deficiency impairs telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem cells (iPSCs) from patients with dyskeratosis congenita with PARN mutations, we show that PARN is required for the 3′-end maturation of the telomerase RNA component (TERC). Patient-derived cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3′ termini shows that PARN is required for removal of post-transcriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased proportion of oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results demonstrate a new role for PARN in the biogenesis of TERC and provide a mechanism linking PARN mutations to telomere diseases.",
"title": "Poly(A)-specific ribonuclease (PARN) mediates 3′-end maturation of the telomerase RNA component"
},
{
"docid": "33370",
"text": "Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioblastoma stem cells (GSCs). GSCs are regulated by molecular pathways distinct from the bulk tumor that may be useful therapeutic targets. We determined that A20 (TNFAIP3), a regulator of cell survival and the NF-kappaB pathway, is overexpressed in GSCs relative to non-stem glioblastoma cells at both the mRNA and protein levels. To determine the functional significance of A20 in GSCs, we targeted A20 expression with lentiviral-mediated delivery of short hairpin RNA (shRNA). Inhibiting A20 expression decreased GSC growth and survival through mechanisms associated with decreased cell-cycle progression and decreased phosphorylation of p65/RelA. Elevated levels of A20 in GSCs contributed to apoptotic resistance: GSCs were less susceptible to TNFalpha-induced cell death than matched non-stem glioma cells, but A20 knockdown sensitized GSCs to TNFalpha-mediated apoptosis. The decreased survival of GSCs upon A20 knockdown contributed to the reduced ability of these cells to self-renew in primary and secondary neurosphere formation assays. The tumorigenic potential of GSCs was decreased with A20 targeting, resulting in increased survival of mice bearing human glioma xenografts. In silico analysis of a glioma patient genomic database indicates that A20 overexpression and amplification is inversely correlated with survival. Together these data indicate that A20 contributes to glioma maintenance through effects on the glioma stem cell subpopulation. Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival. A20 anticancer therapies should therefore be viewed with caution as effects will likely differ depending on the tumor type.",
"title": "Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth"
},
{
"docid": "26495128",
"text": "B23 (NPM/nucleophosmin) is a multifunctional nucleolar protein and a member of the nucleoplasmin superfamily of acidic histone chaperones. B23 is essential for normal embryonic development and plays an important role in genomic stability, ribosome biogenesis, and anti-apoptotic signaling. Altered protein expression or genomic mutation of B23 is encountered in many different forms of cancer. Although described as multifunctional, a genuine molecular function of B23 is not fully understood. Here we show that B23 is associated with a protein complex consisting of ribosomal proteins and ribosome-associated RNA helicases. A novel, RNA-independent interaction between ribosomal protein S9 (RPS9) and B23 was further investigated. We found that S9 binding requires an intact B23 oligomerization domain. Depletion of S9 by small interfering RNA resulted in decreased protein synthesis and G(1) cell cycle arrest, in association with induction of p53 target genes. We determined that S9 is a short-lived protein in the absence of ribosome biogenesis, and proteasomal inhibition significantly increased S9 protein level. Overexpression of B23 facilitated nucleolar storage of S9, whereas knockdown of B23 led to diminished levels of nucleolar S9. Our results suggest that B23 selectively stores, and protects ribosomal protein S9 in nucleoli and therefore could facilitate ribosome biogenesis.",
"title": "Ribosomal protein S9 is a novel B23/NPM-binding protein required for normal cell proliferation."
},
{
"docid": "24705390",
"text": "BACKGROUND & AIMS Helicobacter pylori is an important etiologic factor in the development of gastric cancer. The aim of this study was to analyze the role of H. pylori infections in the induction of mutagenic events in gastric epithelial cells. The effect of a high-salt diet as a genotoxic risk factor was also investigated. METHODS Big Blue transgenic male mice (C57Bl/6) were inoculated with H. pylori (strain SS1) or Helicobacter felis (strain CS1) for 6 and 12 months. The frequency and spectrum of mutations at the stomach level were assessed. Inflammatory host response and inducible nitric oxide synthase (iNOS) expression by reverse-transcription polymerase chain reaction and immunohistochemistry analysis were also performed. RESULTS After 6 months, the gastric mutant frequency was 4-fold and 1.7-fold higher in mice infected with H. pylori and H. felis, respectively, than in uninfected mice. It was associated with a high frequency of transversions (AT --> CG and GC --> TA) known to result from oxidative damages. The Helicobacter-infected mice exhibited severe gastritis and a high level of iNOS messenger RNA expression. Hyperplasia developed 12 months after inoculation, and both the mutagenic effects and iNOS expression decreased in H. pylori- and H. felis-infected mice. No synergistic effects of a high-salt diet and Helicobacter infection were observed regarding the frequency of gastric mutation. CONCLUSIONS A direct gastric mutagenic effect due to H. pylori infection in the Big Blue transgenic mouse model has been shown 6 months after inoculation. This genotoxicity can be attributable to oxidative DNA damage involving the inflammatory host response.",
"title": "Chronic Helicobacter pylori infections induce gastric mutations in mice."
},
{
"docid": "7317051",
"text": "Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.",
"title": "Mutant KRAS is a druggable target for pancreatic cancer."
},
{
"docid": "15248287",
"text": "Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.",
"title": "Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival"
},
{
"docid": "25014337",
"text": "We previously identified a rare mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), I132M, which confers high-level resistance to the nonnucleoside RT inhibitors (NNRTIs) nevirapine and delavirdine. In this study, we have further characterized the role of this mutation in viral replication capacity and in resistance to other RT inhibitors. Surprisingly, our data show that I132M confers marked hypersusceptibility to the nucleoside analogs lamivudine (3TC) and tenofovir at both the virus and enzyme levels. Subunit-selective mutagenesis studies revealed that the mutation in the p51 subunit of RT was responsible for the increased sensitivity to the drugs, and transient kinetic analyses showed that this hypersusceptibility was due to I132M decreasing the enzyme's affinity for the natural dCTP substrate but increasing its affinity for 3TC-triphosphate. Furthermore, the replication capacity of HIV-1 containing I132M is severely impaired. This decrease in viral replication capacity could be partially or completely compensated for by the A62V or L214I mutation, respectively. Taken together, these results help to explain the infrequent selection of I132M in patients for whom NNRTI regimens are failing and furthermore demonstrate that a single mutation outside of the polymerase active site and inside of the p51 subunit of RT can significantly influence nucleotide selectivity.",
"title": "The human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor resistance mutation I132M confers hypersensitivity to nucleoside analogs."
},
{
"docid": "4409524",
"text": "In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal–fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.",
"title": "Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy"
},
{
"docid": "16172576",
"text": "BACKGROUND High genetic diversity at both inter- and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. METHODS AND PRINCIPAL FINDINGS We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. CONCLUSIONS AND SIGNIFICANCE Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.",
"title": "Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak"
},
{
"docid": "19828689",
"text": "Key features of diabetic nephropathy (DN) include the accumulation of extracellular matrix proteins such as collagen 1-alpha 1 and -2 (Col1a1 and -2). Transforming growth factor beta1 (TGF-beta), a key regulator of these extracellular matrix genes, is increased in mesangial cells (MC) in DN. By microarray profiling, we noted that TGF-beta increased Col1a2 mRNA in mouse MC (MMC) but also decreased mRNA levels of an E-box repressor, deltaEF1. TGF-beta treatment or short hairpin RNAs targeting deltaEF1 increased enhancer activity of upstream E-box elements in the Col1a2 gene. TGF-beta also decreased the expression of Smad-interacting protein 1 (SIP1), another E-box repressor similar to deltaEF1. Interestingly, we noted that SIP1 is a target of microRNA-192 (miR-192), a key miR highly expressed in the kidney. miR-192 levels also were increased by TGF-beta in MMC. TGF-beta treatment or transfection with miR-192 decreased endogenous SIP1 expression as well as reporter activity of a SIP1 3' UTR-containing luciferase construct in MMC. Conversely, a miR-192 inhibitor enhanced the luciferase activity, confirming SIP1 to be a miR-192 target. Furthermore, miR-192 synergized with deltaEF1 short hairpin RNAs to increase Col1a2 E-box-luc activity. Importantly, the in vivo relevance was noted by the observation that miR-192 levels were enhanced significantly in glomeruli isolated from streptozotocin-injected diabetic mice as well as diabetic db/db mice relative to corresponding nondiabetic controls, in parallel with increased TGF-beta and Col1a2 levels. These results uncover a role for miRs in the kidney and DN in controlling TGF-beta-induced Col1a2 expression by down-regulating E-box repressors.",
"title": "MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors."
},
{
"docid": "6315132",
"text": "We describe a case of severe neonatal anemia with kernicterus caused by compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1-null human. The phenotype of severe nonspherocytic hemolytic anemia, jaundice, hepatosplenomegaly, and marked erythroblastosis is more severe than that present in congenital dyserythropoietic anemia type IV as a result of dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found that human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell-cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control, and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis.",
"title": "KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome."
},
{
"docid": "711256",
"text": "Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation detection. To test whether EGFR analysis from RNA is less prone to interference from nontumour cells that have no or lower EGFR expression, we compared three methods (sequencing from cell-derived RNA versus sequencing and mass-spectrometric analysis from genomic DNA), in parallel, for EGFR mutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus 44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance, EGFR sequencing from RNA provided satisfactory detection of T790M (54.2%). These results demonstrated that EGFR sequencing using RNA as template greatly improves sensitivity for EGFR mutation detection from samples of MPE, highlighting RNA as the favourable source for analysing EGFR mutations from heterogeneous MPE specimens in NSCLC.",
"title": "RNA is favourable for analysing EGFR mutations in malignant pleural effusion of lung cancer."
},
{
"docid": "13108582",
"text": "Osteopontin (OPN), a key component of the extracellular matrix, is associated with the fibrotic process during tissue remodeling. OPN and the cytokine interleukin (IL)-18 have been shown to be overexpressed in an array of human cardiac pathologies. In the present study, we determined the role of IL-18 in the regulation of cardiac OPN expression and the subsequent interstitial fibrosis and diastolic dysfunction. We demonstrated parallel increases in IL-18, OPN expression, and interstitial fibrosis in murine models of left ventricular pressure and volume overload. Exogenous recombinant (r)IL-18 administered for 2 wk increased cardiac OPN expression, interstitial fibrosis, and diastolic dysfunction. Stimulation of the T helper (Th)1 lymphocyte phenotype with a selective toll-like receptor (TLR)9 agonist induced cardiac IL-18 and OPN expression, which was associated with increased cardiac fibrillar collagen concentrations and interstitial fibrosis resulting in diastolic dysfunction. rIL-18 induced OPN expression and protein levels in primary of cardiac fibroblast cultures. Conditioned media from TLR9-stimulated T lymphocyte cultures induced IL-18 and OPN expression in cardiac fibroblasts, while blockade of the IL-18 receptor with a neutralizing antibody abolished the increase in OPN expression. Furthermore, a mutation in the transcriptional factor interferon regulatory factor (IRF)1 or IRF1 small interfering RNA (siRNA) resulted in the decreased expression of IL-18 and OPN in cardiac fibroblasts. With pressure overload, IRF1-mutant mice showed downregulation of IL-18 and OPN expression in cardiac tissue, reduced cardiac fibrotic development, and increased left ventricular function compared with wild type. These results provide direct evidence that the induction of IL-18 regulates OPN-mediated cardiac fibrosis and diastolic dysfunction.",
"title": "IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice."
},
{
"docid": "12652963",
"text": "MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.",
"title": "miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA."
},
{
"docid": "17648235",
"text": "De-regulation of the wingless and integration site growth factor (WNT) signaling pathway via mutations in APC and Axin, proteins that target β-catenin for destruction, have been linked to various types of human cancer. These genetic alterations rarely, if ever, are observed in breast tumors. However, various lines of evidence suggest that WNT signaling may also be de-regulated in breast cancer. Most breast tumors show hypermethylation of the promoter region of secreted Frizzled-related protein 1 (sFRP1), a negative WNT pathway regulator, leading to downregulation of its expression. As a consequence, WNT signaling is enhanced and may contribute to proliferation of human breast tumor cells. We previously demonstrated that, in addition to the canonical WNT/β-catenin pathway, WNT signaling activates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in mouse mammary epithelial cells via epidermal growth factor receptor (EGFR) transactivation. Using the WNT modulator sFRP1 and short interfering RNA-mediated Dishevelled (DVL) knockdown, we interfered with autocrine WNT signaling at the ligand-receptor level. The impact on proliferation was measured by cell counting, YOPRO, and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay; β-catenin, EGFR, ERK1/2 activation, and PARP (poly [ADP-ribose]polymerase) cleavages were assessed by Western blotting after treatment of human breast cancer cell lines with conditioned media, purified proteins, small-molecule inhibitors, or blocking antibodies. Phospho-DVL and stabilized β-catenin are present in many breast tumor cell lines, indicating autocrine WNT signaling activity. Interfering with this loop decreases active β-catenin levels, lowers ERK1/2 activity, blocks proliferation, and induces apoptosis in MDA-MB-231, BT474, SkBr3, JIMT-1, and MCF-7 cells. The effects of WNT signaling are mediated partly by EGFR transactivation in human breast cancer cells in a metalloprotease- and Src-dependent manner. Furthermore, Wnt1 rescues estrogen receptor-positive (ER+) breast cancer cells from the anti-proliferative effects of 4-hydroxytamoxifen (4-HT) and this activity can be blocked by an EGFR tyrosine kinase inhibitor. Our data show that interference with autocrine WNT signaling in human breast cancer reduces proliferation and survival of human breast cancer cells and rescues ER+ tumor cells from 4-HT by activation of the canonical WNT pathway and EGFR transactivation. These findings suggest that interference with WNT signaling at the ligand-receptor level in combination with other targeted therapies may improve the efficiency of breast cancer treatments.",
"title": "Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation"
},
{
"docid": "12582729",
"text": "BACKGROUND Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2. METHODS AND RESULTS Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA. In silico analysis predicted that miR-92a could bind to the 3' untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow. CONCLUSIONS Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.",
"title": "Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a."
},
{
"docid": "42065070",
"text": "Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four mandrills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected mandrill. Two noninfected control animals were monitored in parallel. Blood and lymph nodes were collected at three time points before infection, twice a week during the first month, and at days 60, 180, and 360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 x 10(6) to 2 x 10(8) RNA equivalents/ml). Viremia then decreased 10- to 1,000-fold, reaching the viral set point between days 30 to 60 p.i. The levels during the chronic phase of infection were similar to that in the naturally infected donor mandrill (2 x 10(5) RNA equivalents/ml). The CD4(+) cell numbers and percentages in blood and lymph nodes decreased slightly (<10%) during primary infection, and CD8(+) cell numbers increased transiently. All values returned to preinfection infection levels by day 30 p.i. CD8(+) cell numbers or percentages, in peripheral blood and lymph nodes, did not increase during the 1 year of follow-up. In conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in mandrills. Despite high levels of viremia, CD4(+) and CD8(+) cell numbers remained stable in the post-acute phase of infection, raising questions regarding the susceptibility of mandrill T cells to activation and/or cell death in response to SIVmnd-1 infection in vivo.",
"title": "High levels of viral replication contrast with only transient changes in CD4(+) and CD8(+) cell numbers during the early phase of experimental infection with simian immunodeficiency virus SIVmnd-1 in Mandrillus sphinx."
},
{
"docid": "15692098",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.",
"title": "Hutchinson-Gilford progeria syndrome: review of the phenotype"
},
{
"docid": "24725136",
"text": "BACKGROUND The combination of ataxia and hypogonadism was first described more than a century ago, but its genetic basis has remained elusive. METHODS We performed whole-exome sequencing in a patient with ataxia and hypogonadotropic hypogonadism, followed by targeted sequencing of candidate genes in similarly affected patients. Neurologic and reproductive endocrine phenotypes were characterized in detail. The effects of sequence variants and the presence of an epistatic interaction were tested in a zebrafish model. RESULTS Digenic homozygous mutations in RNF216 and OTUD4, which encode a ubiquitin E3 ligase and a deubiquitinase, respectively, were found in three affected siblings in a consanguineous family. Additional screening identified compound heterozygous truncating mutations in RNF216 in an unrelated patient and single heterozygous deleterious mutations in four other patients. Knockdown of rnf216 or otud4 in zebrafish embryos induced defects in the eye, optic tectum, and cerebellum; combinatorial suppression of both genes exacerbated these phenotypes, which were rescued by nonmutant, but not mutant, human RNF216 or OTUD4 messenger RNA. All patients had progressive ataxia and dementia. Neuronal loss was observed in cerebellar pathways and the hippocampus; surviving hippocampal neurons contained ubiquitin-immunoreactive intranuclear inclusions. Defects were detected at the hypothalamic and pituitary levels of the reproductive endocrine axis. CONCLUSIONS The syndrome of hypogonadotropic hypogonadism, ataxia, and dementia can be caused by inactivating mutations in RNF216 or by the combination of mutations in RNF216 and OTUD4. These findings link disordered ubiquitination to neurodegeneration and reproductive dysfunction and highlight the power of whole-exome sequencing in combination with functional studies to unveil genetic interactions that cause disease. (Funded by the National Institutes of Health and others.).",
"title": "Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination."
},
{
"docid": "19368793",
"text": "BACKGROUND Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the serum and tissue expression of miR 21 and miR 199-a to be applied as early detectors for HCC. METHODS A total of 40 serum and tissue samples (17 samples from chronic hepatitis and 23 samples from HCC patients) were collected. The levels of the two mature miRNAs (miR-21 and miR-199-a) were detected by real time quantitative reverse-transcriptase PCR (RT-qPCR) in sera and tissues of chronic hepatitis and HCC patients. Besides, miR-21 and miR-199-a levels in relation to clinical and pathological factors were explored. RESULTS We found that the expression of serum miR-21 was distinctly increased in HCC compared with chronic hepatitis (P<0.001). miR 199-a was distinctly decreased in HCC compared with chronic hepatitis (P<0.001). In addition, median of miR 21 was increased in malignant when compared to adjacent non-malignant tissues without significant differences (P=0.191) while miR 199-a was significantly decreased in malignant when compared to adjacent nonmalignant tissues (P<0.001). ROC analysis showed that miR-21 and miR-199-a might be potential biomarkers for HCC. CONCLUSIONS In conclusion, the expression of miR-21 was significantly up-regulated and miR-199-a was significantly down regulated in serum of patients with HCC. Due to their reasonable sensitivity and specificity for disease progression, miR-21 and miR-199-a could be used as potential circulating biomarkers for HCC.",
"title": "The potential role of miRNAs 21 and 199-a in early diagnosis of hepatocellular carcinoma."
},
{
"docid": "19822046",
"text": "BACKGROUND Deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA. Little is known about the biological significance of germline mutations in PARN. METHODS We identified mutations in PARN in patients with haematological and neurological manifestations. Genomic, biochemical and knockdown experiments in human marrow cells and in zebrafish have been performed to clarify the role of PARN in the human disease. RESULTS We identified large monoallelic deletions in PARN in four patients with developmental delay or mental illness. One patient in particular had a severe neurological phenotype, central hypomyelination and bone marrow failure. This patient had an additional missense mutation on the non-deleted allele and severely reduced PARN protein and deadenylation activity. Cells from this patient had impaired oligoadenylation of specific H/ACA box small nucleolar RNAs. Importantly, PARN-deficient patient cells manifested short telomeres and an aberrant ribosome profile similar to those described in some variants of dyskeratosis congenita. Knocking down PARN in human marrow cells and zebrafish impaired haematopoiesis, providing further evidence for a causal link with the human disease. CONCLUSIONS Large monoallelic mutations of PARN can cause developmental/mental illness. Biallelic PARN mutations cause severe bone marrow failure and central hypomyelination.",
"title": "Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN)."
},
{
"docid": "42441846",
"text": "INTRODUCTION Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD. MATERIALS AND METHODS We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype. RESULTS The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively). CONCLUSION We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.",
"title": "Gene--nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population."
},
{
"docid": "9539248",
"text": "Mosquito-borne viruses cause significant levels of morbidity and mortality in humans and domesticated animals. Maintenance of mosquito-borne viruses in nature requires a biological transmission cycle that involves alternating virus replication in a susceptible vertebrate and mosquito host. Although the vertebrate infection is acute and often associated with disease, continual transmission of these viruses in nature depends on the establishment of a persistent, nonpathogenic infection in the mosquito vector. An antiviral RNAi response has been shown to limit the replication of RNA viruses in flies. However, the importance of the RNAi pathway as an antiviral defense in mammals is unclear. Differences in the immune responses of mammals and mosquitoes may explain why these viruses are not generally associated with pathology in the invertebrate host. We identified virus-derived small interfering RNAs (viRNAs), 21 nt in length, in Aedes aegypti infected with the mosquito-borne virus, Sindbis (SINV). viRNAs had an asymmetric distribution that spanned the length of the SINV genome. To determine the role of viRNAs in controlling pathogenic potential, mosquitoes were infected with recombinant alphaviruses expressing suppressors of RNA silencing. Decreased survival was observed in mosquitoes in which the accumulation of viRNAs was suppressed. These results suggest that an exogenous siRNA pathway is essential to the survival of mosquitoes infected with alphaviruses and, thus, the maintenance of these viruses in nature.",
"title": "Alphavirus-derived small RNAs modulate pathogenesis in disease vector mosquitoes."
},
{
"docid": "8496132",
"text": "Overexpression of the proto-oncogene bcl-2 promotes abnormal cell survival by inhibiting apoptosis. Expression of bcl-2 is determined, in part, by regulatory mechanisms that control the stability of bcl-2 mRNA. Elements in the 3'-untranslated region of bcl-2 mRNA have been shown to play a role in regulating the stability of the message. Previously, it was found that the RNA binding proteins nucleolin and Ebp1 have a role in stabilizing bcl-2 mRNA in HL60 cells. Here, we have identified HuR as a component of bcl-2 messenger ribonucleoprotein (mRNP) complexes. RNA coimmunoprecipitation assays showed that HuR binds to bcl-2 mRNA in vivo. We also observed an RNA-dependent coprecipitation of HuR and nucleolin, suggesting that the two proteins are present in common mRNP complexes. Moreover, nucleolin and HuR bind concurrently to bcl-2 AU-rich element (ARE) RNA in vitro, suggesting separate binding sites for these proteins on bcl-2 mRNA. Knockdown of HuR in A431 cells leads to down-regulation of bcl-2 mRNA and protein levels. Observation of a decreased ratio of bcl-2 mRNA to heterogeneous nuclear RNA in HuR knockdown cells confirmed a positive role for HuR in regulating bcl-2 stability. Recombinant HuR retards exosome-mediated decay of bcl-2 ARE RNA in extracts of HL60 cells. This supports a role for HuR in the regulation of bcl-2 mRNA stability in HL60 cells, as well as in A431 cells. Addition of nucleolin and HuR to HL60 cell extracts produced a synergistic protective effect on decay of bcl-2 ARE RNA. HuR knockdown also leads to redistribution of bcl-2 mRNA from polysomes to monosomes. Thus, HuR seems to play a positive role in both regulation of bcl-2 mRNA translation and mRNA stability.",
"title": "Regulation of Bcl-2 expression by HuR in HL60 leukemia cells and A431 carcinoma cells."
},
{
"docid": "7029990",
"text": "One type of RNA editing involves the conversion of adenosine residues into inosine in double-stranded RNA through the action of adenosine deaminases acting on RNA (ADAR). A-to-I RNA editing of the coding sequence could result in synthesis of proteins not directly encoded in the genome. ADAR edits also non-coding sequences of target RNAs, such as introns and 3'-untranslated regions, which may affect splicing, translation, and mRNA stability. Three mammalian ADAR gene family members (ADAR1-3) have been identified. Here we investigated phenotypes of mice homozygous for ADAR1 null mutation. Although live ADAR1-/- embryos with normal gross appearance could be recovered up to E11.5, widespread apoptosis was detected in many tissues. Fibroblasts derived from ADAR1-/- embryos were also prone to apoptosis induced by serum deprivation. Our results demonstrate an essential requirement for ADAR1 in embryogenesis and suggest that it functions to promote survival of numerous tissues by editing one or more double-stranded RNAs required for protection against stress-induced apoptosis.",
"title": "Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene."
},
{
"docid": "34733465",
"text": "BACKGROUND Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.",
"title": "Association of cystic fibrosis with abnormalities in fatty acid metabolism."
},
{
"docid": "11016410",
"text": "Within hosts, RNA viruses form populations that are genetically and phenotypically complex. Heterogeneity in RNA virus genomes arises due to error-prone replication and is reduced by stochastic and selective mechanisms that are incompletely understood. Defining how natural selection shapes RNA virus populations is critical because it can inform treatment paradigms and enhance control efforts. We allowed West Nile virus (WNV) to replicate in wild-caught American crows, house sparrows and American robins to assess how natural selection shapes RNA virus populations in ecologically relevant hosts that differ in susceptibility to virus-induced mortality. After five sequential passages in each bird species, we examined the phenotype and population diversity of WNV through fitness competition assays and next generation sequencing. We demonstrate that fitness gains occur in a species-specific manner, with the greatest replicative fitness gains in robin-passaged WNV and the least in WNV passaged in crows. Sequencing data revealed that intrahost WNV populations were strongly influenced by purifying selection and the overall complexity of the viral populations was similar among passaged hosts. However, the selective pressures that control WNV populations seem to be bird species-dependent. Specifically, crow-passaged WNV populations contained the most unique mutations (~1.7× more than sparrows, ~3.4× more than robins) and defective genomes (~1.4× greater than sparrows, ~2.7× greater than robins), but the lowest average mutation frequency (about equal to sparrows, ~2.6× lower than robins). Therefore, our data suggest that WNV replication in the most disease-susceptible bird species is positively associated with virus mutational tolerance, likely via complementation, and negatively associated with the strength of selection. These differences in genetic composition most likely have distinct phenotypic consequences for the virus populations. Taken together, these results reveal important insights into how different hosts may contribute to the emergence of RNA viruses.",
"title": "Experimental Evolution of an RNA Virus in Wild Birds: Evidence for Host-Dependent Impacts on Population Structure and Competitive Fitness"
},
{
"docid": "4459491",
"text": "Alzheimer’s disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer’s disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer’s disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer’s disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer’s disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer’s disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.",
"title": "A three-dimensional human neural cell culture model of Alzheimer’s disease"
},
{
"docid": "4993011",
"text": "ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers.",
"title": "Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers"
}
] |
2184
|
Ideal investments for a recent college grad with very high risk tolerance?
|
[
{
"docid": "17823",
"text": "\"I'd suggest you start by looking at the mutual fund and/or ETF options available via your bank, and see if they have any low-cost funds that invest in high-risk sectors. You can increase your risk (and potential returns) by allocating your assets to riskier sectors rather than by picking individual stocks, and you'll be less likely to make an avoidable mistake. It is possible to do as you suggest and pick individual stocks, but by doing so you may be taking on more risk than you suspect, even unnecessary risk. For instance, if you decide to buy stock in Company A, you know you're taking a risk by investing in just one company. However, without a lot of work and financial expertise, you may not be able to assess how much risk you're taking by investing in Company A specifically, as opposed to Company B. Even if you know that investing in individual stocks is risky, it can be very hard to know how risky those particular individual stocks are, compared to other alternatives. This is doubly true if the investment involves actions more exotic than simply buying and holding an asset like a stock. For instance, you could definitely get plenty of risk by investing in commercial real estate development or complicated options contracts; but a certain amount of work and expertise is required to even understand how to do that, and there is a greater likelihood that you will slip up and make a costly mistake that negates any extra gain, even if the investment itself might have been sound for someone with experience in that area. In other words, you want your risk to really be the risk of the investment, not the \"\"personal\"\" risk that you'll make a mistake in a complicated scheme and lose money because you didn't know what you were doing. (If you do have some expertise in more exotic investments, then maybe you could go this route, but I think most people -- including me -- don't.) On the other hand, you can find mutual funds or ETFs that invest in large economic sectors that are high-risk, but because the investment is diversified within that sector, you need only compare the risk of the sectors. For instance, emerging markets are usually considered one of the highest-risk sectors. But if you restrict your choice to low-cost emerging-market index funds, they are unlikely to differ drastically in risk (at any rate, far less than individual companies). This eliminates the problem mentioned above: when you choose to invest in Emerging Markets Index Fund A, you don't need to worry as much about whether Emerging Markets Index Fund B might have been less risky; most of the risk is in the choice to invest in the emerging markets sector in the first place, and differences between comparable funds in that sector are small by comparison. You could do the same with other targeted sectors that can produce high returns; for instance, there are mutual funds and ETFs that invest specifically in technology stocks. So you could begin by exploring the mutual funds and ETFs available via your existing investment bank, or poke around on Morningstar. Fees will still matter no matter what sector you're in, so pay attention to those. But you can probably find a way to take an aggressive risk position without getting bogged down in the details of individual companies. Also, this will be less work than trying something more exotic, so you're less likely to make a costly mistake due to not understanding the complexities of what you're investing in.\"",
"title": ""
},
{
"docid": "96110",
"text": "If you're sure you want to go the high risk route: You could consider hot stocks or even bonds for companies/countries with lower credit ratings and higher risk. I think an underrated cost of investing is the tax penalties that you pay when you win if you aren't using a tax advantaged account. For your speculating account, you might want to open a self-directed IRA so that you can get access to more of the high risk options that you crave without the tax liability if any of those have a big payout. You want your high-growth money to be in a Roth, because it would be a shame to strike it rich while you're young and then have to pay taxes on it when you're older. If you choose not to make these investments in a tax-advantaged account, try to hold your stocks for a year so you only get taxed at capital gains rates instead of as ordinary income. If you choose to work for a startup, buy your stock options as they vest so that if the company goes public or sells privately, you will have owned those stocks long enough to qualify for capital gains. If you want my actual advice about what I think you should do: I would increase your 401k percentage to at least 10% with or without a match, and keep that in low cost index funds while you're young, but moving some of those investments over to bonds as you get closer to retirement and your risk tolerance declines. Assuming you're not in the 25% tax bracket, all of your money should be in a Roth 401k or IRA because you can withdraw it without being taxed when you retire. The more money you put into those accounts now while you are young, the more time it all has to grow. The real risk of chasing the high-risk returns is that when you bet wrong it will set you back far enough that you will lose the advantage that comes from investing the money while you're young. You're going to have up and down years with your self-selected investments, why not just keep plugging money into the S&P which has its ups and downs, but has always trended up over time?",
"title": ""
},
{
"docid": "560395",
"text": "Congratulations on being in this position. Your problem - which I think that you identified - is that you don't know much about investing. My recommendation is that you start with three goals: The Motley Fool (www.fool.com) has a lot of good information on their site. Their approach may or may not align with what you want to do; I've subscribed to their newsletters for quite a while and have found them useful. I'm what is known as a value investor; I like to make investments and hold them for a long time. Others have different philosophies. For the second goal, it's very important to follow the money and ask how people get paid in the investment business. The real money in Wall Street is made not by investment, but by charging money to those who are in the investment business. There are numerous people in line for some of your money in return for service or advice; fees for buying/selling stocks, fees for telling you which stocks to buy/sell, fees for managing your money, etc. You can invest without spending too much on fees if you understand how the system works. For the third goal, I recommend choosing a few stocks, and creating a virtual portfolio. You can then then get used to watching and tracking your investments. If you want a place to put your money while you do this, I'd start with an S&P 500 index fund with a low expense ratio, and I'd buy it through a discount broker (I use Scottrade but there are a number of choices). Hope that helps.",
"title": ""
},
{
"docid": "150475",
"text": "\"You have a high risk tolerance? Then learn about exchange traded options, and futures. Or the variety of markets that governments have decided that people without high income are too stupid to invest in, not even kidding. It appears that a lot of this discussion about your risk profile and investing has centered around \"\"stocks\"\" and \"\"bonds\"\". The similarities being that they are assets issued by collections of humans (corporations), with risk profiles based on the collective decisions of those humans. That doesn't even scratch the surface of the different kinds of asset classes to invest in. Bonds? boring. Bond futures? craziness happening over there :) Also, there are potentially very favorable tax treatments for other asset classes. For instance, you mentioned your desire to hold an investment for over a year for tax reasons... well EVERY FUTURES TRADE gets that kind of tax treatment (partially), whether you hold it for one day or more, see the 60/40 rule. A rebuttal being that some of these asset classes should be left to professionals. Stocks are no different in that regards. Either educate yourself or stick with the managed 401k funds.\"",
"title": ""
},
{
"docid": "313127",
"text": "Cryptocurrencies like Bitcoin or Ethereum. Then check their prices daily. With daily price swings of over 10% (both up and down) being a common occurrence, you'll quickly learn how high your risk tolerance really is. :) A lot of IT people believe that cryptocurrencies will stay. Whether Bitcoin or Ethereum will be among them is anyone's guess. Compare to the Dotcom boom, which will be Amazon.com and which will be Pets.com?",
"title": ""
},
{
"docid": "303561",
"text": "An ideal investment for a highly risk tolerant college grad with a background in software and programming, is a software company. That's because it's the kind of investment that you will be able to judge better than most other people, including yours truly. Hopefully, one day the software company for a highly risk tolerant investor will be your own.(Ask Bill Gates or even Michael Dell, although the latter was more involved in hardware.)",
"title": ""
},
{
"docid": "369342",
"text": "Sorry to be boring but you have the luxury of time and do not need high-risk investments. Just put the surplus cash into a diversified blue-chip fund, sit back, and enjoy it supporting you in 50 years time. Your post makes me think you're implicitly assuming that since you have a very high risk tolerance you ought to be able to earn spectacular returns. Unfortunately the risks involved are extremely difficult to quantify and there's no guarantee they're fairly discounted. Most people would intuitively realise betting on 100-1 horses is a losing proposition but not realise just how bad it is. In reality far fewer than one in a thousand 100-1 shots actually win.",
"title": ""
},
{
"docid": "314300",
"text": "If you have been putting savings away for the longer term and have some extra funds which you would like to take some extra risk on - then I say work yourself out a strategy/plan, get yourself educated and go for it. If it is individual shares you are interested then work out if you prefer to use fundamental analysis, technical analysis or some of both. You can use fundamental analysis to help determine which shares to buy, and then use technical analysis to help determine when to get into and out of a position. You say you are prepared to lose $10,000 in order to try to get higher returns. I don't know what percentage this $10,000 is of the capital you intend to use in this kind of investments/trading, but lets assume it is 10% - so your total starting capital would be $100,000. The idea now would be to learn about money management, position sizing and risk management. There are plenty of good books on these subjects. If you set a maximum loss for each position you open of 1% of your capital - i.e $1,000, then you would have to get 10 straight losses in a row to get to your 10% total loss. You do this by setting stop losses on your positions. I'll use an example to explain: Say you are looking at a stock priced at $20 and you get a signal to buy it at that price. You now need to determine a stop price which if the stock goes down to, you can say well I may have been wrong on this occasion, the stock price has gone against me so I need to get out now (I put automatic stop loss conditional orders with my broker). You may determine the stop price based on previous support levels, using a percentage of your buy price or another indicator or method. I tend to use the percentage of buy price - lets say you use 10% - so your stop price would be at $18 (10% below your buy price of $20). So now you can work out your position size (the number of shares to buy). Your maximum loss on the position is $2 per share or 10% of your position in this stock, but it should also be only 1% of your total capital - being 1% of $100,000 = $1,000. You simply divide $1,000 by $2 to get 500 shares to buy. You then do this with the rest of your positions - with a $100,000 starting capital using a 1% maximum loss per position and a stop loss of 10% you will end up with a maximum of 10 positions. If you use a larger maximum loss per position your position sizes would increase and you would have less positions to open (I would not go higher than 2% maximum loss per position). If you use a larger stop loss percentage then your position sizes would decrease and you would have more positions to open. The larger the stop loss the longer you will potentially be in a position and the smaller the stop loss generally the less time you will be in a position. Also as your total capital increases so will your 1% of total capital, just as it would decrease if your total capital decreases. Using this method you can aim for higher risk/ higher return investments and reduce and manage your risk to a desired level. One other thing to consider, don't let tax determine when you sell an investment. If you are keeping a stock just so you will pay less tax if kept for over 12 months - then you are in real danger of increasing your risk considerably. I would rather pay 50% tax on a 30% return than 25% tax on a 15% return.",
"title": ""
},
{
"docid": "102501",
"text": "Theoretically there is limited demand for risky investments, so higher-risk asset classes should outperform lower-risk asset classes over sufficiently long time periods. In practice, I believe this is true, but it could be several decades before a risky portfolio starts to outperform a more conservative one. Stocks are considered more risky than most assets. Small-cap stocks and emerging market stocks are particularly high-risk. I would consider low-fee ETFs in these areas, like VB or VWO. If you want to seek out the absolute riskiest investments, you could pick individual stocks of companies in dire financial situations, as Bank of America was a couple years ago. Most importantly, if you don't expect to need the money soon, I would maximize your contribution to tax-advantaged accounts since they will grow exponentially faster than taxable accounts. Over 50 years, a 401(k) or IRA will generally grow at least 50% more than a taxable account, maybe more depending on the tax-efficiency of your investments. Try to contribute the maximum ($17,500 for most people in 2014) if you can. If you can save more than that, I'd suggest contributing a Roth 401k rather than a traditional 401(k) - since Roth contributions are post-tax, the effective contribution limit is higher. Also contribute to a Roth IRA (up to $5,500 in 2014), using a backdoor Roth if necessary.",
"title": ""
},
{
"docid": "285918",
"text": "I am in a very similar situation as you (software engineer, high disposable income). Maximize your contributions to all tax-advantaged accounts first. From those accounts you can choose to invest in high risk funds. At your age and date-target funds will invest in riskier investments on your behalf; and they'll do it while avoiding the 30%+/- haircut that you'll be paying in taxes anyhow. If, after that, you're looking for bigger risk plays then look into a brokerage account that will let you buy and sell options. These are big risk swingers and they are sophisticated, complicated products which are used by many people who likely understand finance far better than you. You can make money with them but you should consider it akin to gambling. It might be more to your liking to maintain a long position in a stock and then trade options against your long position. Start with trading covered calls, then you could consider buying options (defined limited downside risk).",
"title": ""
}
] |
[
{
"docid": "515060",
"text": "I completely agree that there are experts that recognize it as a very serious problem, and I agree that it is a serious problem that could cause a large recession or crash (my large chunk of remaining loans definitely agrees). My point is that this article isn't looking at economic data. It's looking at a survey of recent college grads and asking them to rank the risk of student loan debt vs the risk of North Korea. I wouldn't consider that a very useful indicator.",
"title": ""
},
{
"docid": "204227",
"text": "Stay away from college debt. You can't default on it. Your wages will be garnished if you're unable to pay it back. Even when your and old man, they will garnish your social security money. In effect college debt makes you an indentured servant. Maybe even worse than the 7 years of servitude people served in early America. Lots of grads are working in restaurants and retail stores.... even some computer science grads. There is great risk in the college investment compared to 40 years ago when it was a sure thing. Do not take debt for college. If that means you can't go to college then so be it. You're future self will than you.",
"title": ""
},
{
"docid": "599436",
"text": "\"1. Interest rates What you should know is that the longer the \"\"term\"\" of a bond fund, the more it will be affected by interest rates. So a short-term bond fund will not be subject to large gains or losses due to rate changes, an intermediate-term bond fund will be subject to moderate gains or losses, and a long-term bond fund will be subject to the largest gains or losses. When a book or financial planner says to buy \"\"bonds\"\" with no other qualification, they almost always mean investment-grade intermediate-term bond funds (or for individual bonds, the equivalent would be a bond ladder averaging an intermediate term). If you want technical details, look at the \"\"average duration\"\" or \"\"average maturity\"\" of the bond fund; as a rough guide, if the duration is 10, then a 1% change in interest rates would be a 10% gain or loss on the fund. Another thing you can do is look at long-term (10 years or ideally longer) performance history on some short, intermediate, and long term bond index funds, and you can see how the long term funds bounced around more. Non-investment-grade bonds (aka junk bonds or high yield bonds) are more affected by factors other than interest rates, including some of the same factors (economic booms or recessions) that affect stocks. As a result, they aren't as good for diversifying a portfolio that otherwise consists of stocks. (Having stocks, investment grade bonds, and also a little bit in high-yield bonds can add diversification, though. Just don't replace your bond allocation with high-yield bonds.) A variety of \"\"complicated\"\" bonds exist (convertible bonds are an example) and these are tough to analyze. There are also \"\"floating rate\"\" bonds (bank loan funds), these have minimal interest rate sensitivity because the rate goes up to offset rate rises. These funds still have credit risks, in the credit crisis some of them lost a lot of money. 2. Diversification The purpose of diversification is risk control. Your non-bond funds will outperform in many years, but in other years (say the -37% S&P 500 drop in 2008) they may not. You will not know in advance which year you'll get. You get risk control in at least a few ways. There's also an academic Modern Portfolio Theory explanation for why you should diversify among risky assets (aka stocks), something like: for a given desired risk/return ratio, it's better to leverage up a diverse portfolio than to use a non-diverse portfolio, because risk that can be eliminated through diversification is not compensated by increased returns. The theory also goes that you should choose your diversification between risk assets and the risk-free asset according to your risk tolerance (i.e. select the highest return with tolerable risk). See http://en.wikipedia.org/wiki/Modern_portfolio_theory for excruciating detail. The translation of the MPT stuff to practical steps is typically, put as much in stock index funds as you can tolerate over your time horizon, and put the rest in (intermediate-term investment-grade) bond index funds. That's probably what your planner is asking you to do. My personal view, which is not the standard view, is that you should take as much risk as you need to take, not as much as you think you can tolerate: http://blog.ometer.com/2010/11/10/take-risks-in-life-for-savings-choose-a-balanced-fund/ But almost everyone else will say to do the 80/20 if you have decades to retirement and feel you can tolerate the risk, so my view that 60/40 is the max desirable allocation to stocks is not mainstream. Your planner's 80/20 advice is the standard advice. Before doing 100% stocks I'd give you at least a couple cautions: See also:\"",
"title": ""
},
{
"docid": "424717",
"text": "\"Specifically, what does my broker mean when they say an asset or investment strategy is high risk? In this context, it is a statement based on past events and probability. It is based on how confident s/he is that the investment will perform to certain benchmarks. This is a math question, primarily (with some opinion mixed in, granted). This is where the Sharpe ratio and others fit well. How am I supposed to answer a question like \"\"rate your risk tolerance from low to high\"\"? This is the hard question, as you have seen. In this context, risk tolerance is derived from your current position and future plans (goals). This is a planning, goal setting, and strategy question, primarily (with some math mixed in, granted). How vulnerable is your current position and future plans to an under-performing investment? If you answer \"\"very\"\", then you choose investments that have a lower probability of under-performing. The Sharpe ratio has little to do with answering this question. It is a tool to find investments that better match your answer to this question.\"",
"title": ""
},
{
"docid": "433003",
"text": "Using a simple investment calculator to get a sense of scale here, to have 70k total, including the 500 a month invested, after ten years you just need returns of 2%. To earn 70k on top of the money invested you would need returns over 20%. To do that in five years you would need over 50% annual return. That is quite a big difference. Annualized returns of 20% would require high risk and a very large amount of time invested, skill and luck. 2% returns can be nearly guaranteed without much effort. I would encourage you to think about your money more holistically. If you get very unlucky with investments and don't make any money will you not go on the vacations even if your income allows? That doesn't make a lot of sense. As always, spend all your money with the current and future in mind. Investment return Euros are no different from any other Euros. At that point, the advice is the same for all investors try to get as much return as possible for the risk you are comfortable with. You seem to have a high tolerance for risk. Generally, for investors with a high risk tolerance a broadly diversified portfolio of stocks (with maybe a small amount of bonds, other investments) will give the most return over the long term for the risk taken. After that generally the next most useful way to boost your returns is to try to avoid taxes which is why we talk about 401(k)s so much around here. Each European country has different tax law, but please ask questions here about your own country as well as you mention money.se could use more ex-US questions.",
"title": ""
},
{
"docid": "53244",
"text": "The one thing we know for certain is that holding large amounts of cash isn't ideal - inflation will eat away at your wealth. It's understandable that you're hesitant to put all your wealth in common stock. The S&P 500's price/earnings is 18.7 right now - a little high by historical standards. But consider that the S&P 500 has given a CAGR of approximately 10% (not inflation-adjusted) since 1970. If you don't time the market correctly, you could miss out on considerable gains. So it's probably best to invest at least a portion of your wealth in common stocks, and just accept the risk of short-term losses. You'll likely come out ahead in the long run, compared to an investor who tries to time the market and ends up holding cash positions for too long. If you really think US stocks are overpriced, you could look at other markets, but you'll find similar P/Es in Europe and Japan. You could try an emerging market fund like VEMAX if you have the risk tolerance. Let's say you're not convinced, and don't want to invest heavily in stocks right now. In the current market, safe cash alternatives like Treasury bills offer very low yields - not enough to offset inflation tax. So I would invest in a diversified portfolio of long-term bonds, real estate, maybe precious metals, and whatever amount of stock you're comfortable with.",
"title": ""
},
{
"docid": "212004",
"text": "There are a couple of reasons that a person might choose to use insurance even if they could handle the financial loss if something went wrong. They know their risk better than the insurance company. While it might seem odd at first glance that an individual can be better at assessing risk than a large company with thousands of actuaries. There are limits to the amount of knowledge that an insurance company can have or use to price their insurance products. For instance if you were a very aggressive driver but didn't have any recent tickets or accidents because you were in college and didn't have a car on a regular basis, but now you have a job and drive 30 miles to work every day. You know your risk is relatively high but the insurance company sees you as relatively low risk and aren't able to price that extra risk into your premium. Just because a person can survive financial after losing something like a car or a house doesn't mean it isn't desirable to pay a small price to mitigate that risk. If you are using your savings to pay for an emergency then that money needs to be semi liquid in case you need it limiting your investment options. Where as if you purchase insurance you pay a small amount of money to be able to invest the rest of your money. Liquidity is a big deal particularly if you are a small business and investing into your business where your money can make your more money but you may or may not be able to access that money very easily.",
"title": ""
},
{
"docid": "189678",
"text": "\"Remember that risk should correlate with returns, in an investment. This means that the more risk you take on, the more return you should be receiving, in an efficient marketplace. That's why putting your money in a savings account might earn you <1% interest right now, but putting money in the stock market averages ~7% returns over time. You should be very careful not to use the word 'interest' when you mean 'returns'. In your post, you are calling capital gains (the increase in value of owned property) 'interest'. This may be understating in your head the level of risk associated with property ownership. In the case of the bank, they are not in the business of home construction. Rather than take that risk themselves, they would rather finance many projects being done by construction companies that know the business. The bank has a high degree of certainty of getting its money back, because its mortgages are protected by the value of the property. Part of the benefit of an efficient marketplace is that risk gets 'bought' by individuals who want it. This means that people with a low-risk tolerance (such as banks, people on fixed incomes, seniors, etc.) can avoid risk, and people with a high risk tolerance (stock investors, young people with high income, etc.) can take on that risk for higher average returns. The bank's reasoning should remind you of the risk associated with property ownership: increases in value are not a sure thing. If you do not understand the risk of your investment, you cannot be certain that you are being well compensated for that risk. Note also that most countries place regulations on their banks that limit the amount of their funds that can be placed in 'higher risk' asset classes. Typically, this something along the lines of \"\"If someone places a deposit with your bank, you can only invest that deposit in a low-risk debt-based asset [ie: you can take money deposited by customer A and use it to finance a mortgage for customer B]\"\". This is done in an attempt to prevent collapse of the financial sector, if risky investments start failing.\"",
"title": ""
},
{
"docid": "134542",
"text": "\"When you invest in a single index/security, you are completely exposed to the risk of that security. Diversification means spreading the investments so the losses on one side can be compensated by the gains on the other side. What you are talking about is one thing called \"\"risk apettite\"\", more formally known as Risk Tolerance: Risk tolerance is the degree of variability in investment returns that an investor is willing to withstand. (emphasis added) This means that you are willing to accept some losses in order to get a potential bigger return. Fidelity has this graph: As you can see in the table above, the higher the risk tolerance, the bigger the difference between the best and worst values. That is the variability. The right-most pie can be one example of an agressive diversified portfolio. But this does not mean you should go and buy exactly that security compostion. High-risk means playing with fire. Unless you are a professional stuntman, playing with fire usually leaves people burnt. In a financial context this usually means the money is gone. Recommended Reading: Investopedia; Risk and Diversification: The Risk-Reward Tradeoff Investopedia; How to construct a High Risk portfolio Fidelity: Guide to Diversification KPMG: Understanding and articulating Risk Appetite (pdf)\"",
"title": ""
},
{
"docid": "136515",
"text": "\"Bonds still definitely have a place in many passive portfolios. While it is true that interest rates have been unusually low, yields on reasonable passive bond exposures are still around 2-4%. This is significantly better than both recent past inflation and expected inflation both of which are near zero. This is reasonable if not great return, but Bonds continue to have other nice properties like relatively low risk and diversification of stock portfolios (the \"\"offset[ing] losses\"\" you mention in the OP). So to say that bonds are \"\"no longer a good idea\"\" is certainly not correct. One could say bonds may no longer be a good idea for some people that have a particularly high risk tolerance and very high return requirements. However, to some extent, that has always been true. It is worth remembering also that there is some compelling evidence that global growth is starting to broadly slow down and many people believe that future stock returns and, in general, returns on all investments will be lower. This is much much harder to estimate than bond returns though. Depending on who you believe, bond returns may actually look relatively better than the have in the past. Edit in response to comment: Corporate bond correlation with stocks is positive but generally not very strong (except for high-yield junk bonds) so while they don't offset stock volatility (negative correlation) they do help diversify a stock portfolio. Government bonds have essentially zero correlation so they don't really offset volatility as much as just not add any. Negative correlation assets are generally called insurance and you tend to have to pay for them. So there is no free lunch here. Assets that reduce risk cost money, assets that add little risk give less return and assets that are more risky tend to give more return in the long run but you can feel the pain. The mix that is right for you depends on a lot of things, but for many people that mix involves some corporate and government bonds.\"",
"title": ""
},
{
"docid": "439459",
"text": "Paying off the debt is low-risk, low-reward. You're effectively guaranteed a 4% return. If you buy a mutual fund, you're going to have to take some risk to have a decent chance of getting better than 4% and change return in the long run, which probably means a fund that invests primarily in stocks. Buying a stock mutual fund is high-risk, high reward, especially when you're in significant debt. On the other hand, 4% and change is very low-interest. If you wanted to buy stocks on margin, financing stock investments directly with debt, you'd pay a heck of a lot more. Bottom line: It comes down to your personal risk tolerance.",
"title": ""
},
{
"docid": "160105",
"text": "\"I was going to ask, \"\"Do you feel lucky, punk?\"\" but then it occurred to me that the film this quote came from, Dirty Harry, starring Clint Eastwood, is 43 years old. And yet, the question remains. The stock market, as measured by the S&P has returned 9.67% compounded over the last 100 years. But with a standard deviation just under 20%, there are years when you'll do better and years you'll lose. And I'd not ignore the last decade which was pretty bad, a loss for the decade. There are clearly two schools of thought. One says that no one ever lost sleep over not having a mortgage payment. The other school states that at the very beginning, you have a long investing horizon, and the chances are very good that the 30 years to come will bring a return north of 6%. The two decades prior to the last were so good that these past 30 years were still pretty good, 11.39% compounded. There is no right or wrong here. My gut says fund your retirement accounts to the maximum. Build your emergency fund. You see, if you pay down your mortgage, but lose your job, you'll still need to make those payments. Once you build your security, think of the mortgage as the cash side of your investing, i.e. focus less on the relatively low rate of return (4.3%) and more on the eventual result, once paid, your cash flow goes up nicely. Edit - in light of the extra information you provided, your profile reads that you have a high risk tolerance. Low overhead, no dependents, and secure employment combine to lead me to this conclusion. At 23, I'd not be investing at 4.3%. I'd learn how to invest in a way I was comfortable with, and take it from there. Disclosure (Updated) - I am older, and am semi-retired. I still have some time left on the mortgage, but it doesn't bother me, not at 3.5%. I also have a 16 year old to put through college but her college account i fully funded.\"",
"title": ""
},
{
"docid": "438294",
"text": "Not all debt is bad. If it carries a reasonable interest rate, you don't need to clear it immediately. As for investing in an index fund, they're an affordable, easy way to spread your money over various assets. However, asset allocation is just one of many investment strategies. Ideally, you want to invest according to your goals, tax situation, and risk tolerance. You want a portfolio that dynamically allocates to various investment strategies, both beta and alpha, according to changing market conditions. Most importantly, you want systematic risk management for every aspect of your investments.",
"title": ""
},
{
"docid": "402950",
"text": "\"Math says invest in the Market (But paying off your mortgage early is a valid option if you are very risk averse.) You are going to get a better return by investing in the stock market. In the US in 2015/2016, mortgages are 3%-4%, and give you a tax break. The rate of return on the stock market is ~10%, (closer to 6% after you subtract out inflation, taxes, fees, etc.) Since 10 > 3, (or 6% > 4%, to use the pessimistic numbers) investing in the market is the better deal. But... The market has risk, and your mortgage does not. If you are very risk averse paying off the mortgage may make sense. As an example: Family A has a single \"\"breadwinner\"\", who works a low skilled job. Family B has 2 working spouses, both in high skill white collar positions. These two families are going to have wildly different risk tolerances. It may make sense for family A to \"\"invest\"\" its extra money in paying off the mortgage, after they have tackled high interest debt, built an emergency fund, maxed the 401k, etc. Personally I would not: in the US you cannot recoup pre-payments if you lose your job. If I was very risk averse, I would keep my extra money as cash, so I could pay my mortgage after I lost my job. It is never going to make sense for family B to pay the mortgage early. At that point, any decision to pre-pay is going to be based on emotion and not logic.\"",
"title": ""
},
{
"docid": "118800",
"text": "I think we resolved this via comments above. Many finance authors are not fans of target date funds, as they have higher fees than you'd pay constructing the mix yourself, and they can't take into account your own risk tolerance. Not every 24 year old should have the same mix. That said - I suggest you give thought to the pre-tax / post tax (i.e. traditional vs Roth) mix. I recently wrote The 15% solution, which attempts to show how to minimize your lifetime taxes by using the split that's ideal for your situation.",
"title": ""
},
{
"docid": "481683",
"text": "\"Here are my reasons as to why bonds are considered to be a reasonable investment. While it is true that, on average over a sufficiently long period of time, stocks do have a high expected return, it is important to realize that bonds are a different type of financial instrument that stocks, and have features that are attractive to certain types of investors. The purpose of buying bonds is to convert a lump sum of currency into a series of future cash flows. This is in and of itself valuable to the issuer because they would prefer to have the lump sum today, rather than at some point in the future. So we generally don't say that we've \"\"lost\"\" the money, we say that we are purchasing a series of future payments, and we would only do this if it were more valuable to us than having the money in hand. Unlike stocks, where you are compensated with dividends and equity to take on the risks and rewards of ownership, and unlike a savings account (which is much different that a bond), where you are only being paid interest for the time value of your money while the bank lends it out at their risk, when you buy a bond you are putting your money at risk in order to provide financing to the issuer. It is also important to realize that there is a much higher risk that stocks will lose value, and you have to compare the risk-adjusted return, and not the nominal return, for stocks to the risk-adjusted return for bonds, since with investment-grade bonds there is generally a very low risk of default. While the returns being offered may not seem attractive to you individually, it is not reasonable to say that the returns offered by the issuer are insufficient in general, because both when the bonds are issued and then subsequently traded on a secondary market (which is done fairly easily), they function as a market. That is to say that sellers always want a higher price (resulting in a lower return), and buyers always want to receive a higher return (requiring a lower price). So while some sellers and buyers will be able to agree on a mutually acceptable price (such that a transaction occurs), there will almost always be some buyers and sellers who also do not enter into transactions because they are demanding a lower/higher price. The fact that a market exists indicates that enough investors are willing to accept the returns that are being offered by sellers. Bonds can be helpful in that as a class of assets, they are less risky than stocks. Additionally, bonds are paid back to investors ahead of equity, so in the case of a failing company or public entity, bondholders may be paid even if stockholders lose all their money. As a result, bonds can be a preferred way to make money on a company or government entity that is able to pay its bills, but has trouble generating any profits. Some investors have specific reasons why they may prefer a lower risk over time to maximizing their returns. For example, a government or pension fund or a university may be aware of financial payments that they will be required to make in a particular year in the future, and may purchase bonds that mature in that year. They may not be willing to take the risk that in that year, the stock market will fall, which could force them to reduce their principal to make the payments. Other individual investors may be close to a significant life event that can be predicted, such as college or retirement, and may not want to take on the risk of stocks. In the case of very large investors such as national governments, they are often looking for capital preservation to hedge against inflation and forex risk, rather than to \"\"make money\"\". Additionally, it is important to remember that until relatively recently in the developed world, and still to this day in many developing countries, people have been willing to pay banks and financial institutions to hold their money, and in the context of the global bond market, there are many people around the world who are willing to buy bonds and receive a very low rate of return on T-Bills, for example, because they are considered a very safe investment due to the creditworthiness of the USA, as well as the stability of the dollar, especially if inflation is very high in the investor's home country. For example, I once lived in an African country where inflation was 60-80% per year. This means if I had $100 today, I could buy $100 worth of goods, but by next year, I might need $160 to buy the same goods I could buy for $100 today. So you can see why simply being able to preserve the value of my money in a bond denominated in USA currency would be valuable in that case, because the alternative is so bad. So not all bondholders want to be owners or make as much money as possible, some just want a safe place to put their money. Also, it is true for both stocks and bonds that you are trading a lump sum of money today for payments over time, although for stocks this is a different kind of payment (dividends), and you only get paid if the company makes money. This is not specific to bonds. In most other cases when a stock price appreciates, this is to reflect new information not previously known, or earnings retained by the company rather than paid out as dividends. Most of the financial instruments where you can \"\"make\"\" money immediately are speculative, where two people are betting against each other, and one has to lose money for the other to make money. Again, it's not reasonable to say that any type of financial instrument is the \"\"worst\"\". They function differently, serve different purposes, and have different features that may or may not fit your needs and preferences. You seem to be saying that you simply don't find bond returns high enough to be attractive to you. That may be true, since different people have different investment objectives, risk tolerance, and preference for having money now versus more money later. However, some of your statements don't seem to be supported by facts. For example, retail banks are not highly profitable as an industry, so they are not making thousands of times what they are paying you. They also need to pay all of their operating expenses, as well as account for default risk and inflation, out of the different between what they lend and what they pay to savings account holders. Also, it's not reasonable to say that bonds are worthless, as I've explained. The world disagrees with you. If they agreed with you, they would stop buying bonds, and the people who need financing would have to lower bond prices until people became interested again. That is part of how markets work. In fact, much of the reason that bond yields are so low right now is that there has been such high global demand for safe investments like bonds, especially from other nations, such that bond issues (especially the US government) have not needed to pay high yields in order to raise money.\"",
"title": ""
},
{
"docid": "373645",
"text": "I used to like Applebee's when I was in Undergrad and Grad school... it was open late, it was relatively cheap (late night specials), and the food was better than your average college fair. I recently went back with my SO for some nostalgia at like 8:30 p.m. and I realized very quickly that: * Late night specials start at 10:00 p.m. - who the fuck stays out that late to eat on a weeknight? * Food was awful, definitely went downhill from what I remember * And it was super overpriced - like 9.99 for wings as an appetizer GTFO here Applebee's",
"title": ""
},
{
"docid": "1377",
"text": "\"I don't have a crystal ball but chances are your tenant is definitely lying. Rent was late and now the money intended to cover the rent; miraculously is lost in the mailbox. Anyhow, you were already nice to tolerate the late \"\"payment\"\". Keshlam's option 1.5 in the comments above is the ideal way to settle in which both parties have learned a lesson and are at a loss. Demand the rent payment but settle for half as a one time courtesy. If this continues or this tenant has shown shady predicaments such as this, you should look for legal means to evict this tenant. College students are very creative and who's to say this won't happen again? \"\"The neighbors dog took my wallet.\"\"\"",
"title": ""
},
{
"docid": "124230",
"text": "A general rule of thumb is to avoid having more than 5% of your investments in any single stock, to avoid excessive risk; it's usually even more risky if you're talking company stock because an adverse event could result in an inferior stock price and you getting laid off. Under other circumstances, the ideal amount of company stock is probably 0%. But there are tax benefits to waiting, as you've noted, and if you're reasonably confident that the stock isn't likely to jerk around too much, and you have a high risk tolerance (i.e. lots of extra savings besides this), and you're comfortable shouldering the risk of losing some money, it might make sense to hold onto the stock for a year - but never any longer. The real risk to holding a lot of company stock doesn't depend on how often you buy it and sell it per se, but having period purchases every month should make it easier for you to ladder the funds, and regularly sell your old shares as you purchase new shares. You might also consider a stop-loss order on the stock at or near the price you purchased it at. If the stock is at $100, then you buy at $85, and then the stock drops to $85, there are no more outstanding tax benefits and it makes no sense to have it as part of your portfolio instead of any other speculative instrument - you probably get better diversification benefits with any other speculative instrument, so your risk-adjusted returns would be higher.",
"title": ""
},
{
"docid": "175226",
"text": "\"As JoeTaxpayer notes in his comment, \"\"answers\"\" to this are really just opinions, so here's mine, for what it's worth. If your risk tolerance is 5 out of 5, you shouldn't have anything in Treasuries. Those are basically the most conservative of all investments. This would probably mean no TIPS as well. If you're more like 4.5 out of 5, you could have some, but just a little; a 30% allocation to government securities is quite conservative. If you want to diversify across different asset classes, you could consider a bond fund like (for instance VBMFX, the Vanguard total bond market index fund). Your portfolio doesn't currently contain any (non-government) bonds, which is something to consider. 20% seems like quite a large allocation to REITs. Most sample portfolios I've seen allocate no more than 10% to REITs, often no more than 5%. There are some that have more like the 20% you're envisioning, but you might want to ponder that a bit more especially in light of your concerns about REITs being at an all-time high. As for your question about all-time highs, it's reasonable to think about, but I think waiting for 30-50% off all-time highs is unrealistic. Looking at a chart of VFINX (essentially the S&P 500), I see that at the nadir of the recent downturn, in early 2009, the market was at about 50% of its pre-crash all-time high. At the nadir of the dot-com bust, the market was about 45% off its pre-crash high. If you're waiting for it to be 50% off it's all-time high, you're not just waiting for \"\"a good time to invest\"\", you're waiting for a major crash. It could certainly make sense not to immediately put everything into US stocks, but that doesn't mean you should put nothing in. As Trevor Wilson commented, you could put some of the money in and then gradually add the rest over time, reducing the risk of unluckily buying at the peak. (This can also reduce the psychological angst of worrying about whether you're doing the right thing, which is worth taking into account.) Also note that if you get rid of the treasuries, you eliminate a good chunk of the stuff that you thought was too close to the peak anyway. Your two basic points (asset allocation and low-cost funds) have a strong Boglehead flavor. You may already have looked at the Bogleheads wiki; if not you should take a look. If you are comfortable with that philosophy (and I think it's a sound one), you should remember that part of that philosophy is not worrying about \"\"timing the market\"\". You pursue a buy-and-hold strategy if you believe the market will go up in the long term and don't care much about what it does in the short term. That said, as mentioned above, you might want to ease in your investment over time, rather than buying all at once, if only to avoid tearing your hair out if the market goes down in the short term. Incidentally, your proposed portfolio is similar to this one that they mention, although as I said above I think this is too conservative if you are 30 years old and consider yourself a \"\"5 out of 5\"\" in terms of risk tolerance. I'm not sure if you already saw that in your research, but since that portfolio apparently has a name and is known, you might be able to find information about its risks and benefits by searching for discussion of it by name.\"",
"title": ""
},
{
"docid": "372417",
"text": "\"Here are some things to consider if you want to employ a covered call strategy for consistent returns. The discussion also applies to written puts, as they're functionally equivalent. Write covered calls only on fairly valued stock. If the stock is distinctly undervalued, just buy it. By writing the call, you cap the gains that it will achieve as the stock price gravitates to intrinsic value. If the stock is overvalued, sell it, or just stay away. As the owner of a covered call position, you have full exposure to the downside of the stock. The premium received is normally way too small to protect against much of a drop in price. The ideal candidate doesn't change in price much over the life of the position. Yes, this is low volatility, which brings low option premiums. As a seller you want high premiums. But this can't be judged in a vacuum. No matter how high the volatility in absolute terms, as a seller you're betting the market has overpriced volatility. If volatility is high, so premiums are fat, but the market is correct, then the very real risk of the stock dropping over the life of the position offsets the premium received. One thing to look at is current implied volatility for the at-the-money (ATM), near-month call. Compare it to the two-year historical volatility (Morningstar has this conveniently displayed). Moving away from pure volatility, consider writing calls about three months out, just slightly out of the money. The premium is all time value, and the time value decay accelerates in the final few months. (In theory, a series of one-month options would be higher time value, but there are frictional costs, and no guarantee that today's \"\"good deal\"\" will be repeatable twelve time per year.) When comparing various strikes and expirations, compare time value per day. To compare the same statistic across multiple companies, use time value per day as a percent of capital at risk. CaR is the price of the stock less the premium received. If you already own the stock, track it as if you just bought it for this strategy, so use the price on the day you wrote the call. Along with time value per day, compare the simple annualized percent return, again, on capital at risk, measuring the return if a) the stock is called away, and b) the stock remains unchanged. I usually concentrate more on the second scenario, as we get the capital gain on the stock regardless, without the option strategy. Ideally, you can also calculate the probability (based on implied volatility) of the stock achieving these price points by expiration. Measuring returns at many possible stock prices, you can develop an overall expected return. I won't go into further detail, as it seems outside the scope here. Finally, I usually target a minimum of 25% annualized if the stock remains unchanged. You can, of course, adjust this up or down depending on your risk tolerance. I consider this to be conservative.\"",
"title": ""
},
{
"docid": "197241",
"text": "Do developing country equities have a higher return and/or lower risk than emerging market equities? Generally in finance you get payed more for taking risk. Riskier stocks over the long run return more than less risky bonds, for instance. Developing market equity is expected to give less return over the long run as it is generally less risky than emerging market equity. One way to see that is the amount you pay for one rupee/lira/dollar/euro worth of company earnings is fewer rupees/lira and more dollars/euros. when measured in the emerging market's currency? This makes this question interesting. Risky emerging currencies like the rupee tend to devalue over time against less risky currencies euro/dollars/yen like where most international investment ends up, but the results are rather wild. Think how badly Brazil has done recently and how relatively well the rupee has been doing. This adds to the returns (roughly based on interest rates) of foreign stocks from the point of view of a emerging market investor on average but has really wild variations. Do you have data for this over a long timeframe (decades), ideally for multiple countries? Not really, unfortunately. Good data for emerging markets is a fairly new phenomenon and even where it does exist decades ago it would have been very hard to invest like we can now so it likely is not comparable. Does foreign equity pay more or less when measured in rupees (or other emerging market currency)? Probably less on average (theoretically and empirically) all things included though the evidence is not strong, but there is a massive amount of risk in a portfolio that is 85% in a single emerging market currency. Think about if you were a Brazilian and needed to retire now and 85% of your portfolio was in the Real. International goods like gas would be really expensive and your local currency portfolio would seem paltry right now. If you want to bet on emerging markets in the long run I would suggest that you at least spread the risk over many emerging markets and add a good chunk developed to the mix. As for investing goals, it's just to maximize my return in INR, or maximize my risk-adjusted return. That is up to you, but the goal I generally recommend is making sure you are comfortable in retirement. This usually involves looking for returns are high in the long run, but not having a ton of risk in a single currency or a single market. There are reasons to believe a little bias toward your homeland is good as fees tend to be lower on local investments and local investments tend to track closer to your retirement costs, but too much can be very dangerous even for countries with stronger currencies, say Greece.",
"title": ""
},
{
"docid": "373360",
"text": "Currently, in the US, you won't be able to get 4% return on a risk free investment (savings account, CDs, treasury bonds). If the banking system in India guarantees your money and the cost of transferring them to India is not prohibitive, that's the safest option. Buying a house usually is only worth it if you plan to live in it for a while, 5 years or more being the commonly cited figure. Every case is different, if you rent is very high, it might be worth to buy. I suggest posting another question specifically about that with more details about your situation. If you can tolerate a bit more risk, you might want to talk to a financial adviser and invest in the stock market.",
"title": ""
},
{
"docid": "343965",
"text": "Very unlikely to get 200k out of college, but not out of reach of as you gain experience and if you live in a high CoL area. 200k and higher is about right for all-in comp (base + bonus) as you reach IT management / specialty / sales roles. This is why talent is a concern across finance right now. Grads are going to tech instead of banks because the pay is about a wash but work environment is better. They're not wrong.",
"title": ""
},
{
"docid": "566069",
"text": "The simplest way is to invest in a few ETFs, depending on your tolerance for risk; assuming you're very short-term risk tolerant you can invest almost all in a stock ETF like VOO or VTI. Stock market ETFs return close to 10% (unadjusted) over long periods of time, which will out-earn almost any other option and are very easy for a non-finance person to invest in (You don't trade actively - you leave the money there for years). If you want to hedge some of your risk, you can also invest in Bond funds, which tend to move up in stock market downturns - but if you're looking for the long term, you don't need to put much there. Otherwise, try to make sure you take advantage of tax breaks when you can - IRAs, 401Ks, etc.; most of those will have ETFs (whether Vanguard or similar) available to invest in. Look for funds that have low expense ratios and are fairly diversified (ie, don't just invest in one small sector of the economy); as long as the economy continues to grow, the ETFs will grow.",
"title": ""
},
{
"docid": "178303",
"text": "\"Some thoughts: 1) Do you have a significant emergency fund (3-6 months of after-tax living expenses)? If not, you stand to take a significant loss if you have an unexpected need for cash that is tied up in investments. What if you lose/hate your job or your car breaks down? What if a you want to spend some time with a relative or significant other who learns they only have a few months to live? Having a dedicated emergency fund is an important way to avoid downside risk. 2) Lagerbaer has a good suggestion. Given that if you'd reinvested your dividends, the S&P 500 has returned about 3.5% over the last 5 years, you may be able to get a very nice risk-free return. 3) Do you have access to employer matching funds, such as in a 401(k) at work? If you get a dollar-for-dollar match, that is a risk-free pre-tax 100% return and should be a high priority. 4) What do you mean by \"\"medium\"\" volatility? Given that you are considering a 2/3 equity allocation, it would not be at all out of the realm of possibility that your balance could fall by 15% or more in any given year and take several years to recover. If that would spook you, you may want to consider lowering your equity weights. A high quality bond fund may be a good fit. 5) Personally, I would avoid putting money into stocks that I didn't need back for 10 years. If you only want to tie your money up for 2-5 years, you are taking a significant risk that if prices fall, you won't have time to recover before you need your money back. The portfolio you described would be appropriate for someone with a long-term investment horizon and significant risk tolerance, which is usually the case for young people saving for retirement. However, if your goals are to invest for 2-5 years only, your situation would be significantly different. 6) You can often borrow from an investment account to purchase a primary residence, but you must pay that amount back in order to avoid significant taxes and fees, unless you plan to liquidate assets. If you plan to buy a house, saving enough to avoid PMI is a good risk-free return on your money. 7) In general, and ETF or index fund is a good idea, the key being to minimize the compound effect of expenses over the long term. There are many good choices a la Vanguard here to choose from. 8) Don't worry about \"\"Buy low, sell high\"\". Don't be a speculator, be an investor (that's my version of Anthony Bourdain's, \"\"don't be a tourist, be a traveler\"\"). A speculator wants to sell shares at a higher price than they were purchased at. An investor wants to share in the profits of a company as a part-owner. If you can consistently beat the market by trying to time your transactions, good for you - you can move to Wall Street and make millions. However, almost no one can do this consistently, and it doesn't seem worth it to me to try. I don't mean to discourage you from investing, just make sure you have your bases covered so that you don't have to cash out at a bad time. Best of luck! Edit Response to additional questions below. 1) Emergency fund. I would recommend not investing in anything other than cash equivalents (money market, short-term CDs, etc.) until you've built up an emergency fund. It makes sense to want to make the \"\"best\"\" use of your money, but you also have to account for risk. My concern is that if you were to experience one or more adverse life events, that you could lose a lot of money, or need to pay a lot in interest on credit card debt, and it would be prudent to self-insure against some of those risks. I would also recommend against using an investment account as an emergency fund account. Taking money out of investment accounts is inefficient because the commissions/taxes/fees can easily eat up a significant portion of your returns. Ideally, you would want to put money in and not touch it for a long time in order to take advantage of compounding returns. There are also high penalties for early disbursements from retirement funds. Just like you need enough money in your checking account to buy food and pay the rent every month, you need enough money in an emergency fund to pay for things that are a real possibility, even if they are less common. Using a credit card or an investment account is a relatively expensive way to do this. 2) Invest at all? I would recommend starting an emergency fund, and then beginning to invest for retirement. Once your retirement savings are on track, you can begin saving for whatever other goals you may have\"",
"title": ""
},
{
"docid": "193012",
"text": "The 'standard' in such moving average crossover systems is 50/200. The numbers are essentially arbitrary as long as the long term average is greater than the short term and there is some different between the averages in terms of the smoothing they provide (i.e. comparing a 74 day MA to a 75 day MA isn't what the system is intended for) There are plenty of software programs that will let you run through many possible values for the system over historical data. I concur with the other answers in that this system/indicator alone isn't very good. However, I disagree with their blanket brushing off of technical analysis. There are many successful traders out there. The moving average cross over system is perhaps the second most primitive example of technical strategies categorized as trend following systems (buying new recent highs and selling new recent lows being the most simple). This particular system isn't very powerful because of its poor use of simple moving averages. A simple moving average is intended to smooth out data, but smoothing comes at the cost of lagging from the present. A simple moving average essentially gives you an idealized smoothing of price action for the day at that is one half of their period ago. So your 200 day simple moving average shows you an idealized smoothing of price action 100 days ago. A lot can happen in 100 days and that is why this system is far from ideal.",
"title": ""
},
{
"docid": "424511",
"text": "Your asset mix should reflect your own risk tolerance. Whatever the ideal answer to your question, it requires you to have good timing, not once, but twice. Let me offer a personal example. In 2007, the S&P hit its short term peak at 1550 or so. As it tanked in the crisis, a coworker shared with me that he went to cash, on the way down, selling out at about 1100. At the bottom, 670 or so, I congratulated his brilliance (sarcasm here) and as it passed 1300 just 2 years later, again mentions how he must be thrilled he doubled his money. He admitted he was still in cash. Done with stocks. So he was worse off than had he held on to his pre-crash assets. For sake of disclosure, my own mix at the time was 100% stock. That's not a recommendation, just a reflection of how my wife and I were invested. We retired early, and after the 2013 excellent year, moved to a mix closer to 75/25. At any time, a crisis hits, and we have 5-6 years spending money to let the market recover. If a Japanesque long term decline occurs, Social Security kicks in for us in 8 years. If my intent wasn't 100% clear, I'm suggesting your long term investing should always reflect your own risk tolerance, not some short term gut feel that disaster is around the corner.",
"title": ""
},
{
"docid": "368338",
"text": "Short time horizon, small pot of money, and low appetite for risk? That smells like low return situation to me. I guess it depends on how low your appetite for risk is, though. You could open a brokerage account (free) and purchase $10K worth of a fully diversified ETF like VTI, optionally putting maybe 20% of it in a diversified bond ETF. I consider that a reasonably conservative investment, but if you are of the mindset that you cannot tolerate a drop in your wealth, it's not going to work. Plus if you don't have any other investments, this will be the thing that requires you to report capital gains to the IRS, and that paperwork is never fun. As an alternative, you have CD's, which will make you very little. Or a high-ish interest rate electronic savings account like Capital one 360 or Emigrant Direct (there are probably newer ones now that outcompete even these). Still, with anything in this paragraph you will be lucky to beat inflation. The real interest rate was negative last time I checked, so every risk-free investment will lose money in purchasing power terms. To beat inflation you will need to take on nonnegligible risk.",
"title": ""
},
{
"docid": "53820",
"text": "Hello all, Ive recently accepted a job at one of the big banks as a marketer. Ideally this role leads to becoming a financial advisor. I was wondering if there is anyone here has experience with that career path-starting as a marketer and becoming an FA- and if it was worth doing it over going to grad school or whatever other career interests you had. Also, what were your hours like when you first started? Ive heard horror stories about people coming in before 7 and staying after 7...",
"title": ""
}
] |
7542
|
How can OTC scams affect you?
|
[
{
"docid": "68187",
"text": "\"Am I being absurd? No. Should I be worrying? Yes. If I sell in the morning, I've only lost a couple hundred dollars, and learned a valuable lesson. Is there any reason to believe it won't be that simple? If you're lucky, you'll be able to dump your stocks to someone like you who'll be punching himself in the face tomorrow night. If not - you're stuck. You may end up selling them to your broker as worthless. You might have become a victim of a \"\"pump and dump\"\" fraud. Those are hard to identify in real-time, but after been burned like that myself (for much lesser amounts than you though), I avoid any \"\"penny\"\" stocks that go up for no apparent (and verifiable) reason. In fact, I avoid them altogether.\"",
"title": ""
}
] |
[
{
"docid": "416941",
"text": "Merrill charges $500 flat fee to (I assume purchase) my untraded or worthless security. In my case, it's an OTC stock whose management used for a microcap scam, which resulted in a class action lawsuit, etc. but the company is still listed on OTC and I'm stuck with 1000s of shares. (No idea about the court decision)",
"title": ""
},
{
"docid": "271116",
"text": "Absolute scam. Any time anyone asks you to open a bank account so they can send you money and then you have to send some portion of it back to them, it's a guarantee that it's a scam. What happens is that your dad will deposit the check and transfer it to this woman, then the check will bounce (or turn out to be fake altogether) and your dad will be on the hook for the money to the bank. These schemes are dependent on the fact that people want hope and believe in quick, easy money, and it works as long as the con artists are able to get the 'mark' (the person who deposits the check and sends them the money) to send the money before the check (always drawn on some obscure foreign bank) has a chance to clear. This is another variation of a long-running type of bank scam, and if you get involved, you'll regret it. I hope you can keep your dad from getting involved, because it will create a financial mess and affect his credit as well. The basic premise of this scam is this: In the interests of providing good customer service, most banks will make some or all of a deposit available right away, even though the check hasn't cleared. The scammer has you withdraw the money (either a cashier's check, have you send a wire transfer, etc) immediately and send it to them. Eventually the check is returned because it is The bank charges the check back against your account, often imposing pretty substantial penalties and fees, so you as the account holder are left without the money you sent the scammer and all of the fees. This is the easy version of events. You could end up in legal trouble, depending on the nature of the scam and what they determine your involvement to be. It will certainly badly affect your banking history (ChexSystems tracks how we all treat bank accounts, much like the credit agencies do with our credit), so you may have trouble opening bank accounts. So there are many consequences to this to think about, and it's why you JUST SAY NO!! Don't walk away from this -- RUN!!!",
"title": ""
},
{
"docid": "390779",
"text": "\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \"\"Get Rich on Penny Stock\"\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\"",
"title": ""
},
{
"docid": "421688",
"text": "It's not enough just to check if your order doesn't exceed 10% of the 20 day average volume. I'll quote from my last answer about NSCC illiquid charges: You may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. The NSCC issues a charge to the clearing firm if in aggregate, their orders exceed the limits, and the clearing firm usually passes these charges on to the broker(s) that placed the orders. Your broker may or may not pass the charges through to you; they may simply charge you significantly higher commissions for trading OTC securities and use those to cover the charges. Since checking how the volume of your orders compares to the average past volume, ask your broker about their policies on trading OTC stocks. They may tell you that you won't face illiquid charges because the higher cost of commissions covers these, or they may give you specifics on how to verify that your orders won't incur such charges. Only your broker can answer this with certainty.",
"title": ""
},
{
"docid": "346407",
"text": "\"This is colloquially referred to as a \"\"pump and dump\"\" scheme. You basically buy up some stock, and then try to pump up the demand through false and misleading positive statements and market activity. You then close your position once market interest is sufficiently high. If your firm has access to high frequency trading mechanisms, you may even be able to front run other market participants attracted by your buying activities. >I am wondering what is the best route to go down. Definitely micro-cap stocks. Things listed on the OTC markets, especially penny stocks, have this tendency to attract retail buyers just begging to be scammed. Emerging biotech firms also have a lot of potential due to investors' hopes of successful clinical trials. I should warn you though, this is very illegal and falls under market manipulation [according to the SEC](https://www.sec.gov/fast-answers/answerspumpdumphtm.html) and can lead to up to 25 years in prison. So make sure you stay small enough to avoid the regulatory radar. (But seriously, this belongs in r/personalfinance or elsewhere, r/finance isn't the sub you want).\"",
"title": ""
},
{
"docid": "528576",
"text": "I am in complete agreement with you. The place i have found with the sort of charts you are looking for is stockcharts.com. To compare the percentage increase of several stocks over a period of 2 market-open days or more, which is quite useful to follow the changes in various stocks… etc., an example: Here the tickers are AA to EEEEE (OTC) and $GOLD / $SILVER for the spot gold / silver price (that isn't really a ticker). It is set to show the last 6 market days (one week+)...the '6' in '6&O'. You can change it in the URL above or change it on the site for the stocks you want... up to 25 in one chart but it gets really hard to tell them apart! By moving the slider just left of the ‘6’ at the bottom right corner of the chart, you can look at 2 days or more. For a specific time period in days, highlight the ‘6’ and type any number of market-open days you want (21 days = about one month, etc.). By setting a time period in days, and moving the entire slider, you can see how your stocks did in the last bull/bear run, as an example. The site has a full how-to, for this and the other types of charts they offer. The only problem is that many OTC stocks are not charted. Save the comparison charts you use regularly in a folder in your browser bookmarks. Blessings. I see the entire needed link isn't in blue... but you need it all.",
"title": ""
},
{
"docid": "63848",
"text": "The only way for a mutual fund to default is if it inflated the NAV. I.e.: it reports that its investments worth more than they really are. Then, in case of a run on the fund, it may end up defaulting since it won't have the money to redeem shares at the NAV it published. When does it happen? When the fund is mismanaged or is a scam. This happened, for example, to the fund Madoff was managing. This is generally a sign of a Ponzi scheme or embezzlement. How can you ensure the funds you invest in are not affected by this? You'll have to read the fund reports, check the independent auditors' reports and check for clues. Generally, this is the job of the SEC - that's what they do as regulators. But for smaller funds, and private (i.e.: not public) investment companies, SEC may not be posing too much regulations.",
"title": ""
},
{
"docid": "545752",
"text": "If your concern is scams, we should be talking about counterparties, not bitcoin itself. Unless you think the protocol itself is a scam, which imo it most certainly is not. You're conflating the trustworthiness of counterparties with the trustworthiness of the underlying protocol, which imo is not a very good model to operate by. You'll understand the situation better of you look at them independently. Bitcoin isn't trying to be a credit agency or the better business bureau, it's just trying to be digital money. Don't expect it to protect you from scams any more than cash will. That's not its job, and does not affect its trustworthiness as money.",
"title": ""
},
{
"docid": "545789",
"text": "\"How can I say this more clearly? SCAM, SCAM, SCAM! This is another one of the oldest scams out there, where you've won a prize or an inheritance has come in, and all you have to do is pay the taxes on it to claim it. Don't be a sucker! Ask yourself why the government couldn't (and wouldn't) just take the taxes due out of the funds they have and give the rest to the person they belong to? Wouldn't that be the smartest and easiest thing to do? As an example, let's say that you have $1,000 that belongs to me, and I owe you $100. Would you tell me to pay you the $100 and then you'll give me the $1,000 or would you take the $100 I owe you out of the $1,000 and give me the remaining $900? The fact this is someone you know from the internet and they want your \"\"help\"\" to claim their money should tell you how much of a scam this is. Stop talking to this person, and don't tell them anything personal about you. They are scam artists, and whatever you tell them could be used to steal your identity or take your money. Be careful, my friend!\"",
"title": ""
},
{
"docid": "42347",
"text": "Something to consider is that in the case of the company you chose, on the OTC market, that stock is thinly traded and with such low volume, it can be easy for it to fluctuate greatly to have trades occur. This is why volume can matter for some people when it comes to buying shares. Some OTC stocks may have really low volume and thus may have bigger swings than other stocks that have higher volume.",
"title": ""
},
{
"docid": "339268",
"text": "\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \"\"T\"\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \"\"ANET\"\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \"\"P\"\" to the end for \"\"preferreds\"\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\"",
"title": ""
},
{
"docid": "597519",
"text": "it looks like using an ADR is the way to go here. michelin has an ADR listed OTC as MGDDY. since it is an ADR it is technically a US company that just happens to be a shell company holding only shares of michelin. as such, there should not be any odd tax or currency implications. while it is an OTC stock, it should settle in the US just like any other US OTC. obviously, you are exposing yourself to exchange rate fluctuations, but since michelin derives much of it's income from the US, it should perform similarly to other multinational companies. notes on brokers: most US brokers should be able to sell you OTC stocks using their regular rates (e.g. etrade, tradeking). however, it looks like robinhood.com does not offer this option (yet). in particular, i confirmed directly from tradeking that the 75$ foreign settlement fee does not apply to MGDDY because it is an ADR, and not a (non-ADR) foreign security.",
"title": ""
},
{
"docid": "225030",
"text": "\"It's a scam. The cashier's check will be forged. Craigslist has a warning about it here (item #3). What kind of payment do you think is not fakable? Or at least not likely to be used in scams? When on craigslist - deal only locally and in person. You can ask to see the person's ID if you're being paid by check When being paid by check, how can seeing his/her ID help? In case the check isn't cashable, I can find that person by keeping record of his/her ID? If you're paid by check, the payers details should be printed on the check. By checking the ID you can verify that the details match (name/address), so you can find the payer later. Of course the ID can be faked too, but there's so much you can do to protect yourself. You'll get better protection (including verified escrow service) by selling on eBay. Is being paid by cash the safest way currently, although cash can be faked too, but it is the least common thing that is faked currently? Do you recommend to first deposit the cash into a bank (so that let the bank verify if the cash is faked), before delivering the good? For Craigslist, use cash and meet locally. That rules out most scams as a seller. What payment methods do you think are relatively safe currently? Then getting checks must be the least favorite way of being paid. Do you think cash is better than money order or cashier order? You should only accept cash. If it is a large transaction, you can meet them at your bank, have them get cash, and you receive the cash from the bank. Back to the quoted scam, how will they later manipulate me? Are they interested in my stuffs on moving sale, or in my money? They will probably \"\"accidentally\"\" overpay you and ask for a refund of some portion of the overpayment. In that case you will be out the entire amount that you send back to them and possibly some fees from your bank for cashing a bad check.\"",
"title": ""
},
{
"docid": "346669",
"text": "The OTC market is a marketplace, the location it definitely relied on the purchaser marketplace. The OTC market is mostly used to exchange bonds among the two occasions and all this technique are executed by way of manner of the third celebration. They are able to also be used to alternate equity, such because of the OTC QX and purple marketplaces within the USA. The minamargroup is the Florida, USA situated agency, who elements their purchase investor relation with to present organization into to make new ones. OTC way it's far a protection traded in some context other, changing between parties or groups inclusive of New York Stock trade.",
"title": ""
},
{
"docid": "343518",
"text": "\"This is clearly a scam, and you should stay away from it. Anyone reading this knew that from the title alone - and it seems that you know it too. Don't \"\"test\"\" whether something is a scam by putting your own money in it. That is exactly how these scammers make money, and how you lose it. How their scam works is irrelevant. The simple fact is that there is no way you can safely earn 20% return over the course of a year, let alone in 1 day*. You know this is true. Don't bother trying to figure out what makes it true in this case. There is no free lunch. Best case scenario, this is a hyper-risky investment strategy [on the level of putting your money down at a roulette wheel]. Worst case scenario, they simply steal your money. Either way, you won't come out ahead. Although I agree with others that this is likely a Ponzi scheme, that doesn't really matter. What matters is, there is no way they can guarantee those returns. Just go to a casino and throw your money away yourself, if you want that level of risk. *For reference, if you invested $100 for a year, earning 20% returns every day, you would have 6 million trillion trillion dollars by the end of the year. that's $6,637,026,647,624,450,000,000,000,000,000. that number doesn't even make sense. It's more money than exists on earth. So why would they need your $100?\"",
"title": ""
},
{
"docid": "263659",
"text": "There are several red flags here. can they get my bank account info in any way from me transferring money to them? Probably yes. Almost all bank transactions are auditable, and intentionally cause a money track. This track can be followed from both sides. If they can use your bank account as if they were you, that is a bit deeper than what you are asking, but yes they (and the polish cops) can find you through that transfer. I did look up the company and didn't find any scam or complaints concerning them. Not finding scams or complains is good, but what did you find? Did you find good reviews, the company website, its register, etc, etc? How far back does the website goes (try the wayback machine) Making a cardboard front company is very easy, and if they are into identity theft the company is under some guy in guam that never heard of poland or paypal. As @Andrew said above, it is probably a scam. I'd add that this scam leverages on the how easier is to get a PayPal refund compared to a regular bank transfer. It is almost impossible to get the money back on an international transaction. Usually reverting a bank transfer requires the agreement in writing of the receiver and of both banks. As for paypal, just a dispute from the other user: You are responsible for all Reversals, Chargebacks, fees, fines, penalties and other liability incurred by PayPal, a PayPal User, or a third party caused by your use of the Services and/or arising from your breach of this Agreement. You agree to reimburse PayPal, a User, or a third party for any and all such liability. (source) Also, you might be violating the TOS: Allow your use of the Service to present to PayPal a risk of non-compliance with PayPal’s anti-money laundering, counter terrorist financing and similar regulatory obligations (including, without limitation, where we cannot verify your identity or you fail to complete the steps to lift your sending, receiving or withdrawal limit in accordance with sections 3.3, 4.1 and 6.3 or where you expose PayPal to the risk of any regulatory fines by European, US or other authorities for processing your transactions); (emphasis mine, source) So even if the PayPal transfer is not disputed, how can you be sure you are not laundering money? Are you being paid well enough to assume that risk?",
"title": ""
},
{
"docid": "282196",
"text": "\"In general I don’t think you can blame the news stories. You can blame everyone’s preconceived notion that any sort of LBO or leveraged restructuring is the devil’s work. Every American is of course well-versed in the subject. From the Sealy example, you clearly have a journalist who has no idea what they are talking about. All you have is a cherry-picked summary of what took place. As such, the “finance scholars” jump in and explain how it’s all a giant scam. Bain LBO’d Sealy in 1997. As a part of that, it was saddled with ~$700m in debt. That of course is fodder for the \"\"finance scholars\"\" because they don't understand the benefits of debt and more generally how LBOs work, none of which are noted in the article. The article then notes that Sealy has recently encountered trouble. To the \"\"geniuses\"\" this is of course because of Romney's work and the ~$700m in debt. No one notices the fact that Bain unloaded this in 2004 for double what it paid for it. For those that did, the unloading was a textbook Bain scam. Bain unloaded this to KKR, perhaps the sharpest and most successful PE firm in history. Would KKR put $1.5b into this if it were a scam? According to the \"\"geniuses\"\", of course they would. How could Mitt Romney actually improve a business? No one looks at the fact that revenues were up considerably, margins had expanded tremendously, growth prospects were higher, and FCF yields were fantastic. This is why KKR bought the company, and this is what an LBO is supposed to be. I haven't done a ton of work on this case, it was before my time, but I would be very surprised if the growth wasn't accompanied by employee expansion as well. You also get the “I wish I had a way to just walk away from my debt” comment. I don’t even know where to begin explaining how asinine that is. Equity is subordinated to debt. That’s the definition of equity. The article also notes the one-sided-mattress idea, which is construed as Romney's giant scam to screw the average American while flipping this company and making his millions. The article of course didn't note that this one-sided mattress idea was a mere fraction of revenue. This was designed as an economy mattress, with an advertised shorter shelf life. Plus how can this be a scam? Would you go into the mattress store and pay the same amount for a mattress with only one side? If you would you deserve to get half of a mattress. So the crux of it is, this is in actuality an example of what an LBO should be. At least for Bain’s part. Bain took a business that was ripe for an LBO (reasonable steady FCF, low leverage), did the LBO, improved the business, and came out on top. What KKR did with it afterwords I have no idea. I would imagine it has more to do with deteriorating business conditions than the debt on its balance sheet. I work with restructurings over 100 hours a week. I of course don’t come up with the plans (I’m a lowly analyst building models and associated bitchwork) but I see just how brilliant these ideas are. In a lot of cases restructurings prevent the tripping of covenants and associated bankruptcy and allow for strategy to play out and for companies to grow. I can of course give a more detailed rant on the article, but I figured no one will read this anyway.\"",
"title": ""
},
{
"docid": "593644",
"text": "NSCC illiquid charges are charges that apply to the trading of low-priced over-the counter (OTC) securities with low volumes. Open net buy quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net buy quantity must be less than 5,000,000 shares per stock for your entire firm Basically, you can't hold a long position of more than 5 million shares in an illiquid OTC stock without facing a fee. You'll still be assessed this fee if you accumulate a long position of this size by breaking your purchase up into multiple transactions. Open net sell quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net sell quantity must be less than 10% percent of the 20-day average volume If you attempt to sell a number of shares greater than 10% of the stock's average volume over the last 20 days, you'll also be assessed a fee. The first link I included above is just an example, but it makes the important point: you may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. Technically, these fees are assessed to the clearing firm, not the individual investor, but usually the clearing firm will pass the fees along to the broker (and possibly add other charges as well), and the broker will charge a fee to the individual account(s) that triggered the restriction. Also, remember that when buying OTC/pink sheet stocks, your ability to buy or sell is also contingent on finding someone else to buy from/sell to. If you purchase 10,000 shares one day and attempt to sell them sometime in the future, but there aren't enough buyers to buy all 10,000 from you, you might not be able to complete your order at the desired price, or even at all.",
"title": ""
},
{
"docid": "467352",
"text": "Depends on how you measure liquidity. There's papers out there that approach this very question. Measured in order book spreads for a consolidated $100m trade, I'd say the second biggest market is FX swaps, followed or par'd by the money market (government bonds). If you disallow OTC venues, it's most definitely exchange listed government bonds. If, however, you happen to think in terms of sheer volume per time, the most liquid market phase could be considered the NYSE closing auction, as you can move billions in a matter of minutes, or expressed in speed terms: several m$/s (million dollars per second). You should pick a definition and we can provide you with a more accurate list of candidates and actual data.",
"title": ""
},
{
"docid": "123511",
"text": "\"What can I do to help him out, but at the same time protect myself from any potential scams? Find out why he can't do this himself. Whether your relative is being sincere or not, if he owns both accounts then he should be able to transfer money between them by himself. If you can find a way to solve that issue without involving your bank account, so much the better. Don't settle for \"\"something about authorized payees and expired cards.\"\" Get details, write them down. If possible, get documents. Then go to a bank or financial adviser you can trust and run those details by them to see what they have to say. Even if there's no scam, if what he's trying to do is illegal (even if he doesn't realize it himself) then you want to know before you get involved. You say you're willing to deal with \"\"other issues\"\" separately, but keep in mind that, even if there's no external scam here, those \"\"other issues\"\" could include hefty fees, censures on your own account, or jail time. Ask yourself: Does it make sense that this relative has an account overseas? I don't have any overseas accounts, because I don't do business in other countries. Is your relative a dual-citizen? Does he travel a lot? What country is the overseas account in? How long has he had this account? What bank is it with? Where the money is going is just as important as how it gets there (ie: through your account.) Arguably more so. Keep in mind that many scammers tell their marks not to share what's going on with anyone else. (Because doing so increases the odds of someone telling them to snap out of it.) It's entirely possible he's being scammed himself and just not telling you the whole story because the 419er is telling him to keep it quiet. (Check out that link for more details on common scams that your relative may be unwittingly part of, btw.) Get as many details as possible about what he's doing and why. If he's communicating with anyone else regarding this transfer, find out who. If there are emails, ask his permission to read them and watch for anything suspicious (ie: people who can't spell their own name consistently, constant pressure to act quickly, etc.)\"",
"title": ""
},
{
"docid": "432727",
"text": "\"Shares sold to private investors are sold using private contracts and do not adhere to the same level of strict regulations as publicly traded shares. You may have different classes of shares in the company with different strings attached to them, depending on the deals made with the investors at the time. Since public cannot negotiate, the IPO prospectus is in fact the investment contract between the company and the public, and the requirements to what the company can put there are much stricter than private sales. Bob may not be able to sell his \"\"special\"\" stocks on the public exchange, as the IPO specifies which class of stock is being listed for trading, and Bob's is not the same class. He can sell it on the OTC market, which is less regulated, and then the buyer has to do his due diligence. Yes, OTC-sold stocks may have strings attached to them (for example a buy back option at a preset time and price).\"",
"title": ""
},
{
"docid": "249643",
"text": "In a perfect the world, the most ideal solution would be to find a way to pay back all of your debt so that your credit will not be affected any further. Unfortunately, it does not work this way most of the time. Debt settlement is where you work with a creditor to settle your a credit card debt for less than the full amount owed. This could be a very viable solution for you instead of filing for bankruptcy. However, there are many scams out there when it applies to debt settlement so you must tread carefully. Debt settlement can only occur when you're behind on your payments. If you are currently paying off your payments successfully, the creditor has no obligation to settle when they think you should be able to pay it fully back.",
"title": ""
},
{
"docid": "517573",
"text": "\"Affinity fraud. You see, Madoff really didn't have to sell himself, people recommended him to their friends. In a similar way, it's easy once a scammer reels in one sucker to keep him on the hook long enough to get 10 friends to invest as well. I've written about Mortgage Acceleration scams, and the common thread is that they are first sold to friends, relatives, neighbors. People tell their fellow church goer about it and pretty soon people's belief just takes over as they want it to work. Edit - the scam I referenced above was the \"\"Money Merge Account\"\" and its reincarnated \"\"Wealth Unlimited.\"\" It claimed to use sophisticated software to enable one to pay their mortgage in less than half the time while not changing their budget. The sellers of the product weren't able to explain how it was supposed to work, since it was nonsense anyway. You were supposed to be able to borrow against a HELOC at a rate higher than your mortgage, yet come out ahead, enough to cut the time in half or less. The link I posted above leads to a spreadsheet I wrote in a weekend, which was better at the math than their software and free. It also linked to 66 pages of accumulated writing I did over a number of months starting in 2008. In the end, I never saw any prosecution over this scam, I suppose people were too embarrassed once they realized they wasted $3500. How can I get scammed buying S&P ETFs through Schwab? Easy, I can't.\"",
"title": ""
},
{
"docid": "319599",
"text": "Well I'm not going to advise whether it's a good idea to invest in this company (though often OTC is pretty scary), but it DOES have a product (vivio, an ad blocker), it did post financials and it's trading on the OTC-QB (which is better than the pink sheets), so you need to look these over and study up on the product to decide if it is overpriced or not. What might have occurred (viz the Patriot Berry Farm becoming Cyberfort) is that the latter bought up the stock of the former (this is, I believe, called using a shell, which is not necessarily a bad thing) and is using this as a way to be registered, i.e. sell to non-accredited investors via the OTC market. So I'm really just answering your third question: yes, you have to do a lot of due diligence to see if buying this stock is a good deal or not. It might be the next big thing. Or it might not. It certainly is the case that low trading volume allows a relatively small trade to really change the stock price, so the penny stocks do tend to be easier to 'inflate'. Side comment: the bid/ask spreads are pretty big, with a best bid of 0.35 and best ask of 0.44.",
"title": ""
},
{
"docid": "29571",
"text": "how are the ways he could scam me? There are hundreds of different ways the scam can progress ... broadly;",
"title": ""
},
{
"docid": "214518",
"text": "\"It is likely a scam. In fact the whole mystery shopping \"\"job\"\" may be a scam. There is a Snopes page about cashier's check scams, as well as a US government page which specifically mentions mystery shopping as a scam angle. As for how the scam works, from the occ.gov site I just linked: However, cashier’s checks lately have become an attractive vehicle for fraud when used for payments to consumers. Although, the amount of a cashier’s check quickly becomes \"\"available\"\" for withdrawal by the consumer after the consumer deposits the check, these funds do not belong to the consumer if the check proves to be fraudulent. It may take weeks to discover that a cashier’s check is fraudulent. In the meantime, the consumer may have irrevocably wired the funds to a scam artist or otherwise used the funds—only to find out later, when the fraud is detected—that the consumer owes the bank the full amount of the cashier’s check that had been deposited. It is somewhat unusual in that, from what you say, there has been no attempt thus far to get money back. However, your sister-in-law may have received that info separately, or received it as part of her mystery shopping job but didn't mention it to you with regard to this check. Typically the scam involves telling the recipient to transfer money to a third party (e.g., by buying goods as a mystery shopper, or via wire transfer to \"\"reimburse\"\" someone associated with a sham operation). By the time the cashier's check is revealed as fraudulent, the victim has already transferred away his/her own real money. It's probably worth taking the check to your or her bank and asking them about it. They may have more info. Also, banks usually want to know about scams like this because, in the long run, they accumulate data on them and share that with law enforcement and can eventually catch some of the scammers. Edit: Just to help anyone who may be reading this later. The letter you added confirms it is absolutely a scam. My boss was once contacted via a scam operation very similar to this. The huge red flag (in addition to others already mentioned) is that you are being \"\"given\"\" a check for over $2000, of which only $25 is purportedly for actual mystery shopping and $285 is payment for you, the mystery shopper. The whole rest of the $2000+ amount is for you to wire to \"\"another Mystery/Secret Shopper in order for them to complete their assignment\"\". They are giving you $2000 to give to someone else who is supposedly another one of their own employees/contractors. Ask yourself what sane business would conduct their operations in this way. If you work at a law office, or a hamburger stand, or a school, or anything you like, does your boss ever say \"\"Here is your paycheck for $5000. I know you only earned $1000, but I'm just going to give you the whole $5000, and you're supposed to use $4000 of it to pay your coworker Joe his wages.\"\" No. There is no reason to do that except that the \"\"other mystery shopper\"\" is actually the scammer.\"",
"title": ""
},
{
"docid": "526073",
"text": "Publicly traded companies perform dilution via an FPO (Follow-up Public Offer). It is a process similar to IPO, with announcements, prospectus, etc. You will know ahead of time when that happen. Stocks traded OTC are not required to file a lot of regulatory documents that publicly traded stocks are required to file, and may not disclose dilutions or additional issues. By buying OTC you agree to these terms. You will probably get a notice and a chance to vote on that in your proxy statement, but that happens when you already own the stock.",
"title": ""
},
{
"docid": "208507",
"text": "$15 being how much it costs to drive a car about 10 miles, and does not account for a driver's time. Hilarious shit, from the biggest payday loan scam the planet has ever seen. Because Uber is nothing but a scam where you work your ass off, to steal money from your future self, and give 25% of it to Uber! But if you think 6 cents a mile is a decent wage for a cab driver (which is what you can make, if you are lucky), then by all means, please sign up!",
"title": ""
},
{
"docid": "510163",
"text": "\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \"\"IPO Date\"\" is wrong on this one. However, there are several companies that appear to do an \"\"IPO\"\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \"\"IPO\"\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \"\"IPO\"\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \"\"IPO\"\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \"\"Initial\"\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\"",
"title": ""
},
{
"docid": "496370",
"text": "\"Yeah, I'll take the challenge...:) How trustworthy these are and what are their sources of income? These are in fact two separate questions, but the answers are related. How trustworthy? As trustworthy as they're clear about their own sources of income. If you cannot find any clue as to why, what for and how they're paying you - you probably should walk away. What's too good to be true usually is indeed too good to be true. For those of the sites that I know of their sources of income, it is usually advertisements and surveys. To get paid, you have to watch advertisements and/or answer surveys. I know of some sites who are legit, and pay people (not money, but gift cards, airline miles, etc) for participating in surveys. My own HMO (Kaiser in California) in fact pays (small amounts) to members who participate in enough surveys, so its legit. Are these sites worthwhile to consider for extra income? Not something you could live off, but definitely can get you enough gift cards for your weekly trip to Starbucks. What do I need to consider tax wise? Usually the amounts are very low, and are not paid in cash. While it is income, I doubt the IRS will chase you if you don't report the $20 Amazon gift card you got from there. It should, strictly speaking, be reported (probably as hobby income) on your tax return. Most people don't bother dealing with such small amounts though. In some cases (like the HMO I mentioned), its basically a rebate of the money paid (you pay your copays, deductibles etc. Since the surveys are only for members, you basically get your money back, not additional income). This is in fact similar to credit card rebates. Is there a best practice for handling the income? If we're talking about significant amounts (more than $20-30 a year), then you need to keep track of the income and related expenses, and report it as any other business income on your taxes, Schedule C. Is there a good test to determine what is and isn't a scam? As I said - if it looks too good to be true - it most likely is. If you're required to provide your personal/financial information without any explanation as to why, what it will be used for, and why and what for you're going to be paid - I'd walk away. Otherwise, you can also check Internet reviews, BBB ratings, FTC information and the relevant state agencies and consumer watchdogs (for example: http://www.scamadviser.com) whether they've heard of that particular site, and what is the information they have on it. A very good sign for a scam is contact information. Do they have a phone number to call to? Is it in your own country? If its not in your own country - definitely go away (for example the original link that was in the question pointed to a service whose phone number is in the UK, but listed address is in Los Angeles, CA. A clear sign of a scam). If they do have a phone number - try it, talk to them, call several times and see how many different people you're going to talk to. If its always the same person - run and hide. Do they have an address? If not - walk away. If they do - look it up. Is it a PMB/POB? A \"\"virtual\"\" office? Or do they have a proper office set up, which you can see on the map and in the listings as their office? And of course your guts. If your guts tell you its a scam - it very likely is.\"",
"title": ""
}
] |
9410
|
What's the difference between shares outstanding and regular shares?
|
[
{
"docid": "98654",
"text": "outstanding shares are the shares(regular shares) that are still tradable in the market, where the firm in question is listed. The term is primarily used to distinguish from shares held in treasury(treasury stock), which have been bought back(buybacks) from the market and aren't currently tradable in the market. Wikipedia is a bit more clearer and mentions the diluted outstanding shares(used for convertible bonds, warrants, etc) which is used to calculated diluted EPS.",
"title": ""
}
] |
[
{
"docid": "313372",
"text": "\"There are a few other items that you should be aware of when getting options: The strike price is usually determined by an independent valuation of the common shares (called a 409a valuation). This should give you a sense on what the options are worth. Obviously you are hoping that the value becomes many multiple of that. There are two kinds in the US: Non-quals (NQO) and Incentive Stock Options (ISOs). The big difference is that when you exercise Non-quals, you have to pay the tax on the difference between the \"\"fair\"\" market value on the shares and what you paid for them (the strike price). This is important because if the company is private, you likely can not sell any shares until it is public. With ISOs, you don't pay any tax (except AMT tax) on the gain until you actually sell the shares. You should know what kind your getting. Some plans allow for early exercise, essentially allowing you to buy the shares early (and given back if you leave before they vest) which helps you establish capital gains treatment earlier as well as avoid AMT if you have ISOs. This is really complicated direction and you would want to talk to a tax professional. And always a good idea to know how many total shares outstanding in the Company. Very few people ask this question but it is helpful for you to understand the overall value of the options.\"",
"title": ""
},
{
"docid": "582736",
"text": "In Australia the ATO can determine if you are considered a shareholder or a share trader. The ATO defines a shareholder as: A shareholder is a person who holds shares for the purpose of earning income from dividends and similar receipts. Whilst they define a share trader as: A share trader is a person who carries out business activities for the purpose of earning income from buying and selling shares. To find out the differences between them you can refer to the following link describing The difference between a share trader and a shareholder. The ATO also describes: To be classed as a share trader, you may be asked to provide evidence that demonstrates you are carrying on a business of share trading, for example: the purchase of shares on a regular basis through a regular or routine method a trading plan use of share trading techniques in managing your share acquisitions, such as decisions based on thorough analysis of relevant market information a contingency plan in the event of a major shift in the market. Losses incurred in the business of share trading are treated the same as any other losses from business. If your activities change from investor to trader, your investment changes from a CGT (capital gains tax) asset to trading stock. This can trigger CGT event for any investments you currently hold as they change from CGT assets to trading stock. Once you have changed over to a trader you will not be entitled to the 50% CGT discount for stocks held over 12 months. You will, however, be able to count any paper losses at the end of Financial Year to reduce your other income.",
"title": ""
},
{
"docid": "427859",
"text": "\"I think it's easiest to illustrate it with an example... if you've already read any of the definitions out there, then you know what it means, but just don't understand what it means. So, we have an ice cream shop. We started it as partners, and now you and I each own 50% of the company. It's doing so well that we decide to take it public. That means that we will be giving up some of our ownership in return for a chance to own a smaller portion of a bigger thing. With the money that we raise from selling stocks, we're going to open up two more stores. So, without getting into too much of the nitty gritty accounting that would turn this into a valuation question, let's say we are going to put 30% of the company up for sale with these stocks, leaving you and me with 35% each. We file with the SEC saying we're splitting up the company ownership with 100,000 shares, and so you and I each have 35,000 shares and we sell 30,000 to investors. Then, and this depends on the state in the US where you're registering your publicly traded corporation, those shares must be assigned a par value that a shareholder can redeem the shares at. Many corporations will use $1 or 10 cents or something nominal. And we go and find investors who will actually pay us $5 per share for our ice cream shop business. We receive $150,000 in new capital. But when we record that in our accounting, $5 in total capital per share was contributed by investors to the business and is recorded as shareholder's equity. $1 per share (totalling $30,000) goes towards actual shares outstanding, and $4 per share (totalling $120,000) goes towards capital surplus. These amounts will not change unless we issue new stocks. The share prices on the open market can fluctuate, but we rarely would adjust these. Edit: I couldn't see the table before. DumbCoder has already pointed out the equation Capital Surplus = [(Stock Par Value) + (Premium Per Share)] * (Number of Shares) Based on my example, it's easy to deduce what happened in the case you've given in the table. In 2009 your company XYZ had outstanding Common Stock issued for $4,652. That's probably (a) in thousands, and (b) at a par value of $1 per share. On those assumptions we can say that the company has 4,652,000 shares outstanding for Year End 2009. Then, if we guess that's the outstanding shares, we can also calculate the implicit average premium per share: 90,946,000 ÷ 4,652,000 == $19.52. Note that this is the average premium per share, because we don't know when the different stocks were issued at, and it may be that the premiums that investors paid were different. Frankly, we don't care. So clearly since \"\"Common Stock\"\" in 2010 is up to $9,303 it means that the company released more stock. Someone else can chime in on whether that means it was specifically a stock split or some other mechanism... it doesn't matter. For understanding this you just need to know that the company put more stock into the marketplace... 9,303 - 4,652 == 4,651(,000) more shares to be exact. With the mechanics of rounding to the thousands, I would guess this was a stock split. Now. What you can also see is that the Capital Surplus also increased. 232,801 - 90,946 == 141,855. The 4,651,000 shares were issued into the market at an average premium of 141,855 ÷ 4,651 == $30.50. So investors probably paid (or were given by the company) an average of $31.50 at this split. Then, in 2011 the company had another small adjustment to its shares outstanding. (The Common Stock went up). And there was a corresponding increase in its Capital Surplus. Without details around the actual stock volumes, it's hard to get more exact. You're also only giving us a portion of the Balance Sheet for your company, so it's hard to go into too much more detail. Hopefully this answers your question though.\"",
"title": ""
},
{
"docid": "211343",
"text": "Investopedia has a good definition. Stock dividends are similar to cash dividends; however, instead of cash, a company pays out stock. Stock splits occur when a company perceives that its stock price may be too high. Stock splits are usually done to increase the liquidity of the stock (more shares outstanding) and to make it more affordable for investors to buy regular lots (a regular lot = 100 shares).",
"title": ""
},
{
"docid": "165855",
"text": "\"Treasury stock is not really represented in the Balance Sheet as a \"\"Treasury stock\"\" line item in the assets. Some companies will break out Treasury Shares as a line item in the \"\"Shareholders Equity\"\" heading of the balance sheet but Apple hides it in the \"\"Shares Issued and Outstanding\"\" counts under the \"\"Shareholders Equity\"\" heading. As of the most recent Q2 2017 quarterly report There are 5,205,815,000 shares issued against 5,336,166,000 shares outstanding. This indicates that Apple is retaining about 130,351,000 shares in treasury. On the Q1 10-Q you can see that Apple had 5,255,423,000 shares issued which indicates roughly 49mm shares were repurchased by the end of Q2. You can roughly verify this by looking at page 18 of the Q2 filing in the summary of the share repurchase program. Repurchased as part of an Accelerated Share Repurchase arrangement bleeds between quarters but from February 2017 through May 2017 there have been 17.5mm shares repurchased. 31mm shares were also repurchased on the open market in Q2. The \"\"shares issued\"\" total is on a downward trend as part of Apple's share repurchase initiative that has been underway for the last couple of years.\"",
"title": ""
},
{
"docid": "324470",
"text": "Broadly, there's a bunch of stuff you need to be accounting for that's not reflected in the above, which will impact the A/D profile of an acquisition: * Consideration paid (all cash on substantially the same terms is going to be more accretive than an all-stock transaction...because in the latter, your denominator is much bigger) * Shares outstanding (including repurchases, in-kind dividends and option exercise) * Financing / interest expense * Upside / base / downside case for all of your assumptions - best to have a toggle based on a CHOOSE function that will allow the user to easily toggle between these I'm not sure what EBITDA is getting you. EPS accretion/dilution typically looks at earnings, but you could also look at Cash EPS A/D which measures OCF/shares outstanding. The point is, this really depends on how back of the envelope you want the A/D computation to be. At a minimum, you need an earnings schedule projected over the next 2-3 years, and you need a schedule reflecting outstanding shares over the same time period. Your earnings buildout can have varying degrees of granularity. You can project cost synergies over the forecast period, which most obviously is going to affect your earnings, but you can also drill down further. Financing, transaction fees, etc. Your writeups and writedowns from your B/S combination may result in certain deferred tax items that will affect your bottom line over the forecast period. Your share schedule can also have varying degrees of complexity. One way to do it is to just presume that the company will not issue any more shares, and will not repurchase any shares, and that there will be no options exercised, over the forecast period. This is a bad series of assumptions. It is likely that as options vest, if in the money, they will be exercised, resulting in dilution for existing shareholders. It is also likely that certain preferred shareholders and optionholders are going to experience adjustments to the conversion prices based on antidilution provisions in their securities. These may be but are not always disclosed in the 10K. Last point - models are tools. What are you trying to build an accretion/dilution model for? This will affect and determine the degree of granularity you'll want to go into.",
"title": ""
},
{
"docid": "393439",
"text": "Now assume these shares are vested, held for at least 1 year, and are then sold for $5 each. Everything I've read implies that the grantee now owes long-term capital gains taxes on the difference, which would be 10k * ($5 - $1). No. That's exactly what the SO is NQ for. Read more on the differences between ISO and NQSO here. Now assume these shares are vested, held for at least 1 year, and are then sold for $5 each. Everything I've read implies that the grantee now owes long-term capital gains taxes on the difference, which would be 10k * ($5 - $1). At this point you no longer have NQSO, you have RSU. If you filed 83(b) when you exercised, then you pay capital gains tax when they vest. If you didn't - its ordinary income to you. NQSO is a red herring here since once exercised they no longer exist. If you didn't file 83(b), then when the stock vests the difference between the FMV at vest and the money you spent on it when exercising (if any) is considered wages and taxed as ordinary income (+FICA etc). From that point the RSU becomes a regular stock investment and the capital gains clock starts ticking.",
"title": ""
},
{
"docid": "467936",
"text": "For the case of spinoffs it reflects the market as activities as the specific steps that have to be followed take place. For example the spinoff of Leidos from SAIC in 2013. (I picked this one becasue I knew some of the details) On September 9, 2013, the Board of Directors of SAIC, Inc.(Ticker Symbol (NYSE):SAI) approved the following: The separation of its technical, engineering and enterprise information technology services business through the distribution of shares of SAIC Gemini, Inc. to stockholders. Each stockholder of record of SAIC, Inc. as of September 19, 2013 (Record Date) will receive one (1) share of SAIC Gemini, Inc. common stock for every seven (7) shares of SAIC, Inc. common stock held by such stockholder as of the Record Date. This distribution will be effective after market close on September 27, 2013 (Distribution Date). After the Distribution Date, SAIC Gemini, Inc. will be renamed Science Applications International Corporation (New SAIC). A one (1) for four (4) reverse stock split of the SAIC, Inc. common stock effective as of Distribution Date. After the Distribution Date, SAIC, Inc. will be renamed Leidos Holdings, Inc. (Leidos). Q 11: What are the different trading markets that may occur between Record Date and Distribution Date? A: Beginning two days prior to the Record Date of September 19, 2013 through the Distribution Date on September 27, 2013, there may be three different trading markets available with respect to SAIC, Inc. and the separation. Stock Ticker – SAI (Regular Way Trading with Due Bills): Shares of SAI common stock that trade on the regular-way market will trade with an entitlement to shares of the New SAIC common stock distributed on the Distribution Date. Purchasers in this market are purchasing both the shares of Leidos and New SAIC common stock. Form of Stock Ticker –SAIC (When Issued Trading): Shares of New SAIC common stock may be traded on a “when-issued” basis. These transactions are made conditionally because the security has been authorized, but not yet issued. Purchasers in this market are only purchasing the shares of New SAIC common stock distributed on the Distribution Date. Form of Stock Ticker – LDOS (Ex-Distribution Trading): Shares that trade on the ex-distribution market will trade without an entitlement to shares of New SAIC common stock distributed on the Distribution Date. Purchasers in this market are only purchasing the shares of Leidos common stock. So the stock price for New SAIC starts a few days before the record date of 19 September 2013, while LDOS (new name for the old SAIC) goes back much earlier. But the company didn't split until after the close of business on 27 September 2013. http://investors.saic.com/sites/saic.investorhq.businesswire.com/files/doc_library/file/GeneralStockholder-QuestionsandAnswers.pdf",
"title": ""
},
{
"docid": "56052",
"text": "What I think was being asked (and so this is how I interpreted it) is not the transition from public to private, but a corporation itself buying all its shares back, and as a result having no shareholders. In this case we could envision that all outstanding shares would be become treasury stock. My argument was that this would never happen in a practical setting. Obviously, if you interpret the question differently, for instance to be about all the shares of firm being purchased by someone else (as in a private equity buyout), you get very different answers about practicality. So I'm not disagreeing with you at all, I just read the question differently.",
"title": ""
},
{
"docid": "454224",
"text": "A mutual fund has several classes of shares that are charged different fees. Some shares are sold through brokers and carry a sales charge (called load) that compensates the broker in lieu of a fee that the broker would charge the client for the service. Vanguard does not have sales charge on its funds and you don't need to go through a broker to buy its shares; you can buy directly from them. Admiral shares of Vanguard funds are charged lower annual expenses than regular shares (yes, all mutual funds charge expenses for fund adninistration that reduce the return that you get, and Vanguard has some of the lowest expense ratios) but Admiral shares are available only for large investments, typically $50K or so. If you have invested in a Vanguard mutual fund, your shares can be set to automatically convert to Admiral shares when the investment reaches the right level. A mutual fund manager can buy and sell stocks to achieve the objectives of the fund, so what stockes you are invested in as a share holder in a mutual fund will typically be unknown to you on a day-to-day basis. On the other hand, Exchange-traded funds (ETFs) are fixed baskets of stocks, and you can buy shares in the ETF. These shares are bought and sold through a broker (so you pay a transaction fee each time) but expenses are lower since there is no manager to buy and sell stocks: the basket is fixed. Many ETFs follow specific market indexes (e.g. S&P 500). Another difference between ETFs and mutual funds is that you can buy and sell ETFs at any time of the day just as if you could if you held stocks. With mutual funds, any buy and sell requests made during the day are processed at the end of the day and the value of the shares that you buy or sell is determined by the closing price of the stocks held by the mutual fund. With ETFs, you are getting the intra-day price at the time the buy or sell order is executed by your broker.",
"title": ""
},
{
"docid": "581848",
"text": "During a stock split the only thing that changes is the number of shares outstanding. Typically a stock splits to lower its price per share. Sometimes if a company's value is falling it will do a reverse split where X shares will be exchanged for Y shares. This is typically done to avoid being de-listed from an exchange if the price per share falls below a certain threshold, usually $1. Again the only thing changing is the number of shares outstanding. A 20 for 1 reverse split means for every 20 shares outstanding the shareholder will be granted one new share. Example X Co. has 1,000,000 shares outstanding for a price of $100 per share. It does a 1 for 10 split. Now there are 10,000,000 shares outstanding for a price of $10 per share. Example Y Co has 1,000,000 shares outstanding for a price of $1 per share. It does a 10 for 1 reverse split. Now there are 100,000 shares outstanding for a price of $10. Quickly looking at the news for ASTI it looks like it underwent a 20 for 1 reverse split. You should probably look at your statements and ask your broker how the arithmetic worked in your case. Investopedia links for Reverse Stock Split and Stock Split",
"title": ""
},
{
"docid": "99947",
"text": "I have been asking myself a similar question about the financial statements of Weyerhaeuser. In response to Dheer's comment, whilst treasury shares are treated as a negative, it is issued shares less treasury shares (the negative) which gives the outstanding shares. So the original query remains unanswered. I've searched several sources and all state that outstanding shares will never be greater than issued shares. I've realized that the shares referred to are those authorized followed by those issued and outstanding (current year and prior year respectively) i.e. the shares that are both issued and outstanding as they must be issued in order to be outstanding This is supported in the example of Weyerhaeuser as there was a large increase in shares during Q1 2016 as a result of their merger with Plum Creek. Shares issued and outstanding are 510 million and 759 million respectively.",
"title": ""
},
{
"docid": "595796",
"text": "The Brokerage firm will purchase shares for the dividend paid in a omnibus account for the security of the issuer and then they will distribute fractional shares among all their clients that chose Div Reinvest. They will only have to buy 1 extra share to account for the fractional portion of what they allocate. The structure of the market does not permit trading of fractional shares. There is generally not any impact to the market place for Div Reinvest with the exception of certain securities that pay large dividends that are not liquid. sometimes this occurs in preferred securities where a large amount of Div reinvestment could create a large market order that has market impact. Most brokers place market orders for the opening on the day following the payment of the dividend. When you sell the fractional portion same process as full shares are sold into the market and the fractional if traded between you and the brokers omnibus account. if it creates a full share for the broker (omnibus has .6 shares and you sell him .5 they would likely flip that out to the street with the full share portion of your order. This would not have impact to outstanding shares and all cost are operational and with the broker handling the Div reinvestment service.",
"title": ""
},
{
"docid": "178519",
"text": "You can make a rough calculation of the annual turnover rate of stocks by calculating the institutional investors holding of that stock. Institutional investors are the only firms that are required to provide such data. The good this is they usually make the lion share of trading activity. On the other hand, this task might proof arduous A different ratio that could be used as a substitute Share Turnover which is calculated as: Share Turnover gives the number of shares traded as a fraction of the number of shares outstanding. For example, if you compare the results of stock turnover for three companies and the results came as follows: Company A-share turnover: 1.5 Times Company B share turnover: 3 times Company C share turnover: 0.3 times From the results, we can conclude that for a particular period, company C had the least activity and the number of shares traded for that period was only a small fraction of the shares outstanding while other traders of company C hold most shares and never trade them. If you make a cross sectional analysis of a list of businesses you intend to invest in, you could figure which one has the least number of rapidity in the shares traded.",
"title": ""
},
{
"docid": "472537",
"text": "The price of a share has two components: Bid: The highest price that someone who wants to buy shares is willing to pay for them. Ask: The lowest price that someone who has a share is willing to sell it for. The ask is always higher than the bid, since if they were equal the buyer and seller would have a deal, make a transaction, and that repeats until they are not equal. For stock with high volume, there is usually a very small difference between the bid and ask, but a stock with lower volume could have a major difference. When you say that the share price is $100, that could mean different things. You could be talking about the price that the shares sold for in the most recent transaction (and that might not even be between the current bid and ask), or you could be talking about any of the bid, the ask, or some value in between them. If you have shares that you are interested in selling, then the bid is what you could immediately sell a share for. If you sell a share for $100, that means someone was willing to pay you $100 for it. If after buying it, they still want to buy more for $100 each, or someone else does, then the bid is still $100, and you haven't changed the price. If no one else is willing to pay more than $90 for a share, then the price would drop to $90 next time a transaction takes place and thats what you would be able to immediately sell the next share for.",
"title": ""
},
{
"docid": "133760",
"text": "\"Buying pressure is when there are more buy orders than sell orders outstanding. Just because someone wants to buy a stock doesn't mean there's a seller ready to fill that order. When there's buying pressure, stock prices rise. When there's selling pressure, stock prices fall. There can be high volume where buying and selling are roughly equal, in which case share prices wouldn't move much. The market makers who actually fill buy and sell orders for stock will raise share prices in the face of buying pressure and lower them in the face of selling pressure. That's because they get to keep the margin between what they bought shares from a seller for and what they can sell them to a new buyer for. Here's an explanation from InvestorPlace.com about \"\"buying pressure\"\": Buying pressure can basically be defined as increasingly higher demand for a particular stock's shares. This demand for shares exceeds the supply and causes the price to rise. ... The strength or weakness of a stock determines how much buying or selling interest will be required to break support and resistance areas. I hope this helps!\"",
"title": ""
},
{
"docid": "303112",
"text": "\"The answer to your question has to do with the an explanation of \"\"shares authorized, issued and outstanding.\"\" Companies, in their Articles of Incorporation, specify a maximum number of shares they are authorized to issue. For example purposes let's assume Facebook is authorized to issue 100 shares. Let's pretend they have actually issued 75 shares, but only 50 are outstanding (aka Float, i.e. freely trading stock in the market) and stock options total 25 shares. So if someone owns 1 share, what percentage of Facebook do they own? You might think 1/100, or 1%; you might think 1/75, or 1.3%; or you might think 1/50, or 2%. 2% is the answer, but only on a NON-diluted basis. So today someone who owns 1 share owns 2% of Facebook. Tomorrow Facebook announces they just issued 15 shares to Whatsapp to buy the company. Now there are 65 shares outstanding and 90 issued. Now someone who owns 1 share of Facebook own only 1/65, or 1.5% (down from 2%)! P.S. \"\"Valuation\"\" can be thought of as the price of the stock at the time of the purchase announcement.\"",
"title": ""
},
{
"docid": "297032",
"text": "authorized 100,000,000 shares They cannot issue shares more than that so 102M isn't possible. Common stock - $.01 par value, authorized 100,000,000 shares, issued 51,970,721 and 51,575,743 shares If you look at the right 2 columns it become clear what it means. You missed the $ symbol and on the top (In thousands, except share amounts) ouststanding share 51,970,721 -> 520 On Sept 30, 2014 outstanding shares * 0.01 and rounded off to arrive at 520. ouststanding share 51,575,743 -> 516 On June 30, 2014 outstanding shares * 0.01 and rounded off to arrive at 516.",
"title": ""
},
{
"docid": "139094",
"text": "\"They are similar in the sense that they are transferring money from the company to shareholders, but that's about it. There is different tax treatment, yes, but that's because they are fundamentally different. Dividends transfer money equally to all shareholders, but that also reduces the value of each share by the same amount, since it's cash out the door, which drops the value of the company. Shareholders are taxed on dividends at the capital gains tax rate. A buyback returns the cash to shareholders who decide to sell. Other shareholders get a secondary benefit of now owning a slightly larger portion of the company since there are fewer shares outstanding. Shareholders only pay tax if they sell shares for a gain. It that means when company buyback their stock, the stock price will definitely go up? Not necessarily. It depends on the price that the company buys back the shares for and what the \"\"opportunity cost\"\" of that cash is - meaning what else could the company have done with the cash that would have been better? Buybacks often happen in mature companies with undervalued stock prices and fewer opportunities for further investment. If a company has an intrinsic value of $10 a share but its stock is trading at $8 a share, then it can instantly get a 25% \"\"return\"\" by buying back stock. I use the term \"\"return\"\" loosely since the company does not actually profit from the buyback, but from the shareholder's perspective the company is worth more per share.\"",
"title": ""
},
{
"docid": "64237",
"text": "All shares of the same class are considered equal. Each class of shares may have a different preference in order of repayment. After all company liabilities have been paid off [including bank debt, wages owing, taxes outstanding, etc etc.], the remaining cash value in a company is distributed to the shareholders. In general, there are 2 types of shares: Preferred shares, and Common shares. Preferred shares generally have 3 characteristics: (1) they get a stated dividend rate every year, sometimes regardless of company performance; (2) they get paid out first on liquidation; and (3) they can only receive their stated value on liquidation - that is, $1M of preferred shares will be redeemed for at most $1M on liquidation, assuming the corporation has at least that much cash left. Common Shares generally have 4 characteristics: (1) their dividends are not guaranteed (or may be based on a calculation relative to company performance), (2) they can vote for members of the Board of Directors who ultimately hire the CEO and make similar high level business decisions; (3) they get paid last on liquidation; and (4) they get all value remaining in the company once everyone else has been paid. So it is not the order of share subscription that matters, it is the class. Once you know how much each class gets, based on the terms listed in that share subscription, you simply divide the total class payout by number of shares, and pay that much for each share a person holds. For companies organized other-than as corporations, ie: partnerships, the calculation of who-gets-what will be both simpler and more complex. Simpler in that, generally speaking, a partnership interest cannot be of a different 'class', like shares can, meaning all partners are equal relative to the size of their partnership interest. More complex in that, if the initiation of the company was done in an informal way, it could easily become a legal fight as to who contributed what to the company.",
"title": ""
},
{
"docid": "1034",
"text": "\"What you are describing is a very specific case of the more general principle of how dividend payments work. Broadly speaking, if you own common shares in a corporation, you are a part owner of that corporation; you have the right to a % of all of that corporation's assets. The value in having that right is ultimately because the corporation will pay you dividends while it operates, and perhaps a final dividend when it liquidates at the end of its life. This is why your shares have value - because they give you ownership of the business itself. Now, assume you own 1k shares in a company with 100M shares, worth a total of $5B. You own 0.001% of the company, and each of your shares is worth $50; the total value of all your shares is $50k. Assume further that the value of the company includes $1B in cash. If the company pays out a dividend of $1B, it will now be only worth $4B. Your shares have just gone down in value by 20%! But, you have a right to 0.001% of the dividend, which equals a $10k cash payment to you. Your personal holdings are now $40k worth of shares, plus $10k in cash. Except for taxes, financial theory states that whether a corporation pays a dividend or not should not impact the value to the individual shareholder. The difference between a regular corporation and a mutual fund, is that the mutual fund is actually a pool of various investments, and it reports a breakdown of that pool to you in a different way. If you own shares directly in a corporation, the dividends you receive are called 'dividends', even if you bought them 1 minute before the ex-dividend date. But a payment from a mutual fund can be divided between, for example, a flow through of dividends, interest, or a return of capital. If you 'looked inside' your mutual fund you when you bought it, you would see that 40% of its value comes from stock A, 20% comes from stock B, etc etc., including maybe 1% of the value coming from a pile of cash the fund owns at the time you bought your units. In theory the mutual fund could set aside the cash it holds for current owners only, but then it would need to track everyone's cash-ownership on an individual basis, and there would be thousands of different 'unit classes' based on timing. For simplicity, the mutual fund just says \"\"yes, when you bought $50k in units, we were 1/3 of the year towards paying out a $10k dividend. So of that $10k dividend, $3,333k of it is assumed to have been cash at the time you bought your shares. Instead of being an actual 'dividend', it is simply a return of capital.\"\" By doing this, the mutual fund is able to pay you your owed dividend [otherwise you would still have the same number of units but no cash, meaning you would lose overall value], without forcing you to be taxed on that payment. If the mutual fund didn't do this separate reporting, you would have paid $50k to buy $46,667k of shares and $3,333k of cash, and then you would have paid tax on that cash when it was returned to you. Note that this does not \"\"falsely exaggerate the investment return\"\", because a return of capital is not earnings; that's why it is reported separately. Note that a 'close-ended fund' is not a mutual fund, it is actually a single corporation. You own units in a mutual fund, giving you the rights to a proportion of all the fund's various investments. You own shares in a close-ended fund, just as you would own shares in any other corporation. The mutual fund passes along the interest, dividends, etc. from its investments on to you; the close-ended fund may pay dividends directly to its shareholders, based on its own internal dividend policy.\"",
"title": ""
},
{
"docid": "29306",
"text": "No - there are additional factors involved. Note that the shares on issue of a company can change for various reasons (such as conversion/redemption of convertible securities, vesting of restricted employee shares, conversion of employee options, employee stock purchase programs, share placements, buybacks, mergers, rights issues etc.) so it is always worthwhile checking SEC announcements for the company if you want an exact figure. There may also be multiple classes of shares and preferred securities that have different levels of dividends present. For PFG, they filed a 10Q on 22 April 2015 and noted they had 294,385,885 shares outstanding of their common stock. They also noted for the three months ended March 31 2014 that dividends were paid to both common stockholders and preferred stockholders and that there were Series A preferred stock (3 million) and Series B preferred stock (10 million), plus a statement: In February 2015, our Board of Directors authorized a share repurchase program of up to $150.0 million of our outstanding common stock. Shares repurchased under these programs are accounted for as treasury stock, carried at cost and reflected as a reduction to stockholders’ equity. Therefore the exact amount of dividend paid out will not be known until the next quarterly report which will state the exact amount of dividend paid out to common and preferred shareholders for the quarter.",
"title": ""
},
{
"docid": "435798",
"text": "Well, you won't be double taxed based on what you described. Partners are taxed on income, typically distributions. Your gain in the partnership is not income. However, you were essentially given some money which you elected to invest in the partnership, so you need to pay tax on that money. The question becomes, are you being double taxed in another way? Your question doesn't explain how you invested, but pretty much the options are either a payroll deduction (some amount taken out of X paychecks or a bonus) or some other payment to you that was not treated as a payroll deduction. Given that you got a 1099, that suggests the latter. However, if the money was taken out as a payroll deduction - you've already paid taxes (via your W2)! So, I'd double check on that. Regarding why the numbers don't exactly match up - Your shares in the partnership likely transacted before the partnership valuation. Let's illustrate with an example. Say the partnership is currently worth $1000 with 100 outstanding shares. You put up $1000 and get 100 shares. Partnership is now worth $2000 with 200 outstanding shares. However, after a good year for the firm, it's valuation sets the firm's worth at $3000. Your gain is $1500 not $1000. You can also see if what happened was the firm's valuation went down, your gain would be less than your initial investment. If instead your shares transacted immediately after the valuation, then your gain and your cost to acquire the shares would be the same. So again, I'd suggest double checking on this - if your shares transacted after the valuation, there needs to be an explanation for the difference in your gain. For reference: http://smallbusiness.findlaw.com/incorporation-and-legal-structures/partnership-taxes.html And https://www.irs.gov/publications/p541/ar02.html Here you learn the purpose of the gain boxes on your K1 - tracking your capital basis should the partnership sell. Essentially, when the partnership is sold, you as a partner get some money. That money is then taxed. How much you pay will depend on what you received versus what the company was worth and whether your gain was long term or short term. This link doesn't go into that detail, but should give you a thread to pull. I'd also suggest reading more about partnerships and K1 and not just the IRS publications. Don't get me wrong, they're a good source of information, just also dense and sometimes tough to understand. Good luck and congrats.",
"title": ""
},
{
"docid": "34882",
"text": "Open Google finance and divide the Market Capitalization by the total price. That will give you the total number of shares outstanding. Now see the number of shares you could buy for $1000(40 shares of $25 each or 10 shares of 100 shares each). Now divide the number of shares you own, by the number of shares outstanding in the company and multiply it by 100(i.e (Shares you own/shares Outstanding) * 100). That will give you the percentage or stake of the company you own(With $1000, don't expect it to be a very large number). Now ask your self the question, Is it worth it if I can buy x % of this company for $1000? If the answer is yes, go ahead and buy it. To answer your question in short, NO! it does not matter whether you buy 10 shares for $100 or 40 shares for $25. Cheers",
"title": ""
},
{
"docid": "532171",
"text": "\"An important thing that many people fail to realize is that the number of shares outstanding in a stock, times the current market price of those shares, does not represent anything related to the total value of those shares. If a company has one million shares outstanding and its total value is $10 million, then the real worth of each share is $10. If few people feels like buying or selling, but a few people think the company is worth $50 million and offer $50/share, that could raise the market price to $50/share, but it wouldn't mean that the company became worth five times as much; it would merely mean the stock was overpriced. If, after the price went to $50/share, all the owners of the stock put in stop-loss orders at $45. Note that the real $10/share \"\"real value\"\" of their stock would never have changed. If the people who thought the stock was worth $50 decided to get out of the market, and nobody else was willing to offer more than $10, that would instantly drop the price to $10. The fact that a million shares of stock have stop-loss orders at $45 wouldn't magically generate buyers for those stocks at that price. Indeed, unchecked stop-loss orders would have the reverse effect, since many people who would have been willing if not eager to buy the stock if it had been available for less than $10/share would instead be trying to sell it below that price. It's too bad people think that the number of shares outstanding times the current market price represents some kind of \"\"meaningful quantity\"\". If the present cash value of all future payouts associated with a share of stock is $10, then someone who buys a share of stock for less than that makes money off the seller; someone who pays more loses money to the seller. Many people think they can lose money to the seller and still come out okay if the price goes higher, but what that really means is that they're hoping to find a bigger sucker--a game where it's guaranteed that some people will have losses they don't recoup.\"",
"title": ""
},
{
"docid": "179737",
"text": "Contrary to what you might have heard, moving money between mutual funds, whether or not in the same family of funds, is a taxable event, assuming, of course, that the funds are not in tax-deferred retirement accounts. About the only thing that is not taxable is moving funds between share classes in the same mutual fund, e.g. a conversion from what Vanguard refers to as Investor Shares to Admiral Shares in the same fund. In some cases, the Admiral Shares may have a considerably different price (for example, Vanguard Health Care Fund Investor Shares (VGHCX) and Admiral Shares (VGHAX) are priced at $215.83 and $91.04 respectively and so changing from one class to the other changes the number of shares owned considerably while the net value of the investment remains unchanged.",
"title": ""
},
{
"docid": "454610",
"text": "\"I wonder if ETF's are further removed from the actual underlying holdings or assets giving value to the fund, as compared to regular mutual funds. Not exactly removed. But slightly different. Whenever a Fund want to launch an ETF, it would buy the underlying shares; create units. Lets say it purchased 10 of A, 20 of B and 25 of C. And created 100 units for price x. As part of listing, the ETF company will keep the purchased shares of A,B,C with a custodian. Only then it is allowed to sell the 100 units into the market. Once created, units are bought or sold like regular stock. In case the demand is huge, more units are created and the underlying shares kept with custodian. So, for instance, would VTI and Total Stock Market Index Admiral Shares be equally anchored to the underlying shares of the companies within the index? Yes they are. Are they both connected? Yes to an extent. The way Vanguard is managing this is given a Index [Investment Objective]; it is further splitting the common set of assets into different class. Read more at Share Class. The Portfolio & Management gives out the assets per share class. So Vanguard Total Stock Market Index is a common pool that has VTI ETF, Admiral and Investor Share and possibly Institutional share. Is VTI more of a \"\"derivative\"\"? No it is not a derivative. It is a Mutual Fund.\"",
"title": ""
},
{
"docid": "495066",
"text": "\"Market Capitalization is the value the market attributes to the company shares calculated by multiplying the current trading price of these shares by the total amount of shares outstanding. So a company with 100 shares trading at $10 has a market cap of $1000. It is technically not the same as the value of a company (in the sense of how much someone would need to pay to acquire the company), Enterprise value is what you want to determine the net value of a company which is calculated as the market capitalization + company debt (as the acquirer has to take on this debt) - company cash (as the acquirer can pocket this for itself). The exact boundary for when a company belongs to a certain \"\"cap\"\" is up for debate. For a \"\"large cap\"\" a market capitalization of $10 billion+ is usually considered the cutoff (with $100+ billion behemoths being called \"\"mega caps\"\"). Anything between $10 billion and ~$1 billion is considered \"\"mid cap\"\", from ~$1billion to ~$200 million it's called a \"\"small cap\"\" and below $200 million is \"\"nano cap\"\". Worth noting that these boundaries change quite dramatically over time as the overall average market capitalization increases as companies grow, for example in the 80s a company with a market cap of $1 billion would be considered \"\"large cap\"\". The market \"\"determines\"\" what the market cap of company should be based (usually but certainly not always!) on the historical and expected profit a company makes, for a simple example let's say that our $1000 market cap company makes $100 a year, this means that this company's earnings per share is $1. If the company grows to make $200 a year you can reasonably expect the share price to rise from $10 to ~$20 with the corresponding increase in market cap. (this is all extremely simplified of course).\"",
"title": ""
},
{
"docid": "135216",
"text": "\"The market capitalization of a stock is the number of shares outstanding (of each stock class), times the price of last trade (of each stock class). In a liquid market (where there are lots of buyers and sellers at all price points), this represents the price that is between what people are bidding for the stock and what people are asking for the stock. If you offer any small amount more than the last price, there will be a seller, and if you ask any small amount less than the last price, there will be a buyer, at least for a small amount of stock. Thus, in a liquid market, everyone who owns the stock doesn't want to sell at least some of their stock for a bit less than the last trade price, and everyone who doesn't have the stock doesn't want to buy some of the stock for a bit more than the last trade price. With those assumptions, and a low-friction trading environment, we can say that the last trade value is a good midpoint of what people think one share is worth. If we then multiply it by the number of shares, we get an approximation of what the company is worth. In no way, shape or form does it not mean that there is 32 billion more invested in the company, or even used to purchase stock. There are situations where a 32 billion market cap swing could mean 32 billion more money was invested in the company: the company issues a pile of new shares, and takes in the resulting money. People are completely neutral about this gathering in of cash in exchange for dilluting shares. So the share price remains unchanged, the company gains 32 billion dollars, and there are now more shares outstanding. Now, in some sense, there is zero dollars currently invested in a stock; when you buy a stock, you no longer have the money, and the money goes to the person who no longer has the stock. The issue here is the use of the continuous tense of \"\"invested in\"\"; the investment was made at some point, but the money doesn't really stay in this continuous state of being. Unless you consider the investment liquid, and the option to take money out being implicit, it being a continuous action doesn't make much sense. Sometimes the money is invested in the company, when the company causes stocks to come into being and sells them. The owners of stocks has invested money in stocks in that they spent that money to buy the stocks, but the total sum of money ever spent on stocks for a given company is not really a useful value. The market capitalization is an approximation, which under the efficient market hypothesis (that markets find the correct price for things nearly instantly) is reasonably accurate, of the value the company has collectively to its shareholders. The efficient market hypothesis isn't accurate, but it is an acceptable rule of thumb. Now, this value -- market capitalization -- is arguably not the total value of a company: other stakeholders include bond holders, labour, management, various contract counter-parties, government and customers. Some companies are structured so that almost all value is captured not by the stock owners, but by contract counter-parties (this is sometimes used for hiding assets or debts). But for most large publically traded companies, it (in theory) shouldn't be far off.\"",
"title": ""
},
{
"docid": "327560",
"text": "Generally, when I run across this kind of situation, I look for the Investor Relations section of the corporate website for a 'Stock Information' (or similar) tab or link. This usually contains information explaining the different shares classes, how they relate (if at all), voting and/or dividend rights, and taxation differences for the different classes. However, I have trouble finding such a page on a central BYD corporate investor relations page. I did find this page detailing the HK1211 shares: http://www.byd.com/investor/base_information.html. I don't know what or why, but something tells me this is an older page. Searching on, I also found this page which looks newer and clarifies that the difference you are seeing is between 'A' and 'H' shares. http://www.byd.cn/BYDEnglish/basic/article.jsp?articleId=1524676. (I'm guessing but I'd think somewhere in the announcements on this byd.cn site, you may find more details of any structural differences between share classes -- I just didn't want to page through them all.)",
"title": ""
}
] |
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