The Interest in Betting, Smoking, Alcohol, and Drugs in Malawi: Changing Trends between 2012-2022.

Background: In recent years, the online gambling market has rapidly developed, and betting has become one of the most popular forms of gambling. The aim of this study was to analyse the interest of the Malawian population in terms related to betting, sports betting, alcohol, cigarettes, and some psychoactive drugs through the relative search volumes of Google Trends. Methods: Internet search query data related to betting, sports betting, alcohol, cigarettes, and psychoactive drugs were obtained monthly from Google Trends for the period 2010-2022. Comparisons of interest levels in these topics were conducted in Malawi, and correlation coefficients were calculated. Results: In Malawi, relative search volumes for betting and sports betting terms were the highest (average RSVs: 66% and 30%). It was found that from 2019 onwards, the interest in betting and sports-related search topics and keywords increased significantly (p < 0.001). Strong positive correlations were found between betting-related keywords and alcohol and gross domestic product (r = 0.831 and r = 0.901, p < 0.001). A positive correlation was found between betting and psychoactive drug-related terms (minimum r = 0.417, p < 0.01). Conclusions: This study concludes that the interest of the Malawian population in betting has increased in recent years, while interest in psychoactive drugs and alcohol remains high. Gross domestic product is highly correlated with society's interest in betting. It was additionally found that Google Trends can be used as a tool to predict and monitor future risky behaviours, such as gambling disorder.

Hemichannels contribute to mitochondrial Ca2+ and morphology alterations evoked by ethanol in astrocytes.

Alcohol, a toxic and psychoactive substance with addictive properties, severely impacts life quality, leading to significant health, societal, and economic consequences. Its rapid passage across the blood-brain barrier directly affects different brain cells, including astrocytes. Our recent findings revealed the involvement of pannexin-1 (Panx1) and connexin-43 (Cx43) hemichannels in ethanol-induced astrocyte dysfunction and death. However, whether ethanol influences mitochondrial function and morphology in astrocytes, and the potential role of hemichannels in this process remains poorly understood. Here, we found that ethanol reduced basal mitochondrial Ca2+ but exacerbated thapsigargin-induced mitochondrial Ca2+ dynamics in a concentration-dependent manner, as evidenced by Rhod-2 time-lapse recordings. Similarly, ethanol-treated astrocytes displayed increased mitochondrial superoxide production, as indicated by MitoSox labeling. These effects coincided with reduced mitochondrial membrane potential and increased mitochondrial fragmentation, as determined by MitoRed CMXRos and MitoGreen quantification, respectively. Crucially, inhibiting both Cx43 and Panx1 hemichannels effectively prevented all ethanol-induced mitochondrial abnormalities in astrocytes. We speculate that exacerbated hemichannel activity evoked by ethanol may impair intracellular Ca2+ homeostasis, stressing mitochondrial Ca2+ with potentially damaging consequences for mitochondrial fusion and fission dynamics and astroglial bioenergetics.

Subacute encephalopathy with seizures in alcoholics (SESA) syndrome: Relevant questions.

OBJECTIVE: The aim of this article is to answer three relevant issues: i/What epileptic condition is referred to as subacute encephalopathy with seizures in alcoholics (SESA) syndrome; ii/ Why it can be important to distinguish SESA syndrome in clinical practice and iii/ What do we know about its pathophysiology. METHODS: We reviewed all cases published in the English language from the initial description of the syndrome to the present. All met the previously established criteria for SESA syndrome were included in our analysis. RESULTS: We found 34 patients diagnosed with SESA syndrome Fourteen (41.1%) out of 34 patients were over 60 years of age. In 12 (35.2 %), abstinence, and in 4 (11.7 %) excessive consumption of alcohol, were considered precipitating factors, respectively. Triggering causes were unknown in 18 cases (53.0 %). All cases (100 %) presented with altered mental status. Fourteen (41.1 %) subjects had a history of epileptic seizures in the context of alcohol withdrawal syndrome (AWS). Twenty (58.8 %) patients had focal motor seizures (FMSs), 24 (70.5 %) bilateral tonic-clonic seizures (BTCSs), and 15 (44.1 %) focal impaired awareness seizures (FIASs). In 8 (23.5 %), criteria for focal nonconvulsive status epilepticus (NCSE) were met. Twenty-eight (82.3 %) subjects had transient neurological deficits. In 29 (85.2 %) subjects, lateralized periodic discharges (LPDs) were observed on the EEG. Areas of signal hyperintensities and restricted diffusion in neuroimaging were mentioned in 22 subjects (64.7 %). Transfer to the intensive care unit was necessary in 8 (23.5 %) subjects. Thirteen (38.2 %) had recurrent episodes. Enduring brain damage was mentioned in 9 (26.4 %) cases. The most used anti-seizure medication (ASM) was levetiracetam, followed by phenytoin and lacosamide. CONCLUSIONS: SESA syndrome represents a well-defined subtype of focal NCSE in patients with chronic alcoholism. Its prompt recognition can facilitate the initiation of early ASM therapy and help design appropriate video-EEG evaluation and a treatment strategy.

Effectiveness of the Korean-Patient Placement Criteria for Alcohol Use Disorders: A Prospective Exploratory Study.

OBJECTIVE: Various patient placement criteria (PPC) have been developed to address alcohol use disorder (AUD), which has a high relapse rate and imposes substantial socioeconomic costs. Although research has shown PPC to be an effective tool, evidence supporting the Korean-PPC (K-PPC) is insufficient. This paper investigated whether treatment matching with the K-PPC was effective, based on variables related to AUD. METHODS: In total, 524 participants were evaluated using the 6 dimensions of the K-PPC and levels of care (LoC) were recommended based on the results. Participants whose treatment matched with the recommended LoC were classified into the matched group, and those whose treatment did not match were classified into the mismatched group. Subsequently, treatment was planned according to the determined LoC, and a total of 3 follow-up evaluations were conducted at 1 month, 3 months, and 6 months. RESULTS: There was no significant difference in the follow-up rate between the K-PPC matched group and the mismatched group. Of the variables measured by the 6 dimensions of the K-PPC, alcohol-related variables, depression, insight, and biomedical outcomes showed the most significant results (especially alcohol-related variables) from the baseline evaluation to the 6-month follow-up. In addition, the average adherence to the treatment program in the 6-month period was found to be higher in the matched group than in the mismatched group. CONCLUSION: The K-PPC could be effective for placing patients and providing treatment by matching patient characteristics. Enhancing treatment program retention can also have a positive effect on clinical outcomes.

Identification of phosphodiesterase-7A (PDE7A) as a novel target for reducing ethanol consumption in mice.

BACKGROUND: Ethanol elicits a rapid stimulatory effect and a subsequent, prolonged sedative response, which are potential predictors of EtOH consumption by decreasing adenosine signaling; this phenomenon also reflects the obvious sex difference. cAMP-PKA signaling pathway modulation can influence the stimulatory and sedative effects induced by EtOH in mice. This study's objective is to clarify the role of phosphodiesterase (PDE) in mediating the observed sex differences in ethanol responsiveness between male and female animals. METHODS: EtOH was administered intraperitoneally (i.p.) for 7 days to identify the changes in PDE isoforms in response to EtOH treatment. Additionally, EtOH consumption and preference of male and female C57BL/6J mice were assessed using the drinking-in-the-dark (DID) and two-bottle choice (2BC) tests. Further, pharmacological inhibition of PDE7A heterozygote knockout mice was performed to investigate its effects on ethanol-induced stimulation and sedation in both male and female mice. Finally, Western blotting analysis was performed to evaluate the alterations in cAMP-PKA/Epac2 pathways. RESULTS: Ethanol administration resulted in an immediate upregulation in PDE7A expression in female mice, indicating a strong association between PDE7A and ethanol stimulation. Through the pharmacological inhibition of PDE7A KD mice, we have demonstrated, for the first time, that PDE7A selectively attenuates ethanol responsiveness and consumption exclusively in female mice may be associated with the cAMP-PKA/Epac2 pathway and downstream phosphorylation of CREB and ERK1/2. CONCLUSIONS: PDE7A inhibition or knockdown attenuates EtOH responsiveness and consumption exclusively in female mice associated the change of cAMP-PKA/Epac2 signaling pathways, thereby highlighting its potential as a novel therapeutic target for alcohol use disorder.

Identifying a perforated prepyloric ulcer during laparoscopy in a patient presumed to have cholecystitis.

Abdominal pain in patients with significant alcohol use and smoking history presents diagnostic challenges due to overlapping clinical features of complications like acute cholecystitis and peptic ulcers. The unreliable physical examinations of intoxicated patients often complicate accurate diagnosis. We present a case of a 56-year-old male with a history of alcoholism and smoking, who presented to the emergency department with nonspecific abdominal pain. Initial imaging suggested cholecystitis, but due to the patient's intoxication, his physical examination was unreliable. During a laparoscopic cholecystectomy, a perforated prepyloric ulcer was unexpectedly discovered, sealed by the gallbladder. This case highlights the limitations of relying solely on imaging for diagnosing abdominal conditions in intoxicated patients. The intraoperative discovery of the perforated ulcer necessitated a shift in the surgical approach, emphasizing the need for flexibility in surgical planning and a high index of suspicion for other abdominal pathologies in patients with significant lifestyle risks. The successful management of this patient through adaptive surgical techniques and comprehensive postoperative care, including Helicobacter pylori eradication therapy, underscores the importance of maintaining a broad differential diagnosis and readiness to adapt surgical plans. This approach is essential for managing complex cases effectively, ensuring that both the immediate surgical issues and underlying causes are addressed to optimize recovery and prevent recurrence.

Atypical presentation of pellagra with black urine: A clinical conundrum.

Niacin (Vitamin B3) plays a crucial role as a vitamin in cellular energy production, metabolism, and DNA repair. A severe deficiency of this vitamin can lead to pellagra, which is characterized by dermatitis, dementia, diarrhoea and eventually death if untreated. A 68-year-old woman with a poor socioeconomic background presented with photosensitive dermatitis, fever, abdominal pain, and diarrhoea. Her urine changed to port wine colour following sun exposure. Porphyria cutanea tarda was excluded in the absence of demonstrable urine spectrophotometry. A diagnosis of pellagra was made, and timely management led to a complete cure. Proper diagnosis and effective treatment of pellagra are imperative as this condition can be life-threatening if left untreated.

Changes of attentional bias in patients with alcohol use disorder during abstinence: A longitudinal study.

BACKGROUND: Alcohol Use Disorder (AUD) is linked to an attentional bias towards alcohol-related cues (e.g. images, smells), which acquire incentive properties and promote continued consumption. METHOD: We investigated how the general and alcohol attentional bias evolved longitudinally in AUD patients along two periods of abstinence: t = 0 (baseline, 1-3 months of abstinence) and t = 1 (follow-up; 6 months of abstinence), as well as their relationship with alcohol-related variables. General and alcohol-specific attentional bias were evaluated by the Classic and the Alcohol Stroop tests (neutral and alcohol conditions) in abstinent AUD patients and controls. RESULTS: At t = 0, the AUD group exhibited both general and alcohol-specific attentional biases, with greater effect in the general bias. At t = 1, alcohol-specific attentional bias decreased specifically in the AUD group and reached control levels (with interference index levels increasing from 1-3 months to 6 months). However, general attentional bias showed a trend toward improvement but it did not significantly change through abstinence process (linear mixed models, controlling for age, BMI, sex and education). CONCLUSIONS: In AUD patients, general and alcohol attentional biases exhibit different trajectories during abstinence, with the attentional bias toward alcohol improving significantly throughout this process whereas general attentional bias is maintained.

Wernicke Encephalopathy: Typical and Atypical Findings in Alcoholics and Non-Alcoholics and Correlation with Clinical Symptoms.

PURPOSE: Clinical diagnosis of Wernicke encephalopathy (WE) can be challenging due to incomplete presentation of the classical triad. The aim was to provide an update on the relevance of standard MRI and to put typical and atypical imaging findings into context with clinical features. METHODS: In this two-center retrospective observational study, the local radiology information system was searched for consecutive patients with clinical or imaging suspicion of WE. Two independent raters evaluated T2-weighted imaging (WI), fluid-attenuation inversion recovery (FLAIR), diffusion WI (DWI), T2*WI and/or susceptibility WI (SWI), and contrast-enhanced (CE)-T1WI, and noted the involvement of typical (i.e., mammillary bodies (MB), periaqueductal grey (PAG), thalamus, hypothalamus, tectal plate) and atypical (all others) lesion sites. Unusual signal patterns like hemorrhages were also documented. Reported clinical features together with the diagnostic criteria of the latest guidelines of the European Federation of Neurological Societies (EFNS) were used to test for relationships with MRI biomarkers. RESULTS: 47 patients with clinically confirmed WE were included (Jan '99-Apr '23; mean age, 53 yrs; 70% males). Interrater reliability for imaging findings was substantial (κ = 0.71), with lowest agreements for T2WI (κ = 0.85) compared to all other sequences and for PAG (κ = 0.65) compared to all other typical regions. In consensus, 77% (n = 36/47) of WE cases were rated MRI positive, with FLAIR (n = 36/47, 77%) showing the strongest relation (χ2 = 47.0; P < 0.001) compared to all other sequences. Microbleeds in the MB were detected in four out of ten patients who received SWI, not visible on corresponding T2*WI. Atypical findings were observed in 23% (n = 11/47) of cases, always alongside typical findings, in both alcoholics (n = 9/44, 21%) and non-alcoholics (n = 2/3, 67%). Isolated involvement of structures, explicitly PAG (n = 4/36; 11%) or MB (n = 1/36; 3%), was present but observed less frequently than combined lesions (n = 31/36; 86%). A cut-off width of 2.5 mm for the PAG on 2D axial FLAIR was established between cases and age- and sex-matched controls. An independent association was demonstrated only between short-term memory loss and changes in the MB (OR = 2.2 [95% CI: 1.1-4.5]; P = 0.024). In retrospect, EFNS criteria were positive (≥ 2 out of 4) in every case, but its count (range, 2-4) showed no significant (P = 0.427) relationship with signal changes on standard MRI. CONCLUSION: The proposed sequence protocol (FLAIR, DWI, SWI and T1WI + CE) yielded good detection rates for neuroradiological findings in WE, with SWI showing microbleeds in the MB with superior detectability. However, false negative results in about a quarter of cases underline the importance of neurological alertness for the diagnosis. Awareness of atypical MRI findings should be raised, not only in non-alcoholics. There is limited correlation between clinical signs and standard MRI biomarkers.

An Observational Study of a Digital Substance Use and Recovery Program.

OBJECTIVE: Digital substance use treatment programs present an opportunity to provide nonresidential care for people with problematic substance use. In June 2021, the provincial government in Ontario provided free access to Breaking Free Online (BFO), a digital behavioral change program for people with substance use disorders. METHODS: An observational study was conducted with retrospective data to characterize clients' use and engagement patterns in BFO and examine changes in self-reported outcomes. RESULTS: In total, 6,370 individuals registered for BFO between June 2021 and October 2022, of whom 3,650 completed the intake assessment. Most of these clients were self-referred (64%), with 37% having been referred by health service providers. More than one-half of the clients (52%) resided in Ontario West or East regions. Support for addressing problematic alcohol use was the most requested program (40%). By October 2022, about 44% of the clients had completed between one and four of 12 program strategies. Analysis revealed significant changes in pre-post scores across four validated scales (p<0.001), indicating a decrease in anxiety and depression, an increase in quality of life, an improvement in recovery progression, and a decrease in severity of symptoms associated with substance use disorders. CONCLUSIONS: BFO clients with higher completion rates had the most improvement across the scales used; however, clients with lower and medium completion rates also had improvements. Because of the shame and stigma associated with substance use, digital supports with low barriers to entry can help support the autonomy, privacy, and preferences of individuals seeking help for problematic substance use.

Equivalence of Alcohol Use Disorder Symptom Assessments in Routine Clinical Care When Completed Remotely via Online Patient Portals Versus In Clinic via Paper Questionnaires: Psychometric Evaluation.

BACKGROUND: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommends the paper-based or computerized Alcohol Symptom Checklist to assess alcohol use disorder (AUD) symptoms in routine care when patients report high-risk drinking. However, it is unknown whether Alcohol Symptom Checklist response characteristics differ when it is administered online (eg, remotely via an online electronic health record [EHR] patient portal before an appointment) versus in clinic (eg, on paper after appointment check-in). OBJECTIVE: This study evaluated the psychometric performance of the Alcohol Symptom Checklist when completed online versus in clinic during routine clinical care. METHODS: This cross-sectional, psychometric study obtained EHR data from the Alcohol Symptom Checklist completed by adult patients from an integrated health system in Washington state. The sample included patients who had a primary care visit in 2021 at 1 of 32 primary care practices, were due for annual behavioral health screening, and reported high-risk drinking on the behavioral health screen (Alcohol Use Disorder Identification Test-Consumption score ≥7). After screening, patients with high-risk drinking were typically asked to complete the Alcohol Symptom Checklist-an 11-item questionnaire on which patients self-report whether they had experienced each of the 11 AUD criteria listed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) over a past-year timeframe. Patients could complete the Alcohol Symptom Checklist online (eg, on a computer, smartphone, or tablet from any location) or in clinic (eg, on paper as part of the rooming process at clinical appointments). We examined sample and measurement characteristics and conducted differential item functioning analyses using item response theory to examine measurement consistency across these 2 assessment modalities. RESULTS: Among 3243 patients meeting eligibility criteria for this secondary analysis (2313/3243, 71% male; 2271/3243, 70% White; and 2014/3243, 62% non-Hispanic), 1640 (51%) completed the Alcohol Symptom Checklist online while 1603 (49%) completed it in clinic. Approximately 46% (752/1640) and 48% (764/1603) reported ≥2 AUD criteria (the threshold for AUD diagnosis) online and in clinic (P=.37), respectively. A small degree of differential item functioning was observed for 4 of 11 items. This differential item functioning produced only minimal impact on total scores used clinically to assess AUD severity, affecting total criteria count by a maximum of 0.13 criteria (on a scale ranging from 0 to 11). CONCLUSIONS: Completing the Alcohol Symptom Checklist online, typically prior to patient check-in, performed similarly to an in-clinic modality typically administered on paper by a medical assistant at the time of the appointment. Findings have implications for using online AUD symptom assessments to streamline workflows, reduce staff burden, reduce stigma, and potentially assess patients who do not receive in-person care. Whether modality of DSM-5 assessment of AUD differentially impacts treatment is unknown.

Changes in alcohol consumption during the COVID-19 among first-year university students in Spain, considering the risk of problematic use - UniHcos project.

The aim of this study was to evaluate the possible impact of the COVID-19 pandemic on prevalence rates and self-reported changes in patterns of alcohol use among first-year university students in Spain, considering the risk of problematic alcohol use. A serial cross-sectional study based on the uniHcos project was carried out. Data from 10 518 first-year university students (73.3% female, mean age 19 (SD = 1.6)) collected between 2012 and 2022 were analysed. The evolution of the pooled prevalence rates during the time series was analysed and the risk of problematic alcohol consumption was assessed using the AUDIT. Also, self-reported changes in alcohol use patterns during the pandemic were assessed. According to the results, during the COVID-19 pandemic, the prevalence of alcohol use in the past 30-days was reduced (76.3% in 2019 vs. 63.7% in COVID-19) increasing again in the New Normal period. Thus, a similar pattern in the practice of binge drinking was observed. Regarding the AUDIT score, 21.7% (95%CI 20.9, 22.6) of the students had harmful alcohol consumption, with a higher proportion among males. In the multivariable logistic models, a higher AUDIT score was significantly associated (p-value < 0.001) with being male and living with roommates. According to self-reported changes in consumption patterns during the COVID-19 pandemic, a higher proportion of participants with harmful use reported an increase in alcohol consumption compared to those at low-risk (43% vs 19%). Finally, despite the overall reduction in drinking prevalence during COVID-19, changes were not equal for all students and depended on their previous level of problematic drinking, highlighting that this should be considered in the development of strategies against alcohol use in this population.

Subacute encephalopathy with seizures in alcoholics (SESA) syndrome.

PURPOSE: To describe four patients with subacute encephalopathy with seizures in alcoholics (SESA) syndrome and to review its clinical, electroencephalogram (EEG), neuroimaging and diagnostic criteria. METHODS: We conducted a retrospective analysis of a series of prospectively collected patients who met the previously established criteria for SESA syndrome. Subsequently, we reviewed all cases published in the English language from the initial description to the present. RESULTS: We found 34 patients diagnosed with SESA syndrome to date, including the four cases of SESA in this report. Fourteen out of 34 (41.1 %) patients were over 60 years of age. Twelve (35.2 %) were abstinent from alcohol and in 4 (11.7 %) there was excessive alcohol consumption. Triggering causes were unknown in 18 cases (53.0 %). All cases (100 %) presented with an altered mental status. Fourteen (41.1 %) subjects had a history of epileptic seizures in the context of acute withdrawal syndrome (AWS). Twenty (58.8 %) patients had focal motor seizures (FMSs), 24 (70.5 %) bilateral tonic-clonic seizures (BTCSs), and 15 (44.1 %) focal impaired awareness seizures (FIASs). In 8 (23.5 %), criteria for focal nonconvulsive status epilepticus (NCSE) were met. Twenty-eight (82.3 %) subjects had transient neurological deficits. In 29 (85.2 %) subjects, lateralized periodic discharges (LPDs) were observed in the EEG. Areas of increased T2/FLAIR signal and restricted diffusion were mentioned in 22 subjects (64.7 %). Transfer to the intensive care unit (ICU) was necessary in 8 (23.5 %) subjects. Thirteen (38.2 %) had recurrent episodes. Enduring cerebral sequelae had been mentioned in 9 (26.4 %) cases. The most used anti-seizure medication (ASM) was levetiracetam, followed by phenytoin and lacosamide. CONCLUSION: SESA syndrome represents a well-defined subtype of focal NCSE in patients with chronic alcoholism. Its prompt recognition can facilitate the initiation of early ASM therapy and help implement a video-EEG evaluation and neuroimaging strategy.

Acute activation of hemichannels by ethanol leads to Ca2+-dependent gliotransmitter release in astrocytes.

Multiple studies have demonstrated that acute ethanol consumption alters brain function and cognition. Nevertheless, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity, and recently, the opening of hemichannels has been found to play a relevant role in this process. Hemichannels are plasma membrane channels composed of six connexins or seven pannexins, respectively, that oligomerize around a central pore. They serve as ionic and molecular exchange conduits between the cytoplasm and extracellular milieu, allowing the release of various paracrine substances, such as ATP, D-serine, and glutamate, and the entry of ions and other substances, such as Ca2+ and glucose. The persistent and exacerbated opening of hemichannels has been associated with the pathogenesis and progression of several brain diseases for at least three mechanisms. The uncontrolled activity of these channels could favor the collapse of ionic gradients and osmotic balance, the release of toxic levels of ATP or glutamate, cell swelling and plasma membrane breakdown and intracellular Ca2+ overload. Here, we evaluated whether acute ethanol exposure affects the activity of astrocyte hemichannels and the possible repercussions of this phenomenon on cytoplasmatic Ca2+ signaling and gliotransmitter release. Acute ethanol exposure triggered the rapid activation of connexin43 and pannexin1 hemichannels in astrocytes, as measured by time-lapse recordings of ethidium uptake. This heightened activity derived from a rapid rise in [Ca2+]i linked to extracellular Ca2+ influx and IP3-evoked Ca2+ release from intracellular Ca2+ stores. Relevantly, the acute ethanol-induced activation of hemichannels contributed to a persistent secondary increase in [Ca2+]i. The [Ca2+]i-dependent activation of hemichannels elicited by ethanol caused the increased release of ATP and glutamate in astroglial cultures and brain slices. Our findings offer fresh perspectives on the potential mechanisms behind acute alcohol-induced brain abnormalities and propose targeting connexin43 and pannexin1 hemichannels in astrocytes as a promising avenue to prevent deleterious consequences of alcohol consumption.

Examining the association between the FTO gene and neuroticism reveals indirect effects on subjective well-being and problematic alcohol use.

Associations between the fat mass and obesity-associated (FTO) gene and obesity are well-established. However, recent studies have linked FTO to addiction phenotypes and dopaminergic signaling, thus suggesting broader psychiatric implications. We explored this assumption by conducting a phenome-wide association study across 4756 genome-wide association studies, identifying 23-26 psychiatric traits associated with FTO at the multiple-corrected significance level. These traits clustered into four categories: substance use, chronotype/sleep, well-being, and neuroticism. To validate these findings, we analyzed a functionally suggestive FTO variant (rs1421085) in a separate cohort, examining its impact on (i) alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), (ii) subjective well-being based on the WHO (Ten) Well-Being Index, and (iii) neuroticism based on Schafer's Five Factor Model or the Karolinska Scales of Personality. Our results confirmed a direct association between rs1421085 and neuroticism that was independent of age, sex, alcohol use, body mass index (BMI), and childhood adversities. Interestingly, while no direct association with alcohol intake was observed, both cross-sectional and lagged longitudinal mediation analyses uncovered indirect relationships between rs1421085 and problematic alcohol use (AUDIT-P), with increased neuroticism acting as the intermediary. Mediation analyses also supported an indirect effect of rs1421085 on lower well-being through the pathways of increased neuroticism and BMI. Our study is the first to validate a direct association between FTO and neuroticism. However, additional studies are warranted to affirm the causal pathways linking FTO to well-being and alcohol use through neuroticism.

Increased alcohol consumption during the COVID-19 pandemic: A cross-sectional study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted health, mental well-being, and societal functioning, particularly for individuals with psychiatric conditions and substance use disorders. Recent evidence highlights a concerning increase in alcohol consumption during the pandemic, with a study spanning 2015-2020 indicating heightened usage, especially among young and middle-aged adults, for relaxation and tension relief. Additionally, addressing challenges exacerbated by the pandemic, another study underscored persistent barriers to healthcare access, resulting in increased alcohol and tobacco use rates and limited healthcare options. These findings shed light on the unique vulnerabilities exposed by the pandemic, emphasizing the need to investigate further its impact on alcohol consumption in diverse non-urban American communities. AIM: To investigate the impact of the COVID-19 pandemic on alcohol abuse using socioeconomic and medical parameters in diverse non-urban community in America. METHODS: Based on a cross-sectional analysis of 416 participants the United States in 2021, the study utilized The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria to categorize alcohol consumption levels. Participants aged 21 years and above were surveyed through an online platform due to COVID-19 challenges. The survey was conducted from January 14 to January 31, 2022, recruiting participants via social media and ensuring anonymity. Informed consent was secured, emphasizing the voluntary nature of participation, and participants could only take the survey once. RESULTS: Out of 416 survey respondents, 396 met eligibility criteria, with 62.9% reporting increased alcohol consumption during COVID-19. Males (68.8%) and ages 21-29 years (34.6%) predominated. Low alcohol consumption decreased by 2.8% (P = 0.237), moderate by 21.4% (P < 0.001), and heavy increased by 14.9% (P < 0.001). Alcohol abuse rose by 6.5% (P = 0.0439), with a 7% increase in self-identified alcohol abusers/alcoholics. Seeking treatment during COVID-19 rose by 6.9%. Easier alcohol access (76.0%) was reported, while 80.7% found it harder to access medical care for alcohol-related issues. These findings highlight the pandemic's impact on alcohol consumption and healthcare access, emphasizing the need for targeted interventions during public health crises. CONCLUSION: The COVID-19 pandemic exacerbated alcoholism and abuse, with increased heavy consumption (P < 0.001) and abuse (P = 0.0439). Access to medical programs for addressing alcohol abuse declined, highlighting the need for targeted intervention.

Alcohol promotes liver fibrosis in high fat diet induced diabetic rats.

OBJECTIVES: Type 2 diabetes (T2DM) and alcoholism are considered to be lifestyle-associated independent risk factors in fatty liver diseases (FLD) mediated cirrhosis and hepatocellular carcinoma (HCC). A combined effect of both these conditions may exacerbate the pathological changes and a pre-clinical exploration of this is expected to provide a mechanical detail of the pathophysiology. The present study aims to understand the effect of alcohol on pre- diabetic and type 2 diabetic female Wistar rats. METHODS: In this experimental study, 12 Wistar rats (180-220 g) were randomly assigned into three groups: Normal (fed normal rat chow), alcohol (20 %) fed diabetic (HFD + STZ), and pre-diabetic rats (HFD alone). After, two months of the experimental period, blood and liver tissues were collected lipid metabolic alteration, liver injury, and fibrosis were determined following biochemical and histological methods. Data were analyzed using one-way ANOVA and Dunnett's Post Hoc test. RESULTS: Significant dyslipidemia was observed in the liver tissues of diabetic and pre-diabetic rats following alcohol ingestion. A significant (p<0.05) increase in lipid peroxidation status, and hepatic marker enzyme activities (p<0.0001) were observed in diabetic animals. In corroborating with these observations, hematoxylin and eosin staining of hepatic tissue revealed the presence of sinusoidal dilation along with heavily damaged hepatocytes and inflammatory cell infiltration. Further, significantly (p<0.001) increased hepatic hydroxyproline content and extended picrosirius red stained areas of collagen in liver tissue indicated initiation of fibrosis in alcohol-fed diabetic rats. CONCLUSIONS: Overall, the results indicate that alcohol consumption in T2DM conditions is more deleterious than pre diabetic conditions in progressing to hepatic fibrosis.

Supporting direct acting antiviral medication adherence and treatment completion in a sample of predominantly rural veterans with hepatitis C and substance use disorders.

BACKGROUND: Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with substance use disorders (SUDs) among rural Veterans. METHODS: We implemented a clinic-based intervention which used motivational interviewing (MI) techniques to promote medication adherence and treatment completion with 12 weeks of DAA treatment among rural Veterans with chronic HCV and SUDs. Patients received an MI session with a licensed psychologist at baseline and at each two-week follow-up visit during DAA treatment. Patients received $25 per study visit completed. Patients were to attend a laboratory visit 12 weeks after treatment completion to assess for sustained virologic response (SVR). RESULTS: Of the 20 participants who enrolled, 75% (n = 15) completed the planned 12-week course of treatment. Average adherence by pill count was 92% (SD = 3%). Overall SVR was 95% (19/20). CONCLUSIONS: We demonstrated that a clinic-based intervention which incorporated frequent follow up visits and MI techniques was feasible and acceptable to a sample of predominantly rural Veterans with chronic HCV and SUDs. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov (NCT02823457) on July 1, 2016. https://clinicaltrials.gov .

Preparation of Pueraria lobata Root-Derived Exosome-Like Nanovesicles and Evaluation of Their Effects on Mitigating Alcoholic Intoxication and Promoting Alcohol Metabolism in Mice.

Purpose: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice. Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers. Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (-31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation. Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.

Effect of the COVID-19 pandemic on clinical characteristics and outcomes of adult pneumococcal meningitis patients - a Dutch prospective nationwide cohort study.

PURPOSE: To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic. METHODS: In a Dutch prospective cohort, risk factors and clinical characteristics of pneumococcal meningitis episodes occurring during the COVID-19 pandemic (starting March 2020) were compared with those from baseline and the time afterwards. Outcomes were compared with an age-adjusted logistic regression model. RESULTS: We included 1,699 patients in 2006-2020, 50 patients in 2020-2021, and 182 patients in 2021-2023. After March 2020 relatively more alcoholism was reported (2006-2020, 6.1%; 2020-2021, 18%; 2021-2023, 9.7%; P = 0.002) and otitis-sinusitis was less frequently reported (2006-2020, 45%; 2020-2021, 22%; 2021-2023, 47%; P = 0.006). Other parameters, i.e. age, sex, symptom duration or initial C-reactive protein level, remained unaffected. Compared to baseline, lumbar punctures were more frequently delayed (on admission day, 2006-2020, 89%; 2020-2021, 74%; 2021-2022, 86%; P = 0.002) and outcomes were worse ('good recovery', 2020-2021, OR 0.5, 95% CI 0.3-0.8). CONCLUSION: During the COVID-19 pandemic, we observed worse outcomes in patients with pneumococcal meningitis. This may be explained by differing adherence to restrictions according to risk groups or by reduced health care quality.