Effects Of Alcohol Research Articles

From consumption to withdrawal: A broad synopsis of the effects of alcohol

AbstractThe consumption of alcohol reflects both societal norms and personal choices and has major clinical implications. Long‐term excess alcohol consumption leads to a domino effect of pathological outcomes and onset of chronic illness. However, the risks of alcohol consumption extend beyond long‐term health issues. Because habitual alcohol drinkers reach a state of systemic homeostasis, when they attempt withdrawal, they experience many negative physiological effects and may develop alcohol withdrawal syndrome. The complex interplay between alcohol consumption and withdrawal does not result solely in behavioral issues. Rather, a substantial number of important physiological adaptations and potential problems underly habitual drinking. Addressing these issues requires comprehensive medical observation and intervention. Here, we summarize the pathophysiological mechanisms, clinical diseases, and related treatment methods of alcohol consumption and withdrawal. The aim was to provide a reference to improve understanding of alcohol use and promote an informed approach to alcohol withdrawal.

Supplemental Material for Retrospective Self-Reports of Sensitivity to the Effects of Alcohol: Trait-Like Stability and Concomitant Changes With Alcohol Involvement

Supplemental Material for Retrospective Self-Reports of Sensitivity to the Effects of Alcohol: Trait-Like Stability and Concomitant Changes With Alcohol Involvement

Chronic Alcohol Exposure Causes Myeloid-Biased Hematopoiesis Via Double-Strand RNA Sensors and Type 1 Interferon Response

Excessive alcohol use is well-known to cause cytopenias and bone marrow (BM) suppression. However, the mechanisms by which alcohol suppresses BM are poorly understood. Moreover, even though the prevalence of moderate drinking is high worldwide, the effects of chronic moderate alcohol consumption on the human hematopoietic system remain unknown. To fill this knowledge gap, we sought to investigate the effects of chronic moderate alcohol consumption on human hematopoiesis using cell-based and animal models. To examine the effects of alcohol on hematopoietic cells in vitro, we tested varying doses of alcohol (0-100 mM) on four leukemia cell lines (Jurkat, MOLM13, MV-4-11, and THP1) and measured population doubling over 6 days. Population doubling levels significantly decreased in a dose-dependent manner in all cell lines tested. We also measured mitochondrial (mt) ROS by MitoSOX-Red flow cytometry in Jurkat, which showed a dose-dependent increase of mtROS (trends only at 10, 25 mM; significantly increased at 50, 100 mM alcohol) compared to untreated. These findings confirm that alcohol negatively affects cell growth and increases mtROS in a physiologic range of doses. To determine the effects of alcohol on human hematopoietic stem progenitor cells (HSPCs) in vitro, we treated human BM CD34+ cells with 0 vs. 50 mM alcohol for 48 hours and performed bulk RNA-sequencing in triplicate. Gene Set Enrichment Analysis (GSEA) revealed that multiple pathways related to platelet activation and coagulation were enriched in alcohol-treated HSPCs, suggesting the induction of inflammation and/or platelet-biased differentiation by alcohol. To assess the effects of chronic moderate alcohol consumption on HSPCs in vivo, we employed a xenotransplant model. In brief, human BM CD34+ cells were transplanted to 5-to-6-week-old female NBSGW mice. We confirmed their engraftment by bone marrow aspiration at six weeks post-transplant, and then they were randomly assigned to the alcohol vs. control groups. After 2 weeks of adjustment, mice were fed a liquid diet (their only source of water and food) containing alcohol 5% vol/vol vs. iso-caloric control diet for 8 weeks. At 4 and 8 weeks, the alcohol-fed group showed significant myeloid bias, reaching greater than 3 times higher myeloid-to-lymphoid ratio than the control group at 8 weeks, while overall engraftment levels were not different. We will report the results of the secondary transplantation of this experiment at the annual meeting. After 8-week alcohol feeding, sorted human CD45+CD34+ cells from mouse BM were subject to 10x Genomics Chromium X 3' HT single-cell RNA-sequencing (scRNA-seq). Complementing the flow data, our transcriptomic data portrayed stark differences between the two groups. Over 50% of cells in the alcohol group comprised granulocyte progenitors, with B cell progenitors representing less than 25%. Inversely, control group data revealed approximately 30% granulocyte progenitors and 55% B cell progenitors, confirming the myeloid bias of HSPC caused by alcohol. Examining differentially expressed genes and GSEA highlighted a significant upregulation of genes associated with the response to virus and type 1 interferon (IFN-1) signature across all HSPC types. A closer look into the gene set showed increased expression of genes tied to cytosolic double-strand (ds) RNA sensing pathways and subsequent interferon type 1 response. Specifically, dsRNA sensors like MDA5, RIG1, PKR, and OAS1-3, as well as interferon regulatory or responsive genes, such as IRF7, ISG15, IFI6, IFI44L, MX1, and STAT1, were notably increased in HSCs and most progenitor populations. Unexpectedly, alcohol-exposed HSCs tended to be in the G0/G1 phase rather than the S or M phase compared to their counterpart upon cell cycle analysis using scRNA-seq data. This may be due to the activation of the PKR pathway, a known cell cycle inhibitor in mouse HSCs. In summary, our findings demonstrate that chronic moderate alcohol consumption can significantly reshape the hematopoietic system through myeloid-biased differentiation and potentiate inflammation by activating the cytosolic dsRNA sensing pathways and IFN-1 response.

Bioactive Fe Foam for Degradable Bone Graft Cages

Fe foams when combined with a proper surface coating can be effectively used as a biodegradable metal with improved biocompatibility and bioactivity. Herein, Fe foams prepared via powder metallurgy route coated with two different bioactive coatings namely polyvinyl alcohol (PVA)/bioglass (BG) and polylactic acid (PLA)/BG are investigated. The effect of hydrophilic PVA and hydrophobic PLA, in conjunction with BG, has been examined. The study of biomineralization, degradation, and weight loss of the composite‐coated material over a period of 28 days is compared with that of the uncoated Fe foam samples in simulated body fluid. The composite coatings on the Fe foam effectively tailor the degradation with enhanced biomineralization. The composite‐coated material exhibits viability toward the L929 fibroblast cell line. The work reveals the great potential of Fe foams to be used as a biodegradable metallic material for temporary implant applications such as bone graft cages.

Spur Cell Anemia: A Rare and Under-Diagnosed Cause of Anemia in Alcoholic Patients with Advanced Liver Disease

Anemia in patients with alcohol use disorder (AUD) has a wide range of differential diagnoses, which can be challenging to interpret. It is often multifactorial, such as due to blood loss with or without coagulopathy, direct toxic effect of alcohol on hematopoietic cells, chronic inflammation, abnormalities in red blood cells (RBC) membranes, and nutritional deficiencies. Alcohol-induced liver disease may contribute to anemia through coagulopathy, splenomegaly, and hypersplenism. Macrocytosis is a common finding in patients with AUD due to B12 or folate deficiency or RBC membrane abnormality due to changes in lipid composition of RBC membranes. Patients with cirrhosis may have low haptoglobin due to impaired synthetic liver function. However, non-autoimmune hemolytic anemia and concomitant alcohol-induced liver damage should raise suspicion for spur cell anemia (SCA) and Zieve's syndrome. These medical conditions tend to be underreported or misdiagnosed. We describe a 44 year old male patient with a past medical history of AUD who presented with alcohol intoxication and was found to have newly diagnosed decompensated cirrhosis with severe macrocytic anemia with Hgb of 5.9 g/dl. Patient denied overt bleeding. Initial workup revealed high absolute reticulocyte count of 10.8% with retic index of 3, low haptoglobin of <15 mg/dl, elevated LDH of 275 u/l, negative Coombs test consistent with non-autoimmune hemolytic anemia, normal folate and B12 levels, and mixed direct and indirect hyperbilirubinemia. Peripheral blood smear showed anisopoikilocytosis, macrocytes, many spur cells, increased reticulocytes, but no schistocytes. Endo-colonoscopy showed grade 1 esophageal varices without evidence of recent bleeding. Given the history of heavy alcohol intake and cirrhosis, combined with Coombs-negative hemolytic anemia and peripheral blood smear findings of numerous spiculated red cells, our patient was diagnosed with SCA. At the time, due to active alcohol use, the patient was deemed not to be a candidate for liver transplant. This case report aims to aid physicians with the recognition of acute hemolytic anemia in patients with alcoholic liver injury and consideration of SCA and Zieve's syndrome as potential underlying causes. Prompt recognition and differentiation between these medical conditions are crucial as prognosis and treatment are different. Early recognition of SCA and timely consideration of liver transplantation can significantly improve patient outcomes.

The Application Value of Sanitary Wipes and Medical Alcohol + Gauze Disinfection Method in the Management and Use of Medical Equipment

Objective: To analyze the effect of sanitary wipes and medical alcohol + gauze disinfection methods on the management and use of medical equipment in hospitals. Methods: From February 2023 to August 2023, 80 anorectal surgery medical instruments and equipment were randomly sampled as observation samples, and they were grouped using the random number table method (40 instruments in each group). One group was managed with sanitary wipes and medical alcohol + gauze disinfection method (observation group), and the other group was managed with medical alcohol + gauze disinfection method (control group). The degree of contamination on the surface of instruments and equipment and the staff satisfaction of both groups was noted and compared. Results: After cleaning and disinfection, the relative luminescence luminosity (RLU) value of the surface contamination of the sample instruments and equipment decreased significantly (P < 0.05); and after cleaning and disinfection, the relative luminescence luminosity (RLU) of the observation group’s instruments and equipment decreased significantly, and the value was lower than that of the control group, (P < 0.05); the results of the nursing job satisfaction questionnaire showed that the scores of each survey item in the observation group were higher than those in the control group, (P < 0.05). Conclusion: Integrating sanitary wipes and medical alcohol + gauze disinfection method into the management and use of medical equipment not only improves the disinfection of medical instruments but also improves the job satisfaction of nursing staff. Therefore, this method should be popularized.

Energy drinks and waterpipe smoking associated with disordered eating habits among male Palestinian refugees

This cross-sectional study highlights the concerning relationship between stimulants, alcohol use, and weight-related problems among Palestinian refugee men in the West Bank. Self-administered questionnaires were used to gather data on stimulants and alcohol use and eating attitudes and behaviors (EAT-26). The findings revealed that many refugee men were daily cigarette (61.4%) and waterpipe smokers (15.5%), while 30.6% and 2.3% were daily energy drink and alcohol users, respectively. Moreover, most refugee men (67.3%) were obese, and 23.5% were terrified about being obese. They had disordered eating habits, including the impulse to vomit after meals (63.3%). Moreover, 30.7% scored ≥20 using EAT-26 scale, and 44.4% scored at least one positive behavior, including binge eating (40.4%), purging (10.0%), using laxatives or diet pills (8.3%), excessive exercise (30.9%), and losing weight (24.6%). The results of the adjusted binary logistic regression indicated that risk factors associated with self-induced vomiting were daily (OR = 2.71, p-value = 0.004) and weekly energy drink intake (OR = 2.41, p-value = 0.023), weekly alcohol intake (OR = 10.83, p-value = 0.036), and obesity (OR = 2.57, p-value = 0.002), while inversely associated with weekly waterpipe smoking (OR = 0.297, p-value = 0.007). Obesity was inversely associated with daily (OR = 0.146, p-value < 0.01) and weekly waterpipe smoking (OR = 0.259, p-value = 0.002), and weekly cigarette smoking (OR = 0.251, p-value < 0.01). The study underscores the urgent need for community awareness, professional evaluation, and treatment for obesity and disordered eating habits among Palestinian refugee men. It is essential to address the detrimental effects of alcohol and energy drink intake and tobacco smoking to improve the health outcomes of this vulnerable population.

The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice.

Both excessive alcohol consumption and exposure to high levels of arsenic can lead to neurodegeneration, especially in the hippocampus. Co-exposure to arsenic and alcohol can occur because an individual with an Alcohol Use Disorder (AUD) is exposed to arsenic in their drinking water or food or because of arsenic found directly in alcoholic beverages. This study aims to determine if co-exposure to alcohol and arsenic leads to worse outcomes in neurodegeneration and associated mechanisms that could lead to cell death. To study this, mice were exposed to a 10-day gavage model of alcohol-induced neurodegeneration with varying doses of arsenic (0, 0.005, 2.5, or 10 mg/kg). The following were examined after the last dose of ethanol: (1) microglia activation assessed via immunohistochemical detection of Iba-1, (2) reactive oxygen and nitrogen species (ROS/RNS) using a colorimetric assay, (3) neurodegeneration using Fluoro-Jade® C staining (FJC), and 4) arsenic absorption using ICP-MS. After exposure, there was an additive effect of the highest dose of arsenic (10 mg/kg) in the dentate gyrus of alcohol-induced FJC+ cells. This additional cell loss may have been due to the observed increase in microglial reactivity or increased arsenic absorption following co-exposure to ethanol and arsenic. The data also showed that arsenic caused an increase in CYP2E1 expression and ROS/RNS production in the hippocampus which could have independently contributed to increased neurodegeneration. Altogether, these findings suggest a potential cyclical impact of co-exposure to arsenic and ethanol as ethanol increases arsenic absorption but arsenic also enhances alcohol's deleterious effects in the CNS.

Adolescent alcohol and nicotine exposure alters the adult response to alcohol use.

Adolescence through young adulthood is a unique period of neuronal development and maturation. Numerous agents can alter this process, resulting in long-term neurological and biological consequences. In the clinical literature, it is frequently reported that adolescent alcohol consumption increases the propensity to develop addictions, including alcohol use disorder (AUD), during adulthood. A general limitation of both clinical and human pre-clinical adolescent alcohol research is the high rate of co-using/abusing more than one drug during adolescence, such as co-using/abusing alcohol with nicotine. A primary goal of basic research is elucidating neuroadaptations produced by adolescent alcohol exposure/consumption that promote alcohol and other drug self-administration in adulthood. The long-term goal is to develop pharmacotherapeutics for the prevention or amelioration of these neuroadaptations. This review will focus on studies that have examined the effects of adolescent alcohol and nicotine exposure on adult alcohol consumption, the hypersensitivity of the mesolimbic dopaminergic system, and enhanced responses not only to alcohol but also to nicotine during adulthood. Again, the long-term goal is to identify potential cholinergic agents to prevent or ameliorate the consequences of, peri-adolescent alcohol abuse.

Alcohol’s Effects on the Bystander Decision-Making Model: A Systematic Literature Review

ABSTRACT To decrease rates of sexual assault victimization, young people are encouraged to become involved when they see questionable sexual situations (i.e., be a prosocial bystander). Several factors can facilitate or inhibit intervention, including alcohol use. To inform bystander prevention programs that aim to address alcohol’s impact on bystanders, the current study reviewed research focused on alcohol use and bystander decision making. In December 2022, the authors searched published studies from six major electronic databases. Empirical articles were deemed eligible if they examined alcohol and the bystander decision-making model within the context of sexual assault, were based in the United States or Canada, and not an intervention study; 32 studies were included in the final review. Across 32 studies published between 2015–2022, 12 assessed the proximal effects of alcohol on bystander constructs and the additional studies examined the distal effects of alcohol on bystander constructs. Alcohol use appeared to impede earlier steps of the bystander decision-making model; however, alcohol use was associated with impeding and facilitating bystander decision making at the latter half of the model. Overall, alcohol use appears to be negatively rather than positively associated with bystander constructs. Bystander intervention programs may want to move beyond the narrative of alcohol as a risk factor for sexual assault and discuss how alcohol impairs a bystanders’ ability to recognize risk. More work is needed to ensure researchers assess alcohol consistently and with similar methods (number of drinks, subjective intoxication) to increase generalizability of findings to prevention programs.

An emerging sustainable approach for development and characterization of gluten-based nanocomposite films reinforced with starch nanocrystals in conjugation with chitosan

The present study aimed to access the influence of starch nanocrystals (SNCs) with chitosan on functionality of gluten-based bionanocomposite films. Films were reinforced with SNCs (1, 2, and 3 %) along with chitosan (1.5 % and 2.5 %) and characterized for their functional, barrier, morphological, biodegradable, and antimicrobial properties. Results showed that water absorption capacity, solubility, and water vapour transmission rate were significantly (P < 0.05) reduced with the incorporation of SNCs and chitosan, however, highest tensile strength (40.82 MPa) and elongation at break (31.09 %) were observed in 2 % of SNCs and 2.5 % of chitosan. The multifunctional films have high opacity (lightness value >90) confirming with higher thickness (0.17–0.22 mm) of films. X-ray diffraction studies interpret no significant change in A-type crystallinity of the base biopolymer. Field emission scanning electron microscopy showed that bionanocomposite films have fewer surface cracks, less configuration, and crystallinity changes in the composite structure of biopolymer. Fourier transform infrared spectra revealed no differences in the bands, suggesting a positive molecular association confirming the synergistic effect of polyvinyl alcohol (PVOH) and SNCs on gluten in comparison to control film. However, chitosan in films enhanced antioxidant and antimicrobial properties, showing 13.05 mm and 16.66 mm of a zone of inhibition against Staphylococcus aureus and Escherichia coli, respectively. Furthermore, all films showed noticeable degradation >95 % within 55 days under soil conditions. In summary, the addition of SNCs and chitosan produced a stronger/antibacterial film comparable to plastic films for commercialized food packaging industries.

Experimental study on flexural toughness of fiber reinforced concrete beams: Effects of cellulose, polyvinyl alcohol and polyolefin fibers

Flexural toughnesses of concrete reinforced by cellulose fibers (CTFs), polyvinyl alcohol fibers (PFs) and polyolefin fibers (VSs) are studied through notched beam tests. Flexural strength, ultimate strength, residual flexural and tensile strength, fracture energy, the relationship between crack mouth opening displacement and deflection, as well as the synergistic effect of hybrid fibers are investigated. The results show the following. (1) With the increase of fiber dosage, CTFs enhance the flexural strength and ultimate strength of concrete, while high dosages of PFs and VSs weaken the flexural and ultimate strengths. (2) CTF-PF hybrid fibers have a positive synergistic effect on the flexural strength and ultimate strength of concrete. (3) With the increase of fiber dosage, CTFs firstly strengthen and then weaken the fracture energy of concrete, while PFs weaken and then strengthen the fracture energy, and VSs strengthen the fracture energy. CTF1.2PF2.0VS2.0 is considered the optimal combination of hybrid fibers. (4) It is significant that there is a three-stage linear functional relationship between the crack mouth opening displacement and deflection of fiber reinforced concrete.

Quantitative evaluation of choroidal and retinal microvasculature post-alcohol consumption: A pilot study

PurposeThe aim of this study was to assess the impact of acute, heavy alcohol consumption on the ocular microvasculature, providing insight into the largely unexplored response of microvascular structures to excessive drinking. MethodsHealthy volunteers in this prospective pilot study were tasked with consuming spirits, wine, and water at different times. Alcohol intake was measured according to body weight (g/kg). The ocular microvascular parameters primarily including choroidal volume (CV) and choroidal vessel volume (CVV) reflecting arteriolovenularity, and choroidal capillary density (CCD) reflecting capillary, were evaluated using swept-source optical coherence tomography angiography at baseline and 0.5-, 1-, 2-, and 3-hour post-consumption. ResultsA total of 34 eyes underwent 170 successful examinations in this study. After consuming spirits or wine, we observed significant decreases in CV and CVV values (all P < 0.01 for 0.5-, 1-, 2-, and 3-hour post-consumption), along with significant increase in CCD (P < 0.05 at 0.5-, 1-, 2-hour post-spirits consumption and 1-hour post-wine consumption). The most pronounced changes occurred 1-hour after spirits or wine consumption (all P < 0.001 in both univariate and multivariate model). However, post-consumption changes in the ocular microvasculature showed no significant differences between spirits and wine (P > 0.05). Additionally, no significant differences were observed in any parameters after water intake (all P > 0.05). ConclusionsExcessive alcohol consumption leads to ocular arteriolovenular vasoconstriction and capillary vasodilation, most evident 1-hour post-consumption of spirits and wine. Our research provides insight into alcohol's immediate ocular microvascular effects, hinting at systemic microvascular effects.

Does habitual moderate alcohol consumption enhance working memory performance?

The present study aimed to establish whether habitual alcohol consumption benefits verbal and spatial working memory performance after addressing the main criticisms that have been raised against the finding that alcohol benefits cognition. An adult lifespan sample of 1,652 healthy adults between 21 and 80 years of age participated in the study. Participants were classified as lifetime nondrinkers or drinkers, and several demographic and biological variables were controlled. Alcohol consumption was assessed through a lifestyle questionnaire created for the study. Working memory was measured through a 2-back computerized task. Discrimination and speed in verbal and spatial working memory among drinkers were superior to those among nondrinkers. Total alcohol intake across life and the amount of alcohol intake per week predicted higher verbal and spatial working memory discrimination. Beer drinkers showed more accurate and faster responses in verbal and spatial working memory than nondrinkers, wine drinkers and spirit drinkers. The optimal amount of alcohol intake to benefit working memory for women and men was 100 g per week, which is equivalent to one drink per day. After consuming 350 g of alcohol per week, equivalent to 25 drinks per week, the effects of alcohol on working memory become more negative than the effects of alcohol abstinence. While alcohol consumption is considered a risk factor for several diseases, we found that moderate alcohol intake benefits working memory performance throughout the adult lifespan to a greater extent than whole-life abstinence.

Towards personalized drug delivery via semi-solid extrusion: Exploring poly(vinyl alcohol-co-vinyl acetate) copolymers for hydrochlorothiazide-loaded films

The increasing need for personalized drug delivery requires developing systems with tailorable properties. The copolymer poly(vinyl alcohol-co-vinyl acetate) (PVA/PVAc) allows for adjusting the monomer ratio. This study explored the effect of vinyl alcohol (VA) and vinyl acetate (VAc) monomer ratio on the properties of hydrochlorothiazide (HCT) films. Five copolymers with different VA/VAc ratios were selected and characterized. Semi-solid extrusion was employed as a method for the preparation of HCT-PVA/PVAc films to address the challenges of HCT´s low water solubility, high melting point, and low permeability. All copolymers were suitable for semi-solid extrusion, however, the mechanical properties of films with higher VA proportions were more suitable. The drug was found to be homogeneously distributed on a micrometer level throughout the prepared films. It was found that using different monomer ratios in the copolymer allows for drug release tuning – higher VA proportions showed an increased rate of drug release. Experiments through HT29-MTX cell monolayers revealed differences in HCT permeability between the different formulations. In addition, no cytotoxicity was observed for the tested formulations. The results highlight the effect of monomer ratio on film properties, providing valuable guidance for formulators in selecting PVA/PVAc copolymers for achieving desired high-quality films. In addition, varying the monomer ratio allows tuning of the film properties, and can be applied for personalization, with flexible-dose adjustment and design of appealing shapes of the pharmaceutics, not least attractive for pediatric drug delivery.

Alcohol Consumption During Adolescence Alters the Cognitive Function in Adult Male Mice by Persistently Increasing Levels of DUSP6.

Binge alcohol drinking during adolescence has long-term effects on the adult brain that alter brain structure and behaviors, but the underlying mechanisms remain poorly understood. Extracellular signal-regulated kinase (ERK) is involved in the synaptic plasticity and pathological brain injury by regulating the expression of cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF). Dual-specificity phosphatase 6 (DUSP6) is a critical effector that dephosphorylates ERK1/2 to control the basal tone, amplitude, and duration of ERK signaling. To explore DUSP6 as a regulator of ERK signaling in the mPFC and its impact on long-term effects of alcohol, a male mouse model of adolescent intermittent alcohol (AIA) exposure was established. Behavioral experiments showed that AIA did not affect anxiety-like behavior or sociability in adulthood, but significantly damaged new object recognition and social recognition memory. Molecular studies further found that AIA reduced the levels of pERK-pCREB-BDNF-PSD95/NR2A involved in synaptic plasticity, while DUSP6 was significantly increased. Intra-mPFC infusion of AAV-DUSP6-shRNA restored the dendritic spine density and postsynaptic density thickness by reversing the level of p-ERK and its downstream molecular expression, and ultimately repaired adult cognitive impairment caused by chronic alcohol exposure during adolescence. These findings indicate that AIA exposure inhibits ERK-CREB-BDNF-PSD95/NR2A by increasing DUSP6 in the mPFC in adulthood that may be associated with long-lasting cognitive deficits.

A case study of a virtual reality-based drink driving educational tool

Road traffic accidents are of major concern and could be reduced by better education. This paper describes the development of a virtual reality (VR) app that mimics the effects of alcohol on a driver. It was developed using Unity (version 2019.3.14), smartphone and Google Cardboard™. The user experiences a car following a predetermined route that is lined with trees and objects (traffic lights, road signs and other cars) which they need to spot and react to. By using graphical filters and time delays the driver has a feeling of being under the influence of alcohol. Twenty volunteers (18–60 years old; mean age ± sd 25.5 ± 11.6) participated in its evaluation. Data were collected on concentration times, reaction speed and observation of objects in both the alcohol simulated (impaired) and non-simulated (unimpaired) runs. Data were analysed using paired t-test. The result showed that people spent longer concentrating on objects in the impaired vs unimpaired run (10.72 ± 5.07 vs 5.30 ± 4.22 s n:20; p < 0.0001). The average reaction speed to objects in the unimpaired run was lower than in the impaired run (1.44 ± 0.66 vs 2.66 ± 0.28 s n:20; p < 0.001). Seventeen out of twenty subjects spotted all the required objects in the unimpaired whereas only seven out of twenty spotted all the objects in the impaired run (p < 0.001). The authors have shown that an inexpensive VR app can be used to demonstrate to users the effect that alcohol can have on concentration, reaction speeds and observational skills.

Alcohol induces ER stress and apoptosis by inducing oxidative stress and disruption of calcium homeostasis in glial cells

Alcohol has teratogenic effects that can cause developmental abnormalities and alter anatomical and functional characteristics of the developed brain and other organs. Glial cells play a crucial role in alcohol metabolism and protect neurons from toxic effects of alcohol. However, chronic alcohol exposure can lead to uncontrollable levels of reactive oxygen species, resulting in the death of glial cells and exposing neuronal cells to the toxic effects of alcohol. The exact molecular mechanism of alcohol-induced glial cell death has not been fully explored. This study reported that different concentrations of alcohol induce different expressions of ER stress markers in glial cells, focusing on the role of endoplasmic reticulum (ER) stress. Alcohol-induced concentration-dependent toxicity in both cells also induced oxidative stress, leading to mitochondrial damage. The expression of p53 and apoptotic proteins was significantly up-regulated after alcohol exposure, while Bcl2 (anti-apoptotic) was down-regulated. The signalling pathway for ER stress was activated and up-regulated marker proteins in a concentration-dependent manner. Cells pre-treated with BAPTA-AM and NAC showed significant resistance against alcohol assault compared to other cells. These in vitro findings will prove valuable for defining the mechanism by which alcohol modulates oxidative stress, mitochondrial and ER damage leading to glial cell death.

Brain Volume in Fetal Alcohol Spectrum Disorders Over a 20-Year Span

Anomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD. To test whether brain tissue declines faster with aging in individuals with FASD compared with control participants. This cohort study used magnetic resonance imaging (MRI) data collected from individuals with FASD and control individuals (age 13-37 years at first magnetic resonance imaging [MRI1] acquired 1997-2000) compared with data collected 20 years later (MRI2; 2018-2021). Participants were recruited for MRI1 through the University of Washington Fetal Alcohol Syndrome (FAS) Follow-Up Study. For MRI2, former participants were recruited by the University of Washington Fetal Alcohol and Drug Unit. Data were analyzed from October 2022 to August 2023. Intracranial volume (ICV) and regional cortical and cerebellar gray matter, white matter, and cerebrospinal fluid volumes were quantified automatically and analyzed, with group and sex as between-participant factors and age as a within-participant variable. Of 174 individuals with MRI1 data, 48 refused participation, 36 were unavailable, and 24 could not be located. The remaining 66 individuals (37.9%) were rescanned for MRI2, including 26 controls, 18 individuals with nondysmorphic heavily exposed fetal alcohol effects (FAE; diagnosed prior to MRI1), and 22 individuals with FAS. Mean (SD) age was 22.9 (5.6) years at MRI1 and 44.7 (6.5) years at MRI2, and 35 participants (53%) were male. The FAE and FAS groups exhibited enduring stepped volume deficits at MRI1 and MRI2; volumes among control participants were greater than among participants with FAE, which were greater than volumes among participants with FAS (eg, mean [SD] ICV: control, 1462.3 [119.3] cc at MRI1 and 1465.4 [129.4] cc at MRI2; FAE, 1375.6 [134.1] cc at MRI1 and 1371.7 [120.3] cc at MRI2; FAS, 1297.3 [163.0] cc at MRI1 and 1292.7 [172.1] cc at MRI2), without diagnosis-by-age interactions. Despite these persistent volume deficits, the FAE participants and FAS participants showed patterns of neurodevelopment within reference ranges: increase in white matter and decrease in gray matter of the cortex and decrease in white matter and increase in gray matter of the cerebellum. The findings of this cohort study support a nonaccelerating enduring, brain structural dysmorphic spectrum following prenatal alcohol exposure and a diagnostic distinction based on the degree of dysmorphia. FASD was not a progressive brain structural disorder by middle age, but whether accelerated decline occurs in later years remains to be determined.

Multi-omics analysis of alcohol effects on the liver in young and aged mice.

Excessive alcohol consumption has detrimental effects on the entire organism, especially on the liver. The toxicity is partly dependent on age, as older individuals metabolize alcohol more slowly leading to increased cellular injury. This study aimed to investigate the effects of moderate binge drinking on the liver of young and aged mice in a genome-wide multi-omics approach. We determined DNA methylation (DNAm) using the Illumina MouseMethylation array and gene expression by RNA sequencing in 18 female Balb/c mice in a 2 × 2 design. The animals underwent three moderate binge drinking cycles (ethanol vs. vehicle) and liver tissue was harvested at 4 or 19 months of age. We tested differential gene expression (DE) and DNAm associated with ethanol intake in linear models separately in young and aged mice, performed enrichment analyses for pathways and GWAS signatures of problematic alcohol use, and analysed the overlap of DNAm and gene expression. We observed DE in young and aged animals and substantial overlap in genes such as Bhlhe40, Klf10, and Frmd8. DE genes in aged animals were enriched for biological processes related to alcohol metabolism, inflammation, liver fibrosis, and GWAS signatures of problematic alcohol use. We identified overlapping signatures from DNAm and gene expression, for example, Frmd8 in aged and St6galnac4 in young mice. This study offers converging evidence of novel age-related targets in a moderate alcohol consumption model highlighting dysregulations in genes related to alcohol metabolism, inflammation, and liver fibrosis. Future studies are needed to confirm these results and elucidate the underlying mechanisms.