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Interviews were conducted with eight Japanese immigrant youth about their experiences with respect to adjusting to life in the United States, dealing with discrimination, and coping with cultural challenges. They were also questioned about their mental health and family and peer relations. Results indicate that participants managed to maintain bicultural identities and to cope with the problems that they encountered. Nevertheless, they experienced the following difficulties: racism and prejudice, language barriers, and conflict regarding identity and values. In terms of coping, participants mostly relied on friends for support; only one had sought the help of a professional counselor. The implications of the findings are discussed in terms of working with immigrant youth from Japan. [ABSTRACT FROM AUTHOR]

Background/aims: To report the long-term visual outcomes and side effects in patients with small choroidal melanoma (CM) undergoing ruthenium-106 (Ru-106) plaque brachytherapy., Methods: Retrospective, interventional, consecutive series of small CM ≤2.5 mm in height and ≤16 mm in largest basal diameter treated with Ru-106 plaque with a median radiation dose of 100 Gy prescribed to tumour apical height., Results: 310 patients (160 men) with a mean (SD) age of 58.4±14.1 years met the study inclusion criteria. The median follow-up was 57.5 (range 3.4-170.5) months. The mean tumour baseline thickness was 1.9±0.4 (range 0.4-2.5) mm. The mean baseline logarithm of the minimum angle of resolution (logMAR) of best corrected visual acuity (BCVA) was 0.21±0.4 (Snellen equivalent 6/9; range -0.1 to 1.5). Mean final BCVA was ≤0.3 logMAR (Snellen equivalent 6/12) in 161 patients (54.2%), better than 1.0 logMAR (Snellen equivalent 6/60) and <0.3 logMAR in 59 patients (19.9%), and ≥1.0 logMAR in 77 patients (25.9%). Kaplan-Meier estimates of poor final VA (≥1.0 logMAR) were 13.2% at 5 years and 54.5% at 10 years. Early and late complications developed in 20.6% and 42.6% of cases, respectively. Radiation maculopathy was the most frequent late side effect (29% of patients) with Kaplan-Meier rates of 18.2%, 31.7% and 42.1% at 3, 5 and 10 years, respectively. Older age, lipofuscin, proximity to fovea, final tumour elevation and radiation maculopathy predicted visual loss ≥5 Snellen lines., Conclusion: Despite early and late complications in 20.6% and 42.6% of cases, Ru-106 brachytherapy for small CM allows retention of BCVA ≤0.3 logMAR in half of the eyes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Chimeric Antigen Receptor (CAR) T-cell therapies represents a major advancement in the treatment of refractory hematologic malignancies, with high remission rates for relapsed B-cell lymphomas and leukemias. However, it is associated with a broad spectrum of potentially life-threatening toxicities, many of which require intensive care unit (ICU) management. Key complications include Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), as well as severe infections, Immune Effector Cell-associated Hematotoxicity (ICAHT), coagulopathies, and organ dysfunctions resulting from the intense inflammatory response induced by CAR T-cells. Approximately one third of patients undergoing CAR T-cell therapy require ICU admission. Among those patients, CRS is the leading indication. ICANS and sepsis are other major causes of admission to the ICU. This review provides a comprehensive overview of ICU considerations for managing CAR T-cell-related toxicities, covering criteria for ICU admission, approaches to grading and treating complications, and interdisciplinary recommendations to optimize patient outcomes. Enhanced awareness and early intervention are critical in reducing ICU mortality and improving overall survival in patients receiving CAR T-cell therapy., Competing Interests: Declaration of competing interest 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., (Copyright © 2025. Published by Elsevier Ltd.)

Background: As people living with HIV (PWH) age, they face new challenges that can have a negative impact on their quality of life (QOL) and mental health., Setting: This study enrolled PWH at the end of life (EOL) who were actively engaged in cure-related research in Southern California, United States. EOL was defined as having a prognosis of 6 months or less to live. We examined the relationship between QOL, mental health, and research participation., Methods: Structured assessments were used to collect comprehensive data on QOL and mental health., Results: From 2017 to 2023, 35 PWH in their final stages of life who were actively engaged in cure-related research were enrolled. Their median age was 62.7 years, and most were White or otherwise non-Hispanic/non-Latino (90.6%), and male (86.7%). Changes in QOL and the presence of neurologic and psychiatric conditions, with a focus on depression and anxiety, were the primary outcomes assessed in this study. Participants had stable QOL scores throughout the study. There was an inverse relationship between QOL and Beck Depression Inventory scores, with higher mean QOL scores being associated with lower mean Beck Depression Inventory scores ( P < 0.001)., Conclusions: QOL remained stable among PWH who participate in cure-related research at EOL. The inverse relationship between QOL and depressive symptoms suggests that participation in cure-related research may improve QOL or reduce depressive symptoms in this population. Future interventions should look into ways to improve the well-being of PWH at EOL through research and customized mental health interventions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory illness in older adults. A major cause of COPD-related morbidity and mortality is acute exacerbation of COPD (AECOPD). Bacteria in the lungs play a role in exacerbation development, and the most common pathogen is non-typeable Haemophilus influenzae (NTHi). A vaccine to prevent AECOPD containing NTHi surface antigens was tested in a clinical trial. This study measured IgG and IgA against NTHi vaccine antigens in sputum. Sputum samples from 40 COPD patients vaccinated with the NTHi vaccine were collected at baseline and 30 days after the second dose. IgG and IgA antibodies against the target antigens and albumin were analyzed in the sputum. We compared antibody signals before and after vaccination, analyzed correlation with disease severity and between sputum and serum samples, and assessed transudation. Antigen-specific IgG were absent before vaccination and present with high titers after vaccination. Antigen-specific IgA before and after vaccination were low but significantly different for two antigens. IgG correlated between sputum and serum, and between sputum and disease severity. Sputum albumin was higher in patients with severe COPD than in those with moderate COPD, suggesting changes in transudation played a role. We demonstrated that immunization with the NTHi vaccine induces antigen-specific antibodies in sputum. The correlation between IgG from sputum and serum and the presence of albumin in the sputum of severe COPD patients suggested transudation of antibodies from the serum to the lungs, although local IgG production could not be excluded. Clinical Trial Registration : NCT02075541.

A comparative cross-sectional study was conducted on farmed eggs (n: 480) and environmental samples (n: 72; feed, water, and poultry droppings) from twenty-four deep litter and caged poultry layer farms across Punjab, India. The study noted a significantly higher occurrence of Staphylococcus aureus (31.67%; 95% CI 26.37-36.96%) and methicillin-resistant S. aureus (MRSA) (32.5%, 95% CI 23-43.3%) in deep litter farms (P < 0.05). The logistic regression analysis revealed while the odds of presumptive MRSA from egg isolates were high (Odds ratio: 2.714; 95% CI 1.172, 6.284) in deep litter, conversely, resistance against ceftriaxone (0.279; 95% CI 0.129, 0.605), tetracycline (0.227; 95% CI 0.104, 0.497), and erythromycin (0.46; 95% CI 0.218, 0.973) was low. The multi-drug resistance was high and nearly equal; 68.53%, and 72.22% in deep litter and cage systems respectively. Additionally, around 89.65% and 77.7% of MRSA from deep litter and cage systems had multiple antibiotic resistance index > 0.2 respectively. Among the resistance genes under study, the odds of mecA and tetL were 2.417 and 8.029 times higher in deep litter. The hierarchical clustering of MRSA isolates based on the antibiogram profile depicted the formation of a large number of cluster solutions with a mix of isolates from both systems. The SCCmec typing revealed a predominance of type V in both the systems (34.4%; deep litter and 33.3%; cage), with a scarce distribution of other types and subtypes viz., deep litter: types III; 13.7%, IVc; 6.8%, II; 6.8%, IVa, and IVb; 3.4% and cage system: types III and IVc; 11.1%. To, the best of our knowledge current study is the first-ever comprehensive study on comparative occurrence, AMR profile, molecular characterization, and typing of MRSA from farmed eggs and environment from India., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To report local tumour control, metastasis and survival rates of patients with small choroidal melanoma (CM) after treatment with ruthenium-106 (Ru-106) plaque brachytherapy., Methods: Retrospective case series of 353 consecutive eyes with small CM (thickness ≤2.5 mm and largest basal diameter ≤16 mm) treated with Ru-106 brachytherapy at the London Ocular Oncology Service, between October 2004 and May 2019., Results: The final cohort included 310 eyes and tumour recurrence was observed in 52 (17%) eyes. Ocular retention rate was 96%. Metastatic disease and tumour-related death occurred in 18 (5.8%) and 12 (3.9%) patients, respectively. Metastases were diagnosed after a median of 54 (54±35; range 3.6-118) months from initial treatment. Kaplan-Meier estimates for tumour recurrence, melanoma-related metastases and survival were 17% (95% CI 13.3% to 22.9%), 4.8% (95% CI 2.6% to 8.5%) and 98% (95% CI 94.4% to 99.1%) at 5 years and 26% (95% CI 18.3% to 35.3%), 16% (95% CI 8.7% to 27.7%) and 92% (95% CI 84.5% to 95.7%) at 10 years, respectively. On multivariable analysis, factors predictive for tumour recurrence included juxtapapillary location, larger plaque and final tumour thickness, and for metastasis exudative retinal detachment., Conclusion: Small CMs treated with Ru-106 brachytherapy show recurrence and death rates of 17% and 2% at 5 years and 26% and 8% at 10 years. As small CMs have better prognosis than large tumours, early treatment is the key for better survival outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

RNA interference (RNAi) is a promising technology for controlling insect pests of agriculture. This technology is mediated through the application of double-stranded RNAs (dsRNAs), which are processed within the insect cells into small interfering RNAs (siRNAs). These molecules then target and reduce the expression of the insect-specific genes that can kill or reduce the performance of the pest. The application of these RNA biopesticides generally falls under two methods: foliar sprays and expression of RNAi constructs within transgenic plants. Here, we provide evidence supporting feasibility of using transgenic plants to deliver RNAi-based biopesticides against their aphid pests. Our findings suggest that, under the Cucumis melo galactinol synthase 1 promoter, the companion cells of transformed Arabidopsis thaliana plants express dsRNAs but not siRNAs at detectable levels. Further, oral application of either siRNAs or dsRNAs is equally effective in reducing the expression of transcripts of the integral membrane protein aquaporin 1 in Acyrthosiphon pisum pea aphids. We did not find any dsRNAs or siRNAs remaining in the insects or honeydew 48 h post-exposure, suggesting a low risk of contamination of these molecules beyond the target phloem-piercing insect pests., (© 2024 Wiley Periodicals LLC.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and can progress to serious complications, including metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Predisposing risk factors for MASH include obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. Patients with MASH often experience significant impairments in their health-related quality of life and other patient-reported outcomes (PROs), particularly in physical functioning domains, fatigue, and vitality. Incorporating PROs offers valuable insights into patients' perspectives on their symptoms, treatment efficacy, and overall well-being, thereby guiding more holistic and patient-centered care strategies. This review aims to investigate the utilization of patient-reported outcome measures (PROMs) in the context of MASLD and MASH care, identify which PROMs are employed, and summarize the outcomes reported., Competing Interests: Z.M.Y. has received research funding and/or serve as consultant to Intercept, Cymabay, Boehringer Ingelheim, Ipsen, B.M.S., G.S.K., NovoNordisk, Siemens, Madridgal, Merck, Akero and Abbott., (Thieme. All rights reserved.)

The present study evaluated the occurrence, antibiogram profile, and sequence types (STs) of multidrug resistant (MDR) Escherichia coli from freshly laid eggs ( n = 480), feed ( n = 24), water ( n = 24), poultry droppings ( n = 24), and hand swab samples ( n = 10) collected from 24 deep litter (DL) and caged poultry layer farms (12 per category) across Punjab, India. The overall E. coli contamination rate in DL and cage farms was 32% (95% confidence intervals [CI], 26.6-37.8%) and 16.7% (95% CI, 12.6-21.6%), respectively. The logistic regression analysis revealed that the DL system had higher odds of occurrence (odds ratio [OR]) of extended-spectrum beta-lactamase (ESBL) (2.195, 95% CI, 1.065, 4.522) and ESBL/AmpC coproducers (2.69, 95% CI, 1.122, 6.45) compared to the cage system. Additionally, isolates from the DL were 4.065 (95% CI, 1.477, 11.188) times more tetracycline resistant compared to the latter; however, resistance to amoxyclavulanate (OR, 0.437; 95% CI, 0.209, 0.912), and ampicillin (OR, 0.343; 95% CI, 0.163, 0.720) was lesser in DL system. Notably, around 97.7% and 87.2% of the isolates from the DL and cage system were MDR, with the DL system having 6.439 (95% CI, 1.246, 33.283) times more chances of harboring MDR E. coli . Additionally, among the resistance genes, the DL system demonstrated significantly high presence of bla AmpC (56%), qnr A/B/S (42.3%), and tet A/B (30.6%). Furthermore, multilocus sequence typing of 11 MDR isolates ( n = 5, DL, and 6, cage) revealed the presence of 10 STs, of which ST10, ST155, and ST156 were found to be of public health importance. Therefore, the present study highlights the burden of MDR, ESBL, and AmpC-producing E. coli on poultry eggs and farm environment, which could be carried over to human handlers and consumers upon direct contact during handling and processing.

Background: We report data from stage 1 of an ongoing 2-staged, phase 1/2 randomized clinical trial with a 4-component generalized modules for membrane antigens-based vaccine against Shigella sonnei and Shigella flexneri 1b, 2a, and 3a (altSonflex1-2-3; GSK)., Methods: Europeans aged 18-50 years (N = 102) were randomized (2:1) to receive 2 injections of altSonflex1-2-3 or placebo at 3- or 6-month interval. Safety and immunogenicity were assessed at prespecified time points., Results: The most common solicited administration-site event (until 7 days after each injection) and unsolicited adverse event (until 28 days after each injection) were pain (altSonflex1-2-3, 97.1%; placebo, 58.8%) and headache (32.4%; 23.5%), respectively. All serotype-specific functional IgG antibodies peaked 14-28 days after injection 1 and remained substantially higher than prevaccination at 3 or 6 months postvaccination; the second injection did not boost but restored the initial immune response. The highest seroresponse rates (≥4-fold increase in titers over baseline) were obtained against S. flexneri 2a (enzyme-linked immunosorbent assay [ELISA] after injection 1, 91.0%; after injection 2 [day 113; day 197], 100%; 97.0% and serum bactericidal activity [SBA] after injection 1, 94.4%; after injection 2, 85.7%; 88.9%) followed by S. sonnei (ELISA after injection 1, 77.6%; after injection 2, 84.6%; 78.8% and SBA after injection 1, 83.3%; after injection 2, 71.4%; 88.9%). Immune responses against S. flexneri 1b and S. flexneri 3a, as measured by both ELISA and SBA, were numerically lower compared to those against S. sonnei and S. flexneri 2a., Conclusions: No safety signals or concerns were identified. altSonflex1-2-3 induced functional serotype-specific immune responses, allowing further clinical development in the target population. Clinical Trials Registration . NCT05073003., Competing Interests: Potential conflicts of interest. U. N. N., F. Ma., E. S., J. J., G. L. C., A. S. B., C. G. V., P. F., E. M., F. N., R. R., I. D. R., J. A., A. M. C., F. B. S., O. R., V. C., F. Mi., A. K. A., and A. P. are or were employees of GSK when the study was designed, initiated, and/or conducted. U. N. N., J. J., G. L. C., A. S. B., C. G. V., F. N., I. D. R., J. A., F. B. S., O. R., V. C., F. Mi., A. K. A., and A. P. hold shares in GSK as part of their remuneration. A. K. A. reports GSK scientific writer support for this study. F. Mi. reports a patent issued on the 4-component Shigella GMMA formulation. I. L. R. reports funding to her institution for the conduct of GSK Vaccines Institute for Global Health (GVGH) studies; being a data safety monitoring board member of a phase 3 (non-Shigella) vaccine trial for Janssen Vaccines; and funding to her institution for the conduct of various vaccine trials (none were Shigella vaccine studies) from GSK, Janssen, Curevac, Osivax, Vaccitech, Icosavax, OSE Immunotherapeutics, Icon Genetics, Virometix, and MSD. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: Strong primary health care (PHC) systems require well-established PHC education systems to enhance the skills of general practitioners (GPs). However, the literature on the experiences of international collaboration in primary care education in low- and middle-income countries remains limited. The purpose of this study was to evaluate the implementation and perceived impact of the McGill-Tongji Blended Education Program for Teacher Leaders in General Practice (referred to as the "Tongji Program")., Methods: In 2020-2021, the McGill Department of Family Medicine (Montreal, Canada) and Tongji University School of Medicine (TUSM, Shanghai, China) jointly implemented the Tongji Program in Shanghai, China to improve the teaching capacity of PHC teachers. We conducted an exploratory longitudinal case study with a mixed methods design for the evaluation. Quantitative (QUAN) data was collected through questionnaire surveys and qualitative (QUAL) data was collected through focus group discussions., Results: The evaluation showed that learners in Tongji Program were primarily female GPs (21/22，95%) with less than 4 years of experience in teaching (16/22，73%). This program was considered a successful learning experience by most participants (19/22, 86%) with higher order learning tasks such as critical thinking and problem-solving. They also agreed that this program helped them feel more prepared to teach (21/22，95%), and developed a positive attitude toward primary care (21/22，95%). The QUAL interview revealed that both the Tongji and McGill organizers noted that TUSM showed strong leadership in organization, education, and coordination. Both students and teachers agreed that by adapting training content into contextualized delivery formats and settings, the Tongji Program successfully overcame language and technology barriers., Conclusions: Committed partnerships and contextualization were key to the success of the Tongji Program. Future research should focus on how international primary care education programs affect learners' behavior in their practice settings, and explore barriers and facilitators to change., Competing Interests: Bertrand Lebouché has received research support and consulting fees from ViiV Healthcare, Merck, and Gilead. The remaining authors declare no conflict of interest. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript., (© 2024 The Author(s). Health Care Science published by John Wiley & Sons Ltd on behalf of Tsinghua University Press.)

People living with HIV are particularly susceptible to developing metabolic disorders, including metabolic dysfunction-associated steatotic liver disease and other forms of SLD. However, people living with HIV have been historically excluded from clinical trials and large cohort studies of SLD. Therefore, our understanding of the risk factors and natural history of SLD in this population is poor. Moreover, relevant knowledge gaps on the epidemiology and barriers for adequate health care, such as stigma, hamper adequate responses to the ongoing HIV and SLD syndemic. This Viewpoint provides a comprehensive perspective on how to tackle SLD in people living with HIV by examining the role of social determinants of health in the development of liver disease and metabolic syndrome comorbidities among this population, emphasising the importance of prioritising SLD management, summarising the most urgent needs in the field, and offering recommendations for advancing research to fill key data gaps and protect liver health of people living with HIV., Competing Interests: Declaration of interests JMP reports having received consulting fees from Boehringer Ingelheim, MSD and Novo Nordisk. He has received speaking fees from Gilead, Intercept, and Novo Nordisk, and travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk. He has received educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, AbbVie, ViiV, and MSD. CR reports honoraria for speaking activities from ViiV Healthcare. GG reports speaking fees from ViiV Healthcare. AB acknowledges having received consulting fees from Boehringer Ingelheim and speaking fees by GE Healthcare and Hologic. GW received research grants from Gilead Sciences and Roche Diagnostics. MBB has received grant support from National Institute of Health, US Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health, Pfizer, The Kinetix Group, Histoindex, and serves as a consultant for The Kinetix Group, Madrigal, Pfizer, Theratechnologies, Fibronostics, Novo Nordisk, and GSK. JN has received honoraria, speaking fees, and financial support for attending conferences from AbbVie, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare, and consulting fees from ViiV Healthcare, Gilead Sciences, Janssen Cilag, and Merck Sharp & Dohme, outside the submitted work. JVL acknowledges grants from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Madrigal, MSD, Novo Nordisk, Pfizer, and Roche Diagnostics; speaker fees from AbbVie, Echosens, Gilead Sciences, Janssen, Moderna, MSD, Novo Nordisk, and Pfizer; and consulting fees from Echosens, NovoVax, GSK, Novo Nordisk, and Pfizer, all outside the current work. JVL also acknowledges participation on the advisory board for the “Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (The QuickStart Study): a cluster randomised control trial–Australia” trial; had roles in the following committees: Member, European Association for the Study of the Liver, Public Health and Policy Committee; Healthy Livers, Health Livers (formed by AASLD, ALEH, APASL, European Association for the Study of the Liver) Global NASH Council; and was the Co-chair of HIV Outcomes. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Scholars recommend providing migrants living with HIV (MLWH) with free treatment, rapidly, once linked to care to optimize their HIV-related experiences and health outcomes. Quantitative evaluations of patient-reported measures for MLWH in such models are necessary to explore the viability of these recommendations., Methods: Within a 96-week prospective cohort study at a multidisciplinary HIV clinic, participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for free and rapidly following care linkage. Eight patient-reported measures were administered at weeks 4, 24, and 48: (1) mMOS-SS to measure perceived social support; (2) IA-RSS to measure internalized stigma; (3) K6 to measure psychological distress; (4) PROMIS to measure self-efficacy with treatment taking; (5) G-MISS to measure perceived compliance with clinicians' treatment plans; (6) HIVTSQ to measure treatment satisfaction; (7) CARE to measure perceived provider empathy; and (8) PRPCC to measure perceived clinician cultural competence. Linear mixed modelling with bootstrapping was conducted to identify significant differences by sociodemographics and time., Results: Across weeks 4, 24, and 48, results suggest that MLWH enrolled in this study experienced moderate levels of social support; elevated levels of HIV-related stigma; moderate levels of distress; high self-efficacy with daily medication self-management; great compliance with clinicians' treatment plans; high treatment satisfaction; high perceived empathy; and high perceived cultural competence. Experience of social support (i.e., mMOS-SS scores) differed significantly by birth region. Experience of HIV-related stigma (i.e., IA-RSS scores) differed significantly by birth region, age, and language. Experience of distress (i.e., K6 scores) differed significantly by sexual orientation. Experience of treatment satisfaction (i.e., HIVTSQ scores) differed significantly by birth region and age. No significant differences were identified by time for any measure., Conclusion: Overall, participants expressed positive experiences around treatment and care, alongside comparably lower perceptions of social support, internalized stigma, and distress, potentially underscoring a need to embed targeted, well-funded, and accessible mental health support within HIV care models., (© 2024. The Author(s).)

Objective: Multidisciplinary care with free, rapid, and on-site bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) dispensation may improve health outcomes among migrants living with HIV. However, models for rapid B/F/TAF initiation are not well studied among migrants living with HIV, and an understanding of how social determinants of health (SDH) may affect HIV-related health outcomes for migrants enrolled in such care models is limited., Methods: Within a 96-week pilot feasibility prospective cohort study at a multidisciplinary HIV clinic, participants received free B/F/TAF rapidly after care linkage. The effects of SDH (i.e., birth region, sexual orientation, living status, education, employment, French proficiency, health coverage, use of a public health facility outside our clinic for free blood tests, and time in Canada) and other covariates (i.e., age, sex) on median time to antiretroviral therapy (ART) initiation and HIV viral undetectability from care linkage were calculated via survival analyses., Results: Thirty-five migrants were enrolled in this study. Median time to ART initiation and HIV undetectability was 5 days (range 0-50) and 57 days (range 5-365), respectively. Those who took significantly longer to initiate ART were aged <35 years, identified as heterosexual, had less than university-level education, or were unemployed. No factor was found to significantly affect time to undetectability., Conclusion: Despite the provision of free B/F/TAF, several SDH were linked to delays in ART initiation. However, once initiated and engaged, migrants living with HIV reached HIV undetectability efficiently. Findings provide preliminary support for adopting this care model with migrants living with HIV and suggest that SDH should be considered when designing clinical interventions for more equitable outcomes., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18-50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis., (© 2024. GlaxoSmithKline Biologicals S.A.)

Superficial infections with Streptococcus pyogenes (Strep A), pharyngitis and impetigo can induce acute rheumatic fever, an autoimmune sequela manifesting mostly with arthritis and rheumatic carditis. Valvular heart damage can persist or advance following repeated episodes of acute rheumatic fever, causing rheumatic heart disease. Acute rheumatic fever and rheumatic heart disease disproportionately affect children and young adults in developing countries and disadvantaged communities in developed countries. People living with rheumatic heart disease are at risk of experiencing potentially fatal complications such as heart failure, bacterial endocarditis or stroke. Transthoracic echocardiography plays a central role in diagnosing both rheumatic carditis and rheumatic heart disease. Despite the obvious medical need, no licensed Strep A vaccines are currently available, as their clinical development process faces several challenges, including concerns for cardiac safety. However, the development of Strep A vaccines has been recently relaunched by many vaccine developers. In this context, a reliable and consistent safety evaluation of Strep A vaccine candidates, including the use of transthoracic echocardiography for detecting cardiac adverse events, could greatly contribute to developing a safe and efficacious product in the near future. Here, we propose a framework for the consistent use of transthoracic echocardiography to proactively detect cardiac safety events in clinical trials of Strep A vaccine candidates., (© 2024. GlaxoSmithKline Biologicals S.A.)

Introduction: The Last Gift study at the University of California San Diego (UCSD), United States enrolls terminally ill people with HIV (PWH) in HIV cure research., Methods: From 2017 to 2022, we conducted surveys with Last Gift participants and their next-of-kin/loved ones to evaluate willingness to participate in different types of HIV cure research at the end of life (EOL). We analyzed willingness data descriptively., Results: We surveyed 17 Last Gift participants and 17 next-of-kin/loved ones. More than half of Last Gift participants ( n  = 10; 58.8%) expressed willingness to participate in studies involving totally new treatments or approaches ('first-in-human' studies), a combination of different approaches, the use of unique antibodies, proteins or molecules, or therapeutic vaccines. Under one-quarter of Last Gift participants ( n  = 4; 23.5%) expressed willingness to participate in research involving interventions that may shorten their life expectancy to benefit medical research. Most Last Gift participants and their next-of-kin/loved ones also expressed high acceptance for various types of donations and biopsies at the EOL (e.g. hair donations and skin, lymph node or gut biopsies)., Discussion: Knowing whether people would be willing to participate in different types of EOL HIV cure research can help inform the design of future innovative studies. As a research community, we have a duty to design studies with adequate safeguards to preserve the public trust in research and honor PWH's important gift to humanity., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The primary aim of this study is to validate the Blended Learning Usability Evaluation–Questionnaire (BLUE-Q) for use in the field of health professions education through a Bayesian approach. As Bayesian questionnaire validation remains elusive, a secondary aim of this article is to serve as a simplified tutorial for engaging in such validation practices in health professions education., Methods: A total of 10 health education-based experts in blended learning were recruited to participate in a 30-minute interviewer-administered survey. On a 5-point Likert scale, experts rated how well they perceived each item of the BLUE-Q to reflect its underlying usability domain (i.e., effectiveness, efficiency, satisfaction, accessibility, organization, and learner experience). Ratings were descriptively analyzed and converted into beta prior distributions. Participants were also given the option to provide qualitative comments for each item., Results: After reviewing the computed expert prior distributions, 31 quantitative items were identified as having a probability of “low endorsement” and were thus removed from the questionnaire. Additionally, qualitative comments were used to revise the phrasing and order of items to ensure clarity and logical flow. The BLUE-Q’s final version comprises 23 Likert-scale items and 6 open-ended items., Conclusion: Questionnaire validation can generally be a complex, time-consuming, and costly process, inhibiting many from engaging in proper validation practices. In this study, we demonstrate that a Bayesian questionnaire validation approach can be a simple, resource-efficient, yet rigorous solution to validating a tool for content and item-domain correlation through the elicitation of domain expert endorsement ratings.

A candidate AS01-adjuvanted vaccine containing four surface proteins from non-typable Haemophilus influenzae and Moraxella catarrhalis (NTHi-Mcat) has been developed to help prevent exacerbations of chronic obstructive pulmonary disease (COPD). Sequential administration of different vaccines containing the same AS01-adjuvant system could lead to immune interference. We compared administration of NTHi-Mcat following AS01-adjuvanted recombinant zoster vaccine (RZV) versus NTHi-Mcat alone. This phase 2a, open-label trial (NCT03894969) randomized healthy current or former smokers (50-80 years) without COPD to administration of NTHi-Mcat at 1, 3 or 6 months after RZV or to NTHi-Mcat alone (2-dose for both vaccines). Primary outcome was non-inferiority of the humoral immune response to NTHi-Mcat administered 1 month after RZV versus NTHi-Mcat alone, evaluated by specific antibody geometric mean concentration (GMC) ratio with 95% confidence intervals (CIs). The per-protocol set included 411 participants. Primary objective was met; lower limit of the 95%CI for the GMC ratio above 0.667 for all four vaccine antigens, 1 month after the second NTHi-Mcat dose. NTHi-Mcat induced similar immune response regardless of whether administered alone or 1, 3 or 6 months following RZV. Safety and reactogenicity profiles were acceptable; adverse event frequency was similar among study groups. Injection site pain was the most common symptom. No new safety concerns were identified. The study demonstrated non-inferiority of the immune response elicited by NTHi-Mcat administered sequentially to RZV versus NTHi-Mcat alone, indicating no immune interference. Starting from 1 month, no specific interval is required between RZV and NTHi-Mcat containing the same AS01-adjuvant system components in different quantities.

Introduction: Alzheimer's disease (AD) is characterized by the presence of both amyloid and tau pathology. In vivo diagnosis can be made with amyloid and tau positron emission tomography (PET) imaging. Emergent evidence supports that amyloid and tau accumulation are associated and that amyloid accumulation may precede that of tau. This report further investigates the relationship between amyloid and tau to assess whether elevated cortical tau can predict elevated amyloid in participants with early symptomatic AD., Methods: Florbetapir F18 and flortaucipir F18 uptake were evaluated from baseline PET scans collected in three multi-center studies with cognitively impaired participants, including A05 ( N = 306; NCT02016560), TB ( N = 310; TRAILBLAZER-ALZ; NCT03367403), and TB2 ( N = 1165; TRAILBLAZER-ALZ 2; NCT04437511). Images were assessed using visual and quantitative approaches to establish amyloid (A+) and tau (T+) positivity, as well as a combination method (tauVQ) to establish T+. Associations between global amyloid and tau were evaluated with positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-). Predictive values within subgroups according to ethnicity, race, cognitive score, age, and sex were also evaluated. The relationship between regional tau (four target and two reference regions were tested) and global amyloid was investigated in A05 participant scans using receiver-operating characteristic (ROC) curves., Results: PPV for amyloid positivity was ≥93% for all three trials using various A+ and T+ definitions, including visual, quantitative, and combination methods. Population characteristics did not have an impact on A+ predictability. Regional analyses (early tau (Eτ) volume of interest (VOI), temporal, parietal, frontal) revealed significant area under the ROC curve in Eτ VOI compared to frontal region, regardless of reference region and consistent among visual and quantitative A+ definitions ( p < 0.001)., Discussion: These findings suggest that a positive tau PET scan is associated (≥93%) with amyloid positivity in individuals with early symptomatic AD, with the potential benefits of reducing clinical trial and health care expenses, radiation exposure, and participant time., Highlights: Positron emission tomography (PET) evaluates candidates for Alzheimer's disease (AD) research. A positive tau PET scan is associated (≥93%) with amyloid positivity.A positive amyloid PET is not necessarily associated with tau positivity.Tau PET could be the sole diagnostic tool to confirm candidates for AD trials., Competing Interests: All authors are employees and shareholders of Eli Lilly and Company. No other disclosures were reported. Any author disclosures are available in the Supporting Information., (© 2023 Eli Lilly and Company. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

This study evaluated the potential pathogenicity and antimicrobial resistance (AMR) of Vibrio species isolated from inland saline shrimp culture farms. Out of 200 Vibrio isolates obtained from 166 shrimp/water samples, 105 isolates were identified as V. parahaemolyticus and 31 isolates were identified as V. alginolyticus and V. cholerae, respectively. During PCR screening of virulence-associated genes, the presence of the tlh gene was confirmed in 70 and 19 isolates of V. parahaemolyticus and V. alginolyticus, respectively. Besides, 10 isolates of V. parahaemolyticus were also found positive for trh gene. During antibiotic susceptibility testing (AST), very high resistance to cefotaxime (93.0%), amoxiclav (90.3%), ampicillin (88.2%), and ceftazidime (73.7%) was observed in all Vibrio species. Multiple antibiotic resistance (MAR) index values of Vibrio isolates ranged from 0.00 to 0.75, with 90.1% of isolates showing resistance to ≥ 3 antibiotics. The AST and MAR patterns did not significantly vary sample-wise or Vibrio species-wise. During the minimum inhibitory concentration (MIC) testing of various antibiotics against Vibrio isolates, the highest MIC values were recorded for amoxiclav followed by kanamycin. These results indicated that multi-drug resistant Vibrio species could act as the reservoirs of antibiotic resistance genes in the shrimp culture environment. The limited host range of 12 previously isolated V. parahaemolyticus phages against V. parahaemolyticus isolates from this study indicated that multiple strains of V. parahaemolyticus were prevalent in inland saline shrimp culture farms. The findings of the current study emphasize that routine monitoring of emerging aquaculture areas is critical for AMR pathogen risk assessment., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Although current antiretroviral therapy allows most people with HIV (PWH) to experience normal longevity with a good quality of life, an HIV cure remains elusive due to HIV reservoir formation within deep tissues. An HIV cure remains highly desirable to the community of PWH. This study reports on the perceived risks and benefits of participation in the Last Gift study, a study aimed at characterizing HIV reservoirs via post-mortem autopsy, among PWH at the end of life (EOL) and their next-of-kin (NOK)/loved ones., Methods: Last Gift participants (PWH with a terminal illness and/or near the end of life) and their NOK/loved ones were surveyed for perceptions of risks, benefits, and meaning for participation in the Last Gift study., Results: The average age of the 17 Last Gift participants was 66.6 years, 3 were females, 1 person identified as Hispanic, and 15 as Caucasian. The average age of the 17 NOK/loved ones was 56.7 years, and relationships to Last Gift participants included partner/spouse, sibling, friend, child, parent, grandparent, and nephew. The only perceived personal risk of the Last Gift among participants was the blood draws (3/17). NOK/loved ones perceived the following risks: blood draws (2/17), physical pain (3/17), worry that something bad will happen (2/17), and unpleasant side effects (1/17). Participants in Last Gift and NOK/loved ones indicated the study had various positive social effects. For both participants and NOK/loved ones, the most frequent perceived personal benefit of the Last Gift was the satisfaction of supporting HIV cure research., Discussion: Participants perceived minimal personal and societal risks and valued the altruistic benefits of participating in the Last Gift study. Last Gift participants and NOK/loved ones were cautious about possible personal risks of EOL HIV cure research but still viewed that the emotional, psychological and societal benefits of participation outweighed potential risks., 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.)

Background: To assess the long-term visual outcomes in patients with posteriorly located choroidal melanoma treated with ruthenium plaque brachytherapy between January 2013 and December 2015., Methods: A retrospective review was conducted on consecutive patients treated with ruthenium plaque brachytherapy for post-equatorial choroidal melanoma with available Snellen visual acuity before and after treatment, and the development and treatment of radiation complications., Results: There were 219 patients with posterior choroidal melanoma treated with ruthenium plaque brachytherapy. Median follow up was 56.5 months, range 12-81 months. Final visual acuity was ≥6/12 in 97 (44.3%) patients, 6/12 to 6/60 in 57 (26.0%), <6/60 in 55 (25.1%) and 10 (4.6%) eyes were enucleated. Radiation maculopathy was the most common radiation complication encountered, occurring in 53 (24.2%) patients. Of these, final visual acuity was 6/12 in 10 patients (18.9%), 6/12 to 6/60 in 26 (49.1%), <6/60 in 16 (30.2%) and 1 eye (1.9%) was enucleated. Twenty-five (47%) with radiation maculopathy were treated with intravitreal anti-angiogenic therapy, 27 (51%) were monitored and one (2%) was treated with scatter photocoagulation. Eyes treated with intravitreal anti-angiogenic therapy had better final vision than those observed or treated with retinal laser (chi-square, p = 0.04). On multivariate analysis, close proximity to the optic nerve and fovea, and large or notched plaque type was associated with final vision worse than 6/12., Conclusion: Most patients treated with ruthenium plaque brachytherapy for posterior choroidal melanoma retain 6/60 vision, with almost half retaining 6/12 vision at long term follow up., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

The present study aimed to evaluate the antimicrobial usage (AMU) pattern in dairy herds of Punjab, India. The on-farm quantification of AMU in adult bovine animals by the manual collection of empty drug containers ("bin method") along with the records of the treatment was carried out in 38 dairy farms involving 1010 adult bovines for 1 year from July 2020 to June 2021. The farm owners were asked to record the antibiotic treatments as well as to deposit empty antibiotic packaging/vials into the provided bins placed at the farms. A total of 14 different antibiotic agents in 265 commercial antibiotic products were administered to the dairy herds during the study. A total of 179 (67.55%) administered products contained antimicrobials of "critical importance" as per the World Health Organization (WHO). Mastitis (54.72%), followed by the treatment of fever (19.62%), reproductive problems (15.47%), and diarrhea (3.40%) accounted for the majority of drugs administered in the herds during the study period. The most commonly used antibiotics were enrofloxacin (89.47% herds; 21.51% products), followed by ceftriaxone (50% herds; 12.83% products), amoxicillin (50% herds; 12.83% products), oxytetracycline (55.26% herds; 11.70% products), and procaine penicillin (47.37% herds; 12.83% products). The highest quantity of AMU [in terms of antimicrobial drug use rate (ADUR)] was observed for ceftiofur, followed by ceftriaxone, procaine benzyl penicillin ceftizoxime, enrofloxacin, cefoperazone, amoxicillin and ampicillin. A total of 125 (47.17%) products contained "highest priority critically important antimicrobials" (HPCIA) and 54 (20.37%) products contained "high priority critically important antimicrobials". In terms of overall number of animal daily doses (nADD), the highest priority critically important antimicrobials (HPCIA) of the WHO such as third-generation cephalosporins and quinolones, respectively accounted for 44.64 and 22.35% of the total antibiotic use in the herds. The bin method offers an alternative to monitoring AMU as a more accessible approach for recording the actual consumption of antimicrobials. The present study, to the best of our knowledge, is the first of its kind to provide an overview of the qualitative and quantitative estimate of AMU among adult bovines from India., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vijay, Bedi, Dhaka, Singh, Singh, Arora and Gill.)

Introduction: We compared the performance of real-time PCR with culture-based methods for identifying bacteria in sputum samples from patients with chronic obstructive pulmonary disease (COPD) in three studies., Methods: This was an exploratory analysis of sputum samples collected during an observational study of 127 patients (AERIS; NCT01360398), phase 2 study of 145 patients (NTHI-004; NCT02075541), and phase 2b study of 606 patients (NTHI-MCAT-002; NCT03281876). Bacteria were identified by culture-based microbiological methods in local laboratories using fresh samples or by real-time PCR in a central laboratory using frozen samples. Haemophilus influenzae positivity with culture was differentiated from H. haemolyticus positivity by microarray analysis or PCR. The feasibility of bacterial detection by culture-based methods on previously frozen samples was also examined in the NTHI-004 study., Results: Bacterial detection results from both culture-based and PCR assays were available from 2,293 samples from AERIS, 974 from the NTHI-004 study, and 1736 from the NTHI-MCAT-002 study. Quantitative real-time PCR (qPCR) showed higher positivity rates than culture for H. influenzae (percentages for each study: 43.4% versus 26.2%, 47.1% versus 23.6%, 32.7% versus 10.4%) and Moraxella catarrhalis (12.9% versus 6.3%, 19.0% versus 6.0%, 15.5% versus 4.1%). In the NTHI-004 and NTHI-MCAT-002 studies, positivity rates were higher with qPCR for Streptococcus pneumoniae (15.6% versus 6.1%, 15.5% versus 3.8%); in AERIS, a lower rate with qPCR than with culture (11.0% versus 17.4%) was explained by misidentification of S. pseudopneumoniae/mitis isolates via conventional microbiological methods. Concordance analysis showed lowest overall agreement for H. influenzae (82.0%, 75.6%, 77.6%), due mainly to culture-negative/qPCR-positive samples, indicating lower sensitivity of the culture-based methods. The lowest positive agreement (culture-positive/qPCR-positive samples) was observed for S. pneumoniae (35.1%, 71.2%, 71.2%). Bacterial load values for each species showed a proportion of culture-negative samples with a load detected by qPCR; for some samples, the loads were in line with those observed in culture-positive samples. In the NTHI-004 study, of fresh samples that tested culture-positive, less than 50% remained culture-positive when tested from freeze/thawed samples. In the NTHI-004 study, of fresh samples that tested culture-positive, less than 50% remained culture-positive when tested from freeze/thawed samples., Discussion: Real-time PCR on frozen sputum samples has enhanced sensitivity and specificity over culture-based methods, supporting its use for the identification of common respiratory bacterial species in patients with COPD., Competing Interests: SS, J-LI, SB, ND, J-MD, LT, SR, AKA, TP, and LM are employed by GSK. SS, ND, J-MD, LT, TP, and LM hold shares in GSK. J-MD is also a designated inventor on patents owned by GSK., (Malvaux, Schoonbroodt, Ichanté, Boffé, Devos, Devaster, Taddei, Rondini, Arora and Pascal, © 2023 GSK.)

Background: Antimicrobial resistance (AMR) is a burning issue in the present era. Mastitis in dairy animals is one of the most important causes of huge production loss to dairy farmers. Aims: The study aims to find the prevalence, antimicrobial resistance profile, and resistance genes in the extended-spectrum beta-lactamase-producing Escherichia coli in mastitic milk., Methods: A total of 125 milk samples were collected from Beetal goats suffering from clinical mastitis from different districts of Punjab and processed for bacterial isolation and further identification. The drug resistance profile of ESBL-producing E. coli and its associations with molecular markers was analyzed using statistical analysis., Results: The prevalence of ESBL-producing E. coli in dairy goats of Punjab was recorded as 6.4%. The isolates showed the highest resistance to the beta-lactam group of antibiotics. The resistance percentages of streptomycin, gentamicin, tetracycline, chloramphenicol, clotrimazole, and colistin were 50%, 37.5%, 50%, 25%, 25%, and 50%, respectively. The isolates showed intermediate resistance to imipenem (12.5%) and tetracycline (25%). The ESBL-producing E. coli isolates harbored the resistance genes blaCTXM (100%), blaTEM (62.5%), blaSHV (25%), blaOXA (37.5%), tetA (37.5%), tetB (25%), aadA (37.5%), sul1 (25%), MOXM (12.5%), DHAM (25%), and blaCMY-2 (50%). Tetracycline and sulphonamide resistances were statistically associated with their respective resistance genes (P<0.05). Streptomycin resistance was not statistically associated with the presence of the aadA gene (P>0.05). The genes blaIMP and blaNDM were not recorded in any of the isolates. In this study, 12.5% of the isolates showed co-resistance to colistin and carbapenem., Conclusion: Antimicrobial resistance is a hot topic and requires immediate attention., Competing Interests: The authors declare that there is no conflict of interest.

Hemipteran pests are among the most important threats to agricultural production. Losses associated with these insects result from both feeding-associated damage and the transmission of plant pathogens by some species. Key among hemipteran pests of agricultural importance are stink bugs, whitefly, aphids and psyllids. While bacteria provide an excellent resource for identification of environmentally benign pesticidal proteins for use against pest insects, relatively few with activity against hemipteran species have been identified. In this comprehensive review including the patent literature, we describe physiological features unique to Hemiptera that may restrict the toxicity of bacterial pesticidal proteins, provide an overview of Hemiptera-active pesticidal proteins and associated structural classes, and summarize biotechnological strategies used for optimization of toxicity against target hemipteran species., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Calls for stakeholders across the global HIV landscape to widely and systematically adopt person-centered care and patient-oriented research approaches have been made by HIV scholars, clinicians, patients, and groups such as the Joint United Nations Programme on HIV/AIDS (UNAIDS). Such calls implicitly acknowledge that the end goal of HIV care, research, and advocacy goes beyond HIV viral suppression or undetectability toward ensuring optimal health-related quality of life (HrQoL) for people living with HIV (PLWH). Indeed, global efforts have focused on keeping people alive yet have failed to ensure that they feel alive., Approach: In this brief report, we highlight the progress that has been made toward evolving the HIV care cascade to better represent actual experiences of PLWH, especially those that are most vulnerable and marginalized. We then describe what person-centered care, patient-oriented research, and HrQoL are and why they are important for our current context in HIV. We conclude by sharing 2 propositions for the global HIV community to consider moving forward., Conclusions: HIV care must not only focus on viral suppression but also better recognize the intersecting and multifaceted challenges faced by PLWH when taking HIV treatment and engaging in care. Evaluating HrQoL at each step of the cascade using validated patient-reported outcome and experience measures would assist in systematically tracking and addressing challenges faced by PLWH. Measures chosen through global consensus may facilitate rigorous comparisons across jurisdictions. Adopting a patient-oriented research paradigm will also be crucial for empowering and meaningfully engaging patients throughout the research process., Competing Interests: No funding was received to support this work directly. The first author is supported by a Vanier Canada Graduate Scholarship awarded by the Canadian Institutes of Health Research. B.L. is the holder of a Canadian Institutes for Health Research, Strategy for Patient-Oriented Research Mentorship Chair in Innovative Clinical Trials for HIV Care, and is supported by a Senior Salary Award from Fonds de recherche du Québec–Santé (FRQS) (#311200) and by a career award, LE 250, from the Quebec's Ministry of Health for researchers in Family Medicine. B.L. has had research support from ViiV Healthcare, Merck, and Gilead and received consulting fees from ViiV, Merck, and Gilead. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Common variable immunodeficiency syndrome (CVID) is a diverse entity characterized by hypogammaglobinemia and a propensity for recurrent infections. Involvement of the gastrointestinal tract has a variable manifestation ranging from asymptomatic involvement to florid signs and symptoms. Due to these incongruous findings, multiple concurrent biopsies are to be done for tissue diagnosis. Here, we present two cases diagnosed with CVID on the basis of clinical findings, lab investigations, and morphological features on biopsy., Competing Interests: Conflict of Interest The authors declare no conflict of interest related to this work., (© 2022 Middle East Journal of Digestive Diseases.)

Despite their evolutionary, molecular biology and biotechnological significance, relatively fewer numbers of single-stranded DNA (ssDNA) filamentous phages belonging to the family Inoviridae have been discovered and characterized to date. The present study focused on genome sequencing and characterization of an ssDNA Vibrio parahaemolyticus phage V5 previously isolated from an inland saline shrimp culture farm. The complete circular genome of phage V5 consisted of 6658 bp with GC content of 43.7%. During BLASTn analysis, only 36% of phage V5 genome matched with other Vibrio phage genomes in the NCBI database with a sequence identity value of 79%. During the phylogenetic analysis, phage V5 formed a separate branch in the minor clade. These features indicate the novel nature of the phage V5 genome. Among 10 predicted open reading frames (ORFs) in the phage V5 genome, 6 encoded for the proteins of known biological functions, whereas the rest were classified as hypotheticals. Proteins involved in replication and structural assembly were encoded by the phage genome. However, the absence of genes encoding for DNA/RNA polymerases and tRNAs signified that phage V5 is dependent on the host`s molecular machinery for its propagation. As per our knowledge, this is the first study describing the novel genome sequence of an ssDNA V. parahaemolyticus phage from the inland saline environment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: An investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation., Methods: Patients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2-4), 40-80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses., Results: Of 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6-12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p &lt; 0.001)., Conclusion: Results suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial., Trial Registration: ClinicalTrials.gov, NCT03281876., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

Background: The burden of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region is projected to increase. Data from other regions show bacterial and viral infections can trigger acute exacerbations of COPD (AECOPD)., Methods: This 1-year prospective epidemiological study (ClinicalTrials.gov identifier: NCT03151395) of patients with moderate to very severe COPD in Hong Kong, the Philippines, South Korea and Taiwan assessed the prevalence in sputum samples (by culture and PCR) of bacterial and viral pathogens during stable COPD and AECOPD. The odds of experiencing an exacerbation was evaluated for pathogen presence, acquisition and apparition. Health-related quality of life (HRQOL) was assessed., Results: 197 patients provided 983 sputum samples, with 226 provided during exacerbation episodes. The mean yearly AECOPD incidence rate was 1.27 per patient. The most prevalent bacteria by PCR at exacerbation were Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mcat); Mcat prevalence was higher at exacerbation than at stable state. Virus prevalence was low, other than for human rhinovirus (HRV) (8.1%, stable state; 16.6%, exacerbation). The odds ratio (95% CI) for an exacerbation ( versus stable state) was statistically significant for the presence, acquisition and apparition of Hi (2.20, 1.26-3.89; 2.43, 1.11-5.35; 2.32, 1.20-4.46, respectively), Mcat (2.24, 1.30-3.88; 5.47, 2.16-13.86; 3.45, 1.71-6.98, respectively) and HRV (2.12, 1.15-3.91; 2.22, 1.09-4.54; 2.09, 1.11-3.91, respectively). HRQOL deteriorated according to the number of exacerbations experienced., Conclusion: In patients with COPD in the Asia-Pacific region, the presence of Hi, Mcat or HRV in sputum samples significantly increased the odds of an exacerbation, providing further evidence of potential roles in triggering AECOPD., Competing Interests: Conflict of interest: L. Taddei, L. Malvaux and A.K. Arora are employed by GSK. L. Taddei and L. Malvaux hold shares in GSK. L. Malvisi was employed by GSK at the time the study was conducted. L. Taddei, L. Malvaux, A.K. Arora and L. Malvisi declare no other financial and non-financial relationships and activities. D. Hui, R.Z. Samoro, S.H. Lee, Y.C. Yeung and Y-C. Liu declare no financial or non-financial relationships or activities and no conflicts of interest., (Copyright ©The authors or their employers 2022.)

This study aimed to explore the experiences of migrant people living with HIV (MLWH) enrolled in a Montreal-based multidisciplinary HIV care clinic with rapid antiretroviral treatment (ART) initiation and cost-covered ART. Between February 2020 and March 2022, 32 interviews were conducted with 16 MLWH at three time-points (16 after 1 week of ART initiation, 8 after 24 weeks, 8 after 48 weeks). Interviews were analyzed via the Framework Method. Thirty categories were identified, capturing experiences across the HIV care cascade. At diagnosis, most MLWH described "initially experiencing distress". At linkage, almost all MLWH discussed "navigating the health system with difficulty". At treatment initiation, almost all MLWH expressed "being satisfied with treatment", particularly due to a lack of side effects. Regarding care retention, all MLWH noted "facing psychosocial or health-related challenges beyond HIV". Regarding ART adherence, most MLWH expressed "being satisfied with treatment" with emphasis on their taking control of HIV. At viral suppression, MLWH mentioned "finding more peace of mind since becoming undetectable". Regarding their perceived health-related quality of life, most MLWH indicated "being helped by a supportive social network". Efficient, humanizing, and holistic approaches to care in a multidisciplinary setting, coupled with rapid and free ART initiation, seemed to help alleviate patients' concerns, address their bio-psycho-social challenges, encourage their initial and sustained engagement with HIV care and treatment, and ultimately contribute to positive experiences.

The rising prevalence of antimicrobial resistance in animal foods and injudicious antibiotic use in the dairy sector pose significant threats to public health. Focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with a strategic sample of four stakeholder groups (114 participants) associated with antibiotic usage in the dairy sector of Punjab. The FGDs were conducted among veterinarians ( n = 56), para-veterinarians ( n = 28), and KIIs were conducted among chemists ( n = 18) and dairy quality managers ( n = 12) during 2020-2021. FGDs and qualitative interviews of various stakeholders depict existing risk practices in the fields that may promote antimicrobial resistance. The present study revealed that widely prevalent quackery (treatment practices carried out by unauthorized persons without any recognized diploma/degree) and self-treatment by farmers, over-the-counter availability of antibiotics, low veterinarian per animal ratio, and lack of awareness among the society about the potential public health effects of antimicrobial resistance were the main risk factors for injudicious antibiotic use in the dairy sector. The present study involved a comprehensive approach targeting the stakeholders in the dairy sector and their reflections on judicious antimicrobial usage and antimicrobial resistance adapted to the dairy farming of Punjab. There is an urgent need for the advocation of policies that consider the specific challenges faced by the dairy sector to simultaneously improve access to veterinary services as well as strengthen antibiotic stewardship.