Emerging evidence suggests that a single bout of physical exercise can induce rapid antidepressant effects, yet the underlying neural mechanisms remain largely unknown. We established a mouse model designed to mimic the mood-elevating effects of acute exercise observed in humans. We found that this rapid antidepressant response in exercised mice correlated with increased brain levels of adiponectin, an adipocyte-secreted hormone. Using whole-brain c-Fos mapping, immunofluorescence staining of glutamatergic neurons using the marker CaMKII, and in vivo calcium imaging, we identified ACC glutamatergic neurons that were rapidly activated by single-bout physical exercise. Chemogenetic manipulation of these neurons modulated the rapid antidepressant effects of exercise. Genetic manipulations demonstrated that the global knockout of adiponectin or the selective deletion of its receptor, AdipoR1, in ACC-glutamatergic neurons abolished both neural activation and the rapid antidepressant response. Mechanistically, acute exercise upregulated adiponectin, activating AdipoR1 and promoting nuclear translocation of APPL1 in ACC-glutamatergic neurons. This molecular cascade enhanced the epigenetic regulation of synaptic protein expression and spinogenesis, culminating in a rapid antidepressant response. These findings not only elucidate a novel role for APPL1 nuclear translocation in mediating the antidepressant effects of acute exercise but also identify AdipoR1 as a potential therapeutic target for developing rapid-acting antidepressant interventions.

Non-linear associations between sleep duration and health outcomes are well-documented, but the role of circadian timing in these relationships remains scantly explored. This study examined linear and non-linear associations between self-reported sleep duration and mental and physical health-related quality of life in Italian university students, accounting for the moderating effect of bedtime.

A total of 1,234 students (mean age 23.3 ± 2.5 years; 87.3% women) responded to an online survey that included standardized measures of sleep quality, sleep timing, and health-related quality of life (HRQoL). Multiple regression models including quadratic and cubic terms and interactions were used to investigate linear and non-linear associations between sleep and circadian timing preferences and mental and physical HRQoL.

Later bedtimes were independently associated with lower mental HRQoL (β = -0.10, p < .001). In early sleepers, mental HRQoL showed an inverted U-shaped association with sleep duration, with poorer outcomes at short and long durations. For physical HRQoL, a U-shaped quadratic effect of sleep duration was observed (β = -0.10, p = .007), independent of bedtime.

These preliminary findings support the integration of circadian variables into sleep-health models using accessible self-report measures.

With the outbreak of the COVID-19 pandemic and the subsequent imposition of mobility restrictions in many nations, traffic volumes and driving behaviors have changed worldwide. This study aims to investigate the effect of COVID-19 restrictions and fuel prices on traffic volume and offenses (speeding, tailgating, and illegal overtaking) in Iran's provincial and aggregated data in the study period of March 21, 2019, to May 20, 2020. A time-series analysis was conducted to capture the effects of interventions in level and trend, followed by a spatial autocorrelation of the interventions among provinces to identify the provinces that formed clusters in terms of traffic volume and offenses before and after each intervention. Most of the COVID-19 restrictions (and the pandemic itself) did not reduce traffic volume and rate of traffic offenses whereas an increase in fuel prices decreased traffic volume and offenses (except for illegal overtaking). Furthermore, traffic volume showed an increasing trend after the imposition of mobility restrictions, suggesting that preventive measures could not control intercity trips during the pandemic. Spatiotemporal analysis showed mobility restrictions effectively removed some provinces from the clusters with above-average volume, tailgating, and overtaking data. The possible reasons for these findings and potential solutions are discussed.

Non-communicable diseases (NCDs) pose a major public health challenge worldwide, particularly in low- and middle-income countries (LMICs) like Indonesia, driven by urbanization, lifestyle changes, and environmental risks. Challenges such as constrained healthcare resources and socio-economic disparities hinder the effectiveness of NCD prevention and management. In response, Indonesia has implemented the Community-Based Chronic Disease Management Program (Prolanis), designed to promote regular monitoring, medication adherence, lifestyle modifications, and health education through primary health centers. This scoping review aimed to identify and map the barriers to Prolanis implementation across different regions and communities in Indonesia. A comprehensive literature search was performed in Scopus, ScienceDirect, and PubMed for peer-reviewed publications between 2014 and 2024. After the screening process, 38 peer-reviewed works met the inclusion criteria and were analyzed thematically. Thematic analysis indicated five major categories of barriers, including infrastructure and staffing constraints, low coverage, participation and adherence, socioeconomic and cost barriers, cultural and health literacy barriers, and pandemic-related disruptions. Key issues included inadequate human resources, inconsistent medical supplies, geographic barriers, patient time conflicts, and a lack of perceived benefit. Additionally, socio-economic challenges such as out-of-pocket expenses and transportation costs further restricted participation. Addressing these identified barriers is critical for improving the effectiveness of Prolanis and enhancing chronic disease management in Indonesia. These findings also contribute valuable insights for the implementation of community-based NCD programs in other LMIC settings.

Hyperglycemia and hypertriglyceridemia, two key elements of insulin resistance, are linked with developing kidney dysfunction. The Triglyceride-glucose (TyG) index, composed of blood lipids and glucose, may help assess the risk of kidney dysfunction. This study aimed to clarify the effect of TyG on estimated glomerular filtration rate (eGFR) reduction in adults in western Iran.

This cross-sectional study involved a total of 9,661 participants, aged 35 to 65 years, drawn from the Ravansar Non-Communicable Diseases (RaNCD) cohort. Among these, 1,044 individuals were identified with chronic kidney disease (CKD), while 8,617 were classified as healthy. The triglyceride-glucose index (TyG) was calculated using the formula ln [triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Additionally, an eGFR less than of 60 ml/min per 1.73 m² was employed to indicate kidney dysfunction.

48% of participants were male, and 40.14% were from rural areas. The prevalence of reduced eGFR was 10.81%. Compared to the first quartile, the fourth had significantly higher rates of hypertension, type 2 diabetes, cardiovascular disease, and dyslipidemia (P < 0.001). The odds of kidney dysfunction (eGFR reduction) were 47% in the third quartile (OR: 1.47; 95% CI: 1.20, 1.81) and 75% in the fourth quartile (OR: 1.75; 95% CI: 1.42, 2.17), significantly higher than those in the first quartile of the TyG index (P trend < 0.001), after adjustment for confounding factors.

Lipid and glucose imbalances may be markers for decreased kidney function, and it is recommended that patients with such imbalances be screened for kidney disease.

The optimal timing of left ventricular unloading in patients with cardiogenic shock receiving venoarterial extracorporeal membrane oxygenation therapy remains controversial. This systematic review evaluated the latest evidence on the impact of left ventricular unloading timing in patients with cardiogenic shock receiving venoarterial extracorporeal membrane oxygenation.

The PubMed, Embase and Cochrane Library databases were searched from inception to February 2025. The identified studies were screened based on predefined inclusion and exclusion criteria, and eligible studies were subjected to quality assessment and data extraction. Heterogeneity testing and meta-analysis were performed using Review Manager software version 5.4.

Eight studies involving 2,117 patients (proactive unloading, 1,338; passive unloading, 779) were included in the meta-analysis, which revealed no statistically significant differences in extracorporeal membrane oxygenation weaning rates (relative risk = 1.06, 95% confidence interval: 0.87-1.28; P = 0.59), in-hospital mortality (relative risk = 0.95, 95% confidence interval: 0.86-1.04; P = 0.28), or 30-day all-cause mortality (relative risk = 0.75, 95% confidence interval: 0.52-1.10; P = 0.14) between the proactive and passive unloading groups. However, the risks of sepsis (relative risk = 0.79, 95% confidence interval: 0.64-0.96; P = 0.02) and abdominal complications (relative risk = 0.67, 95% confidence interval: 0.46-0.96; P = 0.03) were lower following proactive unloading than following passive unloading.

Compared to passive left ventricular unloading, proactive left ventricular unloading did not confer significant benefits in terms of extracorporeal membrane oxygenation weaning success or short-term survival outcomes, but was associated with reduced risks of sepsis and abdominal complications.

The review protocol was registered in PROSPERO (ID: CRD42024499028).

The aim of the study was to present estimates of mortality from noncommunicable diseases attributable to low physical activity in Brazil in 2019.

An epidemiologic and descriptive study. We retrieved the data during the month of September 2023. Two independent researchers accessed the indicators in the Global Burden of Disease database: (i) number of cases and (ii) mortality from cardiovascular diseases, diabetes, kidney diseases, and neoplasms, and (iii) level of physical activity in Brazilian individuals for the year 2019. Data were extracted by two researchers independently for the states of Brazil, stratified by sex (male and female), age groups (15-49 years, 50-69 years, and 70 or more years), cause of death and corresponding mortality (cardiovascular diseases, diabetes and kidney diseases, and neoplasms) and classified by regions according to geographic and administrative distribution in North, Northeast, Southeast, South, and Central-West. The number of deaths, age-standardized mortality, and years of life lost due to the disease were extracted, gross and in rates per 100,000 inhabitants.

Mortality from noncommunicable diseases associated with low levels of physical activity in Brazil in 2019 was 293.39 deaths per 100,000 inhabitants, highest in Maranhão, with 407.98 deaths per 100,000 inhabitants, and lowest in the Distrito Federal and Minas Gerais, respectively.

Cardiovascular disease was the most prominent risk factor among the results of this study.

Sub-Saharan Africa faces a substantial burden from both communicable and non-communicable diseases, yet gaps in health data tracking hinder understanding of health impacts and treatment affordability. This study examined disease patterns in the Rwenzori region (2013–2022) using Disability-Adjusted Life Years (DALYs) and assessed treatment costs and affordability perceptions through ordinary least squares (OLS) and Bayesian regression. DHIS2 records provided annual disease data, while survey data from 284 households informed analyses of treatment expenses and perceived affordability. Findings indicate that malaria, coughs, and intestinal diseases remain prevalent, with hypertension and cancer increasing in incidence. DALY analysis identified hypertension as the leading contributor to disease burden, followed by pregnancy-related hemorrhage and malaria. OLS regression showed that treatment costs were highest in private facilities, in households managing multiple conditions within a given period, and especially among elderly patients with persistent NCDs, highlighting a strong age–disease interaction (β = 173,013, p = 0.014). Bayesian regression indicated that caring for individuals over 60 (Median = 1.71, 95% CI: [0.54, 2.72]) and households with seven or more members (Median = 0.78, 95% CI: [0.25, 1.29]) exerted the greatest influence on perceived affordability. While distance to healthcare facilities did not directly affect treatment costs, it significantly shaped affordability perceptions. The study underscores the need for policies that improve healthcare affordability for vulnerable populations, including the elderly and large households. Strengthening health information systems and prioritizing preventive care for NCDs are essential. Bayesian approaches provide valuable insights to support evidence-based healthcare planning in resource-limited settings.

Self-rated health status is a subjective but important indicator of an individual's perception of overall health. However, it remains unclear whether lifestyle may mediate or modify the association of self-rated health status with overall and cause-specific mortality.

This prospective cohort analysis included 401,410 US adults from the National Institutes of Health-AARP Diet and Health Study. Self-rated health was categorized as "very good to excellent," "good," or "poor to fair." A healthy lifestyle was defined by a normal body mass index, never smoking, moderate alcohol consumption, adequate physical activity, and a higher diet quality score. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cause-specific mortality were estimated using multivariable-adjusted Cox models.

During a median follow-up of 23.6 years, we ascertained 181,776 deaths. Compared with individuals reporting "very good to excellent" health, those reporting "poor to fair" health had an elevated risk of overall mortality (HR = 1.90, 95% CI: 1.87-1.93) as well as mortality from cardiovascular disease (CVD), heart disease, stroke, cancer, respiratory disease, diabetes, infection, and injuries and accidents (risk increment ranged from 24% to 361%). Mediation analysis showed that 5.1% to 33.6% of the observed associations were mediated by lifestyle. Self-rated health was more strongly associated with overall mortality than traditional risk factors except smoking. Compared with individuals reporting "very good to excellent" health who adhered to a healthier lifestyle, those reporting "poor to fair" health with a less healthy lifestyle experienced a significantly elevated risk of overall mortality and mortality from CVD, heart disease, cancer, and respiratory disease (relative excess risk due to interaction > 0).

Poor self-rated health was significantly associated with higher risk of overall and cause-specific mortality, and these associations were partially mediated by lifestyle. A positive additive interaction between self-rated health and lifestyle was noted for overall mortality and for mortality from CVD, heart disease, cancer, and respiratory disease. These findings underscore the clinical importance of self-rated health and suggest that lifestyle modification may improve health and longevity, particularly among individuals with low or moderate self-rated health.

The heterogeneous subtypes in dilated cardiomyopathy (DCM) are poorly characterized, thus posing challenges to risk stratification. This study aimed to establish a DCM subtype framework based on metabolic and immunoinflammatory factors.

DCM subtypes were identified using unsupervised clustering based on the expression patterns of metabolism-related genes in the left ventricular myocardium of 89 DCM patients. By comparing metabolic pathways, clinical characteristics, immune cell infiltration, inflammatory responses, and immunotherapy efficacy between the subtypes, key metabolic genes were identified through correlation analysis and validated at both bulk and single-cell levels. The alterations in gene expression were verified using the DCM mouse model. Molecular docking was performed to assess the binding affinity between the target protein and potential therapeutic small molecules.

Two subtypes were identified; subtypes 1 and 2 were characterized by increased amino acid metabolism and decreased glucose and energy-related metabolisms, respectively. Subtype 2 displayed worse left ventricular structure and function, higher levels of immune and inflammatory activity, and a more favorable response to immunotherapy. The integrative analysis identified DHRS7C as a key regulator of glucose/energy metabolism; its expression was inversely correlated with left ventricular impairment. The DCM mice showed downregulated DHRS7C expression, which positively correlated with cardiac dysfunction. Additionally, molecular docking identified 17beta-estradiol as a potential therapeutic agent targeting DHRS7C.

This study suggested two heterogeneous DCM subtypes with different metabolic and immunoinflammatory profiles. Furthermore, DHRS7C was inversely correlated with DCM indices and could be targeted by 17beta-estradiol.