Early midlife ovarian removal is associated with lower posterior hippocampal function.

Introduction: Women with early bilateral salpingo-oophorectomy (BSO) have greater Alzheimer's disease (AD) risk than women with spontaneous menopause (SM), but the pathway toward this risk is understudied. Considering associative memory deficits may reflect early signs of AD, we studied how BSO affected brain activity underlying associative memory.

Methods: Early midlife women with BSO (with and without 17β-estradiol therapy [ET]) and age-matched controls (AMCs) with intact ovaries completed a face-name associative memory task during functional magnetic resonance imaging.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Family Physicians' Feedback on the Feature Design of a Digital Health Platform to Streamline the Care of Older Adults.

: Family physicians are essential to a well-functioning healthcare system; however, they face significant administrative and cognitive burdens that contribute to their burnout and reduce the quality of patient care they provide. Digital health tools offer potential solutions to these problems. This study examined the interface design and features of a digital health platform, Carmi, designed to mitigate administrative inefficiencies and cognitive overload by asynchronous patient data gathering and automated report generation.

How Does Deep Neural Network-Based Noise Reduction in Hearing Aids Impact Cochlear Implant Candidacy?

Background/objectives: Adult hearing-impaired patients qualifying for cochlear implants typically exhibit less than 60% sentence recognition under the best hearing aid conditions, either in quiet or noisy environments, with speech and noise presented through a single speaker. This study examines the influence of deep neural network-based (DNN-based) noise reduction on cochlear implant evaluation.

Methods: Speech perception was assessed using AzBio sentences in both quiet and noisy conditions (multi-talker babble) at 5 and 10 dB signal-to-noise ratios (SNRs) through one loudspeaker.

Psychometric validation of the Diagnostic Assessment Research Tool: Alcohol use disorder module.

Aims: Structured clinical interviewing is considered the gold standard in psychiatric diagnosis. The Diagnostic Assessment Research Tool (DART) is a novel modularized, non-copywritten, semi-structured interview; however, no studies have examined the psychometric properties of its alcohol use disorder (AUD) module. The primary aims of this study were to: (i) validate the factor structure of the DART AUD module and (ii) examine measurement invariance across several key demographic and subgroup factors.

Dutch Nationwide Cohort Experience with a New PROMs Set in Metabolic and Bariatric Surgery: BODY-Q Obesity Module.

Purpose: Patient-reported outcomes are important as obesity is a chronic disease with a substantial impact. A multidisciplinary task force selected six scales (48 questions) from the validated BODY-Q questionnaire. This subset was gradually introduced and evaluated in a mandatory nationwide registry.

Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.

Outcomes of Total Ankle Replacement Versus Ankle Arthrodesis for the Treatment of End-Stage Ankle Arthritis: A Concise Follow-up, at a Minimum of 10 Years, of a Previous Report.

Abstract: Despite the increasing utilization of total ankle replacement (TAR) for end-stage ankle arthritis, there remains a paucity of long-term follow-up data comparing arthroplasty to arthrodesis. The aim of the current paper was to provide the long-term clinical outcomes of TAR and ankle arthrodesis (AA), measured with use of validated scoring instruments, in a prospective multicenter cohort of patients with ankle arthritis. This cohort from the Canadian Orthopaedic Foot and Ankle Society (COFAS) Prospective Ankle Reconstruction Database comprised patients who underwent TAR or AA between 2001 and 2007.

Microglia internalize tau monomers and fibrils using distinct receptors but similar mechanisms.

Introduction: Alzheimer's disease (AD) and other tauopathies are characterized by intracellular aggregates of microtubule-associated protein tau that are actively released and promote proteopathic spread. Microglia engulf pathological proteins, but how they endocytose tau is unknown.

Methods: We measured endocytosis of different tau species by microglia after pharmacological modulation of macropinocytosis or clathrin-mediated endocytosis (CME) or antagonism/genetic depletion of known tau receptors heparan-sulfate proteoglycans (HSPGs) and low-density lipoprotein receptor-related protein 1 (LRP1).

Cardiovascular events in patients with gout initiating urate-lowering therapy with or without colchicine for flare prophylaxis: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data.

Background: Initiating urate-lowering therapy can trigger gout flares. Gout flares have been associated with a temporally increased risk of cardiovascular events. Therefore, we aimed to estimate the risk of cardiovascular events in patients with gout initiating urate-lowering therapy with flare prophylaxis using colchicine (the drug recommended for gout flare prohphylaxis by many international societies) compared with no prophylaxis.

The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.

Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3+ regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR'336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor α chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR'336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8+ T cells' proliferation and function.

Impact of gender on the willingness to participate in clinical trials and undergo related procedures in individuals from an Alzheimer's prevention research cohort.

Background: Although there is growing evidence of the association between gender and early diagnosis of preclinical Alzheimer's disease, little attention has been given to the enrolment ratio of men and women in clinical trials and data reporting.

Methods: This study aims to analyze gender differences in sociodemographic factors associated with the willingness to participate in clinical trials and undergo specific procedures in the context of an Alzheimer's disease prevention research cohort. 2544 cognitively unimpaired participants from the ALFA parent cohort (age 45-75 years) of the Barcelonaβeta Brain Research Center were contacted through a structured phone call to determine their willingness to participate in Alzheimer's disease clinical trials and undergo trial-related procedures (magnetic resonance imaging, lumbar puncture, positron emission tomography, and cognitive assessment).

The evolution of academic advisor and resident dyadic coaching relationships: a two-year longitudinal qualitative study.

Implementing competency based medical education (CBME) has generated enormous amounts of assessment data. To help residents synthesize and use these data, some programs have appointed academic advisors (AA) to 'coach over time'. This study explored how resident and faculty AA dyads perceived their relationship developing and evolving, and the extent to which it aligned with 'coaching over time'.

Knowledge Acquisition and Audience Retention in Stroke Education: Results From a Global Study by the World Stroke Organization.

Background: The World Stroke Academy (WSA), the educational platform of the WSO, provides high-quality stroke education to health care professionals worldwide. Understanding the learning needs and preferences of WSA members is crucial for effective knowledge translation. This study aims to (1) assess demographics and professional backgrounds of WSA members, (2) identify preferences in knowledge acquisition, and (3) evaluate audience retention during WSA webinars.

Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.

Background: Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair.

Medical chart-reported alcohol consumption, substance use, and mental health issues in association with HIV pre-exposure prophylaxis (PrEP) nonadherence among gay, bisexual, and other men-who-have-sex-with-men.

Background: Although some evidence suggests that alcohol, substance use, and mental health issues diminish adherence to HIV Pre-Exposure Prophylaxis (PrEP) among gay, bisexual, and other men-who-have-sex-with-men (gbMSM), findings are somewhat inconsistent and have primarily derived from studies involving non-random samples. Medical chart extraction can provide unique insight by in part surmounting sampling-related limitations, as data for entire PrEP clinic populations can be examined. Our investigation entailed comprehensive chart extraction to assess the extent to which chart-reported alcohol, substance use, and mental health issues were associated with chart-reported PrEP nonadherence.

Severe hypophosphataemia and hypocalcaemia following intravenous ferric derisomaltose and denosumab administration.

Serum calcium and phosphorus levels are tightly regulated by the calciotropic hormone parathyroid hormone, fibroblast growth factor 23 and 1,25(OH) vitamin D. Commonly prescribed therapies for iron-deficiency anaemia (IDA) such as ferric carboxymaltose and ferric derisomaltose (FDM) have been shown to disrupt phosphorus homeostasis, resulting in hypophosphataemia. Similarly, denosumab use can result in hypocalcaemia due to the inhibition of osteoclastic maturation, activity and survival.

Long-term follow-up of patients with a first clinical demyelinating event (clinically isolated syndrome) who received cladribine tablets in CLASSIC-MS: Findings for the ORACLE-MS cohort.

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo.

Pharmaco-Invasive Strategy With Half-Dose Tenecteplase in Patients With STEMI: Prespecified Pooled Analysis of Patients Aged ≥75 Years in STREAM-1 and 2.

Background: In STREAM-1 (Strategic Reperfusion Early After Myocardial Infarction), excess intracranial hemorrhage occurred in patients aged ≥75 years receiving full-dose tenecteplase as part of a pharmaco-invasive strategy, whereas no further intracranial hemorrhage occurred after halving the tenecteplase dose. In STREAM-2 (Second Strategic Reperfusion Early After Myocardial Infarction), half-dose tenecteplase was an effective and safe pharmaco-invasive strategy in older patients with ST-segment-elevation myocardial infarction presenting within <3 hours, compared with primary percutaneous coronary intervention (PCI). We prespecified evaluating the efficacy and safety of a half-dose versus full-dose pharmaco-invasive strategy and compared the half-dose pharmaco-invasive strategy to primary PCI in patients aged ≥75 years.

Validation and Optimization of a Stable Isotope-Labeled Substrate Assay for Measuring AGAT Activity.

L-arginine: glycine amidinotransferase (AGAT) gained academic interest as the rate-limiting enzyme in creatine biosynthesis and its role in the regulation of creatine homeostasis. Of clinical relevance is the diagnosis of patients with AGAT deficiency but also the potential role of AGAT as therapeutic target for the treatment of another creatine deficiency syndrome, guanidinoacetate N-methyltransferase (GAMT) deficiency. Applying a stable isotope-labeled substrate method, we utilized ARG 15N (ARG-δ2) and GLY 13C15N (GLY-δ3) to determine the rate of 1,2-13C,15N guanidinoacetate (GAA-δ5) formation to assess AGAT activity in various mouse tissue samples and human-derived cells.

Efficient Transfer of Chirality in Complex Hybrid Materials and Impact on Chirality-induced Spin Selectivity.

Transfer of chirality, or transmission of asymmetric information from one system to another, plays an essential role in fundamental biological and chemical processes and, therefore, is essential for life. This phenomenon also holds immense potential in spintronics in the context of chirality-induced spin selectivity (CISS). In the CISS, the spatial arrangement of chiral molecules influences the spin state of electrons during the charge-transfer processes.

Weight and metabolic changes with long-acting cabotegravir and rilpivirine or bictegravir/emtricitabine/tenofovir alafenamide.

Background: Modest weight and lipid changes have been observed in cabotegravir plus rilpivirine long-acting (CAB+RPV LA) Phase 3/3b studies. The SOLAR study included standardized evaluations of weight and metabolic changes in people living with HIV switching to CAB+RPV LA dosed every 2 months (Q2M) vs. continuing bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF).

Multicenter Validation of the Ocular Myasthenia Gravis Rating Scale Questionnaire.

Background And Objectives: Ocular myasthenia gravis (OMG) causes disabling ocular symptoms of ptosis and diplopia, but a validated disease-specific patient-reported outcome measure (PROM) has not been reported. We sought to validate a novel PROM for OMG, OMG Rating Scale Questionnaire (OMGRate-q), as a measure of visual functioning to support patient-centered care.

Methods: This was a prospective study of patients aged 18 years and older with OMG receiving care at 3 medical centers (January 2022-October 2023).