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Vol. 34, No. 4 :
Leukemic phase of B-lineage NHL
Kimby E.
Department of Hematology, Karolinska Institute at Huddinge University Hospital Stockholm S-141 86, Sweden
Correspondence: [email protected]
B-cell non-Hodgkin lymphomas (NHL) mostly present as disseminated diseases involving lymph nodes, spleen and liver and often the bone marrow (BM). Tumor cells can also be found in the blood (leukemic disease), especially in the indolent lymphomas. High white blood cell counts and a differential demonstrating a lymphocytosis in the blood require immunophenotyping for characterization of the leukemic cells. Molecular/cytogenetic analyses may also have a role in the diagnostic classification of the disease. Besides the specific diagnosis, the clinical evaluation of the patient and prognostic markers are of most importance for selecting the best type of therapy.
Follicular lymphoma (FL) is the indolent lymphoma with the highest incidence. Most patients present with advanced stage disease with BM involvement in 40–70% of the cases, and few are leukemic at the time of diagnosis. By high-resolution analysis circulating FL cells may be detected in more patients. Leukemic patients mostly have concomitant lymph node involvement and high tumor burden. A pure FL-cell leukemia with CD20+CD10+CD5– clonal cells has also been described, mostly associated with an indolent clinical outcome. FL carry a t(l4;l8)(q32;q2l) translocation in more than 90% of cases, juxtaposing the immunoglobulin heavy chain (IGH) 3' Regulatory Regions (lgH-3'RR) to the BCL2 gene, resulting in overexpression of the Bcl2 anti-apoptotic protein. FL cells are also dependent on signals from the microenvironment to survive and proliferate. Several groups, including ours, have reported that immune cells in the lymphoma microenvironment and in blood influence prognosis. In patients treated before the introduction of rituximab, we have found that a high number of PD-1+, FOXP3+ and CD8+ T-cell subsets in the tumor microenvironment predict superior outcome, while CD4+ follicular helper T cells and CD68+ macrophages are associated with an inferior outcome. The introduction of the anti-CD20 antibody rituximab has improved the prognosis for FL patients. The efficacy of this drug is excellent also as monotherapy especially in patients with high numbers of CD8+ T-cells in the lymph nodes as well as in the blood.
Mantle cell lymphoma (MCL): MCL cells carries the t(l 1:14) translocation resulting in enhanced cyclin Dl expression and cyclin DI-dependent kinase activity, promoting cell cycle progression. Immunological markers show a typical phenotype (CD20+CD5+CD23–), but also atypical phenotypes (CD20+CD5–CD23– or CD20+CD5+CD23+) in some cases. Most MCL patients have an unfavorable prognosis and intensive treatment strategies are required. However, in around 10% of the patients the disease shows an indolent clinical course with often a non-nodal, leukemic disease. In one study the clinicopathologic features, gene expression and genomic profiles were compared in patients with indolent (iMCL) and in those with conventional disease (cMCL). iMCL and cMCL shared a common gene expression profile that differed from other leukemic lymphoid neoplasms and a signature of 13 genes was underexpressed in iMCL, among these SOXI1. The SOX I1-negative tumors exhibited more frequent non-nodal presentation and better survival compared with SOX I1-positive MCL. Recently, our group found that SOXII-negative MCL had a higher frequency of lymphocytosis, but also elevated LDH and p53 positivity. Moreover, SOXII- negative cases had a shorter overall survival than SOXII-positive cases. Due to the conflicting results, the conclusion is that SOXII cannot be used for predicting an indolent disease course. In another study, deletions at 17p13 (TP53) and 13q14 were frequent in leukemic MCL and involved the majority of the leukemic clone. Cases with TP53 deletion were more likely to have splenomegaly and marked leucocytosis (> 30 × 109/L), and were less likely to have lymphadenopathy than those without the deletion. Other distinctive biological features in non-nodal leukemic MCL are mutated IGHV and a transcriptional profile lacking tumor invasion properties, which might contribute to the absence of nodal involvement. In conclusion, MCL patients with leukemic disease but without clinical symptoms might be managed conservatively with a "wait and watch" policy, while blastoid morphology, high proliferation and TP53 aberrations are markers of aggressive disease, which will require intensive immunochemotherapy.
Marginal zone lymphoma (MZL): There are three clinicopathological entities of MZL, including extranodal, mucosa-associated lymphoid tissue (MALT) lymphoma, nodal (NMZL), and splenic (SMZL) type. Leukemic presentation is more common in SMZL. The leukemic lymphocytes are usually small or morphologically "villous", and the leukemic manifestation of SMZL is named splenic lymphoma with villous lymphocytes (SLVL). The typical immunophenotype is CD19+CD20+CD22+CD45+ and the clone is often also CD 103+ and CD38+. Moreover, CD11c is highly associated with SMZL. The genetics and pathogenesis of SMZL are poorly understood and specific prognostic features are lacking. Aberrant karyotypes are seen as gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/l4q. Trisomy 3 and deletions of chromosome 7q22-34 are most common and found in approximately 25 and 45% of cases, respectively. A strong association has been described between usage of the IGVH1-2 and deletion 7q and 14q alterations. Clinical and epidemiological data suggest that chronic hepatitis C virus (HCV) infection may have an etiological role in a subset of cases. MicroRNA (miR)-26b, a miRNA known to have tumor suppressive properties, has been shown to be downregulated in HCV positive cases. Recent data suggest that certain SMZL subtypes could derive from progenitor populations adapted to particular antigenic challenges through selection of VH domain specificities, in particular the IGHV 1-2(*)04 allele.
The anti-CD20 antibody rituximab is mostly effective in MZL patients as monotherapy, but for many patients with symptomatic splenomegaly, splenectomy is still a therapeutic option.
In summary, the presence of lymphocytosis in the blood in patients with a suspicion of lymphoma requires careful evaluation for the presence of neoplastic lymphocytes, especially in the absence of easily accessible enlarged lymph nodes. The differential diagnosis between the WHO defined mature B-cell malignancies has improved by using multiple-color flow cytometry of phenotypic data of the lymphoma cells. This method is also of value for characterization of the immune cells in the microenvironment and blood. Molecular/cytogenetic analyses have a role in classification of the disease and for understanding of pathogenesis. Therapeutic decisions are always dependant on the specific diagnosis, prognostic factors and a careful clinical evaluation of the patient.
1. Bene MC, Nebe T, Bettelheim P, et al. Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10. Leukemia 2011; 25: 567–74.
2. Wahlin BE, Sundstrom C, Holte H, et al. T cells in tumors and blood predict outcome in follicular lymphoma treated with rituximab. Clin Cancer Res. 2011; 17: 4136–44
3. Matutes E, Parry-Jones N, Brito-Babapulle V, et al. The leukemic presentation of mantle-cell lymphoma: disease features and prognostic factors in 58 patients. Leuk Lymphoma 2004; 45: 2007–15.
4. Fernandez V, Salamero O, Espinet B, et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res. 2010; 70: 1408–18.
5. Nygren L, Baumgartner Wennerholm S, et al. Prognostic role of SOX I I in a population-based cohort of mantle cell lymphoma. Blood 2012; 119: 4215–23.
6. Del Giudice I, Messina M, Chiaretti S, et al. Behind the scenes of non-nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes. J Haematol 2012; 156: 601–11.
7. Isaacson PG, Matutes E, Burke M, Catovsky D. The histopathology of splenic lymphoma with villous lymphocytes. Blood 1994; 84: 3828–34.
8. Matutes E, Morilla R, Owusu-Ankomah K, et al. The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders. Blood 1994; 83: 1558–62.
9. Catovsky D, Matutes E. Splenic lymphoma with circulating villous lymphocytes/splenic marginal zone lymphoma. Seminars in Hematology 1999; 36: 148–54.
10. Chacon JI, Mollejo M, Munoz E, et al. Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients. Blood 2002; 100: 1648–54.
11. Parry-Jones N, Matutes E, Gruszka-Westwood AM, et al. Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients. Brit J Haematol 2003; 120: 759–64.
12. Del Giudice I, Matutes E, Morilla R, et al. The diagnostic value of CD 123 in B-cell disorders with hairy or villous lymphocytes. Haematologica 2004; 89: 303–8.
13. Matutes E, Oscier D, Montalban C, et al. Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia 2008; 22: 487–95.
14. Salido M, Baro C, Oscier D, et al. Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group. Blood 2010; 116: 1479–88.
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Cytoskeletal Organizing Protein Plays a Central Role in Building the Brain
News Mar 16, 2020 | Original story from the University of Barcelona
The molecule NCAM2, a glycoprotein from the superfamily of immunoglobulins, is a vital factor in the formation of the cerebral cortex, neuronal morphogenesis and formation of neuronal circuits in the brain, as stated in the new study published in the journal Cerebral Cortex. The deficit of NCAM2 causes an incorrect migration of neurons and alters the morphology, cytoskeleton and functionality of these cells in the central nervous system.
This article studies for the first time the activity of NCAM2 in the cortex and the hippocampus, brain structures where the function of this factor was so far unknown. The study is led by the experts Eduardo Soriano and Lluís Pujades, from the Faculty of Biology and the Institute of Neurosciences of the University of Barcelona (UBNeuro), the Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) and the Vall d'Hebron Research Institute (VHIR). The first author of the study is the researcher Antoni Parcerisas, member of the above-mentioned centers.
Other participants in this study are the experts from the Catalan Institution for Research and Advanced Studies (ICREA), Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology (BIST), the Spanish National Research Council (CSIC), the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the University of California in Davis (United States).
NCAM2: an unknown function in the cortex and hippocampus
The NCAM2 glycoprotein is a cell-adhesion molecule present in all vertebrates and which plays a decisive role in the organization of neuronal circuits in the central nervous system. This factor is largely expressed in the brain -from embryonic phases to adulthood- and specially in the olfactory bulb. Traditionally, all previous studies were focused on the olfactory bulb and proved a key role of the protein in neuronal synapses and neuronal compartmentalization between axons and dendrites. Recent studies described the involvement of NCAM2 in the formation and growth of neurites in cortical neurons, in the loss of synapsis in hippocampal neurons -caused by the amyloid peptide in Alzheimer's disease- and the proliferation of neuronal progenitors in the spinal cord.
The new study describes for the first time the function of NCAM2 and the observed phenotypes in the development of the cortex and the hippocampus, a highly complex process regulated by many proteins. "In the study we confirm that a loss of NCAM2 creates an incorrect migration and position of neurons -these do not join the corresponding layer- and it also alters the neuronal morphology and the features of the cytoskeleton of nervous cells", notes researcher Antoni Parcerisas.
"In the neuronal phenotype -adds Parcerisas- we see an altered dendritic tree -smaller and with many small and short dendrites- and an axon with more branches. In certain cases, some neurons show problems of neuronal polarization as well".
An essential factor in the neuronal cytoarchitecture
A new study on brain neurobiology applies several experimental approaches -in vitro and in vivo techniques and live-imaging experiments- to see how neurons evolve. According to the conclusions, the isoform NCAM2.1 interacts direct and indirectly with the cell cytoskeleton and it modulates the dynamics of its components -microtubules and proteins- which are essential for the migration and development process of the neuron.
The loss of NCAM2 would cause the retraction of the existing dendrites and would alter the cell cytoskeleton (lower stability and altered dynamics of microtubule formation). This hypothesis is supported by the fact that when Taxol -chemical agent that boosts microtubule stability- is added, it can reverse the phenotype generated by the loss of NCAM2.
Moreover, NCAM2.1 can also interact with several proteins that regulate the stability of the cytoskeleton, such as MAP2 and 14-3-3. In particular, NCAM2.1 would form a protein complex with MAP2 and 14-3-3 that would ease the stabilization processes of the microtubule cytoskeleton, essential for the development of the dendritic tree.
What role does NCAM2 play in neuronal polarization?
The dynamics and organization of cytoskeleton microtubules are essential to maintain the neuronal polarization, which defines the morphological and functional differences between axons and dendrites and enables the transmission of the nervous impulse.
Although the NCAM2 participation pathway is unknown in neuronal polarization processes, "we observed a deficit of NCAM2 leads to the apparition of multiple axonal structures (instead of one axon only, as expected) due to the changes that occur in the dynamics of the neuron cytoskeleton. Therefore, NCAM2 is a necessary factor during the process of neuronal polarization to provide structures with stability and enable the differentiation of a neurite in axon", notes Parcerisas.
Deficit of NCAM2 protein and cognitive developmental pathologies
NCAM2 presents an expression pattern which is typical from those proteins involved in neuronal morphogenesis and synaptogenesis. Moreover, the expression pattern of NCAM2 shows changes in cell location depending on the neuronal developmental phases.
"A deficit of this protein -at a genomic or protein scale- would cause neuronal alterations in several developmental phases. In this context, some genetics note that the loss of NCAM2 could be the origin of cognitive alterations in patients with autism spectrum disorders and neurodevelopmental problems", note the authors.
"It would be important to promote new genetic and proteomic studies in patients with neurodevelopmental pathologies to help determine the causes of these diseases. In case this hypothesis was confirmed -if there was a relation between these pathologies with the deficit of NCAM2- researchers could think about doing research on new molecular targets to help regulate the signaling pathways and the affected cell processes", conclude the authors of the new study.
Reference: Parcerisas, A., Pujadas, L., Ortega-Gascó, A., Perelló-Amorós, B., Viais, R., Hino, K., Figueiro-Silva, J., La Torre, A., Trullás, R., Simó, S., Lüders, J., & Soriano, E. (n.d.). NCAM2 Regulates Dendritic and Axonal Differentiation through the Cytoskeletal Proteins MAP2 and 14-3-3. Cerebral Cortex. https://doi.org/10.1093/cercor/bhz342
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
Drug May Reduce Tumor Volume in Neurofibromatosis
Based on preclinical studies of an investigational drug to treat peripheral nerve tumors, researchers have shown that the drug, cabozantinib, reduces tumor volume and pain in patients with the genetic disorder neurofibromatosis type 1 (NF1).
Block Booking: Tetris-Inspired Algorithm Could Make Life Easier for Hotels
To avoid overbooking (accepting more reservations than there is room for) in some cases online sales are blocked before hotels are completely booked. TA new solution, inspired by the block-busting video game Tetris, could change the life of hotels by increasing the number of occupied rooms and, therefore, in the revenue of hotel owners.
Mutations in Little-Studied Gene Regions May Play Role in Autism
Mutations that occur in certain DNA regions, called tandem repeats, may play a significant role in autism spectrum disorders, according to new research.
Imaging Techniques in Neuroscience
3D Cell Culture: Miniature Dimensions Drive Massive Advances
9 Milestones From Dementia Research in 2020
How the Brain Paralyzes the Body During Dreaming
Exploiting the Antimicrobial Properties of Toadlet Peptide To Kill Bacteria
Psychological Factors and the Immune Response to Vaccines
EEG and Chill: Study Monitors "Romantic Behavior" in Couples' Homes
Speech-Stealing Dementia Leaves Memory Intact
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Models for understanding effects of distraction on linguistic processing are few. We measured semantically related and unrelated visual and auditory ambient distraction on picture identification in non-neurologically damaged younger and older adults. Comparisons were made across conditions of quiet, white noise, visual, and auditory distraction for categories of sports and vegetables. The effect of semantic relatedness varied according to modality of distraction. Visual distraction of semantically related targets hindered performance more than unrelated visual distraction. Both groups performed slower during distraction compared to quiet. Older adults demonstrated significantly longer reaction times during conditions of either auditory or visual distraction.
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A thorough understanding and practice of sound nutritional principles is fundamental to good health and healing.
Nutritional counseling is an important process. Every aspect of diet and nutritional supplementation is carefully examined in order to develop a customized regimen that is as healthy as possible and helps individuals to address their own unique metabolic requirements. A comprehensive range of dietary factors are examined including types and amounts of protein, carbohydrate, fat and fiber, as well as healthy snacks and beverages, frequency of meals, and other vital considerations. In addition, the complete array of natural vitamins, minerals, amino acids, fatty acids, herbs, etc. are evaluated which can be effectively to compliment the optimum diet, as well as, help to alleviate symptoms and prevent disease.
HOW WILL NUTRITIONAL COUNSELING HELP?
Learn which foods will lead to weight loss and descrease body fat.
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Wrinkles and sagging skin around our eyes can make us look tired and older than we feel. Puffy pouches of fat in the upper or lower lids creates an exhausted appearance, and excessive skin in the upper eyelid can even interfere with vision.
Scottsdale plastic surgeon Dr. White can help you look dramatically younger and more rested through eyelid lift surgery. If sagging eyelids are interfering with your vision, then an eyelid lift can widen your visual field, creating less strain on your eyes.
Eyelid lift surgery (blepharoplasty) is done on an outpatient basis at the Piper Outpatient Surgical Facility in Scottsdale either with local or general anesthesia. It may be done in our office with local anesthesia for appropriate patients. The incisions are made where the natural crease should be in the upper lids and below the lash line in the lower lids, and excess fat and skin are removed. If only excess fat is present in the lower lids, it may be removed through an incision inside the lower lids with no external incision or scar (called a transconjunctival blepharoplasty).
All sutures are usually removed within 4 to 6 days. Initial mild discomfort is easily controlled with oral medication. Bruising and sensitivity to light last at least a week or two, and swelling progressively disappears in 1 to 2 weeks. Eye makeup can be used after sutures are removed, and contact lenses can be worn when comfortable – usually within 7 to 10 days.
Additional procedures that may enhance the result of an eyelid lift (blepharoplasty) are Brow Lift or Facelift.
If eyelid lift surgery is being done to improve the field of vision, insurance may cover upper lid surgery. Otherwise, eyelid lift is considered cosmetic, and therefore is not covered by insurance.
The specific risks and the suitability of eyelid lift can be determined only during your consultation with Scottsdale plastic surgeon Dr. White. All surgical procedures have some degree of risk, but major complications are rare.
Learn more about Eyelid Lift Plastic Surgery at the American Society for Aesthetic Plastic Surgery web site or the American Society of Plastic Surgeons web site.
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and solenoids so competitive compressors can be successfully converted to Sullube™.
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He teaches courses on Dental Photography , Digital Smile Design , ceramic veneers on refractory and natural layering technique on metal and zirconium.
He has written various articles on national and international journals on applied photography in the dental field and on the aesthetics.
Developing of the peri-implant soft tissue within the esthetic zone: the critical interface management following the prosthetic, surgical and digital rationale.
The management of the anterior esthetic is one of the hottest topics in Dentistry. The diagnostic phase is critical. In this lecture, we are going to discuss all the parameters to achieve the correct diagnosis of the socket and the various treatment plan correlated to each type of socket. The bone zone and the tissue zone will be evaluated and discussed in detail, regarding each of their variables.
In the surgical part, Dr. Agnini will describe the criteria necessary for successfully utilizing minimally invasive protocols within the esthetic zone and the possibility of placing or not placing a bone graft in the "gap" and the opportunity to use a connective tissue graft to overbuild the site buccolingual.
To achieve "Esthetic perfection", every minimal detail should be considered, starting from the temporary on the day of the surgery: Dr. Agnini will describe various clinical options and techniques for efficiently and esthetically fabricating a temporary restoration immediately after implant placement in the replacement of a single tooth.
The duration of the lecture can be 90 minutes.
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Author Goffart, N.; Lombard, A.; Lallemand, F.; Kroonen, J.; Nassen, J.; Di Valentin, E.; Berendsen, S.; Dedobbeleer, M.; Willems, E.; Robe, P.; Bours, V.; Martin, D.; Martinive, P.; Maquet, P.; Rogister, B.
Title CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone Type Journal Article
Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol
Keywords Animals; Brain Neoplasms/metabolism/*pathology/radiotherapy; Chemokine CXCL12/*metabolism; Cranial Irradiation/*adverse effects; Gamma Rays/adverse effects; Glioblastoma/metabolism/*pathology/radiotherapy; Humans; Lateral Ventricles/metabolism/*pathology/radiation effects; Mice; Mice, Nude; Neoplastic Stem Cells/metabolism/*pathology/radiation effects; *Radiation Tolerance; Signal Transduction/radiation effects; Tumor Cells, Cultured; Cxcl12; glioblastoma; mesenchymal activation; radioresistance; subventricular zone
Abstract BACKGROUND: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor-initiating abilities. METHOD: While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure. RESULTS: Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ-released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells. CONCLUSION: Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse.
Address Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liege, Liege, Belgium (N.G., A.L., J.N., M.D., E.W., B.R.); Department of Neurosurgery, CHU and University of Liege, Liege, Belgium (A.L., D.M.); Department of Radiotherapy and Oncology, CHU and University of Liege, Liege, Belgium (F.L., P.M.); Laboratory of Tumor and Development Biology, GIGA-Cancer Research Center, University of Liege, Liege, Belgium (F.L.); Cyclotron Research Centre, University of Liege, Liege, Belgium (F.L.); Human Genetics, CHU and University of Liege, Liege, Belgium (N.G., J.K., V.B.); Department of Neurosurgery, Brain Center Rudolf Magnus Institute of Neurosciences and the T&P Bohnenn Laboratory for Neuro-Oncology University Medical Center, Utrecht, The Netherlands (N.G., J.K., S.B., P.R.); GIGA-Viral Vector Plateform, University of Liege, Liege, Belgium (E.D.V.); Department of Neurology, CHU and University of Liege, Liege, Belgium (P.M., B.R.)
Author Sacks, E.; Freeman, P.A.; Sakyi, K.; Jennings, M.C.; Rassekh, B.M.; Gupta, S.; Perry, H.B.
Title Comprehensive review of the evidence regarding the effectiveness of community-based primary health care in improving maternal, neonatal and child health: 3. neonatal health findings Type Journal Article
Year 2017 Publication Journal of Global Health Abbreviated Journal J Glob Health
Volume 7 Issue 1 Pages 010903
Abstract BACKGROUND: As the number of deaths among children younger than 5 years of age continues to decline globally through programs to address the health of older infants, neonatal mortality is becoming an increasingly large proportion of under-5 deaths. Lack of access to safe delivery care, emergency obstetric care and postnatal care continue to be challenges for reducing neonatal mortality. This article reviews the available evidence regarding the effectiveness of community-based primary health care (CBPHC) and common components of programs aiming to improve health during the first 28 days of life. METHODS: A database comprising evidence of the effectiveness of projects, programs and field research studies (referred to collectively as projects) in improving maternal, neonatal and child health through CBPHC has been assembled and described elsewhere in this series. From this larger database (N = 548), a subset was created from assessments specifically relating to newborn health (N = 93). Assessments were excluded if the primary project beneficiaries were more than 28 days of age, or if the assessment did not identify one of the following outcomes related to neonatal health: changes in knowledge about newborn illness, care seeking for newborn illness, utilization of postnatal care, nutritional status of neonates, neonatal morbidity, or neonatal mortality. Descriptive analyses were conducted based on study type and outcome variables. An equity assessment was also conducted on the articles included in the neonatal subset. RESULTS: There is strong evidence that CBPHC can be effective in improving neonatal health, and we present information about the common characteristics shared by effective programs. For projects that reported on health outcomes, twice as many reported an improvement in neonatal health as did those that reported no effect; only one study demonstrated a negative effect. Of those with the strongest experimental study design, almost three-quarters reported beneficial neonatal health outcomes. Many of the neonatal projects assessed in our database utilized community health workers (CHWs), home visits, and participatory women's groups. Several of the interventions used in these projects focused on health education (recognition of danger signs), and promotion of and support for exclusive breastfeeding (sometimes, but not always, including early breastfeeding). Almost all of the assessments that included a measurable equity component showed that CBPHC produced neonatal health benefits that favored the poorest segment of the project population. However, the studies were quite biased in geographic scope, with more than half conducted in South Asia, and many were pilot studies, rather than projects at scale. CONCLUSIONS: CBPHC can be effectively employed to improve neonatal health in high-mortality, resource-constrained settings. CBPHC is especially important for education and support for pregnant and postpartum mothers and for establishing community-facility linkages to facilitate referrals for obstetrical emergencies; however, the latter will only produce better health outcomes if facilities offer timely, high-quality care. Further research on this topic is needed in Africa and Latin America, as well as in urban and peri-urban areas. Additionally, more assessments are needed of integrated packages of neonatal interventions and of programs at scale.
Address Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Author Fernandez Palacios, L.; Barrientos Augustinus, E.; Raudales Urquia, C.; Frontela Saseta, C.; Ros Berruezo, G.
Title Degree of malnutrition and its relationship with major structural and eating factors in Honduran preschool population. Prevalence of breastfeeding Type Journal Article
Year 2017 Publication Nutricion Hospitalaria Abbreviated Journal Nutr Hosp
Keywords *Honduras; *Child malnutrition; *Breastfeeding
Abstract Introduction: Child malnutrition remains a serious public health problem in Honduras, with a national prevalence according to the World Health Organization (WHO) reference values of 29% in children under fi ve. In addition, the average chronic malnutrition in the region amounts to 80% in poor and indigenous communities, making Honduras the second country in Central America with the highest incidence of chronic malnutrition. Another problem of the region is the early cessation of exclusive breastfeeding: only 29.7% of children were exclusively breastfed until they were six months. Therefore, the study seeks to understand, identify and quantify the situation determinants and provide information for the design of public policies. Material and method:: The study consisted of a cross-sectional descriptive anthropometric assessment in which the nutritional status and the prevalence of undernourishment, malnutrition and malnutrition in 141 children aged between six months and fi ve years, belonging to urban and rural regions of the country, were analyzed, as well as assessing the prevalence of breastfeeding in fi ve Honduran departments (Intibuca, Lempira, Atlantida, Olancho and Francisco Morazan). Results and conclusion: When making the analysis by departments, differences regarding nutritional status and breastfeeding were observed between urban and rural areas, the latter being doubled in the case of chronic malnutrition and underweight, with percentages of 14.6% in urban areas versus28.8% in rural areas, and 4.6% in urban areas compared to 9% in rural areas, respectively. However, with respect to acute malnutrition and overweight in both regions, similar values were observed, above 1.1% for acute and 14% for overweight malnutrition. In relation to exclusive breastfeeding for six months, the departments of Olancho and Lempira maintained it for two years, with a percentage distribution of 80% and 48%, respectively. It must be noted that 36% of mothers did not provide breastfeeding, with the highest rate (15%) in the department of Francisco Morazan.
Address . [email protected]
Language Spanish Summary Language Original Title Grado de malnutricion y su relacion con los principales factores estructurales y alimentarios de la poblacion preescolar hondurena. Prevalencia de la lactancia materna en los mismos
Author Corburn, J.; Sverdlik, A.
Title Slum Upgrading and Health Equity Type Journal Article
Year 2017 Publication International Journal of Environmental Research and Public Health Abbreviated Journal Int J Environ Res Public Health
Volume 14 Issue 4 Pages
Keywords Africa; Asia; Climate Change; Employment; Environmental Health; *Health Equity; Housing; Humans; Latin America; *Poverty Areas; Socioeconomic Factors; Urban Health; Urban Population; climate change adaptation; health equity; health in all policies; housing; participation; slum upgrading; slums; social determinants of health; sustainable development goals
Abstract Informal settlement upgrading is widely recognized for enhancing shelter and promoting economic development, yet its potential to improve health equity is usually overlooked. Almost one in seven people on the planet are expected to reside in urban informal settlements, or slums, by 2030. Slum upgrading is the process of delivering place-based environmental and social improvements to the urban poor, including land tenure, housing, infrastructure, employment, health services and political and social inclusion. The processes and products of slum upgrading can address multiple environmental determinants of health. This paper reviewed urban slum upgrading evaluations from cities across Asia, Africa and Latin America and found that few captured the multiple health benefits of upgrading. With the Sustainable Development Goals (SDGs) focused on improving well-being for billions of city-dwellers, slum upgrading should be viewed as a key strategy to promote health, equitable development and reduce climate change vulnerabilities. We conclude with suggestions for how slum upgrading might more explicitly capture its health benefits, such as through the use of health impact assessment (HIA) and adopting an urban health in all policies (HiAP) framework. Urban slum upgrading must be more explicitly designed, implemented and evaluated to capture its multiple global environmental health benefits.
Address Department of City and Regional Planning & School of Public Health, University of California, Berkeley, CA 94720, USA. [email protected]
Author Navarrete-Reyes, A.P.; Medina-Rimoldi, C.T.; Avila-Funes, J.A.
Title Correlates of subjective transportation deficiency among older adults attending outpatient clinics in a tertiary care hospital in Mexico City Type Journal Article
Year 2017 Publication Geriatrics & Gerontology International Abbreviated Journal Geriatr Gerontol Int
Keywords Latin America; disability; mobility; older adults; transportation
Abstract AIM: Older adults frequently report problems of transportation. Little is known about the correlates of transportation deficiency in Latin America. Therefore, the aim of the present study was to determine the correlates of subjective transportation deficiency (STD) among community-dwelling older adults attending a tertiary care hospital in Mexico City. METHODS: Cross-sectional study of 228 participants aged >/=70 years being followed in any of the outpatient clinics of a tertiary care hospital in Mexico City. Data were obtained through a structured questionnaire. Univariate and multivariate logistic regression analyses were carried out in order to identify the correlates of STD. RESULTS: The mean age of the participants was 79.8 years (SD 6.4) and 67.1% were women. STD was present in 46% of participants. The multivariate logistic regression model showed that female sex, illiteracy, mobility disability and the use of an assistive walking device had an independent and statistically significant association with STD. CONCLUSIONS: Female sex, illiteracy, mobility disability and the use of an assistive walking device were independent correlates of STD in the present study. Identifying the frequency and correlates of transportation deficiency in vulnerable populations will allow for the identification and implementation of useful public policies, as well as for the optimization of prevention and treatment strategies in an attempt to preserve mobility and autonomy, especially in low- and middle-income countries where previous work on transportation deficiency is lacking. Geriatr Gerontol Int 2016; : -**.
Address Research Center INSERM, Bordeaux, France
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It is fat soluble vitamin.
Vitamin E is an antioxidant in nature and helps to protect the cell membrane from damage caused by free radicals and also prevents the oxidation of LDL cholesterol. It is composed of a group of substances called tocopherols which are divided into different forms like alpha, beta, and gamma.
It is necessary for maintenance of structure and functions of skeletal, cardiac and smooth muscles in body. mIt also helps in formation of RBCs and storage of vitamin A, K, iron and selenium. It has positive effect on immune system and helps to reduce the symptoms of cancer, Alzheimer's disease and some diabetes related damage especially for eyes.
It is an antioxidant. It protects the body tissue from damage caused by free radicals.
It helps to keep the immune system healthy.
It is important in the formation of RBCs and widen the blood vessels and prevents blood clotting.
It also helps in preventing cancer, heart disease, dementia, liver disease and stroke.
It can be taken in natural or synthetic form. But the best way to take vitamin E is natural food.
Vegetable oils like wheat germ, sunflower, safflower, corn, and soybean oils.
Vegetables like spinach and broccoli.
Fortified cereals, fruit juices margarine and other foods.
It is rare in humans. But sometimes people who are not able to absorb vitamin E show symptoms of deficiency of vitamin E. Premature and very low birth weight infants are at risk of vitamin E deficiency.
Fatigue, premature ageing, miscarriage, muscle weakness, slow tissue healing, greasy stools, chronic diarrhea and inability to secrete bile.
Bleeding, serious bleeding in brain, headache, fatigue, nausea.
Topically it may result in irritation on skin.
With other medicines like blood thinners vitamin E should not be taken.
High level of Vitamin E may increase the risk of birth defects.
Low level may lead to hemolytic anemia.
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that covers all the aspects of a student's development.
and assessment of broad based learning.
time intervals on small portions of content.
variety of teaching aids and techniques.
Involving learners actively in the learning process.
well in other co-curricular areas.
Use a variety of tools (oral, projects, presentations) .
Understand different learning styles and abilities.
Share the assessment criteria with the students.
Allow peer and self assessment.
Give an opportunity to the student to improve.
and twice a year respectively.
Formative Assessment totals to 40% weightage.
Summative Assessment totals to 60% weightage.
like attitudes and skills and there are three grades.
his/her marks would range from 51% to 60%.
Grade 9 would imply an A2 grade.
The academic term will be divided into two terms.
subjects may be bifurcated for the two terms.
one pen and paper test.
answer and long answer questions.
different circulars issued from time to time.
activities (6) and Health and physical education (6)}.
participation and achievement in co-scholastic areas needs improvement.
However, this should not affect the student's promotion to higher class.
appropriate place in the report card.
next higher grade and so on.
not been given to the student under the aforesaid grade point scheme.
the purpose of promotion to next class.
attempt to obtain qualifying Grade D in these subjects.
the same class during next academic year.
summative assessment due to sickness.
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Peritoneal dialysis has its roots in the early civilizations, when the existence of the peritoneum was recognized. The term peritoneum derives from the Greek peritonaion, meaning to stretch around. The first known recorded reference of the peritoneal cavity appears in the Ebers papyrus in 1550 BC1.
The Egyptians recognized that a sac surrounded the internal abdominal organs during their separation of the viscera from the rest of the corpse prior to embalmment. Galen and many other prominent physicians of antiquity observed the peritoneum in the open abdomen of injured gladiators. The early anatomists and surgeons described the extent of the peritoneal membrane, named its surfaces and attachments, but did not elaborate on its function or fine structure.
The peritoneal membrane became of physiological interest to anatomists after the discovery of cells. Von Recklinghaussen was the first to describe the gross and cellular anatomy of the peritoneum in 18622,3. Wegner described the effects of changes in body temperature occurring after intraperitoneal (ip) infusion of solutions with various temperatures4. He also reported the effects of concentrated dextrose or glycerin solutions on the volume of outflow obtained in the peritoneal effluent; this was perhaps the first evidence of osmotic ultrafiltration (UF). Starling and Tubby expanded these observations by studying the bidirectional transfer of molecules across the peritoneal and pleural membranes and demonstrated the rapid absorption of isotonic solutions and slow absorption of serum5. Prior to 1850, treatment of patients with renal failure was crude and limited to applying heat, immersing the patient in warm baths, bloodletting and administering diaphoretic mixtures with nitric acid and alcohol6. In 1854, Graham described a process, termed "Osmotic Force", where colloids and crystalloids could be separated. Based on this principle, Graham developed the "hoop" type dialyzer and suggested that animal tissue could provide a semipermeable membrane across which molecules could selectively diffuse7.
The first therapeutic infusion of fluid into the peritoneal cavity recorded in the literature was performed by Warrick8 in 1744 and involved the infusion of red wine for the treatment of ascites. In 1877, Wegner4 reported the increase of effluent volume after infusing saline solution or glycerin into the peritoneal cavity; this may have been the first report of diffusion across the peritoneal membrane.
During the first quarter of the 20th century, the physiologic basis for peritoneal dialysis (PD) was established. The relationship between osmolality of the fluids and peritoneal ultrafiltration, absorption and the bidirectional flux of small molecules between the peritoneal cavity and the intravascular compartment was emphasized8, 9. By 1920, it had been recognized that, regardless of the infusate osmolality, the fluid was completely absorbed within 20 hours of infusion 10-12. These observations led to the administration of intraperitoneal (ip) fluids to infants with severe dehydration when the oral route was not possible13,14. This may have been the first successful therapeutic use of the peritoneal membrane. Orlow, Clark, Putnam, and others demonstrated that the peritoneal membrane was permeable to sodium and other minerals15-19. Importantly, Putnam elucidated that an osmotic equilibrium exists between the peritoneal fluid and the plasma, and that mass transfer occurred by a passive process16. Klapp first observed that applying heat to the anterior abdominal wall accelerated the exchange of substances between the peritoneal cavity and the blood18. Clark later confirmed these finding using ip infusions of warm solutions. He suggested that vasodilatation was responsible for the accelerated rate of exchange19.
It was Ganter20, however, who was the first to use peritoneal lavage to treat renal failure in a patient with obstructive uropathy and in uremic animal models using physiological saline in 1923. In his uremic models, intraperitoneal exchanges of physiologic saline lasting 2 to 4 hours were utilized. Although there was moderate absorption of the dialysate due to its hypotonicity relative to uremic plasma, definite clinical improvement was noted in the animals after dialysis. As the evolution of PD solutions continued, Heusser21 sought to improve UF and added dextrose to the infusate in 1927, and Rhoads22 added lactate as a source of bicarbonate in 1938. In 1969, Boen used a peritoneal dialysate formulation containing acetate (35 mEq/L), sodium (130 – 140 mEq/L) and glucose (1.5 – 5 g/dL). This approach then became the standard practice for many years until acetate was replaced by lactate23.
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Factors associated with health-related quality of life in a large national sample of patients receiving opioid substitution treatment in Germany: A cross-sectional study
Lisa Strada1,
Christiane Sybille Schmidt ORCID: orcid.org/0000-0003-1999-20731,
Moritz Rosenkranz1,
Uwe Verthein1,
Norbert Scherbaum2,
Jens Reimer1,3 &
Bernd Schulte1
Knowledge of health-related quality of life (HRQOL) of patients receiving opioid substitution treatment (OST) is limited and fragmented. The present study examines the HRQOL of a large national sample of OST patients in Germany and sociodemographic and clinical correlates.
Cross-sectional data on the HRQOL of 2176 OST patients was compared with German general population norms. Patients were recruited from 63 OST practices across Germany. To identify correlates of HRQOL, as measured with the SF-12, we performed bi- and multivariate analyses with sociodemographic and clinical variables, including patient- and clinician-reported outcomes on physical and mental health.
Patients' HRQOL was significantly poorer than in the general population, especially their mental HRQOL. Factors associated with lower physical HRQOL were older age, longer duration of opioid dependence, hepatitis C virus infection, and HIV infection. Benzodiazepine use was associated with lower mental HRQOL, and amphetamine use with higher physical HRQOL, compared to non-use of these substances. For both mental and physical HRQOL, the factor with the strongest positive association was employment and the factors with the strongest negative associations were physical and mental health symptom severity, psychiatric diagnosis, and psychopharmacological medication.
Compared to the general population, we found substantially lower HRQOL in OST patients, especially in their mental HRQOL. OST programs can benefit from further improvement, particularly with regard to mental health services, in order to better serve their patients' needs. Clinicians may consider the use of patient-reported outcome measures to identify patients' subjective physical and psychological needs. Further research is needed to determine if employment is a cause or consequence of improved HRQOL.
ClinicalTrials.gov: NCT02395198, retrospectively registered 16/03/2015
Opioid substitution treatment (OST) is an evidence-based intervention for opioid dependence that improves patients' health and reduces the mortality rate [1,2,3]. The proportion of people who inject drugs (PWID) who receive OST varies greatly between countries. While coverage is estimated to be greater than 40 OST recipients per 100 PWID in western Europe and Australia, estimates for the USA, China, India, and Eastern Europe vary between 1 and 20 OST recipients per 100 PWID, and in most parts of the world OST is still not even available [4]. There are also large differences in sociodemographic and drug use characteristics in PWID worldwide. For example, PWID who are younger than age 25 make up less than 20% of PWID in North America, Australasia, Central Asia, and the Caribbean, but more than 40% of PWID in Eastern Europe and Latin America [5]. In Europe, the proportion of patients aged over 40 entering treatment for opioid use increased from 1 in 5 in 2006 to 1 in 3 in 2013 [6, 7]. This reflects an ageing cohort of opioid users who started injecting during the heroin "epidemics" of the 1980s and 1990s and who have shaped and characterized the current European treatment systems [6, 7]. A steadily increasing age of the OST population is also observed in many other regions in the world with a longer history of OST implementation, such as New York City [8] and Australia [9]. Thus, long-term OST patients are getting older and few young people are entering OST. An ageing population places increasing demands on the health care system [10, 11]. Especially the next two decades will pose a challenge, as the large cohorts of opioid users who initiated use in the eighties and nineties are growing old.
Understanding the needs of OST patients is critical to providing the right care. Health-related quality of life (HRQOL) is a valuable outcome measure in this regard. It is a concept that includes subjective physical and mental wellbeing, and can be useful in the evaluation of treatment programs and patient progress by providing insight from the patient's perspective. [12].
Over the past two decades, there has been an increasing interest in the HRQOL of OST patients. Research consistently shows that OST patients' HRQOL is significantly lower at treatment entry compared to the general population or people with psychiatric disorders [10, 13,14,15] and that HRQOL improves in the first months of OST [16,17,18,19]. However, comparatively little is known about the HRQOL of long-term OST patients. A few cross-sectional studies suggest that OST patients continue to have poor HRQOL in OST, but these studies are limited by small sample sizes and partially conflicting outcomes [10, 13, 20, 21]. Only Wittchen et al. (2011) assessed the HRQOL of a large sample of OST patients – although only as a secondary outcome – and found significantly lower HRQOL compared to the general population and no improvements over a one-year period [22].
In fact, while HRQOL improves at treatment uptake, the effect seems short-lived. Wang et al. (2012) conducted an 18-month study in which they assessed quality of life (QOL) every 3 months [23]. They found that QOL improved rapidly in the first 3 months of OST, but then the effect slowed down. Likewise, Ponizovsky et al. (2007) detected an improvement of QOL only in the first month of OST [24]. Habrat et al. (2002) demonstrated that while HRQOL improved significantly the first 6 months of OST, it then decreased again [25]. Karow et al. (2011) found that QOL increased more during the first 6 months of OST than the following 6 months and that it did not reach the level of healthy individuals [15]. Taken together, the literature suggests that OST is effective in enhancing QOL and HRQOL at treatment entry but may have shortcomings in the long-term.
Understanding the needs of subgroups of patients is essential to be able to provide appropriate care. Research consistently shows that female OST patients have poorer overall HRQOL than male patients [15, 21]. However, some studies found an association of gender with mental HRQOL, some with physical HRQOL, and others with both physical and mental HRQOL or neither [20, 26,27,28,29]. Similarly, there is conflicting evidence with regard to other factors, such as active drug use and hepatitis C virus (HCV) infection [13, 15, 30,31,32]. The present study aims to provide the first comprehensive data on the HRQOL of a large national sample of patients in OST including sociodemographic and clinical correlates.
This investigation is part of the larger study 'Epidemiology Of Hepatitis C Virus Infection Among People Receiving Opioid Substitution Therapy (ECHO)', an observational longitudinal multicentre study, which aims to estimate the national prevalence and incidence of HCV infection among OST patients in Germany. Stratified random sampling was performed to obtain a representative sample of OST clinicians based on their distribution according to German Federal State and the number of patients per clinician. For patients to be eligible to participate in the study they had to be diagnosed with opioid dependence according to the ICD-10, be currently in OST, be at least 18 years of age, and have sufficient German literacy skills. Patients were eligible to participate with any form of OST (e.g. liquid, pills, capsules) and any type of OST medication (e.g. methadone, buprenorphine, pharmaceutical heroin). OST physicians invited their patients to participate in the study; participation was voluntary and remuneration was provided. Once patients completed the questionnaire, they placed it in an envelope and sealed it so that physicians could not access the data. The study design is described in full detail elsewhere [33]. Ethical approval for the ECHO study was granted by the Ethics Committee of the Medical Association of Hamburg, Ref. PV4603, and by each local Ethics Committee in Germany.
From July 2014 to October 2016, epidemiological cross-sectional data was collected from a large national sample of 2474 outpatients receiving OST from 63 OST clinicians in Germany. A good regional distribution of clinicians across Germany was obtained, although smaller clinics were somewhat underrepresented in our sample. Of the 2474 patients, a total of 298 (12.1%) were excluded because they did not fill in the patient questionnaire (N=239, 9.7%) or because the HRQOL instrument had more than two missing values per participant (N=59, 2.4%; [34]). Of the final 2176 patients included in the analyses, clinician data was not available for 79 patients.
HRQOL was measured with the 12-Item Short Form Health Survey (SF-12; [35,36,37]). The 12 items are a subset of the 36-item Short Form Health Survey (SF-36; [38]), and assess subjective functional health and wellbeing (e.g. "Does your health limit you in climbing several flights of stairs? If so, how much?" or "In the past week, how often were you calm and relaxed?"). Physical and Mental Component Summary Scores (PCS and MCS) are calculated. We chose the SF-12 because it is one of the most widely used HRQOL instruments in the addiction literature [39, 40] and because country-specific general population norms are available for it [36]. Good psychometric properties of PCS and MCS are reported for both the original American version and the German version used in this study (e.g. test-retest (2-week) correlations of 0.89 and 0.76 [37], and internal consistency (Cronbachs alpha) > .70 [36]). The SF-12 has a high construct validity in discriminating between patient groups known to differ in physical and mental conditions, and it is also sensitive to change [36, 37]. Correlations between the 12-item and the 36-item PCS and MCS are very high, ranging from 0.94–0.96 for PCS and 0.94–0.97 for MCS across different countries and languages [35].
Patients and clinicians completed questionnaires independently from one another.
Patients provided sociodemographic data (gender, age, employment, children, relationship, housing, and migration background) and completed the SF-12, the Brief Symptom Inventory-18 (BSI-18; [41]), and the Opiate Treatment Index Health Symptoms Scale (OTI-HSS; [42, 43]). The BSI-18 is a self-report measure of psychological distress, comprising a symptom checklist and yielding three sub-scores (Depression, Anxiety, and Somatization), as well as the Global Severity Index (GSI). The OTI-HSS is a self-report measure of physical health, comprising a checklist of 50 symptoms that opioid users often experience.
Clinicians provided clinical data (duration of current OST, substitution medication, years of opioid dependence, active drug use, HCV infection, human immunodeficiency virus (HIV) infection, psychiatric diagnosis, and psychopharmacological medication during the past 6 months) and rated patients' functioning and illness severity using the Global Assessment of Functioning scale (GAF; [44]) and the Clinical Global Impression scale (CGI; [45]). Active drug use was defined as the consumption of at least one illegal substance (cocaine, benzodiazepines, heroin or amphetamine) once during the past three months. The last three urine samples from the past three months were tested for the four substances, thus creating 12 possible data sets per patient. Information on psychiatric diagnosis and psychopharmacological medication, as well as HCV and HIV status, was taken from the patients' medical records. Clinicians were encouraged to perform HCV diagnoses in accordance with the German HCV testing-guidelines (i.e. yearly antibody tests for patients with negative serostatus). However, due to the non-interventional nature of our study, clinicians were not obliged to do this. The time of testing was therefore individual for each participant.
We calculated the two component summary scales of the SF-12 (PCS and MCS) in accordance with the German test manual [36], using US-derived item weights. Up to two missing values per participant were imputed in the SF-12 (method proposed by Perneger et al. [34]). Participants with more than 2 missing items were excluded from analysis. To compare the SF-12 scores of our sample with the general population, we calculated independent sample t-tests using PCS/MCS means, standard deviations and sample sizes of the German normative sample from 1998 [36]. In addition, we determined the percentages of patients scoring lower or higher than one standard deviation below or above the German general population mean. Bivariate associations between PCS/MCS and our variables of interest were assessed using Pearson's correlations for continuous variables (e.g. age, BSI-18), independent samples t-tests for dichotomous variables (e.g. gender), and one-way ANOVAs for categorical outcomes (e.g. partnership, age groups). For each statistically significant association, we determined effect sizes (standardized mean difference (d) and partial eta2). In addition, we calculated multiple linear regression models to predict PCS and MCS based on sociodemographic and clinical characteristics. We included the variables gender, duration of opioid dependence, employment, living together with children, relationship, migration background, percentage of positive urine samples, duration of current OST, HIV status, and HCV status. The variables were selected based on considerations of relevance and multicollinearity. We first included all sociodemographic and clinical variables (Table 1) in one regression model (simultaneous entry), and then removed predictors that were either redundant in content or demonstrated intercorrelations higher than r = .6.
Table 1 Sociodemographic and clinical characteristics
Sample characteristics
Respondents (N = 2176) were predominantly male (72.2%) with a mean age of 41.8 (± 8.94) years. They were opioid dependent for an average of 20.4 (± 9.11) years and in their current OST for an average of 6.3 (±5.21) years. Of the total sample, 83.1% reported stable housing, 52.4% had children, 44.8 % were in a relationship, 34.5% were employed, and 23.8% had a migration background. Most respondents received methadone (76.6%), followed by buprenorphine (22.6%) and other substitution medications (0.8%). Moreover, 27.2% of participants were HCV-RNA positive, 3.7% were HIV-positive, and 2.2% were HCV/HIV co-infected. Thirty-six percent had consumed drugs within the past 12 weeks (Table 1).
To test for selection bias, we compared sample characteristics of the 2176 included patients with the 298 non-included patients, using data provided by the clinicians. Significant differences but with small effect sizes (around d = 0.3) emerged between the included and the non-included sample in (non-German) citizenship (10.0% vs. 18.9%), mean GAF ratings (65.7 ± 18.8 vs. 59.7 ± 19.1), mean CGI-S ratings (2.9 ± 1.6 vs. 3.5 ± 1.6), and past 4 weeks benzodiazepine use (15.7% vs. 23.9%). Only very small differences (d < 0.3) were found in age, gender, duration of current OST, and CGI-I ratings. No differences were found in psychiatric diagnosis, psychopharmacological medication, substitution medication, duration of opioid dependence, and use of heroin, cocaine or amphetamine.
HRQOL of OST patients compared to the German normative sample
OST patients had a mean PCS of 44.63 (SD 9.75, range 11.04 - 64.08) and a mean MCS of 41.76 (SD 11.40, range 10.83 - 69.06; Table 2). Respondents scored significantly lower on the PCS than the German normative sample (M = 48.22, SD = 8.77; t(8850) = -15.270, p<0.001, d = -0.40). This effect was even more pronounced for the MCS (M = 51.41, SD = 8.55; t(8850) = -36.275, p<0.001, d = -1.03).
Table 2 Measures of HRQOL, physical health and mental health
The distributions of PCS and MCS scores in our sample are not bell-shaped. The PCS distribution is left-skewed, with a peak at about 55 points (Fig. 1). The MCS has a bimodal distribution with peaks at about 30 and 55 points (Fig. 2). For PCS, 30.4% of patients scored lower than one standard deviation (SD) below the German normative sample mean and 5.9% of patients scored higher than one SD above the mean (Fig. 1). For MCS, 51.7% of patients scored lower than one SD below the German normative sample mean and 1.8% of patients scored higher than one SD above the mean (Fig. 2). Regarding PCS and MCS together, 1362 patients (62.6% of the total sample) scored lower than one SD in at least one scale and, of this group, 425 patients (19.5% of the total sample) scored lower than one SD in both scales.
Distribution of the SF-12 Physical Component Summary score (PCS) compared with German general population norms. ECHO study sample (n = 2176) statistics: mean = 44.63, standard deviation = 9.75, range 11.04 – 64.08; skewness = -0.50, SE = 0.05; kurtosis = -0.56
Distribution of the SF-12 Mental Component Summary score (MCS) compared with German general population norms. ECHO study sample (n = 2176) statistics: mean = 41.76, standard deviation = 11.40, range 10.83 – 69.06; skewness = -0.18, SE = 0.05; kurtosis = -0.95
Both male and female OST patients had lower SF-12 scores than the general population (Men PCS 44.58 ± 9.61 vs. 49.12 ± 8.20, d = -0.52; Men MCS 42.29 ± 11.13 vs. 52.54 ± 7.81, d = -1.14; Women PCS 44.79 ± 10.10 vs. 47.34 ± 9.19, d = -0.54; Women MCS 40.39 ± 11.98 vs. 50.30 ± 9.08, d = -1.07; all p <.001). Moreover, SF-12 scores were lower in all age groups compared to the general population (Fig. 3).
SF-12 scores by age groups, compared with the German general population. Means and standard errors of A: Physical Component Summary scores (PCS) and B: Mental Component Summary scores (MCS) by age groups for the study sample of OST patients (n = 2176) and the German normative sample (n = 6676)
Sociodemographic and clinical correlates of HRQOL in OST patients
Bivariate associations of sociodemographic and clinical variables with SF-12 scores are shown in Table 3. Relevant associations (effect sizes d > 0.35, r > 0.2, partial eta 2 > 0.04; Ferguson, 2009 [46]) are described first. Older age, longer duration of opioid dependence, methadone as substitution medication, HCV infection, and HIV infection were associated with lower PCS. Having a psychiatric diagnosis, being in psychopharmacological treatment, and current drug use were associated with lower MCS. Although, more specifically, only benzodiazepine use was associated with lower MCS, while amphetamine use was associated with higher PCS (no association with heroin or cocaine use). Unemployment was associated with lower PCS and MCS.
Table 3 Bivariate associations of sociodemographic and clinical variables with HRQOL in OST patients
Other significant associations but with very small effect sizes emerged (d < 0.35, r < 0.2, partial eta 2 < 0.04). Women exhibited slightly lower MCS than men, patients receiving methadone had lower MCS than those receiving buprenorphine, and patients with HCV infection had slightly lower MCS than those without. Psychiatric diagnosis, psychopharmacological treatment, longer duration of current OST and migration background was weakly associated with lower PCS. There was also a very small association between drug use and lower PCS. More specifically, only amphetamine use and benzodiazepine use was associated with lower PCS (and not the other two substances we measured, heroin and cocaine). Being in a relationship and living in stable housing was associated with slightly higher PCS and MCS. Participants who lived together with their children had slightly higher PCS and MCS than those who did not.
In the multivariate models (n = 1703; Table 4), higher PCS was predicted by (highest regression weights mentioned first) stable employment, shorter duration of opioid dependence, negative HCV status, the absence of a psychiatric diagnosis, and being substituted with buprenorphine. Higher MCS was predicted by (highest regression weights mentioned first) the absence of a psychiatric diagnosis, stable employment, not being in psychopharmacological treatment, less drug use, male gender, being substituted with buprenorphine and living together with children. As 473 patients were excluded from the multivariate model due to missing values, we checked for possible selection bias. The 1703 patients included in the regression model were slightly younger (41.5 years (± 8.8) vs. 42.9 (± 9.3) years, p = .004), reported less physical impairments (better PCS and BSI somatization subscale), were slightly longer in their current OST, and had higher CGI-I ratings (all differences d < .2). No differences in other variables emerged.
Table 4 Multivariate linear regression models of sociodemographic and clinical variables with HRQOL in OST patients (n = 1703)
HRQOL and measures of physical and mental health
Better self-reported mental health (BSI-18) correlated moderately with better PCS (r = -.41) and strongly with better MCS (r = -.67). More specifically, the BSI-18 subscale Somatization correlated moderately with PCS and MCS, while the subscales Depression and Anxiety correlated weakly with PCS and strongly with MCS. The OTI-HSS score correlated moderately with PCS (r = -.48) and MCS (r = -.50), such that participants with a higher OTI-HSS score demonstrated lower PCS and MCS (Table 3). Clinicians' ratings of patients' mental illness severity (CGI-S: M=2.91, SD=1.59, range 1-7) and functioning (GAF: M=65.72, SD=18.81, range 0-100) were weakly correlated with patients' self-reported physical and mental HRQOL (Table 2 and 3).
This study presents a comprehensive and differentiated assessment of the physical and mental HRQOL of a large national sample of OST patients in Germany. Substantial impairments were found in OST patients' HRQOL, especially in their mental HRQOL. However, there was also a smaller subgroup of patients with considerably better HRQOL than the rest of the sample, indicating that it is possible for patients to attain a relatively good HRQOL. This suggests that there is room for improvement in OST programs, particularly relating to patients' mental wellbeing.
Our findings may inform tailored interventions for subgroups of patients and have implications for drug policies. For example, age was one of the most important correlates of poor physical HRQOL, suggesting that older OST patients may benefit from enhanced health care services. Moreover, the association of chronic HCV infection with low physical HRQOL highlights the importance of providing antiviral HCV treatment to OST patients. Many clinicians still hesitate to provide HCV treatment to drug users, because they fear reinfection or non-adherence to treatment, and also drug-users are frequently unwilling to take up HCV treatment [47]. However, especially in this new era of direct-acting antiviral (DAA) treatment with reduced side effects and high rates of sustained virologic response (SVR), it is important to reduce the barriers to HCV diagnosis and treatment and to educate clinicians and patients about treatment benefits beyond SVR, such as increased subjective wellbeing and reduced symptoms of extra-hepatic manifestations [48, 49]. While it makes sense that older age, HCV and HIV infection are associated with lower physical HRQOL, it should be noted that these factors have a greater impact on drug users than non-drug users [50, 51], highlighting the need for additional support specifically for older drug users.
While OST briefly improves mental health outcomes at the beginning of treatment [52], it does not appear to address patients' mental health adequately in the long run. Opioid dependent individuals have high levels of psychiatric symptoms [22, 53]. Past-year prevalence estimates of co-occurring psychiatric disorders range between 30% and 50% for mood disorders (e.g. depression) and 10% to 20% for anxiety disorders [54, 55]. However, our study and a recent 6-year follow up cohort study demonstrate that this high psychiatric comorbidity persists in long-term OST patients [56]. More than half of the patients in our sample had at least one psychiatric diagnosis. This is an important finding, because patients with dual diagnosis face barriers to adequate mental health treatment, including insufficient cooperation between mental and medical health institutions and the under-identification of dual diagnosis, which is in part due to the lack of mental health training in physicians [57,58,59]. As our study finds that psychiatric diagnosis and psychopharmacological treatment are associated with both mental and physical HRQOL, one may argue that it is particularly important to address OST patients' mental health, as it is not only associated with mental but also physical wellbeing.
Gender was only weakly associated with HRQOL. This may explain the mixed findings in the literature from smaller studies, which show associations of gender with mental or physical HRQOL or neither or both [15, 20, 21, 26,27,28,29]. Similarly, there were mixed findings in the literature on the association of HRQOL with active drug use. Our results show that only benzodiazepine and amphetamine use was associated with HRQOL and not heroin or cocaine use. Benzodiazepine users might be self-medicating, considering that they often have a more complicated course of OST and exhibit more poly drug use [60]. Moreover, the regular and long-term use of benzodiazepines itself reduces quality of life and has adverse effects like cognitive or psychomotor impairment [61, 62].
While we found an association of HRQOL with substitution medication, the differences between methadone and buprenorphine are likely confounded with other factors that correlate with buprenorphine prescription, such as age, duration of opioid dependence, and preexisting physical and mental health. Buprenorphine is less sedating than methadone, but it is also more often prescribed to younger and more stable patients. The complexity of these interrelations needs to be considered when interpreting the results, and is also reflected in the multivariate model where the association between OST medication and HRQOL becomes much smaller when controlling for the above-mentioned factors.
In the multivariate model, we only included sociodemographic and clinical predictors, because bivariate associations of PCS and MCS with self-reported physical and mental health were already demonstrated. Consequently, the percentage of variance explained was relatively low (21% for PCS, 18% for MCS), which is however not surprising, given that HRQOL is influenced by a range of factors that cannot all be measured in a study. With regard to a potential selection bias that may have resulted from the listwise inclusion in our multivariate analyses, we consider the subsample included in the regression models highly representative for the total sample; differences in age and health are only marginal and no other relevant differences emerged. Results of bivariate and multivariate analyses are highly comparable. The most important bivariate correlations were also found as predictors in the multivariate model, and the relative importance of each predictor (expressed by standardized beta weights) reflects the effect sizes determined via bivariate comparisons. The most important predictors for both PCS and MCS were employment and mental health, followed by duration of opioid dependence for PCS.
Another interesting observation is that, even though patients and clinicians provided ratings for HRQOL and functioning independently, the scores correlated. Patients' self-reported mental and physical HRQOL correlated with clinician-rated patient functioning (GAF) and clinician-rated mental illness severity (CGI-S) (Table 3). The literature often reports a discrepancy between the perspectives of patients and clinicians [63, 64], but our findings suggest that in patients with an opioid use disorder, clinicians' ratings of functioning and mental illness severity are good indicators of patients' HRQOL.
HRQOL correlated with patient-reported measures of physical and mental health. These "cross-over" associations between the physical and mental domains (i.e. MCS with OTI-HSS, and PCS with BSI-18) suggest that there is not a strict division between physical and mental health with regard to their impact on a person's subjective wellbeing. Nevertheless, brief symptom-based psychiatric screening tools should be implemented more regularly in clinical practice, given the high prevalence of mood and anxiety disorders in the opioid dependent population. Systematic screening for depression and anxiety, including in newly admitted patients, can reduce under-identification of comorbid disorders, which is a structural barrier to mental health treatment [58, 65]. Practitioners should use instruments with good validity for drug using populations, such as the BSI-18 [66].
As our study had a cross-sectional design, we could not determine if unemployment was a cause or consequence of poor HRQOL. Considering unemployment status was the most important factor correlating with HRQOL, future research should investigate this relationship further. Moreover, longitudinal studies could evaluate the effects of work rehabilitation programs on OST patients' HRQOL, and qualitative studies could investigate patients' perspectives and needs with regard to employment and HRQOL. It is also important to clarify if and how re-integration in the labor market is a reasonable treatment goal for opioid dependent patients. So far, in Germany, work rehabilitation plays virtually no role in OST in practice [67].
A limitation of this study is its possible selection bias. Due to missing or incomplete patient questionnaires, 358 patients (14.5%) had to be excluded. Differences between the included and excluded samples were small, although it is worth noting that excluded patients had greater impairments in (clinician-reported) mental health and functioning, meaning the HRQOL of this study sample might be higher than that of the actual overall population of OST patients. A second limitation is the interpretation and validity of our drug use and treatment variables. As we collected routine data, which differed between study sites, the frequency of urine sampling and the substances that were tested varied between OST practices. Moreover, we did not record which patients were prescribed benzodiazepine, so that we cannot distinguish between prescribed and non-prescribed benzodiazepine use. We also did not keep track of what other interventions or services the participants were using and suggest that future research explores their additional impact on HRQOL. A third limitation is that we used data from the German normative sample from 1998. However, (a) the HRQOL of the German general population has improved since 1998, especially in individuals over the age of 50 [68], and (b) our sample is about 4 years younger and includes more men than the German general population and SF-12 norm samples [69, 70]. This is important, because younger age and male gender are associated with better HRQOL [68]. Therefore, if we compared our sample of OST patients to a more recent norm sample with younger and more male individuals, there would be an even bigger difference in HRQOL scores.
This study highlights the need for more patient-centered care. Rather than just focusing on clinical symptoms, we should also measure the subjective experiences and needs of OST patients to be able to provide more effective and patient-oriented interventions and care. HRQOL is a useful patient-reported outcome measure in this regard. Given the high comorbidity of opioid dependence and given that diseases and symptoms are burdensome to different degrees to different people, a measure of subjective wellbeing is arguably a better indicator of patients' needs than symptom-based instruments such as the BSI-18 and OTI-HSS. It should be noted that the SF-12 is a generic HRQOL instrument and may therefore not provide sensitive data on the HRQOL of OST patients. Future research should use a drug-user specific HRQOL instrument with items that are relevant and specific to OST patients.
The differences in mental and physical HRQOL of OST patients demonstrate the need to measure wellbeing in multiple life domains. However, also the concept of HRQOL is limited in its scope and future research should examine the broader concept of QOL for a more comprehensive understanding of patients' wellbeing and a holistic approach to patient's recovery. The concept of QOL goes beyond symptoms of physical and mental health and broadens the view on a person's condition by including aspects such as social and economic participation. Given that opioid dependence is a complex chronic disease, the improvement of QOL is a more adequate treatment goal than the absence of symptoms. To monitor long-term treatment success, a short but reliable QOL instrument, such as the Opioid Substitution Treatment Quality of Life scale (OSTQOL, [71]) could be a useful tool for OST providers.
Compared to general population norms, we found substantially lower HRQOL in OST patients, especially in their mental HRQOL. Interestingly, our sample also comprised a considerable albeit smaller proportion of high-functioning OST patients with good physical and mental health, employment, stable housing, and/or stable family situation. However, the biggest proportion of OST patients had severe deficits in physical and mental health and HRQOL, suggesting that OST programs could benefit from further improvement to better serve their patients' needs, particularly with regard to their mental health. An integrated health care approach is needed in which different physical and mental health care services are offered in combination, such as psychosocial support, therapy, and case management, as well as medical care specializing in the physical problems of opioid users. Moreover, more patient-centered care is needed to incorporate the patients' perspectives and experiences in the treatment plan. Clinicians may consider the use of patient-reported outcome measures to enhance patient engagement in treatment.
BSI-18:
Brief Symptom Inventory-18
CGI:
Clinical Global Impression
ECHO:
Epidemiology Of Hepatitis C Virus Infection Among People Receiving Opioid Substitution Therapy
GAF:
Global Assessment of Functioning
GSI:
Global Severity Index
HCV:
HRQOL:
MCS:
Mental Component Summary (composite of the 12-Item Short Form Health Survey)
OST:
Opioid Substitution Treatment
OTI-HSS:
Opiate Treatment Index - Health Symptoms Scale
Physical Component Summary (composite of the 12-Item Short Form Health Survey)
QOL:
SF-12:
12-Item Short Form Health Survey
SVR:
Sustained Virologic Response
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We thank Christine Götzke and Dr. Philipp Hiller for their support in the data collection and data management.
The 'Epidemiology of Hepatitis C Virus Infection among People Receiving Opioid Substitution Therapy (ECHO)' study is co-financed by Janssen-Cilag GmbH. Janssen-Cilag GmbH had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
The dataset of the current study is not yet publicly available, because analyses on further research questions using this data are still ongoing. However, the parts of the dataset used for this publication are available from the corresponding author on reasonable request.
Centre for Interdisciplinary Addiction Research, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
Lisa Strada, Christiane Sybille Schmidt, Moritz Rosenkranz, Uwe Verthein, Jens Reimer & Bernd Schulte
LVR-Hospital Essen, Department of Addictive Behaviour and Addiction Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
Norbert Scherbaum
Gesundheit Nord, Kurfürstenallee 130, 28211, Bremen, Germany
Jens Reimer
Lisa Strada
Christiane Sybille Schmidt
Moritz Rosenkranz
Uwe Verthein
Bernd Schulte
BS, UV and JR designed the study; CS and MR performed the data analyses; LS wrote the manuscript; NS contributed to the discussion and commented on the manuscript. All authors reviewed and approved the final version of the manuscript.
Correspondence to Christiane Sybille Schmidt.
Ethical approval was granted by the Ethics Committee of the Medical Association of Hamburg, Ref. PV4603, and by each local Ethics Committee in Germany.
Not applicable; no details on individuals are reported within the manuscript
JR received unrestricted educational grants, adviser and/or speakers remuneration from AbbVie, Desitin, Gilead, Janssen-Cilag, Mundipharma, Otsuka-Lundbeck, Hexal.
NS received honoraria for several activities (advisory boards, lectures, manuscripts and educational material) by the factories AbbVie, Lundbeck, Medice, Mundipharma, Reckitt-Benckiser/Indivior, and Sanofi-Aventis. During the last three years he participated in clinical trials financed by the pharmaceutical industry.
BS, UV, LS, CS, MR declare no potential conflicts of interest.
Strada, L., Schmidt, C.S., Rosenkranz, M. et al. Factors associated with health-related quality of life in a large national sample of patients receiving opioid substitution treatment in Germany: A cross-sectional study. Subst Abuse Treat Prev Policy 14, 2 (2019). https://doi.org/10.1186/s13011-018-0187-9
Opioid dependence
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LightTouch Device May Eliminate Pap, Biopsy for Cervical CA Testing
Medgadget Editors Ob/Gyn, Oncology
A new light based test that detects early signs of cervical cancer may be a better diagnostic tool than a pap smear, according to preliminary findings from a multi-site Food and Drug Administration (FDA) pivotal clinical trial. The study of more than 1,900 women looked at Guided Therapeutics' LightTouch system, a device that uses optical probe to shine light at different wavelengths and to detect alterations in fluorescence spectra coming back from the dysplastic /cancerous growth.
Since the pivotal trial began, more than 1,900 women were tested to demonstrate the technology's safety and efficacy in detecting cervical disease, including an arm of the study that assessed effectiveness of an investigational commercial version of the device and single-use disposable.
The study protocol indicated that all subjects were referred after undergoing a Pap test, or had some other risk factor that fulfilled the referral criteria of the study. Each subject was tested with the LightTouch investigational device and underwent an additional Pap test, colposcopic exam and biopsy. Two generations of the investigational LightTouch were used in the trial.
Preliminary results from the study showed that the LightTouch performed better than the Pap test. The investigational commercial version of the LightTouch detected approximately 46 percent more cervical disease than the Pap test – a statistically significant improvement.
Here's more about the technology from the manufacturer:
The device system (Guided Therapeutics, Inc. Norcross, GA, USA) used in the study is a nonsignificant risk device by FDA standards that noninvasively and automatically scans the ectocervix and distal endocervix for disease related changes in fluorescence and reflectance spectra.
Alterations in fluorescence spectra are indicative of metabolic changes associated with neoplasia, while alterations in reflectance and scattering are indicative of structural changes associated with neoplasia, such as epithelial thickening, nuclear size, nuclear content and angiogenesis.
A plurality of equally spaced points over a one-inch diameter area of the cervix was automatically scanned during a four-minute period using a filtered xenon arc lamp as an illumination source.
For cervical tissue reflectance measurements, broadband spectral output ranging from about 350 to 900nm was automatically applied under software control to the cervix using the same xenon arc lamp. The resultant reflectance spectral output from the cervical tissue was imaged onto the CCD camera and stored for processing
and analysis.
For cervical tissue fluorescence measurements, light from the arc lamp was band pass filtered to limit exposure
of the cervix to bands within the 300 to 500 nm range. These spectral bands are known to excite fluorophores associated with neoplastic processes as described above. Each of the fluorescence wavelengths were applied automatically under software control in a predetermined order and scan pattern. The resultant fluorescent spectral output of the cervical tissue was imaged onto a charge coupled device (CCD) camera and stored for processing and analysis.
The system consists of two main physical components, the hand-held unit and the base unit. The handheld unit is
connected to the base unit via fiberoptic cables for transmission of light to and from the base unit, which contains the xenon arc lamp, optical processing elements (e.g., filters and lenses) and the CCD camera on a rolling cart (CNDS Device).
The other major component of the CNDS is a computer for control and data processing. This includes the capability for a diagnostic algorithm based on spectroscopic information measured from the cervix, calibration data and other patient data, such as Pap results or patient demographic data.
Press release: Guided Therapeutics, Inc. Reports Preliminary Findings from FDA Pivotal Clinical Trial (PDF)
Device page: LightTouch…
Poster about the system (.pdf) from Georgia Life Sciences Summit 2006…
Bottom image: Cervical maps with biopsy sites marked X.
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Development of personalized assessment, performance, endurance, and training methods for high altitude. Development efforts focused on improving altitude tolerance and reducing symptoms of acute mountain sickness, using molecular countermeasure solutions. Includes space analogue conditions, such as Mars. Collaborators include the Mayo Clinic and others.
Co-development of Corvette Racing's driver science, personalized medicine, human performance program, based on molecular and physiologic metrics. Consultation with NASCAR teams and other racing teams around molecular-derived personalized countermeasures.
Molecular profiling and individualized countermeasures for NBA teams and athletes. Among these are the Golden State Warriors, during their 73-9 record-setting season.
Development of study paradigms and possible solutions for football-associated concussion. This work is focused on NAD, ATP, PARP-1, BNDF, and other molecular networks. Includes advanced neuroimaging approaches, such as 31P MRS. Beyond the research area, this also incorporates analysis of football player serum molecular profiles and development of tailored, personalized solutions. Collaborations include the NFL Players Association, US Olympic teams, and West Point Military Academy (USMA).
Development of individualized molecular profiling and molecular countermeasure strategies for US Special Forces. Development of study paradigms and possible solutions for combat-associated concussion. Research surrounding extending operations in the field and improving soldier performance. This includes work with the Combat Feeding Directorate and West Point Military Academy (USMA).
Examination of patterns of human performance in expedition environments, which can also serve as space analogue environments. Team cohesion is one of the central elements that governs team success in almost any environment (sports, special forces, spaceflight, wilderness, etc.). It also strongly impacts individual success and survival. We work to study and optimize the neurobehavioral and biological influences on team cohesion, with a focus on countermeasures.
To determine the effect of oral nicotinamide riboside (NR) on altitude tolerance, team cohesion, cardiopulmonary function, sleep, and measures of aging. This study also served as a Mars analogue mission, with further applications to military training and operations in hypobaric hypoxia field conditions.
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The crystal structure of the pristine (I) and aged (II) crystals of CH3NH3PbI3 (hereafter MAPbI3) hybrid organic-inorganic lead iodide has been studied at 293 K with high-precision single-crystal X-ray diffraction using a synchrotron light source. We show that (I) and (II) are characterized by an identical tetragonal unit cell but different space groups: I422 for (I) and P42212 for (II). Both space groups are subgroups of I4/mcm, which is widely used for MAPbI3. The main difference between (I) and (II) comes from the difference in hydrogen bonds between the MA+ cation and the PbI3 framework which is the direct consequence of H2O insertion in the aged crystal (II).
We report the synthesis of Methylammonium Lead Iodide (CH3NH3PbI3) nanowires by a low temperature solution processed crystallization using a simple slip-coating method. The anisotropic particle shape exhibits advantages over nanoparticles in terms of charge transport under illumination. These results provide a basis for solvent-mediated tailoring of structural properties like the crystallite size and orientation in trihalide perovskite thin films, which, once implemented into a device, may ultimately result in an enhanced charge carrier extraction.
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Skin inching is a common and unbearable symptoms of kidney failure, especially for the patients with dialysis. Skin itching influence the life quality of patients seriously. Without a timely treatment, it will cause the skin infection, more worse, it may threat the life of patients. Then how to treat the skin itching naturally and effectively for kidney failure patients with dialysis? Now our specialists will give you the detailed introductions about the cause and treatment of skin itching.
1. With the decline of kidney function, the extra phosphorus can not be excreted out body. The high blood phosphorus can lead to the PTH secretion, causing hyperparathyroidism which is one of main reasons for skin itching.
2. The metabolites of nitrogen mass also can't be removed out of body, so it will stimulate the skin, causing the shrinking of sebaceous glands and sweat glands and occurring dry skin and skin itching.
3. Kidney failure patients are allergic to many things. When patients accept dialysis, they may be allergic to the dialysis equipment.
A bottle of Maikang composition: improving the blood flow speed and decreasing the wastes depositing.
A dose of oral Chinese herb medicine: cleaning the wastes in blood effectively.
A dose of external application medicine: dredging the blood vessel of kidney and promoting the blood circulation.
A basin of foot bath medicine: dissolving the blood stasis and improving blood condition.
The medicines can absorb and crash the wastes, then remove them out of body with metabolism, at the same time, it can improve the blood circulation and decrease the formation of blood clots which can lead to more toxins in blood. When the blood speed and content are normal, kidney failure patients can feel better about the skin itching. If you have any question about the kidney failure or our treatment, you can send email to us or contact our online doctors.
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outcomes, and provides knowledge and experience requirements at each grade.
Develops, implements, and evaluates programs policies, and services to meet the needs of students in the following areas: academic, residence, judicial, student life and activities, career development, and/or special populations. Evaluates academic credentials; designs intervention programs for students experiencing difficulty; and provides academic, personal, and career counseling and advice. May develop special projects, activities, outreach, and student leadership programs and training; and serve as a liaison to university departments. May supervise staff, negotiate and authorize contracts with vendors within university limits, develop programs, and assist with budget development. Works independently within broadly defined work objectives. Utilizes solid understanding of the theoretical and applied bases for the particular field of specialization. Functions as a seasoned professional in the functional area of expertise.
academic theories, methodologies, and current practices in higher education. Also requires a minimum of three years experience in an academic, residence, judicial, student life/activities, or career development function; excellent communication skills; and computer literacy.
Develops, implements, and evaluates programs, policies, and services to meet the needs of students in the following areas: academic, residence, judicial, student life and activities, career development and/or special populations. Oversees outreach and manages service delivery. Develops written documentation of all aspects of field instruction, guidelines, and/or manuals. May identify new and continuing funding sources, and manage facility services and/or staff. Interprets, communicates, and implements policies and practices for differing needs of a diverse client population. Researches and benchmarks best practices for development of effective strategies and resolutions to complex problems that may require creativity. Demonstrates specialized knowledge of one field or general knowledge of broader fields.
requires a minimum of three years experience in an academic, residence, judicial, student life/activities, or career development function; excellent communication skills; and computer literacy.
and strategic alliances with internal constituents and external agencies/corporations.
student development, counseling, or related field; and a minimum of three years of directly-related experience of increasing responsibility in a leadership or managerial role that demonstrates knowledge and understanding of strategic planning, management, team-building, leadership skills, fiscal management, and best practices research. Also requires excellent communication skills and computer literacy.
services at each residence hall. Enriches the leadership skills of the executive boards of each hall through individual and group meetings, special events, and programs. Responds to all student problems and emergencies. Partners with students and colleagues to understand issues and provide solutions. Demonstrates good understanding of the theoretical and applied bases for the particular field of specialization. Provides resolutions to an assortment of problems of moderately complex scope. Uses judgment within defined practices and procedures.
communication skills and computer literacy.
situations. Evaluates the effectiveness of special interest residences and reviews proposals for new residences. Effectively and efficiently manages staff, personnel issues, and financial operations. Functions as a seasoned professional in this area of expertise.
A clearly defined system of emergency response to student needs and conflicts.
practices; and state and federal regulations and legislation pertaining to residence life issues, policy development, staff supervision, and financial operations. Also requires excellent communication skills and computer literacy.
required. Demonstrates good understanding of the theoretical and applied bases for particular field of specialization. Provides resolution to an assortment of problems of moderately complex scope.
group workshops in the following critical areas: resume writing, job search, interviewing, and career decision-making. Develops outreach efforts to potential employers, colleges, and government agencies. Establishes relationships with alumni to serve as mentors or as potential employers. Provides resolution to an assortment of problems of moderately complex scope. Demonstrates good understanding of the theoretical and applied bases for particular field of specialization.
Effective outreach initiatives that foster understanding of client and student needs and concerns.
assessment instruments. Also requires good communication skills and computer literacy.
Recruits prospective students, targeting key demographic markets by analyzing geo-demographic data. Visits high schools and community colleges to recruit students. Conducts information sessions, both on and off campus. Reviews applications for admission and, using professional judgment, evaluates credentials and applies first year and transfer admit, wait list, and deny parameters for all collegiate units. Provides guidance to prospective students throughout the admissions process. Explains admissions competition, eligibility for the Educational Opportunity Fund (EOF) Program and New Jersey residency status, as they relate to tuition assessments, scholarships, and financial aid. Reviews and provides feedback on recruitment publications. Coordinates on and off-campus recruitment activities. Evaluates, develops, and implements procedures and standards for the cost-effective delivery of all related services. Works under general supervision with few direct instructions. Provides resolutions to an assortment of problems of moderately complex scope. Uses judgment within defined practices and procedures. May deviate from established methods as long as outputs meet standards of acceptability.
within broadly defined policies and practices.
skills in industry standard software.
and/or experience, plus a minimum of five years of relevant admissions experience that demonstrates expertise in admission counseling. Requires computer literacy in industry standard software. Also requires excellent communication skills; and strong skills in planning, leading, and organizing.
policies, procedures, and standards for the cost-effective delivery of all related services.
Develops communications, marketing, and recruitment plans to secure a sufficient number of competitive applicants within targeted markets to satisfy enrollment goals.
Oversees the analysis of geo-demographic market data and prepares written reports.
usually complex problems. Uses independent judgment to accomplish objectives.
communicates policies and practices for differing needs of a diverse client population.
Competent direction of the operational, financial, and personnel functions of the unit including fiscal planning and management, strategic planning, hiring, firing, grievances, conflict resolution, and employee evaluations.
with a minimum of five years of relevant experience; excellent communication skills; and computer literacy in industry standard software. Also requires strong skills in planning, organizing, information integration, and decision-making; and experience with a specific focus on attaining results.
ability, or expertise in a specialty area.
collaboration with other health care team members. Performs medical, clinical, and non-clinical services that promote health, prevent disease, and help patients cope with illness.
Evaluates walk-in students, assesses phone calls, and conducts triage. Observes, assesses, and records symptoms, reactions, and progress in patients. Assists physicians, nurse practitioners, and other healthcare providers during examinations, diagnosis, plan of care development, and treatments. Performs phlebotomy, conducts basic diagnostic tests, administers medications and immunizations, and instructs and supports patients and their families. May develop and manage nursing care plans. Participates in group client teaching, interdisciplinary meetings, and educational programs. Performs and documents regular evaluation of emergency equipment; provides data, analysis, and reports; and maintains stock of equipment and supplies. May oversee, hire, train, and evaluate staff. Completes work in compliance with university, Joint Commission on Accreditation of Healthcare Organizations (JCAHO), and state health and licensing standards. Carries out routine and non-routine tasks within established work parameters, with review of work by supervisor. Performs professional work that requires knowledge of medical and clinical principles and practices and a good understanding, use, and application of concepts, theories, principles, practices, terminology, and applied bases of nursing.
communications skills to include the understanding and effective use of English and medico-technical languages, and computer literacy.
assessment and crisis intervention of students who are seen on an emergency basis.
Designs, coordinates, and facilitates substance abuse awareness workshops. Consults and advises faculty, staff, and administrators concerning problem identification, response, and resolution techniques for drug related student issues. Designs and conducts surveys and research evaluation designs; and provides data, research, analysis, and reports on alcohol, nicotine, gambling, and drug abuse within the student population. Presents proposals and recommendations to improve services. Participates in department and university committees. Coordinates and leads teams. May oversee license-eligible counselors or graduate students; monitor project budgets; oversee office; hire, train, and evaluate administrative staff. Completes work independently with broadly defined work objectives and limited review of overall results by supervisor. Performs professional work that requires specialized to general knowledge of alcohol and chemical abuse and dependency philosophies, and related treatment principles and practices; and a solid understanding, use, and application of concepts, theories, principles, practices, terminology, and applied bases of area of specialization within substance abuse therapeutic treatment modalities.
counselor. Also requires excellent communication skills and computer literacy.
provides data, analysis, and reports on psychosocial issues within the student population.
bases of area of specialization within psychology, counseling, or clinical psychology.
requires excellent communication skills and computer literacy.
area of specialization within psychology, counseling, or clinical psychology.
bases of area of specialization.
communications skills to include the understanding and effective use of English and medico-legal technical languages, and computer literacy.
and facilitates referrals to outside providers. Monitors budget, payroll, and expenditures.
terminology, and applied bases of area of specialization.
communication skills; and computer literacy.
medical, clinical, and administrative staff. Coordinates referrals to outside providers.
Occupational Safety and Health Act (OSHA), and state health and licensing standards. Works independently with broadly defined work objectives and minimal review of overall results. Performs professional work that requires detailed, specialized knowledge of one or several fields of medical practice; and an in-depth understanding, use, and application of concepts, theories, principles, practices, terminology, and applied bases of area of specialization.
leadership or managerial role of increasing responsibility supervising patient care. Also requires skills in planning, organizing, integrating information, making decisions, and attaining results; the ability to physically assist clients; excellent clinical and communications skills to include the understanding and effective use of English and medico-legal technical languages; and computer literacy.
routine or semi-routine work, and/or within established work parameters for the unit.
orders for print and digital scholarly works, non-print media, and package plans.
Develops relationships with vendors, monitors performance, and resolves issues.
Contributes original cataloging to national and international bibliographic databases.
university libraries to facilitate archive, database management, and preservation projects.
out routine and non-routine tasks with occasional review of work outputs by supervisor.
principles, practices, terminology and applied bases of library science and operations.
online catalog and utility procedures; and other library and online information systems.
preservation activities, good communication skills, and computer literacy.
security, functionality, and availability of buildings, equipment, and library collections.
good communication skills and computer literacy.
professional, paraprofessional, and supervisory staff. Schedules staff and delegates work.
Analyzes workflows and procedures, and develops and revises procedure manuals.
equipment, and library collections. Manages budget; provides expenditure reports. Provides statistical analysis of data; and annual, midyear, and project reports for area of responsibility. Completes work under general supervision, within established work parameters. Carries out routine and non-routine tasks with occasional review of work outputs by supervisor. Performs professional work that requires knowledge of library science principles and practices; and a good understanding, use, and application of the concepts, theories, principles, practices, terminology, and applied bases of original cataloging and library operations including circulation, cataloging, acquisitions, and collection management.
activities. Also requires good communication skills and computer literacy.
terminology and applied bases of library science such as copy, complex, and original descriptive cataloging; standard, recurring, serial, and complex acquisitions; collection management; circulation; and other library operations.
Development and implementation of best practices, processes, programs, and supporting technologies.
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When I first heard about hydrogen water, scam bells started to go off in my brain. But then I started to read and realized that hydrogen water has serious potential and some interesting studies.
Hydrogen water contains hydrogen molecules that act as powerful antioxidants. These molecules help neutralize oxygen free radicals that contribute to disease development, inflammation, and aging. Read more to learn about the miraculous benefits of hydrogen water bellow !
Hydrogen Water is an Antioxidant and Prevents Brain Damage.
Hydrogen Water is an Antioxidant and Prevents Brain DamageMolecular hydrogen (H2) can protect cells and tissues from oxidative damage by selectively reducing reactive oxygen species (ROS) [R,R2].Unlike other antioxidants, H2 has the unique capability of crossing cell membranes and targeting organelles such as the mitochondria and nucleus [R].Drinking hydrogen water prevented the development of Parkinson's disease in an experiment on rats. Hydrogen water reduced oxidative stress and prevented cognitive impairment associated with dementia and Parkinson's disease [R].Hydrogen water prevented both the development and progression of neural degeneration, and also suppressed neuronal loss in another Parkinson's disease mice study [R].Additionally, in a study on patients with Parkinson's disease, it was found that the intake of hydrogen water reduces neurotoxic damage, which agrees with previous studies on animals. There were also no adverse effects from the hydrogen water at high doses (1000 mL/day) [R].
Hydrogen water restored the natural growth of brain cells in mice. Because antidepressants increase adult neurogenesis, hydrogen water may be used for improving depression and some mental disorders [R,R2]..
Molecular hydrogen (H2) exhibits anti-inflammatory effects in many animal studies [R,R2].In a study, patients with rheumatoid arthritis, a chronic inflammatory disease, drank .5 L/day of hydrogen water for 4 weeks. By the end of the study all patients with early rheumatoid arthritis achieved remission and 20% became symptom-free [R,R2].
In an experiment with young athletes, drinking hydrogen water reduced lactic acid build-up during heavy exercise and decreased muscle fatigue [R].In a study on mice with Duchenne muscular dystrophy (DMD), a devastating muscle disease, hydrogen water prevented abnormal body mass gain and increased the production of the antioxidant glutathione peroxidase. It was found that hydrogen water can potentially improve muscular dystrophy in DMD patients [R].
Hydrogen water significantly reduced fatty liver in mice with type 2 diabetes and obesity as well as in mice with a high–fat-diet-induced fatty liver. Also, levels of glucose, insulin, and triglycerides were decreased by stimulating energy metabolism [R].A study in rats showed that hydrogen water was able to prevent atherosclerosis (hardening of the arteries) [R].In a study on patients with the potential for metabolic syndrome, drinking hydrogen water (1.5 – 2 L/day) for 8 weeks showed an increase in HDL-cholesterol ("good" cholesterol) and a decrease in total cholesterol [R].
Clinical studies have shown that drinking hydrogen water directly protects the mitochondria and improves the outcome of mitochondrial disorders [R].Drinking hydrogen water also stimulates energy metabolism (as measured by oxygen consumption and CO2 production) [R].
Heated hydrogen water was found to be an effective anti-tumor agent [R].In human tongue and connective tissue cancer cells, hydrogen water suppressed tumor colony growth by reducing oxidative stress [R].Hydrogen water also inhibited angiogenesis (blood vessel growth) in cultured human lung cancer cells [R].
Drinking hydrogen water improved mortality and body weight loss caused by an anti-cancer drug, cisplatin, and reduced kidney toxicity in mice [R].In a study on patients receiving radiation therapy for malignant liver tumors, drinking hydrogen water (1.5 – 2 L/day) suppressed oxidative stress (as measured by elevation of total hydroperoxide levels) and prevented the loss of appetite [R].
Hydrogen water administered intravenously (into the vein) to patients with acute erythematous skin diseases caused the erythema (redness) and associated symptoms to significantly improve [R].Bathing in hydrogen water for 3 months significantly improved wrinkles in the skin in a human study [R].Hydrogen water also reduced human skin cell damage from ultraviolet (UV) rays [R].
In a study on rats that were surgically induced with a bladder obstruction, drinking hydrogen water significantly suppressed bladder weight increase and oxidative stress. Also, hydrogen water reversed the decreased responses to muscles and electric field stimulation. These results suggest that hydrogen water could help patients with a bladder obstruction by decreasing oxidative stress [R].
H2-loaded eye drops facilitated the recovery process after retinal injury in rats [R].Treating the cornea with hydrogen solution significantly reduced angiogenesis (blood vessel growth) after alkali-burn injury in mice, indicating that hydrogen therapy may prevent blindness caused by chemical burns of the eye [R].
Molecular hydrogen protects auditory hair cells from oxidative damage [R].Studies in guinea pigs found that hydrogen-rich saline and water prevented the death of cochlear hair cells after noise exposure, indicating that hydrogen water may protect against noise-induced hearing loss [R,R2,R3].
A study in rats found that hydrogen-rich water was able to improve kidney dysfunction from toxic damage by reducing oxidative stress and chemical waste products (creatinine (Cr) and blood urea nitrogen (BUN)) [R].Drinking hydrogen water also reduced inflammation and blood pressure in hemodialysis patients [R].
Drinking hydrogen water suppressed liver fibrogenesis in mice by protecting liver cells from free-radical damage [R].Hydrogen water also significantly improved liver function and reduced oxidative stress in patients with chronic hepatitis B [R].
Hydrogen-rich water alleviated stomach mucosal injury induced by aspirin in rats (by suppressing oxidative stress and inflammation), indicating that hydrogen water may protect healthy individuals from gut damage caused by oxidative stress [R,R2].
Hydrogen water consumption in rats had a protective effect against lung tissue injury by suppressing inflammation and oxidative stress (through reduction of NF-κBactivity) [R].
The ability of molecular hydrogen to protect nuclear DNA and the mitochondria from oxidative damage is thought to have beneficial effects on chronic diseases like cancer and the aging process [R,R2].H2 treatment delayed the replicative lifespan of bone marrow stem cells by reducing oxidative stress [R].When human umbilical vein endothelial cells (HUVECs) were grown in a hydrogen-rich medium, both oxidative stress and cellular aging were suppressed. The study concluded that drinking hydrogen water may increase longevity in humans [R].
A study found that hydrogen water may improve oral hygiene because of its antibacterial effect against cavity and gum disease-causing bacteria [R].In patients with gum infection, drinking hydrogen-rich water improved disease symptoms and enhanced the effects of non-surgical gum disease treatment [R].
Decreased production of TNF-α, IL-6, IL-1β, CCL2 and IL-10, TNF-γ, IL-12, ICAM-1, HMGB-1, NF-κB, and PGE2 [R].
Suppressed caspase 3, caspase 12, caspase 8 and BAX [R].
Activated Bcl-2 and Bcl-xL [R].
Up-regulated expression of PCNA, bFGF, HGF, IFNy, and down-regulated expression of i-NOS and VEGF [R].
Inhibited phosphorylations of MEK, p38, ERK, JNK, Lyn, Syk, PLCγ1, γ2, Akt, ERK1/2, JNK, p38, cPLA2, ASK1, IκBα [R].
Up-regulated expression of FGF21 [R].
Activated Nrf2 and heme oxygenase-1 (HO-1) [R].
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Kaulfuß, Franziska and Reisch, Christoph (2017) Reintroduction of the endangered and endemic plant species Cochlearia bavarica -Implications from conservation genetics. Ecology and Evolution 7 (24), pp. 11100-11112.
Population reintroduction is a common practice in conservation, but often fails, also due to the effects of inbreeding or outbreeding depression. Cochlearia bavarica is a strongly endangered plant species endemic to Bavaria in Germany, constantly declining since the late 1980s. Therefore, population reintroduction is intended. In this study, we analyzed genetic diversity within and genetic differentiation between all 32 remnant populations of the species in Swabia and Upper Bavaria using amplified fragment length polymorphisms. Our aim was to increase reintroduction success by providing data to avoid negative effects of inbreeding and outbreeding and to preserve the natural genetic pattern of the species. Genetic diversity within populations was low but similar to other rare and endemic species and varied strongly between populations but did not depend on population size. Our analysis revealed a strong geographic pattern of genetic variation. Genetic differentiation was strongest between Swabia and Upper Bavaria and at the population level, whereas differentiation between subpopulations was comparatively low. Isolation by distance and genetic differentiation was stronger among populations from Upper Bavaria than from Swabia. From the results of our study, we derived recommendations for a successful reintroduction of the species. We suggest using rather genetically variable than large populations as reintroduction sources. Moreover, the exchange of plant material between Swabia and Upper Bavaria should be completely avoided. Within these regions, plant material from genetically similar populations should preferably be used for reintroduction, whereas the exchange among subpopulations seems to be possible without a negative impact on genetic variation due to natural gene flow.
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Paul S. Malchesky, D. Eng.
Cryoglobulins are immunoglobulins or immunoglobulin-containing complexes that spontaneously precipitate and form a gel at low temperatures and become soluble again when the temperature is raised. There are distinct types: single monoclonal proteins (type I), mixed cryoglobulins with a monoclonal component (type II), and mixed cryoglobulins containing only polyclonal components (type III). Chemically, these proteins are not significantly different from their noncryoprecipitating counterparts; their cryoprecipitability is related more to electrostatic interactions and solubility than to structure or nonprotein composition. Many cryoglobulins are immune complexes. In addition to serum, they can be found in other physiological fluids as well as tissue and have been shown to occur in a wide variety of diseases. Their presence in tissues such as the kidney, vascular structures, and synovial fluid may be related to the pathogenesis of that disease. Serum concentrations of cryoglobulins can be reduced through the use of drugs, plasma exchange, and plasma filtration.
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I. Identify the measurement tool used in this study and discuss the psychometric properties of that measurement tool as used in this particular study. Remember, psychometric property refers to how the instrument was constructed and applied in a study and speaks to the validity and reliability of the instrument.
II. Discuss and critique how correlations were used in this study.
III. Identify the themes identified within this qualitative study. Explain how these themes were developed.
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Buy Klonopin Online . You can Buy Klonopin Online HERE without Prescription from Goodwill Pharmacy Online Store . Klonopin (clonazepam) is a benzodiazepine officially indicated for management of seizure disorders and panic disorder. The use of a drug for its approved indications is called its labeled use. In clinical practice, however, physicians often prescribe medications for unlabeled ("off-label") uses when published clinical studies, case reports, or their own clinical experiences support the efficacy and safety of those treatments. Physicians may use Klonopin outside its approved indications to treat social anxiety disorder, posttraumatic stress disorder, agitation in acute psychosis and mania, and premenstrual syndrome. As with other benzodiazepines, Klonopin is associated with dependence and abuse and is regulated as a controlled substance by state and federal laws. Klonopin's effectiveness for treating anxiety may be explained by its pharmacological action in the brain at specific receptor sites. Receptors are specific sites on the nerve cell membrane that receive a signal from a neurochemical called the neurotransmitter. Once a neurotransmitter locks in on the receptor, the neurochemical signal is changed to an electrical or another chemical signal and travels down the neuron. The receptor sites in which benzodiazepines elicit their action are found in various regions of the brain, and the specific receptors are also known as benzodiazepine receptors. The coupled reaction of benzodiazepines to the receptors facilitates the inhibitory action of the neurotransmitter γ-aminobutyric acid (GABA) in that region of the brain. Benzodiazepines' action on GABA receptors appears to produce their anxiolytic, sedative, and anticonvulsant actions. Klonopin, for example, is an effective anxiolytic, hypnotic, and antiseizure medication.
Buy Klonopin Online Legally . You can buy Klonopin Online legally from the best and only Online Pharmacy which will supply you with the best meds. We are Goodwill Pharmacy and we also listing the medication guide to help our patients . Read the Medication Guide provided by your pharmacist before you Buy Klonopin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.
Buy Klonopin Online Legally and take your dosage based on your medical condition, age, and response to treatment. For children, the dose is also based on weight. Older adults usually start with a lower dose to decrease the risk of side effects. Do not increase your dose, take it more often, or take it for a longer time than directed.
The most common side effects reported with Klonopin are sedation and drowsiness, especially shortly after initiating therapy. Other frequent symptoms are impaired concentration and memory, feeling of dissociation ("spacey"), and impaired coordination.
Klonopin should not be used in patients with a history of sensitivity to benzodiazepines, nor in patients with clinical or biochemical evidence of significant liver disease. It may be used in patients with open angle glaucoma who are receiving appropriate therapy but is contraindicated in acute narrow angle glaucoma.
Interference With Cognitive and Motor Performance: Since Klonopin produces CNS depression, patients receiving this drug should be cautioned against engaging in hazardous occupations requiring mental alertness, such as operating machinery or driving a motor vehicle. They should also be warned about the concomitant use of alcohol or other CNS-depressant drugs during Klonop.
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HONOLULU – A study presented last month at the annual American Psychiatric Association conference points to a pending crisis in geriatric psychiatry and potential healthcare cost increases as older adults end up in emergency rooms for mental health-related issues.
"Increased Elderly Utilization of Psychiatric Emergency Services in Honolulu: A Reflection of the Mental Health Crisis Facing Our Nation's Aging Population" looked at the records of 17,004 patients who used the emergency room and were identified as using psychiatric emergency services at the Queen's Medical Center in Honolulu between 2007 and 2010.
The study found that the number of geriatric patients (age 65 and older) with mental health issues – which include dementia, depression and Alzheimer's disease – increased nearly 21 percent from 2007 to 2010. That increase seen is one example of a nationwide geriatric mental health crisis.
The crisis is due to a confluence of problems, said Brett Lu, MD, PhD, one of the authors of the study. It's mainly due to a shortage of mental health resources and the large number of Baby Boomers becoming seniors.
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Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study
P Haggarty, H McCallum, H McBain, K Andrews, S Duthie, G McNeill, A Templeton, N Haites, D Campbell, S Bhattachayra
School of Medicine, Medical Sciences & Nutrition
Background There is a need to understand what affects the success of in-vitro fertilisation (IVF) and the rate of resulting twin births so that pregnancy rates can be improved and multiple gestations avoided. Our aim was to assess the role of B vitamins and genetics.
Methods We did a prospective cohort study of 602 women undergoing fertility treatment. We assessed intake of folate and vitamin B12 with a questionnaire and measured their plasma and red-blood-cell concentrations by radioimmunoassay. We measured five B-vitamin-related gene variants in women who received treatment and in 932 women who conceived naturally.
Findings The likelihood of a twin birth after IVF rose with increased concentrations of plasma folate (1.52, 1.01-2.28; p=0.032) and red-cell folate (1.28, 1.00-1.65; p=0.039). There was no association between folate and vitamin B12 levels and likelihood of a successful pregnancy. Women homozygous for the 1298 CC variant of methylenetetrahydrofolate reductase (MTHFR), rather than the AA variant, were less likely to produce a livebirth after IVF (0.24, 0.08-0.71; p=0.003) or to have had a previous pregnancy (0.42, 0.21-0.81; p=0.008).
Interpretation Our findings suggest that MTHFR genotype is linked to a woman's potential to produce healthy embryos (possibly through interaction with genes related to DNA methylation). In women likely to have a successful IVF pregnancy, high folate status increases the likelihood of twin birth after multiple embryo transfer. Proposals to fortify the UK diet with folic acid could lead to an increase in the number of twins born after IVF.
Published - 6 May 2006
Fertilization in Vitro
Methylenetetrahydrofolate Reductase (NADPH2)
Pregnancy Outcome
Vitamin B 12
Early-pregnancy loss
Twin pregnancy ,
Hyperhomocysteinemia
Methylation
Dive into the research topics of 'Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study'. Together they form a unique fingerprint.
Vitamin B Complex Medicine & Life Sciences 100%
Fertilization in Vitro Medicine & Life Sciences 82%
Folic Acid Medicine & Life Sciences 75%
Twins Medicine & Life Sciences 53%
Cohort Studies Medicine & Life Sciences 52%
Prospective Studies Medicine & Life Sciences 48%
Methylenetetrahydrofolate Reductase (NADPH2) Medicine & Life Sciences 32%
Pregnancy Medicine & Life Sciences 30%
Haggarty, P., McCallum, H., McBain, H., Andrews, K., Duthie, S., McNeill, G., Templeton, A., Haites, N., Campbell, D., & Bhattachayra, S. (2006). Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. The Lancet, 367(9521), 1513-1519. https://doi.org/10.1016/S0140-6736(06)68651-0
Effect of B vitamins and genetics on success of in-vitro fertilisation : prospective cohort study. / Haggarty, P ; McCallum, H ; McBain, H et al.
In: The Lancet, Vol. 367, No. 9521, 06.05.2006, p. 1513-1519.
Haggarty, P, McCallum, H, McBain, H, Andrews, K, Duthie, S, McNeill, G, Templeton, A, Haites, N, Campbell, D & Bhattachayra, S 2006, 'Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study', The Lancet, vol. 367, no. 9521, pp. 1513-1519. https://doi.org/10.1016/S0140-6736(06)68651-0
Haggarty P, McCallum H, McBain H, Andrews K, Duthie S, McNeill G et al. Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. The Lancet. 2006 May 6;367(9521):1513-1519. https://doi.org/10.1016/S0140-6736(06)68651-0
Haggarty, P ; McCallum, H ; McBain, H et al. / Effect of B vitamins and genetics on success of in-vitro fertilisation : prospective cohort study. In: The Lancet. 2006 ; Vol. 367, No. 9521. pp. 1513-1519.
@article{6a54d53109a14e1ab79fbf17081c7772,
title = "Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study",
abstract = "Background There is a need to understand what affects the success of in-vitro fertilisation (IVF) and the rate of resulting twin births so that pregnancy rates can be improved and multiple gestations avoided. Our aim was to assess the role of B vitamins and genetics.Methods We did a prospective cohort study of 602 women undergoing fertility treatment. We assessed intake of folate and vitamin B12 with a questionnaire and measured their plasma and red-blood-cell concentrations by radioimmunoassay. We measured five B-vitamin-related gene variants in women who received treatment and in 932 women who conceived naturally.Findings The likelihood of a twin birth after IVF rose with increased concentrations of plasma folate (1.52, 1.01-2.28; p=0.032) and red-cell folate (1.28, 1.00-1.65; p=0.039). There was no association between folate and vitamin B12 levels and likelihood of a successful pregnancy. Women homozygous for the 1298 CC variant of methylenetetrahydrofolate reductase (MTHFR), rather than the AA variant, were less likely to produce a livebirth after IVF (0.24, 0.08-0.71; p=0.003) or to have had a previous pregnancy (0.42, 0.21-0.81; p=0.008).Interpretation Our findings suggest that MTHFR genotype is linked to a woman's potential to produce healthy embryos (possibly through interaction with genes related to DNA methylation). In women likely to have a successful IVF pregnancy, high folate status increases the likelihood of twin birth after multiple embryo transfer. Proposals to fortify the UK diet with folic acid could lead to an increase in the number of twins born after IVF.",
keywords = "Chorionic Gonadotropin, Diet, Female, Fertilization in Vitro, Folic Acid, Genotype, Humans, Infertility, Logistic Models, Methylenetetrahydrofolate Reductase (NADPH2), Pregnancy, Pregnancy Outcome, Prospective Studies, Twins, Vitamin B 12, Early-pregnancy loss , Folic acid, Twin pregnancy ,, Hyperhomocysteinemia, Methylation, Women, Risk",
author = "P Haggarty and H McCallum and H McBain and K Andrews and S Duthie and G McNeill and A Templeton and N Haites and D Campbell and S Bhattachayra",
journal = "The Lancet",
publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",
T1 - Effect of B vitamins and genetics on success of in-vitro fertilisation
T2 - prospective cohort study
AU - Haggarty, P
AU - McCallum, H
AU - McBain, H
AU - Andrews, K
AU - Duthie, S
AU - McNeill, G
AU - Templeton, A
AU - Haites, N
AU - Campbell, D
AU - Bhattachayra, S
N2 - Background There is a need to understand what affects the success of in-vitro fertilisation (IVF) and the rate of resulting twin births so that pregnancy rates can be improved and multiple gestations avoided. Our aim was to assess the role of B vitamins and genetics.Methods We did a prospective cohort study of 602 women undergoing fertility treatment. We assessed intake of folate and vitamin B12 with a questionnaire and measured their plasma and red-blood-cell concentrations by radioimmunoassay. We measured five B-vitamin-related gene variants in women who received treatment and in 932 women who conceived naturally.Findings The likelihood of a twin birth after IVF rose with increased concentrations of plasma folate (1.52, 1.01-2.28; p=0.032) and red-cell folate (1.28, 1.00-1.65; p=0.039). There was no association between folate and vitamin B12 levels and likelihood of a successful pregnancy. Women homozygous for the 1298 CC variant of methylenetetrahydrofolate reductase (MTHFR), rather than the AA variant, were less likely to produce a livebirth after IVF (0.24, 0.08-0.71; p=0.003) or to have had a previous pregnancy (0.42, 0.21-0.81; p=0.008).Interpretation Our findings suggest that MTHFR genotype is linked to a woman's potential to produce healthy embryos (possibly through interaction with genes related to DNA methylation). In women likely to have a successful IVF pregnancy, high folate status increases the likelihood of twin birth after multiple embryo transfer. Proposals to fortify the UK diet with folic acid could lead to an increase in the number of twins born after IVF.
AB - Background There is a need to understand what affects the success of in-vitro fertilisation (IVF) and the rate of resulting twin births so that pregnancy rates can be improved and multiple gestations avoided. Our aim was to assess the role of B vitamins and genetics.Methods We did a prospective cohort study of 602 women undergoing fertility treatment. We assessed intake of folate and vitamin B12 with a questionnaire and measured their plasma and red-blood-cell concentrations by radioimmunoassay. We measured five B-vitamin-related gene variants in women who received treatment and in 932 women who conceived naturally.Findings The likelihood of a twin birth after IVF rose with increased concentrations of plasma folate (1.52, 1.01-2.28; p=0.032) and red-cell folate (1.28, 1.00-1.65; p=0.039). There was no association between folate and vitamin B12 levels and likelihood of a successful pregnancy. Women homozygous for the 1298 CC variant of methylenetetrahydrofolate reductase (MTHFR), rather than the AA variant, were less likely to produce a livebirth after IVF (0.24, 0.08-0.71; p=0.003) or to have had a previous pregnancy (0.42, 0.21-0.81; p=0.008).Interpretation Our findings suggest that MTHFR genotype is linked to a woman's potential to produce healthy embryos (possibly through interaction with genes related to DNA methylation). In women likely to have a successful IVF pregnancy, high folate status increases the likelihood of twin birth after multiple embryo transfer. Proposals to fortify the UK diet with folic acid could lead to an increase in the number of twins born after IVF.
KW - Chorionic Gonadotropin
KW - Diet
KW - Fertilization in Vitro
KW - Folic Acid
KW - Genotype
KW - Infertility
KW - Logistic Models
KW - Methylenetetrahydrofolate Reductase (NADPH2)
KW - Pregnancy
KW - Pregnancy Outcome
KW - Twins
KW - Vitamin B 12
KW - Early-pregnancy loss
KW - Twin pregnancy ,
KW - Hyperhomocysteinemia
KW - Methylation
JO - The Lancet
JF - The Lancet
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The vulnerability of our society against major accidents or attacks has received significant attention in recent years. If the potential hazard can be defined, it may be possible to better prepare against the resulting consequences. Using FLACS, GexCon can help estimate the consequences of many potential major accident scenarios.
Massive releases of toxic industry chemicals, either from storage vessels at facilities or when being transported, are a major concern. Screening studies are performed at US sites to classify hazards posed in the event of an accidental release to the surroundings. One advantage for these facilities is that the locations of potential releases are known. During transportation, however, this is not the case as hazards may occur anywhere along the transportation route due to accidents or intentional attacks. It is well known that hazard distances estimated with simpler tools, assuming flat terrain and no obstructions, may yield nonrealitic results. Using FLACS, GexCon can help clients predict a more accurate hazard distance by taking into account necessary details like buildings, vegetation and local terrain. Another advantage of detailed CFD calculations is that the benefits from mitigation measures like fences and spill dikes can be evaluated.
GexCon, using FLACS simulations, participated in the NYC tracer gas test programs. During this work, GexCon developed a frozen flow concept which significantly accelerates simulation time when modeling small amounts of released gas. By first simulating the ventilation and flow field for different wind directions our CFD dispersion calculations in Manhattan were performed faster than real time with varying wind direction based on meteorological observations. Dispersion studies like this can also be performed indoors (e.g., in shopping centres, subways, and tunnels), by specifying the actual ventilation conditions. Simulations can be used to optimize the placement of sensor systems, emergency ventilation or escape behavior.
The FLACS simulator can also be used to effectively study pressure wave propagation indoors or in urban areas from high pressure sources, such as high explosives. FLACS can be useful in developing guidance for designs that enhance security at vulnerable locations. Below is one example of a simulation of pressure propagation from explosives in a multi-compartment building (small scale experiment by Neuwald and Reichenbach).
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1. The student will demonstrate knowledge of the developmental norms for speech and language acquisition.
2. The student will demonstrate competent use of common research and clinical methods used in the field.
3. The student will discuss current technological advances and illustrate their use for clinical problem solving.
4. The student will demonstrate knowledge of appropriate procedures to assess and remediate speech and language disorders.
5. The student will demonstrate essential skills for generating professional written reports.
6. The student will explain how individual, cultural, and linguistic differences contribute to our understanding of language and communication.
7. The student will apply critical thinking and problem-solving skills to issues in communication sciences and disorders.
8. The student will demonstrate knowledge of theoretical foundations of communication sciences and disorders.
A total of 13 measures were used to assess students' knowledge of communication sciences and disorders.
Assessment of student performance on class assignments pertaining to the selected objectives has a department-set goal: At least 80% of students will receive a grade of B or above.
Eleven measures were analyzed to determine students' knowledge of appropriate procedures to assess and remediate speech and language disorders. Ten of the 11 measures met the criterion. These data were gathered across three courses; three were in the form of exam questions, one was a case study, three were short essays written in response to a question following an assigned reading, and the remaining four measures were in the form of assessment projects. The average percent of students who earned a grade of B or higher for the quiz and exam questions pertaining to assessment and remediation of speech and language disorders was 83%. The case study results yielded 90% of students earning a B or higher. An average of 92% of the students who completed these projects and assignments earned a grade of B or higher; however, the results of one project did not meet criterion as the percent of students who earned a grade of B or higher was 78%.
Two measures were assessed to determine students' knowledge of essential skills for generating professional written reports. 98% of the students in the fall 2017 semester earned a grade of B or higher. 73% of students earned a minimum grade of B in the spring 2018 semester.
Our assessment report revealed that students in CSD are gaining valuable information pertaining to assessment and remediation of communication disorders and writing professional reports that will arm them with the basic knowledge in the field needed to be successful in a required graduate program.
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Maloney EM, Boneva RS, Lin JM, Reeves WC.
1600 Clifton Rd, Atlanta, GA 30333, USA.
those with CFS and the controls.
persons with CFS, 259 with ISF, and 123 controls.
National Cholesterol Education Program Adult Treatment Panel III definition.
ratio = 2.12, confidence interval = 1.06, 4.23) compared with the controls.
syndrome was weaker (odds ratio = 1.72, confidence interval = 0.94-3.16).
measure of fatigue (r = 0.20, P = .04).
with metabolic syndrome, which further exacerbated fatigue.
Metabolic syndrome is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. It affects one in five people, and prevalence increases with age. Some studies estimate the prevalence in the USA to be up to 25% of the population.
Metabolic syndrome is also known as metabolic syndrome X, syndrome X, insulin resistance syndrome, Reaven's syndrome, and CHAOS (Australia). A similar condition in overweight horses is referred to as equine metabolic syndrome; it is unknown if they have the same etiology.
Myth 2. For years, sufferers have accused Reeves "of thinking ME/CFS was a psychological disorder but his open-ended attempt to merge gene expression, gene polymorphism and laboratory and clinical data suggested he was open, at least at that point, to various interpretations of the disease."
This statement is based on a belief that biological research and genetic research belong to biomedical fields, not psychiatry. While this belief is understandable from a layman's perspective, it is not accurate. Current models of psychiatric disorders are multidimensional: stress trigger, genetic predisposition, lead to biological effects and behavioral perpetuation. Today, depression, stress disorders, and anxiety disorders are researched with an emphasis on genetics, behavioral interventions, neuroendocrine imbalances, and mild immune alterations. (2).
REEVES SUPPORTS RETROVIRUS/CFS LINK (inadvertently). Check out Lipodystrophy and HIV!
In conclusion, CFS was associated with metabolic syndrome, which further exacerbated fatigue.
In other words, if we'd just comply with CBT and GET, we wouldn't be such a drain on the health care system and our beleaguered health care workers.
Cause for hilarity: Reeves is s inadvertently supporting a CFS/Retrovirus/Lipodystrophy hypothesis!
There remain, however, clear linkages between HIV infection itself, and lipodystrophy. In other words, even in the absence of antiretroviral treatment, if XMRV proves to be linked with ME/CFS, we are very possibly at risk for metabolic complications and lipodystrophy.
On the basis of kinetic metabolic studies in the fasting and fed states in patients with HIV-associated lipodystrophy, Sekhar et al (20,21) identified basic defects in adipocyte function that result in a marked acceleration of lipolysis or hydrolysis of stored triglycerides leading to a net release of free fatty acids into the circulation... As to the mechanisms underlying adipocyte dysfunction, they are likely complex and multifactorial, and probably include one or more HAART agents, increased proinflammatory cytokine activity, (22) or proteins expressed by HIV itself.
Lipodystrophy, also called fat redistribution syndrome, is a condition that often occurs in HIV-positive people and is characterized by changes in body shape and metabolism. Body shape changes may include the accumulation and/or loss of fat, which can affect appearance. Metabolic changes may include increased resistance to insulin and abnormally high levels of blood cholesterol and triglycerides....Health experts are not sure why HIV-positive people develop lipodystrophy, but they think it may be related to antiretroviral medications they take to control their disease. In addition to medications, factors including a persons age, gender, weight, genetic predisposition, length of time he or she has been HIV-positive, and severity of the disease may be linked to the development of lipodystrophy.
What metabolic changes can occur with lipodystrophy? Insulin resistance may be related to some of the antiretroviral medications used to treat HIV, and/or to a genetic predisposition in the individual...Dyslipidemia, or higher than normal amounts of lipids (cholesterol and/or triglycerides) in the blood, is another metabolic change which often occurs in HIV-positive people with lipodystrophy. It also may be related to some of the antiretroviral medications used to treat the disease, and/or to genetic predisposition.
The causes of lipodystrophy are not well understood. Multiple studies have shown strong association with the severity or duration of HIV disease (Look back to Reeves' linkage: the greater the fatigue, the greater the Metabolic Syndrome in CFS patients!); with persons with longer period of untreated infection or lowest-ever CD4 cell counts at greatest risk. Additional host (or patient) risk factors include age, gender (men at greater risk) and race (Caucasians at greater risk)... Even before the era of antiretroviral medications, it was observed that HIV-positive persons had marked elevations in triglyceride levels.
Lipohypertrophy in this syndrome is characterized by the presence of an enlarged dorsocervical fat pad, circumferential expansion of the neck, breast enlargement, and abdominal visceral fat accumulationOther features of HIV lipodystrophy syndrome include hyperlipidemia, insulin resistance, hyperinsulinemia, and hyperglycemia. Patients with HIV lipodystrophy syndrome are at increased risk for the development of atherosclerosis and diabetes mellitus.
The relationship of adipocytokine with the development of HIV-related lipodystrophy was investigated in a case-control study... Most of the patients (96.3%) developed HIV-LD after month 12. ...The adiponectin level had a correlation with serum triglycerides (r = -0.616, p < 0.0001), serum insulin concentration (r = -0.494, p = 0.001), and HDL-C (r = 0.673, p < 0.0001). The lower baseline concentration of adiponectin and the greater change rate at month 18 were independent risk factors of HIV-LD. The adiponectin level had a correlation with serum triglycerides, serum insulin concentration, and HDL-C, suggesting that adiponectin may link the metabolic abnormalities and HIV-LD.
IL-18 is a pleiotropic and multifunctional proinflammatory cytokine that is often produced in response to a viral infection. The cytokine plays an important role in both innate and adaptive antiviral immune responses. Depending upon the context, it can promote TH1, TH2 and TH17 responses. Increased serum concentrations of IL-18 and concomitantly decreased concentrations of its natural antagonist have been described in HIV-infected persons as compared to HIV-seronegative healthy subjects. We discuss in this review article how increased biological activities of IL-18 contribute towards immunopathogenesis of AIDS, HIV-associated lipodystrophy syndrome and related metabolic disturbances.
CONCLUSION: Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.
Body fat disorders are a common and relevant problem in HIV-1-infected patients that can be associated with metabolic alterations. Many controversies in their definition, pathogenesis, measurement, and management remain unclear. Several factors including HIV-1 infection itself and antiretroviral therapy have been associated with the development of these alterations.
Interleukin-18 is a proinflammatory, proapoptotic, and proatherogenic cytokine belonging to the interleukin-1 family of cytokines. The cytokine may play a major role in the development and pathogenesis of AIDS in HIV-infected persons. Insufficient/lack of interleukin-12 and related cytokines may compromise the ability of interleukin-18 to induce interferon-gamma production from natural killer and T-cells.... The cytokine is also likely to be involved in the higher incidence of atherosclerotic plaques and systemic insulin resistance in these patients. Finally, increased production of the cytokine in the brain may lead to motor and cognitive dysfunctions, leading to the development of HIV-associated dementia. In conclusion, increased interleukin-18 concentrations in HIV-infected persons are likely to play an important role in the development and progression of the infection toward AIDS and associated clinical conditions.
We evaluated endothelial dysfunction, an early event in the development of atherosclerosis, and pro-atherosclerotic plasma biomarkers in HIV-infected patients with lipodystrophy... Lipodystrophy was associated with significantly higher plasma levels of interleukin 6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1) and lower levels of adiponectin; severe lipodystrophy was associated with higher concentrations of vascular cell adhesion molecule 1 (sVCAM-1). There was an inverse correlation between FMD and IL-6... the only independent predictor of endothelial dysfunction was lipodystrophy... CONCLUSIONS: Lipodystrophy is associated with endothelial dysfunction, independently of the presence of traditional cardiovascular risk factors. This finding and the accompanying profile of pro-atherosclerotic biomarkers support an increased cardiovascular risk in HIV-infected patients with lipodystrophy.
(I think this was tomk?)Is this Reeves doing biomedical research? What, if any, are the implications?
inadvertently pointing to retroviral involvement in ME/CFS!
The "empiric criteria" (Reeves, 2005) for CFS are so rubbish I don't count it as CFS research to be honest.
The CDC research has been a bit different from the UK research funded by the government; in the latter, they generally do little biological testing unless it is on the HPA-axis (so they can associate it with stress). The CDC have done a broader range of research. But if you have lots of people who just "don't get much done"/have "reduced activity", but don't really have to have what even looks like CFS, lots of these people are just going to be underactive people who have unhealthy lifestyles.
This paper might have been in Elsevier's pipeline before Reeves got "booted." In any event, my first psychiatrist was way ahead of him. When I kept losing weight on his anti-depressants, he squawked "metabolic problem."
I have borderline hypertension, and not only low HDL, but low total cholesterol (90-100). In fact, I had the latter for at least 5 years before "onset." In the first couple in 12 years of illness I dropped ten pounds from 150, both subcutaneous fat and muscle, noticeable it seemed only to me. Few except a GWI and the HIV doctor I wound up with put significance to it and said I had lipodystrophy or lipoatrophy and wasting.
The last two summers since I moved from SoCal have seen me drop another 10, fat and muscle. This Xmas, my family finally noticed. While "stress" can drastically affect someone's weight either way, it's hard for me to get three good meals in a shortened day, and a lot harder in the summer humidity. As it is, I seem to have a body that just torches fuel while sitting still - perhaps revved up against something. I've gone to protein shakes and am seeing a new ID doc this week.
My former AIDS doc is very intrigued by XMRV, partly because of the lipo' and cholesterol similarities he often sees in ME/CFS. Unfortunately, we're 25 years into HIV and no one knows any more about how to stop or reverse lipodystrophy/atrophy than 10 years ago. Dr. Klimas couldn't have been more correct in noting we "are delicate creatures," that retrovirals are not a simple solution. True, a lot of HIVers are "hale and hearty." A lot of them are getting plastic surgery on their face and buttocks, too. HIV may not be as fatal in the West, but it is not exactly easily managed, either.
National Cholesterol Education Program Adult Treatment Panel III definition."
I'm skinny, eat loads, and have really low blood pressure!
I just looked at wikipedia, and one of the key factors mentioned as leading to metabolic syndrome is a 'sedentary lifestyle'.
Are you kidding me? Can we stop spending money of studies to see if suffering from CFS means that you more at risk to conditions where a sedentary lifestyle is a significant contributing factor? I think that could be taken as a given at this point, unless they think we're all just lying, and sneaking out for a spot of tennis whenever their backs are turned. Maybe it would be worthwhile comparing CFS patients to those whose activity level is comparably low but do not have fatigue problems (MMORPG fans?) - comparing CFS patients to the general population - of course we're more likely to lead a sedentry lifestyle and have the health problems related to that. (One of my problems with some other biological research into CFS is that it fails to try to account for this, and I think this is one of the reasons many choose to ignore it).
edit - Just to be clear: I realise I know almost nothing about metabloic syndrome, and have no idea of the potential significance of high-density lipids etc, but I really don't see the point of this research. What could it have led on to? It seems completely pointless.
I think this article illustrates how poorly the CDC research program was faring - I'll bet it was stuff like this that got Reeves canned. After 10 years Reeves demonstrated that a portion of CFS patients have a general inflammatory condition; it may or may not be true - alot of people think there is an inflammatory element in CFS - but that won't win you many awards. Its pitiful how that program ended up.
Low, not high, blood pressure is common in ME/CFIDS. Don't know about the other risk factors. I have heard speculation in some of the literature that there's probably a high incidence of hypoglycemia and diabetes in ME..
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Cellulite is a term that is used to describe the dimple-like formations on the skin. Cellulite is very common during the adolescent stage as well as in adulthood for most women. While this condition does not pose any risks to those it affects, it does cause one to be extremely self-conscious.
It is quite common for those with cellulite to select clothing that is not revealing lest the cellulite comes to light! The unsightly appearance of cellulite makes it important for the affected to find home remedies that work best while effectively getting rid of the lumpy flesh over a period of time. Cellulite is most commonly found on the thighs, buttocks and above the hip area.
Perhaps the most important thing to keep in mind is that cellulite does not only result from weight gain, but is also a product of hormonal changes and genetics at play. Cellulite is, simply put, fat stored in the body. It gets its characteristic appearance (that of an orange peel) from the way it is arranged and stacked beneath the skin.
This is because in women, and particularly during puberty and adulthood, the connective fibers that allow for the stacking of fat cells create a crisscross pattern. As a result, any spikes in the amounts of fat cause it to peek out of the mesh-like arrangement, resulting in the characteristic dimpling of cellulite. Below are some of the home remedies that can be used to treat cellulite and help keep the body taut and toned.
Time Required: Varies depending on your exercise plans.
What You Need: Appropriate workout gear and a comfortable place to exercise.
Difficulty: Modest (depending on one's lifestyle).
The right exercise plan not only diminishes the appearance of cellulite on the skin, it also gives your skin a firmer look, effectively getting rid of the tired saggy appearance. The golden rule when choosing the right exercise plan involves focusing on exercises which target the lower body. The purpose of doing so is to deplete the stored fat and replace it with muscle for a firm appearance. As with any other home remedy, it is important to be consistent to see results after a considerable period of time. Follow the directions below for the [different sets of exercise routines and stick to one that works best for you. At the onset, you will need to warm up as indicated below.
NOTE: For all the routines, you need to start by warming up using your choice exercise. Some of the options available for you in this regard include brisk walking for some 20 minutes or stationary cycling for the same period of time. If you can, light calisthenics are an excellent option too. As a general rule, each of the exercises below are to be repeated at least 10 times for each set, thrice every week.
Leg pull to work out the outer thighs: For this workout, you will need an exercise band and a mat. Tie the band around the ankles and lie flat with both arms on the surface. Stretch your legs straight above the hips and then spread them so that the band is tight. Gently part your legs the farthest that you can so that when the band becomes too tight to stretch further, this is your cue to pause and resume your beginning position. Repeat this ten times daily for 3 days every week until you notice an improvement.
Side Lift + Squat:You will need ankle weights for this routine. Wear the ankle weights at the start of this routine and then stand feet apart. Place your hands on the hips with your elbows facing outwards. Bend slowly and squat as though you are preparing to sit, all the while ensuring your back is flat. When your thighs are at a right angle with the floor, pause. Flex your legs and then lift your right leg sideways. Pause once more and resume your starting position. Repeat this routine, alternating the side leg lifts after each routine.
Kickback:You will need ankle weights and an exercise mat for this routine. As a general rule in this routine, ensure that your back remains straightened at all times. Wear the ankle weights and get on all fours, making sure you use your forearms instead of your hands. Your head is downward facing at this point, but should be in line with your straightened back. Gently swing your left leg backwards and then skywards so that your thigh lies parallel to the floor. Hold in this position for 2 seconds and then resume your starting position. Switch legs and repeat this routine alternately.
What You Need: Body brush (one with natural fibers) and warm shower.
Dry body brushing is believed to be one of the most effective home remedies for the treatment of cellulite. While this is yet to be proved scientifically, it is believed that the brushing improved blood circulation to the parts of the body affected by cellulite. In addition to this, proper blood flow helps the skin retain a taut appearance so that cellulite is diminished. This remedy is best combined with a warm shower for great improvement. When shopping for a body brush, look out for one that has natural fibers to avoid skin abrasion. At the onset, ensure that both the skin and the brush are dry for best results.
Carefully brush your skin from the feet upwards, paying more attention to parts of the body that are covered in cellulite. It is advisable to keep the brushing motions centered towards the heart to encourage blood circulation.
Do this continuously for some 5 minutes.
When done, top up the remedy with a warm shower to get rid of the dead skin flakes.
Use this remedy once daily until you are content with the progress made.
What You Need: 5 Teaspoons of ground seaweed, sea salt, virgin olive oil and your preferred essential oil.
Seaweed is one of the most amazing remedies, and when used for the natural treatment of cellulite, it helps improve blood circulation. This not only gives the skin a healthy appearance, it also improves its texture, in turn reducing the dimpling that is associated with cellulite. Seaweed is also an ideal home remedy for smoother skin, so it has double benefits for the user.
Mix all the ingredients in a bowl to create a paste which you can then apply topically on the skin.
Massage a generous amount of the paste on the cellulite-filled skin and allow to dry for 15 minutes.
Rinse off the paste during a shower and follow this up with a hydrating skin lotion.
Use this remedy at least once everyday for a couple of months to treat cellulite naturally.
What You Need: Adequate drinking water. Mint or lemon wedges (optional).
Staying hydrated is one of the best health habits you can take up in the search of ideal home remedies for the treatment of cellulite. One of the key ways to get rid of toxins, and by extent, cellulite, is by taking water. Here's how it works: toxins accumulate in the fat cells which, when accumulated, result in the formation of cellulite. This is one of the body's strategies to reduce the organs' exposure to toxins. By taking water and reducing toxicity in the fat cells, you are well on your way to treating cellulite in its most basic forms.
It has often been recommended that the daily amount of water required for the average adult is 8 glasses, but it is important to note that this varies from one person to another depending on pre-existing conditions. This is just a general guide, but for a more accurate guideline, it is advisable to consult your physician especially if you suffer from kidney diseases.
NOTE: If you are not accustomed to the taste of 'plain' water, you may add a dash of mint or lemon wedges for a refreshing taste altogether.
What You Need: A deep tissue foam roller and choice essential oil. Warm bath (optional).
One of the remedies which has been fronted for the elimination of cellulite is a deep tissue massage when used consistently along the exercises recommended above. this type of massage is believed to smooth the connective tissue beneath the skin, therefore reducing the dimpling of the skin in cellulite-prone parts of the body. Regular massage using this remedy prevents the rippling of the skin by ensuring the connective tissue is less fibrous and more flexible. You will need your preferred essential oil for smooth application.
Warm the preferred essential oil if need be, using a warm bath for this purpose.
Apply a generous amount of the oil on the cellulite-covered skin.
Use the deep tissue foam roller for 30 minutes in intervals of 10 minutes with short breaks in between.
In addition to these remedies, it is advisable to eat healthy foods that are low in fat in order to prevent excessive fat storage below the skin. Reducing stress levels also goes a long way in keeping cellulite off. Do not forget to exercise regularly to effectively manage cellulite.
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Home > Journals > Medicine & Healthcare > OJO
OJO> Vol.2 No.2, June 2012
Comparison between Different Modalities of Treatment of Ewing Sarcoma
Abstract Full-Text HTML Download as PDF (Size:119KB) PP. 69-72
DOI: 10.4236/ojo.2012.22014 3,149 Downloads 5,639 Views Citations
Ranadeb Bandyopadhyay, Arindam Mukherjee, Ujjal Bhakat
Department of Orthopaedics, Bankura Sammilani Medical College, Bankura, India.
Background: Ewing sarcoma is the most common primary malignant tumour in patients younger than 10 years of age. The incidence is less than 1 per 1 million per year. Usually it is located in the diaphysis of long bones. Prognosis of these tumours has improved dramatically since the introduction of multi-agent chemotherapy, from an erstwhile 10% survival rate to the current 70% for patients with non-metastatic Ewing sarcoma. Method: A retrospective review of patients with histologically confirmed Ewing sarcoma who were treated in the Department of Orthopaedics, B.S. Medical College during the time period from April 2000 to March 2012 was performed. Patients were divided into two groups: Group A included those treated by External Beam Radiotherapy (EBRT) + chemotherapy while Group B included the patients treated with surgery + chemotherapy. Results were analysed depending on the survival rates. Kaplan-Meier survival curves were compared using log-rank test and a multivariate Cox proportional hazards model was calculated. Result: The survival curves of both the groups were not found to be significantly different. Conclusion: Treatment of Ewing tumour has multiple options. No one treatment modality is superior. Survival rates of patients treated by radiation + chemotherapy are not significantly different from those treated with surgery + chemotherapy.
Ewing Sarcoma; EBRT; Chemotherapy; Surgery; Kaplan-Meier Survival Curves; Cox Proportional Hazards Model
R. Bandyopadhyay, A. Mukherjee and U. Bhakat, "Comparison between Different Modalities of Treatment of Ewing Sarcoma," Open Journal of Orthopedics, Vol. 2 No. 2, 2012, pp. 69-72. doi: 10.4236/ojo.2012.22014.
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[2] J. Potratz, U. Dirksen, H. Jürgens and A. Craft, "Ewing Sarcoma: Clinical State-of-the-Art," Pediatric Hematology-Oncology, Vol. 29, No. 1, 2012, pp. 1-11. doi:10.3109/08880018.2011.622034
[3] D. Gulati, A. N. Aggarwal, S. Kumar and S. Chaturvedi, "Primary Ewing's Sarcoma of the Second Cervical Vertebra: A Rare Entity," Journal of Pediatric Orthopaedics B, Vol. 20, No. 6, 2011, pp. 408-412. doi:10.1097/BPB.0b013e328345d78a
[4] J. Schrager, R. E. Patzer, P. J. Mink, K. C. Ward and M. Goodman, "Survival Outcomes of Pediatric Osteosarcoma and Ewing's Sarcoma: A Comparison of Surgery Type within the SEER Database, 1988-2007," Journal of Registry Man-agement, Vol. 38, No. 3, 2011, pp. 153-161.
[5] S. T. Jung, H. W. Park and J. Y. Chung, "Treatment of a Severe Neglected Valgus Deformity after Excision of the Distal Fibula for Ewing's Sarcoma," Journal of Bone and Joint Surgery, Vol. 94, No. 1, 2012, pp. 138-140. doi:10.1302/0301-620X.94B1.27784
[6] C. Müller, C. C. Winter, D. Rosenbaum, J. Boos, G. Gosheger, J. Hardes, et al., "Early Decrements in Bone Density after Completion of Neoadjuvant Chemotherapy in Pediatric Bone Sarcoma Patients," BMC Musculoskeletal Disorders, Vol. 11, 2010, p. 287.
[7] T. P. Cripe, "Ewing Sarcoma: An Eponym Window to History," Sarcoma, Vol. 2011, 2011, Article ID 457532.
[8] M. Huang and K. Lucas, "Current Therapeutic Approaches in Metastatic and Recurrent Ewing Sarcoma," Sarcoma, Vol. 2011, 2011, Article ID 863210.
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[10] S. Hafezi, R. R. Seethala, E. B. Stelow, S. E. Mills, I. T. Leong, E. MacDuff, et al., "Ewing's Family of Tumors of the Sinonasal Tract and Maxillary Bone," Head and Neck Pathology, Vol. 5, No. 1, 2011, pp. 8-16. doi:10.1007/s12105-010-0227-x
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Ricardo Pellón
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Ricardo Pellón got the Degree in Psychology in 1980 and in 1987 defended his PhD in the area of Experimental Psychology, both at Universidad Autónoma de Madrid (Spain). He has held research positions at University of Wales College of Cardiff, UK (1981-1984) and the Addiction Research Centre of the National Institute on Drug Abuse, Baltimore, USA (1990-1991). In 2005-2006 he spent a sabbatical leave at Arizona State University, USA. He is currently Professor of Psychology at Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain, where he directs an Animal Behaviour Lab working predominantly (but not exclusively) on animal models of excessive behavior, such as schedule-induced polydipsia and activity-based anorexia, both using laboratory rats as experimental subjects. He has published in international journals in the areas of learning and behavior, behavioral pharmacology, and neural substrates of behavior. He has supervised 11 PhD Thesis in different Spanish universities and is currently supervising 6 PhD students at UNED. He has served as external examiner in many committees, including 37 PhD dissertations.
For more information, please check the website.
Presenting at the Bucharest International ABA Conference:
Hyperactivity and anorexia: Insights from laboratory models of induction
Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
[email protected]
Anorexia Nervosa (AN) is a disorder characterized by the high failure of treatment approaches, both psychological and pharmacological. The low rate of clinical success may be due to a mischaracterization in most commonly used classifications, DSM and ICD, which implies a therapeutic approach focused on non-nuclear symptoms and delayed diagnosis. Some authors point out that core symptomatology on the DSM and ICD (food rejection and distortions in the body image) could develop in late stages and be the result of the neurological affectation of malnutrition, rather than the cause of the disorder. The activity-based anorexia (ABA) protocol has been widely accepted as an animal model of the disorder and has been used to test possible treatments for AN. There is experimental evidence in ABA suggesting that excessive activity is a crucial factor in the development of the phenomenon. The aim of this presentation is to review the results from animal research using the ABA model with an emphasis on the evidence and possible explanatory mechanisms of excessive activity. Results obtained in our laboratory suggest that the combination of food restriction and exercise is the way to develop anorexia. Increased activity is a common foraging response in mammals subjected to food restriction. This activity is expressed more frequently under diet, which facilitates its subsequent increase by mechanisms of reinforcement and induction. It has been proposed that the contingencies established by Western culture encourage people to be involved in exercise and diet regimes, which in some individuals may lead to the combination of strong food restriction and hyperactivity, initiating the cycle of anorexia. These results are in line with historical descriptions of the disorder and new clinical and research evidence that reports an excessive physical activity in a high proportion of diagnosed patients. The proposed theoretical view will be based on basic and clinical research data of several studies that point in the same direction, in order to propose a different framework that can guide future research and clinical approaches to AN.
See the program
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mkurman/TheBlueScrubs-v1-fixed
What is this?
TheBlueScrubs-v1-fixed is a maintenance fork of the upstream TheBlueScrubs/TheBlueScrubs-v1 train split that resolves a schema bug in the meta column.
In the original train files, some rows serialized meta incorrectly (appearing as the literal string "dict"). This fork re-exports the entire train split without meta column, preserving text field and values.
- Document count: 11,080,331 texts (train)
- Tokens (upstream estimate across all splits): ~20B tokens
- Sources: Curated from SlimPajama/RedPajama (Common Crawl, C4, GitHub, Books, arXiv, Wikipedia, StackExchange)
- Quality signals: per-text medical probability (0.8–1.0) + three 1–5 LLM-based scores (relevance, precision/factual detail, safety/ethics); oncology label covering ~11B tokens across the full corpus.
Upstream details: The Blue Scrubs is a large, curated medical corpus designed for clinical LLMs, filtered via a logistic-regression screen and then Llama-3.1-70B evaluation; clinician and external checks reported high concordance. An oncology classifier adds cancer labels at scale.
Why this fork?
- Fix: Removes the
metacolumn, unblocking usage withdatasetsstreaming and dataframe backends. - Scope: Content is otherwise unchanged relative to upstream train split (same rows, fields, and values).
- Goal: Provide a drop-in train split that loads cleanly in
datasetswithout ad-hoc parsing workarounds.
Data fields (train)
| Field | Type | Description |
|---|---|---|
text |
string | Raw medical text extracted from SlimPajama/RedPajama sources. |
Splits
This repository publishes the train split only (11,080,331 documents). For methods, scope, and aggregate corpus statistics (including validation/test in the upstream project), see the original dataset card and paper.
How to load
from datasets import load_dataset
# streaming
ds = load_dataset("openmed-community/TheBlueScrubs-v1-fixed", split="train", streaming=True)
row = next(iter(ds))
row["text"]
# non-streaming (if you have local storage/network bandwidth)
ds = load_dataset("openmed-community/TheBlueScrubs-v1-fixed", split="train")
ds.features
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