Effect of Triheptanoin on Caudate Atrophy and Motor Scores in Patients With Early-Stage Huntington Disease: A Phase II Study.

Background And Objectives: Brain energy deficiency occurs at the early stage of Huntington disease (HD). Triheptanoin, a drug that targets the Krebs cycle, can restore a normal brain energetic profile in patients with HD. In this study, we aimed at assessing its efficacy on clinical and neuroimaging structural measures in HD.

Antiseizure Medications and Cardiovascular Events in Older People With Epilepsy in the Canadian Longitudinal Study on Aging.

Importance: How epilepsy may promote cardiovascular disease remains poorly understood.

Objective: To estimate the odds of new-onset cardiovascular events (CVEs) over 6 years in older people with vs without epilepsy, exploring how enzyme-inducing antiseizure medications (EIASMs) and traditional cardiovascular risk factors mediate these odds.

Design, Setting, And Participants: This was a prospective cohort study using the comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA), with 6 years of follow-up (2015-2021, analysis performed in December 2023).

TAK-925 (danavorexton), an Orexin Receptor 2 Agonist, Reduces Opioid-Induced Respiratory Depression and Sedation Without Affecting Analgesia in Healthy Adult Males.

Background: Orexin neuropeptides help regulate sleep/wake states, respiration, and pain. However, their potential role in regulating breathing, particularly in perioperative settings, is not well understood. TAK-925 (danavorexton), a novel, orexin receptor 2-selective agonist, directly activates neurons associated with respiratory control in the brain and improves respiratory parameters in rodents undergoing fentanyl-induced sedation.

Temporal Trends in Hippocampal Sclerosis Surgery: An Observational Study From a Tertiary Epilepsy Centre.

Objective: Temporal lobe epilepsy with hippocampal sclerosis (HS) is a surgically remediable syndrome. We determined temporal trends in the prevalence of hippocampal sclerosis surgeries and related factors.

Methods: We analysed a prospective cohort of adults who underwent epilepsy surgery at the NHNN, London, between 1990 and 2019.

Identification of a circulating carbohydrate antigen as a highly specific and sensitive target for schistosomiasis serology.

Unlabelled: The World Health Organization (WHO) 2030 roadmap for schistosomiasis calls for development of highly sensitive and specific diagnostic tools to continue and sustain progress towards elimination. Serological assays are excellent for sensitive detection of primary schistosome infections and for schistosomiasis surveillance in near- and post-elimination settings. To develop accurate assay formats, it is necessary to identify defined antibody targets with low cross-reactivity and potential for standardized production.

Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy.

Recently, avacopan has been approved for the treatment of ANCA-associated vasculitis (AAV). Avacopan is an inhibitor of the C5a-receptor, which plays an important role in chemotaxis and the amplification loop of inflammation in AAV. In the most recent, international guidelines avacopan is recommended as steroid-sparing agents for the management of AAV.

Right Ventricular Restrictive Physiology Is Associated With Right Ventricular Direct Flow From 4D Flow CMR.

Background: Right ventricular restrictive physiology (RVRP) is a common occurrence in repaired tetralogy of Fallot (rTOF). The relationship of RVRP with biventricular blood flow components and kinetic energy (KE) from 4-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is unclear.

Objectives: The purpose of this study was to investigate the association of 4D flow CMR parameters with RVRP in rTOF patients.

Clinical epidemiology, genetic diversity, and drug susceptibility patterns by whole genome sequencing of complex isolates in Gabon from 2012 to 2022.

Objectives: This study aimed to investigate genotypic characteristics and drug resistance profiles of complex (Mtbc) strains isolated from patients with suspected tuberculosis (TB) in Gabon.

Methods: We performed whole genome sequencing of 430 Mtbc strains cultured between 2012 and 2022. Phylogenetic strain classification, genomic resistance prediction, and cluster analysis were also performed.

Activated CD27PD-1 CD8 T Cells and CD4 T Regulatory Cells Dominate the Tumor Microenvironment in Refractory Celiac Disease Type II.

Background And Aims: Refractory celiac disease type II (RCDII) is characterized by a clonally expanded aberrant cell population in the small intestine. The role of other tissue-resident immune subsets in RCDII is unknown. Here, we characterized CD8 and CD4 T cells in RCDII duodenum at the single-cell level and .

River co-learning arenas: principles and practices for transdisciplinary knowledge co-creation and multi-scalar (inter)action.

This paper develops the methodological concept of river co-learning arenas (RCAs) and explores their potential to strengthen innovative grassroots river initiatives, enliven river commons, regenerate river ecologies, and foster greater socio-ecological justice. The integrity of river systems has been threatened in profound ways over the last century. Pollution, damming, canalisation, and water grabbing are some examples of pressures threatening the entwined lifeworlds of human and non-human communities that depend on riverine systems.

Coronary Artery Calcium Scores After Prophylactic Premenopausal Bilateral Salpingo-Oophorectomy.

Background: Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at high familial risk of ovarian cancer leads to immediate menopause. Although early natural menopause is associated with increased cardiovascular disease risk, evidence on long-term cardiovascular disease risk after early surgical menopause is scarce.

Objectives: We sought to determine the long-term influence of the timing of RRSO on the development of coronary artery calcium (CAC), an established marker for cardiovascular disease risk.

Conquering Overtreatment of DCIS: Lessons from PRECISION.

As we cannot reliably distinguish indolent, low-risk ductal carcinoma in situ (DCIS) from potentially progressive, high-risk DCIS, all women with DCIS diagnosis undergo intensive treatment without any benefit. The PREvent ductal Carcinoma In Situ Invasive Overtreatment Now team was established to unravel DCIS biology and develop new multidisciplinary approaches for accurate risk stratification to tackle the global problem of DCIS overdiagnosis and overtreatment. See related article by Bressan et al.

Cancer vaccines compensate for the insufficient induction of protective tumor-specific immunity of CD3 bispecific antibody therapy.

Background: CD3 bispecific antibody (CD3 bsAb) therapy has become an established treatment modality for some cancer types and exploits endogenous T cells irrespective of their specificity. However, durable clinical responses are hampered by immune escape through loss of tumor target antigen expression. Induction of long-lasting tumor-specific immunity might therefore improve therapeutic efficacy, but has not been studied in detail yet for CD3 bsAbs.

Multi-Gene Panel for Thrombophilia Testing in Venous Thromboembolism.

Background: Conventional tests for inherited thrombophilia focus on the five most-established inherited thrombophilias; i.e. deficiencies in antithrombin, protein C, and protein S, and the factor V Leiden and prothrombin G20210A variants.

Acute pulmonary embolism with and without hemodynamic instability (2003-2022): A Swiss nationwide epidemiological study.

Background: Data on the epidemiological burden of acute pulmonary embolism (PE) in Switzerland is unavailable. Knowledge gaps remain on trends in PE-related comorbidities, PE severity, and length of in-hospital stay (LOS) at a nationwide level.

Methods: We used nationwide, patient-level data including all patients aged 15 years or older hospitalized for PE in Switzerland from 2003 to 2022, amounting to N=180,600.

A distinct immunophenotype in children carrying the Blautia enterotype: The generation R study.

Objective: Studies in mouse models and human adults have shown that the intestinal microbiota composition can affect peripheral immune cells. We here examined whether the gut microbiota compositions affect B and T-cell subsets in children.

Methods: The intestinal microbiota was characterized from stool samples of 344 10-year-old children from the Generation R Study by performing 16S rRNA sequencing.

Histopathological marks of tongue in a mouse model for oculopharyngeal muscular dystrophy suggest biomechanical defects.

The tongue facilitates vital activities such as swallowing. Swallowing difficulties (dysphagia) are common in the elderly and in many adult-onset neuromuscular diseases. In oculopharyngeal muscular dystrophy (OPMD), dysphagia is often the first symptom.

How many people in the Netherlands live with a hip, knee, or shoulder replacement?

Aims: We estimated the prevalence of people living with at least one hip, knee, or shoulder arthroplasty in the Netherlands.

Methods: We included the first hip (n = 416,333), knee (n = 314,569), or shoulder (n = 23,751) arthroplasty of each patient aged ≥ 40 years between 2007 and 2022 (hip/knee) or 2014 and 2022 (shoulder) from the Dutch Arthroplasty Register (LROI). Data on the size of the Dutch population were obtained from Statistics Netherlands.

Evaluation of an interprofessional education program involving medical and pharmacy students: a mixed-method study.

Background: Effective pharmacotherapy requires strong collaboration between physicians and pharmacists, highlighting the need for interprofessional education (IPE) in university curricula. This study evaluated the impact of an IPE program on medical and pharmacy students, focusing on their perceived development of interprofessional collaborative competencies, perceived learning outcomes, and clinical collaboration perceptions.

Methods: A mixed-method approach was employed to evaluate an IPE program that consisted of three mandatory activities with increased complexity and autonomy, that were integrated into the medical and pharmacy students' curricula.

Axial spondyloarthritis.

Axial spondyloarthritis manifests as a chronic inflammatory disease primarily affecting the sacroiliac joints and spine. Although chronic back pain and spinal stiffness are typical initial symptoms, peripheral (ie, enthesitis, arthritis, and dactylitis) and extra-musculoskeletal (ie, uveitis, inflammatory bowel disease, and psoriasis) manifestations are also common. Timely and accurate diagnosis is challenging and relies on identifying a clinical pattern with a combination of clinical, laboratory (HLA-B27 positivity), and imaging findings (eg, structural damage on pelvic radiographs and bone marrow oedema on MRI of the sacroiliac joints).

Students' perspective on the Dutch National Pharmacotherapy Assessment, a national survey study among final-year medical students.

Introduction: The Dutch National Pharmacotherapy Assessment (DNPA) was introduced in 2013 to improve clinical pharmacology and therapeutics (CPT) education. This study investigated final-year medical students' perceived motivation and level of preparation for the DNPA in different scenarios: mandatory vs. non-mandatory, and traditional high-stakes assessment programme vs.

The impact of summative, formative or programmatic assessment on the Dutch National Pharmacotherapy Assessment: a retrospective multicentre study.

Background: The Dutch National Pharmacotherapy Assessment (DNPA), which focuses on assessing medication safety and essential drug knowledge, was introduced to improve clinical pharmacology and therapeutics education in the Netherlands. This study investigated how the performance of final-year medical students on the DPNA was affected by the assessment programme (traditional with summative or formative assessment, and programmatic assessment).

Methods: This multicentre retrospective longitudinal observation study (2019-2023) involved final-year medical students from four medical schools in the Netherlands.