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20358020
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The pathophysiology, diagnosis and treatment of allergic rhinitis.
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Treatment of AR requires a stepwise approach depending on the severity and duration of symptoms. Treatment options for AR consist of allergen avoidance, pharmacotherapy, immunotherapy and surgery. For the mechanisms of AR, anti-IgE antibody and specific antibody to cytokines such as IL-4 or IL-5 that correlate with allergic inflammation have recently emerged. SLIT is currently widely used due to its efficacy, safety and convenience, which replaces subcutaneous immunotherapy. Although allergen avoidance and immunotherapy are theoretically ideal, antihistamines and intranasal corticosteroids will play the main role in the management of AR until an innovative treatment develops. However, patients' main symptom, the duration and severity of AR, patients' compliance, safety of medication and cost-effectiveness should be considered when treatment options are chosen. In conclusion, physicians should be aware of etiology, pathophysiology, symptoms, signs and diseases related to AR in order to make a correct diagnosis and choose a proper treatment option for each patient.
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10.4168/aair.2010.2.2.65
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22006684
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Adding more muscle and nerve to clinical trials.
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In this review we illustrate both the fundamentals and challenges of randomized clinical trials in neuromuscular disorders and suggest directions for prospective efforts to improve the design, conduct, rigor, and objectivity of these trials. Current research in clinical trials for neuromuscular disorders and key issues affecting these trials are reviewed. This perspective addresses the planning of clinical research, level of preclinical data needed to justify trials, patient recruitment and retention, and opportunities to access federal funding and infrastructure in support of clinical trials. The need for innovation in trial design and conduct, rigorous standards for the preclinical efficacy and safety data that support trial rationale, novel collaborative paradigms, objective interpretations of outcomes, and sharing of the lessons learned from trials in any one disorder among all neuromuscular trialists are imperative to improving the heretofore limited success in delivering novel, safe, and effective therapies to patients burdened by neuromuscular disorders. Copyright © 2011 Wiley Periodicals, Inc.
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10.1002/mus.22130
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25668421
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New paradigms in PCOS: impaired glucose tolerance and cardiovascular risk. Clinical approach.
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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age and is associated with various metabolic risk factors, in addition to chronic anovulation and factors related to androgen excess. Women with PCOS have a higher risk of insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and an increased prothrombotic state, resulting in a higher risk of type 2 diabetes mellitus, subclinical atherosclerosis, vascular dysfunction, and apparently cardiovascular disease and mortality. The aim of the present article was to summarize current knowledge with focus on a suggestion to the clinical approach and handling of these metabolic risk factors.
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7575362
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Unequal rate of monozygotic and like-sex dizygotic twin birth: evidence from the Minnesota Twin Family Study.
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It is generally believed that in Caucasian populations the rate of monozygotic (MZ) twinning is approximately equal to the rate of like-sex dizygotic (DZ) twinning so that representative samples of like-sex twins should contain approximately equal numbers of MZ and DZ twins. Recent evidence suggests, however, that the rate of DZ twinning in Caucasian populations has declined over the past 50 years so that there are now many more MZ than like-sex DZ twin births (Jeanneret and MacMahon, 1962; James, 1972; Mosteller et al., 1981; Doherty and Lancaster, 1986; Lykken et al., 1990). We report additional evidence of a higher rate of MZ than like-sex DZ twinning from Minnesota for the birth years 1971-1984. The convergence of evidence thus suggests that the observation of a greater number of MZ than DZ twins in a volunteer twin sample can no longer necessarily be taken as a sign of ascertainment bias.
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10.1007/BF02197282
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38510288
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Heart Failure Readmission in Patients With ST-Segment Elevation Myocardial Infarction and Active Cancer.
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Although numerous studies have examined readmission with heart failure (HF) after acute myocardial infarction (AMI), limited data are available on HF readmission in cancer patients post-AMI. This study aimed to assess the rates and factors associated with HF readmission in cancer patients presenting with ST-segment elevation myocardial infarction (STEMI). A nationally linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project registry and the UK national Hospital Episode Statistics Admitted Patient Care registry. Multivariable Fine-Gray competing risk models were used to evaluate HF readmission at 30 days and 1 year. A total of 326,551 STEMI indexed admissions were included, with 7,090 (2.2%) patients having active cancer. The cancer group was less likely to be admitted under the care of a cardiologist (74.5% vs 81.9%) and had lower rates of invasive coronary angiography (62.2% vs 72.7%; P < 0.001) and percutaneous coronary intervention (58.4% vs. 69.5%). There was a significant prescription gap in the administration of post-AMI medications upon discharge such as an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (49.5% vs 71.1%) and beta-blockers (58.4% vs 68.0%) in cancer patients. The cancer group had a higher rate of HF readmission at 30 days (3.2% vs 2.3%) and 1 year (9.4% vs 7.3%). However, after adjustment, cancer was not independently associated with HF readmission at 30 days (subdistribution HR: 1.05; 95% CI: 0.86-1.28) or 1 year (subdistribution HR: 1.03; 95% CI: 0.92-1.16). The opportunity-based quality indicator was associated with higher rates of HF readmission independent of cancer diagnosis. Cancer patients receive care that differs in important ways from patients without cancer. Greater implementation of evidence-based care may reduce HF readmissions, including in cancer patients. © 2024 The Authors.
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10.1016/j.jaccao.2023.10.011
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1775318
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Combined localized current field hyperthermia and irradiation for intraocular tumors.
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Ten patients with large melanomas and one patient with recurrent retinoblastoma were treated with combined localized current field (LCF) hyperthermia and iodine 125 irradiation delivered by episcleral plaque. Tumors were heated to 43 degrees to 45 degrees C for 28 to 45 minutes. Localized current field hyperthermia when combined with irradiation appeared to induce rapid tumor necrosis. One eye enucleated 17 hours after treatment showed only focal necrosis of the melanoma, while another eye demonstrated extensive necrosis 60 hours after treatment. In all remaining eyes, tumor regression occurred within the first month of treatment. Complications included cataract formation in six eyes, hemorrhagic retinal detachment in five eyes, and phthisis in two eyes. Complications from combined therapy of large intraocular tumors in this series appeared to result from the rapid necrosis of the tumor and secondary intraocular inflammation. Intraocular temperature dosimetry measurements demonstrated a temperature gradient of not more than -0.23 degrees C/mm-1 per axial millimeter from the episcleral plaque surface to the apex of the tumor. The authors believe that LCF hyperthermia could be a suitable means of application of hyperthermia in patients with intraocular tumors if further modifications were performed to reduce ocular complications.
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10.1016/s0161-6420(91)32042-6
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10282205
|
Practice bulletin. Private review entities.
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Practice Bulletin is the first in a series to be presented at the behest of the Council on Professional Practice, in response to issues arising in medical record practice today. Clear, useful points listing areas of responsibility as well as policies and procedures are given for both the private review organization, a new protagonist seeking access to patient records, and the facility, traditional guardian of health care records.
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16088793
|
Hospital-based surveillance for rotavirus diarrhea in children in Yangon, Myanmar.
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Diarrhea is a common childhood illness in Myanmar, and rotavirus is the single most important etiological agent of diarrhea. Surveillance for rotavirus diarrhea in children <5 years of age was conducted in a tertiary pediatric hospital in Yangon, Myanmar, from January 2002 through December 2003. Stool specimens obtained from children admitted to the hospital for acute diarrhea were tested for the presence of rotavirus by use of an enzyme-linked immunosorbent assay. Diarrhea was the cause of 5671 (18%) of all hospitalizations of children <5 years of age during the 2-year study period (n = 30,869). Rotavirus was identified in 923 (53%) of the 1736 stool specimens tested, and rotavirus infection was associated with approximately 10% of all hospitalizations of children. Rotavirus diarrhea most frequently occurred in children 6-17 months of age, and it was more commonly identified in boys (62% of children with rotavirus diarrhea were boys). The seasonal pattern of rotavirus disease mimicked that of diarrheal illness due to all causes, with the peak season for rotavirus disease occurring from November through February (i. e., during the cool, dry season). During the study period, 53 of the children who were hospitalized for diarrhea died. The present study confirms the importance of the etiological role that rotavirus plays in childhood diarrhea.
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10.1086/431509
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22615404
|
Empoasca leafhoppers attack wild tobacco plants in a jasmonate-dependent manner and identify jasmonate mutants in natural populations.
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Choice of host plants by phytophagous insects is essential for their survival and reproduction. This choice involves complex behavioral responses to a variety of physical and chemical characteristics of potential plants for feeding. For insects of the order Hemiptera, these behavioral responses involve a series of steps including labial dabbing and probing using their piercing mouthparts. These initial probing and feeding attempts also elicit a rapid accumulation of phytohormones, such as jasmonic acid (JA), and the induced defense metabolites they mediate. When Nicotiana attenuata plants are rendered JA deficient by silencing the initial committed step of the JA biosynthesis pathway, they are severely attacked in nature by hemipteran leafhoppers of the genus Empoasca. By producing N. attenuata plants silenced in multiple steps of JA biosynthesis and perception and in the biosynthesis of the plant's three major classes of JA-inducible insecticidal defenses, we demonstrate that the choice of plants for feeding by Empoasca leafhoppers in both nature and the glasshouse is independent of the accumulation of major insecticidal molecules. Moreover, this choice is independent of the presence of Candidatus Phytoplasma spp. and is not associated with detectable changes in plant volatiles but instead depends on the plant's capacity to mediate JA signaling. We exploited this trait and used Empoasca leafhoppers to reveal genetic variation in JA accumulation and signaling hidden in N. attenuata natural populations.
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10.1073/pnas.1200363109
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36679994
|
Immune Response to Vaccination against COVID-19 at Different Second-Dose Intervals and Their Associations with Metabolic Parameters.
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Obesity and diabetes are associated with severe outcomes of coronavirus disease (COVID-19). Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proven protective against infection and severe COVID-19. However, the immune response of metabolically burdened individuals to the vaccines remains unclear. Thus, we aimed to assess whether the metabolic status of individuals affects their humoral immune responses to the vaccination. Moreover, we evaluated whether the interval between the first two doses influenced antibody concentration. Sixty-seven individuals (21 males, 46 females) were vaccinated with the BNT162b2 mRNA COVID-19 vaccine. Fifty-four individuals were vaccinated with the second dose after 3 weeks and 13 after 5 weeks. We measured the antibody titers in all participants during the 19-week follow-up period. Patients diagnosed with COVID-19 were excluded. In the 5-week interval group, a significantly higher level of maximal antibody titers was observed. However, there were no differences in antibody concentrations after 19 weeks and no significant correlation between cardiometabolic factors and humoral response. The elongation of second-dose timing to 5 weeks leads to a higher acute antibody response but does not change long-term levels of antibody titers. Moreover, dysregulation of metabolic parameters does not lead to a diminished immune response to vaccination.
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10.3390/vaccines11010149
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17236825
|
Systematic and comprehensive strategy for reducing matrix effects in LC/MS/MS analyses.
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A systematic, comprehensive strategy that optimizes sample preparation and chromatography to minimize matrix effects in bioanalytical LC/MS/MS assays was developed. Comparisons were made among several sample preparation methods, including protein precipitation (PPT), liquid-liquid extraction (LLE), pure cation exchange solid-phase extraction (SPE), reversed-phase SPE and mixed-mode SPE. The influence of mobile phase pH and gradient duration on the selectivity and sensitivity for both matrix components and basic analytes was investigated. Matrix effects and overall sensitivity and resolution between UPLC technology and HPLC were compared. The amount of specific matrix components, or class of matrix components, was measured in the sample preparation extracts by LC/MS/MS with electrospray ionization (ESI) using both precursor ion scanning mode and multiple reaction monitoring (MRM). PPT is the least effective sample preparation technique, often resulting in significant matrix effects due to the presence of many residual matrix components. Reversed-phase and pure cation exchange SPE methods resulted in cleaner extracts and reduced matrix effects compared to PPT. The cleanest extracts, however, were produced with polymeric mixed-mode SPE (both reversed-phase and ion exchange retention mechanisms). These mixed-mode sorbents dramatically reduced the levels of residual matrix components from biological samples, leading to significant reduction in matrix effects. LLE also provided clean final extracts. However, analyte recovery, particularly for polar analytes, was very low. Mobile phase pH was manipulated to alter the retention of basic compounds relative to phospholipids, whose retention tends to be relatively independent of pH. In addition to the expected resolution, speed and sensitivity benefits of UPLC technology, a paired t-test demonstrated a statistically significant improvement with respect to matrix effects when this technology was chosen over traditional HPLC. The combination of polymeric mixed-mode SPE, the appropriate mobile phase pH and UPLC technology provides significant advantages for reducing matrix effects resulting from plasma matrix components and in improving the ruggedness and sensitivity of bioanalytical methods.
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10.1016/j.jchromb.2006.12.030
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2282785
|
Sex differences in social reinstatement motivation of the domestic chick (Gallus gallus) revealed by runway tests with social and nonsocial reinforcement.
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Male and female chicks (Gallus gallus) were trained at 4 days old to run along a corridor to reach a goal box that contained either cagemates (social reinforcement) or food (nonsocial reinforcement). Females ran faster when social reinforcement was used, whereas males ran faster with nonsocial reinforcement. When social reinforcement was used with a V-shaped runway, in which chicks had to proceed toward the goal object in an indirect fashion, sex differences were reversed. The results may be due to stronger social reinstatement tendencies in females than in males: Higher levels of social motivation facilitate behavioral performance when the task is easy (straight runway) and inhibit it when the task is difficult (V-shaped runway).
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10.1037/0735-7036.104.4.361
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22194031
|
Technical feasibility of robot-assisted ventral hernia repair.
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The da Vinci robotic laparoscopic incisional hernia repair with intracorporeal closure of the fascial defect and circumferential suturing of the mesh may offer an alternative to current fascial closure and transabdominal sutures and tackers. From 2009 to 2011, a retrospective review of 13 patients with a mean age of 51 years, median body mass index (BMI) of 31.53 kg/m(2), and small and medium-sized ventral hernias (mean fascial defect 37.39 cm(2)) were treated with the da Vinci robot system using intracorporeal primary closure of the fascial defect with a running O-absorbable suture followed by underlay mesh fixation using a continuous running, circumferential, nonabsorbable suture. This study aimed to assess the technical feasibility of the procedure. In addition, the operating time and specific morbidity of postoperative pain, and long-term recurrence were recorded. The mean operating time was 131 min. There were no conversions to open or standard laparoscopic techniques. There were no postoperative deaths. The overall morbidity rate was 13%. One patient remained in hospital for pain control, and another experienced urinary retention that required a Foley catheter. The mean hospital stay was 2.4 days. During a median follow-up period of 23 months, one of the patients experienced a recurrent hernia. None experienced chronic suture site pain or discomfort. This is a retrospective series review of robot-assisted ventral hernia repair using intracorporeal primary closure followed by continuous running, circumferential fixation. The findings show that this technique is feasible and may not be associated with chronic postoperative pain. Further evaluation is needed, and long-term data are lacking to assess the benefit to the patient, but this series can be the basis for future studies.
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10.1007/s00268-011-1389-8
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10975603
|
Genetic variation in in-vitro cytokine-induced production of nitric oxide by murine peritoneal macrophages.
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Quantitative aspects of the in-vitro interferon (IFN)-gamma-induced nitric oxide (NO) production by peritoneal macrophages of eight inbred strains of mice were investigated. Animals employed in the study can be assorted into three phenotype categories: high, moderate, and low NO-responders. Concentration of nitrites in the 24-h supernatants of cells stimulated with recombinant murine IFN-gamma (25 U/ml) reached the following values (mean +/- SEM; in microM): C57BL/10 (33.7+/-1.88) = C57BL/6 (32.1+/-2.10) > SIL (24.0+/-1.55) > CBA/J (18.1+/-1.79) = C3H/HeN (18.0+/-1.10) > DBA/2 (11.4+/-1.16) = DBA/1 (11.0+/-1.20) = Balb/c (11.0+/-1.16). Approximately 80% of the total variation was found to be controlled by genetic factors. No association between the extent of NO formation and variation in the constitutive expression of macrophage IFN-gamma receptor was observed. Similar magnitude of inter-strain differences was sustained after enhanced NO-stimulation of the cells with IFN-gamma + tumour necrosis factor (TNF)-alpha, but only high (strains BL/10, BL/6, SJL, CBA/J, C3H/HeN) and low (DBA/1, DBA/2, Balb/c) NO-responder phenotypes were detected after the triple cytokine cocktail composed of IFN-gamma + TNF-alpha + interleukin (IL)-10. The strain differences remained unchanged after the supplementation of culture medium with L-arginine or tetrahydrobipopterin. Genetically governed differences in IFN-gamma-induced NO production have been found to be tightly associated with differential expression of inducible nitric oxide synthase mRNA. Possible implications of the findings for various fields of NO biomedical research are discussed.
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10.1097/00008571-200008000-00002
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19842358
|
Depressive symptoms, gender, and sexual risk behavior among African-American adolescents: implications for prevention and intervention.
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African-American youths are disproportionately affected by deleterious outcomes associated with risky sexual activity. Arguably, females are at greater risk for these adverse outcomes due to physiological and emotional risk factors, such as depression. The current study examines the relationship between depressive symptomology and sexual risk behavior within a sample of 1,970 inner-city, economically disadvantaged African-American adolescents in grades nine and eleven. The findings of this study support a relationship between sexual risk behavior and depressive symptomology for the sample, such that as depressive symptomology increases so does sexual risk behavior. Furthermore, an interaction for gender was found, with depressive symptomology being a stronger predictor of sexual risk behavior for African-American females as compared to African-American males. Implications of these findings for the design of prevention programs specifically tailored to African-American adolescent women are discussed.
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10.1300/j005v35n02_05
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16491955
|
Decoy molecules based on PNA-DNA chimeras and targeting Sp1 transcription factors inhibit the activity of urokinase-type plasminogen activator receptor (uPAR) promoter.
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The expression levels of urokinase-type plasminogen activator receptor (uPAR) are strongly correlated with metastatic potential in human cancer cell lines of melanoma, breast, lung, and colon. Therefore, targeting of uPAR could have practical implications in the treatment of neoplastic diseases. Because the expression of uPAR is regulated at the level of transcription in part by Sp1, we designed and tested transcription factors decoy molecules targeting Sp1 with the aim of inhibiting uPAR gene expression. The main objective of the present study was to determine whether decoy molecules based on peptide nucleic acids (PNA)-DNA chimeras mimicking Sp1 binding sites might be proposed as useful reagents to alter expression of Sp1-regulated genes involved in tumor invasion and metastasis. The results obtained firmly indicate that Sp1 binding molecules based on PNA-DNA-PNA chimeras are powerful decoys, as they efficiently inhibit the interactions between Sp1 and the uPAR promoter elements. Experiments performed on hepatoma HepG2 cells transfected with a plasmid containing the firefly luciferase gene reporter under the control of the human uPAR promoter demonstrate that PNA-DNA-PNA-based decoy molecules are potent inhibitors of the transcriptional activity of the uPAR promoter. Our results suggest that these molecules warrant attention for the design of novel antimetastatic drugs.
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10.3727/096504005776449734
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39643487
|
Use of stool molecular panel in hospitalized patients with diarrhea. Experience in a tertiary care center.
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Infectious diarrhea is a common health issue that affects a large number of individuals each year. It causes significant morbidity and mortality, greatly impacting healthcare system costs. Rapid detection of the causative organism and timely treatment alters the management and outcome of the condition. Molecular panels in stool allow to analyze a wide range of pathogens quickly and easily. For this study, a cross-sectional cohort analysis with a retrospective analysis of adult patients hospitalized with diarrhea and negative conventional stool bacteriological studies was conducted. Data obtained from the use of molecular panels in stool and the role of endoscopy in the diagnostic pathway were analyzed. A positivity rate of 52% (n=41) out of a total of 79 samples was reported. The test contributed to a change in therapeutic approach in 58% (n=46) of the patients. Among the patients with a negative molecular panel, 39.5% underwent further evaluation with colonoscopy involving biopsies, resulting in a diagnostic yield of 87%. Based on these results, we can conclude that molecular techniques contribute to the diagnosis and change in therapeutic approach in hospitalized patients with diarrhea. Copyright © 2024 The Author(s). Publicado por Elsevier España, S. L. U. All rights reserved.
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10.1016/j.ram.2024.10.005
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34078475
|
Questionnaire for the assessment of adherence barriers of intravitreal therapy: the ABQ-IVT.
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To develop and validate a questionnaire for the investigation of non-adherence (NA) barriers in patients receiving intravitreal injection (IVT). Questionnaire development and cross-sectional patient survey combined with a retrospective medical chart review. German patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) receiving anti-vascular endothelial growth factor (anti-VEGF) treatment via IVT. The previously validated (indications: atrial fibrillation, human immunodeficiency virus, chronic inflammatory lung disease) Adherence Barriers Questionnaire (ABQ) was revised according to specifications of IVT, within the framework of an expert panel. The ABQ-IVT, which initially consisted of 24 items formulated as statements (4-point-Likert-scale ranging from "strongly agree" to "strongly disagree"), was applied in a cross-sectional survey. Evaluation of the questionnaire included an assessment of internal consistency and factor analysis. The occurrence of potential barriers in the patient sample was evaluated using descriptive statistics. To identify patient subpopulations, hierarchical cluster analysis was performed using ABQ-IVT answers as predictors. Due to difficulties in capturing NA as an external criterion, the evaluation of the questionnaire was limited to its internal validity and reliability. Patients' answers to the ABQ-IVT questionnaire and interviews. Of 253 patients, 234 (92%) were able to complete the ABQ-IVT questionnaire. Within the reliability analysis, the ABQ-IVT was reduced to 17 items. The condensed questionnaire demonstrated good internal consistency (Cronbach's alpha = 0.78), and factor analysis showed no evidence for subscales of the questionnaire. Nearly half of the patients (49%) reported being affected by at least three different barriers. On average, a patient was affected by 3.1 barriers. The most frequently reported barriers were "Challenge due to time commitment of physician visits" (45% of the patients), "Depression" (29%) and "Travel and opportunity costs" (27%). Cluster analysis identified six patient subpopulations, each affected by different sets of barriers and differed regarding their patient characteristics. The ABQ-IVT is a practical and reliable instrument for identifying patient-specific barriers to IVT treatment adherence. In practice, the questionnaire may be useful in assessing whether individual patients are at higher risk of NA due to specific adherence barriers. Aside from better awareness, this allows earlier interventions, though these still need to be validated. Patient subpopulations face different barriers and may, therefore, need distinct preventative care.
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10.1186/s40942-021-00311-x
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25618248
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Study of viral pathogenesis in humanized mice.
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Many of the viral pathogens that cause infectious diseases in humans have a highly restricted species tropism, making the study of their pathogenesis and the development of clinical therapies difficult. The improvement of humanized mouse models over the past 30 years has greatly facilitated researchers' abilities to study host responses to viral infections in a cost effective and ethical manner. From HIV to hepatotropic viruses to Middle East Respiratory Syndrome coronavirus, humanized mice have led to the identification of factors crucial to the viral life cycle, served as an outlet for testing candidate therapies, and improved our abilities to analyze human immune responses to infection. In tackling both new and old viruses as they emerge, humanized mice will continue to be an indispensable tool. Copyright © 2015 Elsevier B. V. All rights reserved.
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10.1016/j.coviro.2015.01.002
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33046895
|
vLUME: 3D virtual reality for single-molecule localization microscopy.
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vLUME is a virtual reality software package designed to render large three-dimensional single-molecule localization microscopy datasets. vLUME features include visualization, segmentation, bespoke analysis of complex local geometries and exporting features. vLUME can perform complex analysis on real three-dimensional biological samples that would otherwise be impossible by using regular flat-screen visualization programs.
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10.1038/s41592-020-0962-1
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34424025
|
Spatial cueing effects are not what we thought: On the timing of attentional deployment.
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Extensive research has shown that objects that are salient or match our task goals are most likely to capture our attention. But are we at the mercy of the constant changes occurring in our environment, and automatically move our attention to the ever-changing location with the highest priority? Or do we wait for clues that the appropriate moment has arrived to deploy our attention? We addressed this hitherto neglected issue in three experiments. Using a spatial-cuing paradigm, we examined whether attention is deployed as soon as a salient change occurs (the cue), or only when the context signaling that attention should be deployed appears (the search display). The cue matched the target color and was expected to enjoy high attentional priority. We used two separate response compatibility manipulations, one pertaining to the cue, in the cuing display, and the other to the cued distractor, in the search display. Neutral conditions allowed us to disentangle the respective effects of these manipulations. Participants deployed their attention in the search display when they could rely on contextual information, and in the cue display when such information was absent. These findings challenge the traditional interpretation of spatial-cuing effects. They are discussed within the Priority Accumulation Framework (PAF) that we confront to other attention models. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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10.1037/xhp0000918
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6235105
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Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders.
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Isotretinoin is a new orally active retinoic acid derivative for the treatment of severe refractory nodulocystic acne. The pharmacological profile of isotretinoin suggests that it acts primarily by reducing sebaceous gland size and sebum production, and as a result alters skin surface lipid composition. Bacterial skin microflora is reduced, probably as a result of altered sebaceous factors. Isotretinoin 1 to 2 mg/kg/day for 3 to 4 months produces 60 to 95% clearance of inflammatory lesions in patients with severe, recalcitrant nodulocystic acne, with evidence of continued healing and prolonged remissions in many patients after treatment withdrawal. Doses as low as 0.1 mg/kg/day have also proven successful in the clearance of lesions; however, with such low doses the duration of remission after discontinuation of therapy is usually shorter. Encouraging results have also been seen in small numbers of patients with rosacea, Gram-negative folliculitis, Darier's disease, ichthyosis and pityriasis rubra pilaris, the response in keratinising disorders resembling that with the related drug etretinate. While long term follow-up studies in these patients have not been reported, prolonged remission after withdrawal of isotretinoin in disorders of keratinisation is unlikely, as with other drugs used in these conditions. Isotretinoin is only partially effective in psoriasis, in contrast to etretinate which is very effective in psoriasis but ineffective in severe acne. Some encouraging results have also been reported with isotretinoin in patients with squamous and basal cell carcinomas, but isotretinoin has proven unsuccessful in non-squamous cell epithelial and non-epithelial cancer. Side effects affecting the mucocutaneous system occur in nearly all patients receiving isotretinoin, but rarely lead to drug withdrawal. Raised serum triglyceride levels are also commonly reported. The possibility of long term spinal or skeletal bone toxicity may restrict the use of isotretinoin in severe disorders of keratinisation requiring prolonged administration. Isotretinoin is strictly contraindicated in women of childbearing potential due to its severe teratogenic properties, unless an effective form of contraception is used. Thus, isotretinoin offers an effective advance on the treatment options available in a difficult therapeutic area - those patients with severe, nodulocystic acne not responding to 'traditional' therapy.
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10.2165/00003495-198428010-00002
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12780976
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Randomized clinical trials in pediatric critical care: Rarely done but desperately needed.
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OBJECTIVE: To review the benefits and challenges of using the randomized, controlled trial (RCT) study design to evaluate preventive and therapeutic interventions in pediatric critical care medicine. CONCLUSIONS: The RCT design is able to control for many sources of potential bias that other types of study designs cannot. The findings of RCTs often contradict the findings of less rigorous study designs. Before performing an RCT, there must exist a state of clinical equipoise, a sufficient number of eligible patients must be available, and the epidemiology of the disorder in question must be well studied. There are many challenges to performing high-quality RCTs. Studying multiple element support strategies in the critically ill patient population is more complex than studying a single drug therapy. High patient and practice variability and hazy diagnostic definitions can dilute the signal-to-noise ratio. Most interventions in critical care are expected to have a modest or small effect. This markedly increases the requisite sample size. There is a paucity of accepted clinically important measurements of the outcome of critical care, making mortality a common outcome to evaluate with a not-so-common incidence. Developmental issues, the inability to give informed consent, and the failure to perform the appropriate pharmacokinetic and safety studies are additional challenges facing pediatric investigators. Despite these limitations, a good RCT remains the best way to prove that an intervention is working or not. Indeed, RCTs are and will remain the "gold standard" method to estimate the efficacy of a therapeutic or prophylactic intervention.
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10.1097/00130478-200204000-00002
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31902108
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Ampelopsin alleviates sevoflurane-induced cognitive dysfunction by mediating NF-κB pathway in aged rats.
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Cancer-induced bone pain (CIBP) is the pain caused by bone metastasis from malignant tumors, and the largest source of pain for cancer patients. miR-300 is an important miRNA in cancer. It has been shown that miR-300 regulates tumorigenesis of various tumors. This study aims to investigate the role of miR-300 in CIBP and its underlying molecular mechanisms in vitro and in vivo. We constructed CIBP model in rats and investigated the mechanism through which miR-300 affects CIBP. We first examined expression level of miR-300 in CIBP rats and then tested the effect of its overexpression. Next, we identified the target of miR-300 using TargetScan analysis and double luciferase assay. Finally, we studied genetic interactions between miR-300 and its target and their roles in CIBP. We found that miR-300 was downregulated in CIBP rats. Overexpression of miR-300 significantly attenuated cancer-induced neuropathic pain (p < 0.01). Furthermore, TargetScan analysis and double luciferase assay show High Mobility Group Box 1 (HMGB1) is a target of miR-300. Notably, HMGB1 is overexpressed in CIBP rats, while up-regulation of miR-300 significantly suppresses expression of HMGB1 (p < 0.01). Moreover, knockdown of HMGB1 by siRNA significantly relieves cancer-induced neuropathic pain in rats (p < 0.01). On the other hand, HMGB1 overexpression partially blocked the effect of miR-300 on cancer-induced nerve pain. miR-300 relieves cancer-induced neuropathic pain by inhibiting HMGB1 expression. These results may be beneficial for the treatment of CIBP in clinical practice.
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10.1007/s13258-019-00897-5
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28545786
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The associations between insomnia and health-related quality of life in rehabilitation units at 1month after stroke.
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The principal objective of this study was to investigate the relationship between insomnia and health-related quality of life (HRQoL) during the early stage of stroke rehabilitation. The subjects were 214 first-time stroke patients admitted to a rehabilitation unit at one of three Korean hospitals. Within 7days after stroke, functions were evaluated using; the Berg Balance Scale, the Modified Barthel Index, the Mini Mental State Examination, the Frontal Assessment Battery, Screening Tests for Aphasia and Neurologic-Communication Disorders, and the National Institute of Health Stroke Scale. Insomnia, depression, anxiety, and HRQoL were investigated at one month after stroke. Insomnia was defined as presence of at least one of the four following; difficulty initiating sleep, difficulty maintaining sleep, early morning awakening, and non-restorative sleep. HRQoL was assessed using the Short Form Health survey SF-8. Depression and anxiety were measured using the Hospital Anxiety Depression Scale. Multivariate linear regression analysis was conducted to examine the association between insomnia and HRQoL. The prevalence of insomnia at one month after stroke was 59.5%. Patients with insomnia were more likely to be older and female and to have depression and anxiety. Patients with insomnia had poorer physical and mental HRQoL. By multivariate analyses, physical HRQoL was significantly associated with type of stroke, hypnotic usage, balancing function, and insomnia. Mental HRQoL was significantly associated with balancing function, depression, and insomnia. Insomnia was found to be negatively associated with physical and mental HRQoL in stroke patients during the early stage of rehabilitation. Copyright © 2017 Elsevier Inc. All rights reserved.
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10.1016/j.jpsychores.2017.02.008
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12890738
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Normospermic versus teratospermic domestic cat sperm chromatin integrity evaluated by flow cytometry and intracytoplasmic sperm injection.
|
Teratospermia (>60% of morphologically abnormal spermatozoa) is well documented in felids. Even morphologically normal spermatozoa from teratospermic ejaculates have reduced ability to undergo tyrosine phosphorylation, acrosome react, and bind and penetrate oocytes compared with normospermic ( 0.05) proportions of oocytes fertilized after ICSI using spermatozoa from normo- and teratospermic cats. Results reveal that teratospermia in the cat is expressed at the nuclear level as increased sperm chromatin heterogeneity, but ICSI showed that this does not apparently affect fertilization rates if the zona pellucida and oolemma can be bypassed.
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10.1095/biolreprod.103.016089
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15640584
|
5-(1-Hydroxyethylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione and four amino derivatives.
|
In the structures of 5-(1-hydroxyethylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, C8H10N2O4, (I), 1,3-dimethyl-5-[1-(propylamino)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione, C11H17N3O3, (II), and 5-[1-(2,2-dimethoxyethylamino)ethylidene]-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, C12H19N3O5, (III), there are no direction-specific intermolecular interactions. The molecules in 5-[1-(benzylamino)ethylidene]-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, C15H17N3O3, (IV), are linked into chains of edge-fused rings by a combination of one C-H... O hydrogen bond and one C-H... pi(arene) hydrogen bond, while the molecules in 5-(1-hydrazinoethylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, C8H12N4O3, (V), are linked into a continuous framework structure by three distinct N-H... O hydrogen bonds, each involving a different O-atom acceptor. Each of compounds (I)-(V) contains an intramolecular hydrogen bond, of the O-H... O type in (I) and of the N-H... O type in (II)-(V).
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10.1107/S0108270104028859
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24233436
|
Three novel SNPs in the coding region of the bovine MC3R gene and their associations with growth traits.
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The involvement of melanocortin-3 receptor (MC3R) is well recognized in the regulation of feeding efficiency, body weight, and energy homeostasis. The objective of this study was to investigate the associations between MC3R gene polymorphisms and growth traits. Three novel SNPs (c.24C→T, c.220T→A, c.734G→C) and five haplotypes were identified in 234 Xiangxi cattle. The associations between MC3R gene polymorphisms and growth traits indicated that the individuals with TT and AT genotypes maintained higher body weight than those with the AA genotype at the c.220T→A locus (P < 0.05). The animals with GG and CG genotypes had higher heart girth and body weight than those with the CC genotype at c.734G→C (P < 0.05). The animals with H3H3 and H2H3 haplotype combinations had higher body weight than those with other haplotype combinations (P < 0.05). The results suggest that these SNPs in the MC3R gene might be useful genetic markers for marker-assisted selection and cattle breeding.
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10.1007/s10528-013-9632-7
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38212649
|
Simultaneous quantification of seven glycols in antifreeze liquids using direct liquid injection gas chromatography coupled with mass spectrometry.
|
Glycol-based antifreeze liquids, commonly composed of ethylene glycol or propylene glycol, have important uses in automotive cooling, but they should be handled with care due to their toxicity. Ethylene glycol is highly toxic to humans and animals. A fast, accurate, precise, and robust method was developed for the simultaneous quantification of seven most important glycols and their isomers. Glycols were analyzed from diluted sample solution of coolants using gas chromatography coupled with mass spectrometry (GC-MC) in single ion monitoring mode. The method was developed and validated for seven individual glycols (ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, propylene glycol, dipropylene glycol, and tripropylene glycol). Limits of detection (1-2 μg/mL) and limits of quantification (10 μg/mL) obtained were appropriate. The present method was applied for the determination of glycols in 10 different antifreeze liquids commercially available on the Romanian market, proving to be reliable. A method that requires only a two-step dilution of antifreeze samples combined with direct liquid injection GC-MS was validated for the simultaneous quantification of seven glycols (and their isomers) in 10 different types of antifreeze liquids. The results obtained in the validation procedure proved that the GC-MS method is sensitive and precise for the quantification of glycols. © 2023 John Wiley & Sons Ltd.
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10.1002/rcm.9686
|
26375717
|
Alcoholic Pancreatitis Masquerading as Preeclampsia.
|
Coexisting medical complications in pregnancy can present in a fashion similar to preeclampsia and can be challenging to differentiate. We present a patient who, at 27 3/7 weeks of gestation, fulfilled diagnostic criteria for severe preeclampsia, including hypertension, proteinuria, headache, abnormal serum creatinine levels, thrombocytopenia, and liver function abnormalities, but who nevertheless did not have preeclampsia. Instead, she was diagnosed with alcoholic pancreatitis based on a history of heavy alcohol use and elevated amylase and lipase. Abnormal laboratory values resolved with supportive therapy, and she continued to term without subsequent recurrence of proteinuria or hypertension. Alcoholic pancreatitis can be mistaken for preeclampsia.
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10.1097/AOG.0000000000001057
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36958024
|
Blackwater Fever Treated with Steroids in Nonimmune Patient, Italy.
|
Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.
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10.3201/eid2904.221267
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32443686
|
Special Issue: Conductive Polymers: Materials and Applications.
|
Intrinsically conductive polymers (CPs) combine the inherent mechanical properties of organic polymers with charge transport, opto-electronic and redox properties that can be easily tuned up to those typical of semiconductors and metals. The control of the morphology at the nanoscale and the design of CP-based composite materials have expanded their multifunctional character even further. These virtues have been exploited to advantage in opto-electronic devices, energy-conversion and storage systems, sensors and actuators, and more recently in applications related to biomedical and separation science or adsorbents for pollutant removal. The special issue "Conductive Polymers: Materials and Applications" was compiled by gathering contributions that cover the latest advances in the field, with special emphasis upon emerging applications.
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10.3390/ma13102344
|
630682
|
Thallium-201 scintigraphy in unstable angina pectoris.
|
Thallium-201 scintigraphy was performed during the pain free period in 98 patients with unstable angina. Scintiscans were positive in 39 patients, questionable in 27 patients and normal in 32 patients. Eighty-one patients responded favorably to treatment (group I). Seventeen patients had complicated courses (group II) and despite maximal treatment with propranolol either developed infarction (six patients) or continued to have angina necessitating coronary surgery (11 patients). In group I during the pain free period 26 of 81 patients had positive thallium-201 scans, whereas 20 patients had an abnormal ECG at that time; during angina 18 patients had transient ECG changes. In group II during the pain free period 13 of 17 patients had positive scans, whereas two patients had abnormal ECG at that time; during angina 12 patients showed transient ECG changes. The sensitivity to recognize group II was 76% for thallium-201 scintigraphy, 11% for ECG during the pain free period; 70% for ECG during angina; 94% for the combination of either positive scans or abnormal ECG. Thus, 1) positive thallium-201 scans occur in patients with unstable angina, 2) positive scans can be obtained during the pain free period, 3) thallium-201 scans are more frequently positive in patients with complicated course.
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10.1161/01.cir.57.4.738
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473832
|
[Hemodynamics of the liver. I. Liver perfusion after ligation of the dog hepatic artery and portal vein].
|
By means of direct method hepatic blood supply was examined after ligation of hepatic artery and portal vein. 15 per cent of the total blood supply to the liver were arterial. This amount can rise to 30 per cent under extreme conditions, caused by an increase of arteriovenous pressure difference as well as by a decrease of the arterial flow resistance in the liver.
| |
972169
|
Inhibition of sulfate transport in Ehrlich ascites tumor cells by 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid(SITS).
|
The effects of the nonpenetrating amino reactive reagnet 4-acetamido-4'-isothiocyano-stilbene-2-2'-dilsulfonic acid (SITS) on anion transport (sulfate, chloride, and inorganic phosphate) were investigated in Ehrlich ascites tumor cells. Short time exposure to SITS produces a reversible inhibition (92%) of sulfate transport. The kinetics of interaction suggest that reversibly bound SITS competitively inhibits sulfate transport, Ki = 3 X 10(-6)M. Incubation of tumor cells with SITS (1 X 10(-4)M) for longer periods of time results in a time dependent irreversible inhibition of sulfate transport which obeys first order kinetics. The rate coefficient for the inactivation process is 0.040 min-1. The kinetics of irreversible inhibition is best explained by the irreversible binding of SITS to the sulfate transport site, and therefore makes SITS a potentially useful probe for the quantiation of these sites in the tumor cell. The lack of effect of irreversibly bound SITS on either chloride or inorganic phosphate transport points to a specificity in the interaction of SITS with the tumor cell membrane, as well as indicating that an alternate pathway exists for the movement of these anions across the membrane.
|
10.1002/jcp.1040890213
|
19291315
|
Effects of statins on the secretion of human serum albumin in cultured HepG2 cells.
|
Statins reduce cholesterol biosynthesis by inhibiting HMG-CoA reductase and thereby lower total cholesterol and LDL cholesterol levels in serum, which in turn lower the incidence of cardiovascular disease (CVD). Statins are also known to modulate various cellular functions such as gene expression, cell proliferation, and programmed cell death through inhibition of downstream intermediates in cholesterol synthesis. In this study, we have investigated the possible effects of statins on the secretion of serum albumin from cultured HepG2 cells since high levels of serum albumin are associated with reduced risks for CVD and statins are effective in lowering the risk of CVD through other effects in addition to their effects on serum total cholesterol and LDL cholesterol levels, known as pleiotropic effects. Our results showed that simvastatin increased HSA secretion up to 32.3% compared to the control group. Among 3 statin analogs we tested, simvastatin exhibited the highest stimulatory effects on HSA secretion compared to the control group. Our study also showed that the increased HSA secretions from HepG2 cells by simvastatin treatments were due to the increased rate of HSA synthesis, not due to the reduced posttranslational degradation rate of HSA. Our finding suggests another added benefit of statins' treatments in preventing CVD through stimulation of HSA biosynthesis.
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10.1186/1423-0127-16-32
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38530726
|
Towards Co-Operative Beaming Displays: Dual Steering Projectors for Extended Projection Volume and Head Orientation Range.
|
Existing near-eye displays (NEDs) have trade-offs related to size, weight, computational resources, battery life, and body temperature. A recent paradigm, beaming display, addresses these trade-offs by separating the NED into a steering projector (SP) for image presentation and a passive headset worn by the user. However, the beaming display has issues with the projection area of a single SP and has severe limitations on the head orientation and pose that the user can move. In this study, we distribute dual steering projectors in the scene to extend the head orientation and pose of the beaming display by coordinating the dual projections on a passive headset. For cooperative control of each SP, we define a geometric model of the SPs and propose a calibration and projection control method designed for multiple projectors. We present implementations of the system along with evaluations showing that the precision and delay are 1.8 ∼ 5.7 mm and 14.46 ms, respectively, at a distance of about 1 m from the SPs. From this result, our prototype with multiple SPs can project images in the projection area ($20\ \text{mm} \times 30\ \text{mm}$) of the passive headset while extending the projectable head orientation. Furthermore, as applications of cooperative control by multiple SPs, we show the possibility of multiple users, improving dynamic range and binocular presentation.
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10.1109/TVCG.2024.3372118
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6131698
|
Purification of detergent-solubilized form and membrane-binding domain of rat gamma-glutamyltransferase by immuno-affinity and hydrophobic chromatography.
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A new method to purify papain- or detergent-solubilized form (papain or detergent form) of gamma-glutamyltransferase from rat hepatomas as well as from rat kidney by immuno-affinity column chromatography is presented. The antibody-column was prepared by coupling the anti-kidney papain form antibody, which had been purified by using a kidney papain form-Sepharose column, to CNBr-activated Sepharose 4B. The enzyme bound to the antibody-column was eluted with 0.04 M NH4OH. By this method, detergent forms were purified 300 and 1600-fold in approx. 50% yields from rat kidney and rat ascites hepatoma AH 13, respectively, and the papain form was also purified 16 000-fold in a similar yield from primary hepatoma which has a very low activity of this enzyme. Preparations thus obtained apparently did not contain any peptide other than heavy and light subunit peptides of this enzyme on SDS-polyacrylamide gel electrophoresis. The detergent form of kidney enzyme was preferentially absorbed to a hydrophobic column of aminooctyl-Sepharose, while the papain form was not, suggesting that the detergent form might be adsorbed to the column through hydrophobic interaction of the membrane-binding domain. The domain peptide was also purified by the hydrophobic column after release from the detergent form by papain treatment. The molecular weight of the peptide was estimated to be about 16 000 on SDS-polyacrylamide gel electrophoresis. On double immunodiffusion, the domain peptide reacted with anti-detergent form antibody but not with anti-papain form antibody. The domain-specific antibody was also purified from the anti-detergent form antibody.
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10.1016/0304-4165(83)90343-4
|
32814310
|
Metabolic Cost of Paddling on Different Commercially Available Kayak Ergometers.
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To compare the metabolic cost of paddling on different commercially available kayak ergometers using a standardized kayak incremental exercise protocol. Six male sprint kayak athletes undertook an incremental exercise protocol on 3 different kayak ergometers utilizing a randomized counterbalanced pair-matched design. Mean maximal aerobic power on the WEBA ergometer (265 [14] W) was significantly higher than on the Dansprint (238 [9] W) and KayakPro® (247 [21] W, P <.01, effect size [ES] = 0.80). At the fifth stage, absolute oxygen consumption on the WEBA (3.82 [0.25] L·min-1) was significantly lower (P < 0.05, ES = 0.20) than KayakPro and Dansprint (4.10 [0.28] and 4.08 [0.27] L·min-1, respectively). Blood lactate concentration response at the sixth stage was significantly lower for the WEBA (3.5 [0.8] mmol·L-1), compared with KayakPro and Dansprint (5.4 [1.2] and 5.6 [1.5] mmol·L-1, P =.012, ES = 0.20). Stroke rate was significantly higher, without any effect of pacing during the submaximal stages for the Dansprint, compared with the WEBA (P <.001, ES = 0.28) and KayakPro (P <.001, ES = 0.38). A pacing effect was present at the maximal stage for all ergometers. This study demonstrated that paddling on different kayak ergometers when controlling power output elicits different metabolic and work outputs. It is recommended that scientists and coaches avoid testing on different ergometers and regularly calibrate these devices. Moreover, when an ergometer has been calibrated against a first principle device, it is necessary to consider calibration of various drag settings, due to their impact on stroke rate. Further research should explore the relationship between drag settings and stroke rate.
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10.1123/ijspp.2019-0561
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22554188
|
Studying "invisible" excited protein states in slow exchange with a major state conformation.
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Ever since its initial development, solution NMR spectroscopy has been used as a tool to study conformational exchange. Although many systems are amenable to relaxation dispersion approaches, cases involving highly skewed populations in slow chemical exchange have, in general, remained recalcitrant to study. Here an experiment to detect and characterize "invisible" excited protein states in slow exchange with a visible ground-state conformation (excited-state lifetimes ranging from ∼5 to 50 ms) is presented. This method, which is an adaptation of the chemical exchange saturation transfer (CEST) magnetic resonance imaging experiment, involves irradiating various regions of the spectrum with a weak B(1) field while monitoring the effect on the visible major-state peaks. The variation in major-state peak intensities as a function of frequency offset and B(1) field strength is quantified to obtain the minor-state population, its lifetime, and excited-state chemical shifts and line widths. The methodology was validated with (15)N CEST experiments recorded on an SH3 domain-ligand exchanging system and subsequently used to study the folding transition of the A39G FF domain, where the invisible unfolded state has a lifetime of ∼20 ms. Far more accurate exchange parameters and chemical shifts were obtained than via analysis of Carr-Purcell-Meiboom-Gill relaxation dispersion data.
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10.1021/ja3001419
|
8631999
|
Differential heparin inhibition of skeletal muscle alpha-dystroglycan binding to laminins.
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The laminin binding properties of alpha-dystroglycan purified from rabbit skeletal muscle membranes were examined. In a solid phase microtiter assay, 125I-laminin (laminin-1) bound to purified alpha-dystroglycan in a specific and saturable manner with a half-maximal concentration of 8 nM. The binding of 125I- alpha-dystroglycan to native laminin and merosin (a mixture of laminin-2 and -4) was also compared using the solid phase assay. The absolute binding of 125I- alpha-dystroglycan to laminin (6955 +/- 250 cpm/well) was similar to that measured for merosin (7440 +/- 970 cpm/well). However, inclusion of 1 mg/ml heparin in the incubation medium inhibited 125I-alpha-dystroglycan binding to laminin by 84 +/- 4.3% but inhibited 125I-alpha-dystroglycan binding to merosin by only 17 +/- 5.2%. Similar results were obtained with heparan sulfate, while de-N-sulfated heparin, hyaluronic acid, and chondroitin sulfate had no differential effect. These results were confirmed by iodinated laminin and merosin overlay of electrophoretically separated and blotted dystrophin-glycoprotein complex. In contrast to the results obtained with skeletal muscle alpha-dystroglycan, both laminin and merosin binding to purified brain alpha-dystroglycan was significantly inhibited by heparin. Our data support the possibility that one or more heparan sulfate proteoglycans may specifically modulate the interaction of alpha-dystroglycan with different extracellular matrix proteins in skeletal muscle.
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10.1074/jbc.271.7.3817
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3016329
|
Putative glycoprotein gene of varicella-zoster virus with variable copy numbers of a 42-base-pair repeat sequence has homology to herpes simplex virus glycoprotein C.
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A strain variation of varicella-zoster virus that maps to the UL region of the genome was found to be due to different copy numbers of a high GC 42-base-pair repeat. DNA sequence analysis of this variable region showed the sequence to be 5-GCGGGATCGGGCTTTCGGG(A/T)AGCGGCCGAGGTGGGCGCGACG-3. Strains Scott and Webster both contain 7 and 32/42 copies of the repeat, whereas strain Oka has exactly 4 copies less. Microheterogeneity exists within the repeated sequences, depending on the strain and the repeat number. Sequencing of the entire EcoRI P fragment (which contains the repeated sequences) and part of the adjacent EcoRI M and EcoRI Q fragments from strain Scott showed that the repeats are part of a large open reading frame that could code for a polypeptide core with a molecular weight of 66,000. Several potential TATA boxes exist upstream and two polyadenylation signals are found downstream of the open reading frame. The predicted protein bears several characteristics of a glycoprotein. The region is transcriptionally active in varicella-zoster virus-infected cells, specifying at least three RNA species of 1.7, 1.95, and 2.5 kilobases, which are transcribed from the same DNA strand. Part of the predicted protein has a high degree of homology to the herpes simplex virus type 1 glycoprotein gC.
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10.1128/JVI.59.3.660-668.1986
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26953860
|
Reciprocal Feedback: Closing the Loop on Postactivity Surveys.
|
Those who conduct feedback surveys, which follow almost every CME presentation and medical-school lecture, would do well to offer participants' reciprocal feedback. That is, the course director should provide each survey respondent, on request, a brief summary of the comments received from this survey and the extent to which the recommendations will lead to objective improvements in the future. Surveyors who provide respondents with reciprocal feedback can expect heightened credibility, more reliable feedback in the future, and an added incentive to effect significant change for the better. Feedback has not circled all the way back until we have provided a succinct summary of results to those who have offered us their comments and suggestions. Let us close the loop; let reciprocal feedback become the last word in CME surveys.
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10.1097/CEH.0000000000000006
|
2946953
|
Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves' disease.
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Thyrostatic drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels. The mechanism of this immunosuppression is unknown. We studied methimazole-induced immunoregulatory effects prospectively in 14 patients with Graves' disease treated for up to six months. The numbers of circulating activated, HLA-DR-positive T helper/inducer cells decreased gradually, from 8.3+1.7 percent (+SD) to 1.0+1.7 percent (P less than 0.001). HLA-DR-positive T suppressor/cytotoxic cells increased transiently at one month, from 2.0+1.9 percent to 12.6+6.4 percent (P less than 0.001), and returned to 2.9+3.7 percent at six months. Methimazole did not alter the HLA-DR expression of T cells in vitro. In two patients, the helper activity of T cells in inducing autoantibody secretion in vitro was substantially reduced after one month of methimazole treatment. Before treatment, large proportions of thyroid-infiltrating T-cell subsets expressed the activation markers HLA-DR, interferon-gamma, and interleukin-2 receptors, which were partially lost during therapy. Methimazole treatment was accompanied by a gradual reduction in circulating levels of thyrotropin-receptor, microsomal, and thyroglobulin autoantibodies. These results are compatible with the view that methimazole-induced immunoregulation in Graves' disease is mediated by a direct inhibitory effect on thyrocytes. This inhibition is in turn accompanied by marked changes in the proportions of activated T helper-like and T suppressor-like cells. This altered T-cell activation profile reflects, at least in part, the functional suppression of autoantibody production observed in methimazole-treated patients with Graves' disease.
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10.1056/NEJM198701013160104
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17611168
|
Physical activity across the curriculum (PAAC): rationale and design.
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Over the years schools have reduced physical education and recess time in favor of more academic instruction. Due to the drastic rise in obesity levels among children, some states have begun to mandate minimum amounts of physical activity (PA) that school children receive, causing schools to find alternative methods for increasing PA levels. Physical Activity Across the Curriculum (PAAC) is a 3-year randomized clinical trial incorporating moderate-intensity PA in elementary schools to reduce childhood obesity. This paper describes the rational, design, and methods of the PAAC intervention study. Twenty-two elementary schools were randomized to either a control or intervention condition. In schools randomized to the intervention condition (PAAC), regular classroom teachers were taught how to incorporate PA into standard academic lessons. Teachers were asked to accumulate 90-100 min/week of PAAC each week through out the 3-year study period. Schools randomized to the control group did not alter their teaching methods. Direct observation of PA levels in the classroom was collected weekly. Height and weight was measured twice a year to calculate BMI. Two years of the intervention have been completed and only one school has left the study. The remaining 21 schools are participating in the final intervention year. The results from the PAAC intervention may provide schools with an alternative method to increase PA levels in children and reduce childhood obesity.
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10.1016/j.cct.2007.05.004
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3736765
|
[Cannulation of the internal jugular vein with 2 silastic catheters. A new method of vascular access for hemodialysis].
|
The internal jugular vein cannulation (IJV) using two silastic catheters (CT) is a new vascular access method for temporary and immediate use in hemodialysis. From November 1982 to November 1984, 138 pairs of CT were used in 129 uremic patients for a mean duration of 54 days per patient (1 to 17 months) permitting to carry out more than 3000 dialysis sessions. Five complications were observed: 3 skin exit infections with 2 septicemias cured with antibiotics and CT removal, 2 vascular thrombosis treated with urokinase and anticoagulant; 1 anaphylactoid reaction at the time of insertion. IJV CT offers a convenient alternative to conventional percutaneous vascular access method that can be safely proposed in long term hemodialysis.
| |
26367658
|
Mode-locked, 1.94-μm, all-fiberized laser using WS₂ based evanescent field interaction.
|
We demonstrate the use of an all-fiberized, mode-locked 1.94 μm laser with a saturable absorption device based on a tungsten disulfide (WS2)-deposited side-polished fiber. The WS2 particles were prepared via liquid phase exfoliation (LPE) without centrifugation. A series of measurements including Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM) revealed that the prepared particles had thick nanostructures of more than 5 layers. The prepared saturable absorption device used the evanescent field interaction mechanism between the oscillating beam and WS2 particles and its modulation depth was measured to be ~10.9% at a wavelength of 1925 nm. Incorporating the WS2-based saturable absorption device into a thulium-holmium co-doped fiber ring cavity, stable mode-locked pulses with a temporal width of ~1.3 ps at a repetition rate of 34.8 MHz were readily obtained at a wavelength of 1941 nm. The results of this experiment confirm that WS2 can be used as an effective broadband saturable absorption material that is suitable to passively generate pulses at 2 μm wavelengths.
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10.1364/OE.23.019996
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22056338
|
Dynamics and sensitivity analysis of high-frequency conduction block.
|
The local delivery of extracellular high-frequency stimulation (HFS) has been shown to be a fast acting and quickly reversible method of blocking neural conduction and is currently being pursued for several clinical indications. However, the mechanism for this type of nerve block remains unclear. In this study, we investigate two hypotheses: (1) depolarizing currents promote conduction block via inactivation of sodium channels and (2) the gating dynamics of the fast sodium channel are the primary determinate of minimal blocking frequency. Hypothesis 1 was investigated using a combined modeling and experimental study to investigate the effect of depolarizing and hyperpolarizing currents on high-frequency block. The results of the modeling study show that both depolarizing and hyperpolarizing currents play an important role in conduction block and that the conductance to each of three ionic currents increases relative to resting values during HFS. However, depolarizing currents were found to promote the blocking effect, and hyperpolarizing currents were found to diminish the blocking effect. Inward sodium currents were larger than the sum of the outward currents, resulting in a net depolarization of the nodal membrane. Our experimental results support these findings and closely match results from the equivalent modeling scenario: intra-peritoneal administration of the persistent sodium channel blocker ranolazine resulted in an increase in the amplitude of HFS required to produce conduction block in rats, confirming that depolarizing currents promote the conduction block phenomenon. Hypothesis 2 was investigated using a spectral analysis of the channel gating variables in a single-fiber axon model. The results of this study suggested a relationship between the dynamical properties of specific ion channel gating elements and the contributions of corresponding conductances to block onset. Specifically, we show that the dynamics of the fast sodium inactivation gate are too slow to track the high-frequency changes in membrane potential during HFS, and that the behavior of the fast sodium current was dominated by the low-frequency depolarization of the membrane. As a result, in the blocked state, only 5.4% of nodal sodium channels were found to be in the activatable state in the node closest to the blocking electrode, resulting in conduction block. Moreover, we find that the corner frequency for the persistent sodium channel activation gate corresponds to the frequency below which high-frequency stimuli of arbitrary amplitude are incapable of inducing conduction block.
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10.1088/1741-2560/8/6/065007
|
149497
|
Primary intimal fibroplasia in a child with Down's syndrome.
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A 14-year-old girl known to have trisomy 21 and who came to us with weight loss followed by hypertension proved to have diffuse arterial dysplasia involving the intimal layer (primary intimal fibroplasia). This is a rare cause of elevated blood pressure in children and has not been previously reported in a child with Down's syndrome. Unusual features of this case also include the widespread distribution of the lesions limited to the large muscular distributing arteries, the rapidly progressive course, and the predominance of abdominal signs and symptoms.
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10.1001/archpedi.1978.02120320060014
|
14651755
|
Critical appraisal skills of family physicians in Ontario, Canada.
|
Our primary objective in this study was to measure family physicians' knowledge of the key elements that go into assessing the validity and interpreting the results in three different types of studies: i) a randomized controlled trial (RCT); ii) a study evaluating a diagnostic test; and iii) a systematic review (SR). Our secondary objectives were to determine the relationship between the above skills and age, gender, and type of practice. We obtained a random sample of 1000 family physicians in Ontario from the College of Family Physicians of Canada database. These physicians were sent a questionnaire in the mail with follow-up mailings to non-responders at 3 and 8 weeks. The questionnaire was designed to measure knowledge and understanding of the basic concepts of critical appraisal skills. Based on the responses to the questions an Evidence Based Medicine (EBM) Knowledge Score was determined for each physician. A response rate of 30.2% was achieved. The respondents were younger and more likely to be recent graduates than the population of Ontario Family Physicians as a whole. This was an expected outcome. Just over 50% of respondents were able to answer questions concerning the critical appraisal of methods and the interpretation of results of research articles satisfactorily. The average score on the 12-point EBM Knowledge Scale was 6.4. The younger physicians scored higher than the older physicians, and academic physicians scored higher than community-based physicians. Scores of male and female physicians did not differ. We have shown that in a population of physicians which is younger than the general population of physicians, about 50% have reasonable knowledge regarding the critical appraisal of the methods and the interpretation of results of a research article. In general, younger physicians were more knowledgeable than were older physicians. EBM principles were felt to be important to the practice of medicine by 95% of respondents.
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10.1186/1472-6920-3-10
|
35714679
|
Screening for obstructive sleep apnoea in patients with serious mental illness.
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Patients with serious mental illness (SMI) are at increased risk of obstructive sleep apnoea (OSA). Despite this, OSA is frequently under-recognised in the psychiatric population. This study describes the results of OSA screening in SMI patients. Patients with SMI attending a metropolitan mental health clinic were screened for OSA using the OSA50, STOP-BANG Questionnaire (SBQ), Epworth Sleep Score (ESS) and the Pittsburgh Sleep Quality Index (PSQI). They were then offered diagnostic sleep testing via ResMed ApneaLink TM and polysomnography. Of the 65 patients recruited, 65% had a primary diagnosis of schizophrenia or schizoaffective disorder, 85% were on antipsychotic medications and the majority were obese. Approximately 50% of patients reported poor sleep quality via the PSQI, in contrast to 12% with elevated daytime sleepiness via the ESS. 46% of our cohort were at risk of OSA due to an elevated OSA50 or SBQ. Of the five patients who agreed to proceed to diagnostic sleep testing, three were diagnosed with OSA. A high proportion of patients with psychiatric illness are at risk of sleep-disordered breathing. Sleep dissatisfaction is high. The low uptake of sleep investigation requires improved patient engagement to improve OSA diagnosis in this high-risk group.
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10.1177/10398562221108632
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32356582
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Vulval hidradenoma papilliferum: a clinical and dermoscopic study.
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Hidradenoma papilliferum (HP) is a rare, slow-growing, benign adnexal tumour with apocrine differentiation. It usually affects the anogenital region in adult women and is clinically polymorphous, mimicking other benign or malignant neoformations. The dermoscopic features of vulval HP have not been reported yet. We report the clinical and dermoscopic features in a case series of histopathologically proven vulval HPs. Dermoscopy may be a useful tool for the diagnosis of vulval HP. To our knowledge, our paper represents the first report of dermoscopic findings in a series of vulval HPs in a multiracial population. © 2020 British Association of Dermatologists.
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10.1111/ced.14254
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36677360
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Mechanisms of BPA Degradation and Toxicity Resistance in Rhodococcus equi.
|
Bisphenol A (BPA) pollution poses an increasingly serious problem. BPA has been detected in a variety of environmental media and human tissues. Microbial degradation is an effective method of environmental BPA remediation. However, BPA is also biotoxic to microorganisms. In this study, Rhodococcus equi DSSKP-R-001 (R-001) was used to degrade BPA, and the effects of BPA on the growth metabolism, gene expression patterns, and toxicity-resistance mechanisms of Rhodococcus equi were analyzed. The results showed that R-001 degraded 51.2% of 5 mg/L BPA and that 40 mg/L BPA was the maximum BPA concentration tolerated by strain R-001. Cytochrome P450 monooxygenase and multicopper oxidases played key roles in BPA degradation. However, BPA was toxic to strain R-001, exhibiting nonlinear inhibitory effects on the growth and metabolism of this bacterium. R-001 bacterial biomass, total protein content, and ATP content exhibited V-shaped trends as BPA concentration increased. The toxic effects of BPA included the downregulation of R-001 genes related to glycolysis/gluconeogenesis, pentose phosphate metabolism, and glyoxylate and dicarboxylate metabolism. Genes involved in aspects of the BPA-resistance response, such as base excision repair, osmoprotectant transport, iron-complex transport, and some energy metabolisms, were upregulated to mitigate the loss of energy associated with BPA exposure. This study helped to clarify the bacterial mechanisms involved in BPA biodegradation and toxicity resistance, and our results provide a theoretical basis for the application of strain R-001 in BPA pollution treatments.
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10.3390/microorganisms11010067
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38832626
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Children and young people's consultation rates for psychosocial problems between 2016 and 2021 in the Netherlands.
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Worldwide, there are concerns about declining mental health of children and young people (CYP). To examine trends in GP consultation rates for psychosocial problems and the impact of the COVID-19 pandemic. We performed a population-based cohort study using electronic GP records of CYP (0-24 years) living in the Rotterdam metropolitan area between 2016 and 2021. We calculated monthly consultation rates for psychosocial problems, stratified by age group and sex. We used negative binomial models to model the pre-COVID-19 trend, and estimate expected rates post-COVID-19 onset. We modelled the effect of COVID-19 infection rate and school closure on consultation rates per sex and age group. The cohort increased from 64801 to 92093 CYP between January 2016 and December 2021. Median age was 12.5 years and 49.3% was female. Monthly consultation rates increased from 2,443 to 4,542 consultations per 100,000 patient months over the six years. This trend (RR 1.009, 95%CI 1.008-1.011) started well before the COVID-19 pandemic. Consultation rates of adolescent girls and young women increased most strongly. Between March and May 2020, there was a temporary reduction in consultation rates, whereupon these returned to expected levels. COVID-19 infection rate and school closures showed small but significant associations with consultation rates for psychosocial problems but this did not affect the overall trend. Although consultation rates for psychosocial problems increased, this increment was stable over the entire study period. The COVID-19 pandemic did not significantly increase consultation rates for psychosocial problems in CYP. The consultation rates increased, especially in adolescent girls and young women.
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10.1080/13814788.2024.2357780
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28531912
|
From Bench to Market: Preparing Human Pluripotent Stem Cells Derived Cardiomyocytes for Various Applications.
|
Human cardiomyocytes (CMs) cease to proliferate and remain terminally differentiated thereafter, when humans reach the mid-20s. Thus, any damages sustained by myocardium tissue are irreversible, and they require medical interventions to regain functionality. To date, new surgical procedures and drugs have been developed, albeit with limited success, to treat various heart diseases including myocardial infarction. Hence, there is a pressing need to develop more effective treatment methods to address the increasing mortality rate of the heart diseases. Functional CMs are not only an important in vitro cellular tool to model various types of heart diseases for drug development, but they are also a promising therapeutic agent for cell therapy. However, the limited proliferative capacity entails difficulties in acquiring functional CMs in the scale that is required for pathological studies and cell therapy development. Stem cells, human pluripotent stem cells (hPSCs) in particular, have been considered as an unlimited cellular source for providing functional CMs for various applications. Notable progress has already been made: the first clinical trials of hPSCs derived CMs (hPSC-CMs) for treating myocardial infarction was approved in 2015, and their potential use in disease modeling and drug discovery is being fully explored. This concise review gives an account of current development of differentiation, purification and maturation techniques for hPSC-CMs, and their application in cell therapy development and pharmaceutical industries will be discussed with the latest experimental evidence.
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10.15283/ijsc17024
|
11417629
|
Molecular diagnosis of microbial contamination in cosmetic and pharmaceutical products: a review.
|
Molecular methodologies such as adenosine triphosphate (ATP) bioluminescence and polymerase chain reaction (PCR)-based assays provide rapid quality control analysis of cosmetic and pharmaceutical finished products and raw materials. Using a single enrichment broth for bacteria, yeast, and mold, ATP bioluminescence detected microbial contamination within 27 h. Samples were automatically lysed to release microbial ATP and light production was quantitated using the Celsis Optocomp. However, to maintain the detection time to within 27 h, different enrichment broths were required for neutralization of antimicrobial ingredients in finished products and to provide specific nutrients for growth optimization. To perform the PCR reaction, bacterial DNA was extracted using a Tris-EDTA-Tween 20-proteinase K buffer at 35 degrees C while yeast and mold DNA were extracted using a Tris-EDTA-SDS buffer at 95 degrees C. Extracted microbial DNA was added to Ready-To-Go PCR beads and specific DNA primers. The primers were targeted to amplify specific regions within Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhimurium, Burkholderia cepacia, Candida albicans, and Aspergillus niger. Furthermore, conserved bacterial ribosomal DNA sequences have also been used for sterility testing of samples. The results from these studies indicate that both ATP bioluminescence and PCR assays provide rapid, reliable, and cost effective methods for quality evaluation. This will ultimately result in faster product release and production optimization.
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21474006
|
Dizziness and vertigo in the adolescent.
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The exact incidence of dizziness and vertigo during adolescence is not known. For those few adolescents who seek outpatient evaluation for these complaints, the majority are diagnosed with migraine headache. The authors provide a discussion of the differential diagnosis, evaluation, and management of vertigo and dizziness in the adolescence with emphasis on migraine headaches, chronic daily headaches, postural orthostatic tachycardia syndrome, and presentations that may require head imaging. Copyright © 2011 Elsevier Inc. All rights reserved.
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10.1016/j.otc.2011.01.004
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37850002
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Patient Preferences for the Management of Gastrointestinal Symptoms in Kidney Transplantation: a Discrete Choice Experiment.
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Gastrointestinal (GI) symptoms in kidney transplant are common and debilitating. We aimed to ascertain patients' preferences for GI symptom management options to help future interventions align with treatment priorities. A discrete choice experiment was conducted with kidney transplant recipients in 3 Australian nephrology units. A multinomial logit model was used to quantify the preferences and trade-offs between 5 characteristics: cost, formulation, symptom burden, dietary changes, and medication quantities. Seventy patients participated (mean age ± SD: 47 ± 15 years, 56% female), 57% had GI symptoms. Patients preferred interventions that will achieve complete resolution of GI symptoms compared to no improvement (odds ratio [95% confidence interval]: 15.3 [1.80, 129.50]), were delivered as a tablet rather than a sachet (1.6 [1.27, 2.08]), retained their current diet compared to eliminating food groups (6.0 [2.19, 16.27]), reduced medication burden (1.4 [1.06, 1.79]), and had lower costs (0.98 [0.96, 1.00]). Participants would be willing to pay AUD$142.20 [$83.90, $200.40] monthly to achieve complete resolution of GI symptoms or AUD$100.90 [$9.60, $192.10] to have moderate improvement in symptoms. Interventions that are highly effective in relieving all GI symptoms without the need for substantive dietary changes, and in tablet form, are most preferred by kidney transplant recipients. © 2023 International Society of Nephrology. Published by Elsevier Inc.
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10.1016/j.ekir.2023.07.034
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29603740
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Nicotine inhibits osteogenic differentiation of human periodontal ligament cells under cyclic tensile stress through canonical Wnt pathway and α7 nicotinic acetylcholine receptor.
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Nicotine, the main psychoactive component of tobacco, affects cell metabolism, proliferation, adhesion and, importantly, the osteogenic differentiation of fibroblasts. Approximately 15% of all orthodontic patients are adults among who one-fifth are smokers. Hence, it is necessary to have insight into the effects of nicotine on the osteogenic differentiation of hPDLCs during orthodontic tooth movement. This study aimed to investigate the effects and mechanisms of nicotine on the osteogenic differentiation of human periodontal ligament cells (hPDLCs) under the application of cyclic tensile stress. hPDLCs were obtained from donor third molars. The hPDLCs were treated with nicotine and/or cyclic tensile stress that was applied with a cell stress plus unit. The effect of nicotine on cell viability was analyzed using the MTT assay. The osteogenic differentiation of hPDLCs was detected by alkaline phosphatase staining, Alizarin Red S staining, quantitative real-time polymerase chain reaction and western blotting. In combination with cyclic tensile stress, nicotine prevented the tensile stress-induced increase in alkaline phosphatase activity, formation of mineralization nodules and the upregulation of mRNA and protein expression of Runt-related transcription factor 2, transcription factor Sp7 and collagen type I; however, canonical Wnt pathway was activated. Furthermore, the addition of Dickkopf-related protein 1 and α-bungarotoxin counteracted the negative effect of nicotine and rescued the osteogenic differentiation of hPDLCs, respectively. These results indicate that nicotine prevents the increased osteogenic potential of hPDLCs induced by cyclic tensile stress by binding to an α7 nicotinic acetylcholine receptor and activating the canonical Wnt pathway. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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10.1111/jre.12545
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27998810
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Advances and limitations of visual conditioning protocols in harnessed bees.
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Bees are excellent invertebrate models for studying visual learning and memory mechanisms, because of their sophisticated visual system and impressive cognitive capacities associated with a relatively simple brain. Visual learning in free-flying bees has been traditionally studied using an operant conditioning paradigm. This well-established protocol, however, can hardly be combined with invasive procedures for studying the neurobiological basis of visual learning. Different efforts have been made to develop protocols in which harnessed honey bees could associate visual cues with reinforcement, though learning performances remain poorer than those obtained with free-flying animals. Especially in the last decade, the intention of improving visual learning performances of harnessed bees led many authors to adopt distinct visual conditioning protocols, altering parameters like harnessing method, nature and duration of visual stimulation, number of trials, inter-trial intervals, among others. As a result, the literature provides data hardly comparable and sometimes contradictory. In the present review, we provide an extensive analysis of the literature available on visual conditioning of harnessed bees, with special emphasis on the comparison of diverse conditioning parameters adopted by different authors. Together with this comparative overview, we discuss how these diverse conditioning parameters could modulate visual learning performances of harnessed bees. Copyright © 2016 Elsevier Ltd. All rights reserved.
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10.1016/j.jphysparis.2016.12.006
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9437784
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Comparison of Roche Cobas Amplicor and Abbott LCx for the rapid detection of Chlamydia trachomatis in specimens from high-risk patients.
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To evaluate two automated amplification systems for the detection of Chlamydia trachomatis in urogenital specimens, the Cobas Amplicor (Roche Diagnostic Systems, Branchburg, NJ) and the LCx (Abbott Laboratories, Abbott Park, IL). The two systems were compared testing specimens from 302 high-risk patients, including 98 female cervical swab specimens and 204 male urine specimens. The patients attended the state STD clinic in Reykjavik, Iceland, either because of symptoms or as a result of contract tracing. The prevalence of C. trachomatis infection was 15.3% in women and 13.2% in men. For the male urine specimens, the sensitivity and specificity were 100% and 99.4% for the Cobas Amplicor and 74.1% and 100% for the LCx. In the cervical swabs, both systems detected all 15 true-positive specimens. The internal control used with the Cobas Amplicor detected inhibition in 2% of the male urine and 20% female cervical swabs, respectively. The Cobas Amplicor demonstrated slightly better sensitivity than LCx in male urine specimens. Both systems offer the benefits of automation for routine diagnostic testing.
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10.1097/00007435-199801000-00009
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15124389
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[Medical and psychological aspects of safety measures maintenance among nuclear and power station personnel].
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The article deals with 15-year experience of medical and psychophysiologic service in Medical and Sanitary Establishment No. 156 and Balakovo nuclear power station on providing reliability of occupational activities for the station personnel.
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24495499
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Procedures of recruiting, obtaining informed consent, and compensating research participants in Qatar: findings from a qualitative investigation.
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Very few researchers have reported on procedures of recruiting, obtaining informed consent, and compensating participants in health research in the Arabian Gulf Region. Empirical research can inform the debate about whether to adjust these procedures for culturally diverse settings. Our objective was to delineate procedures related to recruiting, obtaining informed consent, and compensating health research participants in the extremely high-density multicultural setting of Qatar. During a multistage mixed methods project, field observations and qualitative interviews were conducted in a general medicine clinic of a major medical center in Qatar. Participants were chosen based on gender, age, literacy, and preferred language, i. e., Arabic, English, Hindi and Urdu. Qualitative analysis identified themes about recruitment, informed consent, compensation, and other research procedures. A total of 153 individuals were approached and 84 enrolled; the latter showed a diverse age range (18 to 75 years); varied language representation: Arabic (n = 24), English (n = 20), Hindi (n = 20), and Urdu (n = 20); and balanced gender distribution: women (n = 43) and men (n = 41). Primary reasons for 30 declinations included concern about interview length and recording. The study achieved a 74% participation rate. Qualitative analytics revealed key themes about hesitation to participate, decisions about participation with family members as well as discussions with them as "incidental research participants", the informed consent process, privacy and gender rules of the interview environment, reactions to member checking and compensation, and motivation for participating. Vulnerability emerged as a recurring issue throughout the process among a minority of participants. This study from Qatar is the first to provide empirical data on recruitment, informed consent, compensation and other research procedures in a general adult population in the Middle East and Arabian Gulf. This investigation illustrates how potential research participants perceive research participation. Fundamentally, Western ethical research principles were applicable, but required flexibility and culturally informed adaptations.
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10.1186/1472-6939-15-9
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36937941
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Enhanced external counterpulsation improves dysfunction of forearm muscle caused by radial artery occlusion.
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This study aimed to investigate the therapeutic effect of enhanced external counterpulsation (EECP) on radial artery occlusion (RAO) through the oscillatory shear (OS) and pulsatile shear (PS) models of human umbilical vein endothelial cells (HUVECs) and RAO dog models. We used high-throughput sequencing data GSE92506 in GEO database to conduct time-series analysis of functional molecules on OS intervened HUVECs, and then compared the different molecules and their functions between PS and OS. Additionally, we studied the effect of EECP on the radial artery hemodynamics in Labrador dogs through multi-channel physiological monitor. Finally, we studied the therapeutic effect of EECP on RAO at the histological level through Hematoxylin-Eosin staining, Masson staining, ATPase staining and immunofluorescence in nine Labrador dogs. With the extension of OS intervention, the cell cycle decreased, blood vessel endothelial cell proliferation and angiogenesis responses of HUVECs were down-regulated. By contrast, the inflammation and oxidative stress responses and the related pathways of anaerobic metabolism of HUVECs were up-regulated. Additionally, we found that compared with OS, PS can significantly up-regulate muscle synthesis, angiogenesis, and NO production related molecules. Meanwhile, PS can significantly down-regulate inflammation and oxidative stress related molecules. The invasive arterial pressure monitoring showed that 30Kpa EECP treatment could significantly increase the radial artery peak pressure ( p = 0.030, 95%CI, 7.236-82.524). Masson staining showed that RAO significantly increased muscle interstitial fibrosis ( p = 0.002, 95%CI, 0.748-2.128), and EECP treatment can reduce this change ( p = 0.011, 95%CI, -1.676 to -0.296). ATPase staining showed that RAO significantly increased the area of type II muscle fibers ( p = 0.004, 95%CI, 7.181-25.326), and EECP treatment could reduce this change ( p = 0.001, 95%CI, -29.213 to -11.069). In addition, immunofluorescence showed that EECP increased angiogenesis in muscle tissue ( p = 0.035, 95%CI, 0.024-0.528). EECP improves interstitial fibrosis and hypoxia, and increases angiogenesis of muscle tissue around radial artery induced by RAO. Copyright © 2023 Wang, Yao, Huang, Liang, Zhang, Shi, Wei, Zhou, Zhang and Wu.
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10.3389/fcvm.2023.1115494
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30722940
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Surgical treatment of male infertility: a state-of-the-art overview.
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Surgical treatments offer effective solutions for many couples experiencing male factor infertility. This Views and Reviews collection of articles offers a state-of-the-art overview of the surgical procedures commonly used to treat impaired male reproductive health. Copyright © 2019. Published by Elsevier Inc.
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10.1016/j.fertnstert.2019.01.005
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16384295
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Measurement of the wrong-sign decays D0 --> K+ pi- pi0 and D0 --> K+ pi- pi+ pi-, and search for CP violation.
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Using 281 fb-1 of data from the Belle experiment recorded at or near the (4S) resonance, we have measured the rates of the "wrong-sign" decays D0 --> K+ pi- pi0 and D0 --> K+ pi- pi+ pi- relative to those of the Cabibbo-favored decays D0 --> K- pi+ pi0 and D0 --> K- pi+ pi+ pi-. These wrong-sign decays proceed via a doubly Cabibbo-suppressed amplitude or via D0-D0 mixing; the latter has not yet been observed. We obtain R(WS)(K pi pi0) = [0.229 +/- 0.015(stat)(+0.013)(-0.009)(syst)]% and R(WS)(K3pi) = [0.320 +/- 0.018(stat)(+0.018)(0.013)(syst)]%. The CP asymmetries are measured to be -0.006 +/- 0.053 and -0.018 +/- 0.044 for the K+ pi- pi0 and K+ pi- pi+ pi- final states, respectively.
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10.1103/PhysRevLett.95.231801
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1706888
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Retrograde adriamycin sensory ganglionectomy: novel approach for the treatment of intractable pain.
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Selective sensory ganglionectomy by means of retrograde suicide transport of adriamycin was performed on 3 patients with neuropathic pain in the areas of the trigeminal and intercostal nerves, producing significant pain relief, particularly from hyperalgesic pain. Adriamycin ganglionectomy is considered as a less invasive and highly selective pain treatment, which may possibly become an alternative for surgical ganglionectomy or rhizotomy.
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10.1159/000100196
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6083863
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The basement membrane of bovine corneal endothelial cells in culture with beta-aminopropionitrile: biosynthesis of hexagonal lattices composed of a 160 nm dumbbell-shaped structure.
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Bovine corneal endothelial cells maintained in culture produced an extracellular matrix on their basal surface. In the presence of beta-aminopropionitrile (beta-APN) (100-500 micrograms/ml), an inhibitor of cross-linking, this extracellular matrix contained hexagonal lattices of 150 nm periodicity. The lattice was composed of round densities 60 nm in diameter comprising the nodes of the lattice and rod-like structures 40 nm in thickness comprising its sides. This structure is almost identical to that of bovine Descemet's membrane in situ. The lattice was produced only in the presence of beta-APN. By freeze-etch replica and negative staining of 1 day cultures, the unit component of the lattice appeared to be a novel 160 nm long dumbbell-shaped symmetrical structure. The central rod of the dumbbell-shaped structure was 80 nm long and 20 to 50 nm in diameter with round ends (40-50 nm). In the rod 2 nm fibrillar substructures were discerned by negative staining. The rod-like central portion was resistant to trypsin digestion whereas the round ends were digested by it. Both structures disappeared after bacterial collagenase digestion. By immunoblotting the extracellular matrix contained 160kd and 180kd bands which bound anti-type IV collagen antibodies and a 140kd band which bound anti-type III collagen antibodies. The lattice area was also positively stained with these antibodies by immunoperoxidase. The findings strongly suggest that the hexagonal lattice of bovine Descemet's membranes in situ is composed of this collagenous structure.
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9224228
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Time trends of physician visits and treatment patterns of peptic ulcer disease in the United States.
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In the last 4 decades, the prevalence rates of peptic ulcer disease and our understanding of its pathophysiological features underwent major changes. To analyze how these trends affected physician visits and treatment of ulcer disease. The National Diseases and Therapeutic Index of IMS America Ltd, Plymouth Meeting, Pa, was used as the data source. Survey data were obtained from a representative sample of US physicians 4 times per year during a 48-hour period and extrapolated to a national level. Physician visits for gastric, duodenal, and all peptic ulcers were expressed as rates per 100,000 living US population. Between 1958 and 1995, physician visits for duodenal ulcer showed a marked decline, while those for gastric ulcer remained largely unchanged. In 1995, 4 million patients visited a physician because of peptic ulcer, corresponding to a rate of 1500 per 100,000 US population. The predominant therapy changed from anticholinergics, tranquilizers, and antacids between 1958 and 1977 to histamine2 receptor antagonist from 1978 until 1988, which subsequently became replaced in part by sucralfate and proton pump inhibitors. In 1995, about 75% of ulcers were still treated primarily with antisecretory medications, and only 5% received antibiotic therapy. Peptic ulcer is still common, although duodenal ulcer rates continue to decrease. The historical trends of treatment regimens show a steady change between various medications. No therapeutic class dominated ulcer therapy for more than 20 years. This trend is likely to continue, particularly, in light of the small fraction currently treated by antibiotics to eradicate Helicobacter pylori.
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34802068
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The efficacy and safety of insertable cardiac monitor on atrial fibrillation detection in patients with ischemic stroke: a systematic review and meta-analysis.
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Atrial fibrillation (AF) leads to a high risk of recurrent stroke, and the insertable cardiac monitor (ICM), as a new kind of electrocardiographic monitoring device, has been proven to enhance the recognition rate of AF. The aim of this systematic review was to evaluate the efficacy and safety of the ICM use in AF detection of patients with stroke. We pooled 1233 patients from three randomized controlled trials (RCTs). The detection rate of AF was superior in the ICM group to that in the control group at 6 months (risk ratio [RR], 4.63; P < 0.0001; 95% confidence interval [CI], 2.17-9.90) and 12 months (RR, 5.04; P < 0.00001; 95% CI, 2.93 to 8.68). Patients in the ICM group had a higher rate of oral anticoagulant usage (RR, 2.76; P < 0.00001; 95% CI, 1.89-4.02). However, there was no difference in the time to first detection of AF within 12 months (mean difference, - 8.28; P = 0.82; 95% CI, - 77.84-61.28) or the rate of recurrent ischemic stroke or transient ischemic attack (RR, 0.88; P = 0.51; 95% CI, 0.60-1.28) between the ICM and control groups. In addition, the ICM group experienced more adverse events than the control group within 12 months (RR, 4.42; P = 0.002; 95% CI, 1.69-11.55). To conclude, the sensitivity of ICM is superior to that of conventional external cardiac monitoring. Reducing adverse reactions will be a new development direction of ICM. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
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10.1007/s00415-021-10903-0
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27522322
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BMP4 Cross-talks With Estrogen/ERα Signaling to Regulate Adiposity and Glucose Metabolism in Females.
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Similar to estrogens, bone morphogenetic protein 4 (BMP4) promotes the accumulation of more metabolically active subcutaneous fat and reduction of visceral fat. However, whether there is a cross-talk between BMP4 and estrogen signaling remained unknown. Herein, we found that BMP4 deficiency in white adipose tissue (WAT) increased the estrogen receptor α (ERα) level and its signaling, which prevented adult female mice from developing high fat diet (HFD)-induced obesity and insulin resistance; estrogens depletion up regulated BMP4 expression to overcome overt adiposity and impaired insulin sensitivity with aging, and failure of BMP4 regulation due to genetic knockout led to more fat gain in aged female mice. This mutual regulation between BMP4 and estrogen/ERα signaling may also happen in adipose tissue of women, since the BMP4 level significantly increased after menopause, and was inversely correlated with body mass index (BMI). These findings suggest a counterbalance between BMP4 and estrogen/ERα signaling in the regulation of adiposity and relative metabolism in females. Copyright © 2016. Published by Elsevier B. V.
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10.1016/j.ebiom.2016.07.034
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20150405
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Examining relationships among dialect variation, literacy skills, and school context in first grade.
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This study examined relationships between the use of nonmainstream American English dialects, literacy skills, and school environment among typically developing first graders (n = 617), of whom 48% were African American and 52% were White, in order to describe and better understand the difficulties many children from linguistically diverse backgrounds experience while learning to read. Using hierarchical linear modeling, the authors examined the linear and quadratic relationships between students' dialect variation (DVAR) and their vocabulary, phonological awareness, and word reading skills, taking into account school environment, specifically schoolwide socioeconomic status (SES). The relationships between DVAR and literacy outcomes depended on the outcome of interest and school SES. However, children's race did not generally affect the trajectory or strength of the relationships between outcomes and dialect variation. For vocabulary and word reading, the association was nonlinear, that is, U-shaped, but this depended on school SES. For phonological awareness, a negative linear relationship was observed that did not depend on school SES. The results inform theories on the relationship between DVAR and literacy achievement and suggest a more complex explanation of how nonmainstream American English dialect use might influence how young children learn to read.
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10.1044/1092-4388(2009/08-0058)
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12572118
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[Relationship of insulin dependent metabolic disorders to efficiency of intensive operator's work].
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The purpose was to state correlation between insulin-dependent metabolic disorders and efficiency of intensive operator's work. The investigation included 12-hr mission on a flight simulator performed by 50 normal (aged 23-36) flight-qualified pilots. Increase in the number of erroneous actions was in direct correlation with insulin (r = 0.74, p < 0.01) and in reverse correlation with glucose incretion (r = -0.594, p < 0.01) and STH (r = -0.90, p < 0.006). Metabolic tests (glucose and insulin) showed that psychoemotional loading due to the intensive operator's duties led to early fatigue and sharp straining of tissue structures in people with dysregulatory disorders in insulin metabolism. The psychoemotional loading may also provoke dysregulatory disorders and development of insulin-dependent disturbances.
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38412993
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Artificial intelligence-assisted system for the assessment of Forrest classification of peptic ulcer bleeding: a multicenter diagnostic study.
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Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy. Thieme. All rights reserved.
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10.1055/a-2252-4874
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20619957
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The cost effectiveness of radon mitigation in existing German dwellings--a decision theoretic analysis.
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Radon is a naturally occurring inert radioactive gas found in soils and rocks that can accumulate in dwellings, and is associated with an increased risk of lung cancer. This study aims to analyze the cost effectiveness of different intervention strategies to reduce radon concentrations in existing German dwellings. The cost effectiveness analysis (CEA) was conducted as a scenario analysis, where each scenario represents a specific regulatory regime. A decision theoretic model was developed, which reflects accepted recommendations for radon screening and mitigation and uses most up-to-date data on radon distribution and relative risks. The model was programmed to account for compliance with respect to the single steps of radon intervention, as well as data on the sensitivity/specificity of radon tests. A societal perspective was adopted to calculate costs and effects. All scenarios were calculated for different action levels. Cost effectiveness was measured in costs per averted case of lung cancer, costs per life year gained and costs per quality adjusted life year (QALY) gained. Univariate and multivariate deterministic and probabilistic sensitivity analyses (SA) were performed. Probabilistic sensitivity analyses were based on Monte Carlo simulations with 5000 model runs. The results show that legal regulations with mandatory screening and mitigation for indoor radon levels >100 Bq/m(3) are most cost effective. Incremental cost effectiveness compared to the no mitigation base case is 25,181 euro (95% CI: 7371 euro-90,593 euro) per QALY gained. Other intervention strategies focussing primarily on the personal responsibility for screening and/or mitigative actions show considerably worse cost effectiveness ratios. However, targeting radon intervention to radon-prone areas is significantly more cost effective. Most of the uncertainty that surrounds the results can be ascribed to the relative risk of radon exposure. It can be concluded that in the light of international experience a legal regulation requiring radon screening and, if necessary, mitigation is justifiable under the terms of CEA. Copyright 2010 Elsevier Ltd. All rights reserved.
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10.1016/j.jenvman.2010.06.015
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29450117
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Comparison of response surface methodology and artificial neural network to enhance the release of reducing sugars from non-edible seed cake by autoclave assisted HCl hydrolysis.
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In the current investigation, statistical approaches were adopted to hydrolyse non-edible seed cake (NESC) of Pongamia and optimize the hydrolysis process by response surface methodology (RSM). Through the RSM approach, the optimized conditions were found to be 1.17%v/v of HCl concentration at 54.12 min for hydrolysis. Under optimized conditions, the release of reducing sugars was found to be 53.03 g/L. The RSM data were used to train the artificial neural network (ANN) and the predictive ability of both models was compared by calculating various statistical parameters. A three-layered ANN model consisting of 2:12:1 topology was developed; the response of the ANN model indicates that it is precise when compared with the RSM model. The fit of the models was expressed with the regression coefficient R 2, which was found to be 0.975 and 0.888, respectively, for the ANN and RSM models. This further demonstrated that the performance of ANN was better than that of RSM.
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10.1007/s13205-018-1163-9
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12549871
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Molecularly imprinted polymeric membranes.
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Molecularly imprinted polymeric membranes have been emerged since 1990. Among various kinds of molecular imprinting studies, the application of molecular imprinting to membrane separation is still a novel investigation. In the present review paper, molecularly imprinted polymeric membranes are summarized and examined. The application of molecular imprinting to membrane separation shortly leads to high performance separation membranes.
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10.1023/a:1021537602663
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39337290
|
Hypoxia in Human Obesity: New Insights from Inflammation towards Insulin Resistance-A Narrative Review.
|
Insulin resistance (IR), marked by reduced cellular responsiveness to insulin, and obesity, defined by the excessive accumulation of adipose tissue, are two intertwined conditions that significantly contribute to the global burden of cardiometabolic diseases. Adipose tissue, beyond merely storing triglycerides, acts as an active producer of biomolecules. In obesity, as adipose tissue undergoes hypertrophy, it becomes dysfunctional, altering the release of adipocyte-derived factors, known as adipokines. This dysfunction promotes low-grade chronic inflammation, exacerbates IR, and creates a hyperglycemic, proatherogenic, and prothrombotic environment. However, the fundamental cause of these phenomena remains unclear. This narrative review points to hypoxia as a critical trigger for the molecular changes associated with fat accumulation, particularly within visceral adipose tissue (VAT). The activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor that regulates homeostatic responses to low oxygen levels, initiates a series of molecular events in VAT, leading to the aberrant release of adipokines, many of which are still unexplored, and potentially affecting peripheral insulin sensitivity. Recent discoveries have highlighted the role of hypoxia and miRNA-128 in regulating the insulin receptor in visceral adipocytes, contributing to their dysfunctional behavior, including impaired glucose uptake. Understanding the complex interplay between adipose tissue hypoxia, dysfunction, inflammation, and IR in obesity is essential for developing innovative, targeted therapeutic strategies.
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10.3390/ijms25189802
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17920048
|
Effects of acute cocaine on ERK and DARPP-32 phosphorylation pathways in the caudate-putamen of Fischer rats.
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Activation of extracellular signal-regulated kinase (ERK) and dopamine- and cAMP-regulated phosphoprotein (DARPP-32) pathways has been implicated in biochemical and behavioral effects induced by various drugs of abuse. In this study, we investigated the phosphorylation pathways of these two proteins in response to acute cocaine administration. A single cocaine administration (30 mg/kg) increased ERK-mediated signaling proteins, phosphoryation of cAMP response element-binding protein (CREB) kinase, pp90 ribosomal S6 kinase (RSK), and c-Fos protein levels in the caudate/putamen of Fischer rats. Acute cocaine administration also induced phosphorylation of the striatal-enriched protein tyrosine phosphatase (STEP) and decreased the phosphorylation of DARPP-32 protein at the Thr-75 site. The phosphorylation states of these inhibitors of ERK and DARPP-32 proteins may thus contribute to the effects of cocaine on ERK- and DARPP-32-mediated cascades, on gene expression and on behaviors.
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10.1016/j.brainres.2007.07.051
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33310600
|
Distribution and removal characteristics of microplastics in different processes of the leachate treatment system.
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Microplastics (MPs) in environments are widely concerned in recent years due to the widely occurrence and potential risk to environments. With a large amount of plastic waste discarded into the landfills, leachate generated from landfills was found to be an important pollution source of MPs. However, the removal efficiency and characteristics of MPs in leachate treatment system were not clear. In this study, the concentration variation and the removal performance of MPs in leachate treatment system with the process of pretreatment + biotreatment + advanced treatment were investigated. The results showed that 58.33% of MPs were removed during the leachate treatment process. The Ultrafiltration had the highest efficiency of removing MPs, but the advanced treatment technologies (Nanofiltration and Reverse Osmosis) did not contribute to the removal of MPs. Furthermore, the removal performance of MPs in leachate treatment process was determined by MPs properties, such as size, shape and polymer type. The whole leachate treatment process had higher removal efficiencies for particle MPs compared to fiber MPs, and only 50% of fiber MPs were removed in biological treatment and advanced treatment. Ultrafiltration had better removal effect on microplastics with the size of less than 1 mm, and MPs less than 0.5 mm were almost removed by advanced treatment but accumulated in the sludge with the abundance of 0.893 ± 0.252 items/g. The results showed that a considerable amount of MPs (10 6 items/day) discharged with the effluent (3200 t/d), and most removed MPs from leachate accumulated in sludge, which would cause potential risk to the environments. Copyright © 2020 Elsevier Ltd. All rights reserved.
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10.1016/j.wasman.2020.11.025
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1975452
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Dendritic excitation by glutamate in CA1 hippocampal cells.
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In order to reveal properties and effects of glutamate excitation, CA1 pyramidal cells in rat hippocampal slices were impaled and responses to iontophoresis of glutamate onto sensitive spots in the dendrites were analyzed. The glutamate-elicited response consisted of a steady depolarization; its amplitude was dose-dependent. The cellular response to repeated applications of glutamate showed a striking degree of stability. Both dendritic and somatic depolarization, induced by glutamate and current, respectively, elicited similar discharge patterns. The sensitivity to glutamate was highly localized, corresponding to the dendritic tree of a given cell. Short, repeated glutamate pulses did not interfere with an orthodromic test response, whereas longer glutamate ejections often depressed the EPSP. Combined temporal and spatial pairing of glutamate and orthodromic activation was followed by a lasting increase in synaptic efficiency, similar to LTP.
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10.1016/s0079-6123(08)61246-7
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29806129
|
Infectious pancreatic necrosis virus isolated from farmed rainbow trout and tilapia in Kenya is identical to European isolates.
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Infectious pancreatic necrosis virus (IPNV) is an aquabirnavirus that causes serious diseases in a variety of fish species worldwide. It has been isolated from a large number of healthy fresh and marine water fish. Prior to this study, there was no record of the presence of IPNV infection in Kenya. Here, the presence of IPNV in farmed rainbow trout and tilapia was examined in Nyeri County of central Kenya. Head kidney samples taken from five rainbow trout and three tilapia farms and stored in RNALater ® were processed by PCR followed by sequencing of a segment A fragment covering nucleotide positions 2,120-2,343 bp. IPNV was detected in all the farms sampled with infection ratios ranging from 0.3 to 0.78 although the infections were not associated with any specific clinical signs of disease. These findings were supported by immunohistochemistry staining of the virus in the kidney and exocrine pancreas of rainbow trout. Sequence alignment and phylogenetic analysis revealed that the Kenyan isolates were identical to European isolates, suggesting a common origin. These findings highlight the need for better biosecurity procedures with more stringent surveillance programmes and control for fish diseases, especially focusing on imported breeding materials to Kenya. © 2018 John Wiley & Sons Ltd.
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10.1111/jfd.12807
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7822041
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Dissociation of endotoxic activities in a chemically synthesized lipid A precursor after acetylation.
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In a previous study, a chemically synthesized disaccharide precursor of lipid A (406; identical to lipid IVA) was shown to have dramatically reduced lethality, B-cell mitogenicity, and tumor necrosis factor induction in macrophages when its hydroxyl groups were replaced with either succinyl or acetyl residues (K. Tanamoto, FEBS Lett. 351:325-329, 1994). Succinylated 406 was found to lose Limulus amoebocyte lysate gelation activity completely as a result of the modification (about 10(5)-fold), too, as expected. However, acetyl 406, surprisingly, exhibited activity comparable to that of the original 406. Both succinylated and acetylated 406 lost pyrogenicity completely. These results indicate that one of the typical endotoxic activities was dissociated from the others and that the ability to induce Limulus amoebocyte lysate gelation is not always representative of endotoxin activity.
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10.1128/iai.63.2.690-692.1995
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7121316
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The influence of site of antigen deposition on the local immune response in the mammary gland of the ewe.
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Experiments were carried out to compare the local antibody responses in mammary glands of ewes immunized by infusion of antigen (killed Brucella abortus) into the lactiferous sinuses (trans-epithelial presentation of antigen) or injection into the mammary tissue near the supramammary lymph node (interstitial presentation of antigen). Although both methods of antigen presentation resulted in similar antibody levels in blood, infusion of antigen into the lactiferous sinus resulted in significantly higher levels of agglutinating antibody in milk whey than did injection of antigen. When within-animal comparisons were made, infusion of antigen was also significantly superior to injection of antigen in terms of levels of non-agglutinating antibody in milk as determined by Coomb's antiglobulin assays. Evidence from immunoglobulin estimations in milk whey suggested that any elevation in concentrations of immunoglobulins (including IgA) in milk from ewes, which had received injections of antigen into mammary tissue, was associated with chronic inflammatory damage to these glands.
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10.1111/j.1348-0421.1982.tb00192.x
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24875539
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Loss of hydroxyl groups from the ceramide moiety can modify the lateral diffusion of membrane proteins in S. cerevisiae.
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In the yeast Saccharomyces cerevisiae, structural diversities of complex sphingolipids [inositol phosphorylceramide (IPC), mannosylinositol phosphorylceramide, and mannosyldiinositol phosphorylceramide] are often observed in the presence or absence of hydroxyl groups on the C-4 position of long-chain base (C4-OH) and the C-2 position of very long-chain fatty acids (C2-OH), but the biological significance of these groups remains unclear. Here, we evaluated cellular membrane fluidity in hydroxyl group-defective yeast mutants by fluorescence recovery after photobleaching. The lateral diffusion of enhanced green fluorescent protein-tagged hexose transporter 1 (Hxt1-EGFP) was influenced by the absence of C4-OH and/or C2-OH. Notably, the fluorescence recovery of Hxt1-EGFP was dramatically decreased in the sur2Δ mutant (absence of C4-OH) under the csg1Δcsh1Δ background, in which mannosylation of IPC is blocked leading to IPC accumulation, while the recovery in the scs7Δ mutant (absence of C2-OH) under the same background was modestly decreased. In addition, the amount of low affinity tryptophan transporter 1 (Tat1)-EGFP was markedly decreased in the sur2Δcsg1Δcsh1Δ mutant and accumulated in intracellular membranes in the scs7Δcsg1Δcsh1Δ mutant without altering its protein expression. These results suggest that C4-OH and C2-OH are most probably critical factors for maintaining membrane fluidity and proper turnover of membrane molecules in yeast containing complex sphingolipids with only one hydrophilic head group. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
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10.1194/jlr.M048637
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8684801
|
Lattice corneal dystrophy type II associated with familial amyloid polyneuropathy type IV.
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Finnish-type familial amyloidosis (FAP-IV) is an autosomal, dominantly inherited disorder characterized by progressive polyneuropathy and lattice corneal dystrophy type II. The vast majority of families with this disorder originated from Finland. Only two families, in neighboring districts, have been reported in Japan previously. The authors report two additional Japanese patients with FAF-IV. The proband, a 70-year-old man, had decreased perspiration and abnormal facial muscle movement. Results of neurologic examination showed bilateral facial and hypoglossal nerve palsies, and an autonomic disturbance, including orthostatic hypotension and dysfunction of perspiration. Histochemical, immunohistological, and DNA studies confirmed the diagnosis of FAP-IV. Results of ophthalmologic examination showed asymptomatic lattice corneal dystrophy of both eyes, but the appearance of the cornea was different from that described in the patients from Finland. Lattice lines in the authors' patient were very fine, short, and glassy and could be observed with indirect retroillumination, but might be missed with direct illumination by the slit-lamp microscope. The proband's younger half-sister, a 68-year-old woman, showed clinical findings and laboratory data similar to those of the proband. The authors report two Japanese patients with lattice corneal dystrophy type II related to FAP-IV. This is the third Japanese family with this disorder, and there is no familial relationship to the two previously reported families in Japan.
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10.1016/s0161-6420(96)30560-5
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32512401
|
Automatic post-stroke lesion segmentation on MR images using 3D residual convolutional neural network.
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In this paper, we demonstrate the feasibility and performance of deep residual neural networks for volumetric segmentation of irreversibly damaged brain tissue lesions on T1-weighted MRI scans for chronic stroke patients. A total of 239 T1-weighted MRI scans of chronic ischemic stroke patients from a public dataset were retrospectively analyzed by 3D deep convolutional segmentation models with residual learning, using a novel zoom-in&out strategy. Dice similarity coefficient (DSC), average symmetric surface distance (ASSD), and Hausdorff distance (HD) of the identified lesions were measured by using manual tracing of lesions as the reference standard. Bootstrapping was employed for all metrics to estimate 95% confidence intervals. The models were assessed on a test set of 31 scans. The average DSC was 0.64 (0.51-0.76) with a median of 0.78. ASSD and HD were 3.6 mm (1.7-6.2 mm) and 20.4 mm (10.0-33.3 mm), respectively. The latest deep learning architecture and techniques were applied with 3D segmentation on MRI scans and demonstrated effectiveness for volumetric segmentation of chronic ischemic stroke lesions. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
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10.1016/j.nicl.2020.102276
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23151666
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Activated microglia provide a neuroprotective role by balancing glial cell-line derived neurotrophic factor and tumor necrosis factor-α secretion after subacute cerebral ischemia.
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Microglia are the major immune cells in the central nervous system and play a key role in brain injury pathology. However, the role of activated microglia after subacute cerebral ischemia (SCI) remains unknown. To address this issue, we established a permanent middle cerebral artery occlusion (pMCAO) rat model and treated pMCAO rats with N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide (PJ34) (an inhibitor of microglial activation), or with vehicle alone. Finally, we determined the differences between the PJ34-and vehicle-treated rats with respect to neurological deficits, infarct volume, neuronal loss and the expression of CD11b (a marker of microglial activation), glial cell line-derived neurotrophic factor (GDNF) and tumor necrosis factor-α (TNF-α) at 1, 3 and 7 days after treatment. We found that the PJ34-treated rats had more severe neurological deficits and a larger infarct volume and exhibited a decreased CD11b expression, more neuronal loss, decreased expression of GDNF mRNA and protein but increased expression of TNF-α mRNA and protein compared with the vehicle-treated rats at 3 and 7 days after treatment. These results indicate that activated microglia provide a neuroprotective role through balancing GDNF and TNF-α expression following SCI.
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10.3892/ijmm.2012.1179
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36157327
|
Robotic Emulation of Candidate Prosthetic Foot Designs May Enable Efficient, Evidence-Based, and Individualized Prescriptions.
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The design and selection of lower-limb prosthetic devices is currently hampered by a shortage of evidence to drive the choice of prosthetic foot parameters. We propose a new approach wherein prostheses could be designed, specified, and provided based on individualized measurements of the benefits provided by candidate feet. In this manuscript, we present a pilot test of this evidence-based and personalized process. We previously developed a "prosthetic foot emulator," a wearable robotic system that provides users with the physical sensation of trying on different prosthetic feet before definitive fitting. Here we detail preliminary demonstrations of two possible approaches to personalizing foot design: 1) an emulation and test-drive strategy of representative commercial foot models, and 2) a prosthetist-driven tuning procedure to optimize foot parameters. The first experiment demonstrated large and sometimes surprising differences in optimal prosthetic foot parameters across a variety of subjects, walking conditions, and outcome measures. The second experiment demonstrated a quick and effective simple manual tuning procedure for identifying preferred prosthetic foot parameters. Emulator-based approaches could improve individualization of prosthetic foot prescription. The present results motivate future clinical studies of the validity, efficacy, and economics of the approach across larger and more diverse subject populations. Today, emulator technology is being used to accelerate research and development of novel prosthetic and orthotic devices. In the future, after further refinement and validation, this technology could benefit clinical practice by providing a means for rapid test-driving and optimal selection of clinically available prosthetic feet. Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthotists and Prosthetists.
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10.1097/JPO.0000000000000409
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17112397
|
Use of a rectal snare to remove a hypopharyngeal haemangioma.
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We describe in this case report a new technique for treatment of hypopharyngeal haemangioma, using the surgical diathermy snare. The snare was easily introduced through the direct laryngoscope, without any difficulties. The procedure was simple, rapid and involved minimal bleeding. We also discuss the histological types of haemangioma, clinical picture, radiological findings and other modalities of treatment.
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10.1017/S0022215106004506
|
7601842
|
Escherichia coli alkaline phosphatase localized to the cytoplasm slowly acquires enzymatic activity in cells whose growth has been suspended: a caution for gene fusion studies.
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Alkaline phosphatase is normally localized to the periplasm of Escherichia coli and is unable to fold into its native conformation if retained in the cytoplasm of growing cells. The alkaline phosphatase activity of E. coli expressing a version of the protein without a signal sequence was nonetheless found to increase gradually when the growth of cells was suspended. At least 30% of the protein was activated over the course of several hours when freshly grown exponential-phase cells were held on ice. Similar behavior was observed with cells expressing certain other mutant versions of alkaline phosphatase that are retained in the cytoplasm. The activation resulted not from the passage of the alkaline phosphatase into the periplasm but from the slow folding of alkaline phosphatase into its native conformation in the cytoplasm. These findings indicate that the mechanism by which proteins are normally kept reduced in the cytoplasm fails to function if cells are not growing. It was found that the addition of the sulfhydryl-alkylating agent iodoacetamide to cells after growth blocks this activation completely. This treatment can therefore diminish the likelihood of spurious enzyme activity measurements in studies that make use of alkaline phosphatase fusion proteins.
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10.1128/jb.177.13.3764-3770.1995
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29335705
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Synthesis of 2,5-disubstituted oxazoles via cobalt(iii)-catalyzed cross-coupling of N-pivaloyloxyamides and alkynes.
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An efficient synthesis of 2,5-disubstituted oxazoles via Co(iii) catalysis is described herein. The synthesis is achieved under mild conditions through [3+2] cycloaddition of N-pivaloyloxyamides and alkynes. The reaction operates through an internal oxidation pathway and features a very broad substrate scope. The one-step synthesis of natural products such as texamine and balsoxin has been demonstrated via this protocol.
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10.1039/c7cc08611c
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3248297
|
Depressant effect of acetate in isolated cardiac tissue.
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Because acetate may have cardiodepressant properties in vitro, but previous studies have not separated out effects of acetate from possible effects of osmolality, sodium concentration, or calcium complexing, the effects of isosmotic acetate substitution (at a constant calcium concentration) on contractility were studied in isolated rat atrial tissue and in an isolated perfused non-working whole heart preparation. In spontaneously contracting right atrial tissue acetate induced dose dependent inhibition of isometric tension in the clinically important dose range of 4 to 16 mmol. litre-1. Bath acetate concentrations of 4, 16, or 64 mmol. litre-1 reduced peak tension (mean(SEM] to 78(2.7)%, 56(2.5)%, or 61(4.6)% respectively of control values. Because the calcium concentrations of the acetate baths were set equal to that of the control bath, calcium complexing by acetate could not have accounted for acetate's cardiodepressant effect. The inhibitory action was demonstrable with both isosmotic and hyperosmotic acetate solutions. Acetate had no effect on the spontaneous rate of atrial contraction. Inhibition of contractility (+dP/dt) by acetate in the whole heart preparation was also demonstrable at bath acetate concentrations of 8 and 16 mmol. litre-1. The results suggest that acetate has a myocardial depressant effect in vitro at concentrations achievable in the plasma during haemodialysis. The myocardial depressant action is not dependent on calcium complexing or on changes in bath osmolality or sodium concentration.
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10.1093/cvr/22.8.566
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16272883
|
Expression of cyclic nucleotide-gated channels in the rat medial vestibular nucleus.
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The role of cyclic nucleotide-gated (CNG) channels in sensory signal transduction in retinal and olfactory cells is widely recognized, but there is increasing evidence that they also play more general functions in the central nervous system as downstream effectors of cyclic nucleotides. Here, we demonstrate the expression of the alpha-subunit of rod- and olfactory-type CNG channels (CNG1 and CNG2, respectively) in the rat medial vestibular nucleus (MVN). Nested polymerase chain reaction revealed CNG channel mRNA in the MVN, and CNG1 and CNG2 proteins were also detected by Western blotting and immunohistochemistry. Finally, electrophysiological evidence is provided suggesting that CNG channels play a functional role in the MVN.
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10.1097/01.wnr.0000187633.91375.c8
|
29341044
|
Antenatal Medical Therapies to Improve Lung Development in Congenital Diaphragmatic Hernia.
|
Congenital diaphragmatic hernia (CDH) is a birth defect characterized by failed closure of the diaphragm, allowing abdominal viscera to herniate into the thoracic cavity and subsequently impair pulmonary and vascular development. Despite improving standardized postnatal management, there remains a population of severe CDH for whom postnatal care falls short. In these severe cases, antenatal surgical intervention (fetoscopic endoluminal tracheal occlusion [FETO]) may improve survival; however, FETO increases the risk of preterm delivery, is not widely offered, and still fails in half of cases. Antenatal medical therapies that stimulate antenatal pulmonary development are therefore interesting alternatives. By presenting the animal research underpinning novel antenatal medical therapies for CDH, and considering the applications of these therapies to clinical practice, this review will explore the future of antenatal CDH management with a focus on the phosphodiesterase-5 inhibitor sildenafil. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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10.1055/s-0037-1618603
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31188641
|
In vivo validation of a miniaturized electrochemical oxygen sensor for measuring intestinal oxygen tension.
|
Recent advances in the fields of electronics and microfabrication techniques have led to the development of implantable medical devices for use within the field of precision medicine. Monitoring visceral surface tissue O 2 tension ( P T o 2 ) by means of an implantable sensor is potentially useful in many clinical situations, including the perioperative management of patients undergoing intestinal resection and anastomosis. This concept could provide a means by which treatment could be tailored to individual patients. This study describes the in vivo validation of a novel, miniaturized electrochemical O 2 sensor to provide real-time data on intestinal P T o 2. A single O 2 sensor was placed onto the serosal surface of the small intestine of anesthetized rats that were exposed to ischemic (superior mesenteric artery occlusion) and hypoxemic (alterations in inspired fractional O 2 concentrations) insults. Control experiments demonstrated that the sensors can function and remain stable in an in vivo environment. Intestinal P T o 2 decreased following superior mesenteric artery occlusion and with reductions in inspired O 2 concentrations. These results were reversible after reinstating blood flow or by increasing inspired O 2 concentrations. We have successfully developed an anesthetized rat intestinal ischemic and hypoxic model for validation of a miniaturized O 2 sensor to provide real-time measurement of intestinal P T o 2. Our results support further validation of the sensors in physiological conditions using a large animal model to provide evidence of their use in clinical applications where monitoring visceral surface tissue O 2 tension is important. NEW & NOTEWORTHY This is the first report of real-time continuous measurements of intestinal oxygen tension made using a microfabricated O 2 sensor. Using a developed rodent model, we have validated this sensor's ability to accurately measure dynamic and reversible changes in intestinal oxygenation that occur through ischemic and hypoxemic insults. Continuous monitoring of local intestinal oxygenation could have value in the postoperative monitoring of patients having undergone intestinal surgery.
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10.1152/ajpgi.00050.2019
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12171730
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Manufacture and quality control of CAMPATH-1 antibodies for clinical trials.
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CAMPATH-1 Abs have been used for T-cell depletion in stem-cell transplantation since the early 1980s. During that time there has been substantial progress in manufacturing techniques and quality control procedures. This article summarizes the methods used to produce the Abs for clinical use and describes results of quality control tests on representative batches. Rat hybridoma and recombinant CHO cells were cultured in hollow-fiber fermentors. Antibodies were purified from the culture supernatant by fractionation with ammonium sulphate, or by column chromatography. Additional steps were added to assure the removal of DNA and viruses. A range of analytical methods was used to characterize the antibodies. Samples were stored frozen at -70 degrees C and re-analyzed many years later to assess the long-term stability. Hollow-fiber fermentors provided a simple and reliable means for antibody production, with yields between 3-10 mg/h and a convenient concentration for further processing (0.6-2.0 mg/mL). All of the CAMPATH-1 Abs (rat IgM, rat IgG2b and human IgG1) could be purified by affinity chromatography on Protein A, but the low pH required for elution caused unacceptable aggregation of the IgM. CAMPATH-1H contained approx. 20% dimeric IgG, which could be removed by size exclusion chromatography. Antibodies were stable for at least 6 years at -70 degrees C, but there was unacceptable aggregation of CAMPATH-1M in one batch stored for 9 years. Pilot-scale production of MAbs for clinical studies is feasible in a small academic center, but regulatory requirements now demand that great attention is paid to all aspects of manufacturing and quality assurance. Although the underlying principles of cell culture and protein chemistry remain the same, the level of documentation, validation and quality control has increased greatly over the last 20 years.
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10.1080/146532401753174061
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25644944
|
Curcumin as a putative antidepressant.
|
Due to inadequate efficacy of antidepressants, various new chemical entities and agents of natural origin have been tested for therapeutic efficacy both alone and to augment existing antidepressants, producing varied clinical results. This article summarizes the basic properties of curcumin and its mechanisms of action, with specific emphasis on the etiopathogenesis of depression, preclinical and current clinical evidence, and future research directions, to better understand the possible role of curcumin in treating depression. Curcumin may have antidepressant activities with diverse mechanisms of action involving primarily neurotransmitters, transcription pathways, neurogenesis, the hypothalamic-pituitary-adrenal axis and inflammatory and immune pathways, as demonstrated in various animal and human studies. Current published randomized clinical trials suggest a small, non-significant benefit of curcumin for major depression. More adequately-powered and methodologically improved studies are mandatory.
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10.1586/14737175.2015.1008457
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36320938
|
On the intrinsic nature of viral pathogenesis: The assumption of a Darwinian paradigm to describe COVID-19 pandemic.
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Our hypothesis about evolution of the COVID-19 pandemic foresees an inverse relation between infectivity (R0) and lethality (L) of SARS-CoV-2. The above parameters are driven by a continuing mutation process granting the virus a clear survival advantage over virulence. For interpreting this relation we adopted a simple equation, R0 × L ≈ k, by which R0 and L depend upon a constant k, that corresponds to an intrinsic property of the viral species involved. The hypothesis was verified by following changes of the R0 and L terms of the formula in the different variants of SARS-CoV-2 that progressively appeared. A further validation came when the equation was applied to pandemic and epidemic influenza type A viruses, Ebola virus and measles virus. We believe this equation that considers virus biology in Darwinian terms could be extremely useful to better face infectious viral threats and validate virus-host molecular interactions relevant to viral pathogenesis. © 2022 The Author(s).
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10.1016/j.csbj.2022.10.037
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19936067
|
Feasibility of provider-initiated HIV testing and counselling of tuberculosis patients under the TB control programme in two districts of South India.
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Provider-initiated HIV testing and counselling (PITC) is internationally recommended for tuberculosis (TB) patients, but the feasibility, effectiveness, and impact of this policy on the TB programme in India are unknown. We evaluated PITC of TB patients across two districts in India considered to have generalized HIV epidemics, Tiruchirappalli (population 2.5 million) and Mysore (population 2.8 million). Starting June 2007, healthcare providers in both districts were instructed to ascertain HIV status for all TB patients, and refer those with unknown HIV status to the nearest Integrated Counselling and Testing Centre (ICTC)--often in the same facility--for counselling and voluntary HIV testing. All TB patients registered from June 2007 to March 2008 were followed prospectively. Field investigators assessed PITC practices and abstracted data from routine TB programme records and HIV counselling registers to determine the proportion of TB patients appropriately evaluated for HIV infection. Patient records were traced to determine the efficiency of referral links to HIV care and antiretroviral treatment (ART). Between July 2007 and March 2008, 5299 TB patients were registered in both study districts. Of the 4701 with unknown HIV status at the time of TB treatment initiation, 3368 (72%) were referred to an ICTC, and 3111 (66%) were newly tested for HIV. PITC implementation resulted in the ascertainment of HIV status for 3709/5299 (70%) of TB patients, and detected 200 cases with previously undiagnosed HIV infection. Overall, 468 (8.8%) of all registered TB patients were HIV-infected; 177 (37%) were documented to have also received any ART. With implementation of PITC in India, HIV status was successfully ascertained for 70% of TB patients. Previously undiagnosed HIV-infection was detected in 6.4% of those TB patients newly tested, enabling referral for life-saving anti-retroviral treatment. ART uptake, however, was poor, suggesting that PITC implementation should include measures to strengthen and support ART referral, evaluation, and initiation.
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10.1371/journal.pone.0007899
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