Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base

Imperforate hymen presenting with massive haematocolpos and acute urinary retention in a teenage girl: A case report

Imperforate hymen is relatively rare but it is the most frequently encountered obstructive anomaly of the female lower genital tract. The clinical presentation vary significantly from patient to patient depending on the age at diagnosis but in most cases the diagnosis is missed in early childhood and therefore the diagnosis is made after puberty when the patient present with haematocolpos, heamatometra or both. When this happens, the presentation could even be tricky because the patient may presents with unlikely symptoms apart from cryptomenorhoea like, urinary retention or bowel obstruction or both. Here we present a 16 years old girl with imperforate hymen and presented with history of lower abdominal pain and distension associated with acute urinary retention. She was treated by hymenotomy and improved dramatically and was discharge 6th day post operatively.  This case report is presented to address to clinicians the possibility of imperforate hymen with haematocolpos as a differential diagnosis in adolescent girls particularly those who have not started having their menses in their teens and present with acute urinary retention so that their external genitalia are carefully examined to exclude the possibility of imperforate hymen as a cause of acute urinary retention due to the haematocolpos

One-Lung Ventilation in Anesthesia

The purpose of one-lung ventilation (OLV) is to provide a good surgical exposure of a collapsed lung while ensuring adequate gas exchange with the other. Currently, double-lumen tubes (DLTs) or bronchial blockers (BBs) are used to obtain it. The separation of the lungs today means a completed “anatomical” sealing with DLTs, and the isolation of the lung means a “functional” sealing with BBs [1–3]. In the first case, there are some absolute indications in which a protective strategy for the contralateral lung is needed, including life-threatening conditions such as massive bleeding, pneumonia with pus, and bronchopleural and bronchocutaneous fistulae, since they offer a low-resistance pathway during positive pressure ventilation, as well as giant unilateral bullae that may blow. Some surgical interventions as sleeve pneumonectomy or bronchopulmonary lavage for alveolar proteinosis or cystic fibrosis still require lung separation. In all the other situations, in which lung separation is a relative indication, lung isolation could be used [4, 5]

Medication errors in relation to direct‑acting oral anticoagulants:a qualitative study of pharmacists’ views and experiences

Background: Despite their effectiveness and ease of use, medication errors have been reported to be highly prevalent with direct-acting oral anticoagulants (DOAC).Aim: The aim of this study was to explore views and experiences of pharmacists on contributory factors and mitigation strategies around medication errors in relation to DOAC.Method: This study used a qualitative design. Semi-structured interviews were conducted with hospital pharmacists in Saudi Arabia. The interview topic guide was developed based on previous literature and Reason's Accident Causation Model. All interviews were transcribed verbatim and MAXQDA Analytics Pro 2020 was used to thematically analyse the data (VERBI Software).Results: Twenty-three participants representing a range of experiences participated. The analysis recognised three major themes: (a) enablers and barriers faced by pharmacists in promoting safe utilisation of DOAC, such as opportunities to conduct risk assessments and offer patient counselling (b) factors related to other healthcare professionals and patients, such as opportunities for effective collaborations and patient health literacy; and (c) effective strategies to promote DOAC safety such as empowering the role of pharmacists, patient education, opportunities for risk assessments, multidisciplinary working and enforcement of clinical guidelines and enhanced roles of pharmacists.Conclusion: Pharmacists believed that enhanced education of healthcare professionals and patients, development and implementation of clinical guidelines, improvement of incident reporting systems, and multidisciplinary team working could be effective strategies to reduce DOAC-related errors. In addition, future research should utilise multifaceted interventions to reduce error prevalence

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

In vivo analysis of CRISPR-edited germinal center murine B cells

The germinal center (GC) reaction is crucial for somatic hypermutation, affinity maturation, and the selection of high-affinity B cells, all of which are hallmarks of the humoral immune response. Understanding the distinct roles of various B cell genes is essential for elucidating the selection mechanisms within the GC reaction. Traditionally, studying B cell gene function in the GC reaction involved generating knock-out mice, a highly time-consuming method that necessitates complex vectors. The advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has simplified the creation of knock-out mice. However, even with CRISPR, the generation of knock-out mice still faces challenges, including being time-consuming, costly, having low knock-out efficiency, and raising ethical concerns regarding animal use. To address these challenges, we developed an alternative method to traditional knock-out mouse generation. Our approach entails the ex vivo CRISPR editing of B cells from transgenic donor mice with different B cell receptor affinities followed by their adoptive transfer into recipient mice. We present a cost-effective, rapid, versatile, and adaptable CRISPR-Cas9 method for in vivo loss-of-function studies of individual murine B cell genes within the context of the GC reaction. This method provides a valuable tool for investigating the complex roles of different B cell genes in the GC selection process. As proof of concept, we validated our approach by examining the role of the pro-apoptotic gene Fas in the GC selection process. We adoptively transferred a mix of Fas knock-out (Fas KO ) low-affinity B cells, Fas wild-type (Fas WT ) low-affinity B cells, and Fas WT high-affinity B cells into recipient mice. From our results, Fas KO low-affinity B cells were still outcompeted by the Fas WT high-affinity B cells for selection in the GC. An important observation was the accumulation of Fas KO low-affinity GC B cells when compared to the Fas WT low-affinity B cells, which suggested a role of Fas in the GC selection process

Evaluation of grit and its associated factors among undergraduate pharmacy students from 14 Asian and Middle Eastern countries amid the COVID-19 pandemic

Introduction: Grit is proposed as an essential trait for academic achievement. Thus, evaluating its current status and the associated factors could aid academic support planning. Objective: The present study aimed to assess grit level and its related factors among undergraduate pharmacy students from 14 countries amid the COVID-19 pandemic. Methods: A cross-sectional survey-based study was conducted among pharmacy students from 14 countries in Asia and the Middle East. A 31-item questionnaire was developed, validated, and pilot-tested, including the validated short scale for grit assessment. The data was collected between 1 February and 15 April 2022. Descriptive and inferential statistics were employed as appropriate. Results: A total of 2665 responses were received, mainly from females (68.7 %), living in urban areas (69.2 %) and studying at private universities (59.1 %). The average grit score on a scale of 5 was 3.15 ± 0.54. The responses revealed higher favourable responses to items on the perseverance of efforts (34.9 % to 54 %) compared to items on the consistency of interests (26.5 % to 31.1 %). Students who did not exercise (AOR: 0.47, 95 %CI: 0.33–0.67) or exercised irregularly (AOR: 0.64, 95 %CI: 0.45–0.90) were less likely to have higher grit scores than those who exercised regularly. Additionally, students who did not receive COVID-19 vaccination (AOR: 0.50, 95 %CI: 0.36–0.71) or received only one dose (AOR: 0.67, 95 %CI: 0.46–0.99) were less likely to have higher grit scores than those who received their booster vaccination. Interestingly, students who chose the pharmacy program as their only available or reasonable choice (AOR: 0.33, 95 %CI: 0.17–0.62) and students from public universities (AOR: 0.82, 95 %CI: 0.68–0.98) were less likely to have higher grit scores. On the other hand, students who did not face educational challenges with online learning (AOR: 1.19, 95 %CI: 1.003–1.416) and students with excellent (AOR: 2.28, 95 %CI: 1.57–3.31) and very good (AOR: 2.16, 95 %CI: 1.53–3.04) academic performance were more likely to have higher grit scores. Conclusion: The findings revealed moderate grit levels. Higher grit levels were thought to be associated with several personal, lifestyle and academic factors. Further interventions to support students' grit attributes are required, particularly concerning the consistency of interests

Assessment of Academic Resilience and its associated factors among Pharmacy Students in Twelve Countries

Objective Academic resilience, a critical determinant of academic achievement, is affected by various factors. There is a paucity of large-scale international assessments of academic resilience among pharmacy students. Therefore, this study aimed to assess academic resilience among pharmacy students in 12 countries and to evaluate factors associated with their academic resilience levels. Methods A cross-sectional online survey-based study was conducted among randomly selected pharmacy students in 12 countries: Egypt, Türkiye, Indonesia, Pakistan, Bangladesh, Iraq, Jordan, Nigeria, Malaysia, Saudi Arabia, Sudan, and the United Arab Emirates. After pilot testing, the validated 30-item academic resilience scale (ARS) was used for the assessment. The data were collected between November 1, 2022 and April 15, 2023. Descriptive and inferential statistics were performed, as appropriate. Results A total of 3950 were received from the 12 participating countries. The mean age was 21.68 ± 2.62 years. About two-thirds of the responses were from female participants and those studying for Bachelor of Pharmacy degrees. Overall, the findings show moderate academic resilience, which varied across countries. The median (IQR) of the total ARS-30 was 114 (103−124). Females exhibited lower negative affective and emotional response subscale levels than males. There were significant cross-country variations in the ARS-30 and all subscales. The highest overall levels were reported for Sudan, Pakistan, and Nigeria and the lowest were reported for Indonesia and Türkiye. Students in private universities tended to have higher overall ARS levels than public university students. Higher academic performance was significantly associated with ARS levels, whereas those with excellent performance exhibited the highest ARS levels. Students with exercise routines had higher ARS levels than those without exercise routines. Finally, students who were engaged in extracurricular activities had higher ARS levels than those who did not participate in these activities. Conclusion The study offers insights into the factors affecting academic resilience in pharmacy students across several countries. The findings could guide interventions and support activities to improve resilience and academic outcomes

Variable exponent Besov-Morrey spaces

In this paper we introduce Besov-Morrey spaces with all indices variable and study some fundamental properties. This includes a description in terms of Peetre maximal functions and atomic and molecular decompositions. This new scale of non-standard function spaces requires the introduction of variable exponent mixed Morrey-sequence spaces, which in turn are defined within the framework of semimodular spaces. In particular, we obtain a convolution inequality involving special radial kernels, which proves to be a key tool in this work.publishe