Functional evaluation and clinical classification of BRCA2 variants.

Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.

Voltage Gated Calcium Channel Dysregulation May Contribute to Neurological Symptoms in Calmodulinopathies.

Calmodulinopathies are caused by mutations in calmodulin (CaM), and result in debilitating cardiac arrythmias such as long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). In addition, many patients exhibit neurological comorbidities, including developmental delay and autism spectrum disorder. Until now, most work into these mutations has focused on cardiac effects, identifying impairment of Ca /CaM-dependent inactivation (CDI) of Ca 1.

Stent-in-Stent Intervention for Pulmonary Vein in Stent Restenosis: A Long-Term Follow-Up Case Report.

Introduction: Pulmonary vein (PV) restenosis develops with reported incidence rates of up to 50%. Balloon angioplasty seems to be the widely preferred treatment of choice.

Method And Results: A 54-year-old man with long history of atrial fibrillations developed PVS secondary to multiple radiofrequency ablation procedures.

Effect of Dapagliflozin on Measured vs. Panel-Estimated Glomerular Filtration Rate.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors can cause a reversible decline in glomerular filtration rate (GFR), which may influence dosing recommendations for renally excreted medications. In practice, GFR is typically estimated by serum creatinine concentration, but creatinine may not be a reliable indicator of GFR decline in the setting of SGLT2 inhibitor use. Alternative filtration markers such as cystatin C, β-trace protein (BTP), and β2-microglobulin (B2M) may be more appropriate, but little is known about how these markers are affected by SGLT2 inhibitor use.

Improve time to anti-coagulation reversal for hemorrhagic strokes.

Background: Oral anticoagulation (OAC) is a risk factor for intracerebral hemorrhage (ICH) which is an important source of disability and mortality. OAC-associated ICH (OAC-ICH) patients have worse outcomes as compared to ICH patients not on OAC, likely because of the associated larger stroke volumes, higher propensity to intraventricular hemorrhage, and a higher risk of rebleeding. Although current guidelines recommend that OAC should be reversed quickly, many health care systems have not developed a process for optimizing that aspect of care.

Oligonucleotide-based CRISPR-Cas9 toolbox for efficient engineering of Komagataella phaffii.

Komagataella phaffii (Pichia pastoris) is a methylotrophic yeast that is favored by industry and academia mainly for expression of heterologous proteins. However, its full potential as a host for bioproduction of valuable compounds cannot be fully exploited as genetic tools are lagging behind those that are available for baker's yeast. The emergence of CRISPR-Cas9 technology has significantly improved the efficiency of gene manipulations of K.

A characterization of patients with low soluble urokinase plasminogen activator receptor who died within 90 days of hospital discharge.

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry-based study.

Deep Learning Resolves Myovascular Dynamics in the Failing Human Heart.

The adult mammalian heart harbors minute levels of cycling cardiomyocytes (CMs). Large numbers of images are needed to accurately quantify cycling events using microscopy-based methods. CardioCount is a new deep learning-based pipeline to rigorously score nuclei in microscopic images.

Growth differentiation factor 15 (GDF15) levels are associated with malnutrition in acutely admitted older adults.

Background And Aims: The aging process is often accompanied by high risk of malnutrition and elevated levels of growth differentiation factor 15 (GDF15). GDF15 is an increasingly recognized biomarker for regulation of metabolism, but few studies have investigated the connection between GDF15 and malnutrition in older age and how it relates to other features of aging such as decreased appetite and physical function. Therefore, we investigated the associations between GDF15 levels and nutritional status, appetite, and physical function in acutely admitted older adults.

Comprehensive periodic health evaluations of 454 Norwegian Paralympic and Olympic athletes over 8 years: what did we learn?

Objective: A periodic health evaluation (PHE) is a comprehensive and multidisciplinary investigation of athlete health widely used in elite sport, but its contents and benefits can be questioned. This study aimed to determine the prevalence of conditions identified by a PHE among Paralympic and Olympic athletes over four consecutive Games cycles from Rio de Janeiro 2016 to Beijing 2022 and to assess the benefits and potential pitfalls of a comprehensive PHE programme in detecting existing injuries, illnesses and other health issues.

Methods: We collected extensive health history and clinical examination data on elite athletes: medical history, ECG, blood pressure, blood samples, spirometry, musculoskeletal health, cognitive function, mental health and compliance with public health programmes.

Exploring the impact of stressful life events on quality of life: meaning making and narrative reconstruction.

Purpose: Stressful life events have the capacity to disrupt an individual's worldview and life goals, leading to existential questions and identity loss. The subjective perception of identity is intricately linked with quality of life (QoL), and how individuals derive meaning from these stressful life events significantly influences their well-being. This article explored the impact of stressful life events on individuals' QoL, and examined the potential for enhancing QoL through meaning making and narrative reconstruction.

A diverse portfolio of marine protected areas can better advance global conservation and equity.

Marine protected areas (MPAs) are widely used for ocean conservation, yet the relative impacts of various types of MPAs are poorly understood. We estimated impacts on fish biomass from no-take and multiple-use (fished) MPAs, employing a rigorous matched counterfactual design with a global dataset of >14,000 surveys in and around 216 MPAs. Both no-take and multiple-use MPAs generated positive conservation outcomes relative to no protection (58.

Gas-to-Particle Partitioning of Products from Ozonolysis of Δ-Carene and the Effect of Temperature and Relative Humidity.

Formation of oxidized products from Δ-carene (CH) ozonolysis and their gas-to-particle partitioning at three temperatures (0, 10, and 20 °C) under dry conditions (<2% RH) and also at 10 °C under humid (78% RH) conditions were studied using a time-of-flight chemical ionization mass spectrometer (ToF-CIMS) combined with a filter inlet for gases and aerosols (FIGAERO). The Δ-carene ozonolysis products detected by the FIGAERO-ToF-CIMS were dominated by semivolatile organic compounds (SVOCs). The main effect of increasing temperature or RH on the product distribution was an increase in fragmentation of monomer compounds (from C to C compounds), potentially via alkoxy scission losing a C group.

Regionalization of stroke systems of care in the stroke belt states: The IMPROVE stroke care quality improvement program.

Background: Despite guidelines and strong evidence supporting intravenous thrombolysis and endovascular thrombectomy for acute stroke, access to these interventions remains a challenge. The objective of the IMPROVE stroke care program was to accelerate acute stroke care delivery by implementing best practices and improving the regional systems of care within comprehensive stroke networks.

Methods: The IMPROVE Stroke Care program was a prospective quality improvement program based on established models used in acute coronary care.

The MeSH heading "Call Center" is due for an update: why we recommend the more precise heading "Emergency Medical Communication Center".

Call centers can be found in various industries. However as a Medical Subject Heading (MeSH) the term "Call centers" does not reflect the critical purpose of handling emergency calls. We recommend "emergency medical communication center(s)", as this provides clarity and precision regarding the primary function and purpose of the center.