The brain-predicted age difference (brain-PAD) is considered a marker of neurodegeneration in people with multiple sclerosis (pwMS) and is associated with greater disability and cognitive impairment. However, the impact of disease-modifying factors (DMFs) on brain-PAD remains unknown, as does the extent to which their effect on disability and cognition is mediated through brain-PAD. The goal of this study was to investigate this in pwMS using a same-age cohort to eliminate calendar age as a confounding factor. Brain age was determined using brainageR from 3-dimensional T1-weighted MRI scans, and brain-PAD was calculated as the difference between predicted and chronological age. Disability was evaluated with the Expanded Disability Status Scale (EDSS), the 9-hole peg test (9HPT), and timed 25-foot walk test (T25FWT). Cognitive function was assessed using the Minimal Assessment of Cognitive Function in MS battery and converted to Z-scores. DMFs included lifetime smoking, alcohol consumption, physical activity, diet, leisure, and educational level, as well as body mass index (BMI) at 18 years. The effect of DMFs on brain-PAD was examined using linear regression, adjusting for sex. Mediation analyses were performed to investigate to what extent brain-PAD is a mediator of DMF effects on disability and cognition. The study included 117 healthy controls (mean age 52.8 ± 1.1 years, 74.3% female) and 242 pwMS (mean age 52.8 ± 0.9 years, 70.6% female), with a median disease duration of 15.2 years (interquartile range [IQR] 8.2-24.5) and a median EDSS score of 3.5 (IQR 2.5-4.0). Smoking (β = 0.20, p = 0.002), alcohol consumption (β = 0.18, p = 0.007), and BMI at 18 years (β = 0.15, p = 0.021) were associated with a higher brain-PAD, whereas higher physical activity (β = -0.13, p = 0.041) was linked to a lower brain-PAD. Mediation analysis demonstrated an indirect effect of smoking and alcohol on EDSS score (β = 0.039, p = 0.003; β = 0.039, p = 0.009), 9HPT (β = 0.057, p < 0.0001; β = 0.055, p = 0.004), T25FWT score (β = 0.045, p = 0.009; β = 0.044, p = 0.013), and cognitive performance (β = -0.066, p = 0.0004; β = -0.060, p = 0.016). Physical activity demonstrated an indirect effect of better performance on EDSS score (β = -0.027, p = 0.032) and cognitive performance (β = 0.042, p = 0.034). DMFs unrelated to MS, particularly smoking, alcohol use, and BMI at 18 years, accelerate brain aging. Brain-PAD mediates these effects and contributes to worsening disability and cognition, underscoring the potential of lifestyle interventions to mitigate neurodegeneration and preserve function in pwMS.

Alcohol is embedded in social life; however, alcohol control policies remain insufficiently enforced in Korea. Comprehensive evidence linking alcohol intake to disease and mortality is limited. This study estimated associations between alcohol consumption in Korea and risks of morbidity and mortality for 39 diseases and conditions. Retrospective cohort study using National Health Insurance Service (NHIS) data linked with death records from Statistics Korea. Population-based customized NHIS data, a mandatory single-payer system covering the entire Korean population, between 2006 and 2022. 6 214 569 participants (57.36% males) aged ≥20 years who underwent two general health examinations during 2006-2009 and were disease-free at baseline. Alcohol consumption was categorized by drinking status and daily pure alcohol intake (seven levels in 10 g/day increments), averaged across two measurements (2006-2007, 2008-2009). The reference group comprised current abstainers at both examinations. Outcomes included incident cases, all-cause and cause-specific deaths for 39 diseases, followed through 2022. Covariates included age, income, body mass index, smoking, physical activity and comorbidities. Hazard ratios and lifetime risks were estimated. At baseline, 79.3% of men and 39.0% of women were current drinkers. For cancer (450 738 cases), alcohol consumption was statistically significantly associated with increased risks of seven cancers in men and four in women. On average, lifetime incidence rate of alcohol-related cancers was 9.96% [95% confidence interval (CI) = 9.83-10.09] among current drinkers and 7.88% (95% CI = 7.73-8.03) among current abstainers in men (2.1% difference). Among women, corresponding rates were 10.28% (95% CI = 10.07-10.50) vs. 9.89% (95% CI = 9.78-9.99) (0.4% difference). For diseases of the circulatory system (2 998 902 cases of ten subtypes), alcohol consumption was associated with increased risks of eight subtypes in men and two in women. In contrast, J- or U-shaped association was observed for ischemic heart diseases, heart failure (men) and cardiac arrhythmias (women), which was no longer evident in analyses using light drinking as the reference. Additionally, statistically significant positive association was exhibited in 14 other conditions among men and six among women. For mortality, alcohol consumption was associated with a lifetime incidence rate of death from any cause of 41.70% (95% CI = 41.40-42.01), compared with 39.06% (95% CI = 38.69-39.43) among current abstainers in men, a 2.6% difference. It was also associated with mortality from 15 diseases in men and nine in women. Alcohol consumption in Korea appears to be associated with numerous diseases and conditions, highlighting the need for strengthened national alcohol control policies. Protective effects of alcohol on cardiac health should be interpreted with caution.

Chronic pain and substance use disorders frequently co-occur and may share general addiction-related and substance-specific genetic pathways. Additionally, substance consumption and problematic use may differ in their genetic associations with pain subtypes. We applied genomic structural equation modeling to assess shared genetic and neurological enrichment between general and musculoskeletal-specific chronic pain to general addiction liability, substance use disorder-specific risk and substance use. Cross-trait genomic structural equation modeling using genome-wide association study (GWAS) summary statistics from large-scale global consortia. Data were aggregated from international research collaborations and biobanks in the United States and Europe. Participants were individuals (n = 63 982 to 2 428 851) with European-like ancestry from population-based and clinical cohorts. We analyzed a General Chronic Pain factor from 24 chronic pain GWASs and a Musculoskeletal-specific Pain factor from 11 overlapping conditions. We constructed an Addiction factor from GWASs of alcohol, tobacco, cannabis and opioid use disorders, and partitioned out substance-specific genetic risk. We used alcohol and smoking consumption GWASs to distinguish use from problematic use. We applied molecular neurological annotations to assess brain cell type enrichment in shared genetic effects. The Addiction factor was genetically correlated with General Chronic Pain [genetic correlation (rg)_ = 0.448, false discovery rate (FDR)-corrected P < 0.001, 95% confidence interval (95% CI) = 0.40, 0.49], but not with Musculoskeletal-specific Pain (rg = 0.001, FDR-corrected P = 0.998, 95% CI = -0.07 to 0.07). Controlling for Addiction, General Pain had substance-specific associations: negative correlations with Problematic Alcohol Use (rg= -0.155, FDR-corrected P = 0.049, 95% CI = -0.28 to -0.02) and Alcohol Frequency (rg = -0.334, FDR-corrected P < 0.001, 95% CI = -0.46 to -0.21), and a positive correlation with Cigarette Frequency (rg = 0.274, FDR-corrected P < 0.001, 95% CI = 0.21, 0.34). Musculoskeletal-specific Pain positively associated with Tobacco Use Disorder (rg=0.186, FDR-corrected P = 0.020, 95% CI = 0.05, 0.32) and Alcohol Frequency (rg = 0.161, FDR-corrected P = 0.049, 95% CI = 0.02, 0.30). General Pain related to Cannabis Use Disorder and Opioid Use Disorder entirely through the Addiction factor. Shared genetic components were enriched in excitatory and inhibitory neurons, glia and endothelial cells. General chronic pain appears to share substantial genetic overlap and neuronal enrichment with addiction risk and shows distinct associations with problematic alcohol use, alcohol consumption and cigarette use, reflecting both a broad transdiagnostic mechanism as well as substance-specific paths. In contrast, musculoskeletal-specific pain appears to be more narrowly linked to tobacco use disorder and alcohol use frequency, but not to general addiction liability.

Perceptions and experiential strategies of alcohol use in emerging adults with type 1 diabetes: A qualitative study.

Evidence from the World Health Organization shows that measures exist to regulate both recorded and unrecorded alcohol. In Thailand, comprehensive evidence on the amount of unrecorded alcohol consumed is lacking. This study aims to quantify the prevalence of unrecorded alcohol consumption and determine associated factors. A cross-sectional survey was conducted from July to August 2022. Thai residents aged 15 years or above were recruited from 15 provinces, including Bangkok, using stratified multi-stage sampling. Types of unrecorded alcohol included surrogate, home-brewed, smuggled or industrially produced illegal and duty-free outlet products. Annual alcohol consumption was calculated by multiplying the daily quantity by the estimated number of drinking days. Among 3924 participants, unrecorded alcohol constituted 4.4% (95% CI 4.3-4.4) of the total alcohol consumption (10.9 million of 248.5 million litres/year). The annual unrecorded pure alcohol intake per current drinker was 2.2 L. Drinkers aged 45-59 years had the highest prevalence of unrecorded alcohol consumption (13.2%), while those aged 60 years and over had the largest share (10.0%). Consumption was higher in males (2.5 L/year) compared to females (0.5 L/year) and heavy episodic drinking individuals (3.2 L/year) compared to non-heavy episodic drinking individuals (0.9 L/year). Although middle-aged adults had the highest consumption rates, the greatest intensity of intake and, therefore, potential for harm, was seen among older-aged and heavy episodic drinking individuals. Given the risks of unknown ethanol concentrations and contaminants in unrecorded products, policymakers should prioritise high-intensity users over overall prevalence to better mitigate risks within Thailand's alcohol consumption profile.

Factors associated with chronic low back pain and central sensitization in office workers: a multidimensional analysis.

Joint Association of Healthy Behaviors and Grip Strength With All-Cause Mortality Among European Middle-Aged and Older Adults: A 16-Year Cohort.

Harmful alcohol consumption remains widespread among university students and is associated with numerous academic, social and health-related consequences. Peer-led approaches offer a promising strategy to reduce risky drinking in this population. This study evaluated the long-term effects of a peer-led Brief Alcohol Screening and Intervention for College Students (BASICS) program. A parallel two-group randomised controlled trial with a follow-up period of 12 months was conducted. The study took place at a university in Spain. A total of 308 undergraduate students who had engaged in at least one episode of heavy drinking in the previous month were randomly assigned to either the intervention group (n = 154) or the control group (n = 154). The intervention group received a single individual session of the peer-delivered BASICS program. The control group received no intervention during the study period. The primary outcome was the number of alcoholic drinks consumed during a typical week at the 12-month follow-up. Secondary outcomes included weekly drinking at one month, as well as weekend drinking, drinks on the heaviest occasion, binge drinking episodes, peak blood alcohol concentration during a typical week and on the heaviest occasion, alcohol-related consequences, motivation to reduce alcohol use and self-efficacy, all of which were assessed at both 1 and 12 months. At the primary 12-month follow-up, statistically significant between-group differences were observed for all nine measured outcomes. For the primary outcome, the mean weekly alcohol consumption was 8.93 drinks [95% confidence interval (CI) = 7.7-10.2] in the intervention group and 12.35 drinks (95% CI = 11.1-13.6) in the control group. The between-group difference was 3.42 drinks (95% CI = 1.66-5.18), indicating lower consumption in the intervention group. Among the secondary outcomes, statistically significant differences were also observed for weekend drinking (3.08 drinks, 95% CI = 1.59-4.56), drinks on the heaviest occasion (3.27 drinks, 95% CI = 1.79-4.76), binge drinking frequency (0.93 episodes, 95% CI = 0.54-1.32) and alcohol-related consequences (3.28 points, 95% CI = 1.74-4.82). Among Spanish college students who had engaged in at least one episode of heavy drinking in the previous month, a single peer-led Brief Alcohol Screening and Intervention for College Students (BASICS) session produced sustained improvements in alcohol use, related consequences, and psychological mediators up to 12 months post-intervention.

The emerging role of FGF21 in alcohol consumption and dependence: mechanisms and therapeutic prospects.

Sake, a fermented alcoholic beverage made from rice and Aspergillus oryzae through microbial fermentation, contains thiol compounds that are the primary source of its distinctive sweet aroma. However, to date, there has been no report on the detection of chiral thiol compounds in sake. This study introduces a novel UHPLC-HRMS method utilizing the (R)-(5-(3-isothiocyanatopyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium (NCS-OTPP) chiral mass spectrometry probe for the simultaneous detection of five DL-thiol compounds in sake. Separation was achieved using a YMC Triart C18 column (2.0 × 150 mm, 1.9 μm), employing an isocratic elution method to isolate DD/LL-GSH, γ-L-Glu-L-Cys, DL-Cys, DL-Hcy, and DL-Ac-Cys. The method demonstrated excellent linearity (R2 ≥ 0.9992), intraday precision (0.43%-13.18%), and an average recovery rate of 91.62%-110.40%. A comparative analysis of DL-thiol compound content in seven different types of sake from various countries and manufacturers revealed the presence of five chiral thiol compounds-LL-GSH, γ-L-Glu-L-Cys, DL-Cys, DL-Hcy, and L-Ac-Cys-across Japanese and Korean sake, with L-Cys being the most abundant and D-Ac-Cys the least. Notably, γ-L-Glu-L-Cys was detected only in two types of Korean sake and absent in Japanese sake. Additionally, the study investigated the metabolic kinetics of chiral thiol compounds in human urinary specimens after alcohol ingestion, constructing a metabolic fitting curve. The peak concentrations of DL-Cys, DL-Hcy, and LL-GSH were attained 15 min following consumption, with slow clearance, returning to baseline at 60 min. The metabolic fitting curve effectively captures the dynamic changes in urinary metabolism. This research presents a new method for detecting chiral thiol compounds in sake and monitoring urinary metabolism after alcohol consumption.

The aftermath of alcohol misuse: Linking cellular damage, suboptimal micronutrient nutrition, and organ dysfunction.

Alcohol consumption is a common risk factor for esophageal squamous cell carcinoma (ESCC) and hepatic fibrosis. Mac-2 binding protein glycosylated isomer (M2BPGi), a sensitive marker of fibrosis, may predict postoperative skeletal muscle loss by reflecting the metabolic link between liver function and muscle maintenance. Eighty-nine patients with ESCC undergoing esophagectomy (June 2021-July 2024) with alcohol use and pretherapeutic M2BPGi levels were included; the cutoff was 0.66. Muscle mass was assessed by bioelectrical impedance analysis. The study population was stratified by M2BPGi levels into low (n = 59) and high (n = 30) groups. No significant differences were observed in sex, clinical stage, preoperative skeletal muscle mass, surgical approach, or intraoperative fluid balance. The high M2BPGi group showed lower preoperative albumin levels (4.2 vs. 4.0g/dL, p = 0.01) and higher CRP (0.1 vs. 0.4mg/dL, p < 0.01) and ICG R15 values (9.2% vs. 12.8%, p = 0.04). Although there was no difference in the incidence of complications, the decrease in skeletal muscle mass at 3months was significantly greater in the high M2BPGi group (- 7.6% vs. - 12.0%, p = 0.02). In the propensity score-matched cohort (low n = 40; high n = 20), the high M2BPGi group showed significantly greater muscle loss at 3months (- 7.5% vs. - 12.6%, p = 0.04) and a trend toward longer hospital stays (22 vs. 25.5days, p = 0.06). High pretherapeutic M2BPGi levels are independently associated with postoperative skeletal muscle loss at 3months.

Renal cell carcinoma (RCC) accounts for more than 90% of kidney malignancies worldwide. Matrix metalloproteinase-2 (MMP-2) has been reported to be dysregulated in multiple cancers. However, the relationship between MMP-2 genetic polymorphisms and RCC risk has rarely been investigated. This study aimed to evaluate the associations of two promoter polymorphisms, MMP-2 rs243865 and rs2285053, with RCC susceptibility in a Taiwanese population. A hospital-based case-control study was conducted including 118 RCC patients and 590 cancer-free controls. Genotyping of MMP-2 rs243865 and rs2285053 was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A significant association was observed between MMP-2 rs243865 and RCC susceptibility (p for trend=0.0077). Compared to the CC genotype, individuals carrying the TT genotype exhibited a markedly increased risk of RCC (OR=4.29, 95%CI=1.56-11.83, p=0.0069), whereas the CT genotype showed no significant effect (OR=1.31, 95%CI=0.80-2.16, p=0.3530). The T allele was also associated with elevated RCC risk (OR=1.71, 95%CI=1.15-2.54, p=0.0101). In contrast, rs2285053 showed no significant association with RCC. Stratified analyses revealed significant MMP-2 rs243865 genotype differences among subgroups defined by smoking, alcohol consumption, and hypertension status (p=0.0175, 0.0173, and 0.0063, respectively). MMP-2 rs243865, particularly the TT genotype, may serve as a genetic susceptibility marker for RCC and may interact with lifestyle and clinical factors including smoking, alcohol drinking, and hypertension. Further large-scale studies are warranted to validate these observations and clarify the biological mechanisms underlying MMP-2-mediated RCC carcinogenesis.

Addiction-related behaviors, such as loss of control eating (LOC), cigarette smoking and alcohol consumption, have been associated with high body mass index (BMI). This study aimed to assess genetic and environmental contributions to these associations over time. A longitudinal twin study using data from waves 2 and 3 of the Center on Antisocial Drug Dependence study, employing additive genetic (A), shared environmental (C), nonshared environmental (E) influences and cross-lagged models. Colorado, USA. The sample included 764 male and 997 female same-sex twins. BMI was calculated using self-reported height and weight. LOC was self-reported. Cigarettes smoked per day (CPD) and drinks per week (DPW) were assessed during interviews. We conducted three cross-lagged models: LOC and BMI in males, LOC and BMI in females and CPD and BMI in females, after excluding small phenotypic correlations (|r| < 0.10). Trait stability over time was largely attributable to genetic factors, accounting for 62% of the variance in BMI (both sexes), 11% in LOC (males), 18% in LOC (females) and 56% in CPD (females) at wave 3. Residual effects were mostly from nonshared environmental factors, accounting for 38% of the variance in BMI (both sexes), 76% of LOC (females), 71% of LOC (males) and 44% of CPD (females) at wave 3. A small but statistically significant cross-lagged effect occurred from wave 2 BMI to wave 3 LOC, explaining 12% (males) and 3% (females) of the variance in wave 3 LOC, with genetic factors accounting for most of this effect. No cross-lagged effects emerged from LOC or CPD to BMI. Genetic factors contributing to higher body mass index at an earlier age may also increase the risk of developing loss of control eating later in life, highlighting the importance of early weight-related interventions to prevent the onset of disordered eating behaviors.

Unpacking adverse childhood experiences: Examining the role of ACEs domains in mental health and alcohol consumption in college students.

Both bone and muscle function decline with age and are anatomically and functionally related. However, whether and to what extent muscle function (ie, strength and power) may predict longitudinal changes in bone microarchitecture and strength is unclear. The Osteoporotic Fractures in Men (MrOS) Study included assessments of peak jump power (W) from a force plate and maximum grip strength (kg) from a dynamometer, both normalized to body weight at visit 4 (2014-2016). We investigated the associations of jump power and grip strength with annual percent change in volumetric BMD, microarchitecture, and strength at the distal tibia (DT) and radius (DR) from HR-pQCT between visit 4 and visit 5 (2020-2022; 6.2 ± 0.6yr follow-up; N = 225; age 82.8 ± 3.0yr; 89% White). Mean jump power was 22.9 ± 5.6W/kg and grip strength was 0.49 ± 0.1kg/kg. During follow-up (median [IQR]), failure load (-0.88 [-1.71, -0.31]%), total BMD (-0.57 [-1.12, -0.18]%), cortical BMD (-1.24 [-2.03, -0.67]%), trabecular BMD (-0.05 [-0.47, 0.20]%), and trabecular thickness (-0.37 [-0.64, -0.12]%) declined at the DT, while at the DR, failure load (-1.02 [-2.19, -0.04]%), total BMD (-0.64 [-1.20, -0.18]%), and cortical BMD (-1.38 [-2.15, -0.71]%) declined (all p ≤ .05). Significant increases were observed for total area at both skeletal sites (DT: 0.04 [0.01, 0.08]%; DR: 0.07[-0.06, 0.16]%; both p ≤ .05). Multivariable linear regression models were adjusted for age, White race, clinic site, respective HR-pQCT initial values, percentage weight change, alcohol consumption, medication count, chronic disease history, falls, and hip pain. Higher grip strength was significantly associated with a smaller percent/year increase in total area at the DT (p ≤ .05) but not at the DR. Neither jump power nor grip strength was associated with change in failure load, BMD, or trabecular thickness at either skeletal site. Associations between grip strength and changes in tibial bone geometry provide insight into potential mechanisms for bone loss and targets for musculoskeletal interventions to reduce fracture risk.

Rectal cancer is one of the most common cancers in the Western world. The path toward personalized treatments in medicine includes further determination of sex-associated differences. The objective of this study is to explore sex-related differences in the outcome of rectal surgery. All patients in the German StuDoQ|Rectum Registry who underwent rectal cancer surgery between 2013 and 2023 were included. Propensity score matching was performed to account for comorbidities and factors influencing the surgery-associated outcome. Mediation analysis was performed to show the direct effect of sex on surgical and general complications. The main outcomes were morbidity and mortality. The total cohort included 19,664 patients (36.9% women), of whom 15,011 patients were included in this retrospective study. After propensity score matching, 10,362 patients were analyzed. Compared with men, women had fewer surgical complications (eg, anastomotic leakage, 6.4% vs 12.0%, p < 0.001), lower rates of ileus (2.3% vs 5.7%, p < 0.001), and fewer general complications (eg, pneumonia (1.5% vs 3.6%, p < 0.001). In the propensity score-matched cohort (n = 10,362), female patients had significantly lower odds of experiencing any complication (Clavien-Dindo grade I-V vs 0) in a matched conditional logistic regression analysis (adjusted OR = 0.614; 95% CI, 0.566-0.666). Despite the strong influence of anastomotic leakage on morbidity, the protective effect of female sex was an independent factor for most complications in this cohort in mediation analysis. Our study is limited by its retrospective design and the lack of some information, such as preoperative nicotine and alcohol consumption or the heterogenous definitions of some conditions, such as pelvic abscesses. In this retrospective multicenter registry study, female sex was associated with favorable outcomes after surgery for rectal cancer. See Video Abstract . ANTECEDENTES:El cáncer de recto es uno de los cánceres más comunes en el mundo occidental. El camino hacia los tratamientos personalizados en medicina incluye una mayor determinación de las diferencias asociadas al sexo.OBJETIVO:El objetivo del estudio es explorar las diferencias relacionadas con el sexo en los resultados de la cirugía rectal.ÁMBITO:Se incluyó a todos los pacientes del Registro alemán StuDoQ|Rectum que se sometieron a cirugía rectal por cáncer de recto entre 2013 y 2023.DISEÑO:Se realizó un emparejamiento por puntuación de propensión para tener en cuenta las comorbilidades y los factores que influyen en el resultado asociado a la cirugía. Se llevó a cabo un análisis de mediación para mostrar el efecto directo del sexo sobre las complicaciones quirúrgicas y generales.PRINCIPALES MEDIDAS DE RESULTADO:Los principales resultados son la morbilidad y la mortalidad.PACIENTES:La cohorte total incluyó a 19.664 pacientes (36,9% mujeres), y en este estudio retrospectivo se incluyó a 15.011 pacientes. Tras el emparejamiento por puntuación de propensión, se analizaron 10.362 pacientes.RESULTADOS:Las mujeres presentaron menos complicaciones quirúrgicas (p. ej., fuga anastomótica: 6,4% frente a 12,0%; p < 0,001; íleo: 2,3% frente a 5,7%; p < 0,001) y menos complicaciones generales (p. ej., neumonía: 1,5% frente a 3,6%; p < 0,001). En la cohorte emparejada por puntuación de propensión (n = 10.362), las mujeres tuvieron una probabilidad significativamente menor de experimentar cualquier complicación (Clavien-Dindo I-V frente a 0) en el análisis de regresión logística condicional emparejada (odds ratio ajustado = 0,614; IC del 95%: 0,566-0,666). A pesar de la fuerte influencia de la fuga anastomótica (AL) en la morbilidad, el efecto positivo del sexo femenino constituyó un factor independiente para la mayoría de las complicaciones en esta cohorte, según el análisis de mediación.LIMITACIONES:Nuestro estudio se ve limitado por su diseño retrospectivo y por la falta de cierta información, como el consumo preoperatorio de nicotina y alcohol, o la definición heterogénea de ciertas condiciones (p. ej., los abscesos pélvicos).CONCLUSIONES:En este estudio de registro multicéntrico y retrospectivo, el sexo femenino se asoció con resultados favorables tras la cirugía por cáncer de recto. (AI-generated translation ).

Interest in managing alcohol-related risks through temporary abstinence challenges has grown significantly. Studies on abstinence challenges in the general population show improvements in for example mental health, blood pressure, insulin resistance and alcohol consumption, but studies in clinical samples are lacking, including qualitative research on patients' perspectives on such a clinical intervention. This study aimed to explore the patients' experiences of a sober month before initiating psychological treatment for controlled drinking. A qualitative interview study (n = 14) was conducted at a specialised addiction clinic in Stockholm, Sweden. Participants were recruited within a randomised controlled trial examining a sober month as an adjunct to psychological treatment for controlled drinking. Data were analysed with applied thematic analysis. Four themes were identified: (i) Breaking the cycle of habitual drinking; (ii) Regaining control; (iii) A sober month made abstinence a more prominent part of goals; and (iv) A failed attempt at sobriety as a setback to change. A sober month was perceived as positive for most patients and became a challenge that increased the sense of control and perceived ability to abstain. The benefits of the sober month made participants consider more restrictive goals or abstinence over time. Not being able to abstain made participants less motivated and reconsidered controlled drinking as their goal. Having a sober month can increase awareness of the ability to abstain and guide patients toward lower consumption goals. To reduce the risks of negative consequences, it is important to identify and support those who do not manage to abstain. ClinicalTrials.gov identifier: 47033189.

Early detection of gastric dysplastic lesions and early gastric cancer (EGC) is crucial to enable prompt treatments, such as endoscopic submucosal dissection (ESD). Understanding the distribution and characteristics of these lesions can enhance the efficiency of endoscopic examinations. This study aimed to analyze the locations and characteristics of dysplasia and EGCs in the stomach. Retrospective study reviewing pathologically diagnosed gastric dysplasia and EGCs treated by ESD. Lesions were grouped by location (proximal-cardia, fundus, and body; distal-incisura and antrum) and compared regarding several clinicopathological variables. A predictive model - Search At the Top (SAT) score - was created using three pre-endoscopic variables: male sex (2 points), excessive alcohol consumption (1 point), and smoking (1 point). The score was evaluated for its ability to predict proximal lesions. A total of 215 patients were included (66.5% male; mean age 68 ± 8 years), with 225 lesions analyzed: 50.7% low-grade dysplasia, 30.7% high-grade dysplasia, and 18.6% adenocarcinoma. Most lesions were located in the distal stomach (73.3%) and along the lesser curvature (39.6%).Proximal lesions were more often associated to male sex (P = 0.001), younger age (P = 0.027), alcohol consumption (P = 0.003), and smoking (P = 0.008).The SAT-score showed moderate discriminative performance (area under the curve = 0.674) and identified high-risk patients (score ≥3) with 3.5-fold increased odds of having proximal lesions (odds ratio = 3.459; P < 0.001). Most gastric dysplastic lesions and EGCs were located in the distal stomach and along the lesser curvature. Proximal gastric lesions were more frequent in younger male patients with alcohol and tobacco exposure. These location-specific characteristics can enhance the diagnostic performance of endoscopic screening and surveillance, potentially leading to improved patient outcomes.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and often arises in cirrhosis cases. Current surveillance methods, including ultrasonography and α-fetoprotein, have limited sensitivity for early detection. Blood metabolomics may improve HCC risk prediction. We aimed to identify pre-diagnostic plasma metabolites associated with HCC risk and evaluate whether cirrhosis-related metabolites enhance prediction beyond established risk factors in a multiethnic population. We analyzed data from a nested case-control study with pre-diagnostic blood samples in the Multiethnic Cohort, including 240 HCC cases, 151 cirrhosis cases, and individually matched controls. Metabolome-wide association studies and pathway enrichment analyses were performed, followed by feature selection in the cirrhosis samples to construct HCC prediction models. Of 294 metabolites analyzed, 53 were significantly associated with HCC after false discovery rate correction (odds ratios: 0.25-3.93). Pathway analyses highlighted perturbations in lipid and amino acid metabolism. Two cirrhosis-associated metabolites, glutamate and glycochenodeoxycholate, were consistently selected and improved HCC prediction. Adding these metabolites to known risk factors (age, sex, race/ethnicity, study area, BMI, smoking, alcohol consumption, and diabetes) increased the AUC from 0.64 to 0.73 (P < 0.001). Pre-diagnostic metabolomic profiling revealed metabolic alterations linked to HCC risk, emphasizing dysregulated amino acid and bile acid pathways within the cirrhosis context. Glutamate and glycochenodeoxycholate improved HCC risk prediction beyond established factors, supporting biologically plausible links between hepatic metabolic dysfunction and hepatocarcinogenesis. These findings highlight the potential of metabolomic biomarkers to enhance surveillance and risk stratification among patients with cirrhosis.