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Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has been responsible for an epidemic outbreak of unprecedented magnitude in recent years. Since then, significant efforts have been made to better understand the biology of this virus, but we still have poor knowledge of CHIKV interactions with host cell components at the molecular level. Here we describe the extensive use of high-throughput yeast two-hybrid (HT-Y2H) assays to characterize interactions between CHIKV and human proteins. A total of 22 high-confidence interactions, which essentially involved the viral nonstructural protein nsP2, were identified and further validated in protein complementation assay (PCA). These results were integrated to a larger network obtained by extensive mining of the literature for reports on alphavirus-host interactions. To investigate the role of cellular proteins interacting with nsP2, gene silencing experiments were performed in cells infected by a recombinant CHIKV expressing Renilla luciferase as a reporter. Collected data showed that heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and ubiquilin 4 (UBQLN4) participate in CHIKV replication in vitro. In addition, we showed that CHIKV nsP2 induces a cellular shutoff, as previously reported for other Old World alphaviruses, and determined that among binding partners identified by yeast two-hybrid methods, the tetratricopeptide repeat protein 7B (TTC7B) plays a significant role in this activity. Altogether, this report provides the first interaction map between CHIKV and human proteins and describes new host cell proteins involved in the replication cycle of this virus. [ABSTRACT FROM AUTHOR]

Objectives: We studied the socio-spatial inequalities of three types of general practitioner (GP) density in the Paris metropolitan area: the density of GPs present (that is, practising) in the census block and of those registering new patients for office visits and, separately, for house calls., Study Design: An exhaustive simulated patient survey enabled us to determine the number of GPs practising in the Paris metropolitan region accepting new patient registration for continuing care at their office and/or for house calls., Methods: We measured at the level of a census block three types of GP densities: density of GPs present, density of GPs registering new patients at their office and density of GP registering new patients for house calls. We compared the association between the social deprivation level and each density measurement overall, then by stratifying for the population density of the census block., Results: In 2017-2018, we contacted 8171 physicians (87.6 % of the GPs in the region). Although more than 55 % of Ile-de-France census blocks had (at least) one practising GP, fewer than 40 % had one willing to register a new patient for ongoing office care, and fewer than 20 % for home care. Regardless of the GP density considered, it decreased as the census block's deprivation index rose. However, these inequalities were more marked for registration than for presence and in the most densely populated blocks., Conclusions: In conclusion, the indicators of GPs' mere presence appear to minimise the socio-spatial disparities associated with access to registration., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Direct oral anticoagulants for the treatment of venous thromboembolism are supported by robust clinical trial evidence. Despite published guidance, general practitioners are faced with increasingly complex decisions and implementation remains sub-optimal in certain real-world scenarios., Methods: A two stage formal consensus exercise was performed to formulate consensus statements and a summary guide, facilitating optimal management of direct oral anticoagulants in venous thromboembolism patients by generalist physicians across Europe. An online questionnaire distributed to a broad panel (Phase 1), followed by a virtual panel discussion by an expert group (Phase 2) were conducted. Phase 1 statements covered nine management domains, and were developed via a literature review and expert steering committee. Participants rated statements by their level of agreement. Phase 1 responses were collated and analysed prior to discussion and iterative refinement in Phase 2., Results: In total 56 participants from across Europe responded to Phase 1. The majority had experience working as general practitioners. Consensus indicated that direct oral anticoagulants are the treatment of choice for managing patients with venous thromboembolism, at initiation and for extended treatment, with a review at three to six months to re-assess treatment effect and risk profile. Direct oral anticoagulant choice should be based on individual patient factors and include shared treatment choice between clinicians and patients; the only sub-group of patients requiring specific guidance are those with cancer., Conclusion: Results demonstrate an appreciation of best practices, but highlight challenges in clinical practice. The patient pathway and consensus recommendations provided, aim to highlight key considerations for general practice decision making, and aid optimal venous thromboembolism treatment., (© 2024. The Author(s).)

The objective of our study was to investigate differences in the management of men and women treated for hypertension while considering the gender of their physicians. We used the data from the cross-sectional Paris Prevention in General Practice survey, where 59 randomly recruited general practitioners (42 men and 19 women) from the Paris metropolitan area enroled every patient aged 25-79 years taking antihypertensive medication and seen during a 2-week period (520 men and 666 women) in 2005-6. The presence in the medical files of six items recommended for hypertension management (blood pressure measurement, smoking status, cholesterol, creatinine, fasting blood glucose and electrocardiogram) was analysed with mixed models with random intercepts and adjusted for patient and physician characteristics. We found that the presence of all items was lower in the records of female than male patients (3.9 vs. 6.9%, p = 0.01), as was the percentage of items present (58.5 vs. 64.2%, p = 0.003). The latter gender difference was substantially more marked when the physician was a man (69.3 vs. 63.4%, p = 0.0002) rather than a woman (63.5 vs. 61.0%, p = 0.46). Although all guidelines recommend the same management for both genders, the practices of male physicians in hypertension management appear to differ according to patient gender although those of women doctors do not. Male physicians must be made aware of how their gender influences their practices., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

This article explores information relating to female adolescents knowledge, attitudes, and behaviors toward human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) in Carriacou. The authors aimed at finding out whether adolescent females in Carriacou receive adequate information about HIV and other STDs. Where did students receive most of their information about HIV/STDs and whether the knowledge has influenced their sexual behaviors? Furthermore, this study focused on how female adolescents feel toward people living with HIV/STDs.Focus group method was employed with 2 age groups of female adolescent students. Content analysis was carried out by the researcher to analyze the data. Themes were developed using coding and thematic analysis.The findings revealed that female adolescents were highly aware of HIV/STDs-related facts. They were knowledgeable and have received adequate information about HIV/STDs., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Introduction: Systemic lupus erythematosus (SLE) is a T and B cell-dependent autoimmune disease characterized by the appearance of autoantibodies, a global regulatory T cells (Tregs) depletion and an increase in Th17 cells. Recent studies have shown the multifaceted immunomodulatory effects of vitamin D, notably the expansion of Tregs and the decrease of Th1 and Th17 cells. A significant correlation between higher disease activity and lower serum 25-hydroxyvitamin D levels [25(OH)D] was also shown., Methods: In this prospective study, we evaluated the safety and the immunological effects of vitamin D supplementation (100,000 IU of cholecalciferol per week for 4 weeks, followed by 100,000 IU of cholecalciferol per month for 6 months.) in 20 SLE patients with hypovitaminosis D., Results: Serum 25(OH)D levels dramatically increased under vitamin D supplementation from 18.7±6.7 at day 0 to 51.4±14.1 (p<0.001) at 2 months and 41.5±10.1 ng/mL (p<0.001) at 6 months. Vitamin D was well tolerated and induced a preferential increase of naïve CD4+ T cells, an increase of regulatory T cells and a decrease of effector Th1 and Th17 cells. Vitamin D also induced a decrease of memory B cells and anti-DNA antibodies. No modification of the prednisone dosage or initiation of new immunosuppressant agents was needed in all patients. We did not observe SLE flare during the 6 months follow-up period., Conclusions: This preliminary study suggests the beneficial role of vitamin D in SLE patients and needs to be confirmed in randomized controlled trials.