Heavy Alcohol Drinking Research Articles

Replicability in measures of attentional set-shifting task performance predicting chronic heavy drinking in rhesus monkeys.

This study was designed to replicate and extend a previous report that the increase in performance of an attentional set-shifting task (ASST) in rhesus monkeys predicted their future alcohol drinking status as a heavy drinker (HD) or non-heavy drinker (NHD). A cohort of 6 young adult male monkeys was trained and tested under the same ASST and then underwent a alcohol self-administration protocol that maintained open-access (22 hours/day) choice of alcohol or water 7 days/week for approximately 6 months. The average improvement in performance in the ASST, as measured by a performance index, was replicated in the cohort of 6 monkeys when compared to the increase in the task performance in a previous cohort of 9 male monkeys. The alcohol self-administration protocol was then used to determine the drinking status (HD: n=4 or NHD: n=2) of the replicate cohort, which was accurately predicted by the performance on the ASST. Finally, individuals from both cohorts could be combined based on future drinking status of HD (n=8) or NHD (n=7), and the association with pre-alcohol ASST performance remained. Specifically, monkeys that had lower rates of PI improvement were more likely to become HDs. To our knowledge, this is the first study to replicate that deficits in the set-shifting performance can predict chronic heavy alcohol drinking in primates.

Dose–response relationships of accelerometer‐measured sedentary behaviour and physical activity with non‐alcoholic fatty liver disease

Although a few studies have confirmed the association of accelerometer-measured sedentary behaviour (SB) and physical activity (PA) with non-alcoholic fatty liver disease (NAFLD), PA intensity and co-dependent daily time-use of movement behaviours are yet to be studied. To cross-sectionally examine the dose-response relationship between accelerometer-measured SB or PA and NAFLD using cubic spline analysis and the interdependence of movement behaviours over 24hours with compositional data analysis. Data were obtained between May 2017 and February 2020 from 1914 people who were not heavy alcohol drinkers using health check-ups at the Meiji Yasuda Shinjuku Medical Center, Tokyo. SB, light-intensity PA (LPA) and moderate- to vigorous-intensity PA (MVPA) were evaluated using a triaxial accelerometer. Fatty liver was diagnosed by ultrasonography. A multivariable-adjusted logistic model showed an inverse association between MVPA and NAFLD (odds ratio [OR] per 600 metabolic equivalents [MET]-min/week=0.85, 95% confidence interval [CI]=0.76-0.96). MVPA showed rapidly decreasing odds of NAFLD to approximately 1800 MET-min/week in cubic spline analysis and then a moderate decline. Although SB was significantly associated with NAFLD in a body mass index (BMI)-unadjusted model, it was not significant in a BMI-adjusted model. In the compositional isotemporal substitution, reallocating 60min/day of SB to MVPA decreased the odds of NAFLD by 22% (OR=0.78, 95% CI: 0.65-0.93), whereas reallocating 60min/day of MVPA to SB increased it by 69% (OR=1.69, 95% CI: 1.12-2.38). The inverse dose-response association between MVPA and NAFLD confirms increased MVPA as a target for the prevention of NAFLD.

CBD Alleviates Liver Injuries in Alcoholics With High-Fat High-Cholesterol Diet Through Regulating NLRP3 Inflammasome-Pyroptosis Pathway.

Alcohol abuse and high-fat diet–induced liver diseases have been the most prevalent chronic liver diseases and the leading reasons for liver transplantation around the world. Cannabidiol (CBD) is a botanical component extracted from marijuana plants without psychoactive impact. In our previous reports, we found that CBD can prevent fatty liver induced by Lieber–DeCarli ethanol diet or non-alcoholic fatty liver disease (NAFLD) induced by high-fat high-cholesterol diet. The current work is a further study on whether CBD can alleviate liver injuries induced by ethanol plus high-fat high-cholesterol diet (EHFD), which is a model simulating heavy alcohol drinkers in a Western diet. A mice liver injury model induced by EHFD for 8 weeks was applied to explore the protective properties of CBD and the underlying mechanisms. We found that CBD prevented liver steatosis and oxidative stress induced by EHFD. CBD treatment inhibited macrophage recruitment and suppressed activation of NFκB–NLRP3–pyroptosis pathway in mice livers. The hepatoprotective property of CBD in the current model might be a result of inhibition of inflammation via alleviating activation of the hepatic NFκB–NLRP3 inflammasome–pyroptosis pathway by CBD.

Esophageal cancer in relation to alcohol drinking and tobacco use among men in Kerala, India – Karunagappally cohort

BackgroundIn the Karunagappally cohort, esophageal cancer is the third most common cancer with an age-adjusted incidence rate of 6.2 per 100,000 person-years among men. The present study analyzed the risk of esophageal cancer in relation to alcohol drinking and tobacco use. MethodsThe study included 65,528 men aged 30–84 years in the Karunagappally cohort, India. ResultsPoisson regression analysis showed that alcohol drinking significantly increased (P = 0.027) the risk of esophageal cancer and the relative risk (RR) for current drinkers was 1.6, (95 % confidence interval (CI) = 1.1–2.3). The risk increased significantly in heavy alcohol drinkers (250 g of ethanol or above per day) (RR = 2.1, 95 % CI = 1.2–3.5) (P for trend = 0.014) and among current arrack consumers (RR = 1.8, 95 % CI = 0.99–3.29) (P for trend = 0.025). Current bidi and cigarette smokers showed an increase in the trend of cancer risk. A significantly higher risk was seen in those who had started smoking bidi before the age of 18 years, RR = 1.9 (95 % CI = 1.1–3.3) (P for trend = 0.044). Furthermore, increased RR for heavy bidi and cigarette smokers were 1.6 (95 % CI = 1.1–2.5) and 2.4 (95 % CI = 1.3–4.5), respectively. ConclusionTo the best of our knowledge, this is the first cohort study in India to report an increased esophageal cancer risk with respect to alcohol drinking.

The Patent Fact about Alcohol and Getting Stroke: A Case Control Study

Introduction: Globally 17.9 million people die each year from CVDs (Cardio Vascular Diseases) and 85% of all CVD deaths are due to heart attacks and strokes. According to the World Health Organization (WHO), 15 million people worldwide suffer from stroke every year and after ischemic heart disease, stroke is the second most leading cause of death. Objective: To study alcohol consumption as a risk factor in patients with acute strokes. Method: Case control study was conducted among 148 newly diagnosed cases of CT scan / MRI-confirmed stroke and 148 non-stroke controls attending the tertiary hospital of central Gujarat. Sample size calculation was done, assuming the power ratio of the number of controls same as numbers of cases i.e.,1:1, specifying values for two-sided confidence level=95% (error=5%), power of study=80%, odd ratio=2.15, percent of cases with exposure=82% and percent of controls with exposure=68%. Patients who are willing to participate in the study were included. The data were analyzed using the EPI INFO TM 7.0.8.0 software. Results: Out of the total 148 cases, 100 (67.56 per cent) were male and 48 (32.43 per cent) were female. The odds of getting stroke among alcoholic was two times more as compared to non-alcoholic patients. Heavy alcohol drinkers have a significant association. Conclusion: According to the study results male married patients who drank heavily had a higher risk of stroke than light/moderate alcoholics.

Genetic polymorphism of ALDH2 linkage to kidney function status of East Nusa Tenggara alcohol drinkers and cigarette smokers

Chronic kidney disease is a preventable high-burden disease. Several risk factors for impaired kidney function have been identified, including lifestyles, such as alcohol drinking and cigarette smoking. However, the evidence remains inconsistent. East Nusa Tenggara has the largest proportion of heavy alcohol drinking among all provinces in Indonesia. Genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) is related to alcohol drinking behavior through the inactivity of the ALDH2 enzyme, which leads to toxic acetaldehyde accumulation. This study aims to recognize the linkage of ALDH2 genotypes to kidney function among alcohol drinkers and cigarette smokers in East Nusa Tenggara. This study was a cross-sectional study of East Nusa Tenggara ethnicity, aged 18-60 years old. Demographic and lifestyle data were obtained via a questionnaire. DNA analysis was conducted with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Creatinine and BUN levels were measured with a chemistry analyzer. Afterward, the estimated glomerular filtration rate (eGFR) was calculated from creatinine value using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The association between kidney function status and alcohol drinking and cigarette smoking habits were analyzed using the chi-square test, then stratified based on genotype groups. Fifty-one subjects were included in this study, while the mean age was 26.33±1.33 years and the median age was 22 years. There were 37 (72.5%) alcohol drinkers and 14 (27.5%) non-drinkers; 28 (54,9%) cigarette smokers and 23 (45.1%) non-smokers. This study revealed no significant association between kidney function status and alcohol drinking habits. Cigarette smoking habits were inversely associated with eGFR decline and creatinine elevation in wild-type ALDH2 groups.

Transcriptional, Epigenetic, and Functional Reprogramming of Monocytes From Non-Human Primates Following Chronic Alcohol Drinking.

Chronic heavy drinking (CHD) of alcohol is a known risk factor for increased susceptibility to bacterial and viral infection as well as impaired wound healing. Evidence suggests that these defects are mediated by a dysregulated inflammatory response originating from myeloid cells, notably monocytes and macrophages, but the mechanisms remain poorly understood. Our ability to study CHD is impacted by the complexities of human drinking patterns and behavior as well as comorbidities and confounding risk factors for patients with alcohol use disorders. To overcome these challenges, we utilized a translational rhesus macaque model of voluntary ethanol self-administration that closely recapitulates human drinking patterns and chronicity. In this study, we examined the effects of CHD on blood monocytes in control and CHD female macaques after 12 months of daily ethanol consumption. While monocytes from CHD female macaques generated a hyper-inflammatory response to ex vivo LPS stimulation, their response to E. coli was dampened. In depth scRNA-Seq analysis of purified monocytes revealed significant shifts in classical monocyte subsets with accumulation of cells expressing markers of hypoxia (HIF1A) and inflammation (NFkB signaling pathway) in CHD macaques. The increased presence of monocyte subsets skewed towards inflammatory phenotypes was complemented by epigenetic analysis, which revealed higher accessibility of promoter regions that regulate genes involved in cytokine signaling pathways. Collectively, data presented in this manuscript demonstrate that CHD shifts classical monocyte subset composition and primes the monocytes towards a more hyper-inflammatory response to LPS, but compromised pathogen response.

Prevalence and correlates of sexual violence among adolescent girls and young women: findings from a cross-sectional study in a South African university

BackgroundEpidemiological data on the prevalence and factors associated with sexual violence is critical to understanding the magnitude of the problem and designing effective interventions. Drawing from cross-sectional data from a South African university, we examined the prevalence and correlates of sexual violence among adolescent girls and young women (AGYW).MethodsWe analysed data of 451 AGYW selected using stratified sampling. Sexual violence was defined as any sexual acts, and attempt to obtain sexual acts without consent. We used adjusted and unadjusted logistic regression models to examine the factors associated with exposure to sexual violence while controlling for relevant covariates.ResultsThe lifetime and past-year prevalence of sexual violence was 37.9% and 25.3%, respectively. A higher prevalence of sexual violence was reported by heavy episodic drinkers of alcohol (lifetime 48.4% and past year 34.0%), those who received insufficient financial support (lifetime 58.0% and past year 35.8%) compared to non-users of alcohol (lifetime 27.2% and past year 17.2%),) and those who received adequate financial support (lifetime 20.8% and past year 13.1%). AGYW who reported heavy episodic use of alcohol had higher odds of reporting lifetime (AOR: 1.86; 95% CI: 1.07–3.25) and past year (AOR: 2.03; 95% CI: 1.10–3.75) experience of sexual violence compared to non-users. However, individuals who received adequate family financial support were 76% and 65% less likely to report lifetime and past year experience of sexual violence than those who received inadequate family financial support. Also, AGYW who rated themselves as very religious were 80% and 75% less likely to report lifetime and past year experience of sexual violence compared to those who were not religious.ConclusionOur study shows that sexual violence affects a large proportion of girls, requiring intervention that not only focuses on increasing social support for survivors, facilitating reporting, and ensuring perpetrators are convicted, but also target alcohol use reduction and poverty alleviation.

Antagonism of Sigma-1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice.

Alcohol use disorder (AUD) is a complex psychiatric disease characterized by high alcohol intake as well as hyperkatifeia and hyperalgesia during withdrawal. A role for Sigma-1 receptors (Sig-1Rs) in the rewarding and reinforcing effects of alcohol has started to emerge in recent years, as rat studies have indicated that Sig-1R hyperactivity may result in excessive alcohol drinking. Sig-1R studies in mice are very scarce, and its potential role in alcohol-induced hyperalgesia is also unknown. In this study, we investigated the role of Sig-1R in alcohol drinking and associated hyperalgesia in male mice, using an intermittent access 2-bottle choice model of heavy drinking. The Sig-1R antagonist BD-1063 was found dose dependently to reduce both alcohol intake and preference, without affecting either water or sucrose intake, suggesting that the effects are specific for alcohol. Notably, the ability of BD-1063 to suppress ethanol intake correlated with the individual baseline levels of alcohol drinking, suggesting that the treatment was more efficacious in heavy drinking animals. In addition, BD-1063 reversed alcohol-induced hyperalgesia during withdrawal, assessed using an automatic Hargreaves test, without affecting thermal sensitivity in alcohol-naïve animals or locomotor activity in either group. These data show that Sig-1R antagonism dose-dependently reduced ethanol consumption in heavy drinking mice as well as its efficacy in reducing alcohol-induced hyperalgesia. These findings provide a foundation for the development of novel treatments for AUD and associated pain states.

Activation of hypothalamic oxytocin neurons reduces binge-like alcohol drinking through signaling at central oxytocin receptors.

Preclinical and clinical evidence suggests that exogenous administration of oxytocin (OT) may hold promise as a therapeutic strategy for reducing heavy alcohol drinking. However, it remains unknown whether these effects are mediated by stimulation of endogenous sources of OT and signaling at oxytocin receptors (OTR) in brain or in the periphery. To address this question, we employed a targeted chemogenetic approach to examine whether selective activation of OT-containing neurons in the paraventricular nucleus of the hypothalamus (PVN) alters alcohol consumption in a binge-like drinking ("Drinking-in-the-Dark"; DID) model. Adult male Oxt-IRES-Cre mice received bilateral infusion of a Cre-dependent virus containing an excitatory DREADD (AAV8-hSyn-DIO-hM3Dq-mCherry) or control virus (AAV8-hSyn-DIO-mCherry) into the PVN. Chemogenetic activation of PVNOT+ neurons following clozapine-N-oxide injection reduced binge-like alcohol drinking in a similar manner as systemic administration of the neuropeptide. Pretreatment with a brain-penetrant OTR antagonist (L-368,899) reversed this effect while systemic administration of a peripherally restricted OTR antagonist (Atosiban) did not alter reduced alcohol drinking following chemogenetic activation of PVNOT+ neurons. Altogether, these data are the first to demonstrate that targeted activation of hypothalamic (endogenous) OT reduces alcohol consumption, providing further evidence that this neuropeptide plays a role in regulation of alcohol self-administration behavior. Further, results indicate that the ability OT to reduce alcohol drinking is mediated by signaling at OTR in the brain.

Targeting the Gut Dysbiosis as a Treatment for Alcoholic Liver Disease

Alcohol Use Disorders (AUD) originates due to heavy and uncontrolled drinking of alcohol. It is one of the most prevalent mental disorders, which predominantly affects men globally. In the review article alcohol use disorders and several risk factors like gender, drinking habit, genetic differences, and obesity Hepatitis C virus has been described for the provocation of intestinal dysbiosis. Alcoholic Liver Disease (ALD) is a spectrum of diseases from steatohepatitis to Hepatocellular Carcinoma (HCC). Due to dysbiosis, there are microbial changes also taking place in the liver and it further worsens the conditions. Treatment involves treating gut dysbiosis and altered balance of the micro-organism. The treatment strategy of ALD may also involve a non-dietary approach or dietary approach or by microbiota modulation.

Prevalence of elevated liver transaminases and their relationship with alcohol use in people living with HIV on anti-retroviral therapy in Uganda.

Isoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude "regular and heavy alcohol drinkers" from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use. The Immune Suppression Syndrome Clinic of Mbarara, Uganda. We defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI). Among 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8-21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (p<0.01). In multivariable analyses, those currently using alcohol had higher odds of elevated transaminases compared to those abstaining (aOR 1.65, 95% CI 1.15-2.37) as did males compared to females (aOR 2.68, 95% CI 1.90-3.78). Pre-IPT elevated transaminases among PLWH receiving ART were common, similar to prior estimates, but severe elevations were rare. Current drinking and male sex were independently associated with elevated transaminases. Further research is needed to determine the implications of such transaminase elevations and alcohol use on providing IPT.

Heavy alcohol drinking and subclinical echocardiographic abnormalities of structure and function

ObjectiveThe aim of the study is to assess changes in heart structure and function associated with heavy alcohol use by comparing echocardiographic indices in a population-based sample to those in...

MO831PROGNOSIS OF HEPATOCELLULAR CARCINOMA IN HEMODIALYSIS PATIENTS

Abstract Background and Aims The aim of this study was to compare the prognosis of hepatocellular carcinoma (HCC) between dialysis and non-dialysis patients. Method In this retrospective observational study, we examined consecutive patients with naïve localized HCC, who were treated with radiofrequency ablation (RFA) between February 2000 and December 2017. The patients were categorized into two subgroups based on whether they were on maintenance dialysis (Dialysis Group, n=458) or not (Non-dialysis Group, n=13), and were followed until December 2019. The primary endpoint was overall survival using Kaplan-Meier analysis. As for propensity score matching, we matched 13 pairs of cases by using age, sex, Child-Pugh score, tumor size, number of tumors and HCV positivity. We also compared causes of death between the 2 groups. Results The study cohort were aged 69.9±9.1 years and included 328 male patients (70%). Hepatitis B was positive in 37 patients (7.9%), C in 322 (68.4%) and co-infection of HBV and HCV was detected in 3 (0.6%). Ninety-five (20.2%) were heavy alcohol drinkers. In Dialysis Group, patients were younger (p=0.004), total bilirubin, AST, ALT levels were significantly lower and PT level was significantly higher. In the entire cohort, overall survival was comparable between Dialysis Group and Non-dialysis Group (5-year survival rate 55.2% vs 52.7%, respectively; p =0.144). In the propensity score matching analysis, however, Dialysis Group showed significantly worse overall survival than Non-dialysis Group (5-year survival rate 52.7% vs 92.3%, respectively; p =0.018). During the observational period, 255 (54%) patients died. As for causes of death, liver-related death occurred in 44% in Dialysis Group and 67% in Non-dialysis Group, whereas cardiovascular death was 22% in Dialysis Group and 5% in Non-dialysis Group. Procedure-related major complication in the first RFA session of each patient was 0% in Dialysis Group. Conclusion Prognosis of hepatocellular carcinoma was poorer in dialysis patients compared to non-dialysis ones, which may be explained by a higher rate of non-liver-related death in dialysis population. Since RFA, per se, has been safely preformed in dialysis patients, prognostic improvement may be expected by treating HCC in dialysis patients as aggressively as in non-dialysis cases.

The Drinkers\u2019 Intervention to Prevent Tuberculosis (DIPT) trial among heavy drinkers living with HIV in Uganda: study protocol of a 2\xd72 factorial trial

BackgroundThe risk of tuberculosis (TB) is high among people with HIV (PWH). Heavy alcohol drinking independently increases TB risk and approximately 25% of PWH globally engage in heavy drinking. While isoniazid (INH) preventive therapy decreases TB incidence and mortality among PWH, heavy drinking during INH is associated with liver toxicity and poor adherence. Interventions are, therefore, urgently needed to decrease alcohol use and improve adherence to INH in this population in settings with high prevalence of HIV and TB like Uganda.MethodsThe Drinkers’ Intervention to Prevent TB (DIPT) study is a 2×2 factorial randomized controlled trial among HIV/TB co-infected adults (≥18 years) who engage in heavy alcohol drinking and live in Uganda. The trial will allocate 680 participants with a 1:1:1:1 individual randomization to receive 6 months of INH and one of the following interventions: (1) no incentives (control), (2) financial incentives contingent on low alcohol use, (3) financial incentives contingent on high adherence to INH, and (4) escalating financial incentives for both decreasing alcohol use and increasing adherence to INH. Incentives will be in the form of escalating lottery-based monetary rewards. Participants will attend monthly visits to refill isoniazid medications, undergo liver toxicity monitoring, and, except for controls, determine eligibility for prizes. We will estimate (a) the effect of incentives contingent on low alcohol use on reduction in heavy drinking, measured via a long-term objective and self-reported metric of alcohol use, at 3- and 6-month study visits, and (b) the effect of incentives contingent on high adherence to INH, measured as >90% pill-taking days by medication event monitoring system cap opening. We will use qualitative methods to explore the mechanisms of any influence of financial incentives on HIV virologic suppression.DiscussionThis study will provide new information on low-cost strategies to both reduce alcohol use and increase INH adherence among people with HIV and TB infection who engage in heavy drinking in low-income countries with high HIV and TB prevalence.Trial registrationClinicalTrials.gov NCT03492216. Registered on April 10, 2018

Prevalence, patterns and long-term changes of multimorbidity in adults from 10 regions of China

Objective: To describe the prevalence of multimorbidity and its secular trend, and to explore the common patterns of multimorbidity in Chinese adults. Methods: A total of 25 033 participants who attended the second resurvey of China Kadoorie Biobank (CKB) were included in the study. We used data collected both at baseline (2004-2008) and at resurvey (2013-2014). A total of 13 chronic conditions were included, defined by self-reported, physical examination, and blood sample testing. Multimorbidity was defined as co-existence of two or more chronic conditions. Patterns of multimorbidity were explored using hierarchical cluster analysis. Results: The mean age of participants was (51.5±10.1) years at baseline and (59.5±10.2) years at second resurvey. The prevalence of multimorbidity increased from 33.5% to 58.1% over (8.0±0.8) years of follow-up. The average number of chronic conditions per person increased from 1.15 to 1.82 and all participants increased 0.42 conditions per 5 years on average. Participants who were older, less educated or lived in urban areas had a higher prevalence of multimorbidity and a higher increase in the number of chronic conditions. The increase in the number of chronic conditions was also higher among smokers and heavy alcohol drinkers. The most common multimorbidity pattern in the present population consisted of obesity, hypertension, diabetes, stroke, and heart disease. Conclusions: The prevalence of multimorbidity in Chinese adults is increasing rapidly due to ageing population. Populations of different sociodemographic background and lifestyle habits may have different prevalence of multimorbidity and changes in rates over time.

COVID-19 Vaccine Hesitancy and Its Determinants Among Adults with a History of Tobacco or Marijuana Use.

Decreasing COVID-19 vaccine hesitancy is an urgent challenge in the US. This study aimed to examine COVID-19 vaccine hesitancy among U.S. adults with a history of using tobacco products or marijuana. Data were collected online in 2020–2021 including respondents’ willingness to accept a COVID-19 vaccine, factors that may promote vaccine acceptance, and prior history of influenza vaccination. Logistic regression models were conducted to estimate the associations between vaccine hesitancy and demographic characteristics, substance use, the impact of the COVID-19 pandemic, and prior influenza vaccination. Among 387 respondents, 49.1% were willing to receive a COVID-19 vaccine, 26.0% were unwilling, and 24.9% were “not sure.” Blacks, suburban or rural residents, those who lived by themselves or with a family with five members or above, those who were not stressed because of the COVID-19 pandemic were more likely to say “no” to a COVID-19 vaccine. Respondents who never, only once, or during some years received an influenza vaccine were 7.0, 6.2, and 5.2 times more likely to say “no” to a COVID-19 vaccine than respondents who received an influenza vaccination every year or almost every year. The use of cigarettes, e-cigarettes, and marijuana, as well as heavy drinking of alcohol, were not associated with COVID-19 hesitancy. The associations between demographic factors and vaccine hesitancy were roughly similar for COVID-19 and influenza vaccines. Although various demographic groups have different levels of vaccine hesitancy and also have different factors to increase their acceptance, addressing misinformation related to COVID-19 vaccines, particularly concern about the safety of the vaccines is crucial in general.

Mapping data-driven individualized neurobehavioral phenotypes in heavy alcohol drinkers.

Recent studies have examined the factor structure and associated correlates of three neurofunctional domains, executive function, incentive salience, and negative emotionality in the development and maintenance of alcohol use disorders in clinical samples. The current study sought to replicate and extend prior work by testing this 3-factor model, utilizing both exact and similar phenotypic measures, as well as novel measures, in a non-treatment-seeking sample. Self-report measures of alcohol addiction, impulsivity, behavior, and exposure to early-life stress were collected as part of baseline assessments for alcohol imaging and pharmacotherapy studies in 335 individuals. Confirmatory factor analysis (CFA) was used to examine model structure and fit. A multiple indicators, multiple causes (MIMIC) model identified predictors of latent factors identified by CFA. Results supported an intercorrelated model with three factors: executive function, incentive salience, and emotionality. All factors were associated with current AUD, and incentive salience was uniquely associated with past 30-day drinking frequency. MIMIC results identified multiple significant predictors of these latent factors, including history of alcohol use disorder, positive family history of alcohol dependence, earlier age of first drink, and a history of childhood emotional abuse and physical neglect. Our results support an intercorrelated 3-factor model of neurofunctional domains in alcohol use models, consistent with published findings. Because childhood physical neglect was a significant predictor of all latent factors, these results also highlight the significant negative impact of childhood neglect on later addiction development.

MANF protects pancreatic acinar cells against alcohol-induced endoplasmic reticulum stress and cellular injury.

Heavy alcohol drinking is associated with pancreatitis. Pancreatitis is initiated by the damage to the pancreatic acinar cells. The endoplasmic reticulum (ER) stress has been shown to play an important role in alcohol-induced pancreatic damage. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress-inducible protein. The aim of the study was to determine whether MANF can ameliorate alcohol-induced ER stress and cellular damages to pancreatic acinar cells. Alcohol-induced damage to mouse pancreatic 266-6 acinar cells was determined by MTT and flow cytometry. MANF expression was downregulated by MANF siRNA using the Neon Transfection System. The overexpression of MANF was performed by the infection with the adenoviral vector carrying mouse MANF gene. The expression of ER stress markers was determined by immunoblotting and immunofluorescence. Alcohol caused ER stress, oxidative stress and induced apoptosis of 266-6 acinar cells. Recombinant human MANF alleviated alcohol-induced ER stress and cell death by inhibiting IRE1-caspase 12-caspase 3 apoptotic pathway. Overexpression of mouse MANF also protected cells against alcohol-induced apoptosis. In contrast, inhibiting MANF by siRNA exacerbated alcohol-induced cellular damage. MANF was protective against alcohol-induced ER stress and cellular injury in pancreatic acinar cells. The findings suggest a potential therapeutic value of MANF for alcoholic pancreatitis.

Electrophysiological Detection of Asymptomatic Neuropathy in Alcohol Dependence Syndrome Patients- A Cross Sectional Observational Study

Aim: To detect the prevalence of asymptomatic neuropathy using nerve conduction study among alcohol dependence syndrome patients and to investigate the existence or not of correlation between duration, quantity of alcohol consumption and neuropathy.&#x0D; Study Design: Observational cross-sectional study.&#x0D; Place and Duration of Study: Department of General Medicine and Department of Psychiatry, Mahatma Gandhi Medical College and Research Institute, Pondicherry, affiliated to Sri Balaji Vidyapeeth (Deemed to be) University, India between February 2019 and August 2020.&#x0D; Methods: Alcohol dependence syndrome patients, asymptomatic for neuropathy were prospectively included and, patients who were symptomatic and had other comorbid conditions that can cause neuropathy were excluded. Patients were then submitted to nerve conduction studies. In patients who had neuropathy, duration and quantity of alcohol consumption were compared for correlation.&#x0D; Results: This study included 65 male patients who were mostly middle aged heavy drinkers of alcohol. 73.8% (n=48) had neuropathy. Our research showed longer the duration, larger the quantity of alcohol consumption, and higher the Cut-Annoyed-Guilty-Eye (CAGE score), more were the prevalence of neuropathy. This research also used Severity Of Alcohol Dependence Questionnaire (SAD-Q) scoring for screening alcohol dependence which showed patients with neuropathy were moderate drinkers. We did not find correlation with age of patients and neuropathy.&#x0D; Conclusion: This research results like correlation of prevalence of neuropathy and duration of alcohol consumption and quantity of alcohol consumption were in contrast with previous studies on alcoholic neuropathy. This research used SAD-Q scoring for dependence, future researches can throw light on usage of SAD-Q score in asymptomatic neuropathy and the correlation of neuropathy with alcohol consumption.