Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

Harmonization of alcohol use data and mortality across a multi-national HIV cohort collaboration.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).

Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration.

Pregnenolone effects on parasympathetic response to stress and alcohol cue provocation in treatment-seeking individuals with alcohol use disorder.

Background: Chronic alcohol consumption in alcohol use disorder (AUD) is associated with autonomic nervous system dysregulation, increasing cardiovascular risk, and high alcohol cravings. Heart rate variability (HRV), a marker of autonomic nervous system responsiveness to stressors, may mediate alcohol's impact on the cardiovascular system. While pregnenolone (PREG) has been shown to normalize heart rate and blood pressure in individuals with AUD, its effects on sympathetic and parasympathetic components of HRV and related alcohol craving are not known.

Association of Systemic Thromboxane Generation With Risk of Developing Heart Failure.

Background: Systemic thromboxane A generation, which is readily assessed by quantifying thromboxane B metabolites (TXB-M) in the urine, is associated with impaired cardiac performance and mortality in aspirin (ASA) users with heart failure (HF).

Objectives: This study sought to determine the association of urinary TXB-M with the risk of developing HF in individuals without prior history of HF and with normal left ventricular function irrespective of ASA use.

Methods: Urine TXB-M were measured by immunoassay and adjusted to urine concentration and renal function (TXB-M) in 2,611 Framingham Heart Study participants (54.

Does cyber dating abuse victimization predict next-day alcohol and cannabis use among college students?

Background And Objectives: Cyber dating abuse (CDA) is prevalent on college campuses, with 43% of college students experiencing CDA each year. Yet, the potential impacts of CDA victimization on college students' health outcomes remain poorly understood. Informed by the self-medication hypothesis and longitudinal data linking dating abuse to substance use outcomes, the present study tested the hypothesis that CDA victimization positively associates with college students' next-day alcohol use (number of drinks consumed, odds of any drinking) and odds of cannabis use (yes/no).

The MR1/MAIT cell axis enhances dystrophic neurite development in Alzheimer's disease.

Introduction: Plaques are a hallmark feature of Alzheimer's disease (AD). We found that the loss of mucosal-associated invariant T (MAIT) cells and their antigen-presenting molecule MR1 caused a delay in plaque pathology development in AD mouse models. However, it remains unknown how this axis is impacting dystrophic neurites.

Increased Risk of Patellofemoral Instability Events and Surgical Management in Patients With Joint Hypermobility Syndromes: A Matched Cohort Analysis.

Purpose: To compare the odds of patellofemoral instability events requiring subsequent surgery and revision surgical intervention in patients with joint hypermobility syndromes (JHS) to that of a matched cohort.

Methods: This is a retrospective cohort study using the PearlDiver Mariner Database. Records were queried between 2010 and 2021 with a diagnosis of JHS, including Ehlers-Danlos syndrome (EDS) and Marfan syndrome.

Both English- and Spanish-Language Anterior Cruciate Ligament Reconstruction Online Patient Education Materials Are Written at Higher-Than-Recommended Reading Levels.

Purpose: To examine the overall reading levels of anterior cruciate ligament reconstruction online patient education materials (OPEMs) written in English and Spanish.

Methods: We conducted Google searches for OPEMs using "ACL surgery" and "" as English and Spanish search terms, respectively. Several measures of readability were used to analyze 25 English-language OPEMs (Flesch Reading Ease, Flesch Reading Ease Grade Level, Flesch-Kincaid Grade Level, Coleman-Liau Index, Gunning Fog Index, and Simple Measure of Gobbledygook) and 25 Spanish-language OPEMs (Fernández-Huerta Index, Fernández-Huerta Grade Level, and Índice de Legibilidad de Flesch-Szigriszt).

The etiology and prevention of early-stage tau pathology in higher cortical circuits: Insights from aging rhesus macaques.

Aging rhesus macaques provide a unique model for learning how age and inflammation drive early-stage pathology in sporadic Alzheimer's disease, and for testing potential therapeutics. Unlike mice, aging macaques have extensive association cortices and inflammatory signaling similar to humans, are apolipoprotein E ε4 homozygotes, and naturally develop tau and amyloid pathology with marked cognitive deficits. Importantly, monkeys provide the unique opportunity to study early-stage, soluble hyperphosphorylated tau (p-tau), including p-tau217.

Plasma p-tau and neurofilament/p-tau ratio in differentiating Alzheimer's disease from syndromes associated with frontotemporal lobar degeneration.

Introduction: Plasma-based biomarkers have shown promise for clinical implementation, but their accuracy in differentiating Alzheimer's disease (AD) from syndromes associated with frontotemporal lobar degeneration (FTLD) has yet to be fully investigated. This study assessed the potential of plasma biomarkers for differential diagnosis.

Methods: This cohort study included 374 participants (96 AD, 278 FTLD).

Performance on Activities of Daily Living and User Experience When Using Artificial Intelligence by Individuals With Vision Impairment.

Purpose: This study assessed objective performance, usability, and acceptance of artificial intelligence (AI) by people with vision impairment. The goal was to provide evidence-based data to enhance technology selection for people with vision loss (PVL) based on their loss and needs.

Methods: Using a cross-sectional, counterbalanced, cross-over study involving 25 PVL, we compared performance using two smart glasses (OrCam and Envision Glasses) and two AI apps (Seeing AI and Google Lookout).

Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease.

PROPEL (ATB200-03; NCT03729362) compared the efficacy and safety of cipaglucosidase alfa plus miglustat (cipa + mig), a two-component therapy for late-onset Pompe disease (LOPD), versus alglucosidase alfa plus placebo (alg + pbo). The primary endpoint was change in 6-min walk distance (6MWD) from baseline to week 52. During PROPEL, COVID-19 interrupted some planned study visits and assessment windows, leading to delayed visits, make-up assessments for patients who missed ≥ 3 successive infusions before planned assessments at weeks 38 and 52, and some advanced visits (end-of-study/early-termination visits).

Adjuvant endocrine therapy with cyclin-dependent kinase 4/6 inhibitor, ribociclib, for localized hormone receptor-positive/HER2- breast cancer (LEADER).

Optimal timing and dosing of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor in early breast cancer is controversial. This prospective phase II clinical trial investigated tolerability and safety of two ribociclib dosing schedules. Patients with stage I-III hormone receptor-positive (HR+)/HER2- breast cancer on adjuvant endocrine therapy (ET) were randomized to two ribociclib dosing schedules: 400 mg continuous vs 600 mg intermittent, with initiation in early (prior ET < 2 years) vs delayed (prior ET ≥ 2 years) setting.

Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.

Transgenerational associations between newborn metabolic profiles and bronchopulmonary dysplasia in neonates born to mothers with an obese phenotype.

Maternal obesity increases risk for bronchopulmonary dysplasia (BPD) by up to 42%. Identifying metabolic features that may contribute to the association between maternal pre-pregnancy body mass index (BMI) and BPD is critical in defining the molecular relationship between these conditions. We investigated the association between maternal obesity and BPD using newborn screen metabolites as an explanatory variable.

Impact of early initiation of renal replacement therapy in patients on venoarterial ECMO using target trial emulation with Japanese nationwide data.

While renal replacement therapy (RRT) allows for precise fluid management as well as addressing electrolyte imbalances and the removal of other necessary compounds, its early initiation has not shown benefit in the general critically ill population. Moreover, the effects of early RRT initiation specifically in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) also remain unclear. This retrospective study investigated adult patients who underwent VA-ECMO between April 2018 and March 2022 and used the clone-censor-weight method to emulate a hypothetical target trial and compare two groups: patients who initiated RRT within 2 days of VA-ECMO initiation (Early) and those who did not (Late).

Delayed diagnosis of multiple myeloma in a young patient: a call for vigilance in diagnosis.

Multiple myeloma is a rare haematologic malignancy, representing about 1-2% of all cancers and 17% of haematologic malignancies in the US, predominantly affecting older adults and more common in African Americans (AAs) and men. Light-chain multiple myeloma, a subtype accounting for 15% of multiple myeloma cases, often has a more aggressive clinical course. This case report discusses a rare case of an AA female in her early 30s, diagnosed with light-chain multiple myeloma following a pathological rib fracture.

Sphingosine kinase 2 (SphK2) depletion alters redox metabolism and enhances inflammation in a diet-induced MASH mouse model.

Background: Sphingosine-1 phosphate (S1P) is a bioactive lipid molecule that modulates inflammation and hepatic lipid metabolism in MASLD, which affects 1 in 3 people and increases the risk of liver fibrosis and hepatic cancer. S1P can be generated by 2 isoforms of sphingosine kinase (SphK). SphK1 is well-studied in metabolic diseases.

A germline FLT3 variant in aplastic anemia.

FMS-like tyrosine kinase 3 (FLT3) genetic variants are commonly seen in high-grade myeloid neoplasms and are typically gain-of-function mutations associated with a proliferative disease phenotype. Inactivating FLT3 variants have been less frequently described in non-malignant, autoimmune disorders and are uncommon in aplastic anemia (AA). Herein, we report the first to our knowledge, and unusual case of a germline, gain-of-function, FLT3 variant in a patient with severe AA treated successfully with immunosuppressive therapy.

Perceptions about preclinical Alzheimer's disease biomarker collection procedure influences willingness to participate: Findings from an ethnoracially diverse study.

Background: Past research suggests that ethnoracialized groups differ in their willingness to engage in preclinical Alzheimer's disease (AD) research overall. Studies indicated that participation willingness was affected by attitudes toward research and perceived invasiveness of biomarker collection techniques. However, comparative quantitative studies are few, and minoritized groups are under-included.

Biofilm attachment and mineralizing potential of contemporary restorative materials.

Purpose: To evaluate and compare: (1) the effect of the bacterial biofilm on the dentin mineral density at the restoration-tooth interface and (2) the mineralization potential of three resin-based restorative materials (RBRM).

Methods: 16 extracted human molars free of caries and cracks were collected and stored for disinfection. Each tooth received two standardized Class II preparations with the cervical margin placed in dentin.

Demographic-Based Personalized Left Ventricular Hypertrophy Thresholds for Hypertrophic Cardiomyopathy Diagnosis.

Background: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death. Current diagnosis emphasizes the detection of left ventricular hypertrophy (LVH) using a fixed threshold of ≥15-mm maximum wall thickness (MWT). This study proposes a method that considers individual demographics to adjust LVH thresholds as an alternative to a 1-size-fits-all approach.

Characterization of Hepatitis B Virus Transcripts in Chronically HBV-Infected Chimpanzees and Patients Treated with ARC-520 siRNA Demonstrates Transcriptional Silencing of cccDNA.

Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, as well as transcripts likely to be derived from dimers of dslDNA, and these differed between HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg-) individuals. HBV transcripts from the last follow-up ~30 months post-ARC-520 treatment were categorized from one HBeAg+ (one of two previously highly viremic patients that became HBeAg- upon treatment and had greatly reduced cccDNA products) and four HBeAg- patients. The previously HBeAg+ patient received a biopsy that revealed that he had 3.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques.

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure.