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.

Sleep and circadian rhythms in delayed sleep-wake phase disorder: Phenotypic differences between patients with and without comorbid depression.

Delayed sleep-wake phase disorder involves chronic difficulty going to bed and waking up at conventional times and often co-occurs with depression. This study compared sleep and circadian rhythms between patients with delayed sleep-wake phase disorder with depression (DSWPD-D) and without (DSWPD-ND) comorbid depression. Clinical records of 162 patients with delayed sleep-wake phase disorder (70 DSWPD-D, 92 DSWPD-ND) were analysed, including a subset of 76 patients with circadian phase determined by the dim light melatonin onset.

Feasibility of home-based urine collection in children under 5 years in the ORIGINS birth cohort study: mixed method protocol and sample completion results.

Background: Urine is an attractive biospecimen for nutritional status and population health surveys. It is an excellent non-invasive alternative to blood for appropriate biomarkers in young children and is suitable for home-based collection, enabling representative collections across a population. However, the bulk of literature in this population is restricted to collection in primary care settings.

Refinement of a meaning-centered counseling program for Chinese patients with advanced cancer: integrating cultural adaptation and implementation science approaches.

Background: This mixed methods study identified needed refinements to a telehealth-delivered cultural and linguistic adaptation of Meaning-Centered Psychotherapy for Chinese patients with advanced cancer (MCP-Ch) to enhance acceptability, comprehensibility, and implementation of the intervention in usual care settings, guided by the Ecological Validity Model (EVM) and the Practical, Robust Implementation and Sustainability Model (PRISM).

Methods: Fifteen purposively sampled mental health professionals who work with Chinese cancer patients completed surveys providing Likert-scale ratings on acceptability and comprehensibility of MCP-Ch content (guided by the EVM) and pre-implementation factors (guided by PRISM), followed by semi-structured interviews. Survey data were descriptively summarized and linked to qualitative interview data.

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.

Shear-Mediated Stabilization of Spin Spiral Order in Multiferroic NiI.

Type-II multiferroicity from non-collinear spin order is recently explored in the van der Waals material NiI. Despite the importance for improper ferroelectricity, the microscopic mechanism of the helimagnetic order remains poorly understood. Here, the magneto-structural phases of NiI are investigated using resonant magnetic X-ray scattering (RXS) and X-ray diffraction.

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.

Nurse workforce change and metropolitan medically underserved areas in the United States.

Background: The continued healthcare crisis in the United States (US) is worrisome, especially as workforce shortages, particularly for nurses, are highlighted, often in some of the highest need areas. As the need for healthcare services grows, especially for services that nurses can deliver, the inability to meet those needs exacerbates existing disparities in access to care and can jeopardize the quality and timeliness of healthcare delivery in underserved communities. Prior investigations have used varying definitions to describe underserved, under-resourced, rural, or health professional shortage areas to examine the relationship between these areas and workforce shortages.

SIRT2 and ALDH1A1 as critical enzymes for astrocytic GABA production in Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and HO are associated with memory impairment in AD and synthesized through the Monoamine Oxidase B (MAOB)-mediated multi-step degradation of putrescine. However, the enzymes downstream to MAOB in this pathway remain unidentified.

Causal analysis for multivariate integrated clinical and environmental exposures data.

Electronic health records (EHRs) provide a rich source of observational patient data that can be explored to infer underlying causal relationships. These causal relationships can be applied to augment medical decision-making or suggest hypotheses for healthcare research. In this study, we explored a large-scale EHR dataset on patients with asthma or related conditions (N = 14,937).

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.