Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations.

Neurotransmitter release is triggered in microseconds by the two C domains of the Ca sensor synaptotagmin-1 and by SNARE complexes, which form four-helix bundles that bridge the vesicle and plasma membranes. The synaptotagmin-1 CB domain binds to the SNARE complex via a 'primary interface', but the mechanism that couples Ca-sensing to membrane fusion is unknown. Widespread models postulate that the synaptotagmin-1 Ca-binding loops accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but these models do not seem compatible with SNARE binding through the primary interface, which orients the Ca-binding loops away from the fusion site.

Adapting self-measured blood pressure monitoring to reduce health disparities (ASPIRE): a pilot hybrid effectiveness‑implementation study protocol.

Background: Hypertension is the leading risk factor for cardiovascular disease (CVD). Despite advances in blood pressure management, significant racial and ethnic disparities persist, resulting in higher risks of stroke, heart disease, and mortality among non-White populations. Self-measured blood pressure (SMBP) monitoring, also known as home blood pressure monitoring, has shown promise in improving blood pressure control, especially when combined with feedback from healthcare providers.

Differential effect of nonpharmacological interventions according to prediabetes phenotype: Systematic review and meta-analysis of randomized clinical trials.

Background And Aims: Impaired glucose intolerance (IGT) and impaired fasting glucose (IFG) are totally different. Lifestyle modification is effective in moving from prediabetes to normoglycaemia. There is a lack of information showing the effect of lifestyle modification according to each prediabetes and assessing its effect on the degree of reversibility to normoglycaemia and on cardiometabolic markers.

Redo mitral valve replacement with annular reconstruction of left atrial dissection following mitral valve replacement for infective endocarditis: a case report.

Background: Left atrial dissection is a rare and occasionally fatal complication of cardiac surgery and is defined as the creation of a false chamber through a tear in the mitral valve annulus extending into the left atrial wall. Some patients are asymptomatic, while others present with various symptoms, such as chest pain, dyspnea, and even cardiac arrest. Although there is no established management for left atrial dissection, surgery should be considered in patients with hemodynamic disruption.

High-Field-Blinded Assessment of Portable Ultra-Low-Field Brain MRI for Multiple Sclerosis.

Background And Purpose: MRI is crucial for multiple sclerosis (MS), but the relative value of portable ultra-low field MRI (pULF-MRI), a technology that holds promise for extending access to MRI, is unknown. We assessed white matter lesion (WML) detection on pULF-MRI compared to high-field MRI (HF-MRI), focusing on blinded assessments, assessor self-training, and multiplanar acquisitions.

Methods: Fifty-five adults with MS underwent pULF-MRI following their HF-MRI.

Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated.

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences.

Cardiovascular safety of 5-fluorouracil and capecitabine in colorectal cancer patients: real-world evidence.

Background: Fluoropyrimidines, including 5-fluorouracil and capecitabine, are the most common chemotherapeutic agents for colorectal carcinoma. Although previous studies have suggested varying degrees of cardiotoxicity with these drugs, there is a notable lack of large-scale investigations with appropriate control groups. This study aimed to evaluate cardiovascular outcome among colorectal carcinoma patients treated with fluoropyrimidines.

Genome-wide association studies are enriched for interacting genes.

Background: With recent advances in single cell technology, high-throughput methods provide unique insight into disease mechanisms and more importantly, cell type origin. Here, we used multi-omics data to understand how genetic variants from genome-wide association studies influence development of disease. We show in principle how to use genetic algorithms with normal, matching pairs of single-nucleus RNA- and ATAC-seq, genome annotations, and protein-protein interaction data to describe the genes and cell types collectively and their contribution to increased risk.

Two-stage revision anterior cruciate ligament reconstruction reduces failure risk but leads to lesser clinical outcomes than single-stage revision after primary anterior cruciate ligament graft failure: a retrospective cohort study.

Background: There are no studies that compare the outcomes and complications of single-versus two-stage revision anterior cruciate ligament reconstruction (ACLR) after primary ACLR failure. This purpose of this study is to examine clinical and functional outcomes and complications associated with single and two-stage revision ACLR after primary ACLR failure.

Methods: All patients who underwent single or two-stage revision ACLR after primary ACLR failure between 2012 and 2021 with a minimum of a 2 year follow-up were included.

Optimal allocation of antenatal and young child nutrition interventions: an individual-based global burden of disease calibrated microsimulation.

Background: Undernutrition remains a global crisis and is a focus of Sustainable Development Goals. While there are multiple known, effective interventions, complex interactions between prevention and treatment and resource constraints can lead to difficulties in allocating funding. Simulation studies that use in silico simulation can help illuminate the interactions between interventions and provide insight into the cost-effectiveness of alternative packages of options.

Derivation and validation of a clinical predictive model for longer duration diarrhea among pediatric patients in Kenya using machine learning algorithms.

Background: Despite the adverse health outcomes associated with longer duration diarrhea (LDD), there are currently no clinical decision tools for timely identification and better management of children with increased risk. This study utilizes machine learning (ML) to derive and validate a predictive model for LDD among children presenting with diarrhea to health facilities.

Methods: LDD was defined as a diarrhea episode lasting ≥ 7 days.

Bullying in adolescents across three years in the context of the COVID-19 pandemic: a repeated cross-sectional and prospective analysis.

Background: Bullying has been identified as a risk factor for many issues among adolescents. Although it was already considered a public health issue in Brazil before the COVID-19 pandemic, little is known about how the pandemic and associated public health measures have affected bullying behavior.

Objective: To explore changes in bullying victimization and perpetration among Brazilian high school students from 2019 to 2022.

Larviciding for malaria control and elimination in Africa.

Background: Global progress toward malaria elimination and eradication goals has stagnated in recent years, with many African countries reporting increases in malaria morbidity and mortality. Insecticide-treated nets and indoor residual spraying are effective, but the emergence and increased intensity of insecticide resistance and the challenge of outdoor transmission are undermining their impact. New tools are needed to get back on track towards global targets.

Attitudes and knowledge for CBT-based psychotherapy among medical students and residents in China: a survey study.

Background/aim: Psychotherapy training for medical students and residents in China is still in development. To establish an appropriate training program, understanding medical students' and residents' current knowledge and attitudes toward psychotherapy is needed.

Methods: One hundred and forty-nine participants, including medical students, residents, and other health providers (HCPs), self-reported their understanding of 18 types of psychotherapy, negative attitude towards cognitive behavioral therapy (CBT), and their attitude towards psychological interventions and counseling in primary care (APIC-PC) through an online survey.

Latent class analysis of the capacity of countries to manage diabetes and its relationship with diabetes-related deaths and healthcare costs.

Background: The prevalence of diabetes is escalating globally, underscoring the need for comprehensive evidence to inform health systems in effectively addressing this epidemic. The purpose of this study was to examine the patterns of countries' capacity to manage diabetes using latent class analysis (LCA) and to determine whether the patterns are associated with diabetes-related deaths and healthcare costs.

Methods: Eight indicators of country-level capacity were drawn from the World Health Organization Global Health Observatory dataset: the widespread availability of hemoglobin A1C (HbA1c) testing, existence of diabetes registry, national diabetes management guidelines, national strategy for diabetes care, blood glucose testing, diabetic retinopathy screening, sulfonylureas, and metformin in the public health sector.

Immune responses of cattle vaccinated by various routes with Mycobacterium bovis Bacillus Calmette-Guérin (BCG).

Background: Mycobacterium bovis BCG is the human tuberculosis vaccine and is the oldest vaccine still in use today with over 4 billion people vaccinated since 1921. The BCG vaccine has also been investigated experimentally in cattle and wildlife by various routes including oral and parenteral. Thus far, oral vaccination studies of cattle have involved liquid BCG or liquid BCG incorporated into a lipid matrix.

Chronic and infectious respiratory mortality and short-term exposures to four types of pollen taxa in older adults in Michigan, 2006-2017.

Introduction: Levels of plant-based aeroallergens are rising as growing seasons lengthen and intensify with anthropogenic climate change. Increased exposure to pollens could increase risk for mortality from respiratory causes, particularly among older adults. We determined short-term, lag associations of four species classes of pollen (ragweed, deciduous trees, grass pollen and evergreen trees) with respiratory mortality (all cause, chronic and infectious related) in Michigan, USA.

Spatial analysis and associated risk factors of HIV prevalence in Botswana: insights from the 2021 Botswana AIDS Impact Survey (BAIS V).

Background: The global burden of HIV and AIDS continues to significantly impact public health, particularly in Sub-Saharan Africa. This study investigates the spatial distribution and associated risk factors of HIV prevalence in Botswana using data from the 2021 Botswana AIDS Impact Survey (BAIS V).

Methods: The analysis included 12,653 adults aged 15-64 years and employed chi-square tests, multilevel mixed-effects regression, and spatial analysis techniques.

Prognostic value of albumin-bilirubin grade in patients with cholangiocarcinoma: a systematic review and meta-analysis.

Background: Cholangiocarcinoma (CCA) is a type of cancer that develops in the biliary tract. CCA accounts for 10% of primary hepatic cancers and is characterized by its aggressive nature and poor prognosis. This systematic review and meta-analysis aims to assess the prognostic value of the novel hepatic function assessment measure known as albumin-bilirubin (ALBI) grade in patients with CCA.

A conceptual model for advanced/metastatic gastric or gastroesophageal junction cancer: a review of qualitative studies and results from patient interviews.

Background: Despite approvals of new first-line immunotherapies for advanced/metastatic gastric cancer/gastroesophageal junction cancer (aGC/GEJC), patients' median survival is around 14 months and their health-related quality of life (HRQoL) is affected by disease-related symptoms and treatment-related side effects. Using a targeted literature review (TLR) and patient interviews, this study identified disease- and treatment-related concepts that are important to patients with aGC/GEJC and their HRQoL.

Methods: A TLR was conducted to identify primary qualitative studies from 2018 to 2021 on patients' experiences with aGC/GEJC.

Interpreting positive celiac serology in children with new-onset type 1 diabetes.

Objectives: The association of celiac disease (CD) in type 1 diabetes mellitus (T1DM) is well-established, yet variation exists in screening practices. This study measures the accuracy of early screening with tissue transglutaminase Immunoglobulin A (TTG-IgA) and endomysial antibody (EMA) in newly diagnosed T1DM.

Methods: This is a retrospective study of children with T1DM between 2013 and 2019 with early CD screening and follow-up.

A reflection on how the absence of a psychodynamic perspective may disadvantage gender care and decision-making.

Objective: To reflect on factors that may have led to the widespread implementation of gender affirming care (GAC) for minors by psychiatric clinical leaders despite the absence of a robust evidence base and the known risks of harm.

Conclusions: The progressive rejection of psychodynamic thinking by the profession of psychiatry may have contributed to psychiatrists failing to question key aspects of GAC for minors. Further, numerous unconscious factors potentially contribute to the foreclosure of thinking about the risks of gender medicine.

Methotrexate fixed dosing protocol for ambulatory treatment of ectopic pregnancy.

The primary objective of this study was to review a methotrexate 90-mg fixed-dose protocol for treatment of ectopic pregnancy, and to evaluate if any characteristics were associated with ectopic pregnancy treatment failure. This was a single arm retrospective cohort study conducted at Kaiser Permanente Colorado. The primary outcome was to describe rates of ectopic pregnancy treatment failure among patients who received fixed dose(s) of methotrexate for ectopic pregnancy between January 1, 2007 and August 31, 2017.

Interobserver and intraobserver variability among different vendors for mitral valve assessment: implications for transcatheter mitral valve repair.

Purpose: Pre-procedural imaging is critical for transcatheter mitral valve repair planning in patients with mitral valve disease. As differences among various measurement techniques for valve evaluation are still poorly understood, we sought to assess the intra- and interobserver agreement of complex measurements derived from a prototype mitral evaluation tool (Siemens) and a commercially available tool (CVI42) using both saddle- and D-shaped mitral annulus techniques.

Materials And Methods: Multiphasic cardiac computed tomography angiography data were loaded into each software.

"The Forgotten Minority": Perpetuation of Ableism in Medical Education.

Background: Accounting for approximately 1 in 4 community-dwelling adults in the United States (US), people with disabilities (PWD) experience significant disparities in health care quality, access, and outcomes. At the same time, US physicians have reported feeling unprepared to care for PWD and have revealed significant negative bias about this population.

Objective: To understand how physicians are trained to care for PWD in US medical schools.