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39346119
|
Molecular features of NSCLC patients with liver metastasis.
|
Metastasis is the primary cause of lung cancer-related death. Primary cancer cells invade through the lymphatic or blood vessels to distant sites. Recently, it was proposed that lymphatic metastasis was more a hallmark of tumor aggressiveness or metastatic potential than a gateway to metastases. Therefore, the underlying molecular mechanism of metastasis is not entirely clear. This study aimed to explore the genetic mechanisms underlying liver metastases from lung cancer and to evaluate the efficacy of different therapies in these patients. We retrospectively analyzed the mutation spectrum of different biopsy samples including primary lung tumors, liver, lymph node metastasis, and circulating tumor DNA (ctDNA) from 1090 non-small-cell lung cancer (NSCLC) patients with liver metastasis between the years 2017 and 2022. Demographic and disease characteristics were summarized using descriptive parameters. Time to treatment discontinuation was used to analyze the clinical outcome. More liquid biopsies were performed than tissue biopsies, especially in the treated advanced NSCLC patients. Liver metastasis before treatment was associated with poor response to immune checkpoint inhibitors and targeted therapy. Liver and lymph node metastasis had higher levels of single nucleotide variants and copy number variants than primary lung tumors. In paired lung and liver, lymph nodes, and simultaneous ctDNA, we found actionable mutations were always shared, while metastasis samples had multiple private mutations. Serial ctDNA analysis identifies potential resistant mutations and describes the evolution of tumor cells. Liver and lymph node metastasis in NSCLC showed shared actionable mutations. Of note, the discrepancy of private mutations in liver and lymph node metastases indicated that liver metastases are mainly seeded by the primary tumor rather than the earlier colonized lymph node metastases. © The Author(s), 2024.
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10.1177/17588359241275421
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1273048
|
[Role of different regions of the hypothalamus in regulating the hypophyseal-adrenal cortex system in rats].
|
The effect of electrical stimulation of various structures of the medial hypothalamus on the corticosterone level in the peripheral blood was studied in rats with preliminarily destroyed individual areas of the hypothalamus. Injury of various structures of the medial hypothalamus led the first days after the operation to reduction of the response to the stimulation. Two-three weeks after destruction of the anterior and the middle portions of the hypothalamus reactivity of the hypophyseo-adrenocortical system was restored, although not always completely. Only in destruction of the premamillary nuclei there was no restoration of the reaction. A conclusion was drawn that the area of the posterior hypothalamus was of great necessity for functional regulation of the hypophysis-adrenal cortex system.
| |
15281351
|
Pathology and molecular genetics of the pituitary gland in patients with the 'complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas' (Carney complex).
|
Carney complex (CNC) is a familial multiple neoplasia and lentiginosis syndrome with features overlapping those of McCune-Albright syndrome (MAS) and other multiple endocrine neoplasia (MEN) syndromes like MEN type 1 (MEN 1). Pituitary tumors have been described in a number of patients with CNC; all have been growth hormone (GH) and prolactin (PRL)-producing. In at least some patients, pituitary gland involvement is manifested by hyperplastic areas; hyperplasia appears to involve somatomammotrophs only and to precede GH-producing tumor formation, in a pathway similar to that seen in MAS-related pituitary tumors (and in oncogenesis in other CNC tissues). One patient with CNC and advanced acromegaly had a GH-producing macroadenoma that showed extensive genetic changes at the chromosomal level. These changes appeared to represent secondary or tertiary genetic 'hits' involved in pituitary oncogenesis and were confirmed at the molecular level. So far, almost half of the patients with CNC have germline-inactivating mutations in the PRKAR1A gene; in their pituitary tumors, the normal allele of the PRKAR1A gene is lost. Loss of heterozygosity suggests that PRKAR1A, which codes for the regulatory subunit type 1alpha of the cAMP-dependent protein kinase A (PKA), may act as a tumor-suppressor gene in pituitary tissue. These data provide evidence for a PKA-induced somatomammotroph hyperplasia in the pituitary tissue of CNC patients; hyperplasia leads to additional genetic changes at the somatic level, which in turn cause the formation of adenomas in some, but not all, patients.
|
10.1159/000079049
|
36532385
|
Knowledge of Musculoskeletal Medicine in Junior Doctors in Australia: Is It Adequate?
|
The incidence of musculoskeletal disease is increasing in Australia and around the world. However, medical student education does not necessarily reflect current and projected trends in musculoskeletal medicine. The aim of this study was to assess junior doctors' competency in musculoskeletal medicine using the Freedman and Bernstein Basic Competency Examination in Musculoskeletal Medicine questionnaire. We conducted a cohort study of interns (first year post medical school) across four teaching hospitals in Australia. Interns were asked to take the Freedman and Bernstein examination during organised intern teaching sessions, and results were analysed using the original Freedman and Bernstein marking criteria and validated pass mark. The mean score for the 92 interns was 13.9 out of 25 (55%) with scores ranging from 8 to 20.8 (29-83%). Only 8 of the 92 interns (8.7%) achieved a score of greater than 73%, the pre-specified pass mark. Our study identifies inadequacies in musculoskeletal medical knowledge in Australian interns. Review of undergraduate medical education may be required to reflect current and predicted trends in the prevalence of musculoskeletal disease and adequately prepare junior doctors. © Crown 2022.
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10.1007/s40670-022-01637-3
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22451728
|
Gene expression profiles in genetically different mice infected with Toxoplasma gondii: ALDH1A2, BEX2, EGR2, CCL3 and PLAU.
|
Toxoplasma gondii can modulate host cell gene expression; however, determining gene expression levels in intermediate hosts after T. gondii infection is not known much. We selected 5 genes (ALDH1A2, BEX2, CCL3, EGR2 and PLAU) and compared the mRNA expression levels in the spleen, liver, lung and small intestine of genetically different mice infected with T. gondii. ALDH1A2 mRNA expressions of both mouse strains were markedly increased at day 1-4 postinfection (PI) and then decreased, and its expressions in the spleen and lung were significantly higher in C57BL/6 mice than those of BALB/c mice. BEX2 and CCR3 mRNA expressions of both mouse strains were significantly increased from day 7 PI and peaked at day 15-30 PI (P<0.05), especially high in the spleen liver or small intestine of C57BL/6 mice. EGR2 and PLAU mRNA expressions of both mouse strains were significantly increased after infection, especially high in the spleen and liver. However, their expression patterns were varied depending on the tissue and mouse strain. Taken together, T. gondii-susceptible C57BL/6 mice expressed higher levels of these 5 genes than did T. gondii-resistant BALB/c mice, particularly in the spleen and liver. And ALDH1A2 and PLAU expressions were increased acutely, whereas BEX2, CCL3 and EGR2 expressions were increased lately. Thus, these demonstrate that host genetic factors exert a strong impact on the expression of these 5 genes and their expression patterns were varied depending on the gene or tissue.
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10.3347/kjp.2012.50.1.7
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21085746
|
Relationship between iron deficiency and anemia in children younger than 4 years.
|
To evaluate the prevalence of anemia, iron deficiency and iron deficiency anemia in a cohort of children. A cohort study nested in a randomized field trial. Children were recruited at birth at the maternity unit of the only public hospital in the city of São Leopoldo, southern Brazil. This study assessed iron status (hemoglobin and serum ferritin) when children were 12-16 months old and later at the age of 3-4 years. Anemia was defined as hemoglobin concentration < 11.0 g/dL; iron deficiency as serum ferritin < 15.0 µg/L; and iron deficiency anemia as hemoglobin concentration < 11.0 g/dL with iron deficiency. At age 12-16 months, the overall prevalence of anemia, iron deficiency and iron deficiency anemia was 63.7, 90.3 and 58.8%, respectively. The values for age group 3-4 years were 38.1, 16.1 and 7.4%, respectively. At age 12-16 months, 95% of anemia cases were associated with iron deficiency against only 19.3% of cases at age 3-4 years. Iron deficiency was the main cause of anemia in the second year of life, but not at age 3-4 years. Thus, we point out that anemia in preschool children may have other causes and deserves careful assessment.
|
10.2223/JPED.2039
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22798834
|
3-Methyl-4-[2-(4-nitro-phen-yl)hydrazin-1-yl-idene]-5-oxo-4,5-dihydro-1H-pyrazole-1-carbothio-amide.
|
The asymmetric unit of the title compound, C(11)H(10)N(6)O(3)S, contains two independent mol-ecules, each of which is stabilized by an intra-molecular N-H⋯O hydrogen bond, forming an S(6) ring motif. In one mol-ecule, the pyrazole ring forms a dihedral angle of 10.93 (14)° with the benzene ring. The corresponding dihedral angle in the other mol-ecule is 7.03 (14)°. In the crystal, mol-ecules are linked via pairs of (N,N)-H⋯O bifurcated acceptor bonds which, together with C-H⋯O hydrogen bonds, form sheets parallel to (001).
|
10.1107/S1600536812027134
|
23327091
|
[Effects of oral health care for lung cancer patients with surgery--improvement of cough reflex].
|
The number of lung cancer patients is increasing. One complication of particular concern after surgery for lung cancer is postoperative pneumonia. The present study examined the various effects of oral care cough reflexes (cough reflex test), oral health conditions (OAG and face scale), and immune function (NK cell activity) in patients who underwent surgery for lung cancer. Subjects included 60 patients aged 75 years old or younger who were scheduled to undergo surgery for stage I lung cancer. The average age was 65.3 +/- 6.0 years old. We randomly divided the subjects into an oral care group and a control group. In the oral care group, we observed a significant increase in the normal rate of cough reflex test postsurgery, relative to pre-surgery. In contrast, no significant change in the normal rate of cough reflex test was noted for patients in the control group. Oral health conditions showed similar results. While we observed no significant change in NK cell activity from between pre-surgery and post-surgery in the oral care group, we did note a significant decrease in the control group. Two cases of pneumonia after surgery were identified in the control group. The oral care group did not get postoperative pneumonia. Thus, it was shown that oral care is related to cough reflex, oral health conditions, and immune function.
| |
1992690
|
Reduction of cardiovascular disease-related mortality among postmenopausal women who use hormones: evidence from a national cohort.
|
A national sample of 1944 white menopausal women greater than or equal to 55 years old from the epidemiologic follow-up of participants in the National Health and Nutrition Examination Survey was reviewed to investigate the role of hormone therapy in altering the risk of death from cardiovascular disease. Women in the study were observed for up to 16 years after the baseline survey in 1971 to 1975. By 1987 631 women had died; 347 of these deaths were due to cardiovascular disease. History of diabetes (relative risk, 2.38; 95% confidence interval 1.73 to 3.26), previous myocardial infarction (relative risk, 2.12; 95% confidence interval 1.56 to 2.86), smoking (relative risk, 2.18; 95% confidence interval, 1.69 to 2.81), and elevated blood pressure (relative risk, 1.49; 95% confidence interval, 1.14 to 1.94) were strong predictors of cardiovascular disease-related death in this cohort. After adjusting for known cardiovascular disease risk factors (smoking, cholesterol, body mass index, blood pressure, previous myocardial infarction, history of diabetes, age) and education, the use of postmenopausal hormones was associated with a reduced risk of death from cardiovascular disease (relative risk, 0.66; 95% confidence interval, 0.48 to 0.90). The same protective effect provided by postmenopausal hormone therapy was seen in women who experienced natural menopause (relative risk, 0.69; 95% confidence interval, 0.45 to 1.06).
|
10.1016/s0002-9378(11)80006-2
|
22194124
|
The traumatic brain injury: diagnosis and management at emergency department by general surgeon. A retrospective critical analysis on the use of the CT head scan.
|
In recent decades, considerable progress has been made in diagnosis and management of cranial trauma patients. Computed Tomography has resulted in a revolution in head injury diagnosis, making it possible to detect cases suitable for surgical treatment in a rapid, non-invasive manner. We present our experience in treating patients with head injuries at Emergency Department by describing the process and the criteria under which any diagnostic test is performed focusing in CT head scan. Between 2007-2009 we studied 1356 adult patients (725 male and 631 female) who came at the emergency department claiming head injury. The factors registered were the mechanism of injury, the neurological evaluation, the Glasgow Coma Scale (GCS), the specialty of the doctor who made the first evaluation, and finally in which cases and with which criteria the CT scan was performed. Only a disproportionate small number of the patients who arrive at the emergency room claiming head injury require neurosurgical intervention (4.8% in our study). The majority of the CT scans who are performed as emergency procedure have no pathological findings (53.4%). The general surgeon with the appropriate education is able to evaluate the patients with head injury.
|
10.5137/1019-5149.JTN .3749-10.1
|
24013569
|
Prescription and adherence to lymphedema self-care modalities among women with breast cancer-related lymphedema.
|
To profile the prescription for and adherence to breast cancer-related lymphedema (BCRL) self-care modalities among breast cancer (BrCa) survivors with BCRL in a 12-month randomized weightlifting trial. We developed a questionnaire that assessed prescription for and adherence to 10 BCRL self-care modalities that included physical therapy exercise, pneumatic compression pump, medication, lymphedema bandaging, arm elevation, self-administered lymphatic drainage, therapist-administered lymphatic drainage, compression garments, skin care, and taping. We measured prescription for and adherence to BCRL self-care modalities at baseline, 3, 6, and 12 months. Longitudinal logistic regression was used to estimate the odds ratio (OR) and 95 % confidence interval (95 % CI) associated with prescription for and adherence to BCRL modalities over time. This study included 141 BrCa survivors with BCRL. Women were prescribed an average of 3.6 ± 2.1 BCRL self-care modalities during the study. The prescription for therapist-administered lymphatic drainage (OR = 0.92, 95 % CI 0.88-0.96), pneumatic compression pump use (OR = 0.94, 95 % CI 0.89-0.98), and bandaging (OR = 0.96, 95 % CI 0.93-0.99) decreased over 12 months of follow-up. No other prescribed BCRL self-care modalities changed during the study. Over 12 months, the average adherence to all BCRL self-care modalities varied with 13, 24, 32, and 31 % of women reporting <25, 25-49, 50-74, and ≥75 % adherence, respectively. Over 12 months, there was a noticeable change from high to low adherence in self-administered lymphatic drainage, such that there was a 15 % increased likelihood of adherence <25 % compared to ≥75 % (OR = 1.15 (95 % CI 1.05-1.26); p = 0.002). The adherence patterns of all other modalities did not change over follow-up. Our findings suggest the prescription for BCRL self-care modalities is variable. The average adherence to BCRL self-care was non-optimal. Future research is necessary to prepare BrCa survivors with the knowledge, skills, abilities, and resources necessary to care for this lifelong condition.
|
10.1007/s00520-013-1962-9
|
13677296
|
[Surgical removal of choroidal neovascularization in angioid streaks].
|
All the studies so far on surgical removal of choroidal neovascularization (CNV) in angioid streaks(AS) were conducted on a small number of cases. Therefore, a definitive evaluation of the surgical method was not available. The present study aimed to evaluate this surgical modality. We performed surgical removal of foveal CNV accompanied by AS. Eighteen eyes of seventeen patients were available for follow-up of over 12 months. Surgical indications included foveal CNV, fluorescence leakage from the CNV in late-phase fluorescein angiography, and visual acuity of 0.3 or lower. The best visual acuity was improved in 44% and unchanged in 44%. The final visual acuity was improved in 33% and unchanged in 39%. 22% had a preoperative visual acuity of 0.2 or above; and 44% and 17% achieved best and final visual acuity, respectively, of 0.2 or above. Since all cases developed atrophy of the choriocapillaris in the fovea, none of the cases were capable of fixation within atrophy. The fixation point was localized outside atrophy in 56% and fixation was poor in 44%. The diameter of postoperative atrophy of choriocapillaris was significantly greater (p < 0.05) than the preoperative CNV diameter. CNV recurred in 8 eyes(44%), 88% of which occurred within one year. Surgical removal of CNV in AS is an effective method to maintain preoperative visual acuity.
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9596863
|
[Magnesium and calcium concentration of peripheral serum and mononuclear cells in patients with pregnancy induced hypertension].
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To evaluate the magnesium and calcium concentration of peripheral serum and mononuclear in patients with pregnancy induced hypertension (PIH). Twenty-six patients with PIH and 27 healthy women in their late pregnancy were studied. The serum and mononuclear cells magnesium and calcium contents were measured with atomic absorption spectrophotometry (fire atomization). When compared with the healthy women in their late pregnancy, (1) the peripheral serum magnesium and calcium contents in patients with PIH decreased significantly (P < 0.01 and P < 0.05), (2) the magnesium contents of the peripheral mononuclear cells in patients with moderate and severe degrees of PIH decreased significantly (P < 0.001 and P < 0.01), (3) the calcium contents of the peripheral mononuclear cells in patients with moderate and severe degrees of PIH decreased significantly (P < 0.01 and P < 0.05). The decrease of magnesium and calcium concentration may be one of the important factors responsible for the pathophysiologic changes of PIH.
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34761293
|
C. elegans: out on an evolutionary limb.
|
The natural environment of the free-living nematode Caenorhabditis elegans is rich in pathogenic microbes. There is now ample evidence to indicate that these pathogens exert a strong selection pressure on C. elegans, and have shaped its genome, physiology, and behaviour. In this short review, we concentrate on how C. elegans stands out from other animals in terms of its immune repertoire and innate immune signalling pathways. We discuss how C. elegans often detects pathogens because of their effects on essential cellular processes, or organelle integrity, in addition to direct microbial recognition. We illustrate the extensive molecular plasticity that is characteristic of immune defences in C. elegans and highlight some remarkable instances of lineage-specific innovation in innate immune mechanisms. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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10.1007/s00251-021-01231-8
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10790346
|
Reducing cardiac filling pressure lowers norepinephrine spillover in patients with chronic heart failure.
|
We studied the cardiac sympathetic response to selective unloading of cardiopulmonary baroreceptors in subjects with normal left ventricular (LV) function and congestive heart failure (CHF). Eight patients with normal LV function (age 57+/-5 years, ejection fraction 58+/-2%) and 8 patients with CHF (age 60+/-2 years; ejection fraction 19+/-2%) were studied. Instrumentation consisted of an arterial line, a pulmonary artery catheter, and a coronary sinus thermodilution catheter. The radiotracer technique was used for measurement of cardiac norepinephrine spillover (CANESP) and total-body norepinephrine spillover. Lower-body negative pressure (LBNP) was applied at 2 levels: nonhypotensive and hypotensive LBNP. Nonhypotensive LBNP reduced filling pressures significantly in both groups. Arterial pressure did not change. This reduction in filling pressures caused a significant reduction in CANESP in the CHF group (from 167+/-53 to 125+/-37 pmol/min, P<0.05) but no change in the normal LV function group. Hypotensive LBNP caused a significant increase in CANESP in the normal group (73+/-13 vs 122+/-27 pmol/min, P<0.05) but no significant change in those with CHF. We conclude that selective reduction in filling pressures lowers cardiac norepinephrine spillover in patients with CHF. These findings suggest that a goal of CHF management should be to reduce cardiac filling pressures while avoiding systemic hypotension.
|
10.1161/01.cir.101.17.2053
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36572623
|
Functional assessment of DMRT1 variants and their pathogenicity for isolated male infertility.
|
To study the impact of Doublesex and mab-3-related transcription factor 1 (DMRT1) gene variants on the encoded protein's function and the variants' pathogenic relevance for isolated male infertility caused by azoospermia. This study established a novel luciferase assay for DMRT1 missense variants using 2 different target promotors and validated the assay by analyzing previously published variants associated with differences in sex development. University genetics research institute and tertiary referral center for couples' infertility. Eleven infertile men with severely impaired spermatogenesis resulting in crypto- or azoospermia and carrying rare heterozygous missense variants in DMRT1 were identified within the Male Reproductive Genomics study. Luciferase assays with human DMRT1 variants to test functional effects on the CYP19A1 and Stra8 target promoters. We first developed and refined luciferase assays to reliably test the functional impact of DMRT1 missense variants. Next, the assay was validated by analyzing 2 DMRT1 variants associated with differences in sex development, of which c.240G>C p.(Arg80Ser) displayed highly significant effects on both target promoters compared with the wild-type protein (-40% and +100%, respectively) and c.331A>G p.(Arg111Gly) had a significant effect on the Stra8 promoter (-76%). We then systematically characterized 11 DMRT1 variants identified in infertile men. The de novo variant c.344T>A p.(Met115Lys) showed a pronounced loss of function in both DMRT1 target promoters (-100% and -86%, respectively). Variants c.308A>G p.(Lys103Arg) and c.991G>C p.(Asp331His) showed a significant gain of function exclusively for the CYP19A1 promoter (+15% and +19%, respectively). Based on these results, 3 variants were reclassified according to clinical guidelines. The present study highlights the importance of functionally characterizing DMRT1 variants of uncertain clinical significance. Using luciferase assays for diagnostic purposes enables an improved causal diagnosis for isolated male infertility. Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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10.1016/j.fertnstert.2022.10.032
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15367617
|
Dual role of prostratin in inhibition of infection and reactivation of human immunodeficiency virus from latency in primary blood lymphocytes and lymphoid tissue.
|
To design strategies to purge latent reservoirs of human immunodeficiency virus type 1 (HIV-1), we investigated mechanisms by which a non-tumor-promoting phorbol ester, prostratin, inhibits infection of CD4(+) T lymphocytes and at the same time reactivates virus from latency. CD4(+) T lymphocytes from primary blood mononuclear cells (PBMC) and in blocks of human lymphoid tissue were stimulated with prostratin and infected with HIV-1 to investigate the effects of prostratin on cellular susceptibility to the virus. The capacity of prostratin to reactivate HIV from latency was tested in CD4(+) T cells harboring preintegrated and integrated latent provirus. Prostratin stimulated CD4(+) T cells in an aberrant way. It induced expression of the activation markers CD25 and CD69 but inhibited cell cycling. HIV-1 uptake was reduced in prostratin-stimulated CD4(+) T PBMC and tissues in a manner consistent with a downregulation of CD4 and CXCR4 receptors in these systems. At the postentry level, prostratin inhibited completion of reverse transcription of the viral genome in lymphoid tissue. However, prostratin facilitated integration of the reverse-transcribed HIV-1 genome in nondividing CD4(+) T cells and facilitated expression of already integrated HIV-1, including latent forms. Thus, while stimulation with prostratin restricts susceptibility of primary resting CD4(+) T cells to HIV infection at the virus cell-entry level and at the reverse transcription level, it efficiently reactivates HIV-1 from pre- and postintegration latency in resting CD4(+) T cells.
|
10.1128/JVI.78.19.10507-10515.2004
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22173846
|
Does anti-TNF therapy cause any change in platelet activation in ankylosing spondylitis patients? A comparative study.
|
Recently, it has been reported that ankylosing spondylitis (AS) was characterised by endothelial dysfunction and the development of atherosclerotic complications. In this study, we evaluated platelet and endothelial activation parameters in AS patients. Fiftynine AS patients and 22 healthy controls were included. The clinical features and acute phase parameters were evaluated. In all patients and healthy controls, platelet-monocyte complexes (PMC), platelet-neutrophil complexes, basal and ADP-stimulated P-selectin (CD62P) expression were determined by flow cytometry; soluble E-selectin (sE-selectin) and soluble CD40L (sCD40L) were determined by ELISA. AS patients were divided into two groups as active and inactive by using BASDAI. In 15 AS patients, the evaluated parameters were assessed before and after 12 weeks of anti-TNF therapy. PMC and sCD40L levels in AS patients were significantly higher than in the control group (P values 0.013 and 0.016). The evaluated variables were similar in active and inactive AS groups (P > 0.05). There were no significant changes in platelet and endothelial activation parameters in AS patients after anti-TNF therapy (P > 0.05). Platelet activation which is reflected by high levels of PMC and sCD40L might be responsible for the increased frequency of atherosclerosis in AS. The platelet activation in our AS patients was not associated with disease activity and did not improve after anti-TNF therapy.
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10.1007/s11239-011-0663-9
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23115222
|
The antinociceptive effects of nicotinic receptors α7-positive allosteric modulators in murine acute and tonic pain models.
|
The α7 nicotinic acetylcholine receptor (nAChR) subtype is abundantly expressed in the central nervous system and in the periphery. Recent evidence suggests that α7 nAChR subtypes, which can be activated by an endogenous cholinergic tone, comprising acetylcholine and the α7 nAChR agonist choline, play an important role in subchronic pain and inflammation. This study's objective was to test whether α7 nAChR positive allosteric modulators (PAMs) produce antinociception in in vivo mouse models of acute and persistent pain. Testing type I [N-(5-chloro-2-hydroxyphenyl)-N'-[2-chloro-5-(trifluoromethyl)phenyl] (NS1738)] and type II [1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl) (PNU-120596)] α7 nAChR PAMs in acute and persistent pain, we found that, although neither reduced acute thermal pain, only PNU-120596 dose-dependently attenuated paw-licking behavior in the formalin test. The long-acting effect of PNU-120596 in this test was in discordance with its pharmacokinetic profile in mice, which suggests the involvement of postreceptor signaling mechanisms. Our results with selective mitogen-activated protein kinase kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene monoethanolate (U0126) argues for an important role of extracellular signal-regulated kinase-1/2 pathways activation in PNU-120596's antinociceptive effects. The α7 antagonist MLA, administered intrathecally, reversed PNU-120596's effects, confirming PNU-120596's action, in part, through central α7 nAChRs. Importantly, tolerance to PNU-120596 was not developed after subchronic treatment of the drug. Surprisingly, PNU-120596's antinociceptive effects were blocked by NS1738. Our results indicate that type II α7 nAChR PAM PNU-120596, but not type I α7 nAChR PAM NS1738, shows significant antinociception effects in persistent pain models in mice.
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10.1124/jpet.112.197871
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1915309
|
Mutagenicity of methylazoxymethanol acetate in the presence of alcohol dehydrogenase, aldehyde dehydrogenase, and rat liver microsomes in Salmonella typhimurium His G46.
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Methylazoxymethanol (MAM) is the short-lived toxic and carcinogenic aglycone of cycasin, a natural component of the cycad plant. In the present study, the stable acetate ester of MAM, MAM acetate, was tested in combination with porcine liver esterase and Salmonella typhimurium His G46 to study the comparative mutagenicity of this compound in the presence of rat hepatic alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and rat liver microsomes. In the presence of rat liver microsomes and an NADPH-generating system, mutagenicity of MAM acetate was not significantly altered. However, addition of rat liver 105,000g supernatant fraction and/or NAD+ significantly increased the number of his+ revertants above control. A concentration-dependent increase in mutagenicity of MAM acetate was observed for NAD+ from 50 to 200 microM, while NADP+ caused a decrease in mutagenicity of MAM acetate in this same concentration range. Pyrazole (100-500 microM) had no significant effect on mutagenicity of MAM acetate in the presence of rat liver 105,000g supernatant, while disulfiram at 500 microM resulted in a significant decrease in mutagenicity of MAM acetate. The results of this study implicate ALDH as essential in activation of MAM acetate to a mutagenic species in this system, while the role of ADH and microsomes appears to be minimal.
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10.1002/em.2850180302
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37664250
|
Ayurvedic Treatment Protocol for Hereditary Pancreatitis: A Case Report Demonstrating Disease Arrestation.
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The case report presented here highlights the use of an Ayurvedic treatment protocol (ATP) in managing hereditary pancreatitis (HP) in a 14-year-old boy. HP is a rare form of pancreatitis caused by specific gene mutations that are inherited within families. It is known to be aggressive and can lead to pancreatic cancer in later stages. The boy, in this case, experienced multiple episodes of pancreatitis and required several hospitalizations despite following a conventional treatment approach, which included a dairy-free, protein and fat-restricted diet, and pancreatic enzyme supplementation. However, after starting the ATP in February 2022, which involved a modified diet and the use of herbo-mineral Ayurvedic formulations, the boy reported significant improvement in his general well-being and was able to lead a normal life without experiencing any discomfort. The ATP included a customized diet comprising dairy products with moderate amounts of fat and protein, along with specific herbo-mineral formulations and the withdrawal of pancreatic enzymes. The boy also received vitamin D3 supplementation. After approximately one year of following the ATP, the disease progression was arrested, as indicated by follow-up images and investigations. The size of the pancreatic duct decreased from 8 mm to 2.8 mm. This case report suggests that the ATP may have potential efficacy in managing hereditary pancreatitis and halting disease progression. However, it is important to note that this is a single case report, and further research and clinical studies are needed to validate the long-term benefits and understand the underlying mechanisms of Ayurvedic interventions in hereditary pancreatitis. Copyright © 2023, Prakash et al.
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10.7759/cureus.42876
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2478805
|
Mechanisms of downregulation of beta-adrenergic receptors: perspective on the role of beta-adrenergic receptors in congestive heart failure.
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The impaired inotropic responsiveness of myocardial tissue to catecholamines in congestive heart failure has been ascribed to downregulation of beta-adrenergic receptors. It has been reported recently that resistance to catecholamines is related to a defect in the guanine nucleotide binding protein that couples the beta-adrenergic receptor to adenylate cyclase. Studies of beta-adrenergic receptors were carried out using three different experimental protocols: (a) the interactions of the atypical agonists pindolol and celiprolol with beta-adrenergic receptors from C6 glioma cells (40% beta 1, 60% beta 2) were compared with those of the full agonist isoproterenol; (b) the ability of pindolol, celiprolol, and isoproterenol to induce downregulation and sequestration of beta-adrenergic receptors in wild-type S49 lymphoma cells was compared with the responses observed with a mutant line of S49 cells (cyc-, which lack Gs activity); and (c) the differential response of patients with heart failure and age-matched control subjects to exercise-induced changes in the density of beta-adrenergic receptors and isoproterenol-stimulated adenylate cyclase activity on circulating lymphocytes was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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18923037
|
The stargazin-related protein gamma 7 interacts with the mRNA-binding protein heterogeneous nuclear ribonucleoprotein A2 and regulates the stability of specific mRNAs, including CaV2.2.
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The role(s) of the novel stargazin-like gamma-subunit proteins remain controversial. We have shown previously that the neuron-specific gamma7 suppresses the expression of certain calcium channels, particularly Ca(V)2.2, and is therefore unlikely to operate as a calcium channel subunit. We now show that the effect of gamma7 on Ca(V)2.2 expression is via an increase in the degradation rate of Ca(V)2.2 mRNA and hence a reduction of Ca(V)2.2 protein level. Furthermore, exogenous expression of gamma7 in PC12 cells also decreased the endogenous Ca(V)2.2 mRNA level. Conversely, knockdown of endogenous gamma7 with short-hairpin RNAs produced a reciprocal enhancement of Ca(V)2.2 mRNA stability and an increase in endogenous calcium currents in PC12 cells. Moreover, both endogenous and expressed gamma7 are present on intracellular membranes, rather than the plasma membrane. The cytoplasmic C terminus of gamma7 is essential for all its effects, and we show that gamma7 binds directly via its C terminus to a heterogeneous nuclear ribonucleoprotein (hnRNP A2), which also binds to a motif in Ca(V)2.2 mRNA, and is associated with native Ca(V)2.2 mRNA in PC12 cells. The expression of hnRNP A2 enhances Ca(V)2.2 I(Ba), and this enhancement is prevented by a concentration of gamma7 that alone has no effect on I(Ba). The effect of gamma7 is selective for certain mRNAs because it had no effect on alpha2delta-2 mRNA stability, but it decreased the mRNA stability for the potassium-chloride cotransporter, KCC1, which contains a similar hnRNP A2 binding motif to that in Ca(V)2.2 mRNA. Our results indicate that gamma7 plays a role in stabilizing Ca(V)2.2 mRNA.
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10.1523/JNEUROSCI.2709-08.2008
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10918316
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Comparison of the quantification precision of human short echo time (1)H spectroscopy at 1.5 and 4.0 Tesla.
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Precise quantification of human in vivo short echo time (1)H spectra remains problematic at clinical field strengths due to broad peak linewidths and low signal-to-noise ratio (SNR). In this study, multiple STEAM spectra (TE = 20 ms, volume = 8 cm(3)) were acquired in a single individual at 1.5 T and 4 T to compare quantification precision. Test-retest STEAM spectra (volume = 1.5 cm(3)) were also acquired from the anterior cingulate and thalamus of 10 individuals at 4.0 T. Metabolite levels were quantified using automated software that incorporated field strength-specific prior knowledge. With the distinct methods of data acquisition, processing, and fitting used in this study, peak height SNR increased approximately 80% while peak linewidth increased by approximately 50% in the 8 cm(3) volumes at 4.0 T compared to 1.5 T, resulting in an average increase in quantification precision of 39%. Metabolite levels from test-retest data (1.5 cm(3) voxels at 4.0 T) were quantified with similar inter- and intraindividual variability. Magn Reson Med 44:185-192, 2000. Published 2000 Wiley-Liss, Inc.
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10.1002/1522-2594(200008)44:2<185::aid-mrm4>3.0.co;2-v
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21913340
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Identification of molecular motors in the Woods Hole squid, Loligo pealei: an expressed sequence tag approach.
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The squid giant axon and synapse are unique systems for studying neuronal function. While a few nucleotide and amino acid sequences have been obtained from squid, large scale genetic and proteomic information is lacking. We have been particularly interested in motors present in axons and their roles in transport processes. Here, to obtain genetic data and to identify motors expressed in squid, we initiated an expressed sequence tag project by single-pass sequencing mRNAs isolated from the stellate ganglia of the Woods Hole Squid, Loligo pealei. A total of 22,689 high quality expressed sequence tag (EST) sequences were obtained and subjected to basic local alignment search tool analysis. Seventy six percent of these sequences matched genes in the National Center for Bioinformatics databases. By CAP3 analysis this library contained 2459 contigs and 7568 singletons. Mining for motors successfully identified six kinesins, six myosins, a single dynein heavy chain, as well as components of the dynactin complex, and motor light chains and accessory proteins. This initiative demonstrates that EST projects represent an effective approach to obtain sequences of interest. Copyright © 2011 Wiley Periodicals, Inc.
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10.1002/cm.20531
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799984
|
Nefopam hydrochloride: new analgesic agent.
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Two dose-levels of nefopam hydrochloride (i. e. 30 mg and 60 mg) were compared with two dose-levels of aspirin (i. e. 300 mg and 600 mg) and placebo in 125 male patients having pain associated with muscle disorders. Drugs were given as a single dose and pain intensity and side-effects monitored at thirty minutes and then hourly for four hours. Time-course action of the drugs revealed that aspirin 300 mg failed to achieve statistically significant analgesia at any post-treatment observation, whereas nefopam 60 mg was significantly better than placebo (p less than 0-05) at one and three hours in terms of pain intensity and at one hour in terms of pain intensity difference scores. Aspirin 600 mg was significantly different from placebo (p less than 0-05) at all hourly observations for both efficacy parameters, as was nefopam 30 mg (p less than 0-01). Summation of pain intensity difference scores showed aspirin 600 mg and nefopam 30 mg to be significantly different from placebo at the 0.025 and 0.005 levels respectively.
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10.1177/030006057600400211
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22642985
|
Bone and mucosal dosimetry in skin radiation therapy: a Monte Carlo study using kilovoltage photon and megavoltage electron beams.
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This study examines variations of bone and mucosal doses with variable soft tissue and bone thicknesses, mimicking the oral or nasal cavity in skin radiation therapy. Monte Carlo simulations (EGSnrc-based codes) using the clinical kilovoltage (kVp) photon and megavoltage (MeV) electron beams, and the pencil-beam algorithm (Pinnacle(3) treatment planning system) using the MeV electron beams were performed in dose calculations. Phase-space files for the 105 and 220 kVp beams (Gulmay D3225 x-ray machine), and the 4 and 6 MeV electron beams (Varian 21 EX linear accelerator) with a field size of 5 cm diameter were generated using the BEAMnrc code, and verified using measurements. Inhomogeneous phantoms containing uniform water, bone and air layers were irradiated by the kVp photon and MeV electron beams. Relative depth, bone and mucosal doses were calculated for the uniform water and bone layers which were varied in thickness in the ranges of 0.5-2 cm and 0.2-1 cm. A uniform water layer of bolus with thickness equal to the depth of maximum dose (d(max)) of the electron beams (0.7 cm for 4 MeV and 1.5 cm for 6 MeV) was added on top of the phantom to ensure that the maximum dose was at the phantom surface. From our Monte Carlo results, the 4 and 6 MeV electron beams were found to produce insignificant bone and mucosal dose (<1%), when the uniform water layer at the phantom surface was thicker than 1.5 cm. When considering the 0.5 cm thin uniform water and bone layers, the 4 MeV electron beam deposited less bone and mucosal dose than the 6 MeV beam. Moreover, it was found that the 105 kVp beam produced more than twice the dose to bone than the 220 kVp beam when the uniform water thickness at the phantom surface was small (0.5 cm). However, the difference in bone dose enhancement between the 105 and 220 kVp beams became smaller when the thicknesses of the uniform water and bone layers in the phantom increased. Dose in the second bone layer interfacing with air was found to be higher for the 220 kVp beam than that of the 105 kVp beam, when the bone thickness was 1 cm. In this study, dose deviations of bone and mucosal layers of 18% and 17% were found between our results from Monte Carlo simulation and the pencil-beam algorithm, which overestimated the doses. Relative depth, bone and mucosal doses were studied by varying the beam nature, beam energy and thicknesses of the bone and uniform water using an inhomogeneous phantom to model the oral or nasal cavity. While the dose distribution in the pharynx region is unavailable due to the lack of a commercial treatment planning system commissioned for kVp beam planning in skin radiation therapy, our study provided an essential insight into the radiation staff to justify and estimate bone and mucosal dose.
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10.1088/0031-9155/57/12/3885
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18964689
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Assessment of the feasibility of determination of cholesterol and other blood constituents by near-infrared reflectance analysis.
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Near-infrared reflectance spectrometry of blood serum can yield values for serum cholesterol that correlate reasonably well (r = 0.96) with those from common reference analytical methods. However, the variability of serum can cause ostensibly validated calibrations to fail on new samples. The determination of blood components such as cholesterol and triglycerides by near-infrared reflectance is complicated by their low concentrations, the variety of forms in which they appear, and by the natural variability of the blood matrix. These difficulties, when combined with the problems encountered in obtaining a representative sample from a given individual, can make it almost impossible to select, by a regression procedure, a wavelength combination that is characteristic of the complete blood matrix. The failure of the regression process to find characteristic wavelengths generates a false-sample problem in which even small changes at the analytical wavelengths produce a grossly unreliable cholesterol or triglyceride determination.
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10.1016/0039-9140(89)80095-5
|
30824200
|
Discovery of a small molecule RXFP3/4 agonist that increases food intake in rats upon acute central administration.
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The relaxin family peptide receptors have been implicated in numerous physiological processes including energy homeostasis, cardiac function, wound healing, and reproductive function. Two family members, RXFP3 and RXFP4, are class A GPCRs with endogenous peptide ligands (relaxin-3 and insulin-like peptide 5 (INSL5), respectively). Polymorphisms in relaxin-3 and RXFP3 have been associated with obesity, diabetes, and hypercholesterolemia. Moreover, central administration of relaxin-3 in rats has been shown to increase food intake, leading to body weight gain. Reported RXFP3 and RXFP4 ligands have been restricted to peptides (both endogenous and synthetic) as well as a low molecular weight positive allosteric modulator requiring a non-endogenous orthosteric ligand. Described here is the discovery of the first potent low molecular weight dual agonists of RXFP3/4. The scaffold identified is competitive with a chimeric relaxin-3/INSL5 peptide for RXFP3 binding, elicits similar downstream signaling as relaxin-3, and increases food intake in rats following acute central administration. This is the first report of small molecule RXFP3/4 agonism. Copyright © 2019. Published by Elsevier Ltd.
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10.1016/j.bmcl.2019.02.013
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35116655
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MiRNA-339 targets and regulates ZNF689 to inhibit the proliferation and invasion of gastric cancer cells.
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Gastric cancer (GC) is the most common malignant tumor of the digestive system, and its mortality rate ranks first among malignant tumors. However, the pathogenesis of GC has not yet been fully elucidated. This study found that microRNA (miRNA)-339 is abnormally expressed in GC tissues. However, the role and molecular mechanism of miRNA-339 in the occurrence and development of GC are still unclear. Fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression level of miRNA-339 in GC tissues and adjacent tissues and analyze the correlation with the clinicopathological characteristics of GC patients. Cell counting kit-8 (CCK-8) and Transwell experiments detected the effect of overexpression of miRNA-339 on the proliferation, invasion, and migration of GC cells. The luciferase reporter gene detected the downstream target molecules regulated by miRNA-339, and western blot was employed to detect the effect of overexpression of miRNA-339 on the expression of ZNF689. The results of fluorescence qPCR showed that miRNA-339 was less expressed in GC tissues compared with adjacent tissues, and it was correlated with the patient's clinical tumor, node, metastasis (TNM) grade and lymph node metastasis. Cell function experiments showed that overexpression of miRNA-339 can significantly inhibit the proliferation, invasion, and migration of GC cells. The luciferase reporter gene showed that miRNA-339 can bind to the 3'-UTR region of ZNF689, and overexpression of miRNA-339 can significantly inhibit the expression of ZNF689 in GC cells. Overexpression of ZNF689 can significantly block the ability of overexpression of miRNA-339 to inhibit the proliferation and migration of GC cells. miRNA-339 inhibits the proliferation and invasion of GC cells through targeted regulation of the expression of ZNF689. In addition, the expression level of miRNA-339 can be used as a biomarker for the prognosis of GC. 2021 Translational Cancer Research. All rights reserved.
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10.21037/tcr-21-994
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33827899
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Prevalence of bla CTX-M Genes in Gram-Negative Bloodstream Isolates across 66 Hospitals in the United States.
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Understanding bacterial species at greatest risk for harboring bla CTX-M genes is necessary to guide antibiotic treatment. We identified the species-specific prevalence of bla CTX-M genes in Gram-negative clinical isolates from the United States. Twenty-four microbiology laboratories representing 66 hospitals using the GenMark Dx ePlex blood culture identification Gram-negative (BCID-GN) panel extracted blood culture results from April 2019 to July 2020. The BCID-GN panel includes 21 Gram-negative targets. Along with identifying bla CTX-M genes, it detects major carbapenemase gene families. A total of 4,209 Gram-negative blood cultures were included. bla CTX-M genes were identified in 462 (11%) specimens. The species-specific prevalence of bla CTX-M genes was as follows: Escherichia coli (16%), Klebsiella pneumoniae (14%), Klebsiella oxytoca (6%), Salmonella spp. (6%), Acinetobacter baumannii (5%), Enterobacter species (3%), Proteus mirabilis (2%), Serratia marcescens (0.6%), and Pseudomonas aeruginosa (0.5%). bla CTX-M prevalence was 26%, 24%, and 22% among participating hospitals in the District of Columbia, New York, and Florida, respectively. Carbapenemase genes were identified in 61 (2%) organisms with the following distribution: bla KPC (59%), bla VIM (16%), bla OXA (10%), bla NDM (8%), and bla IMP (7%). The species-specific prevalence of carbapenemase genes was as follows: A. baumannii (5%), K. pneumoniae (3%), P. mirabilis (3%), Enterobacter species (3%), Citrobacter spp. (3%), P. aeruginosa (2%), E. coli (<1%), K. oxytoca (<1%), and S. marcescens (<1%). Approximately 11% of Gram-negative organisms in our US cohort contain bla CTX-M genes. bla CTX-M genes remain uncommon in organisms beyond E. coli, K. pneumoniae, and K. oxytoca Future molecular diagnostic panels would benefit from the inclusion of plasmid-mediated ampC and SHV and TEM extended-spectrum beta-lactamase (ESBL) targets. Copyright © 2021 American Society for Microbiology.
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10.1128/JCM.00127-21
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39396808
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Navigating Dilemmas on Advance Euthanasia Directives of Patients with Advanced Dementia.
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This study revisited the complexities faced by physicians in meeting due care criteria for euthanasia in patients with advanced dementia in The Netherlands. Despite increasing cases and legal provisions for advance euthanasia directives (AEDs), physicians encounter challenges with ethical issues, including patient communication and assessing unbearable suffering in patients who lack decisional capacity. This study examines the perspectives of elderly care physicians (ECPs), support and consultation on euthanasia in The Netherlands (SCEN) physicians, and euthanasia expertise center (EEC) physicians. A multimethod descriptive study using a questionnaire with both closed and open-ended questions. This study explores the complexities faced by physicians in handling AED-based euthanasia requests of patients with advanced dementia. Baseline characteristics of physician subgroups were analyzed descriptively, and subgroup variations were assessed using univariate regression. Qualitative data underwent thematic content analysis. With a 13.8% response rate, the study included 290 participants: 108 ECPs, 188 SCEN physicians, and 53 EEC physicians. Some had combined roles: ECP and SCEN physicians (n = 29), ECP and EEC physician (n = 1), SCEN physicians and EEC physicians (n = 17), and ECP, SCEN physicians, and EEC physicians (n = 6). ECPs received most AED-based euthanasia requests but only 7 EEC physicians and 1 SCEN physician performed euthanasia. All subgroups stressed the importance of patient communication. ECPs found euthanasia ethically justifiable only when communication was possible, highlighting the need to understand current euthanasia wishes and verify unbearable suffering. Effective communication was deemed crucial for confirming request relevance, identifying obstacles, involving patients, fostering trust, and alleviating fears. Physicians generally agreed that unbearable suffering could be assessed through patient expressions, observations, and family input. Despite receiving AED-based euthanasia requests, few physicians proceeded. Subgroup analysis showed varying views, with ECPs emphasizing communication and EEC physicians focusing on determining unbearable suffering. All subgroups highlighted the importance of current patient expressions and involvement in the decision-making process. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
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10.1016/j.jamda.2024.105300
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37656873
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Defining a core microbial necrobiome associated with decomposing fungal necromass.
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Despite growing interest in fungal necromass decomposition due to its importance in soil carbon retention, whether a consistent group of microorganisms is associated with decomposing necromass remains unresolved. Here, we synthesize knowledge on the composition of the bacterial and fungal communities present on decomposing fungal necromass from a variety of fungal species, geographic locations, habitats, and incubation times. We found that there is a core group of both bacterial and fungal genera (i. e. a core fungal necrobiome), although the specific size of the core depended on definition. Based on a metric that included both microbial frequency and abundance, we demonstrate that the core is taxonomically and functionally diverse, including bacterial copiotrophs and oligotrophs as well as fungal saprotrophs, ectomycorrhizal fungi, and both fungal and animal parasites. We also show that the composition of the core necrobiome is notably dynamic over time, with many core bacterial and fungal genera having specific associations with the early, middle, or late stages of necromass decomposition. While this study establishes the existence of a core fungal necrobiome, we advocate that profiling the composition of fungal necromass decomposer communities in tropical environments and other terrestrial biomes beyond forests is needed to fill key knowledge gaps regarding the global nature of the fungal necrobiome. © The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.
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10.1093/femsec/fiad098
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10703751
|
A practical method for non-surgically inserting intra-arterial catheters in European wild boars (Sus scrofa).
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In endocrinological studies, the usual methods for taking blood samples are impractical because of the need for frequent sampling, and catheterization is required. The catheterization methods described for domestic pigs are not suitable for use with European wild boars (Sus scrofa) under field conditions. We describe a method for inserting an intra-arterial catheter into the European wild boar. The animals were sedated with a combination of medetomidin (Domitor 1 mg/ml, Orion-Farmos, Finland) and zolazepam and tiletamine (Zoletil forte vet 50 mg/ml + 50 mg/ml, Virbac Laboratories, France). Four animals were catheterized and sampled at 2-h intervals for 48 h in March under winter conditions and five in June under summer conditions. In March, all the catheters remained in place for the entire sampling period. In June, one animal managed to displace the catheter from its artery, but it was recatheterized and the rest of the samples were collected without problems. This catheterization method is relatively easy to carry out and requires no special facilities.
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10.1023/a:1006321204331
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9344412
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Preparation of enantiomerically pure L-7-azatryptophan by an enzymatic method and its application to the development of a fluorimetric activity assay for tryptophanyl-tRNA synthetase.
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The reaction of D,L-7-azatryptophan (D,L-7AW) with tryptophanyl-tRNA synthetase (TrpRS), adenosine triphosphate (ATP), and Mg2+ in the presence of inorganic pyrophosphatase results in the formation of a highly fluorescent l-7AW-adenylate complex. Detection of this complex is based on its enhanced fluorescence at 315 nm excitation and 360 nm emission after the addition of ATP. This stereoselective reaction was used to develop an activity assay for TrpRS using commercially available racemic D,L-7AW. The assay can be used to determine the activity of TrpRS from samples which contain less than 1 nmol of enzyme in 250 microL of sample. Thus the enzyme activity can be assessed without resorting to a radioactive assay of tRNATrp acylation. A secondary use of the stereoselective assay was for confirming the presence of pure L-7AW, D-7AW, or mixtures of the two enantiomers. D-7AW and L-7AW were prepared by reacting D,L-7AW with chloroacetic anhydride to form N-chloroacetyl-D,L-7AW (ClAc-7AW) followed by stereospecific proteolytic digestion of ClAc-7AW using carboxypeptidase A to produce the free L-7AW. The L-7AW could be separated from unreacted N-chloroacetyl-7AW by reverse-phase HPLC. The TrpRS-based assay was able to unambiguously discriminate between the two enantiomers of 7AW. The assay was then used to identify which enantiomer of 7AW was present in resolved fractions of the tripeptide L-lysyl-D,L-7-azatryptophyl-L-lysine. Digestion of the resolved tripeptides with protease enzymes produced the free L or D enantiomer of 7AW, which was easily identified using the TrpRS assay procedure. Copyright 1997 Academic Press.
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10.1006/abio.1997.2286
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25074561
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Pilot early intervention antenatal group program for pregnant women with anxiety and depression.
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This study aims to examine the acceptability and effectiveness of an antenatal group intervention designed to reduce the severity of depression and anxiety symptoms and improve maternal attachment in pregnant women with current or emerging depression and anxiety. Women who participated in the program completed pre- and posttreatment measures of depression (Centre of Epidemiological Studies Depression Scale) and Edinburgh Postnatal Depression Scale), anxiety (State-Trait Anxiety Inventory) and maternal attachment (Condon Maternal Antenatal Attachment Scale). Participants also completed a satisfaction questionnaire and provided general feedback about the group intervention and experience. A total of 48 women (M = 26 weeks of gestation) commenced and 37 (77 %) completed at least 80 % of the six session group intervention. Significant improvements with moderate to large effect sizes were observed for depression as measured on the Centre of Epidemiological Studies Depression Scale (CES-D) (p < 0.001), Edinburgh Postnatal Depression Scale (EPDS) (p < 0.001), state anxiety (p < 0.001) and maternal attachment (p = 0.006). Improvements in posttreatment depression scores on the EPDS were maintained at 2 months postpartum. Participants reported that the program had met their expectations. Partners (n = 21) who completed evaluation forms indicated that their attendance had improved their awareness of their partner's mental health issues and resources available to their family and would recommend the program to other fathers. These preliminary findings suggest that our antenatal group program is an effective and acceptable intervention for a clinical sample of women and partners. It is a feasible addition or alternative treatment option to perinatal mental health care. Future directions could involve more comprehensive randomised controlled trials (RCT) to examine the effectiveness of the group intervention.
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10.1007/s00737-014-0447-2
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32246954
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Analysis of differences in eating alone attitude of Koreans by dietary habits and age.
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This study compares differences in eating alone attitude according to dietary habits and age in Seoul and Gyeonggi-do region in South Korea. Out of total 411 participants, 207(50.4%) were males and 204(49.6%) were females. 30 types of eating alone attitude were identified to perform a factor analysis; further these 30 types of attitudes were categorized into 8 factors termed as: 'enjoyable eating alone', 'eating alone as a daily routine', 'healthy eating alone', 'self-conscious eating alone', 'choose what I want', 'efficient eating alone', 'lonely eating alone', and 'solo dining'. Our investigation on the link between dietary habits and eating alone attitude revealed significant differences in 3 factors out of those 8 factors: healthy eating alone, solo dining, eating alone as a daily routine. The high healthy meal group was found to have less frequency of eating alone. Among people in their 20s and 30s, the low healthy meal group had more population than the high healthy meal group. There was a tendency that the population of the high healthy meal group increases as age rises. Our data indicated that the younger generation eats alone more frequently as a daily routine (p < 0.01), feels freer when eating alone, eats out alone more frequently (p < 0.01). People in their 20s were found to be more positive on eating alone and tended to be willing solo diners. The high healthy meal group did eat alone in a healthy way whereas the low healthy meal group had a negative view on eating alone. Our study aims at providing a good starting point to develop programs for healthy eating alone by finding gaps between healthy and unhealthy eating alone. Copyright © 2020 Elsevier Ltd. All rights reserved.
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10.1016/j.appet.2020.104695
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1380237
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[Catalytic activity of immune complexes of peroxidase and its conjugates with cortisol in Aerosol OT reverse micelles].
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Conjugates containing 1, 6 or 11 cortisol molecules per peroxidase molecule were obtained by the reaction of the N-hydroxysuccinimide ester of cortisol 3-O-carboxymethyloxime (COR) with horse-radish peroxidase (HRP). Activities of the peroxidase conjugates and their immunocomplexes with antibodies against cortisol in the orthophenylenediamine oxidation in reversed Aerosol OT micelles in heptane at various hydration degrees of the micelles (omega 0) were studied. Catalytic activities of HRP and its conjugates, on one hand, and of the immunocomplexes of HRP with anti-HRP and the conjugates with antibodies against cortisol, on the other hand, differed significantly and depended in a different manner on the hydration degree of AOT micelles. These differences became the basis of a homogeneous enzyme-immunoassay of cortisol in the reversed micelles of AOT in heptane.
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25779638
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A Plant-Derived Multi-HIV Antigen Induces Broad Immune Responses in Orally Immunized Mice.
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Multi-HIV, a multiepitopic protein derived from both gp120 and gp41 envelope proteins of the human immunodeficiency virus (HIV), has been proposed as a vaccine prototype capable of inducing broad immune responses, as it carries various B and T cell epitopes from several HIV strains. In this study, the immunogenic properties of a Multi-HIV expressed in tobacco chloroplasts are evaluated in test mice. BALB/c mice orally immunized with tobacco-derived Multi-HIV have elicited antibody responses, including both the V3 loop of gp120 and the ELDKWA epitope of gp41. Based on splenocyte proliferation assays, stimulation with epitopes of the C4, V3 domain of gp120, and the ELDKWA domain of gp41 elicits positive cellular responses. Furthermore, specific interferon gamma production is observed in both CD4+ and CD8+ T cells stimulated with HIV peptides. These results demonstrate that plant-derived Multi-HIV induces T helper-specific responses. Altogether, these findings illustrate the immunogenic potential of plant-derived Multi-HIV in an oral immunization scheme. The potential of this low-cost immunization approach and its implications on HIV/AIDS vaccine development are discussed.
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10.1007/s12033-015-9856-3
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721673
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Surgical correction of deviated nasal septum and premaxilla in a colt.
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A 6-month-old Appaloosa colt had a deviation of the premaxilla and nasal septum as well as a dorsal hump of the nasal bone and maxillomandibular malocclusion. Two surgical procedures were performed 12 weeks apart to correct these anomalies. An intraoral approach and autogenous rib graft were used to correct the malocclusion and deviation of the premaxilla. Osteotomy of the nasal bone and removal of the nasal septum were performed to help correct the deviation and to facilitate free air passage through the nares.
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20519928
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[A case of testicular tumor with inferior vena cava thrombus].
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A 31-year-old man presented with edema in left lower leg and dyspnea. Computed tomographic scanning detected a right testicular tumor, multiple lung nodules, and inferior vena cava (IVC) thrombus. After insertion of an IVC filter, high inguinal orchiectomy was performed after the first combination chemotherapy. Pathological examination demonstrated an embryonal carcinoma with vascular invasion and direct tumoral extension into the right spermatic cord. According to our survey, this is the 14th case of testicular tumor with IVC thrombus in Japan.
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28993628
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Oxidized g-C 3 N 4 /polyaniline nanofiber composite for the selective removal of hexavalent chromium.
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Nanomaterials with selective adsorption properties are in demand for environmental applications. Herein, acid etching and oxidative decomposition of melon units of graphitic carbon nitride (g-C 3 N 4 ) was performed to obtain the oxidized graphitic carbon nitride (Ox-g-C 3 N 4 ) nanosheets. Ox- g-C 3 N 4 nanosheets were further decorated on the polyaniline nanofiber (Ox-g-C 3 N 4 /Pani-NF). Ox-g-C 3 N 4 /Pani-NF was well characterized and further applied for a selective removal of hexavalent chromium (Cr(VI)) form aqueous solution. The zeta potential analysis indicate that the surface of Ox-g-C 3 N 4 /Pani-NF was positively charged which could be beneficial to bind anionic Cr(VI) ions electrostatically. In addition, nitrogen and oxygen containing functional groups exist on the Ox-g-C 3 N 4 /Pani-NF were mainly responsible for adsorption of Cr(VI) ions from aqueous solution. Moreover, the adsorption of Cr(VI) ions was also dependent on solution pH, reaction temperature and initial concentration of Cr(VI) ions. The maximum monolayer adsorption capacity of Ox-g-C 3 N 4 /Pani-NF for Cr(VI), calculated from Langmuir isotherm was 178.57 mg/g at pH = 2 and 30 °C. The activation energy (Ea = -20.66 kJ/mol) and the enthalpy change (ΔH° = -22.055 kJ/mol) validate the role of physical forces in adsorption of Cr(VI). These results demonstrate that Ox-g-C 3 N 4 /Pani-NF can be used as a potential adsorbent for environmental remediation applications.
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10.1038/s41598-017-12850-1
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574433
|
Neuraminidase activity in the mucolipidoses (types I, II and III) and the cherry-red spot myoclonus syndrome.
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Two neuraminidase (EC 3.2.1.18) comonents, A and B, were distinguished in cultured skin fibroblasts on the basis of thermolability at 37 degrees C. The more labile component (A) t1/2 = 4.7--5.3 min at 37 degrees C, comprises 66--90% of total neuraminidase activity when determined using sodium (4-methylumbelliferyl-alpha-D-N-acetylneuraminate) (MU-alpha-N) as substrate. Activity was assayed at 0 degrees C for 18 h instead of 37 degrees C to fully determine both thermolabile and thermostable components. Diminished activity was noted in cultured fibroblasts from mucolipidoses I, II and III (MLI, MLII, MLIII) and the cherry-red spot myoclonus syndrome (CRSM) patients when assayed at both 0 and 37 degrees C with either MU-alpha-N or each of a series alpha (2 leads to 3)- and alpha (2 leads to 6)-linked N-acetylneuraminyloligosaccharides. Increased sensitivity and rapidity of analyses were achieved using MJ-alpha-N as substrate in determining neuraminidase activity. Results from two obligate heterozygote MLI cell lines (14.5 and 8.0% of control activity) indicate that the MU-alpha-N substrate could be useful for heterozygote detection.
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10.1016/0009-8981(79)90031-7
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3599037
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Reaction of lecturers to analysis results of student ratings of their lecture skills.
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Lecturers in a medical biochemistry course were evaluated by medical students with respect to overall impression and seven specific characteristics expected to predict overall impression. Each lecturer's ratings were subjected to stepwise multiple regression analysis to identify the characteristics that best accounted for the students' overall impression. The results were fed back to the lecturers, and each lecturer was subsequently interviewed. The interviews revealed that 60 percent of the lecturers had not correctly interpreted the analysis. Half of the lecturers expressed interest in improving their performance, and 20 percent of the lecturers requested specific, detailed guidance in overcoming problems. The author concludes that multivariate analysis of student ratings can generate feedback specific enough to guide teacher improvement but that it is essential to present the information to the faculty in conjunction with individual discussions.
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10.1097/00001888-198706000-00006
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14523385
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Roles of the NKG2D immunoreceptor and its ligands.
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According to present concepts, innate immunity is regulated by receptors that determine danger levels by responding to molecules that are associated with infection or cellular distress. NKG2D is, perhaps, the best characterized receptor that is associated with responses to cellular distress, defined as transformation, infection or cell stress. This review summarizes recent findings that concern NKG2D, its ligands, its signalling properties and its role in disease, and provides a framework for considering how the induction of immune responses can be regulated by cellular responses to injury.
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10.1038/nri1199
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2250993
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The pronator compression test revisited. A forgotten physical sign.
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Pronator compression testing is a valuable clinical feature of median nerve entrapment diagnosis. Of 10 patients with this disorder, all developed paresthesias preoperatively in the hand after 30 seconds or less of manual compression of the median nerve at or near the pronator muscle. Eight patients had a positive Tinel's sign at the impingement site, but only one patient had a positive electromyographic result. More than 50% of the patients had undergone previous carpal tunnel release or were diagnosed at presentation with double crush syndrome. All patients had a good or excellent result from surgical decompression of the median nerve in the forearm, except for one workers' compensation case who had excellent postoperative strength testing but multiple residual complaints. Pronator compression testing is a helpful and dependable physical sign in the diagnosis of pronator syndrome.
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39620950
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Biomimetic Cell Membrane Layers for the Detection of Insulin and Glucagon.
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The growing need for reliable and rapid insulin testing to enhance glycemic management has spurred intensive exploration of new insulin-binding bioreceptors and innovative biosensing platforms for detecting this hormone, along with glucagon, in biological samples. Here, by leveraging the native protein receptors on the HepG2 cell membrane, we construct a simple and chemical-free biomimetic molecular recognition layer for the detection of insulin and glucagon. Unlike traditional affinity sensors, which require lengthy surface modifications on the electrochemical transducers and use of two different capture antibodies to recognize each analyte, this new biomimetic sensing strategy employs a simple drop-casting of a natural cell membrane recognition layer onto the electrochemical transducer. This approach allows for the concurrent capture and detection of both insulin and glucagon. We investigate the presence of insulin and glucagon receptors on the HepG2 cell membrane and demonstrate its multiplexing bioelectronic sensing capabilities through the binding of the captured insulin and glucagon to enzyme-tagged signaling antibodies. This new molecular recognition layer offers highly sensitive simultaneous detection of insulin and glucagon under decentralized conditions, holding considerable promise for the management of diabetes and the development of diverse biomimetic diagnostic platforms.
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10.1021/acs.analchem.4c05347
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29201399
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Renewing focus on family planning service quality globally.
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Reducing the global unmet need for contraception is currently a priority for many governments, multi-lateral initiatives, non-governmental organizations, and donors. Evidence strongly suggests that the provision of quality family planning services can increase uptake, prevalence, and continuation of contraception. While an accepted framework to define the components of family planning service quality exists, translating this framework into assessment tools that are accessible, easily utilized, and valid for service providers has remained a challenge. We propose new approaches to improve the standardization and accessibility of family planning service quality assessment tools to simplify family planning service quality evaluation. With easier approaches to program evaluation, quality improvements can be performed more swiftly to help increase uptake and continuation of contraception to improve the health of women and their families.
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10.1186/s40834-016-0021-6
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38719175
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Downregulation of HHATL promotes cardiac hypertrophy via activation of SHH/DRP1.
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HHATL, previously implicated in cardiac hypertrophy in the zebrafish model, has emerged as a prioritized HCM risk gene. We identified six rare mutations in HHATL, present in 6.94 % of nonsarcomeric HCM patients (5/72). Moreover, a decrease of HHATL in the heart tissue from HCM patients and cardiac hypertrophy mouse model using transverse aortic constriction was observed. Despite this, the precise pathogenic mechanisms underlying HHATL-associated cardiac hypertrophy remain elusive. In this study, we observed that HHATL downregulation in H9C2 cells resulted in elevated expression of hypertrophic markers and reactive oxygen species (ROS), culminating in cardiac hypertrophy and mitochondrial dysfunction. Notably, the bioactive form of SHH, SHHN, exhibited a significant increase, while the mitochondrial fission protein dynamin-like GTPase (DRP1) decreased upon HHATL depletion. Intervention with the SHH inhibitor RU-SKI 43 or DRP1 overexpression effectively prevented Hhatl-depletion-induced cardiac hypertrophy, mitigating disruptions in mitochondrial morphology and membrane potential through the SHH/DRP1 axis. In summary, our findings suggest that HHATL depletion activates SHH signaling, reducing DRP1 levels and thereby promoting the expression of hypertrophic markers, ROS generation, and mitochondrial dysfunction, ultimately leading to cardiac hypertrophy. This study provides additional compelling evidence supporting the association of HHATL with cardiac hypertrophy. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
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10.1016/j.yexcr.2024.114072
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826923
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A mass fragmentographic method for the determination of chlorpromazine and two of its active metabolites in human plasma and CSF.
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A mass fragmentographic method for the quantitation of chlorpromazine (CPZ), mono-demethyl-chlorpromazine (nor1-CPZ), and 7-hydroxy-chlorpromazine (7-OH-CPZ) in plasma, cerebrospinal fluid, and tissues has been developed. The deuterated analogues of the compounds are used as internal standards. The high specificity was ascertained by multiple ion determination. The experimental error is below 10%. The sensitivity allows determination of sub ng quantities of CPZ per ml cerebrospinal fluid. The method has been applied to the analysis of drug concentrations in plasma and cerebrospinal fluid (CSF) of chlorpromazine-treated patients. The amount of CPZ in CSF was about 3% of the plasma level. The CPZ levels in plasma and CSF were significantly correlated.
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10.1007/BF00423250
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30594528
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Adrenergic and adenosinergic regulation of the cardiovascular system in an Antarctic icefish: Insight into central and peripheral determinants of cardiac output.
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Icefishes characteristically lack the oxygen-binding protein haemoglobin and therefore are especially reliant on cardiovascular regulation to augment oxygen transport when oxygen demand increases, such as during activity and warming. Using both in vivo and in vitro experiments, we evaluated the roles for adrenaline and adenosine, two well-established cardio- and vasoactive molecules, in regulating the cardiovascular system of the blackfin icefish, Chaenocephalus aceratus. Despite increasing cardiac contractility (increasing twitch force and contraction kinetics in isometric myocardial strip preparations) and accelerating heart rate (ƒ H ), adrenaline (5 nmol kg -1 bolus intra-arterial injection) did not significantly increase cardiac output (Q̇) in vivo because it elicited a large decrease in vascular conductance (G sys ). In contrast, and despite preliminary data suggesting a direct negative inotropic effect of adenosine on isolated atria and little effect on isolated ventricle strips, adenosine (500 nmol kg -1 ) generated a large increase in Q̇ by increasing G sys, a change reminiscent of that previously reported during both acute warming and invoked activity. Our data thus illustrate how Q̇ in C. aceratus may be much more dependent on peripheral control of vasomotor tone than direct regulation of the heart. Copyright © 2018 Elsevier Inc. All rights reserved.
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10.1016/j.cbpa.2018.12.012
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24114443
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Metabolic alteration in tumorigenesis.
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Altered metabolism in cancer was first discovered by Otto Warburg early last century. Although the Warburg Effect has been widely used in tumor detection, relatively little progress had been made in mechanistic understanding of cancer metabolism in the subsequent eight decades. Genetic studies have recently identified mutations in human cancer targeting multiple enzymes involved in intermediate metabolism. One emerging mechanism common to these mutant enzymes is the accumulation of a metabolite that alters the epigenetic control.
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10.1007/s11427-013-4549-2
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12807407
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Voluntary head movement and allocentric perception of space.
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Although visual input is egocentric, at least some visual perceptions and representations are allocentric, that is, independent of the observer's vantage point or motion. Three experiments investigated the visual perception of three-dimensional object motion during voluntary and involuntary motion in human subjects. The results show that the motor command contributes to the objective perception of space: Observers are more likely to apply, consciously and unconsciously, spatial criteria relative to an allocentric frame of reference when they are executing voluntary head movements than while they are undergoing similar involuntary displacements (which lead to a more egocentric bias). Furthermore, details of the motor command are crucial to spatial vision, as allocentric bias decreases or disappears when self-motion and motor command do not match.
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10.1111/1467-9280.14491
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16249279
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Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome.
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Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS). The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS. This was a prospective controlled study. The study was conducted at an academic medical center. The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese). Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (IS(OGTT)). ROS generation and p47(phox) protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion. IS(OGTT) was lower in PCOS, compared with controls (3.1 +/- 0.3 vs. 6.3 +/- 0.9, P < 0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 +/- 21.3 and 154.2 +/- 49.1 vs. 0.6 +/- 12.7, P < 0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P < 0.05), and plasma levels of testosterone (r = 0.59, P < 0.002) and androstenedione (r = 0.50, P < 0.009). The percent change in p47(phox) from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 +/- 18.2 and 39.1 +/- 8.0 vs. -13.7 +/- 8.7, P < 0.02), and correlated negatively with IS(OGTT) (r = -0.39, P < 0.05). ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.
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10.1210/jc.2005-1696
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4353380
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The heterogeneous distribution of acid hydrolases within a homogeneous population of cultured mammalian cells.
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1. Chinese-hamster ovary fibroblasts were cultured to provide a homogeneous cell population. Homogenates obtained from these cells were fractionated by centrifugation techniques and the resulting fractions were analysed for protein and for enzymes representative of certain subcellular particles. 2. Unlike those in rat liver homogenates, the mitochondrial and lysosomal populations proved impossible to separate by differential centrifugation owing to the similarity of their sedimentation properties. Their resolution was possible by using isopycnic centrifugation in a continuous sucrose density gradient. 3. The mitochondrial population equilibrated at a density of 1.17g. cm(-3) as in rat liver homogenates. However, the lysosomal population equilibrated at a lower rather than a higher density position than the mitochondria and the probable reasons for this are discussed. 4. The lysosomal population subdivided into two groups characterized by differences in acid hydrolase content and equilibrium densities. The fraction with a density of 1.15g. cm(-3) contained the majority of arylsulphatases A and B, of cathepsin and of beta-acetylglucosaminidase activities, whereas that with a density of 1.09g. cm(-3) contained the majority of the acid phosphatase and acid ribonuclease activities. The probable division of the lysosomal population of a single cell into a number of distinguishable subgroups is suggested.
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10.1042/bj1320493
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24443848
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Building the bacterial orisome: high-affinity DnaA recognition plays a role in setting the conformation of oriC DNA.
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During assembly of the E. coli pre-replicative complex (pre-RC), initiator DnaA oligomers are nucleated from three widely separated high-affinity DnaA recognition sites in oriC. Oligomer assembly is then guided by low-affinity DnaA recognition sites, but is also regulated by a switch-like conformational change in oriC mediated by sequential binding of two DNA bending proteins, Fis and IHF, serving as inhibitor and activator respectively. Although their recognition sites are separated by up to 90 bp, Fis represses IHF binding and weak DnaA interactions until accumulating DnaA displaces Fis from oriC. It remains unclear whether high-affinity DnaA binding plays any role in Fis repression at a distance and it is also not known whether all high-affinity DnaA recognition sites play an equivalent role in oligomer formation. To examine these issues, we developed origin-selective recombineering methods to mutate E. coli chromosomal oriC. We found that, although oligomers were assembled in the absence of any individual high-affinity DnaA binding site, loss of DnaA binding at peripheral sites eliminated Fis repression, and made binding of both Fis and IHF essential. We propose a model in which interaction of DnaA molecules at high-affinity sites regulates oriC DNA conformation. © 2014 John Wiley & Sons Ltd.
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10.1111/mmi.12525
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33809547
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The Feasibility Study of Hypofractionated Radiotherapy with Regional Hyperthermia in Soft Tissue Sarcomas.
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Management of marginally resectable or unresectable soft tissue sarcomas (STS) in patients who are not candidates for neoadjuvant chemotherapy due to chemoresistant pathology or contraindications remains a challenge. Therefore, in these indications, we aimed to investigate a feasibility of 10x 3.25 Gy radiotherapy combined with regional hyperthermia (HT) that could be followed by surgery or 4x 4 Gy radiotherapy with HT. We recruited patients with locally advanced marginally resectable or unresectable STS who (1) presented chemoresistant STS subtype, or (2) progressed after neoadjuvant chemotherapy, or (3) were unfit for chemotherapy. The primary endpoint was the feasibility of the proposed regimen. Thirty patients were enrolled. All patients received the first part of the treatment, namely radiotherapy with HT. Among them, 14 received the second part of radiotherapy with HT whereas 13 patients underwent surgery. Three patients did not complete the treatment protocol. The feasibility criteria were fulfilled in 90% of patients. Two patients developed distant metastases. One patient died due to distant progression. One patient developed rapid local recurrence after surgery. Hypofractionated radiotherapy with HT is a feasible treatment for marginally resectable or unresectable STS in patients who are not candidates for chemotherapy. Results of this clinical trial support the further validation of RT and HT combinations in STS.
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10.3390/cancers13061332
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12127580
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Activity and properties of alpha-L-fucosidase are dependent on the state of enterocytic differentiation of HT-29 colon cancer cells.
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Previously we have demonstrated an impairment in the activity of alpha-L-fucosidase in colon tumours. In order to establish an in vitro model to study this enzyme in colon cancer, we have determined the activity and properties of the enzyme during the differentiation of HT-29 colon cancer cells. Cultures were committed to differentiate into enterocyte-like cells by placing them in a culture medium without glucose for 18-21 days. The state of differentiation was evaluated by assaying the activity of enterocytic marker enzymes, and the acquisition of enterocyte morphology was assessed by electron microscopy. The alpha-L-fucosidase activity was determined using a fluorometric method. Intracellular levels of alpha-L-fucosidase activity are lower in non-differentiated cells (3.0 +/- 1.01 U/mg) than in differentiated ones (9.2 +/- 4.09 U/mg) (P < 0.001). This variation is not due to a greater secretion of the enzyme to the culture medium, and properties such as pH optimum or the affinity towards substrate are not dependent on differentiation. The enzyme however, is more stable at acidic pH and at high temperatures, and V(max) is higher in differentiated cells. Moreover, in undifferentiated cells the enzyme is mainly in a monomeric form whereas multimeric forms of the enzyme appear only upon differentiation. Most of these changes are very similar to those previously observed between normal colon tissue and colon tumours. Thus, we suggest that differentiation of HT-29 colon cancer cells could be used as a model to study the alterations of the enzyme alpha-L-fucosidase during the progression of the tumoural process. Copyright 2002 Elsevier Science Ltd.
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10.1016/s1357-2725(02)00067-5
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35037670
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Correction: Selective light driven reduction of CO 2 to HCOOH in water using a {MoV 9 } n ( n = 1332-3600) based soft-oxometalate (SOM).
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Correction for 'Selective light driven reduction of CO 2 to HCOOH in water using a {MoV 9 } n ( n = 1332-3600) based soft-oxometalate (SOM)' by Soumitra Barman et al., Chem. Commun., 2018, 54, 2369-2372, DOI: 10.1039/C7CC09520A.
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10.1039/d2cc90018a
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9210926
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Correlation of bovine viral diarrhoea virus induced cytopathic effects with expression of a biotype-specific marker.
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The purpose of this study was the identification antigenic differences between cytopathic (cp) and noncytopathic (ncp) bovine viral diarrhoea viruses (BVDV). Cells infected with 19 strains of each viral biotype were analyzed for reactivity with the monoclonal antibody (mab) BVD/C38. Reactivity was examined using an enzyme immunoassay on fixed infected monolayers of fetal calf kidney cells. In the majority of cases, the mab discriminated between cells infected with each of the two viral biotypes. Three reactivity patterns could be distinguished. Most cpBVDV strains yielded monolayers where 80-100% of infected cells reacted with the mab. Most of the ncpBVDV infected cells showed either no reaction, or only single cells of foci were stained. However, about one third of either cp- or ncpBVDV strains tested yielded infected monolayers where 30-50% of the cells reacted with the antibody. Cell damage other than the typical cytopathic effect might be responsible for the BVD/C38 reactivity of cells infected with BVDV. In addition, it was analyzed whether the antigenic marker associated with cpBVDV was expressed in cells infected with viral isolates from 21 animals with clinical mucosal disease. In 14 cases cpBVDV was isolated and the antigenic marker was found throughout. In seven cases ncpBVDV was cultivated and the antigenic marker was detected in four isolates.
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10.1007/978-3-7091-9153-8_7
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11981653
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Occupational respiratory hypersensitivity in dental personnel.
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The aim was to study the causes of respiratory hypersensitivity in dental personnel based on the statistics of the Finnish Register of Occupational Diseases (FROD; 1975-1998) and the patient material of the Finnish Institute of Occupational Health (FIOH; 1990-1998). Details about the cases of respiratory hypersensitivity were compiled from the FROD. The occupational rhinitis diagnoses studied at the FIOH were based on work-related symptoms and a change in the status of the nasal mucosa during challenge testing; and the diagnosis of occupational asthma based on reactions in challenge testing, or on IgE positivity and peak flow monitoring at work and during days off. A total of 64 cases of occupational respiratory diseases (ORDs) was diagnosed in dental personnel during 1975 to 1998 according to the FROD; two cases in 1975 to 1989, and 62 in 1990 to 1998. Twenty-eight cases were of occupational asthma (18 caused by methacrylates), 28 occupational rhinitis (six caused by methacrylates), seven allergic alveolitis and one organic dust toxic syndrome (ODTS). The non-acrylate-material diagnosed in 1990-1998 at the FIOH comprised three cases of asthma and one of rhinitis caused by chloramine-T (sodium- N-chlorine- p-toluene sulphonamide); as well as one case of asthma, seven cases of rhinitis, and two cases of combined rhinitis and conjunctivitis caused by natural rubber latex (NRL). Furthermore, one case of occupational rhinitis caused by Nobetec containing colophony was diagnosed. The incidence rate (IR) of ORD increased from 0 in 1988 to a peak of 105.1 new cases per 100,000 working years in 1995. During the last observation year, i. e. 1998, the IR was 55 new cases per 100,000 workers. The IR in dental personnel was lower than in the whole working population in Finland up until 1992, but since then has been greater than in the whole population, peaking in 1995 when the IR of dental personnel was 2.55 times greater than in the whole population. The present study shows the increasing frequency of respiratory hypersensitivity among dental personnel. Besides methacrylates, important causes of respiratory hypersensitivity are NRL and chloramine-T.
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10.1007/s00420-001-0302-4
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36968223
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A Phase I Trial of VEGF-A Inhibition Combined with PD-L1 Blockade for Recurrent Glioblastoma.
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The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy. Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells. A total of 12 patients (median age 64; range, 37-73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4-16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5-4.5 months). The decrease in MICA/MICB, γδT cells, and CD4 + T cell EMRA correlated with prolonged survival. Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease. Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI. © 2023 The Authors; Published by the American Association for Cancer Research.
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10.1158/2767-9764.CRC-22-0420
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21519530
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The clinical research center for depression study: baseline characteristics of a korean long-term hospital-based observational collaborative prospective cohort study.
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The Clinical Research Center for Depression (CRESCEND) study is a 9-year observational collaborative prospective cohort study for the clinical outcomes in participants with depressive disorders in Korea. In this study, we examined the baseline characteristics of the depressive participants as the hospital-based cohort. Participants were assessed using various instruments including the Clinical Global Impression scale, 17-item Hamilton Depression Rating Scale (HDRS-17), Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Social and Occupational Functioning Assessment Scale, Beck Depression Inventory-Second Edition, Scale for Suicide Ideation, and World Health Organization Quality of Life assessment instruments-abbreviated version. Also, personal histories of medical and psychiatric illnesses and the range of socio-epidemiologic and clinical data were collected from each participant. One thousand one hundred eighty three participants were recruited from 18 hospitals. The mean age of the participants was 47.9±15.9 year-old, 74.4% were female, 82.9% had been diagnosed of major depressive disorder, 40.9% were experiencing their first depressive episode, and 21.4% had a past history of suicide attempts. The majority (85.3%) of the participants were moderately to severely ill. The average HDRS-17 was 19.8±6.1. Significant gender differences at baseline were shown in age, education, marriage, employment, religion, and first depressive episode. The baseline findings in the CRESCEND study showed some different characteristics of depression in Korea, suggesting a possibility of ethnic and cultural factors in depression.
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10.4306/pi.2011.8.1.1
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37017312
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WhereWulff: A Semiautonomous Workflow for Systematic Catalyst Surface Reactivity under Reaction Conditions.
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This paper introduces WhereWulff, a semiautonomous workflow for modeling the reactivity of catalyst surfaces. The workflow begins with a bulk optimization task that takes an initial bulk structure and returns the optimized bulk geometry and magnetic state, including stability under reaction conditions. The stable bulk structure is the input to a surface chemistry task that enumerates surfaces up to a user-specified maximum Miller index, computes relaxed surface energies for those surfaces, and then prioritizes those for subsequent adsorption energy calculations based on their contribution to the Wulff construction shape. The workflow handles computational resource constraints such as limited wall-time as well as automated job submission and analysis. We illustrate the workflow for oxygen evolution reaction (OER) intermediates on two double perovskites. WhereWulff nearly halved the number of Density Functional Theory (DFT) calculations from ∼240 to ∼132 by prioritizing terminations, up to a maximum Miller index of 1, based on surface stability. Additionally, it automatically handled the 180 additional resubmission jobs required to successfully converge 120+ atoms systems under a 48-h wall-time cluster constraint. There are four main use cases that we envision for WhereWulff: (1) as a first-principles source of truth to validate and update a closed-loop self-sustaining materials discovery pipeline, (2) as a data generation tool, (3) as an educational tool, allowing users (e. g., experimentalists) unfamiliar with OER modeling to probe materials they might be interested in before doing further in-domain analyses, (4) and finally, as a starting point for users to extend with reactions other than the OER, as part of a collaborative software community.
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10.1021/acs.jcim.3c00142
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6280111
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Inhibition of the electrically induced release of [3H]dopamine by serotonin from superfused rat striatal slices.
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The effect of serotonin (5-hydroxytryptamine) on the electrically induced release of [3H]dopamine from superfused slices of the rat striatum has been studied. It was observed that serotonin produced a concentration dependent decrease in the field stimulation-induced release of [3H]dopamine with the threshold concentration being 10(-6) M or lower. Methysergide, in a concentration which did not alter the evoked release, antagonized the inhibitory effect of serotonin. The present results suggest that serotonin should be added to the list of endogenous substances that can influence dopaminergic transmission in the striatum.
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10.1016/0304-3940(82)90153-7
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24130374
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Clinical pharmacology training in India: Status and need.
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Clinical pharmacologists undertake many tasks, and this makes defining a curriculum challenging. This is especially so under the changing circumstances in developing countries, where clinical pharmacology has an expanding role. The clinical pharmacologist may be responsible for conducting ethical clinical trials, supporting the needs of the generic drug industry, providing access to safe, effective and affordable medicines, guiding their rational use, achieving millennium development goals, and supervising medicines management standards for hospital accreditation. Clinical pharmacologists, including those in developing countries, have a great opportunity to contribute to public health and the growth of pharmaceutical industry, but at present, less clinical research is undertaken and fewer clinical trials are done than might be expected. Here we review clinical pharmacology training in India, consider the needs of different professionals contributing to clinical research and medicines utilization, and suggest ways in which current programs can be modified and new programs started. The conclusions are relevant to clinical pharmacology in both the developing and the developed world.
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10.4103/0253-7613.117718
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9602026
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Genomic structure of Unp, a murine gene encoding a ubiquitin-specific protease.
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The murine Unp gene encodes a ubiquitin-specific protease, a member of a family of enzymes that includes the product of the human tre-2 oncogene. The Unp gene has previously been mapped to chromosome 9. We have cloned in bacteriophage a 50 kilobase region of chromosome 9 containing the Unp gene, and have determined the nucleotide sequence of the gene. The gene has 22 exons, distributed over 47.4 kb. A processed ribosomal S2 pseudogene was identified in the third intron of the Unp gene. Expression of Unp is driven by a GC-rich, 'housekeeping' type promoter. Copyright 1998 Elsevier Science B. V. All rights reserved.
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10.1016/s0167-4781(98)00035-9
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24284386
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Differential expression of vascular smooth muscle-modulating microRNAs in human peripheral blood mononuclear cells: novel targets in essential hypertension.
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Vascular smooth muscle cell (VSMC) phenotypic plasticity has a critical role in the pathophysiology of arterial remodeling in essential hypertension. MicroRNAs are emerging as potential biomarkers and therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-143, miR-145, miR-21, miR-133 and miR-1, which are implicated in VSMC phenotypic modulation, in 60 patients with essential hypertension and 29 healthy individuals. All patients underwent 24-h ambulatory blood pressure (BP) monitoring. MicroRNA levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed lower miR-143 (2.20±0.25 versus 4.19±0.57, P<0.001), miR-145 (13.51±1.73 versus 22.38±3.31, P=0.010) and miR-133 (8.15±1.32 versus 37.03±8.18, P<0.001) and higher miR-21 (3.08±0.32 versus 2.06±0.31, P=0.048) and miR-1 (33.94±5.19 versus 12.35±2.13 P=0.006) expression levels compared with controls. In hypertensive patients, we observed correlations of miR-143 (r = -0.380, P=0.003), miR-145 (r=-0.405, P=0.001), miR-21 (r=-0.486, P<0.001) and miR-133 (r=0.479, P<0.001) expression levels with 24-h diastolic BP. Furthermore, we observed correlations of miR-21 (r=-0.291, P=0.024), miR-1 (r=-0.312, P=0.015) and miR-133 (r=0.310, P=0.016) levels with the dipping status. Associations of miR-143 (r=-0.292, P=0.025), miR-145 (r=-0.399, P=0.002), miR-21 (r=-0.343, P=0.008) and miR-133 (r=0.370, P=0.004) levels with 24-h mean pulse pressure were also found. Our data provide important evidence that VSMC-modulating microRNAs are closely related to essential hypertension in humans and they may represent potential therapeutic targets in essential hypertension.
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10.1038/jhh.2013.117
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31004298
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The relation between stressful life events and breast cancer: a systematic review and meta-analysis of cohort studies.
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Breast cancer is the most common cancer among women with high rate of mortality. This systematic review and meta-analysis was conducted to investigate the relation between stressful life events and breast cancer. We searched PubMed, Scopus, ScienceDirect, and Google scholar databases from their inception until June 2018. The keywords and phrases we used in the search were (life events AND stress AND breast cancer OR neoplasm) to identify potentially relevant cohort studies that reported relative risk estimates and confidence intervals of this association. Pooled Risk ratio and 95% confidence intervals (CIs) were calculated using random effects model. Out of 168 potentially relevant publications, 11 documents met the inclusion criteria. The results showed that history of stressful life events slightly increases the risk of breast cancer [pooled Risk Ratio: 1.11 (95% CI 1.03 to 1.19)]. History of stressful life events could be associated with a moderate increase in the risk of breast cancer. We advise that receiving psychological and counseling services after occurrence of stressful life events of women should be taken seriously.
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10.1007/s10549-019-05231-x
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33571748
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Supplementing pregnant Merino ewes with caffeine to improve neonatal lamb thermoregulation and viability.
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Percentages of lamb mortalities prior to weaning are a significant and persistent problem for the Australian sheep industry. Maternal caffeine supplementation reduced stillbirths and improved viability in piglets; however, the efficacy of caffeine in enhancing viability and lamb survival is equivocal. The aim of this study was to determine the optimal concentration and duration of maternal caffeine supplementation to improve lamb viability; time to stand and suck with consumption of colostrum occurring, as well as survival to weaning. Multiparous Merino ewes were supplemented with either 0 (CTL), 10 (C10) or 20 mg/kg (C20) body weight (BW) caffeine in feed after day 120 of gestation (dG), or 20 mg/kg BW (LC20) caffeine from dG 142 until parturition. Ewes were housed indoors in individual lambing pens from dG 130 to 72 -h post-partum (pp). Values for pp ewe and lamb variables were analysed using a generalised linear mixed model in IBM SPSS version 25. While ewes within the CTL, C10 and LC20 groups consumed more caffeine compared to C20 ewes (P = 0.001), lambs of C20 ewes had greater rectal temperatures at 20 -h pp (P = 0.021), greater 4 -h serum IgG concentrations (P = 0.041), a longer latency to first sucking bout (P = 0.030), and a greater number of sucking attempts (P = 0.044) compared to lambs from CTL, C10 and LC20 ewes. These results indicate that caffeine supplementation during late-gestation stimulates neonatal lambs as a result of increased sucking (4 -h serum IgG) and increased temperatures within the first 24 -h. Copyright © 2021 Elsevier B. V. All rights reserved.
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10.1016/j.anireprosci.2021.106715
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26612762
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The classification of hospitalized patients with hyperglycemia and its implication on outcome: results from a prospective observational study in Internal Medicine.
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The relevance of classifying hyperglycemic hospitalized subjects (HS) as known diabetes (D), newly discovered diabetes (ND), and stress hyperglycemia (SH) is unclear. The aim of this study was to determine the prevalence, in-hospital mortality, and length of stay (LOS) of three different phenotypes of HS. Fasting glucose ≥126 mg/dL (7 mmol/L) or random blood glucose ≥200 mg/dL (11.1 mmol/L) defined HS who were categorized into three groups: D; ND (no history of diabetes and HbA1c ≥48 mmol/mol); SH (no history of diabetes and HbA1c <48 mmol/mol). The end points of the study were in-hospital mortality and LOS. Of 1447 consecutive enrolled subjects, the prevalence of HS was 28.6 % (415/1447), of these 71.6 % had D, 21.2 % SH, and 7.2 % ND, respectively. In-hospital death was 3.9 % in normoglycemic and 6.0 % in hyperglycemic subjects. Individuals with SH had an increased risk of in-hospital death (7.9 %) (HR 2.17, 95 % CI 1.18-4.9; p = 0.039), while this was not observed for D and ND patients. The mean LOS was greater in ND and SH subjects. Hyperglycemia is common, and is associated with an increased risk of in-hospital mortality and extension of hospital stay. HbA1c along with clinical history is a useful tool to identify subgroups of hyperglycemic hospitalized subjects. Individuals with SH have a longer LOS, and a double risk of in-hospital mortality. Additionally, identifying previously unknown diabetes represents a remarkable opportunity for prevention of diabetes-related acute and chronic complications.
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10.1007/s11739-015-1358-6
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11192954
|
Home-based exercise is capable of preserving hospital-based improvements in severe chronic obstructive pulmonary disease.
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We examined the feasibility of home-based walking training to maintain the benefits of a short-term exercise training in patients with severe chronic obstructive pulmonary disease (COPD). After initial recovery from an exacerbation, 46 patients were randomized into a training and a control group, and 30 patients completed the programme (mean +/- SD FEV1, 36 +/- 7% predicted). The training group performed a 10-day walking training programme in the hospital, followed by a 6-month programme of supervised walking training at home, integrated into daily activities. The control group did not have exercise training in the hospital or at home. Until 6 months after discharge, lung function, exercise performance and symptom scores were assessed. Six-minute walking distance in the training group improved from day 1 to day 10 (P<0.001) and this effect was maintained over 6 months (P<0.001). On average, daily walking distance at home was 2308 m and walking was reported on 157 days. Quality of life (QoL) scores changed significantly over 6 months (P<0.001). The control group showed no significant changes in exercise performance or QoL scores throughout the whole study period. Therefore, (i) significant improvements in exercise performance and Chronic Respiratory Disease Questionnaire (CRQ) scores could be achieved after recovery from an exacerbation and (ii) these improvements were maintained after discharge, when supported by a home-based walking training.
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10.1053/rmed.2000.0949
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8545529
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Differential cholinergic regulation in Alzheimer's patients compared to controls following chronic blockade with scopolamine: a SPECT study.
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The effects of low-dose chronic scopolamine on measures of cerebral perfusion and muscarinic receptors were tested in eight Alzheimer's disease (AD) subjects and eight elderly controls. Single photon emission computed tomography (SPECT) scans using technetium-labelled hexamethypropylene amine oxide (99mTc-HMPAO) to measure cerebral perfusion before and after chronic scopolamine revealed a significant 12% increase in the normal controls (P < 0.01) while the AD subjects showed no significant change. In contrast, the controls showed decreased muscarinic binding as evidenced by 123I-quinuclidinyl-4-iodobenzilate (123I-QNB) labelling after chronic drug (-10%, P < 0.01) whereas the AD subjects showed increased 123I-QNB labelling (+8%, P < 0.05). The difference between AD and control subjects was even more marked when the ratio of I-QNB to HMPAO uptake was compared, pointing to a double dissociation in the SPECT results. These data cannot be explained by group differences in cerebral perfusion alone and suggest a differential sensitivity between AD and elderly controls to chronic cholinergic blockade.
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10.1007/BF02245634
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2434764
|
Clinical studies with a vascular vasopressin antagonist.
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The effect of circulating arginine vasopressin (AVP) on blood pressure, heart rate, and skin blood flow was assessed in normotensive subjects, mild hypertensive patients, and patients with congestive heart failure, utilizing the specific antagonist of AVP at the vascular receptor level, d(CH2)5Tyr(Me)AVP (5 micrograms/kg i. v.). The renin system of the normal volunteers treated with the AVP antagonist was either intact or acutely blocked with the angiotensin converting-enzyme inhibitor captopril (25 mg p. o.). In some volunteers, the cardiovascular effect of AVP released by Finnish sauna or cigarette smoking was studied. In patients with congestive heart failure, hemodynamic measurements (pressures and cardiac output) were obtained invasively. Acute blockade of AVP vascular receptors produced no cardiovascular effect unless plasma AVP levels were markedly elevated. In our experience, abnormally high circulating AVP appears to be responsible for the decrease in skin blood flow induced by cigarette smoking and to some extent for the maintenance of vascular tone in the rare patients with particularly severe congestive heart failure.
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10.1097/00005344-198600087-00022
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39699626
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An updated examination of gender differences in sexual harassment perception: A meta-analysis and a survey study.
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Twenty years ago, Rotundo et al. (2001) meta-analyzed the gender differences in sexual harassment (SH) perception. They found an overall d of 0.30: Women are more likely than men to label certain behaviors as SH. Much has changed since then, including the increased social awareness and the prevalence of SH training. Given the prevalence of SH in the workplace and the importance of SH perception in SH research, we conducted a mixed-methods research program to explore possible changes in the gender gap. In Study 1 (k = 72, N = 27,767), we meta-analyzed the perceptual gender differences to compare with those in Rotundo et al. and examined several moderators of the differences. We found an overall mean d of 0.33, implying a similar gender gap in SH perception as 20 years ago, yet none of the moderators examined in this study showed significant results. In Study 2, we empirically examined gender differences in mean levels of SH perception using the same measurement scales used in two older studies and compared with the differences found in these two studies. We found higher levels of SH perception for both men and women, but no difference in the mean d between men and women, suggesting that no change over time in mean d does not mean no change in SH perception. The implications of our findings are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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10.1037/ocp0000391
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34359490
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Eco-Efficiency of the Fisheries Value Chains in the Gambia and Mali.
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The Gambian and Malian fisheries and fish processing value chains are predominantly artisanal and represent a key source of protein and livelihoods, yet their eco-efficiency has not been studied to date. A Life Cycle Assessment was used to estimate the associated environmental impacts of those value chains and provide information on the eco-efficiency indicators, which relate technical efficiencies to environmental impacts. The results showed that industrial Gambian fleets' fuel use efficiency is rather low as compared with the global mean fuel use intensity (landed fish/consumed fuel) for both small pelagics and demersal fish. In Mali, the fuel use intensity of motorised artisanal fisheries is lower than the mean values for artisanal inland fisheries in developing countries, but the important increase of frozen imported fish from fish farming multiplies the estimated impacts by four. The least energy-intensive fisheries (cast nets and stow nets in Gambia and opportunistic fishers in Mali) feature better eco-efficiency scores. Based on the identified sources of inefficiencies, we suggest improvements in the landing/processing infrastructure and fishing units' engines, coupled with technical and business training and improved processing methods, to ameliorate seafood eco-efficiency and a stronger recognition of the importance of the artisanal fisheries subsector to overcome challenges and improving resource management.
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10.3390/foods10071620
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39074816
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Efficacy of verdinexor for the treatment of naïve canine epitheliotropic cutaneous T-cell lymphoma: An open-label pilot study.
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Verdinexor (Laverdia-CA1; Dechra Veterinary Products), a selective inhibitor of nuclear export, has been utilised for treatment of non-Hodgkin T-cell lymphoma in dogs. However, the efficacy of verdinexor has not been evaluated for cutaneous epitheliotropic T-cell lymphoma (CETL). To evaluate the efficacy of verdinexor for the treatment of CETL. Eight client-owned animals with CETL. Patients received between 1.28 and 1.45 mg/kg verdinexor per os twice weekly with a minimum of 72 h between doses until disease progression or voluntary withdrawal. Adjunctive therapy with lokivetmab or prednisone was permitted after Day (D)14. Assessment of clinical lesions (canine Response Evaluation Criteria in Solid Tumors [cRECIST v1.0] and novel Canine Epitheliotropic Lymphoma Extent and Severity Index [CELESI]), pruritus (Visual Analog Scale) and treatment efficacy (owner global assessment of treatment efficacy [OGATE]) were evaluated every 14 days for 3 months, then monthly thereafter (mean 70 ± 43.4 days). Seventy-five percent of patients achieved complete response, partial response or stable disease. The mean time to disease progression was 56 ± 41 days. There was a significant reduction (p = 0.026) in total CELESI score when the lowest score for each dog was compared to their score at D0. Verdinexor did not significantly reduce pruritus at any time point (p = 0.45), including when given as a monotherapy or concurrently with lokivetmab ± glucocorticoids. On D28, 75% of owners rated response to treatment as 'fair' to 'excellent'. The most common adverse effects included weight loss, inappetence, vomiting and lethargy. Verdinexor could be considered a safe, palliative treatment for canine CETL. © 2024 ESVD and ACVD.
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10.1111/vde.13280
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12465113
|
Band artifacts due to bulk motion.
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Band artifacts due to bulk motion were investigated in images acquired with fast gradient echo sequences. A simple analytical calculation shows that the width of the artifacts has a square-root dependence on the velocity of the imaged object, the time taken to acquire each line of k-space and the field of view in the phase-encoding direction. The theory furthermore predicts that the artifact width can be reduced using parallel imaging by a factor equal to the square root of the acceleration parameter. The analysis and results are presented for motion in the phase- and frequency-encoding directions and comparisons are made between sequential and centric ordering. The theory is validated in phantom experiments, in which bulk motion is simulated in a controlled and reproducible manner by rocking the scan table back and forth along the bore axis. Preliminary cardiac studies in healthy human volunteers show that dark bands may be observed in the endocardium in images acquired with nonsegmented fast gradient echo sequences. The fact that the position of the bands changes with the phase-encoding direction suggests that they may be artifacts due to motion of the heart walls during the image acquisition period. Copyright 2002 Wiley-Liss, Inc.
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10.1002/mrm.10314
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8670406
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The Argentine Precordillera: A Traveler from the Ouachita Embayment of North American Laurentia
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The Argentine Precordillera is a continental fragment rifted from the Ouachita embayment of the southern margin of Laurentia (North America) during Cambrian time [about 515 million years ago (Ma)] and accreted to the western margin of Gondwana (South America) during Ordovician time (about 455 Ma). Similarities of Cambrian stratigraphic successions and faunas, Grenville basement rocks, and dimensions link the Argentine Precordillera to the Ouachita embayment. Evidence of rifting during Cambrian time and of a wide ocean basin during Ordovician time indicates that the Precordillera traveled as an independent microcontinent to collide with Gondwana.
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10.1126/science.273.5276.752
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21787222
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The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus.
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by a defect in immune tolerance and exacerbated by both the innate and adaptive arms of the immune response. SLE-associated immune hyperactivity can be detected systemically as elevations in levels of cytokines along with their upregulated receptors expressed by hematopoietic cells. Importantly, increased levels of cytokines and their receptors can be observed in target organs, and it is clear that they have important roles in disease pathogenesis. Recent therapeutic strategies have focused on proximal cytokines, such as interferon-α, interleukin (IL)-1, IL-6, and tumor necrosis factor as a result of the efficacious use of biologic agents for intervention in rheumatoid arthritis and other autoimmune diseases. Despite the recent advances in understanding the cytokine networks involved in autoimmune diseases and more specifically in SLE, the diagnosis and prognosis of lupus remain a challenge. Lupus is heterogeneous and unpredictable; moreover, the frequency and severity of flares can be difficult to determine and treat. A better understanding of the regulation of expression of key cytokines and their receptors can likely provide important clues to the pathogenic mechanisms underlying specific forms of SLE, and pave the way toward more effective therapeutics.
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10.1089/jir.2011.0047
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25877041
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Water response to intense electric fields: A molecular dynamics study.
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This paper investigated polarization properties of water molecules in close proximity to an ionic charge in the presence of external electric fields by using an approach based on simulations at the atomic level. We chose sodium and chloride ions in water as examples of dilute ionic solutions and used molecular dynamics simulations to systematically investigate the influence of an external static electric field on structural, dipolar, and polarization properties of water near charged ions. Results showed that a threshold electric field higher than 10(8) V/m is needed to affect water polarization and increase mean dipole moment of water molecules close to the ion. A similar threshold holds for water permittivity profiles, although a field 10× higher is needed to ensure that water permittivity is almost constant independently of the position close to the ion. Electric fields of such intensities can greatly enhance polarizability of water in hydration shells around ions. © 2015 Wiley Periodicals, Inc.
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10.1002/bem.21916
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26073997
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Effects of GLC7 and REG1 deletion on maltose metabolism and leavening ability of baker's yeast in lean dough.
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Maltose metabolism and leavening ability of baker's yeast (Saccharomyces cerevisiae) in lean dough is negatively influenced by glucose repression. To improve maltose metabolism and leavening ability, it is necessary to alleviate glucose repression. In this study, we focus on the effects of regulators (GLC7 encoding the catalytic and REG1 encoding the regulatory subunits of protein phosphatase type 1) of glucose repression on maltose metabolism and leavening ability of baker's yeast in lean dough. To this end, GLC7 and/or REG1 deletions were constructed and characterized in terms of the growth characteristics, maltose metabolism, leavening ability, and enzyme activities. The results suggest that GLC7 and/or REG1 deletions increased maltose metabolism and leavening ability at different level with glucose derepression and increased enzymes (maltase and maltose permease) activities. In a medium containing glucose and maltose, at the point of glucose exhaustion the maltose metabolized and the leavening ability were increased 59.3% and 23.1%, respectively, in the case of a REG1 single gene deletion. Copyright © 2015 Elsevier B. V. All rights reserved.
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10.1016/j.jbiotec.2015.06.386
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12837710
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Results of repeat sigmoidoscopy 3 years after a negative examination.
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The necessary frequency of endoscopic colorectal cancer screening after a negative examination is uncertain. To examine the yield of adenomas and cancer in the distal colon found by repeat flexible sigmoidoscopy (FSG) 3 years after a negative examination. Participants were drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a randomized, controlled community-based study of cancer screening. The mean (SD) age was 65.7 (4.0) years at study entry (1993-1995) and 61.6% were men. Individuals underwent screening FSG at baseline and at 3 years as part of the protocol and were referred to their personal physicians for further evaluation of screen-detected abnormalities. Results from subsequent diagnostic evaluations were tracked in a standardized fashion. Of 11 583 eligible for repeat screening FSG 3 years after an initial negative examination, 9317 (80.4%) returned. Polyp or mass detection in distal colon at year 3 repeat FSG; incidence of adenoma or cancer in distal colon at year 3 examination; determination of reason for detection (increased depth of insertion or improved preparation at the year 3 examination or detection in a previously examined area). A total of 1292 returning participants (13.9%) had a polyp or mass detected by FSG 3 years after the initial examination. In the distal colon, 3.1% (292/9317) were found to have an adenoma or cancer. The incidence of advanced adenoma (n = 72) or cancer (n = 6) in the distal colon was 78 (0.8%) of 9317. Of individuals with advanced distal adenomas detected at the year 3 examination, 80.6% (58/72) had lesions found in a portion of the colon that had been adequately examined at the initial sigmoidoscopy. Repeat FSG 3 years after a negative examination will detect advanced adenomas and distal colon cancer. Although the overall percentage with detected abnormalities is modest, these data raise concern about the impact of a prolonged screening interval after a negative examination.
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10.1001/jama.290.16.2123-b
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17906199
|
Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced cancer.
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Standard treatment for advanced non-small-cell lung cancer (NSCLC) includes the use of a platinum-based chemotherapy regimen. However, response rates are highly variable. Newer agents, such as pemetrexed, have shown significant activity as second-line therapy and are currently being evaluated in the front-line setting. We utilized a genomic strategy to develop signatures predictive of chemotherapeutic response to both cisplatin and pemetrexed to provide a rational approach to effective individualized medicine. Using in vitro drug sensitivity data, coupled with microarray data, we developed gene expression signatures predicting sensitivity to cisplatin and pemetrexed. Signatures were validated with response data from 32 independent ovarian and lung cancer cell lines as well as 59 samples from patients previously treated with cisplatin. Genomic-derived signatures of cisplatin and pemetrexed sensitivity were shown to accurately predict sensitivity in vitro and, in the case of cisplatin, to predict treatment response in patients treated with cisplatin. The accuracy of the cisplatin predictor, based on available clinical data, was 83.1% (sensitivity, 100%; specificity 57%; positive predictive value, 78%; negative predictive value, 100%). Interestingly, an inverse correlation was seen between in vitro cisplatin and pemetrexed sensitivity, and importantly, between the likelihood of cisplatin and pemetrexed response in patients. The use of genomic predictors of response to cisplatin and pemetrexed can be incorporated into strategies to optimize therapy for advanced solid tumors.
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10.1200/JCO.2007.11.0593
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29382134
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Phage-Bacterial Dynamics with Spatial Structure: Self Organization around Phage Sinks Can Promote Increased Cell Densities.
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Bacteria growing on surfaces appear to be profoundly more resistant to control by lytic bacteriophages than do the same cells grown in liquid. Here, we use simulation models to investigate whether spatial structure per se can account for this increased cell density in the presence of phages. A measure is derived for comparing cell densities between growth in spatially structured environments versus well mixed environments (known as mass action). Maintenance of sensitive cells requires some form of phage death; we invoke death mechanisms that are spatially fixed, as if produced by cells. Spatially structured phage death provides cells with a means of protection that can boost cell densities an order of magnitude above that attained under mass action, although the effect is sometimes in the opposite direction. Phage and bacteria self organize into separate refuges, and spatial structure operates so that the phage progeny from a single burst do not have independent fates (as they do with mass action). Phage incur a high loss when invading protected areas that have high cell densities, resulting in greater protection for the cells. By the same metric, mass action dynamics either show no sustained bacterial elevation or oscillate between states of low and high cell densities and an elevated average. The elevated cell densities observed in models with spatial structure do not approach the empirically observed increased density of cells in structured environments with phages (which can be many orders of magnitude), so the empirical phenomenon likely requires additional mechanisms than those analyzed here.
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10.3390/antibiotics7010008
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28155636
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Spectra library assisted de novo peptide sequencing for HCD and ETD spectra pairs.
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De novo peptide sequencing via tandem mass spectrometry (MS/MS) has been developed rapidly in recent years. With the use of spectra pairs from the same peptide under different fragmentation modes, performance of de novo sequencing is greatly improved. Currently, with large amount of spectra sequenced everyday, spectra libraries containing tens of thousands of annotated experimental MS/MS spectra become available. These libraries provide information of the spectra properties, thus have the potential to be used with de novo sequencing to improve its performance. In this study, an improved de novo sequencing method assisted with spectra library is proposed. It uses spectra libraries as training datasets and introduces significant scores of the features used in our previous de novo sequencing method for HCD and ETD spectra pairs. Two pairs of HCD and ETD spectral datasets were used to test the performance of the proposed method and our previous method. The results show that this proposed method achieves better sequencing accuracy with higher ranked correct sequences and less computational time. This paper proposed an advanced de novo sequencing method for HCD and ETD spectra pair and used information from spectra libraries and significant improved previous similar methods.
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10.1186/s12859-016-1330-0
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23099740
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[Men, health and public policies: gender equality in question].
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The scope of this article is to pose questions on the theme of Men, Health and Public Policies to render debate on the subject viable, based on theoretical and empirical references related to these issues. Initially, some historical landmarks on the theme are presented to provide guidelines for debate. An overview of the gender agenda in public policies is then presented to introduce the discussion about the inclusion of a gender perspective in healthcare policies. After this discussion, queries are raised about whether or not policies geared to men's health promote gender equality. In the closing remarks, the complexity involved in the development, implementation and evaluation of health policies aimed at gender equality is highlighted. The need for the Brazilian policy geared towards men's health to be implemented with other policies such that the gender matrix is transversal in the healthcare field is also stressed.
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10.1590/s1413-81232012001000002
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25525422
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Synthesis, Spectroscopic, Molecular Structure, and Antibacterial Studies of Dibutyltin(IV) Schiff Base Complexes Derived from Phenylalanine, Isoleucine, and Glycine.
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New series of organotin(IV) complexes and Schiff bases derived from amino acids have been designed and synthesized from condensation of 1H-indole-2,3-dione, 5-chloro-1H-indole-2,3-dione, and α-amino acids (phenylalanine, isoleucine, and glycine). All compounds are characterized by elemental analyses, molar conductance measurements, and molecular weight determinations. Bonding of these complexes is discussed in terms of their UV-visible, infrared, and nuclear magnetic resonance ((1)H, (13)C, and (119)Sn NMR) spectral studies. The results suggest that Schiff bases behave as monobasic bidentate ligands and coordinate with dibutyltin(IV) in octahedral geometry according to the general formula [Bu2Sn(L)2]. Elemental analyses and NMR spectral data of the ligands with their dibutyltin(IV) complexes agree with their proposed distorted octahedral structures. Few representative compounds are tested for their in vitro antibacterial activity against Gram-positive (B. cereus, Staphylococcus spp.) and Gram-negative (E. coli, Klebsiella spp.) bacteria. The results show that the dibutyltin complexes are more reactive with respect to their corresponding Schiff base ligands.
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10.1155/2014/716578
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25720528
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Allergenicity of pasteurized whole raw Hen's egg compared with fresh whole raw Hen's egg.
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Oral food challenges for diagnosis and management of egg allergy using fresh egg are common; however, to limit the risk of foodborne infection, many allergy units use pasteurized raw egg. Pasteurization and drying processes have the potential to affect the structure of egg proteins in egg powder and thus the allergenicity when compared to fresh egg. Our aim was to compare the binding of serum IgE from egg-allergic children to in vitro digested and undigested pasteurized whole raw egg powder with unpasteurized fresh whole raw egg. Egg proteins from in vitro digested or undigested pasteurized whole raw egg powder, fresh whole egg, egg white and egg yolk were separated by SDS-PAGE, transferred onto nitrocellulose membrane and incubated overnight with pooled sera from egg-allergic children. In both the raw egg samples and the pasteurized whole egg powder, protein bands corresponding to known molecular weights of the major egg allergens were present. Pasteurized whole raw egg powder was bound by serum IgE in a similar manner to unpasteurized whole raw egg and was unaffected by in vitro digestion. Serum IgE also bound egg yolk, indicating sensitization to both egg yolk and egg white proteins. The main egg allergens are present in pasteurized whole raw egg powder, and serum IgE of egg-allergic children binds to them in a similar pattern to those in fresh whole raw egg. Pasteurized whole raw egg powder is a suitable substitute for raw egg in clinical practice for oral food challenges. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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10.1111/pai.12365
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15788805
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Monitoring health inequalities through general practice: the Second Dutch National Survey of General Practice.
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For the second time a plan to monitor public health and health inequalities in the Netherlands through general practice was put into action: the Second National Survey of General Practice (DNSGP-2, 2001). The first aim of this paper is to describe the general design of DNSGP-2. Secondly, to describe self assessed health inequalities in the Netherlands. Thirdly, to present differences in prevalence of chronic conditions by educational attainment using both self-assessed health and medical records of GPs. Finally, inequalities in 1987 (DNSGP-1) and 2001 will be compared. Data were collected from 96 (1987) and 104 (2001) general practices. The data include background information on patients collected via a census, approximately 12,000 health interview surveys per time point and more than one million recorded contacts of patients with their GPs in both years. The method of statistical analysis is logistic regression. The analyses shows that the lower educated have significantly higher odds of feeling unhealthy and having chronic conditions in 2001. Diabetes and myocardial infarction (GP data) showed the largest difference in prevalence between educational groups (OR 2.5 and 2.4, self-reported data). The way the data is collected (self-assessment versus GP registration) hardly affects the magnitude of the educational differences in the prevalence of chronic conditions. The pattern of health inequalities across chronic conditions in 1987 and 2001 hardly differs. Diabetes doubled in prevalence and health inequalities were not significant in 1987, but compared to the other conditions were largest in 2001 (OR 1.1 versus 2.5). Health inequalities were shown to be substantial in 2001 and persistent over time. Socio-economic differences were shown to be similar using self-assessed health data and GP data. Hence, a person's educational attainment did not appear to play a part in presenting health problems to the GP.
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10.1093/eurpub/cki116
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24476142
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The way we teach: basic clinical skills.
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At the University of Adelaide Medical School, students are given additional intensive training in basic clinical skills during a six-week period in the fifth year. The course includes history-taking, physical examination, decision making and problem solving. Teaching activities are based predominantly on a preceptor system, backed by small-group sessions and by activities designed to encourage habits of self-learning. Assessment is competence based: staff attempt to compare students' performance with the objectives of the programme and decide whether or not they have achieved the desired standard. The course attracts positive ratings from students and retains the support of staff.
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10.3109/01421598209034740
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35946330
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Risk factors associated with cardiovascular mortality among gastric cancer patients: a population-based analysis.
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Cancer patients were found at a high risk of death from cardiovascular disease. This study aims to assess cardiovascular mortality risk and identify the potential risk factors associated with cardiovascular mortality among gastric cancer patients. Gastric cancer patients were collected from the Surveillance Epidemiology and End Results database during 1975-2016. Standardized mortality ratios were calculated to compare cardiovascular mortality rates between gastric cancer patients and the general US population. Univariable Cox analysis and multivariable stepwise Cox analysis were adopted to identify the potential risk factors for cardiovascular disease death after gastric cancer diagnosis. There were 10 886 cardiovascular disease deaths identified among 165 433 individuals with gastric cancer observed for 410207.20 person-years. Gastric cancer patients were at a higher cardiovascular disease mortality risk (standardized mortality ratio = 3.35, 95% confidence interval: 3.24-3.47, P 80 years vs. 0-69 years, hazard ratio = 7.05, 95% confidence interval: 6.66-7.46, P < 0.001; 70-80 years vs. 0-69 years, hazard ratio = 3.35, 95% confidence interval: 3.19-3.53, P < 0.001), male sex (vs. female, hazard ratio = 1.39, 95% confidence interval: 1.33-1.45, P < 0.001), black race (vs. white, hazard ratio = 1.31, 95% confidence interval: 1.24-1.38, P < 0.001), without a partner (divorced/separated vs. married/partnered, hazard ratio = 1.35, 95% confidence interval: 1.25-1.45, P < 0.001; single vs. married/partnered, hazard ratio = 1.20, 95% confidence interval: 1.12-1.29, P < 0.001; widowed vs. married/partnered, hazard ratio = 1.41, 95% confidence interval: 1.34-1.48, P < 0.001), living in the northern plains (vs. pacific coast, hazard ratio = 1.23, 95% confidence interval: 1.16-1.29, P < 0.001) and surgery not performed (vs. performed, hazard ratio = 1.70, 95% confidence interval: 1.61-1.79, P < 0.001) were significantly associated with increased risk of cardiovascular disease death. Compared with patients with localized stage, distant staged patients were less likely to die of cardiovascular disease (hazard ratio = 0.88, 95% confidence interval: 0.83-0.94, P < 0.001). Gastric cancer patients were at an increased risk of cardiovascular disease death. Older age at diagnosis, male sex, black race, without a partner, living in the northern plains and surgery not performed were significantly associated with cardiovascular disease death after gastric cancer diagnosis. © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals. permissions@oup. com.
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10.1093/jjco/hyac132
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15871253
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Spatial variability and uncertainty in ecological risk assessment: a case study on the potential risk of cadmium for the little owl in a Dutch river flood plain.
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This paper outlines a procedure that quantifies the impact of different sources of spatial variability and uncertainty on ecological risk estimates. The procedure is illustrated in a case study that estimates the risks of cadmium for a little owl (Athene noctua vidalli) living in a Dutch river flood plain along the river Rhine. A geographical information system (GIS) was used to quantify spatial variability in contaminant concentrations and habitats. It was combined with an exposure and effect model that uses Monte Carlo simulation to quantify parameter uncertainty. Spatial model uncertainty was assessed by the application of two different spatial interpolation methods (classification and kriging) and foraging ranges. The results of the case study show that parameter uncertainty is the main type of uncertainty influencing the risk estimate, and to a lesser extent spatial variability, while spatial model uncertainty was of minor importance. Compared to the deterministically calculated hazard index for the little owl (0.9), inclusion of spatial variability resulted in a median hazard index that can vary between 0.8 and 1.4. It is concluded that a single estimator for a whole flood plain may over- or underestimate risks for specific parts within the flood plain. Further research that expands the procedure presented in this paper is necessary to improve the incorporation of spatial factors in ecological risk assessment.
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10.1021/es049814w
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9221459
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[The role of the stent in non-coronary cardiopathies].
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The stent has demonstrated to be a useful device in the prevention of postangioplasty coronary restenosis and it is expected to have a favourable effect as an alternative or complementary treatment of stenotic lesions in arteries or veins associated with congenital defects. The aim of this study is to analyze our experience in this setting. From February 1992 to March 1996, 28 stenting procedures were performed in 26 patients (mean age: 8.6 +/- 0.7 years; mean weight: 26.2 +/- 3 kg). In 12 patients, stenting was single, and a iliac Palmaz stents were always used. Stenting location was: pulmonary artery branches in 17 patients, right ventricular outflow in 2 patients, in the junction of right atrium with pulmonary artery in 2 patients, systemic veins in 2 patients and in post Mustard intratrial channel stenosis in 2 patients. 25 patients had previously undergone at least one surgical procedure. The stenotic diameter of the treated lesions increased significantly after the procedure (4.4 +/- 0.3 mm before stenting vs 11.6 +/- 0.3 mm after stenting, p < 0.0001) and the transtenotic gradient decreased from 38.1 +/- 5 to 12 +/- 3.8 mmHg. Those changes were associated with a diminution of right ventricular pressure (81.6 +/- 3 vs 56.7 +/- 6 mmHg, p < 0.0001) in patients with pulmonary branch stenosis without septal defects. There was no mortality among the percutaneously treated patients and only one patient needed surgery. Nevertheless, one patient died after bilateral intraoperative stenting. The treatment of proximal or distal stenotic lesions in the pulmonary tree, systemic veins, and obstructed intraatrial channels with stents, can replace or complement conventional balloon angioplasty. It also offers a useful and effective alternative to surgery, when it is impossible or carries a risk.
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12142917
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Fusion Expression, Immunogenicity and Applications of C-terminally Truncated HCV Core Proteins.
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Clones expressing full-length(aa 1-191) or C-terminally truncated forms (aa 1-69 and aa 1-40) of hepatitis C virus core(HCc) protein fused to the C-terminal of glutathione S-transferase(GST) were constructed and their expressions in different strains of Escherichia coli were compared. The expressed proteins were soluble. ELISA and Western blot analyses showed that GSTC191 was poorly expressed and had poor stability, whereas GSTC69 and GSTC40 were stable and could be purified to 90% purity in a single step on glutathione-Sepharose 4B. Mice immunized with these purified proteins produced high-titre antibodies. As an application, purified GSTC69 and GSTC40 were used in a preliminary assay of anti-HCc antibodies in patients'sera, and results showed that they had high specificity in the assay.
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30653714
|
Development and differentiation of the reproductive system of Tropidurus catalanensis (Squamata: Tropiduridae).
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Development and differentiation of the reproductive system in lizards begin in the embryonic period, although the stage and time of their occurrence vary according to populations and species. In this study, the events of the development and differentiation of the reproductive system of males and females of Tropidurus catalanensis were characterized during the embryonic, neonatal, and juvenile periods. Embryos at Stages 27, 34, 37, 40, and 41, neonates and juveniles, from Corrientes, Argentina, were analyzed. At Stage 27, the genital ridge was not observed but primordial germ cells were recorded in the yolk sac as well as the mesenteric mesenchyme, indicating the beginning of germ cell migration. Gonadal differentiation commenced at Stage 34. In males from Stage 37, the testes possessed seminiferous cords with Sertoli cells and spermatogonia, while in hatchlings seminiferous tubules and interstitial tissue with mature Leydig cells were present. Spermatogenesis was observed in a specimen of 51.9 mm snout-vent length, corresponding to the minimum reproductive size. In females, from Stage 37 until hatching, the ovaries had a cavernous medulla and a cortex with somatic cells and abundant oogonia. The onset of meiosis and folliculogenesis occurred in the juvenile period. © 2019 Wiley Periodicals, Inc.
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10.1002/jmor.20940
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721040
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[Pulmonary hypertension and cor pulmonale complicating ventricular vascular shunting for hydrocephalus (author's transl)].
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Obstructive pulmonary vascular disease and pulmonary hypertension are facts daily encountered by pediatric cardiologists. However longterm thromboembolism, pulmonary vascular obstruction and cor pulmonale are rare conditions in children. The case report of a four years old child treated by a Pudenz ventriculo venous shunt for hydrocephalus is presented. Due to fibrin thromboembolism from the Pudenz shunting tube pulmonary vascular obliteration, pulmonary hypertension and chronic cor pulmonale developed. The autopsy findings are in agreement with the ECG, x-ray, cardiac catheterization data and the angiocardiogram.
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16451762
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Comparison of muscle activity associated with structural differences in dental hygiene mirrors.
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Ergonomic studies suggest that the commonly used pinch grasp, held in a static position, is a contributing factor for dental Hygienists' development of work-related musculoskeletal disorders (WMSDs) such as carpal tunnel syndrome (CTS), Trigger Thumb, de Quervain's stenosing tenosynovitis, and carpometacarpal (CMC) osteoarthritis. The pinch grasp is commonly used by the dental hygienist while holding the dental mirror in the non-dominant hand. In response to this concern, manufacturers are redesigning dental mirror handles. The value of these re-designed products is based solely on anecdotal evidence. To date, minimal research has been done to examine the non-dominant mirror hand. The purpose of this study was to objectively evaluate dental mirror handle design using surface electromyography (sEMG) to compare muscle activity associated with grasping the mirror. This randomized controlled clinical trial utilized a two-by-two repeated measures statistical design. Data was collected on a convenience sample of 19 (N=19) healthy dental hygiene students in their last year of study. Data collection was divided into two phases to maintain a balanced study. The independent variables in phase I were diameter and weight. The independent variables in phase II were weight and padding. Muscle activity was measured while grasping various dental hygiene mirrors in 30-second increments using sEMG. Following data collection subjects designated which mirror felt most and least comfortable to compare subjective data with objective data. Three statistically significant results occurred. In phase II, padding (p=.01) demonstrated the largest reduction of muscle activity in the flexor pollicis brevis, by decreasing mean muscle activity by 3.7 microv. The interaction of diameter and weight (p=.01) in phase I reduced the mean muscle activity in the extensor digitorum by.8 microV and weight (p=.02) in phase II decreased the muscle activity in the extensor digitorum by.62 microV. Self-reports of comfort reported by the subjects in this study were not consistent with the measurements of muscle activity using sEMG. Ergonomic adaptations to dental hygiene mirror handles were associated with increases and decreases in muscle activity. The clinical impact of this is amplified as force is exerted. Furthermore, it may be possible to reduce WMSDs for dental hygienists by using instrument designs during the workday. Self-reports of comfort by the subjects in this study did not calibrate with the measurements of muscle activity using sEMG. Additional research is needed to further isolate the external variables of the study and to determine what actual reduction in muscle activity is significant for maintaining musculoskeletal health.
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14591438
|
Preliminary examination of cognitive reserve theory in closed head injury.
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This investigation was designed to provide preliminary support for cognitive reserve theory in closed head injury (CHI), and demonstrate the effectiveness of using the Oklahoma premorbid intelligence estimate (OPIE) in research and clinical activities. Out of a possible 124 consecutive referrals, 26 patients (N=26) who underwent neuropsychological assessment following brain injury met study inclusion/exclusion criteria. Participants were included if they had exited post-traumatic amnesia (PTA), demonstrated uncompromised upper extremity use, displayed adequate verbal communication, and were judged capable of completing a full neuropsychological evaluation. Participants were divided into a closed head injury-negative premorbid history (CHI-) or closed head injury-positive premorbid history (CHI+) group based upon premorbid variables (e. g., history of alcoholism). Groups did not differ in terms of demographic variables or premorbid IQ. Despite having less severe head injuries, the CHI+ group had a greater pre-post difference for PIQ, and a significantly larger VIQ/PIQ discrepancy than the CHI- group. In conclusion, these findings suggest that the CHI+ group had diminished cognitive reserve secondary to the aggregate effects of premorbid insult, which resulted in greater cognitive decline following an additional stressor (i. e., CHI) than what might otherwise be expected from the head injury alone.
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27489576
|
Fundamental awareness: A framework for integrating science, philosophy and metaphysics.
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The ontologic framework of Fundamental Awareness proposed here assumes that non-dual Awareness is foundational to the universe, not arising from the interactions or structures of higher level phenomena. The framework allows comparison and integration of views from the three investigative domains concerned with understanding the nature of consciousness: science, philosophy, and metaphysics. In this framework, Awareness is the underlying reality, not reducible to anything else. Awareness and existence are the same. As such, the universe is non-material, self-organizing throughout, a holarchy of complementary, process driven, recursive interactions. The universe is both its own first observer and subject. Considering the world to be non-material and comprised, a priori, of Awareness is to privilege information over materiality, action over agency and to understand that qualia are not a "hard problem," but the foundational elements of all existence. These views fully reflect main stream Western philosophical traditions, insights from culturally diverse contemplative and mystical traditions, and are in keeping with current scientific thinking, expressible mathematically.
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10.1080/19420889.2016.1155010
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