Chronic Alcohol Use Research Articles

Gastric Cancer Patients’ Pathology and Diagnostic Laparoscopy Evaluation

Background: Gastric cancer is the fourth leading cause of cancer-related mortality worldwide. Objectives: This study describes the epidemiologic, pathologic, imaging, and surgical findings of patients with gastric cancer referred to a tertiary hospital in Tehran, Iran. Methods: This was a single-center cross-sectional study. All the patients referred for a staging laparoscopy of gastric cancer in a tertiary hospital in Tehran, Iran, were included. Results: A total of 30 patients participated in the study. The mean age of the patients was 62 ± 12.6 years, of whom 76.7% were male. None of the patients had a family history of gastric cancer. Four patients were active smokers, 1 had opium addiction, and 1 had a history of chronic alcohol use. Most patients (n = 29) had at least 1 symptom or were symptomatic for 2.8 months (2.8 ± 2.3 months). The most common clinical complaints were abdominal pain, weight loss, and nausea. Within the follow-up period, 43.3% (n = 13) of the patients expired. The Kaplan-Meier diagram of the study revealed a mean survival time of 8.4 ± 2.1 months within the 2-year follow-up, with a median of 6.0 ± 2.3 months. Conclusions: Our results confirmed the previous findings of the clinicopathologic characteristics of gastric cancer patients. Our primary findings were a younger mean age at the diagnosis, advanced stages of cancer at the first visit, low rates of comorbidity and risk factors, an overall survival rate of 43.3%, and a mean survival time of 8.4 ± 2.1 months in 2 years of follow-up.

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

Chronic stress and alcohol (ethanol) use are highly interrelated and can change an individual’s behavior through molecular adaptations that do not change the DNA sequence, but instead change gene expression. A recent wealth of research has found that these nongenomic changes can be transmitted across generations, which could partially account for the “missing heritability” observed in genome-wide association studies of alcohol use disorder and other stress-related neuropsychiatric disorders. In this review, we summarize the molecular and behavioral outcomes of nongenomic inheritance of chronic stress and ethanol exposure and the germline mechanisms that could give rise to this heritability. In doing so, we outline the need for further research to: (1) Investigate individual germline mechanisms of paternal, maternal, and biparental nongenomic chronic stress- and ethanol-related inheritance; (2) Synthesize and dissect cross-generational chronic stress and ethanol exposure; (3) Determine cross-generational molecular outcomes of preconception ethanol exposure that contribute to alcohol-related disease risk, using cancer as an example. A detailed understanding of the cross-generational nongenomic effects of stress and/or ethanol will yield novel insight into the impact of ancestral perturbations on disease risk across generations and uncover actionable targets to improve human health.

Hoe waarheidsgetrouw zijn verklaringen over middelengebruik in het rijgeschiktheidsonderzoek?

How truthful are statements about substance use in the fitness to drive examination? In Belgium, the court can order a fitness to drive examination on indication. One is not fit to drive if there has been excessive alcohol and/or drug use in the past 6 months. Chronic excessive alcohol use corresponds to an average consumption of ≥ 6 units per day or ≥ 42 units per week over several months. Toxicologically, 30 pg/mg ethylglucuronide (direct alcohol marker) in scalp hair strongly suggests this. For drugs, it is sufficient to demonstrate this substance in one of the samples. The anamnesis and toxicology were compared with a McNemar test. The sensitivity, specificity and positive/negative predictive value of the anamnesis as a diagnostic test were calculated. People are more likely to be unfit to drive based on the toxicological analysis than based on the anamnesis (respectively 60% versus 40%). The greatest discrepancy is seen regarding alcohol consumption. In addition, toxicologically more cases of drug use were detected. This study shows that statements regarding alcohol and drug use within the fitness to drive examination are not reliable.

Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction.

Chronic preconception paternal alcohol use adversely modifies the sperm epigenome, inducing fetoplacental and craniofacial growth defects in the offspring of exposed males. A crucial outstanding question in the field of paternal epigenetic inheritance concerns the resilience of the male germline and its capacity to recover and correct sperm-inherited epigenetic errors after stressor withdrawal. We set out to determine if measures of the sperm-inherited epigenetic program revert to match the control treatment 1 month after withdrawing the daily alcohol treatments. Using a voluntary access model, we exposed C57BL/6J males to 6% or 10% alcohol for 10 weeks, withdrew the alcohol treatments for 4 weeks, and used RNA sequencing to examine gene expression patterns in the caput section of the epididymis. We then compared the abundance of sperm small RNA species between treatments. In the caput section of the epididymis, chronic alcohol exposure induced changes in the transcriptional control of genetic pathways related to the mitochondrial function, oxidative phosphorylation, and the generalized stress response (EIF2 signaling). Subsequent analysis identified region-specific, alcohol-induced changes in mitochondrial DNA copy number across the epididymis, which correlated with increases in the mitochondrial DNA content of alcohol-exposed sperm. Notably, in the corpus section of the epididymis, increases in mitochondrial DNA copy number persisted 1 month after alcohol cessation. Analysis of sperm noncoding RNAs between control and alcohol-exposed males 1 month after alcohol withdrawal revealed a ∼100-fold increase in mir-196a, a microRNA induced as part of the nuclear factor erythroid 2-related factor 2 (Nrf2)-driven cellular antioxidant response. Our data reveal that alcohol-induced epididymal mitochondrial dysfunction and differences in sperm noncoding RNA content persist after alcohol withdrawal. Further, differences in mir-196a and sperm mitochondrial DNA copy number may serve as viable biomarkers of adverse alterations in the sperm-inherited epigenetic program.

Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use

Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal–striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.

Methanol poisoning during the COVID-19 pandemic in Iran: A retrospective cross-sectional study of clinical, laboratory, and brain imaging characteristics and outcomes.

To evaluate the frequency and significance of brain imaging findings in methanol poisoning patients and to propose a criterion for prioritizing brain imaging. We retrospectively reviewed the data of 306 patients (286 men and 34 women, mean age 32.10 ± 9.9 years) with confirmed methanol poisoning who were admitted to two hospitals in Iran during the COVID-19 pandemic. We analyzed their demographic, clinical, laboratory, and brain imaging data. The main brain computed tomography(CT) scan findings were hypodensity in the putamen (11.1%), cerebellar nuclei (8.2%), diffuse cerebral edema (7.5%), and intracranial hemorrhage (ICH; 1.6%). These findings were associated with blood pH, Glasgow Coma Scale (GCS), renal failure, bicarbonate, oxygen, carbon dioxide, potassium, and glucose levels (p < 0.05). Poor prognosis was related to blindness, opium addiction, chronic alcohol use, hyperglycemia, and abnormal CT scans (p < 0.001 for all). The most predictive brain imaging findings for poor prognosis were hypodensity in the cerebellar nuclei, diffuse cerebral edema, and ICH. Brain imaging can provide valuable information for the diagnosis and management of methanol poisoning patients. We suggest that patients with severe acidosis, low GCS, low pH, low oxygen saturation, and high glucose levels should undergo brain CT scan as a priority.

Anemia Outside the Box: Nonimmune Intramedullary Hemolytic Anemia Driven By Vitamin B12 Deficiency

Introduction: Vitamin B12 and folate deficiencies are common etiologies of macrocytic anemia, mostly encountered with chronic alcohol use, and uncommon for healthy individuals with unremarkable medical history. The pathogenesis of the resulting anemia is described by two possible mechanisms: either ineffective erythropoiesis, driven by vitamin B12 deficiency, or more rarely, via nonimmune intramedullary hemolysis. We present a very rare case of severe vitamin B12 deficiency leading to nonimmune intramedullary hemolysis and highlight the diagnostic evaluation and tailored management. Case Presentation: A 49-year-old female with history of depression, chronic alcohol use and chronic nitrous oxide inhalation, presented with lethargy, hypotension and fevers with visual hallucinations, and was subsequently admitted for acute encephalopathy. Findings on physical examination included diminished proprioception and diminished sensation to fine touch, pinprick and vibration of the lower extremities with distal hyperreflexia of the patellar and Achilles tendon reflexes bilaterally. Lab work was notable for leukopenia and macrocytic anemia with a significant drop in hemoglobin to 9.6 from a baseline of 13.2 within 5 months and MCV of 103. Extensive investigation of encephalopathy was undertaken, of which we note infectious workup, prompted by the septic presentation, which showed Staphylococcus aureus bacteremia. On the other hand, the patient's anemia was concurrently investigated. Hemolysis workup was positive (LDH 394 U/L; direct bilirubin 1.6 mg/dL; haptoglobin&amp;lt;8 mg/dL; reticulocyte count 6.1%); however, schistocytes were low on peripheral smear (Figures 1 and 2). As such, nonimmune intramedullary hemolysis was suspected. Further anemia workup revealed severe vitamin B12 deficiency (75 ng/L), consistent with the physical exam findings, but normal folate levels. Of note, methylmalonic acid levels and homocysteine were also elevated (respectively 4.39 nmol/mL, and 142 umol/L). The constellation of the clinical presentation and all the laboratory findings confirmed a nonimmune intramedullary hemolytic process, elicited by vitamin B12 deficiency. This deficiency was thought to be multifactorial, mainly caused by chronic alcohol abuse, in addition to persistent nitrous oxide use. It was also suggested that hemolysis could be a consequence of drug-induced carboxyhemoglobinemia (level was 9.4%), whereby carboxyhemoglobin can form during the binding and release of nitric oxide from hemoglobin. Treatment was focused on replacing vitamin B12 with 1000 mcg daily intramuscular injections for 7 days, then weekly thereafter for 4 weeks, followed by monthly injections. Improvement of hemoglobin to 11.1 with improvement of neurologic exam findings were noted prior to discharge. Conclusion: Nonimmune hemolytic anemia must be included in the differential diagnosis when evaluating patients with anemia concurrent with vitamin B12 deficiency, mostly encountered with chronic alcohol use. Vitamin B12 supplementation remains the key treatment to correct this rare, but serious outcome of vitamin B12 deficiency.

Surviving Multiple Cardiac Arrests Secondary to Catastrophic Sero-Negative Antiphospholipid Syndrome: A Case Report

Antiphospholipid syndrome (APS) is an autoimmune disorder which predisposes to venous and arterial thrombosis due to the autoantibodies targeting phospholipids in cell membranes contributing to a pro-thrombotic state. The appropriately named catastrophic anti-phospholipid syndrome (CAPS) is distinguished from classical APS by the rapid involvement of 3+ organs, evidence of areas of small vessel occlusions, and significantly elevated anti-phospholipid titers (Cervera, 2018). To further complicate the matter, there is a growing body of evidence of the existence of sero-negative APS (SNAPS) that are negative for the classical lupus anticoagulant, anticardiolipin antibody (aCL), and anti-beta2 glycoprotein-I but may be positive for non-criteria APS antibodies. Presented below is a patient with SNAPS who responded to the therapy for CAPS despite negative classical autoantibodies. A 34 year old man with a past medical history of chronic alcohol use presented to the ED with a two day history of worsening shortness of breath. The patient was found to have an spO2 of 45-50% on room air and was quickly transitioned to a non-rebreather and subsequently BIPAP. Initial CBC was significant for WBC 22.1, Hg 19.3, Hct 58.5, MCV 100.8, and platelets of 166 consistent with neutrophilic leukocytosis and macrocytic polycythemia. D-dimer &amp;gt;20 was suggestive recent/on-going coagulation and/or fibrinolysis. Due to worsening respiratory failure, he was intubated and admitted to the ICU. While on 3 vasopressors he became bradycardic and a code blue was called for pulseless electrical activity (PEA). After 3 rounds of CPR he achieved return of spontaneous circulation (ROSC) and was taken for urgent CT imaging. After arriving in the radiology department he went into cardiac arrest for two rounds of CPR before achieving ROSC and being scanned and returning to the ICU. Polycythemia tests were drawn which revealed elevated erythropoietin of 52.1 (2.6-18.5) and ultimately negative JAK2. Chest CTA was significant for a PE with a heavy clot burden involving the entire right lung and the left upper and lower lobes. CT C/A/P showed findings of bilateral lower lobe pneumonia, severe gastritis, pancolitis, proctitis, pancreatitis with a 4.6cm pseudocyst, and fatty liver with congestive enhancement. Tissue-type plasminogen activator (tPA) bolus and infusion was initiated based on the imaging findings with the third cardiac arrest occurring 7 minutes later early in the morning. Repeat CBC revealed an Hgb/Hct of 22.2 g/dL and 71.5%, respectively, with a significant drop in platelets down to 103 with occasional large platelets consistent with peripheral destruction of platelets was noted on peripheral blood smear (PBS). Therapeutic phlebotomy of 300mL was subsequently performed with two additional cardiac arrests within 2 hours of each other before vascular surgery was able to perform thrombectomies of the involved pulmonary arteries and initiate catheter-directed thrombolysis. Platelet count dropped while on heparin to 25,000 so a HIT panel was ordered and he was transitioned to argatroban. At this point hematology was consulted who was concerned for CAPS and ordered aPL (anti-phospholipid) tests along with an appropriate panel of labs to rule out alternative causes. Peripheral blood smear did not reveal fragmentation of RBC to suspect TTP. Tests for ACL IgG/IgM and anti-beta2GPI IgG/IgM antibodies, COVID, HIV, ADAMTS deficiency, hereditary thrombophilia, and ANA were negative. High-dose steroids and daily plasma exchanges via vascath was initiated and within 12 hours there was significant improvement. He was extubated and off pressors in 24 hours with improved platelets. Lupus anticoagulant test results were reported after discharge with dVVT mix and PTT LA mix both being prolonged, however, repeat lupus anticoagulant 3 months later was negative. Given the potentially catastrophic effects of a missed CAPS diagnosis, a high level of clinical suspicion is needed as plasma exchange can quickly alleviate an otherwise disastrous condition. Further research into non-criteria APS autoantibodies (IgA)may be able to help guide future SNAPS diagnoses.

Long-lasting mechanical hypersensitivity and CRF receptor type-1 neuron activation in the BNST following adolescent ethanol exposure.

Adolescent alcohol use can produce long-lasting alterations in brain function, potentially leading to adverse health outcomes in adulthood. Emerging evidence suggests that chronic alcohol use can increase pain sensitivity or exacerbate existing pain conditions, but the potential neural mechanisms underlying these effects require further investigation. Here, we evaluate the impact of chronic ethanol vapor on mechanical sensitivity over the course of acute and protracted withdrawal in adolescent and adult male and female mice, and its potential association with alterations in corticotropin-releasing factor (CRF) signaling within the bed nucleus of the stria terminalis (BNST). Adolescent and adult male and female mice underwent intermittent ethanol vapor exposure on 4 days/week for 2 weeks. Mechanical thresholds were evaluated 5 h and 7, 14, 21, and 28 d after cessation of ethanol exposure using the von Frey test. For mice with a history of adolescent ethanol exposure, brains were collected for insitu RNAscope processing after the final test. Messenger RNA expression of c-Fos, Crfr1, and Crf in the BNST subregions was examined. Exposure to intermittent ethanol vapor induced persistent mechanical hypersensitivity during withdrawal in both adolescent and adult mice. Notably, the effect was more transient in mice exposed to ethanol during adulthood, resolving by day 28 after ethanol exposure. Furthermore, both male and female mice with a history of adolescent ethanol exposure exhibited increased activation of CRF receptor type 1 (CRFR1) neurons within the dorsolateral BNST. Our results support the conclusion that intermittent ethanol exposure can induce mechanical hypersensitivity, potentially through the activation of BNST CRFR1 neurons. These findings provide a basis for future studies aimed at evaluating specific subpopulations of BNST neurons and their contribution to pain in individuals with a history of alcohol use.

Adolescent ethanol exposure promotes mechanical allodynia and alters dopamine transmission in the nucleus accumbens shell.

Excessive alcohol consumption in adolescence can disrupt neural development and may augment pain perception. Recent studies have shown that the nucleus accumbens (NAc) shell is involved in mediating pain sensitivity after peripheral inflammation in rodent models of chronic pain and alcohol use disorder. Interestingly, there have been very few studies examining the impact of chronic ethanol exposure during adolescence on pain sensitivity in adulthood. Therefore, in this project, we investigated the impact of adolescent chronic intermittent ethanol (aCIE) exposure on mechanical allodynia. Furthermore, given the involvement of the NAc shell in pain processing and chronic ethanol-mediated changes, we measured changes in accumbal dopamine kinetics during protracted withdrawal. We found that both male and female aCIE rats show mechanical allodynia during withdrawal. Furthermore, male and female aCIE rats show greater evoked tonic dopamine release, maximal rate of dopamine reuptake, and dopamine affinity to the dopamine transporter in the NAc shell compared with controls. With phasic stimulation, aCIE rats also showed greater dopamine release compared with AIR-exposed rats. Inhibition of dopamine transmission targeted in the NAc shell reversed the aCIE-associated facilitation of mechanical allodynia in both sexes. These data suggest that aCIE exposure exacerbates pain sensitivity during withdrawal in an accumbal dopamine-dependent manner.

Impact of proton pump inhibitor on quality of anticoagulant control and outcomes in atrial fibrillation patients treated with an oral anticoagulant in the COOL-AF registry

Abstract Introduction Proton pump inhibitor (PPI) is commonly prescribed in patients treated with antithrombotic therapy, assuming it will reduce bleeding risk irrespective of the risk of bleeding. Although PPI may reduce the risk of gastrointestinal bleeding in those treated with an oral anticoagulant, PPI may increase INR by accelerating warfarin absorption, thereby increasing the risk of bleeding. We aimed to assess the impact of PPI use on outcomes and quality of anticoagulant control in AF patients treated with OAC. Methods The COOL-AF registry was a nationwide prospective observational study enrolling AF patients from 27 hospitals in Thailand between 2014 and 2017. The registry aimed to evaluate antithrombotic patterns, quality of OAC control, and clinical outcomes. Clinical information of patients was collected every six months and until three years. Patients treated with oral anticoagulants (either warfarin or non-vitamin K antagonist OAC (NOAC)) were included in the present analysis. Patients receiving any PPI type and dosage at the registry entry were counted as PPI users. Poor anticoagulant control was defined as time to therapeutic range (TTR) less than 65%. The association between PPI use and outcomes, including GI bleeding, overall bleeding, all-cause mortality, and ischemic stroke or systemic embolization, were assessed in the Cox model adjusted for age, prior GI bleeding, chronic alcohol use, chronic kidney disease, liver disease, smoking, and baseline anemia. Subgroup analyses were performed in patients at high bleeding risk (HAS-BLED score ≥ 3), and in patients concomitantly treated with antiplatelet. Results Of 3,402 patients in the registry, 2568 (75.5%) were treated with OAC at baseline. The prevalence of females was 43.4%, with a mean age of 68.4 years. The majority of patients (91.1%) received warfarin. The incidence of major bleeding was 2.11 (1.79–2.48) per 100 person-years. PPI was used at baseline in 707 patients (20.8%). Compared with their counterpart, PPI was more frequently used in high-bleeding risk patients (27.3% vs. 18.1%, p &amp;lt; 0.001) and in those with concomitant antiplatelet therapy (37.5% vs. 17.1%, p &amp;lt; 0.001). The mean TTR was similar between PPI and non-PPI users (52.5% vs. 53.8%, p 0.37). PPI use was not associated with poor anticoagulant control (adjusted OR 1.12, 95% 0.89-1.40). The risk of GI bleeding in PPI users was similar to non-user (adjusted HR 1.01, 95%CI 0.59-1.75). The risk of all-cause mortality, ischemic stroke or systemic embolization, and overall bleeding was not different between PPI and non-PPI users. There was no significant interaction between PPI use and bleeding risk or concomitant antiplatelet therapy on adverse outcomes. Conclusion PPI use has no impact on major outcomes, including bleeding in AF patients treated with OAC. The practice of concomitant prescribing of PPI in patients treated with OAC is needed to be re-examined, given the potentially high impact of health care costs.PPI use and outcomes

Alcohol after injury: Uncovering the synergistic effects of chronic alcohol use after blast-induced mTBI

Alcohol after injury: Uncovering the synergistic effects of chronic alcohol use after blast-induced mTBI

6 Semantic and Phonemic Fluency in Alcohol Dependent Individuals

Objective:Verbal fluency consists of semantic and phonemic fluency and is often used to detect verbal ability and executive control (Shao et al., 2014). While research has found general verbal fluency impairments in chronic alcohol use, few studies have examined semantic and phonemic fluency separately (Stavro et al., 2012; Stephan et al., 2017). This meta-analytical study examines the performance of abstinent alcohol-dependent individuals on semantic fluency (categories) and phonemic fluency (letters).Participants and Methods:As part of a larger study, two researchers independently searched eight databases, extracted required data, and calculated effect sizes on neuropsychological data in alcohol dependent (AD) individuals. Inclusion criteria for articles were: (a) comparison of abstinent alcohol-dependent patients to healthy controls, (b) matched control group on age, education, or IQ, and (c) standardized neuropsychological testing. Exclusion criteria included: (a) diagnosis of Axis I disorders (other than alcohol dependence), (b) comorbidity with other disorders that impact neuropsychological functioning, or (c) not published or translated into English. A total of 31 articles (AD n=1,080 and HC n=1,090) was analyzed in this study.Results:Semantic fluency evidenced a statistically significant and medium effect size estimate (g = 0.632, p &lt; 0.001). The heterogeneity for semantic fluency was statistically significant (Q=152.468, df=20, p=0.000). Phonemic fluency evidenced a statistically significant and medium effect size estimate (g = 0.572, p &lt; 0.001). The heterogeneity for phonemic fluency was also statistically significant (Q=236.697, df=24, p=0.000).Conclusions:Deficits in semantic and phonemic fluency are both associated with alcohol dependence. Although some previous research has reported more frontal lobe impact of alcohol, which would be expected to impact phonemic more readily than semantic fluency, this is not evident in the current data. There are many possible reasons for this failure to observe this dissociation meta-analytically. Some potential reasons include the possibility that alcohol affects multiple regions of the brain, that both these measures are affected by alcohol but miss the subtlety associated with frontal damage, or the likelihood that when studies are aggregated in meta-analysis the heterogeneity results in a regression to the mean effect size. These and other reasons are not mutually exclusive and future research should attempt to examine these and other hypotheses.

Alcohol and the Brain-Gut Axis: The Involvement of Microglia and Enteric Glia in the Process of Neuro-Enteric Inflammation.

Binge or chronic alcohol consumption causes neuroinflammation and leads to alcohol use disorder (AUD). AUD not only affects the central nervous system (CNS) but also leads to pathologies in the peripheral and enteric nervous systems (ENS). Thus, understanding the mechanism of the immune signaling to target the effector molecules in the signaling pathway is necessary to alleviate AUD. Growing evidence shows that excessive alcohol consumption can activate neuroimmune cells, including microglia, and change the status of neurotransmitters, affecting the neuroimmune system. Microglia, like peripheral macrophages, are an integral part of the immune defense and represent the reticuloendothelial system in the CNS. Microglia constantly survey the CNS to scavenge the neuronal debris. These cells also protect parenchymal cells in the brain and spinal cord by repairing nerve circuits to keep the nervous system healthy against infectious and stress-derived agents. In an activated state, they become highly dynamic and mobile and can modulate the levels of neurotransmitters in the CNS. In several ways, microglia, enteric glial cells, and macrophages are similar in terms of causing inflammation. Microglia also express most of the receptors that are constitutively present in macrophages. Several receptors on microglia respond to the inflammatory signals that arise from danger-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs), endotoxins (e.g., lipopolysaccharides), and stress-causing molecules (e.g., alcohol). Therefore, this review article presents the latest findings, describing the roles of microglia and enteric glial cells in the brain and gut, respectively, and their association with neurotransmitters, neurotrophic factors, and receptors under the influence of binge and chronic alcohol use, and AUD.

Determinants and outcomes of acute pancreatitis in patients hospitalized for COVID-19: Early pandemic experience

ObjectivesTo examine the predictors and outcomes associated with the development of acute pancreatitis (AP) in patients hospitalized with Coronavirus Disease 2019 (COVID-19). MethodsThis is an observational analysis of the 2020 National Inpatient Sample Database. The study includes adult patients who were admitted with a confirmed diagnosis of COVID-19 and stratifies them based on the presence or absence of AP during their hospitalization. Predictors of AP development between the two groups and differences in outcomes are examined. Multivariate logistic regression analysis using Stata/BE 17.0 is conducted, with adjustments made for age, sex, race, and Charlson Comorbidity Index (CCI). Statistical significance is determined at a p-value of <0.05. ResultsSignificant factors associated with an increased risk of AP in COVID-19 patients include Hispanic ethnicity, higher Charlson Comorbidity Index (CCI) score, residence in states located in the southern region, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use. COVID-19 patients who developed AP were also found to be at higher risk of adverse outcomes, including mortality, acute coronary syndrome, acute kidney injury, sepsis, septic shock, in-hospital cardiac arrest, invasive mechanical ventilation, upper gastrointestinal bleeding, prolonged length of stay, and increased healthcare cost. ConclusionsIn hospitalized patients with COVID-19, the presence of AP is associated with increased mortality and morbidity. Risk factors for developing AP in this population include Hispanic ethnicity, residence in the southern region, higher Charlson Comorbidity Index (CCI) score, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use.

Impaired Executive Functioning Associated with Alcohol-Related Neurocognitive Disorder including Korsakoff's Syndrome.

(1) Background: chronic alcohol use is consistently associated with impaired executive functioning, but its profile across the spectrum from mild to major alcohol-related cognitive impairment is, to date, unclear. This study aims to compare executive performances of patients with alcohol-induced neurocognitive disorder, including Korsakoff's syndrome (KS), by using a computerized assessment battery allowing a fine-grained and precise neuropsychological assessment; (2) Methods: performances of 22 patients with alcohol-related cognitive impairment (ARCI) and 20 patients with KS were compared to those of 22 matched non-alcoholic controls. All participants were diagnosed in accordance with DSM-5-TR criteria and were at least six weeks abstinent from alcohol prior to assessment. Executive function was evaluated using four subtests of Cambridge Neuropsychological Test Automated Battery (CANTAB®); (3) Results: significant differences between groups were found on spatial working memory (updating), sustained attention and inhibitory control, set shifting, and planning. Healthy controls performed significantly better than both patient groups (Games-Howell post hoc; p < 0.05), but no differences in performance were found between the ARCI and KS group; (4) Conclusions: ARCI and KS patients showed significant executive impairments, most prominent in updating, set-shifting and general planning abilities. Findings suggest equivalent levels of executive function in ARCI and KS patients. Our results highlight executive function as a significant hallmark of alcohol-induced neurocognitive disorder and stipulate the importance of early assessment and evaluation of skills to guide treatment.

Magnitude, relationship and determinants of attention deficit hyperactivity disorder and depression among University of Gondar undergraduate students, Northwest Ethiopia, 2022: Non-recursive structural equation modeling.

Up to 80% of adults with attention deficit hyperactivity disorder (ADHD) may have a concomitant psychiatric disorder. ADHD and depression, combined with the demands of University life, can pose serious challenges for students. However, there are limited studies conducted on this topic in our country. Therefore, the current study assessed the magnitude, relationship, and determinants of ADHD and depressive symptoms among students at the University of Gondar. An institution-based cross-sectional study was employed among 1514 undergraduate students at the University of Gondar from June 1-20, 2022. A stratified, simple random sampling technique was applied. Structural equation modeling was employed. The degree of relationship was interpreted based on the adjusted regression coefficient with 95% confidence interval (CI) and p-value (<0.05). In our study, 37.6% [CI: 35.2-40.1%] and 20.01% [CI: 18.1-22.1%] of the participants had depressive and ADHD symptoms, respectively. Chronic illness [β = 0.19, CI; 0.09, 0.30], alcohol use [β = 0.10, CI; 0.03, 0.17], social support [β = -0.23, CI; -0.29, -0.17], problematic internet use (PIU) [β = 0.23, CI; 0.18, 0.27], and insomnia [β = 0.24, CI; 0.17, 0.30] had a direct relationship with depressive symptoms. Mother education level [β = -0.09, CI; -0.13, -0.06], birth order [β = -0.09, CI; -0.11, -0.07], chat chewing [β = 0.18, CI; 0.06, 0.30], and depressive symptoms [β = 0.73, CI; 0.62, 0.86] had a direct relationship with ADHD. Chronic illness [β = 0.14, CI; 0.06, 0.22], PIU [β = 0.16, CI; 0.13, 0.21], social support [β = -0.16, CI; -0.22, -0.12], and insomnia [β = 0.17, CI; 0.13, 0.23] had an indirect effect on ADHD. The prevalence of ADHD and depressive symptoms was high. Chronic disease, alcohol use, social support, PIU, and insomnia had a direct effect on depressive symptoms and an indirect effect on ADHD. Mother education, birth order, chat chewing, and depressive symptoms had a direct effect on ADHD. Our study provided useful clues for clinical treatment and school-based interventions that aim to improve college students' mental well-being. It is better to design school-based intervention and prevention programs to achieve timely diagnosis and treatment of these disorders among university students.

Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection.

Alcohol Use Disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to SARS-CoV-2 infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared to non-AUD cells. Bronchial epithelial cells from AUD patients showed a significant decrease in barrier function 72 h post infection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1, indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased β-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple pro-inflammatory cytokines including TNFα, IL-1β, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines EGF and GM-CSF was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and barrier dysfunction in response to infection by SARS-CoV-2.

Chronic alcohol consumption dysregulates innate immune response to SARS-CoV-2 in the lung

Alcohol consumption is widespread with over half of the individuals over 18 years of age in the U.S. reporting alcohol use in the last 30 days. Moreover, 9 million Americans engaged in binge or chronic heavy drinking (CHD) in 2019. CHD negatively impacts pathogen clearance and tissue repair, including in the respiratory tract, thereby increasing susceptibility to infection. Although, it has been hypothesized that chronic alcohol consumption negatively impacts COVID-19 outcomes; the interplay between chronic alcohol use and SARS-CoV-2 infection outcomes has yet to be elucidated. In this study we employed luminex, scRNA sequencing, and flow cytometry to investigate the impact of chronic alcohol consumption on SARS-CoV-2 anti-viral responses in bronchoalveolar lavage cell samples from humans with alcohol use disorder and rhesus macaques that engaged in chronic drinking. Our data show that in both humans (n=6) and macaques (n=11), the induction of key antiviral cytokines and growth factors was decreased with chronic ethanol consumption. Moreover, in macaques fewer differentially expressed genes mapped to Gene Ontology terms associated with antiviral immunity following 6 month of ethanol consumption while TLR signaling pathways were upregulated. These data are indicative of aberrant inflammation and reduced antiviral responses in the lung with chronic alcohol drinking. This study was supported by NIH 1R01AA028735-04 (Messaoudi), U01AA013510-20 (Grant), R24AA019431-14 (Grant), R24AA019661 (Burnham), P-51OD011092 (ONPRC core grant support). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Neural and Psychosocial Mechanisms Underlying Alcohol Use and Pain Interactions: Overview of Current Evidence and Future Directions.

A growing body of research indicates bidirectional associations between alcohol use and pain. In this review, we highlight common neural and psychosocial mechanisms underlying pain and alcohol use and identify current gaps in the literature regarding alcohol/pain interactions. We also suggest future directions for the field moving forward, including more nuanced conceptualization of alcohol's negative reinforcing effects in the context of pain, broader use of clinically-relevant experimental pain induction modalities, and characterization of age, biological sex, gender, race, and ethnicity as moderators of pain/alcohol interactions. Acute alcohol intake has analgesic and negative-reinforcing effects in the context of pain, and chronic heavy alcohol use appears to increase risk for development of chronic pain. At the same time, pain, both acute and chronic, acts as a proximal antecedent for alcohol use and is associated with relapse risk for individuals in recovery from alcohol use disorder. Although the links between alcohol use and pain are increasingly appreciated, significant gaps in understanding remain and systematic study of alcohol/pain interactions at all levels, including basic, preclinical, translational, and interventional, is needed.