Characterization of a cytotoxin from Campylobacter jejuni and its role in pathogenicity

Campylobacter jejuni is a major cause worldwide of human gastroenteritis. In this study, the pathogenicity of the organism was examined in fertile hens\u27 eggs and the mortality data and histopathological findings induced by both the organism and bacteria-free filtered broth were similar. The absence in chick embryo tissues of either bacteria or an inflammatory infiltrate suggested a toxic etiology. A protein was obtained from the filtrate by gel electroelution and this was sensitive to heat, pH changes and trypsin treatment and was lethal for the fertile hen\u27s egg. It showed cytotoxic effects in primary chick embryo fibroblast (PCEF), Chinese hamster ovary (CHO) and intestinal 407 (Int 407) cells. Subsequently, a 68 kilodalton protein was isolated by polyacrylamide gel electrophoresis from the eluted toxic protein (ETP). A monoclonal antibody (CETPMAb\sb4) raised to the ETP abolished toxicity and bound only to the 68 kilodalton protein. No homology between C. jejuni ETP and Vibrio cholerae toxin and their respective antisera was observed. In enzyme-linked immunosorbent assay (ELISA) tests, the ETP did not bind to GM\sb1 ganglioside. Binding of ETP to PCEF and Int 407 host cell membranes was maximal after 2 h and this adherence was significantly reduced by prior treatment of the cells with proteolytic enzymes, neuraminidase or glutaraldehyde but not with $\beta$-galactosidase, lipase, Nonidet P-40 or sodium metaperiodate. In competitive binding assays, sugars (except N-acetyl neuraminic acid), lectins or GM\sb1 ganglioside did not adversely influence uptake of the ETP by these cells. Electron microscopic examination of the Int 407 cells treated with either C. jejuni or ETP showed similar ultrastructural damage. Western blot and ELISA tests of bacterial sub-components probed with CETPMAb\sb4 indicated that the toxin was associated with the outer membranes of the organism. Immunoassays on ETP treated eukaryotic host cells demonstrated that the toxin was attached only to the cell membranes and was not internalized. The present study indicates that the production of a membrane adhering cytotoxin that binds to protein or glycoprotein receptors on host cell membranes may be an important virulence factor responsible for the inflammatory diarrhea caused by many C. jejuni strains

Bayesian and Semi-Bayesian Estimation of the Parameters of Generalized Inverse Weibull Distribution

Bayesian and semi-Bayesian estimators of parameters of the generalized inverse Weibull distribution are obtained using Jeffreys’ prior and informative prior under specific assumptions of loss function. Using simulation, the relative efficiency of the proposed estimators is obtained under different set-ups. A real life example is also given

Lasmiditan: the first neurally acting anti-migraine drug

Lasmiditan is the first neurally acting drug for the treatment of acute migraine. It is a highly selective, orally acting 5-HT1F agonist that was approved in November 2019, for the acute treatment of migraine in adults, with or without aura, by USFDA. Lesmiditan may help in terminating the acute attack of migraine by inhibiting the central and peripheral neuronal activity and the release of CGRP

Functional Status in Older Women Diagnosed with Pelvic Organ Prolapse

Background—Functional status plays an important role in the comprehensive characterization of older adults. Functional limitations are associated with an increased risk of adverse treatment outcomes, but there is limited data on the prevalence of functional limitations in older women with pelvic floor disorders. Objective—The aim of the study was to describe the prevalence of functional limitations based on health status in older women with pelvic organ prolapse. Study Design—This pooled, cross-sectional study utilized data from the linked Health and Retirement Study and Medicare files between 1992 and 2008. The analysis included 890 women ≥65 years with pelvic organ prolapse. We assessed self-reported functional status, categorized in strength, upper and lower body mobility, activities of daily living, and instrumental activities of daily living domains. Functional limitations were evaluated and stratified by respondents self-reported general health status. Descriptive statistics were used to compare categorical and continuous variables, and logistic regression was used to measure differences in the odds of functional limitation by increasing age. Results—The prevalence of functional limitations was 76.2% in strength, 44.9% in upper and 65.8% in lower body mobility, 4.5% in activities of daily living and 13.6% in instrumental activities of daily living. Limitations were more prevalent in women with poor or fair health status than in women with good health status, including 91.5% vs 69.9% in strength, 72.9% vs 33.5% in upper and 88.0% vs 56.8% in lower body mobility, 11.6% vs 0.9% in activities of daily living, and 30.6% vs 6.7% in instrumental activities of daily living, all p Conclusion—Functional limitations, especially in strength and body mobility domains, are highly prevalent in older women with pelvic organ prolapse, particularly in those with poor or fair self-reported health status. Future research is necessary to evaluate if functional status affects clinical outcomes in pelvic reconstructive and gynecologic surgery and whether it should be routinely assessed in clinical decision-making when treating older women with pelvic organ prolapse

Functional Status in Older Women Diagnosed with Pelvic Organ Prolapse

Background—Functional status plays an important role in the comprehensive characterization of older adults. Functional limitations are associated with an increased risk of adverse treatment outcomes, but there is limited data on the prevalence of functional limitations in older women with pelvic floor disorders. Objective—The aim of the study was to describe the prevalence of functional limitations based on health status in older women with pelvic organ prolapse. Study Design—This pooled, cross-sectional study utilized data from the linked Health and Retirement Study and Medicare files between 1992 and 2008. The analysis included 890 women ≥65 years with pelvic organ prolapse. We assessed self-reported functional status, categorized in strength, upper and lower body mobility, activities of daily living, and instrumental activities of daily living domains. Functional limitations were evaluated and stratified by respondents self-reported general health status. Descriptive statistics were used to compare categorical and continuous variables, and logistic regression was used to measure differences in the odds of functional limitation by increasing age. Results—The prevalence of functional limitations was 76.2% in strength, 44.9% in upper and 65.8% in lower body mobility, 4.5% in activities of daily living and 13.6% in instrumental activities of daily living. Limitations were more prevalent in women with poor or fair health status than in women with good health status, including 91.5% vs 69.9% in strength, 72.9% vs 33.5% in upper and 88.0% vs 56.8% in lower body mobility, 11.6% vs 0.9% in activities of daily living, and 30.6% vs 6.7% in instrumental activities of daily living, all p Conclusion—Functional limitations, especially in strength and body mobility domains, are highly prevalent in older women with pelvic organ prolapse, particularly in those with poor or fair self-reported health status. Future research is necessary to evaluate if functional status affects clinical outcomes in pelvic reconstructive and gynecologic surgery and whether it should be routinely assessed in clinical decision-making when treating older women with pelvic organ prolapse

Refractory Idiopathic Urge Urinary Incontinence and Botulinum A Injection

We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence

Limited Progress in Improving Gender and Geographic Representation in Coral Reef Science

Despite increasing recognition of the need for more diverse and equitable representation in the sciences, it is unclear whether measurable progress has been made. Here, we examine trends in authorship in coral reef science from 1,677 articles published over the past 16 years (2003–2018) and find that while representation of authors that are women (from 18 to 33%) and from non-OECD nations (from 4 to 13%) have increased over time, progress is slow in achieving more equitable representation. For example, at the current rate, it would take over two decades for female representation to reach 50%. Given that there are more coral reef non-OECD countries, at the current rate, truly equitable representation of non-OECD countries would take even longer. OECD nations also continue to dominate authorship contributions in coral reef science (89%), in research conducted in both OECD (63%) and non-OECD nations (68%). We identify systemic issues that remain prevalent in coral reef science (i.e., parachute science, gender bias) that likely contribute to observed trends. We provide recommendations to address systemic biases in research to foster a more inclusive global science community. Adoption of these recommendations will lead to more creative, innovative, and impactful scientific approaches urgently needed for coral reefs and contribute to environmental justice efforts.We acknowledge the contributions of the many unrecognized and undervalued individuals in coral reef research whose efforts have made it possible for the field to progress. These scientists have collected data, translated across languages, coordinated field work, welcomed foreign visitors to their countries, shared ideas, trained and mentored students, become friends, inspired, and built the foundation for the discipline we know today. We acknowledge the work of all coral reef scientists who continue day after day to pursue equity, inclusion, and justice in the field and for their colleagues and themselves.Ye

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs