Search Results (195)

Background: Neuropathy and neuropathic pain (NP) are globally prevalent, remain difficult to manage, and are often exacerbated by underlying lifestyle factors. Alcohol use, particularly in the context of chronic consumption or dependence, is a recognized contributor to peripheral nerve damage, yet its association with neuropathy/NP has not been systematically evaluated. This systematic review synthesizes the current evidence on alcohol exposure, including quantity, frequency, and dependency, and its association with the incidence, prevalence, and severity of neuropathy/NP. Methods: This systematic review included observational studies assessing alcohol consumption patterns or dependence in relation to neuropathy/NP outcomes and was conducted in accordance with PRISMA guidelines. Exposure types were analyzed independently, and pooled odds ratios and relative risks were generated when sufficient data were available. The review was registered with PROSPERO number CRD42023484158. Results: Following de-duplication and exclusions, 76 studies were included, comprising cohort (n = 15), case–control (n = 12), and cross-sectional (n = 49) designs. While associations varied by study design and exposure category, alcohol dependence and consumption were more consistently linked with increased neuropathy incidence and severity, including electrophysiological evidence of compromised function. Notably, in studies examining alcohol cessation, abstinence was linked to clinical improvements in neuropathy/NP symptoms such as hypoesthesia and muscle weakness. While heterogeneity and risk of bias were present, largely due to the subjective classification of alcohol exposure and a lack of universally applied objective neuropathy measurement tools, multiple pooled estimates reached statistical significance. Conclusions: Evidence from observational studies supports an association between alcohol use, especially dependence, and the development and progression of neuropathy/NP, although causality remains unproven. Abstinence may offer therapeutic benefit, though further abstinence- and/or harm reduction-related interventional studies are required to clarify causality and guide low-cost, adjunctive strategies for alcohol-related neuropathy/NP. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are increasingly recognized as key drivers of hepatocellular carcinoma (HCC). Unlike HCC caused by viral infections or alcohol, MASLD/MASH-related liver cancer develops within a chronic immunometabolic environment characterized by lipotoxicity, sterile inflammation, fibrogenesis, and remodeling of the microenvironment. In this setting, interleukin-10 (IL-10) has attracted growing attention due to its complex, context-dependent roles in immune regulation and tumor immune tolerance. This review explores IL-10 biology and its connection to MASLD/MASH-associated HCC, emphasizing the paradox that IL-10 may diminish harmful inflammation in early stages while promoting immunosuppressive conditions in advanced disease. To supplement existing research, we performed an exploratory reanalysis of publicly available bulk liver RNA-seq data from a mouse model that progresses from MASLD/MASH to HCC. The reanalysis revealed a receptor- and effector-specific rewiring of the IL-10 pathway: while the expression of canonical signaling genes (Stat3, Jak1, Jak2, Tyk2, Socs3) showed minimal changes across stages, receptor subunits (Il10ra, Il10rb) and IL-10-responsive effectors (such as Scd2, related to lipid metabolism, and Ddit4, involved in mTOR and glycolysis regulation) displayed strong stage-dependent induction. This was accompanied by a decrease in hepatocyte signature profiles and an increase in stromal and immune signatures. These results generate new hypotheses and raise key questions—particularly whether a large portion of IL-10 modulation originates from peripheral or non-parenchymal sources, and whether the transcriptional patterns observed reflect protein-level changes—that will require stage-specific, cell-focused human studies incorporating proteomic and cytokine measurements. Full article

The COVID-19 pandemic introduced unprecedented societal disruptions that may have altered patterns of acute substance-related harm. Despite extensive research on overdose mortality, there remains limited real-time, population-level evidence based on Emergency Medical Services (EMS) data. This study provides a national, multi-year characterization of temporal trends in alcohol- and drug-related overdose incidents in Israel across thirteen defined pandemic phases. A total of 18,348 overdose cases recorded between 1 January 2019 and 31 December 2022 were analyzed. Descriptive statistics were calculated, event frequencies were normalized by period length, and loglinear Poisson models were applied to compare occurrences across periods. Cluster analysis was used to explore joint age- and gender-related patterns. Alcohol-related overdoses demonstrated marked fluctuations across pandemic phases, whereas drug-related overdoses showed comparatively moderate variation and a gradual increase over time. Age- and gender-specific heterogeneity was observed across periods. As an observational study based on EMS records, causal inference cannot be established. These findings provide population-level surveillance evidence of dynamic overdose patterns during prolonged societal disruption and highlight the importance of integrating EMS-based monitoring into public health preparedness strategies. Full article

Background: Cigarette smoking exposes the human body to a complex mixture of toxic and carcinogenic compounds that can exert widespread biological effects across different organ systems. From addictive responses and consequence maladaptive neuroendocrine responses, cigarette smoke delivers a variety of reactive oxygen species, polycyclic aromatic hydrocarbons, nitrosamines, and heavy metals that collectively contribute to oxidative stress, inflammation, endothelial dysfunction, and metabolic disruption. The liver, as the primary organ responsible for xenobiotic metabolism, plays a central role in processing these harmful substances and is therefore uniquely susceptible to their effects. This narrative review will aim to provide an overview of the current evidence of cigarette smoking effects on hepatic structure and function and discuss clinical implications. Methods: This narrative review synthesizes evidence from in vitro studies, animal models, and human clinical research examining the effects of cigarette smoking on liver biology. Mechanistic pathways of injury, metabolic and vascular alterations, and clinical consequences for liver disease were considered. Results: Smoking influences hepatic function both directly—through biotransformation pathways generating reactive intermediates—and indirectly via vascular impairment, immune modulation, hormonal alterations, and changes in lipid and glucose metabolism. Emerging evidence indicates that cigarette smoking contributes to hepatic steatosis, accelerates fibrosis progression, worsens outcomes in viral and alcohol-related liver disease, and increases the risk of hepatocellular carcinoma. Conclusions: Cigarette smoking exerts multifaceted deleterious effects on the liver. Recognition of smoking as a modifiable risk factor for liver-related morbidity underscores the importance of smoking cessation in patients with or at risk for liver disease and highlights implications for research and clinical practice. Full article

Background and Objectives: One of the strongest early factors influencing later psychoactive substance use is adverse childhood experiences (ACEs). Studies investigate a variety of adverse experiences in relation to substance use, yet not all adverse childhood experiences are equal in intensity and harm. Our study aimed to address this gap by examining in detail the associations between individual ACEs, broader ACE categories, and different forms of psychoactive substance use. Materials and Methods: The study included 709 participants who completed self-report questionnaires. ACEs were measured using the MACE questionnaire. Marijuana use was measured using the CUDIT-R, alcohol use using the AUDIT, and heavy psychoactive substance use using the ASSIST. Linear regression analyses were used to predict associations. As expected, only a small part of the sample reported hard drug use; some analyses are limited to substantially fewer observations. Results: All regression models were statistically significant and predicted all three categories of psychoactive substances, but if we count the individual adverse experiences, the results become different. Although the results showed that ACE is a significant predictor of hard drug use and explains 25% of the variance, it is separately only emotional neglect that is associated with hard drug use. The regression analysis also explains 14% of the variance in marijuana use, but when considered separately, we found associations only with emotional neglect. The severity of alcohol use explains 13% of the variance, but only a few ACEs reach statistical significance: peer physical bullying, physical violence, and sexual abuse. Conclusions: The findings of our study suggest that adverse childhood experiences may not be qualitatively equivalent and therefore may not be evaluated only as a cumulative risk score. Separate ACE evaluations, instead of aggregate calculation of ACEs, may be useful to understand better which specific negative experiences have the greatest impact on subsequent use of psychoactive substances. The regression models explain only a small portion of the variance, which suggests that other factors may contribute to a larger share. Full article

Background/Objectives: Alcohol and tobacco use in adolescence are major public health concerns that shape long-term health trajectories and undermine healthy behaviour development. Schools are key settings for health promotion, offering structured environments to foster self-regulation, social skills, and protective behaviours. This scoping review mapped recent school-based educational strategies designed to prevent alcohol and tobacco use among adolescents and to examine whether the included studies reported any involvement of school nurses. Methods: Review followed Arksey and O’Malley’s framework and adhered to JBI guidance and PRISMA-ScR. Searches were conducted in PubMed and Web of Science (2019–2024) to identify school-based educational interventions targeting alcohol and/or tobacco use among primary or secondary school children. The primary search targeted prevention strategies, complemented by nursing-related terms to identify nurse involvement. A standardised charting form captured study characteristics, intervention formats, theoretical foundations, implementation factors, and any reported participation of health professionals. Data extraction was performed independently by two reviewers. Results: Eleven studies met the inclusion criteria. Most were randomised controlled trials (81.8%). Educational strategies included online (45.5%), hybrid (27.3%), and face-to-face (27.3%) formats. Programs focused on social skills, self-regulation, harm reduction, or resilience. Digital formats were cost-effective but showed challenges in engagement and sustained participation, while face-to-face or hybrid approaches offered relational support but were vulnerable to implementation drift. No study reported nurse involvement. Conclusions: School-based prevention strategies can contribute to healthier behaviours related to substance use by reinforcing socioemotional competencies and reducing early exposure to substances. However, persistent barriers such as low engagement, inconsistent delivery, and the absence of health professionals limit their impact. The role of school nurses could be considered in future school-based prevention programmes. Full article

Background/Objectives: Blood biomarkers for estimating alcohol consumption are useful for preventing alcohol-related harms. Although there are conventional blood biomarkers of heavy alcohol drinkers, it remains to be clarified whether their combination is useful for estimation of excessive alcohol consumption from the viewpoint of preventing hypertension. Methods: Participants included 8172 men aged from 31 to 70 years who had undergone health checkups. Overall, participants were classified into three groups of nondrinkers, occasional drinkers, and regular drinkers by frequency; regular drinkers were further classified into four groups of light (<22 g/day), moderate (≥22 and <44 g/day), heavy (≥44 and <66 g/day), and very heavy drinkers (≥66 g/day) according to the amount of average daily alcohol consumption. The relationships of blood biomarkers (mean corpuscular volume [MCV], gamma glutamyl transferase [GGT], and HDL cholesterol [HDL-C]) and their products with alcohol consumption were investigated by using correlation analysis and receiver-operating characteristics (ROC) analysis. Results: Seven variables of blood biomarkers and their products were significantly correlated with frequency and amount of alcohol consumption, and the degrees of the correlations were stronger in the following order: HDL-C alone < product of MCV and HDL-C < MCV alone < GGT alone < product of MCV and GGT < product of GGT and HDL-C < product of MCV, HDL-C and GGT. In the ROC analysis, the area under the ROC curve for the relationship between the product of MCV, HDL-C, and GGT (named the alcohol consumption index [ACI]) and excessive alcohol intake (22 g/day or more) was 0.819 (95% confidence interval: 0.809–0.830), and the cutoff of this index was 194,863 with a sensitivity and specificity of 0.745 and 0.751, respectively. The positive predictive value was 69.2%. Conclusions: Among the three conventional blood biomarkers and their combinations, ACI demonstrated the strongest associations with alcohol consumption and excessive alcohol intake in men. Although the combined biomarkers are unlikely to be useful as a diagnostic tool, there is a possibility of future application by integrating ACI with recent biomarkers including carbohydrate-deficient transferrin for estimation of alcohol consumption. Full article

External causes account for over four million deaths globally each year, with psychoactive substance use being a major risk factor. However, the true impact and regional patterns of psychoactive substance use in these deaths remains undefined in Brazil. To address this critical knowledge gap, this pioneering four-city study sought to elucidate the prevalence of alcohol and drug use by external cause victims. We collected postmortem blood from 3577 victims of violent death across four distinct Brazilian cities (Belém, Recife, Vitória, and Curitiba), representing the North, Northeast, Southeast, and South regions, respectively, using a standardized protocol to identify alcohol, illicit drugs, and psychoactive medicines. Analysis revealed a predominantly male cohort (89.7%; 56.0% aged 30 years or more), with homicide as the primary manner of death (67.3%). Over half of the victims (53.0%) tested positive for at least one psychoactive substance prior to death; cocaine (29.6%) and alcohol (27.7%) were most common. Substance use was highest among homicide victims (55.7%), especially cocaine (36.0%), and among self-harm cases (54.6%), which showed elevated benzodiazepine prevalence (20.0%). Substance use patterns varied regionally: alcohol-related deaths were more common in Recife (Northeast), drug-only deaths concentrated in Vitória (Southeast) and Belém (North), and Curitiba (South) showed a higher prevalence of alcohol use versus drug use. This widespread, regionally heterogeneous prevalence underscores the urgent need for targeted, region-specific interventions. By critically linking psychoactive substance use to various modes of violent death, these data provide crucial forensic and public health insights to inform tailored preventive strategies. Full article

Background/Objectives: To examine trends in tobacco and alcohol consumption among individuals with and without diabetes mellitus (DM) in Spain from 2014 to 2020 and identify sociodemographic, lifestyle, and comorbidity-related predictors of consumption. Methods: Population-based cross-sectional study using data from the 2014 and 2020 European Health Interview Surveys for Spain. Participants’ self-reported tobacco and alcohol consumption were analyzed based on DM status. Results: This study included 7854 participants (3927 participants with DM and 3927 participants without DM). Among participants with DM, tobacco and alcohol consumption remained stable over the study period, with tobacco from 15.2% in 2014 to 14.8% in 2020 (p = 0.761) and alcohol from 37.2% to 39.8% (p = 0.088), respectively. Tobacco consumption did not differ significantly between those with and without DM (15.0% vs. 15.2%, p = 0.777). However, alcohol consumption was significantly lower among those with than without DM (38.6% vs. 48.7%, p < 0.001). In those with DM, predictors of tobacco consumption included male sex, younger age, alcohol consumption, living without a partner, and DM, and predictors of alcohol consumption included male sex, active smoking, higher education, and sedentary lifestyle. Conclusions: Between 2014 and 2020, both tobacco and alcohol consumption remained stable among individuals with DM. The prevalence of alcohol consumption was lower among those with than without DM. Key predictors of tobacco and alcohol consumption included sex, lifestyle behaviors, and socioeconomic factors. These findings highlight the need for targeted public health interventions to reduce harmful substance use in DM populations and mitigate associated health risks. Full article

Urbanicity is a recognized determinant of mental health, yet conventional measures such as population density or the rural–urban divide often fail to capture the complex realities of informal settlements in low- and middle-income countries. This paper conceptualizes neighborhood effects through the lived experiences of young women in Kampala, Uganda, drawing on participatory research from the NIH-funded TOPOWA study. Using community mapping and Photovoice, participants identified neighborhood features that shape wellbeing, including sanitation facilities, drainage systems, alcohol outlets, health centers, schools, boda boda stages (motorcycle taxis), lodges, religious institutions, water sources, markets, and recreational spaces. These methods revealed both stressors—poor waste management, flooding, violence, gendered harassment, crime, and alcohol-related harms—and protective resources, including education, places of worship, health centers, social networks, identity, and sports activities. We argue that urbanicity in slum contexts should be understood as a multidimensional construct encompassing deprivation, fragmentation, exclusion, and resilience. This reconceptualization advances conceptual clarity, strengthens the validity of mental health research in low-resource settings, and informs interventions that simultaneously address structural risks and promote community assets. The case of Kampala demonstrates how participatory evidence can reshape the understanding of neighborhood effects with implications, for global mental health research and practice. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Recent findings suggest that long-term and heavy alcohol consumption can aggravate several pathological processes associated with AD, whereas the impact of light or moderate consumption remains uncertain. Excessive alcohol exposure impairs the structure and function of key brain regions involved in cognition, particularly the hippocampus, prefrontal cortex, amygdala, cerebellum, Basolateral amygdala (BLA), and hypothalamus. Several studies indicate that chronic alcohol consumption affects the brain by multiple mechanisms like increased oxidative stress, microglial activation, neuroinflammation, microtubule instability, tau hyperphosphorylation, and modified amyloid-β turnover. Disruption of cholinergic transmission further contributes to memory deficits and neuronal susceptibility. These alcohol-related alterations closely resemble core features of AD pathology and may accelerate disease progression. Although some epidemiological studies report the potential benefits of low alcohol intake, their interpretation is limited by inconsistent definitions of drinking patterns and the influence of confounding variables. Overall, current evidence supports a dose-dependent relationship in which alcoholism increases vulnerability to AD-related neurodegeneration. Reducing harmful alcohol use may therefore represent a practical approach to lowering long-term dementia risk. This review summarizes the current mechanisms of alcohol induced neuronal damage across different brain regions. Prolonged alcohol consumption accelerates cerebral aging by enhancing oxidative stress, neuroinflammation, disrupting tau protein degradations, and other neuronal damages that intersect with the pathogenesis of AD. Full article

Background/Objectives: Non-alcoholic steatohepatitis (NASH) is a progressive liver condition closely associated with gut microbial dysbiosis and hepatic metabolic abnormalities. Poria cocos polysaccharide (PCP), a bioactive component derived from the medicinal fungus Poria cocos, possesses hepatoprotective properties, yet the therapeutic mechanisms of PCP in NASH, particularly those involving microbial and metabolic regulation, remain incompletely elucidated. This study aimed to investigate the effects of PCP on improving NASH and explore its mechanisms related to prebiotic activity. Methods: Mice were induced to develop NASH using a Western diet, followed by PCP intervention for 12 weeks. Hepatic function, including liver enzymes and lipids, glucose metabolism, and liver histopathological changes, was assessed. Fatigue and neurobehavioral alterations were evaluated via rotarod, open field, and tail suspension tests. Hepatic pro-inflammatory cytokines were measured using RT-qPCR. Gut microbiota were analyzed through 16S RNA gene sequencing, and metabolites of liver tissue were analyzed through untargeted metabolomics. Results: PCP decreased blood glucose and hepatic lipid levels in NASH mice, alleviating liver inflammation, ballooning degeneration, and fibrosis. It also improved fatigue-like performance on rotarod test and reduced the hepatic expression of IL-6, IL-1β, TNF-α, and IL-18. Microbiota analysis revealed that PCP restored gut microbial diversity, promoted the growth of beneficial taxa such as Alistipes and Butyricoccaceae_UCG-009, and inhibited harmful bacteria, including Romboutsia ilealis. Liver metabolomics showed that PCP normalized key metabolites like taurocholate and regulated taurine and hypotaurine metabolism, which were correlated with reduced inflammation, fatigue-like performance, and fibrosis. Conclusions: PCP, as a promising edible agent, alleviates hepatic damage, metabolic disorders, and fatigue-like performance on rotarod test in NASH mice, probably by reshaping gut microbiota and modulating hepatic taurine and hypotaurine metabolism. Full article

Young adulthood is a critical period for preventing alcohol-related harm, as heavy drinking and mental health challenges often peak, yet preventive counseling remains underused. This study examined associations between depressive and anxious symptoms and receipt of alcohol-related advice from healthcare providers among U.S. young adults aged 18–29, with attention to differences across sexual identity groups. Data were drawn from the 2022 National Health Interview Survey, with a final analytic sample of participants aged 18–29 (N = 2256). Weighted logistic regressions estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Overall, 49.0% of participants reported receiving alcohol advice. Odds were higher among lesbian/gay participants (aOR = 1.81; 95% CI: 1.03–3.18) and those with severe anxiety symptoms (aOR = 2.10; 95% CI: 1.11–3.94). Interaction effects indicated disparities by sexual identity, with plurisexual males showing the lowest predicted probability of receiving advice when meeting the clinical threshold for anxiety (20.9% vs. 62.4% for monosexual individuals). The findings underscore the need to strengthen alcohol-related counseling and integrate mental health screening in preventive care for diverse young adult populations. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as steatotic liver disease with at least one cardiometabolic risk factor, in the absence of harmful alcohol intake, and includes a spectrum of conditions. These range from isolated liver steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma. Patients with MASLD and type 2 diabetes are at increased risk of developing MASH and significant/advanced fibrosis. The severity of fibrosis is a key determinant of long-term prognosis in MASLD. The most recent AASLD and EASL-EASD-EASO Guidelines on the Management of MASLD recommend a step-by-step approach to identify patients at higher risk of fibrotic progression. Recent epidemiological trends highlight the socioeconomic impact of MASLD and MASH, particularly in middle- and low-income countries. Given the high cost of new targeted therapies, implementing effective treatment strategies in low-resource settings is essential in managing MASLD and MASH patients. Pioglitazone is an oral antidiabetic agent of the thiazolidinedione class that targets peroxisome proliferator-activated receptors activated by fatty acids and derivatives or pharmacological agonists and involved in lipid metabolism, cell differentiation, and inflammation. Pioglitazone treatment is a potential cost-effective option, particularly for low-resource settings. This review examines recent epidemiological trends in MASLD and MASH, outlines the mechanisms of action of pioglitazone with an emphasis on its role in improving liver fibrosis, and summarizes clinical studies on fibrosis evaluation during pioglitazone treatment. The literature search focused on English-language studies from the past two years in the PubMed database. Full article

Background: Recent advances in childhood cancer treatment and increased survival rates have led to a growing number of adolescents and young adults (AYAs) who are survivors of childhood cancer (CCSs). This study aimed to examine health status, health-related quality of life (HRQoL), and social outcomes in AYA CCSs. Methods: Sixty-two AYAs who were CCSs (treated within the same tertiary Pediatric Hematology–Oncology Department in Crete, Greece) were enrolled in the study. Self-reported HRQoL was assessed using the Short-Form Health Survey (SF-36). Sixty-five never-ill peers constituted the control group. Results: CCSs reach adolescence and young adulthood without significant deviations in HRQoL from their healthy peers. The presence and severity of late effects were significantly correlated with lower scores in physical health. The cancer type seems to play a pivotal role: Langerhans cell histiocytosis survivors displayed significantly lower scores in mental health, and brain tumor survivors scored substantially lower scores in physical functioning. Acute lymphoblastic leukemia survivors reported the highest scores in mental health. Age at diagnosis of neoplasia was negatively correlated with physical functioning. No significant sex differences were identified. Adherence to multiple healthy lifestyle behaviors (regular exercise, abstaining from alcohol consumption and smoking, and using sun protection) and active employment were correlated with significantly higher scores in mental health. Conclusions: Appropriate therapy and regular follow-up after treatment have led to improved clinical and social outcomes, as assessed by CCSs. More efforts are needed to increase awareness of avoiding harmful behaviors that raise the risk of late effects in this specific group. Full article