The Discovery of XY Sex Chromosomes in a \u3cem\u3eBoa\u3c/em\u3e and \u3cem\u3ePython\u3c/em\u3e

For over 50 years, biologists have accepted that all extant snakes share the same ZW sex chromosomes derived from a common ancestor [1, 2, 3], with different species exhibiting sex chromosomes at varying stages of differentiation. Accordingly, snakes have been a well-studied model for sex chromosome evolution in animals [1, 4]. A review of the literature, however, reveals no compelling support that boas and pythons possess ZW sex chromosomes [2, 5]. Furthermore, phylogenetic patterns of facultative parthenogenesis in snakes and a sex-linked color mutation in the ball python (Python regius) are best explained by boas and pythons possessing an XY sex chromosome system [6, 7]. Here we demonstrate that a boa (Boa imperator) and python (Python bivittatus) indeed possess XY sex chromosomes, based on the discovery of male-specific genetic markers in both species. We use these markers, along with transcriptomic and genomic data, to identify distinct sex chromosomes in boas and pythons, demonstrating that XY systems evolved independently in each lineage. This discovery highlights the dynamic evolution of vertebrate sex chromosomes and further enhances the value of snakes as a model for studying sex chromosome evolution

A systematic review of clinical practice guidelines for childhood glaucoma

Objective: To conduct a systematic review to identify and critically appraise clinical practice guidelines on the assessment, diagnosis and management of childhood glaucoma. Methods and analysis: A systematic literature search of databases and professional websites for clinical practice guidelines published on eye conditions between 2010 and April 2020 in English was conducted. Identified guidelines were screened for relevance to childhood glaucoma and exclusion criteria applied. Guidelines that passed the screening and quality appraisal with the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and, if they achieved a mean score of ≥45 and ≥3 on subsets of 9 and 5 AGREE II items, respectively, were selected for inclusion and data extracted using a standardised form. Results: Following screening and critical appraisal, three guidelines were included for data extraction. None of the three guidelines was specifically developed for childhood glaucoma. A consistent recommendation was that children should undergo some form of eye screening examination or a comprehensive eye assessment to detect paediatric eye disease. Children at high risk of childhood glaucoma should undergo additional screening. One clinical practice guideline recommended interventions for childhood glaucoma consisting of tube surgery and topical beta-blockers or carbonic anhydrase inhibitors. Recommended interventions for childhood glaucoma were based on low-quality to moderate-quality evidence or expert opinion. Conclusion: Based on our selection criteria, we did not identify any high-quality clinical practice guidelines specifically targeted at childhood glaucoma. This is compounded by the lack of high-quality evidence on childhood glaucoma

Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer

Objective: New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis. Methods: Asymptomatic patients with relapsed ovarian cancer who had responded to chemotherapy were enrolled and had CA125 measurements taken every 4 weeks, then more frequently when rising. Once levels reached 4 times the upper limit of normal or nadir, they started continuous tamoxifen 20 mg daily, as well as fortnightly CA125 measurements until symptomatic progression. Because of the potentially nonlinear relationship of CA125 over time, it was felt that to enable normal approximations to be utilized a natural logarithmic standard transformation [ln(CA125)] was the most suitable to improve linearity above the common logarithmic transformation to base 10. Results: From 235 recruited patients, 81 started tamoxifen and had at least 4 CA125 measurements taken before and 4 CA125 measurements taken after starting tamoxifen, respectively. The mean regression slopes from using at least 4 1n(CA125) measurements immediately before and after starting tamoxifen were 0I0149 and 0I0093 [ln(CA125)/d], respectively. This difference is statistically significant, P = 0I001. Therefore, in a future trial with a novel agent, at least as effective as tamoxifen, using this effect size, the number of evaluable patients needed, at significance level of 5% and power of 80%, is 56. Conclusions: Further validation of this methodology is required, but there is potential to use comparison of mean regression slopes of ln(CA125) as an interim analysis measure of efficacy for novel cytostatic agents in relapsed ovarian cancer.Peer reviewedFinal Accepted Versio

The plasma membrane-actin linking protein, ezrin, is a glomerular epithelial cell marker in glomerulogenesis, in the adult kidney and in glomerular injury

The plasma membrane-actin linking protein, ezrin, is a glomerular epithelial cell marker in glomerulogenesis, in the adult kidney and in glomerular injury.BackgroundEzrin belongs to a family of plasma membrane-cytoskeleton linking, actin binding proteins (Ezrin-radixin-Moesin family) involved in signal transduction, growth control, cell-cell adhesion, and microvilli formation.MethodsThe expression of ezrin was examined in glomerular cells in culture, during kidney development, in the mature kidney, and in five different experimental kidney disease models in the rat.ResultsEzrin was specifically expressed in glomerular epithelial cells in developing glomeruli in mature glomeruli and in glomerular epithelial cells in culture. Distinct from its other family members, moesin and radixin, which are predominantly expressed in glomerular endothelial and mesangial areas, ezrin protein (by immunohistochemistry) was specifically and exclusively modulated during podocyte injury and regeneration. Ezrin immunohistochemistry was able to visualize cell body attenuation, pseudocysts, and in particular vacuolation of injured podocytes, a feature that usually has to be identified at the ultrastructural level, and was strikingly increased in binucleated podocytes or podocytes that were partially or completely detached from the underlying GBM (frequently also binucleated). Infiltrating macrophages also express ezrin, but can easily be differentiated from podocytes by their round shape and higher level of expression.ConclusionsEzrin likely has a role in the cytoskeletal organization, such as reassembling of actin filaments accompanying podocyte injury and regeneration. Since suitable light microscopic markers for the identification of glomerular epithelial cells are rare, ezrin may also be a useful marker for podocytes in normal and injured glomeruli

Travelling for Umrah:destination attributes, destination image, and post-travel intentions

This paper examines the links between cosmopolitanism, self-identity, and a desire for social interaction perceived destination image and behavioural intentions. A model tested using a sample of 538 Iranian visitors to Mecca for the purpose of Umrah. The result from the structural model suggests that destination attributes influence perceived destination image. Further, such tourists are likely to revisit or recommend Islamic destinations if their experience matches their perceived image of the destination. This implies that, while the religious characteristics of the destination remain important, destination managers cannot disregard the tangential, non-religious attributes of a destination which are crucial in order to satisfy more conventional tourist desires. As such, this study suggests that those managing religious travel destinations should endeavour to foster a welcoming image, where experience, interaction and tolerance are at the forefront of the destination’s offering

Hypoxia during maintenance hemodialysis; the critical role of pH

Background The impact and management of subclinical hypoxia during hemodialysis is a significant medical challenge. As key determinants of O2 availability and delivery, proposed mechanisms contributing to hypoxia include ischemia, alkalemia and pulmonary leukocyte sequestration. However, no study has comprehensively investigated and compared these interrelated mechanisms throughout a typical hemodialysis treatment week. This study aimed to comprehensively assess the physiological mechanisms that contribute to hypoxia during hemodialysis. Methods In 76 patients, we measured arterial blood gases and pH at four time-points during hemodialysis (start, 15 min, 60 min, end) over the course of a standard treatment week. For the mid-week hemodialysis session, we additionally measured central hemodynamics (non-invasive cardiac output monitoring) and white blood cell count. Results Linear regression modelling identified changes in pH, but not central hemodynamics or white blood cell count, to be predictive of changes in PaO2 throughout hemodialysis (e.g. at 60 min, β standardized coefficient pH = 0.45, model R2 = 0.25, P < .001). Alkalemia, hypokalemia, decreased calcium and increased hemoglobin–O2 affinity (leftward shift in the oxyhemoglobin dissociation curve) were evident at the end of hemodialysis. pH and hemoglobin–O2 affinity at the start of hemodialysis increased incrementally over the course of a standard treatment week. Conclusion These data highlight the important role of pH in regulating O2 availability and delivery during hemodialysis. Findings support routine pH monitoring and personalized dialysate bicarbonate prescription to mitigate the significant risk of alkalemia and subclinical hypoxia

A systematic review of clinical practice guidelines for childhood glaucoma.

OBJECTIVE: To conduct a systematic review to identify and critically appraise clinical practice guidelines on the assessment, diagnosis and management of childhood glaucoma. METHODS AND ANALYSIS: A systematic literature search of databases and professional websites for clinical practice guidelines published on eye conditions between 2010 and April 2020 in English was conducted. Identified guidelines were screened for relevance to childhood glaucoma and exclusion criteria applied. Guidelines that passed the screening and quality appraisal with the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and, if they achieved a mean score of ≥45 and ≥3 on subsets of 9 and 5 AGREE II items, respectively, were selected for inclusion and data extracted using a standardised form. RESULTS: Following screening and critical appraisal, three guidelines were included for data extraction. None of the three guidelines was specifically developed for childhood glaucoma. A consistent recommendation was that children should undergo some form of eye screening examination or a comprehensive eye assessment to detect paediatric eye disease. Children at high risk of childhood glaucoma should undergo additional screening. One clinical practice guideline recommended interventions for childhood glaucoma consisting of tube surgery and topical beta-blockers or carbonic anhydrase inhibitors. Recommended interventions for childhood glaucoma were based on low-quality to moderate-quality evidence or expert opinion. CONCLUSION: Based on our selection criteria, we did not identify any high-quality clinical practice guidelines specifically targeted at childhood glaucoma. This is compounded by the lack of high-quality evidence on childhood glaucoma

Systematic review of clinical practice guidelines for uveitis

To facilitate the integration of eye care into universal health coverage, the WHO is developing a Package of Eye Care Interventions (PECI). Development of the PECI involves the identification of evidence-based interventions from relevant clinical practice guidelines (CPGs) for uveitis.A systematic review of CPGs published on uveitis between 2010 and March 2020 was conducted. CPGs passing title and abstract and full-text screening were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and data on recommended interventions extracted using a standard data extraction sheet.Of 56 CPGs identified as potentially relevant from the systematic literature search, 3 CPGs underwent data extraction following the screening stages and appraisal with the AGREE II tool. These CPGs covered screening for, monitoring and treating juvenile idiopathic arthritis (JIA)-associated uveitis, the use of adalimumab and dexamethasone in treating non-infectious uveitis, and a top-level summary of assessment, differential diagnosis and referral recommendations for uveitis, aimed at primary care practitioners. Many of the recommendations were based on expert opinion, though some incorporated clinical study and randomised controlled trial data.There is currently sparse coverage of the spectrum of disease caused by uveitis within CPGs. This may partially be due to the large number of conditions with diverse causes and clinical presentations covered by the umbrella term uveitis, which makes numerous sets of guidelines necessary. The limited pool of CPGs to select from has implications for clinicians seeking guidance on clinical care strategies for uveitis.</jats:p

Incomplete Polyp Resection During Colonoscopy—Results of the Complete Adenoma Resection (CARE) Study

Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice.We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. Associations between IRR and polyp size, morphology, histology, and endoscopist were assessed by regression analysis. Of 346 neoplastic polyps (269 patients; 84.0% men; mean age, 63.4 years) removed by 11 gastroenterologists, 10.1% were incompletely resected. IRR increased with polyp size and was significantly higher for large (10-20 mm) than small (5-9 mm) neoplastic polyps (17.3% vs 6.8%; relative risk = 2.1), and for sessile serrated adenomas/polyps than for conventional adenomas (31.0% vs 7.2%; relative risk = 3.7). The IRR for endoscopists with at least 20 polypectomies ranged from 6.5% to 22.7%; there was a 3.4-fold difference between the highest and lowest IRR after adjusting for size and sessile serrated histology. Neoplastic polyps are often incompletely resected, and the rate of incomplete resection varies broadly among endoscopists. Incomplete resection might contribute to the development of colon cancers after colonoscopy (interval cancers). Efforts are needed to ensure complete resection, especially of larger lesions