Alcoholic Research Articles

Fatal Hemoperitoneum Secondary to a Spontaneous Splenic Vein Rupture.

Spontaneous hemoperitoneum is rare and is often labeled as idiopathic because the source of bleeding is never found. We report the case of a 35-year-old male who died of a splenic vein rupture. The decedent was a chronic alcoholic with a reported history of cirrhosis and medication noncompliance. Internal examination revealed pale visceral organs, marked hemoperitoneum, a fibrotic/nodular liver, esophageal varices, and a ruptured splenic vein. Pertinent microscopic findings include liver parenchyma with bridging fibrous septa, nodules of regenerating hepatocytes, and the presence of Mallory-Denk bodies. The immediate cause of death was determined to be splenic vein rupture with the underlying cause of death being chronic alcoholism. This case is reported to emphasize the importance of correlating past medical history with thorough vascular dissection in cases of spontaneous hemoperitoneum. In a patient with fatal hemoperitoneum and risk factors for splenic vein pathology (ie, cirrhosis, portal vein hypertension), a high suspicion should be kept for splenic vein rupture.

Genome-Wide Analysis to Assess if Heavy Alcohol Consumption Modifies the Association between SNPs and Pancreatic Cancer Risk.

Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted. A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10-8 in the meta-analysis; Pinteraction = 2.1 × 10-9 in the case-control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004). We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer. This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.

Management of Cancer in the Digestive System

Cancer is a non-communicable disease characterized by the presence of abnormal cells/tissues that are malignant, grow quickly and uncontrollably and can spread to other places in the patient's body. Cancer cells are malignant and can invade and damage the function of the tissue. Digestive cancer, also called gastrointestinal cancer, attacks the organs of the digestive system. Digestive cancer also includes gastrointestinal cancer, liver cancer, stomach cancer, colorectal cancer, and pancreatic cancer. Risk factors for digestive cancers are varied because many different organs can be affected. Some factors that contribute to cancer throughout the digestive system include age, heavy drinking (alcohol), smoking, and diabetes sufferers. This type of liver cancer is cancer that grows in liver cells. Liver cancer is a type of cancer that ranks second as the cancer that causes the most deaths in the world. Gastric cancer is a group of malignant diseases that have multifactorial causes, namely genetic, lifestyle and environmental factors. The symptoms caused by stomach cancer are initially not as typical as the symptoms of general digestive complaints. The diagnosis of colorectal cancer can be carried out in stages, including through an appropriate history, physical examination, and supporting examinations in the form of laboratory examinations, both from clinical laboratories and anatomical pathology laboratories. The etiology of colorectal cancer is currently still unknown. Symptoms of colorectal cancer are varied and non-specific. The main complaints of patients with colorectal cancer relate to the size and location of the tumor. Tumors in the right colon, where the contents of the colon are fluid, tend to remain hidden until they are very advanced.

A Disability Studies Analysis of Alcohol Use: Understanding Personal Experiences through Dominant Discourses on Addiction

This paper describes my experiences with coming to understand my own relationship with alcohol dependency and addiction. Disability studies has offered me a lens and guide through which I have critically interrogated discourses about addiction, while examining the ways dominant and counter-narratives have impacted my own recovery process. In this paper, I review historical information about the emergence of culturally accepted recovery ideologies in the United States that have led to a dominant disease model perspective. Then, I explain the disability studies-informed theoretical underpinnings of this paper, which include discourse theory and disability studies as applied to alcohol addiction. Using disability studies and autoethnography as a guide, the body of the paper uses examples from my own journals to elucidate salient themes that emerged about my experiences in early recovery. The paper uncovers the ways I came to understand my own identity related to addiction, how I navigated feelings of stigma and shame, the ways I found recovery spaces that embraced empowering frameworks aligned to a disability studies ethos, and how I discovered community and pride through this experience.

The identification and treatment of alcohol problems in primary care (iTAPP) study: protocol for a stepped wedge cluster randomized control trial testing the 15-method in a primary care setting

BackgroundThe 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as specialized treatment for mild to moderate alcohol dependence in Sweden. A feasibility study of the 15-method in Danish primary care found the method acceptable and feasible.AimsTo evaluate the effectiveness of the 15-method in a Danish primary care setting in (1) lowering the proportion of patients exceeding the Danish low-risk alcohol consumption limit of ten standard units per week and a maximum of four standard units on a single day for men and women, and (2) increasing the likelihood of alcohol use being addressed during a consultation in general practice. Further, the rate of prescribed pharmacological treatment for alcohol problems (Disulfiram, Naltrexone, Acamprosate, and Nalmefene) will be measured along with the use of the biomarkers Alanine Transaminase and Gamma-Glutamyl Transferase.MethodsStepped wedge cluster randomized controlled trial in sixteen general practices in the Region of Southern Denmark. Following a three-month baseline, the practices are randomly assigned to launch dates in one of four clusters. General practitioners and nurses receive three hours of training in the 15-method before launch. Patient questionnaires will collect data on alcohol consumption levels among patients affiliated with the practices. The healthcare professionals will register consultations in which alcohol is addressed in their patient filing system. Pharmacological treatment rates and the use of biomarkers will be collected through Danish national registries. The study follows the Medical Research Council’s guidelines for developing and evaluating complex interventions.DiscussionFrom the patient’s perspective, the 15-method may help identify alcohol-related problems at an earlier stage with flexible treatment offers in a familiar setting. For healthcare professionals, it addresses a traditionally challenging topic by equipping them with concrete tools, communication training, and clear treatment directives. From a societal perspective, primary care holds a unique position to identify hazardous and harmful alcohol use across different age groups, with potential public health and economic benefits through early identification and intervention.Trial registrationClinicaltrials.gov NCT05916027. Retrospectively registered 22 June 2023.

Association between dietary soy prevention of fetal alcohol spectrum disorder and normalization of placental insulin and insulin-like growth factor signaling networks and downstream effector molecule expression

Chronic prenatal alcohol exposure causes fetal alcohol spectrum disorder (FASD), often associated with impaired placentation and intrauterine growth restriction. Ethanol’s inhibition of insulin and insulin-like growth factor Type 1 (IGF-1) signaling compromises trophoblastic cell motility and maternal vascular transformation at the implantation site. Previous studies have demonstrated that dietary soy effectively normalizes placentation and fetal growth in an experimental model of FASD. The studies were extended to better understand the mechanisms underlying soy’s beneficial effects. Pregnant Long Evans rats were pair-fed with isocaloric liquid diets containing either 0% or 36% caloric ethanol from gestation day (GD) 6. The protein source in the diets consisted of either casein (standard and control) or soy isolate. On GD19, placentas were harvested to measure mRNA levels corresponding to major components of the insulin/IGF-1 pathway, as well as aspartyl-asparaginyl-β-hydroxylase (ASPH), Notch, and HES, which play critical roles in placentation. Chronic gestational ethanol exposure in rats fed diets containing casein significantly reduced the expression of insulin, insulin receptor, Igf1, IGF-1 receptor (Igf1r), insulin receptor substrate Type 1 (Irs1), Irs2, Asph, and Hes1. In addition, ethanol significantly decreased ASPH protein expression. Dietary soy mitigated most of these effects and further enhanced signaling by upregulating Igf2, Igf2r, Irs1, Irs2, Irs4, Notch, and Hes1 in rats chronically exposed to ethanol relative to corresponding control samples. The protective effects of dietary soy in FASD act at the mRNA level and positively impact pathways imperative for normal placentation and fetal development. Gestational dietary soy may provide an effective means of preventing FASD in vulnerable populations.

Gut microbial diversity and functional characterization in people with alcohol use disorder: A case-control study.

Individuals with Alcohol Use Disorder (AUD) typically have comorbid chronic health conditions, including anxiety and depression disorders, increased sleep disruption, and poor nutrition status, along with gut microbial dysbiosis. To better understand the effects of gut dysbiosis previously shown in individuals with AUD, gut microbiome and metabolome were investigated between three cohorts. Two groups of individuals with AUD included treatment-seeking newly abstinent for at least six weeks (AB: N = 10) and non-treatment-seeking currently drinking (CD: N = 9) individuals. The third group was age, gender, and BMI-matched healthy controls (HC: N = 12). Deep phenotyping during two weeks of outpatient National Institutes of Health Clinical Center visits was performed, including clinical, psychological, medical, metabolic, dietary, and experimental assessments. Alpha and beta diversity and differential microbial taxa and metabolite abundance of the gut microbiome were examined across the three groups. Metabolites derived from the lipid super-pathway were identified to be more abundant in the AB group compared to CD and HC groups. The AB individuals appeared to be most clinically different from CD and HC individuals with respect to their gut microbiome and metabolome. These findings highlight the potential long-term effects of chronic alcohol use in individuals with AUD, even during short-term abstinence.

Impact of an alcohol withdrawal screening and treatment protocol for hospitalized patients

IntroductionAlcohol Withdrawal Syndrome (AWS) is a potentially life-threatening complication of alcohol use disorder (AUD) that can be challenging to recognize in hospitalized patients. Our institution implemented universal AUD screening for all patients admitted to a non-critical care venue using the Prediction of Alcohol Withdrawal Severity Scale (PAWSS). At risk patients were then further assessed, utilizing the Glasgow Modified Alcohol Withdrawal Scale (GMAWS), and medicated according to a predetermined protocol. This study sought to determine whether this protocol decreased hospital length of stay, lowered the total benzodiazepine dose administered, and decreased adverse events attributable to AWS. MethodsThis retrospective cohort study was conducted over a 6-year period from 2014 to 2020. The study included patients with an ICD-10 code diagnosis of AWS and subsequently divided them into two groups: pre- and post-protocol introduction. Outcome measures were compared pre- versus post-protocol introduction. ResultsThere were 181 patient encounters pre- and 265 patient encounters post-protocol. There was no statistically significant difference in median length of stay between the two groups (2.956 days pre and 3.250 days post-protocol, p = 0.058). Post-protocol, there was a statistically significant reduction in median total benzodiazepine dose (13.5 mg and 9 mg lorazepam equivalents pre- and post-protocol, p < 0.001) and in occurrence of delirium tremens (7.7 % pre and 2.3 % post-protocol, p = 0.006). ConclusionProtocol implementation did not reduce length of stay in patients with AUD but was associated with a significant reduction in total benzodiazepine dose and, when adjusted, a non-statistically significant decrease in progression to delirium tremens in hospitalized patients, after applying Bonferroni adjustment.

Geographical, sex, and socioeconomic differences in non-communicable disease indicators: A cross-sectional survey in Eastern Uganda.

The prevalence of non-communicable diseases (NCDs) is increasing in many low- and middle-income countries (LMICs). This study examined differences in the burden of NCDs and their risk factors according to geographic, sex, and sociodemographic characteristics in a rural and peri-urban community in Eastern Uganda. We compared the prevalence by sex, location, wealth, and education. Unadjusted and adjusted prevalence ratios (PR) were reported. Indicators related to tobacco use, alcohol use, salt consumption, fruit/vegetable consumption, physical activity, body weight, and blood pressure were assessed. Among 3220 people (53.3% males, mean age: 35.3 years), the prevalence of NCD burden differed by sex. Men had significantly higher tobacco (e.g., current smoking: 7.6% vs. 0.7%, adjusted PR (APR): 12.8, 95% CI: 7.4-22.3), alcohol use (e.g., current drinker: 11.1% vs. 4.6%, APR: 13.4, 95% CI: 7.9-22.7), and eat processed food high in salt (13.4% vs. 7.1, APR: 1.8, 95% CI: 1.8, 95% CI: 1.4-2.4) than women; however, the prevalence of overweight (23.1% vs 30.7%, APR: 0.7, 95% CI: 0.6-0.9) and obesity (4.1% vs 14.7%, APR: 0.3, 95% CI: 0.2-0.3) was lower among men than women. Comparing locations, peri-urban residents had a higher prevalence of current alcohol drinking, heavy episodic drinking, always/often adding salt while cooking, always eating processed foods high in salt, poor physical activity, obesity, prehypertension, and hypertension than rural residents (p<0.5). When comparing respondents by wealth and education, we found people who have higher wealth or education had a higher prevalence of always/often adding salt while cooking, poor physical activity, and obesity. Although the findings were inconsistent, we observed significant sociodemographic and socioeconomic differences in the burden of many NCDs, including differences in the distributions of behavioral risk factors. Considering the high burden of many risk factors, we recommend appropriate prevention programs and policies to reduce these risk factors' burden and future negative consequences.

Analysis of the BDNF Gene rs6265 Polymorphism in a Group of Women with Alcohol Use Disorder, Taking into Account Personality Traits.

It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral tegmental area (the region from which the dopaminergic neurons of the mesocorticolimbic dopamine system originate and extend to the dorsolateral and ventromedial striatum) triggers a state of reward similar to that produced by opiates in animal studies. The aims of the study were (1) to analyze the association of the BDNF gene rs6265 polymorphism with AUD (alcohol use disorder) in women, (2) analyze personality and anxiety in alcohol-dependent and control woman, and (3) conduct an interaction analysis of rs6265 on personality, anxiety, and alcohol dependence. Our study found a notable interaction between the anxiety (trait and state), neuroticism, rs6265, and AUD. The alcohol AUD G/A genotype carriers revealed higher level of the anxiety trait (p < 0.0001) and neuroticism (p < 0.0001) compared to the control group with G/A and G/G genotypes. The alcohol use disorder subjects with the G/A genotype displayed higher levels of an anxiety state than the control group with G/A (p < 0.0001) and G/G (p = 0.0014) genotypes. Additionally, the alcohol use disorder subjects with the G/G genotype obtained lower levels of agreeability compared to the controls with G/A (p < 0.0001) and G/G (p < 0.0001) genotypes. Our study indicates that anxiety (trait and state) and neuroticism are interacting with the BDNF gene rs6265 polymorphism in alcohol-dependent women. Characteristics like anxiety (both as a trait and a state) and neuroticism could have a significant impact on the mechanism of substance dependency, particularly in females who are genetically susceptible. This is regardless of the reward system that is implicated in the emotional disruptions accompanying anxiety and depression.

Executive Function as an Underlying Mechanism of Alcohol Use, Aggression, and ADHD.

Executive functioning (EF) has been proposed as a transdiagnostic risk factor for externalizing disorders and behavior more broadly, including attention-deficit/hyperactivity disorder (ADHD), aggression, and alcohol use. Previous research has demonstrated both phenotypic and genetic overlap among these behaviors, but has yet to examine EF as a common causal mechanism. The current study examined reciprocal causal associations between EF and several externalizing behaviors using a Mendelian randomization (MR) approach. Two-sample MR was conducted to test causal associations between EF and externalizing behaviors. Summary statistics from several genome-wide association studies (GWASs) were used in these analyses, including GWASs of EF, ADHD diagnostic status, drinks per week, aggressive behavior, and alcohol use disorder (AUD) diagnostic status. Multiple estimation methods were employed to account for horizontal pleiotropy (e.g., inverse variance weighted, MR-PRESSO, MR-MIX). EF demonstrated significant causal relationships with ADHD (P < 0.01), AUD (P < 0.03), and alcohol consumption (P < 0.01) across several estimation methods. Reciprocally, ADHD showed a significant causal influence on EF (P < 0.03). Nonetheless, caution should be used when interpreting these findings as there was some evidence for horizontal pleiotropy in the effect of EF on ADHD and significant heterogeneity in variant effects in the other relations tested. There were no significant findings for aggression. Findings suggest that EF may be a causal mechanism underlying some externalizing behaviors, including ADHD and alcohol use, and that ADHD may also lead to lower performance on EF tasks.

Esketamine combined with a mindfulness-based intervention for individuals with alcohol problems.

Alcohol use disorder (AUD) is a major public health issue, posing harmful consequences for individuals and society. Recent advances in addiction research have highlighted the therapeutic potential of ketamine-assisted therapy for AUD. However, the exact mechanisms underlying its effectiveness remain unknown. This double-blind, pilot study aimed to investigate esketamine combined with mindfulness-based intervention (MBI) to examine whether esketamine enhances engagement in MBI for individuals with alcohol misuse problems and whether enhanced engagement has any impact on alcohol-related outcomes. In all, 28 individuals with alcohol problems were randomly assigned to receive sublingual esketamine hydrochloride (AWKN002: 115.1 mg) or vitamin C (placebo) in an oral thin film and took part in 2 weeks of daily MBI. Participants were assessed on various self-report measures, including mindfulness, engagement in MBI (physical and psychological), alcohol cravings and consumption. Esketamine enhanced psychological engagement with a daily MBI, compared to placebo, and led to transient decreases in alcohol cravings. Esketamine also resulted in significantly greater mystical experiences and dissociative states compared to placebo. The findings suggest that esketamine may improve treatment outcomes when combined with mindfulness-based therapies through its ability to increase engagement with meditative practice.

Features of the circadian rhythm in the size of mitochondria of rat hepatocytes under conditions of dark deprivation and chronic alcohol intoxication

Background Circadian rhythms (CR) of functions and processes in the body are normally strictly coordinated with each other and with environmental factors, which ensures the maintenance of the functioning of the organs and systems of the body at an optimal level. However, we have not found any studies devoted to the study of CR of hepatocyte organelles under experimental conditions. Aim of study Study of the daily dynamics of the cross-sectional area of hepatocyte mitochondria in rats under conditions of dark deprivation, chronic alcohol intoxication and the combined effect of these factors. Materials and methods The work was performed on 80 males and 80 females Wistar rats, divided into 4 groups of each sex. Group 1 was kept under a fixed light regime; The 2nd group was kept under conditions of dark deprivation; the 3rd group was kept in the same conditions as the animals of the control group, but were subjected to chronic alcohol intoxication; Group 4 was kept in conditions of dark deprivation and subjected to chronic alcohol intoxication. Liver samples, after fixation and wiring, were analyzed using a transmission electron microscope. Micromorphometric methods were used to assess the mitochondrial apparatus of hepatocytes. Results In hepatocytes of rats from experimental groups of both sexes, CR of the cross-sectional area of mitochondria with similar parameters was detected. Dark deprivation and chronic alcohol intoxication, acting both separately and together, cause a restructuring of the mitochondrial size distribution, which is more pronounced in males. Conclusion The study indicates that the CR of mitochondrial size is dependent on the lighting regime and the toxic effect of ethanol and its metabolites. The size ranges of mitochondria in hepatocytes of females, compared to males, are more resistant to the effects of dark deprivation and alcohol intoxication.

Risk of severe mood and anxiety disorders in the adult children of parents with alcohol use disorder: a nationwide cohort study

BackgroundGrowing up with parental alcohol use disorder (AUD) is a risk factor for psychiatric disorders. This study investigated the risk of mood disorders and of anxiety disorders in the adult...

JNK Signaling Positively Regulates Acute Ethanol Tolerance in C. elegans.

Alcohol use disorder (AUD) is a chronic neurobehavioral condition characterized by a cycle of tolerance development, increased consumption, and reinstated craving and seeking behaviors during withdrawal. Understanding the intricate mechanisms of AUD necessitates reliable animal models reflecting its key features. Caenorhabditis elegans (C. elegans), with its conserved nervous system and genetic tractability, has emerged as a valuable model organism to study AUD. Here, we employ an ethanol vapor exposure model in Caenorhabditis elegans, recapitulating AUD features while maintaining high-throughput scalability. We demonstrate that ethanol vapor exposure induces intoxication-like behaviors, acute tolerance, and ethanol preference, akin to mammalian AUD traits. Leveraging this model, we elucidate the conserved role of c-jun N-terminal kinase (JNK) signaling in mediating acute ethanol tolerance. Mutants lacking JNK signaling components exhibit impaired tolerance development, highlighting JNK's positive regulation. Furthermore, we detect ethanol-induced JNK activation in C. elegans. Our findings underscore the utility of C. elegans with ethanol vapor exposure for studying AUD and offer novel insights into the molecular mechanisms underlying acute ethanol tolerance through JNK signaling.

Predictors of concerned others' mental health and quality of life over 12 months following adults' entry into treatment for an alcohol use disorder

IntroductionPeople in treatment for alcohol use disorders (AUDs) can negatively impact their Concerned Others (COs). This longitudinal study examined patient and CO characteristics associated with CO outcomes. MethodParticipants were 279 dyads of patients entering residential treatment and their CO. Outcomes were COs' mental health and quality of life. The study collected patient and CO predictors and CO outcomes at baseline and 3-, 6-, and 12-month follow-ups as part of a randomized controlled trial. In the first set of models, the analytic approach identified baseline patient predictors associated with COs' outcomes measured at baseline and follow-ups. In the second set of models, we examined whether those effects remained after adding baseline CO characteristics. ResultsIn the first set of models, COs of older age and whose patient reported less CO-patient relationship stress had better mental health. Also, married COs and those with higher income and whose patient reported no violence in the CO-patient relationship had better quality of life. In the second set of models, COs whose patient entered treatment due to criminal justice involvement, with more social support, less reported stigma, and less use of avoidance coping had better mental health. Also, married COs, those with higher income, and less reported discrimination stigma had better quality of life. ConclusionsUnderstanding patient and CO characteristics that are associated with COs' outcomes may inform AUD treatment programs' efforts to help COs. Identifying modifiable determinants of CO outcomes is important to clinical practice regardless of whether the patient chooses to obtain treatment.

Evaluation of alcohol use behavior among patients cured through HCV elimination program in Georgia

ObjectiveThe objective of the study was to understand the role of self-reported drinking behavior on liver health after achieving sustained viral response (SVR) among HCV patients.ResultsThe study was conducted in HCV treatment provider clinics in three cities in Georgia: Tbilisi, Batumi, and Telavi. Face-to-face interviews were conducted using a questionnaire developed specifically for this study. 9.5% considered themselves heavy drinkers, while 94.2% were aware that heavy alcohol consumption can progress liver fibrosis. During treatment, 97.8% abstained from alcohol, while 76.6% reported resuming drinking after achieving SVR. Additionally, 52.1% believed that moderate alcohol intake is normal for individuals with low fibrosis scores. Liver fibrosis improvement was more prevalent among individuals who abstained from alcohol after HCV diagnosis (85.4% vs. 71.4%, p < 0.01) and after achieving SVR (87.5% vs. 74.7% of those who resumed drinking after achieving SVR, p < 0.02). In conclusion, the majority of HCV patients abstain from alcohol during treatment but resume drinking after achieving SVR. Those who abstain from alcohol intake after HCV cure have a higher chance of liver fibrosis improvement.

"Alcohol will never run out": Socio-ecological drivers of adolescent boys' alcohol use in Kilimanjaro Region, Tanzania.

Heavy alcohol use amongst adolescent boys is a major public health concern in many countries. It is associated with a range of negative physical and mental health outcomes and predicts alcohol-related problems in adulthood. In Kilimanjaro Region, adolescent boys' alcohol use is widespread, and higher than other regions in Tanzania. An understanding of causal and contextual factors that influence the use of alcohol is needed to inform the development and implementation of effective alcohol prevention interventions. This study aimed to explore these socio-ecological factors in-depth amongst adolescent boys, young men and key stakeholders in Kilimanjaro Region, Tanzania. Between August 2022 and June 2023, multi-method, participatory, qualitative methods including: ethnographic observations (8 weeks), 37 in-depth interviews, 14 focus group discussions and participatory adolescent activities were used to elicit perceptions on factors driving adolescent boys' alcohol use in two (rural/urban) settings. Data were triangulated and deductively analysed, guided by Bronfenbrenner's socio-ecological framework. This study found many dynamic and inter-related factors linked to alcohol use within adolescents' social, cultural, economic, regulatory, and physical environments. In a context of widespread availability of alcohol, low enforcement of alcohol regulation and (mis)conceptions around the benefits of alcohol use (e.g. curative and/or nutritional properties), parental and cultural influences largely determined the initiation of use in childhood and younger adolescence; employment status, peers, lack of alternative recreational activity and social norms around independence appeared to drive continued and increased use in older adolescence. Factors and their impact varied between rural and urban settings. In conclusion, a wide range of determinants and drivers of alcohol use among ABYM work at multiple socio-ecological levels especially parental, cultural and socioeconomic factors. This suggests that effective prevention requires a systems approach intervening across these levels. For example, incorporating education/awareness raising, increased law enforcement, parent-child communication and problem-solving, and income generation activities.

Natural variation in protein kinase D modifies alcohol sensitivity in Caenorhabditis elegans.

Differences in naïve alcohol sensitivity between individuals are a strong predictor of later life alcohol use disorders (AUD). However, the genetic bases for alcohol sensitivity (beyond ethanol metabolism) and pharmacological approaches to modulate alcohol sensitivity remain poorly understood. We used a high-throughput behavioral screen to measure acute behavioral sensitivity to alcohol, a model of intoxication, in a genetically diverse set of over 150 wild strains of the nematode Caenorhabditis elegans. We performed a genome-wide association study to identify loci that underlie natural variation in alcohol sensitivity. We identified five quantitative trait loci (QTL) and further show that variants in the C. elegans ortholog of protein kinase D, dkf-2, likely underlie the chromosome V QTL. We found that resistance to intoxication was conferred by dkf-2 loss-of-function mutations as well as partly by a PKD inhibitor in a dkf-2-dependent manner. Protein kinase D might represent a conserved, druggable target to modify alcohol sensitivity with application towards AUD.

The association between PTSD symptom clusters and religion/spirituality with alcohol use among first responders

Alcohol misuse and posttraumatic stress disorder (PTSD) co-occur at high rates among first responders (e.g., law enforcement, firefighters, paramedics), underscoring the need to better understand these relations to inform intervention efforts. Identifying malleable processes relevant to the association between PTSD and alcohol among first responders could inform tailored interventions. An example of such a malleable process is spirituality. As such, the current study examined the unique relationships between PTSD symptom clusters and alcohol misuse, while also accounting for the role of select demographics and religion/spirituality, in a sample of first responders. A national online sample of first responders (N = 320) completed measures of PTSD symptomology, alcohol misuse, religion/spirituality and demographics. Hierarchical linear regression analyses revealed that PTSD Intrusion (Cluster B) symptom severity was associated with greater alcohol misuse and PTSD Avoidance (Cluster C) was associated with lower alcohol misuse. Additionally, positive and negative spiritual coping were also associated with alcohol misuse. In the context of similar research among military samples, findings suggest potentially unique associations between PTSD symptom clusters and alcohol misuse among first responders. Additionally, findings highlight the potentially protective role of religion/spirituality in this population. Future research should explore nuanced relationships between PTSD symptom clusters and alcohol misuse as well as the salience of spirituality/religion in this unique population.