Life's Essential 8 and midlife trajectories in cognition and brain health: The CARDIA study.

Introduction: Poor cardiovascular health (CVH) is linked to Alzheimer's disease and dementia; however, its association with neurocognitive trajectories earlier in life remains underexplored.

Methods: We included 3224 participants with information on CVH at early midlife (mean age 45.0 ± standard deviation 3.

Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI.

Introduction: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller-scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD.

Methods: Z-score cognitive-domain composites for 311 amyloid-positive sporadic EOAD and 314 amyloid-positive LOAD participants were calculated from baseline data from age-appropriate control cohorts.

Daily or near-daily cannabis and alcohol use by adults in the United States: A comparison across age groups.

Background And Aims: Patterns of daily or near-daily (DND) use of alcohol and cannabis among adults in the United States have been changing. The current study measured how these shifts have occurred across developmental periods of adulthood.

Design, Setting, And Participants: U.

The Safety of Recently Approved Therapeutics in Age-Related Macular Degeneration.

Recent developments in treatments for both forms of advanced age-related macular degeneration (AMD) have led to the approval of multiple agents and modalities within the last few years. Five new medications for both neovascular AMD (nAMD) and geographic atrophy (GA) secondary to nonexudative AMD (neAMD) have been FDA-approved within the last 5 years, along with a new device designed for sustained drug delivery for nAMD. In nAMD, the newest agents approved by the FDA are brolucizumab (Novartis Pharmaceuticals, Basel, Switzerland), faricimab (F.

A randomized controlled trial of Native CHOICES: Impact on alcohol-exposed pregnancy risk reduction among American Indian and Alaska Native women.

Background: Prevention of alcohol-exposed pregnancy (AEP) involves reducing risky alcohol consumption among women at-risk for pregnancy, using effective contraception among women drinking at risky levels to prevent pregnancy, or both. This study presents the outcomes of a randomized controlled trial assessing the efficacy of Native CHOICES, a culturally tailored adaptation of the CHOICES intervention, among American Indian/Alaska Native (AI/AN) women.

Methods: AI/AN women aged 18-44 who were at-risk for an AEP were randomly assigned in a 1:1 ratio to either the Native CHOICES intervention or a waitlist control group.

Transcriptional profile of the rat cardiovascular system at single-cell resolution.

We sought to characterize cellular composition across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We performed single-nucleus RNA sequencing (snRNA-seq) in 78 samples in 10 distinct regions, including the four chambers of the heart, ventricular septum, sinoatrial node, atrioventricular node, aorta, pulmonary artery, and pulmonary veins, which produced 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, with different cellular composition across cardiac regions and tissue-specific transcription for each cell type.

International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

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.

Hypothalamic volume is associated with age, sex and cognitive function across lifespan: a comparative analysis of two large population-based cohort studies.

Background: Emerging findings indicate that the hypothalamus, the body's principal homeostatic centre, plays a crucial role in modulating cognition, but comprehensive population-based studies are lacking.

Methods: We used cross-sectional data from the Rhineland Study (N = 5812, 55.2 ± 13.

Ranking of Health Problems and Prioritization of Cancer Education Topics by African American Communities in South Carolina.

Despite landmark breakthroughs in cancer research, African American adults (AA) bear the highest cancer burden compared to other racial groups in the United States (US). AA adults have twice the likelihood of dying from prostate and uterine cancers compared to White adults, suggesting that there are fundamental issues yet to be addressed when developing and implementing cancer-preventative programs for AA communities. Community-based participatory research (CBPR) empowers community members to identify and prioritize their health problems and preferred strategies to tackle these issues.

Inclisiran as a siRNA Inhibitor of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); Past, Present, and Future.

Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C.

Investigating the role of Wnt3a and Wnt5a as critical factors of hepatic stellate cell activation in acute toxicant-induced liver injury.

Toxicant exposure can lead to acute liver injury, characterized by hepatic reprogramming and wound healing. Hepatic stellate cells (HSC) play a key role in liver regeneration during wound healing by secreting fibrogenic factors and production of extracellular matrix (ECM). However, repetitive injury to the liver can lead to extensive scarring and liver fibrosis, indicating HSCs coordinate both regeneration and disease.

Human AI collaboration for unsupervised categorization of live surgical feedback.

Formative verbal feedback during live surgery is essential for adjusting trainee behavior and accelerating skill acquisition. Despite its importance, understanding optimal feedback is challenging due to the difficulty of capturing and categorizing feedback at scale. We propose a Human-AI Collaborative Refinement Process that uses unsupervised machine learning (Topic Modeling) with human refinement to discover feedback categories from surgical transcripts.

Amino Acid Infusion for Kidney Protection in Cardiac Surgery Patients with Chronic Kidney Disease: A Secondary Analysis of the PROTECTION Trial.

Background: In the PROTECTION trial, intravenous amino acids (AA) decreased the occurrence of acute kidney injury (AKI) in cardiac surgery patients with cardiopulmonary bypass (CPB). Recruitment of renal functional reserve may be responsible for such protection. However, patients with chronic kidney disease (CKD) have diminished renal functional reserve, and AA may be less protective in such patients.

A bacterial methyltransferase that initiates biotin synthesis, an attractive anti-ESKAPE druggable pathway.

The covalently attached cofactor biotin plays pivotal roles in central metabolism. The top-priority ESKAPE-type pathogens, and , constitute a public health challenge of global concern. Despite the fact that the late step of biotin synthesis is a validated anti-ESKAPE drug target, the primary stage remains fragmentarily understood.

Cancer mutations rewire the RNA methylation specificity of METTL3-METTL14.

Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most -methyladenosine (mA) modifications in messenger RNAs (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context for mA can promote oncogenesis.

Protocol for efficient generation of human artery and vein endothelial cells from pluripotent stem cells.

Blood vessels permeate all organs and execute myriad roles in health and disease. Here, we present a protocol to efficiently generate human artery and vein endothelial cells (ECs) from pluripotent stem cells within 3-4 days of differentiation. We delineate how to seed human pluripotent stem cells and sequentially differentiate them into primitive streak, lateral mesoderm, and either artery or vein ECs.

Etiology and correlates of alcohol misuse in early midlife.

Background: Early midlife individuals (ages 30-40) experience demographic shifts that may influence the remainder of adult life. Although new or persistent alcohol misuse is common during this period, early midlife is understudied in alcohol use literature. We examined the heritability of alcohol misuse; the associations between alcohol misuse and sociodemographic factors, physical health, and well-being; and whether these associations were robust in cotwin comparisons.

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.

Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors.

The adenosinergic pathway converting endogenous ATP to adenosine (ADO) is a major immunosuppressive pathway in cancer. Emerging data indicate that plasma small extracellular vesicles (sEV) express CD39 and CD73 and produce ADO. Using a noninvasive, highly sensitive newly developed assay, metabolism of N-etheno-labeled eATP, eADP or eAMP by ecto-nucleotidases on the external surface of sEV was measured using high pressure liquid chromatography with fluorescence detection.

The digestible indispensable amino acid score (DIAAS) in eggs and egg-containing breakfast meals is greater than in toast breads or hash browns served without eggs.

The objectives of this experiment were to determine the digestible indispensable amino acid score (DIAAS) for eggs cooked in different forms and in traditional egg-bread or egg-hash brown combinations, and to test the hypothesis that DIAAS in eggs is greater than in breads or potatoes. Nine ileal cannulated gilts (average initial body weight: 51.1 ± 6.

Retest reliability and reliable change of community-dwelling Black/African American older adults with and without mild cognitive impairment using NIH Toolbox-Cognition Battery and Cogstate Brief Battery for laptop.

Objective: With the increased use of computer-based tests in clinical and research settings, assessing retest reliability and reliable change of NIH Toolbox-Cognition Battery (NIHTB-CB) and Cogstate Brief Battery (Cogstate) is essential. Previous studies used mostly White samples, but Black/African Americans (B/AAs) must be included in this research to ensure reliability.

Method: Participants were B/AA consensus-confirmed healthy controls (HCs) (n = 49) or mild cognitive impairment (MCI) (n = 34) adults 60-85 years that completed NIHTB-CB and Cogstate for laptop at two timepoints within 4 months.

Platelet characteristics in extremely preterm infants after fatty acid supplementation: a randomized controlled trial.

Background: Two risk factors for severe retinopathy of prematurity (ROP) in extremely preterm infants are thrombocytopenia and low levels of arachidonic acid (AA) and docosahexaenoic acid (DHA). To date, these risk factors have not been linked.

Method: Infants born < 28 weeks gestational age (GA) from 2016 to 2019 were randomized to postnatal enteral AA/DHA supplementation or standard care (controls).