Longitudinal Analysis of Cardiovascular Risk Factors Among Older Adults Participating in a Park-Based Fitness Program.

Physical inactivity is a major risk factor for noncommunicable diseases, particularly among older adults. We examined changes in cardiovascular risk factors among older adults in a community-based fitness program in Miami-Dade County, FL. We used repeated measures linear mixed models to examine participants' cardiovascular risk factor changes over 28 months.

Design, synthesis and activity evaluation of novel quinazolinone compounds as TRPC5 inhibitors.

The TRPC5 channel plays an important role in regulating various physiological processes, which is related to various human diseases, especially psychiatric and kidney diseases. Although the TRPC5 channel is one of the essential potential target, no drugs against TRPC5 channels have been granted in the market to date. In this study, based on the structure of hit compound ph1, we further synthesied 49 compounds of novel quinazolinone and heterocyclic fusion pyrimidinone derivatives, and their activities were evaluated by electrophysiological assays.

A Live Video Resiliency Dyadic Intervention for Persons With Dementia and Their Care-Partners Early After Diagnosis: Protocol for Open Pilot of Resilient Together for Dementia.

Background: Alzheimer disease and related dementias (ADRDs) are increasingly common progressive conditions that have a substantial impact on individuals and their primary care partners-together described as a dyad. The stressors experienced by dyad members at around the time of ADRD diagnosis commonly produce clinically elevated emotional distress (ie, depression and anxiety symptoms), which can become chronic and negatively impact health, relationships, and the overall quality of life. Dyads commonly report unmet needs for early support to address these challenges early after diagnosis.

Longitudinal Trends in Physical Activity Among Older Adults With and Without HIV in Uganda.

Introduction: Physical Activity (PA) and its links to frailty, quality of life (QoL), and other comorbidities in older Ugandans living with HIV remain under-explored.

Methods: We analyzed data from three annual assessments of older people living with HIV (PLWH) and age- and sex-similar people not living with HIV (PnLWH). We fitted linear generalized estimating equations (GEE) regression models to estimate the correlates of PA, including demographics, frailty, QoL, HIV, and other comorbidities.

PADS-Net: GAN-based radiomics using multi-task network of denoising and segmentation for ultrasonic diagnosis of Parkinson disease.

Parkinson disease (PD) is a prevalent neurodegenerative disorder, and its accurate diagnosis is crucial for timely intervention. We propose the PArkinson disease Denoising and Segmentation Network (PADS-Net), to simultaneously denoise and segment transcranial ultrasound images of midbrain for accurate PD diagnosis. The PADS-Net is built upon generative adversarial networks and incorporates a multi-task deep learning framework aimed at optimizing the tasks of denoising and segmentation for ultrasound images.

Blockade of neutral sphingomyelinase 2 exerts antitumor effect on metastatic castration resistant prostate cancer cells and promotes tumor regression when combined with Enzalutamide.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among American men. The development of metastatic castration resistant PCa (mCRPC) is the current clinical challenge. Antiandrogens such as Enzalutamide (ENZ) are commonly used for CRPC treatment.

Temporally and Spatially Controlled Age-Related Prostate Cancer Model in Mice.

The initiation and progression of prostate cancer (PCa) are associated with aging. In the history of age-related PCa research, mice have become a more popular animal model option than any other species due to their short lifespan and rapid reproduction. However, PCa in mice is usually induced at a relatively young age, while it spontaneously develops in humans at an older age.

Circulating MicroRNAs in Patients with Psoriasis Treated with Anti-IL-23: A Cohort Study.

Introduction: Psoriasis is characterized by aberrant keratinocyte activity and immune cell infiltration, driven by immune-mediated pathways. MicroRNAs (miRNAs) play crucial roles in regulating these processes, offering insights into disease mechanisms and therapeutic targets.

Objectives: This study aimed to investigate changes in circulating miRNAs in psoriasis patients undergoing risankizumab therapy, an anti-IL-23 monoclonal antibody, to understand its impact on disease pathogenesis and treatment response.

Gut microbial-derived phenylacetylglutamine accelerates host cellular senescence.

Gut microbiota plays a crucial role in the host health in the aging process. However, the mechanisms for how gut microbiota triggers cellular senescence and the consequent impact on human aging remain enigmatic. Here we show that phenylacetylglutamine (PAGln), a metabolite linked to gut microbiota, drives host cellular senescence.

Population pharmacokinetics and pharmacodynamics of HFB30132A, a monoclonal antibody against SARS-CoV-2, in healthy Chinese and US subjects.

Development of neutralizing monoclonal antibody (nAb) is a strategy for treatment of infections caused by SARS-CoV-2. This study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of HFB30132A, a fully human nAb targeting SARS-CoV-2 spike protein receptor binding domain, in healthy subjects. Randomized, double-blind, placebo-controlled phase I trial was performed in healthy Chinese and US subjects, respectively.

Angiotensin type 1 and type 2 receptors-induced mitochondrial dysfunction promotes ferroptosis in cardiomyocytes.

Previous studies suggest that ferroptosis is involved in cardiovascular diseases. The aim of the present study is to investigate the causal relationship between angiotensin II type 1 and type 2 receptors (ATR) activities and mitochondrial dysfunction in induction of cardiomyocyte ferroptosis. Human AC16 cardiomyocytes were first pre-treated with an ATR blockers, before stimulated with angiotensin II (Ang II) for 24 h.

Circulating metabolomic biomarkers of 5-year body weight and composition change in a biracial cohort of community-dwelling older adults.

Unintentional weight loss in older populations is linked to greater mortality and morbidity risks. This study aims to understand the metabolic mechanisms of unintentional weight loss and their relationship with body composition changes in older adults. We investigated plasma metabolite associations with weight and body composition changes over 5 years in 1335 participants (mean age 73.

Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via .

The gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as a key mediator. However, it remains unclear whether specific microbial factors regulate tryptophan metabolism to influence 5-HT production and anxiety regulation.

Modulating mTOR-dependent astrocyte substate transitions to alleviate neurodegeneration.

Traditional approaches to studying astrocyte heterogeneity have mostly focused on analyzing static properties, failing to identify whether subtypes represent intermediate or final states of reactive astrocytes. Here we show that previously proposed neuroprotective and neurotoxic astrocytes are transitional states rather than distinct subtypes, as revealed through time-series multiomic sequencing. Neuroprotective astrocytes are an intermediate state of the transition from a nonreactive to a neurotoxic state in response to neuroinflammation, a process regulated by the mTOR signaling pathway.

Stereo-seq of the prefrontal cortex in aging and Alzheimer's disease.

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in the prefrontal cortex (PFC). We present the first subcellular-resolution spatial transcriptome atlas of the human prefrontal cortex (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages and six age-matched male controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions in laminar structure, and exposed AD-related shifts in layer-to-layer and cell-cell interactions.

Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

Shared decision-making in type 2 diabetes: a systematic review of patients' preferences and healthcare providers' perspectives.

Background: Shared decision-making (SDM) is crucial for type 2 diabetes mellitus (T2DM) management due to the complexity of treatment options. This systematic review sought to understand T2DM patients' preferences and diabetes care providers' perspectives regarding SDM, and the barriers and facilitators to SDM.

Methods: Five databases were searched from 2000 to 2023 (Medline/PubMed, Web of Science, Scopus, PsycINFO, and Embase).

Predicting and Ranking Diabetic Ketoacidosis Risk among Youth with Type 1 Diabetes with a Clinic-to-Clinic Transferrable Machine Learning Model.

To use electronic health record (EHR) data to develop a scalable and transferrable model to predict 6-month risk for diabetic ketoacidosis (DKA)-related hospitalization or emergency care in youth with type 1 diabetes (T1D). To achieve a sharable predictive model, we engineered features using EHR data mapped to the T1D Exchange Quality Improvement Collaborative's (T1DX-QI) data schema used by 60+ U.S.

Quality of Virtual vs. In-Person Outpatient Palliative Care: Disparities by Language and Race.

Context: Virtual visits have increased in outpatient, clinic-based palliative care (OPC). The association between virtual visits and OPC outcomes is largely unknown.

Objectives: (1) Examine the association between visit type (virtual vs.

Machine Learning-based Prognostic Model for Brain Metastasis Patients: Insights from Blood Test Analysis.

Brain metastases, affecting 30% of solid tumor patients, have a substantial impact on clinical outcomes. Developing a clinically feasible and precise prognostic model is crucial for personalized and comprehensive treatment. Parameters from blood test were collected from brain metastases patients, and were used to construct the four models, including univariate Cox regression, stepwise regression, LASSO regression, and random survival forest (RSF).

Association between red blood cell distribution width and genetic risk in patients with rheumatoid arthritis: a prospective cohort study and Mendelian randomization analysis.

Objective: Elevated red blood cell distribution width (RDW) is associated with increased risk of rheumatoid arthritis (RA), but the potential interactions of RDW with genetic risk of incident RA remain unclear. This study aimed to investigate the associations between RDW, genetics, and the risk of developing RA.

Methods: We analysed data from 145,025 healthy participants at baseline in the UK Biobank.

Shared genetic factors and the interactions with fresh fruit intake contributes to four types squamous cell carcinomas.

Studies have reported risk factors for a single-squamous cell carcinoma(Single-SCCs). However, the shared common germline genetic factors and environmental factors have not been well elucidated with respect to augmented risk of pan-squamous cell carcinoma(Pan-SCCs). By integrating a large-scale genotype data of 1,928 Pan-SCCs cases and 7,712 age- and sex-matched controls in the UK Biobank cohort, as well as multiple transcriptome and protein databases, we conducted a multi-omics analysis.

Life-Space Mobility Is Related to Loneliness Among Living-Alone Older Adults: Longitudinal Analysis With Motion Sensor Data.

Background: Life-space mobility can be a behavioral indicator of loneliness. This study examined the association between life-space mobility measured with motion sensors and weekly vs. annually reported loneliness.

I-CONECT intervention effects on weekly time spent outside of home and social contacts among socially isolated older adults.

Background: Socially isolated individuals tend to have less access to cognitively stimulating activities, which could adversely impact their cognitive health. The Internet-Based Conversational Engagement Clinical Trial (I-CONECT) intervention was designed to deliver online conversation sessions to socially isolated older old adults to prevent cognitive decline. The current study examined the intervention efficacy on participants' weekly time spent out-of-home and their social interaction with family and friends.

The moderating role of e-health literacy and patient-physician communication in the relationship between online diabetes information-seeking behavior and self-care practices among individuals with type 2 diabetes.

Background: This study examined the moderating role of e-health literacy (eHL) and patient-physician communication in the relationship between online diabetes information-seeking behavior (online DISB) and self-care practices.

Methods: A total of 1143 individuals with type 2 diabetes mellitus completed a cross-sectional survey assessing sociodemographic characteristics, data relating to diabetes clinical history, online DISB, eHL (eHealth Literacy Scale), aspects of patient-physician communication (IPC survey), patient self-care (Self-Care Inventory-Revised), and medication adherence (measure of adherence to prescribed diabetes medications). The data were analyzed using both bivariate (correlation) and multivariate (multiple linear regression) analyses using maximum likelihood estimation procedures in Mplus.