Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

Tailoring implementation strategies for the healthy actions and lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia Program: Lessons learned from a survey study.

Background: Healthy Actions and Lifestyles to Avoid Dementia Program (HALT-AD) or Hispanos y el ALTo a la Demencia is a recently-developed online educational platform to help individuals identify and modify their own dementia modifiable risk factors (MRF). In light of known challenges in recruiting and retaining diverse participants in research studies, there is a need to identify data-informed strategies that will contribute to effective outreach and tailored implementation of HALT-AD among its intended users of Hispanic and non-Hispanic midlife and older adults in the US.

Objectives: To identify factors (i.

Neonatal inflammation and near-term white matter microstructure in infants born very preterm.

Background: Severe neonatal inflammatory conditions in very preterm infants (VPT: <32 weeks gestational age, GA) are linked to adverse neurodevelopmental outcomes. Differences in white matter (WM) microstructure of the corpus callosum (CC) have been observed at age 6 in VPT children with a history of severe neonatal inflammation. The goal of this study was to determine whether these CC differences can be detected at term-equivalent age using diffusion MRI (dMRI), and whether neonatal inflammation is associated with altered WM in additional tracts implicated in the encephalopathy of prematurity.

Prothrombin prevents fatal T cell-dependent anemia during chronic virus infection of mice.

Thrombin promotes the proliferation and function of CD8+ T cells. To test if thrombin prevents exhaustion and sustains antiviral T cell activity during chronic viral infection, we depleted the thrombin-precursor prothrombin to 10% of normal levels in mice prior to infection with the clone 13 strain of lymphocytic choriomeningitis virus. Unexpectedly, prothrombin insufficiency resulted in 100% mortality after infection that was prevented by depletion of CD8+ T cells, suggesting that reduced availability of prothrombin enhances virus-induced immunopathology.

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.

Barriers to accessing mental health resources as perceived by surgical compared to medical trainees.

Introduction: Despite myriad wellness programs, training demands restrict resident access. This study aimed to evaluate barriers to accessing mental health resources(MHR) and determine if differences exist between medical(MT) and surgical trainees(ST).

Methods: A cross-sectional survey was performed in one health system assessing awareness of and barriers to accessing MHR.

Applying Large Language Models to Assess Quality of Care: Monitoring ADHD Medication Side Effects.

Objective: To assess the accuracy of a large language model (LLM) in measuring clinician adherence to practice guidelines for monitoring side effects after prescribing medications for children with attention-deficit/hyperactivity disorder (ADHD).

Methods: Retrospective population-based cohort study of electronic health records. Cohort included children aged 6 to 11 years with ADHD diagnosis and 2 or more ADHD medication encounters (stimulants or nonstimulants prescribed) between 2015 and 2022 in a community-based primary health care network (n = 1201).

Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease.

Background And Objectives: Nicotinamide is a coenzyme involved in cellular oxidation-reduction reactions that can inhibit Class III histone deacetylases (HDACs) or sirtuins. HDAC inhibition can affect numerous therapeutic pathways, including tau phosphorylation. We tested the hypothesis that nicotinamide treatment could reduce tau phosphorylation in early Alzheimer disease (AD).

Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them.

Multidimensional and Longitudinal Impact of a Genetic Diagnosis for Critically Ill Infants.

Background And Objectives: Many genetic conditions present in the NICU, where a diagnostic evaluation is pursued. However, understanding of the impact of a genetic diagnosis on clinical outcomes and health-related quality of life for these infants remains incomplete. We therefore evaluated parent-reported outcomes complemented by clinical outcomes measures over one year for a cohort of infants in the NICU undergoing genetic evaluation.

Challenging Case: Family Navigation for Autism Spectrum Disorder.

Leo is a 28-month-old boy from a monolingual Spanish-speaking family who was referred to a developmental-behavioral pediatrics (DBP) clinic for concerns regarding autism. His parents migrated to the United States 8 years ago and currently live and work on a farm. He was born in a US hospital after an uncomplicated pregnancy and has been generally healthy.

Symptoms Do Not Predict White Matter Injury in the Watershed Regions in Children with Moyamoya.

Objective: To assess whether white matter injuries differ in symptomatic vs asymptomatic moyamoya-affected hemispheres using diffusion magnetic resonance imaging since there is controversy regarding when or if to revascularize children with asymptomatic moyamoya.

Study Design: We conducted a cross-sectional study of children with moyamoya who underwent diffusion magnetic resonance imaging before revascularization surgery as well as controls without moyamoya. We measured the fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity of white matter tracts in the watershed regions.

Listening to Mom in the Neonatal Intensive Care Unit: A randomized trial of increased maternal speech exposure on white matter connectivity in infants born preterm.

Background: Early speech experiences have been proposed to contribute to the development of brain structures involved in processing spoken language. However, previous research has been limited to correlational studies. Here, we conducted an RCT with preterm neonates to determine whether increased exposure to maternal speech during NICU hospitalization is causally linked to structural white matter maturation.

Potentially Modifiable Dementia Risk Factors in Canada: An Analysis of Canadian Longitudinal Study on Aging with a Multi-Country Comparison.

Background: It has been suggested that up to 40% of dementia cases worldwide are associated with modifiable risk factors; however, these estimates are not known in Canada. Furthermore, sleep disturbances, an emerging factor, has not been incorporated into the life-course model of dementia prevention.

Objective: To estimate the population impact of 12 modifiable risk factors in Canadian adults including sleep disturbances, by sex and age groups, and to compare with other countries.

A framework for translating tauopathy therapeutics: Drug discovery to clinical trials.

The tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. The primary tauopathies meet the definition of rare diseases in the United States. There is no approved treatment for primary tauopathies.

Associations of behavioral problems with white matter circuits connecting to the frontal lobes in school-aged children born at term and preterm.

Introduction: This study investigated whether internalizing and externalizing behavioral problems in children were associated with fractional anisotropy of white matter tracts connecting other brain regions to the frontal lobes. We contrasted patterns of association between children born at term (FT) and very preterm (PT: gestational age at birth =< 32 weeks).

Methods: Parents completed the Child Behavior Checklist/6-18 questionnaire to quantify behavioral problems when their children were age 8 years (N = 36 FT and 37 PT).

Disability health in medical education: development, implementation, and evaluation of a pilot curriculum at Stanford School of Medicine.

Background: People with disabilities face significant healthcare disparities due to barriers to accessing care, negative attitudes of providers, and lack of education on disabilities for healthcare professionals. Physicians report discomfort when interacting with patients with disabilities, adding to the disparity, warranting research on medical school education.

Objective: Two educational interventions were structured: (1) a brief 2-h intervention in the mandatory curriculum and (2) a 9-week elective course which included interactions with individuals with disabilities through workshops and partner programs.

Starting from scratch: Creating a university wellness initiative.

This article addresses the strategies used by one institution to begin a university-wide wellness effort. Mental health challenges in the student population formed the framework for beginning a wellness initiative, including hiring a Chief Wellness Officer (CWO) to lead the way. Initial efforts were spent on understanding the current wellness programs and strategies being offered, as well as areas where additional support was needed.

KLF2 determines the susceptibility of T cells to immunoregulatory NK cells.

Natural killer (NK) cells suppress cellular and humoral immune responses via killing of T cells, resulting in diminished vaccine responses in mice and humans. Efforts to overcome this roadblock and achieve optimal immunity require an improved understanding of the molecular mediators facilitating NK cell-targeting of discrete subsets of CD4 T cells. We employed single-cell forensic victimology and CRISPR-Cas9 editing to delineate a transcriptional program uniquely responsible for the susceptibility of a subpopulation of CD4 T cells to perforin-dependent immunoregulation by NK cells.