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Abdur Rahman Khan, Nauman Saleem Siddiqui, Raja Thotakura, Syed Shafae Hasan, Faraz Khan Luni, Thomas Sodeman, Bryan Hinch, Dinkar Kaw, Imad Hariri, Sadik Khuder, Ragheb Assaly Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH, USA Background: In-training examination (ITE) has been used as a predictor of performance at the American Board of Internal Medicine (ABIM) certifying examination. ITE however may not be an ideal modality as it is held once a year and represents snapshots of performance as compared with a trend. We instituted monthly tests (MTs) to continually assess the performance of trainees throughout their residency. Objective: To determine the predictors of ABIM performance and to assess whether the MTs can be used as a tool to predict passing the ABIM examination. Methods: The MTs, core competencies, and ITE scores were analyzed for a cohort of graduates who appeared for the ABIM examination from 2010 to 2013. Logistic regression was performed to identify the predictors of a successful performance at the ABIM examination. Results: Fifty-one residents appeared for the ABIM examination between 2010 and 2013 with a pass rate of 84%. The MT score for the first year (odds ratio [OR] =1.302, CI =1.004–1.687, P=0.04) and second year (OR =1.125, CI =1.004–1.261, P=0.04) were independent predictors of ABIM performance along with the second-year ITE scores (OR =1.248, CI =1.096–1.420, P=0.001). Conclusion: The MT is a valuable tool to predict the performance at the ABIM examination. Not only it helps in the assessment of likelihood of passing the certification examination, it also helps to identify those residents who may require more assistance earlier during their residency. It may also highlight the areas of weakness in program curriculum and guide curriculum development. Keywords: American Board of Internal Medicine, certification examination, health care, board certification, residency program

Phytomedicine is gaining acceptance as well preference in health care management for various diseases. Drug combinations are mostly used clinically for hyperlipidemia, as single-agent therapy is insufficient. Statins remain the cornerstone of hyperlipidemia. The objective of the present research is to manage hyperlipidemia with the least amount of medicine effective clinically, thereby limiting its side effects. Study was carried out with 140 registered hyperlipidemia patients, divided into two groups. Group-A received simvastatin 20mg oral daily & Group B received a combination of simvastatin and beta-valgaris capsules twice a day for 90 days. Pre and post treatment values were compared within the groups and between the groups. Group B shows statistically significant decrease (p<0.05) in serum total cholesterol, low density lipoprotein (LDL), triglycerides (TG) and CRP levels. Also significant improvement (p<0.05) was noted for high density lipoprotein (HDL) levels (20.1% to 57.4%) in group B after completion of study. On the basis of our study results, we can conclude that statins remained to be the mainstay treatment for patients with elevated cholesterol levels. However, the combination has a synergistic effect and reduces oxidative stress (OS) as well.

Background: Lead, a potent neurotoxin, causes irreversible damage to the nervous system, and low- and middle-income countries face huge health and economic productivity losses due to childhood lead exposure. In Bangladesh, informal Used Lead Acid Battery (ULAB) recycling sites are an important source of lead pollution. Little is known about lead awareness among communities exposed to ULAB recycling. Therefore, this study aims to assess knowledge, attitudes, and practices related to lead pollution among caregivers of young children and adolescents living adjacent to informal ULAB sites., Methods: A cross-sectional study was conducted among 732 mothers of young children and adolescents in 4 districts of Bangladesh (survey and observation). Simple and multiple linear regression was conducted to describe patterns and predictors of lead-related knowledge and practices., Results: 60% of respondents had heard the name 'lead' ("shisha"). The mean knowledge score was low (19 out of 44). Residents of high-risk districts, male respondents, and those with more than 5 years of schooling were significantly more likely to have higher knowledge scores than others. In terms of attitude, 52% of respondents perceived lead to be risky for human health but 43% thought lead pollution was controllable. Observation of households for lead exposure revealed that 63% of children and adolescents play or pass by ULAB sites, 29% ate non-food items, 41% of households had visible paint chips on the walls, 59% households used polished turmeric and 15% used lead-soldered cans to store foods. Among protective practices, 70% reported cleaning floors, 84% consumed iron-rich foods, and 48% consumed calcium-rich foods., Conclusions: The population had a high potential for lead exposure. Their knowledge about lead was limited, and risk perception was moderate. To reduce lead exposure and increase knowledge and awareness among the at-risk population, it is crucial to take measures such as mass awareness campaigns through media and schools. It is important to strengthen the implementation of existing policies, such as policies on leaded gasoline, paints, and lead-acid batteries, that can address the sources of lead exposure for the community., (© 2024. The Author(s).)

Background: Oral anticoagulation (OAC) is the mainstay of treatment for the prevention of strokes in patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) account for increasing OAC in patients with AF. However, prescribing DOACs for patients with established AF poses various challenges and general practice pharmacists may have an important role in supporting their management., Aim: To investigate the effectiveness of pharmacist-led interventions in general practice in optimising the use of OAC therapies in AF., Design & Setting: A retrospective observational study in general practices in Bradford., Method: The data were collected retrospectively from 1 November 2018-31 December 2019 using electronic health record data. The data were analysed: 1) to identify patients with AF not on OAC; 2) to describe inappropriate DOAC prescriptions; and 3) to calculate HAS-BLED scores., Results: Overall, 76.3% ( n = 470) of patients with AF received OAC therapy, and of these, 63.4% received DOACs. Pharmacist-led interventions increased DOAC prescribing by 6.0% ( P = 0.03). Inappropriate DOAC use was identified in 24.5% of patients with AF, with underdosed and overdosed identified in 9.7% and 14.8%, respectively. Post-intervention, inappropriate prescribing was reduced to 1.7%. The mean HAS-BLED score decreased from 3.00 to 2.22 ( P <0.01). Successful transition from vitamin K antagonist (VKA) therapy to DOACs was achieved in 25.7% of patients., Conclusion: Pharmacist-led interventions have successfully improved the use of OAC therapies in patients with AF, and effectively managed the bleeding risks and transition from VKA to DOAC therapy, in line with guidelines., (Copyright © 2024, The Authors.)

Background and Aims: We performed a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of intravenous immunoglobulin (IVIG) on mortality outcomes among hospitalized coronavirus disease 2019 (COVID-19) patients., Methods: We systematically searched electronic databases up to June 1, 2023. Pooled odds ratio (OR) of mortality with a 95% confidence interval (CI) was generated using a random-effects model. The risk of bias was appraised using the Cochrane risk-of-bias Version 2 tool for randomized trials., Results: Nine RCTs were included: three RCTs had an overall low risk of bias, four RCTs had some concerns in the overall risk of bias, and two RCTs trials had an overall high risk of bias. The use of IVIG indicated a significant reduction in the odds of mortality (pooled OR = 0.69; 95% CI 0.50-0.96) relative to nonuse of IVIG. Subgroup analysis in patients with a severe course of COVID-19 revealed no significant reduction in the odds of mortality (pooled OR = 0.58; 95% CI 0.29-1.16)., Conclusions: We suggest exercising caution when interpreting effectiveness of IVIG in reducing mortality among hospitalized patients with COVID-19. Our findings emphasize for larger trials with rigorous study designs to better understand the impact of IVIG, particularly in those with severe COVID-19., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Introduction: This systematic review and meta-analysis assessed the characteristics, types, and impact of interventions to improve adherence to attention-deficit hyperactivity disorder (ADHD) medications within the context of the three phases of adherence, namely, initiation, implementation, and discontinuation., Methods: PubMed, Psychological Information Database, Embase, International Pharmaceutical Abstracts, and Google Scholar were systematically searched for relevant trials using appropriate search terms. Interventions were classified as educational, behavioural, affective, and multifaceted. Data was pooled using odds ratios and proportions., Results: Seventeen studies were included in this review. In a pooled analysis of four RCTs, interventions did not significantly improve medication adherence (OR = 2.32; 95%-Confidence Interval=CI = 0.91-5.90; p  = 0.08). In seven non-randomized trials, a pooled proportion of people who adhered to ADHD medication was considerably higher in the intervention group (85%, 95%CI = 78%-91%) than in the control group (47%, 95%CI = 33%-61%). Interventions varied in terms of study design, methods and their impact on different phases of adherence., Conclusions: Despite some promising results, the lack of consideration of phase-specific adherence factors may limit the effectiveness and sustainability of interventions to improve adherence in clinical practice. Future interventions should be phase-specific, guided by factors which are pertinent to each phase. Meanwhile, clinicians should choose or tailor interventions based on individual needs and preferences.

Lead (Pb) is a neurotoxin, and children are vulnerable due to their evolving physiology and high-risk behaviours. Soil remediation interventions have proven effective in reducing Pb exposure. The primary objective is to measure the effectiveness of soil remediation at abandoned used lead acid battery (ULAB) recycling sites, nearby household cleaning, and community awareness in reducing blood lead levels (BLLs) in children. Additionally, this study aims to examine associations of Pb exposure with hematological, cardiovascular, renal, immunological, and endocrinological parameters in children aged 0-12 years. This study employs a quasi-experimental design, with abandoned ULAB sites as intervention sites and two control sites in Bangladesh. The intervention includes soil remediation coupled with community education. Data will be collected prior to the intervention and at a 12-month follow-up, including a comprehensive Pb exposure survey and collect environmental, turmeric samples, and blood from the child. Pb concentrations in environmental samples and turmeric samples will be determined using XRF analyser. Child BLL will be measured using Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) and proposed biochemical parameters will be analysed using routine laboratory methods. This study could provide valuable insights for designing targeted interventions in similar settings and mitigating exposure to Pb., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Aim: Cannabis-based medication has recently been made available in the NHS for reducing pain and spasticity in patients with multiple sclerosis (MS). The currently available preparation of Sativex (nabiximols) contains a combination of botanical cannabis extracts with cannabidiol (CBD) and tetrahydrocannabinol (THC) with almost equal amounts in addition to minor cannabinoids and terpenoids and is delivered via an oro-mucosal spray. The present study aims to examine the use and trends in prescribing cannabinoid-based Sativex to control pain in patients diagnosed with MS., Methods: Primary care prescribing data for cannabinoid-based Sativex (2013-2022) from the Prescription Cost Analysis were extracted and analysed. Linear regression analyses were performed to examine prescription trends and prescription costs (average change per year)., Results: There was a general increasing trend in the number of prescriptions each year, from 4.42 items dispensed per 100,000 people in 2013 to 5.15 in 2022. Overall, prescription items for cannabinoid-based Sativex increased by 0.34% per year (95% CI:-3.98, 4.67, p  = 0.860) on average between 2013 and 2022. On average, a 2.43% (95% CI: -5.78, 0.92, p  = 0.133) increase per year was observed for the costs of cannabinoid-based Sativex from 2013 to 2022., Conclusion: The results suggested that cannabinoid-based Sativex should be considered an option due to its effectiveness, acceptable tolerance, and safety profile in the prescribing of Sativex., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: This systematic review and meta-analysis evaluates the evidence from randomized controlled trials (RCTs) involving pharmacological interventions for improving sleep in people with Alzheimer's disease (AD)., Methods: A systematic literature search in eight databases from January 2000 to July 2023 focusing on RCTs that compared a pharmacological intervention with a placebo for enhancing sleep in people with AD. The authors registered the study protocol at Prospero, followed the PRISMA guidelines, and produced the pooled estimates using random-effect or IVhet models., Results: Eight different interventions and 29 different sleep outcomes were examined in 14 RCTs included in this review. Eszopiclone positively affected sleep efficiency, as did orexin antagonists. However, there was no difference when melatonin was used. The interventions demonstrated low discontinuation rates and a few adverse drug reactions., Conclusion: Although melatonin was the most investigated intervention, the evidence for its efficacy is inconclusive. On the other hand, trazodone and orexin receptor antagonists showed promising results; however, more RCTs are needed for definite answers.

Aseptic glenoid component loosening after anatomic total shoulder arthroplasty remains an important cause of late clinical failure and revision surgery. We present here the surgical technique of all-arthroscopic removal and glenoid bone grafting. Arthroscopic removal of a loose glenoid component and bone grafting of the glenoid defect without dermal allograft preserves glenoid bone stock and obviates the need for multiple suture anchors to hold the graft in place., Competing Interests: All authors (R.Z., S.J.M., C.M.F., S.S.H.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The anatomic interplay and overlap between the cervical spine and the shoulder constitutes a challenge for shoulder and spine surgeons, as symptoms of spine and shoulder pathologies are often similar and may lead to entity misdiagnosis., Methods: PubMed, Cochrane, and Google Scholar (page 1-20) searches were updated to October 2023 in search of the qualified papers. Boolean Operators were used with a combination of the keywords "spine" OR "neck" And "Shoulder". Furthermore, reference lists from papers were also searched to find literature., Results: It is of pivotal importance to conduct comprehensive preoperative clinical investigation to appropriately evaluate and assess the source of the pathology and the leading causes behind it. Certain markers can help guide surgeons towards etiologies, and these include areas of pain and physical exam findings with the arm squeeze test having the highest sensitivity and specificity for diagnosing cervical radiculopathy. As for the shoulder, despite its low sensitivity, the Yergason test had the highest specificity for diagnosing subacromial impingement. Local anesthetic injection can help as well in the diagnostic approach. Moreover, the interplay between these anatomic locations is not solely related to preoperative diagnosis. Studies have shown that previous surgery for cervical spine pathology may negatively affect the outcomes of shoulder procedures like arthroplasties., Conclusion: Shoulder and spine surgeons should be wary and vigilant of accurately diagnosing the etiology of the presenting symptoms to ensure proper management and optimize prognosis., (© 2024 The Author(s).)

Background: Gut-directed hypnotherapy is effective for patients with irritable bowel syndrome (IBS). Despite its considerable evidence base, gut-directed hypnotherapy is not widely available and remains a limited resource. This emphasises the need to select patients who are most likely to benefit., Aim: To determine whether baseline patient characteristics were predictive of response to gut-directed hypnotherapy in patients with IBS METHODS: We conducted a secondary analysis of outcomes of 448 patients with refractory Rome III IBS who participated in a randomised study confirming non-inferiority of 6 compared to 12 sessions of gut-directed hypnotherapy. We compared baseline patient characteristics, including age, sex, IBS subtype, quality of life and IBS-Symptom Severity Scale (IBS-SSS), non-colonic symptom score and Hospital Anxiety and Depression (HAD) score between responders and non-responders. We defined response as ≥50-point decrease in IBS-SSS or ≥30% reduction in pain severity scores., Results: Overall, 76.3% achieved ≥50-point decrease in IBS-SSS. Responders had a higher baseline non-colonic symptom score (p = 0.005). Those who achieved ≥30% improvement in abdominal pain scores (59.8%) had higher baseline IBS-SSS (p = 0.03), and lower baseline HAD-depression score (p = 0.012). Fifty-four patients (12%) dropped out of gut-directed hypnotherapy. Compared to completers, dropouts had higher baseline HAD-anxiety score (p = 0.034)., Conclusions: These data suggest that patients with a higher burden of gastrointestinal and extraintestinal symptoms are most likely to benefit from gut-specific behavioural intervention for refractory IBS. Clinical assessment of gastrointestinal, somatic and psychological symptom profiles may play a role in selecting patients for gut-directed hypnotherapy., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation into virions or export for cell-cell fusion. Because this C-terminal residue is the key determinant of SARS-CoV-2 assembly and fusogenicity, our work provides a framework for the export of S protein encoded in genetic vaccines for surface display and immune activation., (© 2023. The Author(s).)

Traditional public extension worker-farmer cooperation in rice production demonstration is not working efficiently, therefore, private partnership-based demonstration has been attempted to introduce as its alternative very recently involving dealer-customer farmer. The study evaluated the private extension services rendered through dealer-customer farmer cooperation in Bangladesh. Thirty-three rice seed dealers and ninety-two customer farmers formed the samples for the study. Face-to-face interviews were employed as a quantitative method while focus group discussion was used as a qualitative method in the present study. Involving in the private rice production demonstration approach, customer farmers indicated high profit, greater involvement in decision-making, and improved marketing skills as the major advantages; while the dealers stressed the benefit received by the small farmers, improvement in their decision-making capacity and increased local rice production. However, the slow distribution of inputs during the production period was a weakness in the arrangement, which was mostly because of the dealers' lack of understanding of the customer farmers' needs. The private extension system being a new concept in the country may be observed over a period and gradually extended to the nooks and crannies of the country., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Mobile phones have emerged as the predominant technology in developing countries, especially within agricultural enterprises. This research investigates the influence of mobile phone utilization on the empowerment of female entrepreneurs in rural farming communities. Data were gathered from 150 female agricultural entrepreneurs in the rural regions of Bangladesh. The empowerment of these women was assessed across five dimensions: economic, social, technological, psychological, and political. The findings indicate that the composite empowerment index was notably higher at 61.92% post-mobile phone adoption, in contrast to 37.47% prior to its use. This underscores the positive impact of mobile phone utilization on the empowerment of rural female farmers. The research highlighted significant enhancements in all five empowerment dimensions, with these augmentations being statistically meaningful. The most pronounced improvement was observed in economic empowerment, while political empowerment witnessed the least growth. Furthermore, the shifts were profoundly correlated with the other three dimensions: social, technological, and psychological. The evidence establishes a link between mobile phone adoption by rural female farmers and their subsequent empowerment, with empowerment metrics showing a steady rise from the low-usage to the high-usage categories. Consequently, the correlation is positive. The results advocate that mobile phone utilization assists rural female farmers in augmenting their empowerment. It is thus recommended that policymakers and developmental organizations prioritize mobile technology as a tool to empower rural women in Bangladesh. This can be realized by enhancing accessibility, confronting socio-cultural barriers, and fostering digital literacy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Lymphocyte activation gene 3 protein (LAG3) is an inhibitory receptor that is upregulated on exhausted T cells in tumors. LAG3 is a major target for cancer immunotherapy with many anti-LAG3 antibodies in clinical trials. However, there is no structural information on the epitopes recognized by these antibodies. We determined the single-particle cryoEM structure of a therapeutic antibody (favezelimab) bound to LAG3 to 3.5 Å resolution, revealing that favezelimab targets the LAG3-binding site for MHC class II, its canonical ligand. The small size of the complex between the conventional (monovalent) Fab of favezelimab and LAG3 (∼100 kDa) presented a challenge for cryoEM. Accordingly, we engineered a bivalent version of Fab favezelimab that doubled the size of the Fab-LAG3 complex and conferred a highly identifiable shape to the complex that facilitated particle selection and orientation for image processing. This study establishes bivalent Fabs as new fiducial markers for cryoEM analysis of small proteins., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.

Competing Interests: The authors declare no conflicts of interest.

Competing Interests: None.

Background: Demand for diabetes care and prevention has increased due to Saudi Arabia's high prevalence of diabetes mellitus and its insufficient treatment. This raised awareness of the significance of community pharmacists in Saudi Arabia, who may significantly improve diabetes treatment by setting up pharmacist-led diabetic clinics. Thus, to assess community pharmacists' readiness to lead diabetes clinics in Saudi Arabia, this study evaluated the usefulness of an educational session on diabetes care., Method: The preparation of community pharmacists for diabetes treatment and management was assessed using a validated diabetes-specific questionnaire. An engaging and thorough diabetes education class was presented by two licensed diabetes educators. One-way ANOVA, chi-square, and the Mann-Whitney U-test were used to statistically assess the pre- and post-knowledge and attitude scores of community pharmacists., Results: Following a learning session, the community pharmacists had a significant increase in understanding oral hypoglycemic medicines, monitoring the disease's course, and dosing of insulin for diabetics (p = 0.01). Additionally, the community pharmacist's perspective and attitude score on managing diabetes increased from 49.74 to 52.74 (p = 0.01)., Conclusion: The study's findings demonstrated a marked improvement in community pharmacist's knowledge of and attitude toward running pharmacist-led diabetic clinics following a session on diabetes education in collaboration with the Pharmacy College. The study's findings also emphasized the significance of developing a structured programme for diabetes education in Saudi Arabia to address the demands of community pharmacists in terms of professional development., (© 2023. The Author(s).)

Competing Interests: Authors declare no potential conflicts of interest.

Introduction: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders among the older population. Sleep disruption and circadian rhythm disorders often develop in AD patients, and many experience sleeping difficulties requiring pharmacological and non-pharmacological interventions., Areas Covered: This review appraised the evidence from clinical studies on various pharmacological and non-pharmacological therapies for sleep disturbances in AD patients and proposed an algorithm to manage sleep disturbances in this population of patients., Expert Opinion: Non-pharmacological interventions are generally preferred as the first-line approach to improve sleep-related symptoms in AD due to their favorable safety profile. However, when non-pharmacological interventions alone are insufficient, a range of pharmacological agents can be considered. Trazodone and melatonin are commonly used as adjunctive therapies, while Z-drugs including zopiclone and zolpidem are specifically employed to treat insomnia in patients with late-onset AD. Furthermore, a newer class of agents known as dual orexin receptor antagonists has emerged and gained approval for improving sleep onset and maintenance in AD patients.

Background: Community pharmacy practice in Saudi Arabia is evolving and needs to be at par with the developed world. Community pharmacists can play a vital role in bridging gaps in the delivery of healthcare services by providing patient-centred care to patients and contributing toward the healthcare transformation plan of vision 2030 of Saudi Arabia. The present study is aimed at evaluating the knowledge, attitude, and practices of community pharmacists in delivering patient-centred care services., Method: A nationwide cross-sectional survey using a validated and pre-tested 27-item self-reported questionnaire was conducted amongst 301 (86.4% male, 13/6% female) community pharmacists from all regions of Saudi Arabia. Both descriptive and inferential analysis was employed using the SPSS version, with 0.05 as the level of significance., Results: Community pharmacists from chain pharmacy groups, female gender and staff community pharmacists had statistically better overall practice standards, knowledge, and attitude to conduct patient-centred care services (p less than 0.01). The majority of community pharmacists would expect extra remuneration and participation in structured professional skills development programs to provide patient-centred care efficiently. Inaccessibility of patient data from healthcare facilities, the unavailability of informative literature, and administrative workload were among the barriers cited in delivering patient-centred care., Conclusion: The study findings show that community pharmacists could play a significant role in providing patient-centred care and contribute to the achievement of the healthcare reform agenda of Saudi Arabia. However, some obstacles must be overcome before this practice can be shifted, including the introduction of a formalized continuing professional development program, financial incentives, and a decrease in the administrative burden on pharmacists. The results of this study may help policymakers in Saudi Arabia better comprehend the country's existing approach to community pharmacy practice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

COVID-19 vaccine hesitancy continues to be a widespread problem in Pakistan due to various conspiracy beliefs, myths and misconceptions. Since the hemodialysis population is at a higher risk of contracting infections, we sought to investigate the current COVID-19 immunization status and reasons for any vaccine hesitancy among these patients in Pakistan. This cross-sectional study was conducted among maintenance hemodialysis patients at six hospitals in the Punjab Province of Pakistan. Data were collected anonymously using a questionnaire. A total of 399 hemodialysis patients took part in the survey, the majority of them were male (56%) and aged 45-64 years. A calculated 62.4% of the patients reported receiving at least one dose of the COVID-19 vaccine. Of those vaccinated (249), 73.5% had received two doses and 16.9% had received a booster dose. The most common reasons for vaccination were "being aware they were at high risk" (89.6%), "fear of getting infected" (89.2%) and "willingness to fight against COVID-19-pandemic" (83.9%). Of the 150 patients who had not yet been vaccinated, only 10 showed a willingness to take the COVID-19 vaccine. The major reasons for refusal included "COVID-19 is not a real problem" (75%), the "corona vaccine is a conspiracy (72.1%)" and "I don't need the vaccine" (60.7%). Our study revealed that only 62% patients receiving hemodialysis were partially or completely vaccinated against COVID-19. Consequently, there is a need to initiate aggressive approaches to educate this high-risk population in order to address their concerns with vaccine safety and efficacy as well as correct current myths and misconceptions to improve the COVID-19 immunization status in this population.

Blood vessels form elaborate networks that depend on tissue-specific signalling pathways and anatomical structures to guide their growth. However, it is not clear which morphogenetic principles organize the stepwise assembly of the vasculature. We therefore performed a longitudinal analysis of zebrafish caudal fin vascular assembly, revealing the existence of temporally and spatially distinct morphogenetic processes. Initially, vein-derived endothelial cells (ECs) generated arteries in a reiterative process requiring vascular endothelial growth factor (Vegf), Notch and cxcr4a signalling. Subsequently, veins produced veins in more proximal fin regions, transforming pre-existing artery-vein loops into a three-vessel pattern consisting of an artery and two veins. A distinct set of vascular plexuses formed at the base of the fin. They differed in their diameter, flow magnitude and marker gene expression. At later stages, intussusceptive angiogenesis occurred from veins in distal fin regions. In proximal fin regions, we observed new vein sprouts crossing the inter-ray tissue through sprouting angiogenesis. Together, our results reveal a surprising diversity among the mechanisms generating the mature fin vasculature and suggest that these might be driven by separate local cues., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)