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Several studies have shown that binge drinking of alcoholic beverages leads to non-desirable outcomes, which have become a serious threat to public health. However, the bioactive compounds in some alcohol-containing beverages might mitigate the negative effects of alcohol. In beer, the variety and concentration of bioactive compounds in the non-alcoholic fraction suggests that its consumption at moderate levels may not only be harmless but could also positively contribute to an improvement of certain physiological states and be also useful in the prevention of different chronic diseases. The present review focuses on the effects of non-alcoholic components of beer on abdominal fat, osteoporosis, and body hydration in women, conditions selected for their relevance to health and aging. Although beer drinking is commonly believed to cause abdominal fat deposition, the available literature indicates this outcome is inconsistent in women. Additionally, the non-alcoholic beer fraction might improve bone health in postmenopausal women, and the effects of beer on body hydration, although still unconfirmed seem promising. Most of the health benefits of beer are due to its bioactive compounds, mainly polyphenols, which are the most studied. As alcohol-free beer also contains these compounds, it may well offer a healthy alternative to beer consumers.

Aim: The aim of the study was to examine whether changes in alcohol consumption over time differ according to beverage types, and to what extent socioeconomic, lifestyle and health-related factors predict beverage-specific trajectories in Sweden. Study design: We included participants from the Stockholm Public Health Cohort who were surveyed repeatedly in 2002, 2010 and 2014. Alcohol consumption trajectories were constructed for 13,152 individuals with valid information on amount and frequency of drinking. Preferred beverage types (i.e., beer, wine or spirits) were defined based on the most consumed beverages. Multinomial logistic regression was used to quantify individual predictors of different trajectories, overall and by beverage type. Results: Overall 56.9% of respondents were women, the mean age was 49.2 years, SD (13.1). Wine was cited as the preferred beverage for 72.4% of participants, and stable moderate drinking was the most common trajectory regardless of beverage type (68.2%, 54.9% and 54.2% in individuals with wine, beer and spirits as preferred beverages, respectively). Associations between drinking trajectories and baseline lifestyle factors did not differ by beverage type. Lower socioeconomic position (SEP) was associated with unstable moderate wine drinking (for unskilled manual SEP: adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.23, 1.93), unstable heavy beer drinking (for skilled manual SEP: aOR 1.99, 95% CI 1.14, 3.52; and unskilled manual SEP: aOR 1.72, 95% CI 1.05, 2.82), and former beer drinking trajectory (for skilled manual SEP: aOR 1.81; 95% CI 1.21, 2.72; and unskilled manual SEP: aOR 1.66; 95% CI 1.17, 2.37). Conclusion: Lower SEP was associated with unstable heavy drinking of beer, former beer drinking, and unstable moderate wine drinking trajectories indicating that targeted alcohol prevention programmes need to focus on these groups. [ABSTRACT FROM AUTHOR]

Background: Post-stroke pneumonia is a frequent complication of stroke and is associated with high mortality. Investigators have described its associations with beta-blocker. However, there has been no evaluation of the role of recombinant tissue plasminogen activator (RTPA). We postulate that RTPA may modify the effect of stroke on pneumonia by reducing stroke disability. We explore this using data from neuroprotection trials in Virtual International Stroke Trials Archive (VISTA)-Acute. Method: We evaluated the impact of RTPA and other medications in random forest model. Random forest is a type of supervised ensemble tree-based machine learning method. We used the standard approach for performing random forest and partitioned the data into training (70%) and validation (30%) sets. This action enabled to the model developed on training data to be evaluated in the validation data. We borrowed idea from Coalition Game Theory on fair distribution of marginal profit (Shapley value) to determine proportional contribution of a covariate to the model. Consistent with other analysis using the VISTA-Acute data, the diagnosis of post-stroke pneumonia was based on reports of serious adverse events. Results: The overall frequency of pneumonia was 10.9% (614/5652). It was present in 11.5% of the RTPA (270/2358) and 10.4% (344/3295) of the no RTPA groups. There was significant (p<0.05) imbalance in covariates (age, baseline National Institutes of Health Stroke Scale (NIHSS), diabetes, and sex). The AUC for training data was 0.70 (95% CI 0.65–0.76), validation data was 0.67 (95% CI 0.62–0.73). The Shapley value shows that baseline NIHSS (≥10) and age (≥80) made the largest contribution to the model of pneumonia while absence of benzodiazepine may protect against pneumonia. RTPA and beta-blocker had very low effect on frequency of pneumonia. Conclusion: In this cohort pneumonia was strongly associated with stroke severity and age whereas RTPA had a much lower effect. An intriguing finding is a possible association between benzodiazepine and pneumonia but this requires further evaluation. [ABSTRACT FROM AUTHOR]

Aims To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables. Methods and results In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82–2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13–1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10–1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02–1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index. Conclusion Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively. [ABSTRACT FROM AUTHOR]

Purpose: Alcohol consumption is a major risk factor for colorectal cancer (CRC). It is currently poorly understood, however, how alcohol and different alcoholic beverage types are related to psychosocial outcomes in CRC survivors. Methods: We used data of N = 910 CRC survivors from the pooled EnCoRe and PROCORE cohorts and harmonized them into five time points: at diagnosis and 3, 6, 12, and 24 months post-diagnosis. Generalized estimated equation models were used to examine longitudinal associations of alcohol consumption, including consumption of beer, wine, and liquor, with anxiety, depression, and health-related quality of life (HRQoL), while correcting for sociodemographic, lifestyle, and clinical factors. Results: Survivors were on average 67 years and 37% was female. In the first 2 years post-diagnosis, survivors who consumed more alcoholic drinks/week reported lower anxiety and depressive symptoms and better HRQoL on all domains and symptom scales. This was the case for moderate and heavy amounts of alcohol and mostly for consuming beer and wine, but not for liquor. Associations were more often significant for men and for younger persons (< 67 years at baseline). Conclusions: Generally, alcohol consumption was observed to be longitudinally related to less anxiety and depression and better HRQoL in CRC survivors. Implications for Cancer Survivors: Although alcohol consumption is generally unfavorable due to increased risk of carcinogenesis and worse prognosis after CRC, it seems to be associated with better psychosocial outcomes in the first 2 years after diagnosis and treatment. More research is needed to gain knowledge about reasons for drinking and causality. [ABSTRACT FROM AUTHOR]

Aim: To test the association of alcohol consumption with total and cause‐specific mortality risk. Design Prospective observational multi‐centre population‐based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements Average alcohol intake by food frequency questionnaire, total and cause‐specific mortality. Findings In comparison with life‐time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high‐density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life‐time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality. [ABSTRACT FROM AUTHOR]

Alcohol binge drinking is common among adolescents and may challenge the signalling systems that process affective stimuli, including calcitonin gene-related peptide (CGRP) signalling. Here, we employed a rat model of adolescent binge drinking to evaluate reward-, social- and aversion-related behaviour, glucocorticoid output and CGRP levels in affect-related brain regions. As a potential rescue, the effect of the phytocannabinoid cannabidiol was explored. Adolescent male rats underwent the intermittent 20% alcohol two-bottle choice paradigm; at the binge day (BD) and the 24 h withdrawal day (WD), we assessed CGRP expression in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, hypothalamus and brainstem; in addition, we evaluated sucrose preference, social motivation and drive, nociceptive response, and serum corticosterone levels. Cannabidiol (40 mg/kg, i.p.) was administered before each drinking session, and its effect was measured on the above-mentioned readouts. At BD and WD, rats displayed decreased CGRP expression in mPFC, NAc and amygdala; increased CGRP levels in the brainstem; increased response to rewarding- and nociceptive stimuli and decreased social drive; reduced serum corticosterone levels. Cannabidiol reduced alcohol consumption and preference; normalised the abnormal corticolimbic CGRP expression, and the reward and aversion-related hyper-responsivity, as well as glucocorticoid levels in alcohol binge-like drinking rats. Overall, CGRP can represent both a mediator and a target of alcohol binge-like drinking and provides a further piece in the intricate puzzle of alcohol-induced behavioural and neuroendocrine sequelae. CBD shows promising effects in limiting adolescent alcohol binge drinking and rebalancing the bio-behavioural abnormalities., (© 2023 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Purpose: Alcohol consumption can lead to worse prognosis and mortality among colorectal cancer (CRC) patients. We investigated alcohol consumption of CRC survivors up to 2 years post-diagnosis, and how sociodemographic, lifestyle, and clinical factors were associated longitudinally with these habits. Methods: We pooled longitudinal data of 910 CRC survivors from the ongoing PROCORE and EnCoRe studies with data collected at diagnosis (baseline) and 3, 6, 12, and 24 months post-diagnosis. Both studies assessed alcohol consumption, including beer, wine, and liquor. Generalized estimated equation models were used to examine changes over time in alcohol consumption and multivariable longitudinal associations of sociodemographic, lifestyle, and clinical factors with alcohol consumption. Results: At baseline, participants were on average 67 years old, 332 (37%) were female, and alcohol was consumed by 79%. Most survivors (68–71%) drank less at all follow-ups. Beer, wine, and liquor were consumed by 51%, 58%, and 25% at baseline, respectively, and these declined over time. Males consumed more alcohol, and higher education, more physical activity, and not having a (permanent) stoma were associated with consuming more alcohol. Conclusion: CRC survivors decreased their alcohol consumption in the 2 years post-diagnosis. Future studies should take the significant factors that were associated with alcohol post-diagnosis consumption into account, when they investigate CRC health outcomes or for identifying subgroups for interventions. Males with higher education, more physical activity, and no stoma should be reminded after diagnosis for reducing their alcohol consumption. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and a meta-analysis to assess the association of anticoagulants and their dosage with in-hospital all-cause mortality in COVID-19 patients. Articles were retrieved until January 8, 2021, by searching in seven electronic databases. The main outcome was all-cause mortality occurred during hospitalization. Data were combined using the general variance-based method on the effect estimate for each study. Separate meta-analyses according to type of COVID-19 patients (hospitalized or intensive care unit [ICU] patients), anticoagulants (mainly heparin), and regimens (therapeutic or prophylactic) were conducted. A total of 29 articles were selected, but 23 retrospective studies were eligible for quantitative meta-analyses. No clinical trial was retrieved. The majority of studies were of good quality; however, 34% did not distinguish heparin from other anticoagulants. Meta-analysis on 25,719 hospitalized COVID-19 patients showed that anticoagulant use was associated with 50% reduced in-hospital mortality risk (pooled risk ratio [RR]: 0.50, 95% confidence interval [CI]: 0.40–0.62; I 2 : 87%). Both anticoagulant regimens (therapeutic and prophylactic) reduced in-hospital all-cause mortality, compared with no anticoagulation. Particularly in ICU patients, the anticoagulant therapeutic regimen was associated with a reduced in-hospital mortality risk (RR: 0.30, 95% CI: 0.15–0.60; I 2 : 58%) compared with the prophylactic one. However, the former was also associated with a higher risk of bleeding (RR: 2.53, 95% CI: 1.60–4.00; I 2 : 65%). Anticoagulant use, mainly heparin, reduced all-cause mortality in COVID-19 patients during hospitalization. Due to the higher risk of bleeding at therapeutic doses, the use of prophylactic dosages of anticoagulant is probably to be preferred in noncritically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Aims  There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts. Methods and results  In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11–1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF. Conclusions  In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention. [ABSTRACT FROM AUTHOR]

Background and aims: Epidemiological evidence on the impact of different alcohol drinking patterns on health‐care systems or hospitalizations is sparse. We investigated how the different average volumes of alcohol consumed relate to all‐cause and cause‐specific hospitalizations. Design Prospective cohort study (baseline 2005–10) linked to a registry of hospital discharge records to identify hospitalizations at follow‐up (December 2013). Setting: Molise region, Italy. Participants: A total of 20 682 individuals (48% men, age ≥ 35 years) who participated in the Moli‐sani Study and were free from cardiovascular disease or cancer at baseline. Measurements The alcohol volume consumed in the year before enrolment was classified as: life‐time abstainers, former drinkers, occasional drinkers and current drinkers who drank 1–12 (referent), 12.1–24, 24.1–48 and > 48 g/day of alcohol. Cause‐specific hospitalizations were assigned by Italian Diagnosis Related Groups classification or by ICD‐9 code of main admission diagnoses. Incidence rate ratios (IRR) of hospitalization were estimated by Poisson regression, taking into account the total number of admissions that occurred during the follow‐up per person. Findings During a median follow‐up of 6.3 years, 12 996 multiple hospital admissions occurred. In multivariable analyses, life‐time abstainers and former drinkers had higher rates of all‐cause [IRR = 1.11, 95% confidence interval (CI) = 1.05–1.17 and IRR = 1.19, 95% CI = 1.02–1.31, respectively] and vascular (IRR = 1.14, 95% CI = 1.02–1.27 and IRR = 1.48, 95% CI = 1.24–1.76, respectively) hospitalizations compared with light alcohol consumers. Alcohol consumption > 48 g/day was associated with a higher rate of hospitalization for both alcohol‐related diseases (IRR = 1.74, 95% CI = 1.32–2.29) and cancer (IRR = 1.36, 95% CI = 1.12–1.65). The magnitude of the association between heavier alcohol intake and hospitalization tended to be greater in smokers than non‐smokers. No associations were observed with hospitalization for trauma or neurodegenerative diseases. Conclusions: Moderate alcohol consumption appears to have a modest but complex impact on global hospitalization burden. Heavier drinkers have a higher rate of hospitalization for all causes, including alcohol‐related diseases and cancer, a risk that appears to be further magnified by concurrent smoking. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to determine if xanthohumol, a prenylated chalcone found in Hop (Humulus lupulus), has anti-inflammatory effects in healthy humans if applied in low doses achievable through dietary intake., Methods: In a placebo-controlled single-blinded cross-over design study, 14 healthy young men and women either consumed a beverage containing 0.125 mg xanthohumol or a placebo. Peripheral blood mononuclear cells (PBMCs) were isolated before and 1 h after the intake of the beverages. Subsequently, PBMCs were stimulated with or without lipoteichoic acid (LTA) for 24 and 48 h. Concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6) and soluble cluster of differentiation (sCD14) protein were determined in cell culture supernatant. Furthermore, hTLR2 transfected HEK293 cells were stimulated with LTA in the presence or absence of xanthohumol and sCD14., Results: The stimulation of PBMCs with LTA for 24 and 48 h resulted in a significant induction of IL-1β, IL-6, and sCD14 protein release in PBMCs of both, fasted subjects and subjects after the ingestion of the placebo. In contrast, after ingesting xanthohumol, LTA-dependent induction of IL-1β, IL-6, and sCD14 protein release from PBMCs was not significantly higher than in unstimulated cells after 48 h. In hTLR2 transfected HEK293 cells xanthohumol significantly suppressed the LTA-dependent activation of cells, an effect attenuated when cells were co-incubated with sCD14., Conclusion: The results of our study suggest that an ingestion of low doses of xanthohumol can suppress the LTA-dependent stimulation of PBMCs through mechanisms involving the interaction of CD14 with TLR2. Study registered at ClinicalTrials.gov (NCT04847193, 22.03.2022)., (© 2022. The Author(s).)

Stem cells drive embryonic and fetal development. In several adult tissues, they retain the ability to self-renew and differentiate into a variety of specialized cells, thus contributing to tissue homeostasis and repair throughout life span. Alcohol consumption is associated with an increased risk for several diseases and conditions. Growing and developing tissues are particularly vulnerable to alcohol's influence, suggesting that stem- and progenitor-cell function could be affected. Accordingly, recent studies have revealed the possible relevance of alcohol exposure in impairing stem-cell properties, consequently affecting organ development and injury response in different tissues. Here, we review the main studies describing the effects of alcohol on different types of progenitor/stem cells including neuronal, hepatic, intestinal and adventitial progenitor cells, bone-marrow-derived stromal cell, dental pulp, embryonic and hematopoietic stem cells, and tumor-initiating cells. A better understanding of the nature of the cellular damage induced by chronic and episodic heavy (binge) drinking is critical for the improvement of current therapeutic strategies designed to treat patients suffering from alcohol-related disorders. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA., Methods: Cholangiocarcinogenesis was induced in rats (TAA) and mice (Jnk Δhepa  + CCl 4  + DEN model). We performed proteomic and metabolomic analyses in bile from control and CCA-bearing rats. Differential expression was validated in rat and human CCAs. Mechanisms were addressed in human CCA cells, including Huh28-KRAS G12D cells. Cell signaling, growth, gene regulation and [U- 13 C]-D-glucose-serine fluxomics analyses were performed. In vivo studies were performed in the clinically-relevant iCCA mouse model., Results: Pathways related to inflammation, oxidative stress and glucose metabolism were identified by proteomic analysis. Oxidative stress and high amounts of the oncogenesis-supporting amino acids serine and glycine were discovered by metabolomic studies. Most relevant hits were confirmed in rat and human CCAs (TCGA). Activation of interleukin-6 (IL6) and epidermal growth factor receptor (EGFR) pathways, and key genes in cancer-related glucose metabolic reprogramming, were validated in TAA-CCAs. In TAA-CCAs, G9a, an epigenetic pro-tumorigenic writer, was also increased. We show that EGFR signaling and mutant KRAS G12D can both activate IL6 production in CCA cells. Furthermore, phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in serine-glycine pathway, was upregulated in human iCCA correlating with G9a expression. In a G9a activity-dependent manner, KRAS G12D promoted PHGDH expression, glucose flow towards serine synthesis, and increased CCA cell viability. KRAS G12D CAA cells were more sensitive to PHGDH and G9a inhibition than controls. In mouse iCCA, G9a pharmacological targeting reduced PHGDH expression., Conclusions: In CCA, we identified new pro-tumorigenic mechanisms: Activation of EGFR signaling or KRAS mutation drives IL6 expression in tumour cells; Glucose metabolism reprogramming in iCCA includes activation of the serine-glycine pathway; Mutant KRAS drives PHGDH expression in a G9a-dependent manner; PHGDH and G9a emerge as therapeutic targets in iCCA., (© 2022. The Author(s).)

Inflammasomes are key components of the innate immunity system that trigger the inflammatory response. Inappropriate activity of the inflammasome system has been linked to onset and perpetuation of inflammation in atherosclerotic plaques and cardiovascular disease. Low-to-moderate beer consumption is inversely associated with cardiovascular event presentation, while high levels of alcohol intake are associated with increased cardiovascular risk. Although fermented beverages have been suggested to exert their beneficial effects through their anti-oxidant and anti-inflammatory properties, little is known regarding the capacity of beer to modulate innate immunity cell responses. To this aim, primed or activated THP-1 macrophages were conditioned with human serum obtained from a prospective two-arms longitudinal crossover study to investigate the effect of a moderate and regular daily intake of beer, either alcohol-free or traditional, in the regulation of TLR-mediated inflammatory responses in healthy but overweight individuals. Conditioned macrophages with serum obtained after four-week intervention with alcohol-free beer significantly reduced the transcription of pro-inflammatory interleukins such as IL-1β and TNF. The serum of traditional beer consumers did not exhibit the same capacity as the serum of alcohol-free beer consumers to reduce gene expression of pro-inflammatory interleukins; however, serum from traditional beer consumers showed a regulatory effect at the protein level by significantly decreasing the intracellular protein levels of pro-IL-1β in primed macrophages and preventing cleaved-IL-1β protein release.

Endogenous acetaldehyde production from the metabolism of ingested alcohol exposes hematopoietic progenitor cells to increased genotoxic risk. To develop possible therapeutic strategies to prevent or reverse alcohol abuse effects, it would be critical to determine the temporal progression of acute ethanol toxicity on progenitor cell numbers and proliferative status. We followed the variation of the cell proliferation rate in bone marrow and spleen in response to acute ethanol intoxication in the MITO-Luc mouse, in which NF-Y-dependent cell proliferation can be assessed in vivo by non-invasive bioluminescent imaging. One week after ethanol administration, bioluminescent signals in bone marrow and spleen decreased below the level corresponding to physiological proliferation, and they progressively resumed to pre-treatment values in approximately 4 weeks. Boosting acetaldehyde catabolism by administration of an aldehyde dehydrogenase activity activator or administration of polyphenols with antioxidant activity partially restored bone marrow cells' physiological proliferation. These results indicate that in this mouse model, bioluminescent alteration reflects the reduction of the physiological proliferation rate of bone marrow progenitor cells due to the toxic effect of aldehydes generated by alcohol oxidation. In summary, this study presents a novel view of the impact of acute alcohol intake on bone marrow cell proliferation in vivo.

Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapable stress; (2) stress-axis functionality; and (3) dopaminergic and glutamatergic neuroadaptation in the NAc. We also assess the potential effects of the non-intoxicating phytocannabinoid cannabidiol, to counteract (or reverse) the development of detrimental consequences of binge-like alcohol exposure. Our results show that adolescent binge-like alcohol exposure alters the sensitivity to positive stimuli, exerts social and novelty-triggered anxiety-like behaviour, and passive stress-coping during early and prolonged withdrawal. In addition, serum corticosterone and hypothalamic and NAc corticotropin-releasing hormone levels progressively increase during withdrawal. Besides, NAc tyrosine hydroxylase levels increase at late withdrawal, while the expression of dopamine transporter, D1 and D2 receptors is dynamically altered during binge and withdrawal. Furthermore, the expression of markers of excitatory postsynaptic signaling-PSD95; Homer-1 and -2 and the activity-regulated spine-morphing proteins Arc, LIM Kinase 1 and FOXP1-increase at late withdrawal. Notably, subchronic cannabidiol, during withdrawal, attenuates social- and novelty-induced aversion and passive stress-coping and rectifies the hyper-responsive stress axis and NAc dopamine and glutamate-related neuroplasticity. Overall, the exposure to binge-like alcohol levels in adolescent rats makes the NAc, during withdrawal, a locus minoris resistentiae as a result of perturbations in neuroplasticity and in stress-axis homeostasis. Cannabidiol holds a promising potential for increasing behavioural, neuroendocrine and molecular resilience against binge-like alcohol harmful effects.

The outbreak of the novel coronavirus SARS-CoV-2 epidemic has rapidly spread and still poses a serious threat to healthcare systems worldwide. In the present study, electronic medical records containing clinical indicators related to liver injury in 799 COVID-19-confirmed patients admitted to a hospital in Madrid (Spain) were extracted and analyzed. Correlation between liver injury and disease outcome was also evaluated. Serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyltransferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and AST/ALT ratio were elevated above the Upper Limit of Normal (ULN) in 25.73%, 49.17%, 34.62%, 24.21%, 55.84% and 75% of patients, respectively. Interestingly, significant positive correlation between LDH levels and the AST/ALT ratio with disease outcome was found. Our data showed that SARS-CoV-2 virus infection leads to mild, but significant changes in serum markers of liver injury. The upregulated LDH levels as well as AST/ALT ratios upon admission may be used as additional diagnostic characteristic for COVID-19 patients.

Fermented alcoholic drinks' contribution to the gut microbiota composition is mostly unknown. However, intestinal microorganisms can use compounds present in beer. This work explored the associations between moderate consumption of beer, microbiota composition, and short chain fatty acid (SCFA) profile. Seventy eight subjects were selected from a 261 healthy adult cohort on the basis of their alcohol consumption pattern. Two groups were compared: (1) abstainers or occasional consumption (ABS) ( n = 44; <1.5 alcohol g/day), and (2) beer consumption ≥70% of total alcohol (BEER) ( n = 34; 200 to 600 mL 5% vol. beer/day; <15 mL 13% vol. wine/day; <15 mL 40% vol. spirits/day). Gut microbiota composition (16S rRNA gene sequencing) and SCFA concentration were analyzed in fecal samples. No differences were found in α and β diversity between groups. The relative abundance of gut bacteria showed that Clostridiaceae was lower ( p = 0.009), while Blautia and Pseudobutyrivibrio were higher ( p = 0.044 and p = 0.037, respectively) in BEER versus ABS. In addition, Alkaliphilus, in men, showed lower abundance in BEER than in ABS ( p = 0.025). Butyric acid was higher in BEER than in ABS ( p = 0.032), and correlated with Pseudobutyrivibrio abundance. In conclusion, the changes observed in a few taxa, and the higher butyric acid concentration in consumers versus non-consumers of beer, suggest a potentially beneficial effect of moderate beer consumption on intestinal health.

Rationale: Adolescent binge drinking is common and associated with increased risk of substance use disorders. Transition from recreational to habitual ethanol consumption involves alterations in dorsal striatal function, but the long-term impact of adolescent ethanol exposure upon this region remains unclear. Objectives: This study aimed to characterise and describe relationships between adolescent ethanol exposure, amphetamine self-administration and adult dopamine dynamics in dorsal striatum, including response to amphetamine challenge, in male Wistar rats. Methods: Ethanol (2 g/kg) or water was administered intragastrically in an episodic binge-like regimen (three continuous days/week) between 4 and 9 weeks of age (i.e. post-natal days 28-59). In adulthood, animals were divided into two groups. In the first, dorsal striatal potassium-evoked dopamine release was examined via chronoamperometry, in the basal state and after a single amphetamine challenge (2 mg/kg, i.v.). In the second, amphetamine self-administration behaviour was studied (i.e. fixed and progressive ratio) before chronoamperometric analysis was conducted as described above. Results: Adolescent ethanol exposure suppressed locally evoked dopamine response after amphetamine challenge in adulthood, whereas in the basal state, no differences in dopamine dynamics were detected. Ethanol-exposed animals showed no differences in adult amphetamine self-administration behaviour but an abolished effect on dopamine removal in response to a single amphetamine challenge after self-administration. Conclusion: Amphetamine challenges in adult rats revealed differences in in vivo dopamine function after adolescent ethanol exposure. The attenuated drug response in ethanol-exposed animals may affect habit formation and contribute to increased risk for substance use disorders as a consequence of adolescent ethanol. [ABSTRACT FROM AUTHOR]

The use of a standard definition of ‘binge drinking’ can potentially offer the advantage of ‘objectifying’ the concept of excessive drinking. Nevertheless, the term has become somewhat confusing, as it is often used as a synonym of drunkenness, making cross-cultural comparison difficult. The present study investigates the meaning Italian young people attribute to binge drinking, to explain the gap between self-reported rates of drunkenness and episodes of binge drinking found by comparative youth drinking surveys. About 134 face-to-face semi-structured interviews were conducted, targeting adolescents (aged 15–17) and young adults (aged 22–24) who had admitted to drinking excessively. In addition, an online forum was created, using a video clip as a stimulus and asking for web users' comments (132 were analysed). Results show how in the view of Italian bingers, binge drinking does not necessarily entail drunkenness, but only being tipsy. This is what they aim at when they drink, while they have negative attitudes and expectations regarding intoxication and its effects. This boundary establishes the concept of excess and marks the threshold between socially acceptable and unacceptable drinking. In conclusion, the concept of binge drinking cannot be used as a synonym of drunkenness, which young people in Italy judge severely. [ABSTRACT FROM AUTHOR]

Aim The effectiveness of Preventure was tested on drinking behaviour of young adolescents in secondary education in the Netherlands. Design A cluster randomized controlled trial was carried out, with participants assigned randomly to a two-session coping skills intervention or a control no-intervention condition. Setting Fifteen secondary schools throughout the Netherlands; seven schools in the intervention and eight schools in the control condition. Participants A total of 699 adolescents aged 13-15 years participated, 343 allocated to the intervention and 356 to the control condition, with drinking experience and elevated scores in either negative thinking, anxiety sensitivity, impulsivity or sensation-seeking. Intervention and comparator Preventure is a selective school-based alcohol prevention programme targeting personality risk factors. The comparator was a no-intervention control. Measurements The effects of the intervention on the primary outcome past-month binge drinking, and the secondary outcomes binge drinking frequency, alcohol use, alcohol frequency and problem drinking, were examined. The primary analyses of interest were intervention main effects at 12 months post-intervention. In addition, intervention effects on the linear development of binge drinking using a latent-growth curve approach were examined. Findings Binge drinking rates were not significantly different between the intervention (42.9%) and control group (49.2%) at 12 months follow-up [odds ratio (OR) = 1.05, confidence interval (CI) = 0.99, 1.11]. Intention-to-treat analyses revealed no significant intervention effects on alcohol use (53.9 versus 61.5%; OR = 0.99, CI = 0.86, 1.14) and problem drinking (37.0 versus 44.7%; OR = 1.03, CI = 0.92, 1.10) at 12 months follow-up. The post-hoc latent-growth analyses revealed significant effects on the development of binge drinking ( β = -0.16, P = 0.05), and binge drinking frequency ( β = -0.14, P = 0.05). Conclusion The alcohol prevention programme, Preventure, appears to have little or no effect on overall prevalence of binge drinking in adolescents in the Netherlands but may reduce the development of binge drinking over time. [ABSTRACT FROM AUTHOR]

The article reviews portrayals of 'the addict' in press items from Italy, Finland, Poland, and The Netherlands. The dataset consists of 1,327 items from four national newspapers published in 1991, 1998, 2011. The portrayals varied according to country, period, and type of addiction problem. Results can be read as four cases where different conceptualizations ('the sinner,' 'the sick,' 'the social problem,' 'the criminal,' and 'the famous') assume diverse importance. These conceptual frames-of-reference are clearly neither unambiguous nor fixed. They are constantly modified and part of different trends. [ABSTRACT FROM AUTHOR]

Impulsivity is a multidimensional construct that is related to different aspects of alcohol use, abuse, and dependence. Inhibitory control, one facet of impulsivity, can be assayed using the stop-signal task (SST) and quantified behaviorally via the stop-signal reaction time (SSRT) and electrophysiologically using event-related potentials (ERPs). Research on the relationship between alcohol use and SSRTs, and between alcohol use and inhibitory-control ERPs, is mixed. Here, adult alcohol users (n = 79), with a wide range of scores on the Alcohol Use Disorders Identification Test (AUDIT), completed the SST under electroencephalography (EEG) (70% of participants had AUDIT total scores greater than or equal to 8). Other measures, including demographic, self-report, and task-based measures of impulsivity, personality, and psychological factors, were also recorded. A machine-learning method with penalized linear regression was used to correlate individual differences in alcohol use with impulsivity measures. Four separate models were tested, with out-of-sample validation used to quantify performance. ERPs alone statistically predicted alcohol use (cross-validated r = 0.28), with both early and late ERP components contributing to the model (larger N2, but smaller P3, amplitude). Behavioral data from a wide range of impulsivity measures were also associated with alcohol use (r = 0.37). SSRT was a relatively weak statistical predictor, whereas the Stroop interference effect was relatively strong. The addition of nonimpulsivity behavioral measures did not improve the correlation (r = 0.34) and was similar when ERPs were combined with non-ERP data (r = 0.29). These findings show that inhibitory control ERPs are robustly correlated individual differences in alcohol use., (© 2019 Society for the Study of Addiction.)

Hevin, also known as SPARC-like 1, is a member of the secreted protein acidic and rich in cysteine family of matricellular proteins, which has been implicated in neuronal migration and synaptogenesis during development. Unlike previously characterized matricellular proteins, hevin remains strongly expressed in the adult brain in both astrocytes and neurons, but its precise pattern of expression is unknown. The present study provides the first systematic description of hevin mRNA distribution in the adult mouse brain. Using isotopic in situ hybridization, we showed that hevin is strongly expressed in the cortex, hippocampus, basal ganglia complex, diverse thalamic nuclei and brainstem motor nuclei. To identify the cellular phenotype of hevin-expressing cells, we used double fluorescent in situ hybridization in mouse and human adult brains. In the mouse, hevin mRNA was found in the majority of astrocytes but also in specific neuronal populations. Hevin was expressed in almost all parvalbumin-positive projection neurons and local interneurons. In addition, hevin mRNA was found in: (1) subsets of other inhibitory GABAergic neuronal subtypes, including calbindin, cholecystokinin, neuropeptide Y, and somatostatin-positive neurons; (2) subsets of glutamatergic neurons, identified by the expression of the vesicular glutamate transporters VGLUT1 and VGLUT2; and (3) the majority of cholinergic neurons from motor nuclei. Hevin mRNA was absent from all monoaminergic neurons and cholinergic neurons of the ascending pathway. A similar cellular profile of expression was observed in human, with expression of hevin in parvalbumin interneurons and astrocytes in the cortex and caudate nucleus as well as in cortical glutamatergic neurons. Furthermore, hevin transcript was enriched in ribosomes of astrocytes and parvalbumin neurons providing a direct evidence of hevin mRNAs translation in these cell types. This study reveals the unique and complex expression profile of the matricellular protein hevin in the adult brain. This distribution is compatible with a role of hevin in astrocytic-mediated adult synaptic plasticity and in the regulation of network activity mediated by parvalbumin-expressing neurons.

Rationale: Only in Europe it can be estimated that more than 20 million of people would be affected by hypothyroidism in some moment of their life. Given that ethanol consumption is so frequent, it would be reasonable to ask what the consequences of ethanol consumption in those individuals affected by hypothyroidism are., Objectives: To study the interaction between hypothyroidism and ethanol consumption., Methods: We study ethanol consumption in a rat model of methyl-mercaptoimidazole-induced-adult-onset hypothyroidism and thyroid T4/T3 hormone supplementation. Also, we studied the effects of ethanol on motor activity, memory, and anxiety., Results: We found that hypothyroidism increased the voluntary ethanol consumption and that this was enhanced by thyroid hormone supplementation. Hypothyroidism was associated with motor hyperactivity which was prevented either by T4/T3 supplementation or ethanol. The relationship between hypothyroidism, ethanol, and anxiety was more complex. In an anxiogenic context, hypothyroidism and T4/T3 supplementation would increase immobility, an anxiety-like behavior, while in a less anxiogenic context would decrease rearing, a behavior related to anxiety. Regarding memory, acute ethanol administration did not alter episodic-like memory in hypothyroid rats. Gene expression of enzymes involved in the metabolism of ethanol, i.e., Adh1 and Aldh2, were altered by hypothyroidism and T4/T3 supplementation., Conclusions: Our results suggest that hypothyroid patients would need personalized attention in terms of ethanol consumption. In addition, they point that it would be useful to embrace the thyroid axis in the study of ethanol addiction, including as a possible therapeutic target for the treatment of alcoholism and its comorbid disorders.

The current study investigates whether probiotic fermented milk (PFM) and yogurt consumption (YC) are related to both the ingested bacteria taxa and the overall gut microbiota (GM) composition in healthy adults. PFM and YC habits were analyzed in 260 subjects (51% male) by specific questionnaires, and the following groups were considered: (1) PFM groups: nonconsumers (PFM-NC, n = 175) and consumers (PFM, n = 85), divided as follows: Bifidobacterium -containing PFM (Bif-PFM; n = 33), Lactobacillus -containing PFM (Lb-PFM; n = 14), and mixed Bifidobacterium and Lactobacillus -containing PFM (Mixed-PFM; n = 38); (2) PFM-NC were classified as: yogurt nonconsumers (Y-NC; n = 40) and yogurt consumers (n = 135). GM was analyzed through 16S rRNA sequencing. PFM consumers showed higher Bifidobacteria taxa levels compared to NC, from phylum through to species. Specifically, Bif-PFM consumption was related to higher B. animalis levels ( p < 0.001), whereas Lb-PFM consumption was associated to higher levels of Bifidobacterium ( p < 0.045) and B. longum ( p = 0.011). YC was related to higher levels of the yogurt starter Streptococcus thermophilus ( p < 0.001). Lactobacilli and the overall GM were not related either to YC or PFM consumption. According to these results, healthy adults might benefit from PFM intake by increasing Bifidobacterium levels.

Polyphenols present in some alcoholic beverages have been linked to beneficial effects in preventing cardiovascular diseases. Polyphenols found in beer with anti-proliferative and anti-cancer properties are appealing in the context of the quasi-malignant phenotype of pulmonary arterial hypertension (PAH). Our purpose was to evaluate if the chronic ingestion of a xanthohumol-fortified beer (FB) would be able to modulate the pathophysiology of experimental PAH. Male Wistar rats with monocrotaline (MCT)-induced PAH (60 mg/kg) were allowed to drink either xanthohumol-fortified beer (MCT + FB) or 5.2% ethanol (MCT + SHAM) for a period 4 weeks. At the end of the protocol, cardiopulmonary exercise testing and hemodynamic recordings were performed, followed by sample collection for further analysis. FB intake resulted in a significant attenuation of the pulmonary vascular remodeling in MCT + FB animals. This improvement was paralleled with the downregulation in expression of proteins responsible for proliferation (ERK1/2), cell viability (AKT), and apoptosis (BCL-XL). Moreover, MCT + FB animals presented improved right ventricle (RV) function and remodeling accompanied by VEGFR-2 pathway downregulation. The present study demonstrates that a regular consumption of xanthohumol through FB modulates major remodeling pathways activated in experimental PAH.

It has been well established that moderate alcohol consumption inversely correlates with cardiovascular morbidity and mortality, whereas binge alcohol drinking increases cardiovascular disease risk. The aim of this study was to assess in vivo the impact of different drinking patterns on reverse cholesterol transport (RCT); the atheroprotective process leading to the removal of excess cholesterol from the body. RCT was measured with a standardized, radioisotope-based technique in three groups of atherosclerosis-prone apolipoprotein E knock out mice: Placebo group, receiving water, which would mimic the abstainers; moderate group, receiving 0.8 g/kg alcohol/day for 28 days, which would mimic a moderate intake; binge group, receiving 0.8 g/kg alcohol/day for 5 days/week, followed by the administration of 2.8 g/kg alcohol/day for 2 days/week, which would mimic a heavy intake in a short period. Mice in the binge drinking group displayed an increase in total cholesterol, high density lipoprotein cholesterol (HDL-c) and non-HDL-c (all p < 0.0001 vs. placebo), and a significantly reduced elimination of fecal cholesterol. The moderate consumption did not lead to any changes in circulating lipids, but slightly improved cholesterol mobilization along the RCT pathway. Overall, our data confirm the importance of considering not only the total amount, but also the different consumption patterns to define the impact of alcohol on cardiovascular risk.

Consistent epidemiological evidence indicates that low-to-moderate alcohol consumption is inversely associated with cardiovascular event presentation, while high levels of alcohol intake are associated to increased cardiovascular risk. Little is known on the effects of moderate beer intake in the metabolic syndrome. The aim of this study is to investigate the effects of moderate and regular daily intake of beer with meals in overweight (body mass index (BMI) of 28⁻29.9 kg/m²) or obese class 1 (BMI of 30⁻35 kg/m²) individuals without other cardiovascular risk factors (dyslipidemia, type 2-diabetes, hypertension) focusing on the effects related to changes in weight, in lipoproteins and vascular endothelial function. We have performed an open, prospective two-arms longitudinal crossover study to investigate the effects associated with regular consumption (four week) of alcohol-free-beer (0 g alcohol/day) or traditional-beer (30 g alcohol/day in men and 15 g alcohol/day in women) on anthropometrical and biochemical parameters, liver and kidney function biomarkers, and vascular endothelial function. After four-week intervention with traditional and/or alcohol-free beer, BMI did not show any significant change and values for liver and kidney functions were within the normal levels. Moderate traditional beer intake did not affect lipid levels-however it significantly increased the antioxidant capacity of high density lipoprotein (HDL). In addition, apoB-depleted serum (after the four-week intervention period) showed a higher potential to promote cholesterol efflux from macrophages. Beer consumption did not induce vascular endothelial dysfunction or stiffness. In summary, our results based on a 12-week prospective study provide evidence that moderate intake of beer (traditional and alcohol-free) does not exert vascular detrimental effects nor increases body weight in obese healthy individuals. In contrast, moderate intake of beer increases the anti-oxidative properties of HDL and facilitates cholesterol efflux, which may prevent lipid deposition in the vessel wall.