Excessive Alcohol Drinking Research Articles

Detection of alcoholic EEG signals based on whole brain connectivity and convolution neural networks

Alcoholism is a common complex brain disorder caused by excessive drinking of alcohol and severely affected the basic function of the brain. This paper investigates classification of the alcoholic electroencephalogram (EEG) signals through whole brain connectivity analysis and deep learning methods. The whole brain connectivity analysis is proposed and implemented using mutual information algorithm. Continuous Wavelet transform was applied to extract time–frequency domain information in each selected frequency bands from EEG signal. The 2D and 3D convolutional neural networks (CNN) were used to classify the alcoholic subjects and health control subjects. UCI Alcoholic EEG dataset is employed to evaluate the proposed method, a 96.25 ± 3.11 % accuracy, 0.9806 ± 0.0163 F1-score result in 3D-CNN model was obtained via leaving-one out training method of all the testing subjects.

Development of tolerance upon repeated administration with the GABAB receptor positive allosteric modulator, COR659, on alcohol drinking in rodents

ABSTRACT Background: Recent work has demonstrated that acute administration of the novel positive allosteric modulator of the GABAB receptor, COR659, reduces several alcohol-related behaviors in rodents. Objective: To assess whether COR659 continues to lessen alcohol intake after repeated administration, a fundamental feature of drugs with therapeutic potential. Methods: Male C57BL/6J mice (n = 40) were exposed to daily 2-hour drinking sessions (20% (v/v) alcohol) under the 1-bottle “drinking in the dark” protocol and male Sardinian alcohol-preferring rats (n = 40) were exposed to daily 1-hour drinking sessions under the 2-bottle “alcohol (10%, v/v) vs water” choice regimen. COR659 (0, 10, 20, and 40 mg/kg in the mouse experiment; 0, 5, 10, and 20 mg/kg in the rat experiment) was administered intraperitoneally before 7 consecutive drinking sessions. Results: Alcohol intake in vehicle-treated mice and rats averaged 2.5–3.0 and 1.5–1.6 g/kg/session, respectively, indicative of high basal levels. In both experiments, treatment with COR659 resulted in an initial, dose-related suppression of alcohol intake (up to 70–80% compared to vehicle treatment; P < .0005 and P < .0001 in mouse and rat experiments, respectively). The magnitude of the reducing effect of COR659 on alcohol drinking diminished progressively, until vanishing over the subsequent 2–4 drinking sessions. Conclusion: COR659 effectively reduced alcohol intake in two different rodent models of excessive alcohol drinking. However, tolerance to the anti-alcohol effects of COR659 developed rapidly. If theoretically transposed to humans, these data would represent a possible limitation to the clinical use of COR659.

The GPR88 agonist RTI-13951-33 reduces alcohol drinking and seeking in mice.

GPR88 is an orphan G‐protein‐coupled receptor that is considered a potential target to treat neuropsychiatric disorders, including addiction. Most knowledge about GPR88 function stems from knockout mouse studies, and in vivo pharmacology is still scarce. Here we examine the effects of the novel brain‐penetrant agonist RTI‐13951‐33 on several alcohol‐related behaviours in the mouse. In the intermittent‐access‐two‐bottle‐choice paradigm, the compound reduced excessive voluntary alcohol drinking, while water drinking was intact. This was observed for C57BL/6 mice, as well as for control but not Gpr88 knockout mice, demonstrating efficacy and specificity of the drug in vivo. In the drinking‐in‐the‐dark paradigm, RTI‐13951‐33 also reduced binge‐like drinking behaviour for control but not Gpr88 knockout mice, confirming the alcohol consumption‐reducing effect and in vivo specificity of the drug. When C57BL/6 mice were trained for alcohol self‐administration, RTI‐13951‐33 decreased the number of nose‐pokes over a 4‐h session and reduced the number of licks and bursts of licks, suggesting reduced motivation to obtain alcohol. Finally, RTI‐13951‐33 did not induce any place preference or aversion but reduced the expression of conditioned place preference to alcohol, indicative of a reduction of alcohol‐reward seeking. Altogether, data show that RTI‐13951‐33 limits alcohol intake under distinct conditions that require consummatory behaviour, operant response or association with contextual cues. RTI‐13951‐33 therefore is a promising lead compound to evaluate GPR88 as a therapeutic target for alcohol use disorders. More broadly, RTI‐13951‐33 represents a unique tool to better understand GPR88 function, disentangle receptor roles in development from those in the adult and perhaps address other neuropsychiatric disorders.

Increased Voluntary Alcohol Consumption in Mice Lacking GABAB(1) Is Associated With Functional Changes in Hippocampal GABAA Receptors.

Gamma-aminobutyric acid type B receptor (GABABR) has been extensively involved in alcohol use disorders; however, the mechanisms by which this receptor modulates alcohol drinking behavior remain murky. In this study, we investigate alcohol consumption and preference in mice lacking functional GABABR using the 2-bottle choice paradigm. We found that GABAB(1), knockout (KO), and heterozygous (HZ) mice drank higher amounts of an alcoholic solution, preferred alcohol to water, and reached higher blood alcohol concentrations (BACs) compared to wild-type (WT) littermates. The GABABR agonist GHB significantly reduced alcohol consumption in the GABAB(1) HZ and WT but not in the KO mice. Next, because of a functional crosstalk between GABABR and δ-containing GABAA receptor (δ-GABAAR), we profiled δ subunit mRNA expression levels in brain regions in which the crosstalk was characterized. We found a loss of the alcohol-sensitive GABAAR δ subunit in the hippocampus of the GABAB(1) KO alcohol-naïve mice that was associated with increased ɣ2 subunit abundance. Electrophysiological recordings revealed that these molecular changes were associated with increased phasic inhibition, suggesting a potential gain of synaptic GABAAR responsiveness to alcohol that has been previously described in an animal model of excessive alcohol drinking. Interestingly, voluntary alcohol consumption did not revert the dramatic loss of hippocampal δ-GABAAR occurring in the GABAB(1) KO mice but rather exacerbated this condition. Finally, we profiled hippocampal neuroactive steroids levels following acute alcohols administration in the GABAB(1) KO and WT mice because of previous involvement of GABABR in the regulation of cerebral levels of these compounds. We found that systemic administration of alcohol (1.5 g/kg) did not produce alcohol-induced neurosteroid response in the GABAB(1) KO mice but elicited an expected increase in the hippocampal level of progesterone and 3α,5α-THP in the WT controls. In conclusion, we show that genetic ablation of the GABAB(1) subunit results in increased alcohol consumption and preference that were associated with functional changes in hippocampal GABAAR, suggesting a potential mechanism by which preference for alcohol consumption is maintained in the GABAB(1) KO mice. In addition, we documented that GABAB(1) deficiency results in lack of alcohol-induced neurosteroids, and we discussed the potential implications of this finding in the context of alcohol drinking and dependence.

Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure.

Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. Adolescent alcohol exposure induces epigenetic reprogramming at the enhancer region of the activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as synaptic activity response element (SARE), and decreases Arc expression in the amygdala of both rodents and humans. The causal role of amygdalar epigenomic regulation at Arc SARE in adult anxiety and drinking after adolescent alcohol exposure is unknown. Here, we show that dCas9-P300 increases histone acetylation at the Arc SARE and normalizes deficits in Arc expression, leading to attenuation of adult anxiety and excessive alcohol drinking in a rat model of adolescent alcohol exposure. Conversely, dCas9-KRAB increases repressive histone methylation at the Arc SARE, decreases Arc expression, and produces anxiety and alcohol drinking in control rats. These results demonstrate that epigenomic editing in the amygdala can ameliorate adult psychopathology after adolescent alcohol exposure.

Pituitary adenylate cyclase-activating polypeptide type 1 receptor within the nucleus accumbens core mediates excessive alcohol drinking in alcohol-preferring rats

Alcohol use disorders (AUD) have a strong component of heritability; however, the neurobiological mechanisms mediating the propensity to consume excessive amounts of alcohol are still not well understood. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide which exerts its effects mainly through the PAC1 receptor (PAC1R), has been suggested to be one of the mediators of the effects of drugs of abuse and alcohol. Here, we investigated the role of the PACAP/PAC1R system in excessive alcohol drinking in alcohol-preferring rats, an established animal model of AUD. Intracerebroventricular (i.c.v.) administration of the PAC1R antagonist PACAP(6–38) blocked excessive alcohol drinking and motivation to drink in Sardinian alcohol-preferring (Scr:sP) rats, without affecting water, saccharin, or sucrose intake. Notably, PACAP(6–38) did not affect ethanol responding in outbred Wistar rats. PACAP(6–38) also significantly reduced alcohol-seeking behavior under a second-order schedule of reinforcement. Using immunohistochemistry, a significant increase in the number of PAC1R positive cells was observed selectively in the nucleus accumbens (NAcc) Core of Scr:sP rats, compared to Wistar rats, following alcohol drinking. Finally, excessive drinking in Scr:sP rats was suppressed by intra-NAcc Core, but not intra-NAcc Shell, PACAP(6–38), as well as by virally-mediated PAC1R knockdown in the NAcc Core. The present study shows that hyperactivity of the PACAP/PAC1R system specifically in the NAcc Core mediates excessive drinking of alcohol-preferring rats, and indicates that this system may represent a novel target for the treatment of AUD.

Development and Validation of a GC-EI-MS/MS Method for Ethyl Glucuronide Quantification in Human Hair.

Ethyl glucuronide (EtG) is a minor, non-oxidative ethanol metabolite detectable in several matrices for specific periods of time. In recent years, quantification of EtG in hair has been established as the most reliable biomarker for long-term alcohol consumption, with the Society of Hair Testing offering cut-off values for assessment of both abstinence and heavy drinking. Instrumental constrains and wide inter- and intra-laboratory variability represent the ultimate barriers to widespread acceptance of hair EtG determination in the forensic context. In this study, a new analytical method for hair EtG based on gas chromatographic (GC) separation, electron impact (EI) ionization, and tandem mass spectrometry (MS/MS) detection was developed and validated. At the same time, several parameters for sample pretreatment and instrumental analysis were optimized using real hair samples obtained from different drinking subjects. A full-factorial design-of-experiment approach included procedures for hair washing, pulverization, and extraction. Rigorous multi-step washing proved not to reduce the EtG content extracted in the subsequent sample incubation. Hair pulverization with a ball mill significantly improved the EtG extraction from the keratin matrix and allowed us to reduce the time needed for the subsequent extraction step, without affecting the extraction recovery. The hair extract was derivatized with N-methyl-N-(trimethylsilyl)-trifluoroacetamide. Upon electron impact ionization of the EtG-TMS derivative, triple quadrupole mass analyzers were operated in the selected reaction monitoring (SRM) mode using the fragment m/z 405 as the precursor ion (m/z 410 for the EtG-D5 internal standard), the transitions m/z 405 → 359 and m/z 410 → 359 for quantitation, and m/z 405 → 331 and m/z 405 → 287 for qualification/confirmation, all at 10 V collision energy. The final method was fully validated and then applied to 25 real hair samples. The calibration curve proved linear between 6 and 60 pg/mg. The limit of detection (LOD) was 4 pg/mg. Intra- and inter-assay precision and accuracy tests showed a variability and bias close to 15% or lower over the entire calibration range. The new method is routinely applied in the Italian State Police’s toxicology laboratory for hair analyses addressed to exclude excessive alcohol drinking and verify the psycho-physical requirements of the personnel.

Central amygdala corticotropin-releasing factor neurons promote hyponeophagia but do not control alcohol drinking in mice.

Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) plays a critical role in rodent models of excessive alcohol drinking. However, the source of CRF acting in the CeA during alcohol withdrawal remains to be identified. In the present study, we hypothesized that CeA CRF interneurons may represent a behaviorally relevant source of CRF to the CeA increasing motivation for alcohol via negative reinforcement. We first observed that Crh mRNA expression in the anterior part of the mouse CeA correlates positively with alcohol intake in C57BL/6J males with a history of chronic binge drinking followed by abstinence and increases upon exposure to chronic intermittent ethanol (CIE) vapor inhalation. We then found that chemogenetic activation of CeA CRF neurons in Crh-IRES-Cre mouse brain slices increases gamma-aminobutyric acid (GABA) release in the medial CeA, in part via CRF1 receptor activation. While chemogenetic stimulation exacerbated novelty-induced feeding suppression (NSF) in alcohol-naïve mice, thereby mimicking the effect of withdrawal from CIE, it had no effect on voluntary alcohol consumption, following either acute or chronic manipulation. Furthermore, chemogenetic inhibition of CeA CRF neurons did not affect alcohol consumption or NSF in chronic alcohol drinkers exposed to air or CIE. Altogether, these findings indicate that CeA CRF neurons produce local release of GABA and CRF and promote hyponeophagia in naïve mice, but do not drive alcohol intake escalation or negative affect in CIE-withdrawn mice. The latter result contrasts with previous findings in rats and demonstrates species specificity of CRF circuit engagement in alcohol dependence.

Association between tea consumption and all-cause mortality in Chinese adults

Objective: To investigate the association between tea consumption and the risk of all-cause and cause-specific mortality among Chinese adults. Methods: This study was based on China Kadoorie Biobank (CKB). Tea consumption information was self-reported by participants at baseline. Death was mainly identified by linkage to the death registry system. Cox proportional hazard regression models estimated HR and 95%CI. Results: With a median follow-up of 11.1 years, there were 34 661 deaths in 438 443 participants. Compared with those who never drink tea, all-cause mortality HR(95%CI) were 0.89(0.86-0.91) and 0.92(0.88-0.95) for non-daily tea drinkers and daily tea drinkers, respectively. A statistically significant difference was found in the association of tea consumption and the risk of all-cause mortality between men and women(interaction P<0.05). The protective effect was mainly seen in men. Compared with those who never drink tea, daily tea drinkers had a reduced risk of death from ischemic heart disease, ischemic stroke, hemorrhagic stroke, cancer, respiration diseases and other causes of death, and the corresponding HR(95%CI) were 0.83(0.76-0.92), 0.82(0.69-0.97), 0.86(0.78-0.94), 1.03(0.97-1.09), 1.00(0.87-1.16), 0.84(0.78-0.90). Among never smokers and non-excessive drinkers, there was no statistically significant association between daily tea drinking and the risk of death from cancer. While smokers and excessive drinkers had an increased risk of death from cancer (interaction P<0.001). Conclusions: Tea consumers had reduced risks of all-cause mortality and partial cause-specific mortality, but not for the risk of death from cancer. On the contrary, daily tea drinkers with smoking habits and excessive alcohol drinking had an increased risk of death from cancer.

Excessive alcohol consumption and the risk of knee osteoarthritis: a prospective study from the Osteoarthritis Initiative

To examine the association of alcohol consumption with risk of incident knee osteoarthritis (OA) in a large prospective cohort study. In the Osteoarthritis Initiative, 2,846 participants aged 45-79 years and free from radiographic knee OA in at least one knee at baseline were followed up to 96 months. Information on baseline alcohol consumption was obtained from the Block Brief Food Frequency Questionnaire. Incident cases of radiographic knee OA (ROA) were defined as Kellgren-Lawrence grade changing from zero or one to≥two during the follow-up time. Incident symptomatic OA (SxOA) was defined as ROA with knee pain worsening. The Cox proportional hazards models were used to assess the independent association between alcohol consumption and risk of knee. During 96 months' follow-up, we identified 691 knees with incident ROA, and 496 knees with incident SxOA among 2,846 subjects. Compared to non-drinkers, excessive alcohol consumption was significantly associated with increased risk of ROA (HR≥30g/d vs none=1.93, 95% CI: 1.28-2.89) and SxOA (HR≥30g/d vs none=1.61, 95% CI: 1.04-2.48). Similar association was observed for liquor consumption (HR liquor≥15g/d vs none=1.71, 95% CI: 1.16-2.52 for ROA; HR liquor≥15g/d vs none=1.59, 95% CI: 1.04-2.39 for SxOA). Light to moderate alcohol consumption was not associated with knee OA risk. Our results suggest that excessive alcohol drinking was associated with an increased risk of knee OA. Further studies are needed in other populations.

The Lifelong Health Support 10: a Japanese prescription for a long and healthy life.

BackgroundAlthough the age-adjusted incidence and mortality of cancer and cardiovascular disease (CVD) have been decreasing steadily in Japan, both diseases remain major contributors to morbidity and mortality along with the aging society. Herein, we aim to provide a prescription of 10 health tips for long and healthy life named the “Lifelong Health Support 10 (LHS10).”MethodThe LHS10 was developed by the preventive medicine specialists at the National Cerebral and Cardiovascular Center in Suita, where it has been used for health guidance to prevent CVD, cancer, and cognitive decline in addition to their major risk factors such as hypertension, diabetes, and obesity. It consisted of the lifestyle modification recommendations of the 2014 Japanese Society of Hypertension guidelines and the 2017 Japan Atherosclerosis Society Guidelines for preventing atherosclerotic CVD. Further, it came in line with other international lifestyle modification guidelines. In this narrative review, we summarized the results of several Japanese epidemiological studies investigating the association between the LHS10 items and the risk of cancer, CVD, and other chronic diseases including dementia, diabetes, and chronic kidney disease.ResultsThe LHS10 included avoiding smoking and secondhand smoke exposure, engaging in physical activity, refraining from excessive alcohol drinking, reducing fried foods and sugary soft drinks, cutting salt in food, consuming more vegetables, fruits, fish, soy foods, and fibers, and maintaining proper body weight. All items of the LHS10 were shown to reduce the risk of cancer, CVD, and other chronic diseases.ConclusionsThe LHS10 can be a helpful tool for health guidance.Supplementary informationThe online version contains supplementary material available at https://doi.org/10.1265/ehpm.22-00085.

Genetic association of nucleus accumbens 5-hydroxyindoleacetic acid level and alcohol preference drinking in a quasi-congenic male mice: Potential modulation by Grm7 gene polymorphism

ObjectiveTo test the hypothesis that predisposition to high alcohol drinking behavior is genetically associated with hypoactive serotonergic function in the Nucleus Accumbens (NAc). MethodAlcohol avoiding C5A3 and alcohol preferring I5B25A mice of the Quasi-congenic Recombinant QTL Introgression (RQI) mouse strains were subjected to in vivo microdialysis in the NAc. Neurotransmitter and metabolite contents were analyzed by HPLC and samples were collected in three phases: Baseline, Control, and Alcohol. Samples were collected with 20 min intervals. ResultsBetween-strain differences restricted to small chromosome segments significantly affected both alcohol preference drinking and NAc 5-HIAA levels [F1,13 = 5.569 p=.035 (General Linear Model Repeated Measures ANOVA and Tests of Between-Subjects Effects)]. Whole genome biallelic DNA marker genotyping allowed the identification of 16 differential microsatellite markers associated with low 5-HIAA levels and excessive alcohol drinking. Chromosome 6 markers were linked to Grm7 (51.19 centimorgan), a reported candidate gene for modulation of addiction. The results are consistent with earlier reports of association of low 5-HIAA and high alcohol consumption in rats and primates, including Homo sapiens. ConclusionLow NAc 5-HIAA and high alcohol consumption are genetically associated in a quasi-congenic mouse model carrying variants of the Grm7 gene. We propose that constitutional polymorphism in Grm7 may modulate CRF neuron activity via altered mGluR7 expression thus targeting CRF pathways to substance use circuits. This raises the possibility of modulation of DRN 5-HT neurons leading to hypo- or hyper-serotonergic condition in NAc and higher or lower alcohol preference drinking.

Viral-Mediated Knockdown of Nucleus Accumbens Shell PAC1 Receptor Promotes Excessive Alcohol Drinking in Alcohol-Preferring Rats.

Alcohol use disorder (AUD) is a chronic, relapsing disorder whose genetic and environmental susceptibility components are not fully understood. Neuropeptidergic signaling has been repeatedly implicated in modulating excessive alcohol drinking, especially within sub-regions of the striatum. Here, we investigated the potential involvement of the selective receptor for pituitary adenylate cyclase-activating polypeptide (PACAP), PAC1R, in the nucleus accumbens shell (NAcc Shell) in excessive alcohol drinking in alcohol-preferring rats, an established animal model of the genetic propensity for alcoholism. Scr:sP alcohol-preferring rats were trained to operantly self-administer alcohol and then either an AAV virus short-hairpin RNA (shRNA) targeted to knockdown PAC1R, or an AAV control virus were microinfused into the NAcc Shell. NAcc Shell PAC1R shRNA knockdown virus was confirmed to significantly decrease PAC1R levels in the NAcc Shell. The effects of NAcc Shell PAC1R shRNA knockdown on ethanol self-administration were investigated using a Fixed Ratio (FR) 1 and a Progressive Ratio (PR) schedule of reinforcement. The effect of PAC1R knockdown on self-administration of an alternative reinforcer, saccharin, was also assessed. The results showed that the reduction in PAC1R in the NAcc Shell led to excessive ethanol drinking, increased preference for ethanol, and higher motivation to drink. NAcc Shell PAC1R shRNA knockdown did not comparably increase saccharin self-administration, suggesting selectivity of action. These data suggest that NAcc Shell PAC1R may serves as a “brake” on alcohol drinking, and thereby the loss of function of PAC1R leads to excessive alcohol consumption. Therefore, the PACAP/PAC1R system may represent a novel target for the treatment of AUD.

Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking

A relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p’s < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p’s < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.

FGF2 is an endogenous regulator of alcohol reward and consumption.

Alcohol use disorder (AUD) is a chronic, relapsing disorder, characterized by escalating alcohol drinking and loss of control, with very limited available treatments. We recently reported that the expression of fibroblast growth factor 2 (Fgf2) is increased in the striatum of rodents following long-term excessive alcohol drinking and that the systemic or intra-striatal administration of recombinant FGF2 increases alcohol consumption. Here, we set out to determine whether the endogenous FGF2 plays a role in alcohol drinking and reward, by testing the behavioural phenotype of Fgf2 knockout mice. We found that Fgf2 deficiency resulted in decreased alcohol consumption when tested in two-bottle choice procedures with various alcohol concentrations. Importantly, these effects were specific for alcohol, as a natural reward (sucrose) or water consumption was not affected by Fgf2 deficiency. In addition, Fgf2 knockout mice failed to show alcohol-conditioned place preference (CPP) but showed normal fear conditioning, suggesting that deletion of the growth factor reduces alcohol's rewarding properties. Finally, Fgf2 knockout mice took longer to recover from the loss of righting reflex and showed higher blood alcohol concentrations when challenged with an intoxicating alcohol dose, suggesting that their ethanol metabolism might be affected. Together, our results show that the endogenous FGF2 plays a critical role in alcohol drinking and reward and indicate that FGF2 is a positive regulator of alcohol-drinking behaviours. Our findings suggest that FGF2 is a potential biomarker for problem alcohol drinking and is a potential target for pharmacotherapy development for AUD.

Moderation effect of economic status in the association between early life famine exposure and MAFLD in adulthood.

The double burden of malnutrition (DBM) in China resulted in high prevalence of diet-related non-communicable diseases. The aim of this study was to analyse the moderation of economic status in the association between early famine exposure and metabolic dysfunction associated with fatty liver disease (MAFLD) in adulthood. 10190 participants in the SPECT-China study enrolled from 2014 to 2016 were included in this study. Participants with fetal famine exposure (birth year 1959-1962) or early-childhood famine exposure (birth year 1955-1958) formed the exposure group. The associations with MAFLD were assessed via regression analyses. In men, economic status could not moderate the association between early life famine and MAFLD after adjusting for age, excess alcohol drinking, current smokers, famine severity, waist circumference, diabetes, hypertension, and dyslipidemia (P for interaction=.52). However, in women and in the total population, economic status could moderate the association between early life famine and MAFLD after adjusting for the above confounders (P for interaction=.01). In the total population and in women, early life famine exposure was associated with MAFLD in both low economic status and high economic status. However, in men, early life famine exposure was not associated with MAFLD in low economic status, while in high economic status, early-childhood famine exposure was associated with MAFLD. Economic status could moderate the association between early life famine exposure and MAFLD in total population and in women.

Reactive, Adult Neurogenesis From Increased Neural Progenitor Cell Proliferation Following Alcohol Dependence in Female Rats.

Hippocampal neurodegeneration is a consequence of excessive alcohol drinking in alcohol use disorders (AUDs), however, recent studies suggest that females may be more susceptible to alcohol-induced brain damage. Adult hippocampal neurogenesis is now well accepted to contribute to hippocampal integrity and is known to be affected by alcohol in humans as well as in animal models of AUDs. In male rats, a reactive increase in adult hippocampal neurogenesis has been observed during abstinence from alcohol dependence, a phenomenon that may underlie recovery of hippocampal structure and function. It is unknown whether reactive neurogenesis occurs in females. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by 7 or 14 days of abstinence. Immunohistochemistry (IHC) was used to assess neural progenitor cell (NPC) proliferation (BrdU and Ki67), the percentage of increased NPC activation (Sox2+/Ki67+), the number of immature neurons (NeuroD1), and ectopic dentate gyrus granule cells (Prox1). On day seven of abstinence, ethanol-treated females showed a significant increase in BrdU+ and Ki67+ cells in the subgranular zone of the dentate gyrus (SGZ), as well as greater activation of NPCs (Sox2+/Ki67+) into active cycling. At day 14 of abstinence, there was a significant increase in the number of immature neurons (NeuroD1+) though no evidence of ectopic neurogenesis according to either NeuroD1 or Prox1 immunoreactivity. Altogether, these data suggest that alcohol dependence produces similar reactive increases in NPC proliferation and adult neurogenesis. Thus, reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

Healthcare professionals' knowledge of modifiable stroke risk factors: A cross-sectional questionnaire survey in greater Gaborone, Botswana.

BackgroundStroke remains the second leading cause of deaths and disability globally, with highest mortality in Africa (low- and middle-income countries). It is crucial for healthcare professionals to have sufficient stroke risk factors' knowledge in order to reduce the stroke burden.AimsWe investigated healthcare professionals' knowledge of modifiable stroke risk factors, and identified demographic factors influencing this knowledge.MethodsIn this cross-sectional survey study from Botswana (upper middle-income country), structured questionnaires reflecting recent stroke guidelines were administered to a representative selection of healthcare workers in greater Gaborone. The response rate was 61.4%, comprising 84 doctors, 227 nurses and 33 paramedics. Categorical data were described using percentages and Chi-square tests. Associations between stroke risk factors' knowledge and demographic factors were analyzed with one-way ANOVA using SPSS 25 statistical software.ResultsAwareness rate of individual stroke risk factors was highest for hypertension (96.5%), followed by obesity (93.3%), smoking (91.9%), elevated total cholesterol (91.0%), physical inactivity (83.4%), elevated low-density lipoprotein (LDL) cholesterol (81.1%), excessive alcohol drinking (77.0%), and lowest for diabetes (73.3%). For all-8 risk factors, doctors had the highest knowledge, followed by nurses and paramedics lowest (7.11 vs 6.85 vs 6.06, P < 0.05).ConclusionIn Botswana, specific healthcare professionals' subgroups need to be targeted for continuing education on stroke risk factors for improving stroke prevention and reducing stroke-related disability and mortality.

Deep Convolutional Neural Network Regularization for Alcoholism Detection Using EEG Signals.

Alcoholism is attributed to regular or excessive drinking of alcohol and leads to the disturbance of the neuronal system in the human brain. This results in certain malfunctioning of neurons that can be detected by an electroencephalogram (EEG) using several electrodes on a human skull at appropriate positions. It is of great interest to be able to classify an EEG activity as that of a normal person or an alcoholic person using data from the minimum possible electrodes (or channels). Due to the complex nature of EEG signals, accurate classification of alcoholism using only a small dataset is a challenging task. Artificial neural networks, specifically convolutional neural networks (CNNs), provide efficient and accurate results in various pattern-based classification problems. In this work, we apply CNN on raw EEG data and demonstrate how we achieved 98% average accuracy by optimizing a baseline CNN model and outperforming its results in a range of performance evaluation metrics on the University of California at Irvine Machine Learning (UCI-ML) EEG dataset. This article explains the stepwise improvement of the baseline model using the dropout, batch normalization, and kernel regularization techniques and provides a comparison of the two models that can be beneficial for aspiring practitioners who aim to develop similar classification models in CNN. A performance comparison is also provided with other approaches using the same dataset.

Wokers’ awareness of alcohol breathalyser test in the workplace and their alcohol consumption patterns

Orientation: An alcohol breathalyser test is one of various methods of assessing alcohol consumption behaviour of workers in the workplace. Its awareness can yield insights on behavioural change of alcohol-consuming individuals in safety-sensitive settings when being aware of alcohol breathalyser testing.Research purpose: A breathalyser test provides an efficient means of measuring blood alcohol concentration within seconds of an employee blowing into the device. The purpose of this research was to examine awareness of breathalyser testing to capture meaning that can offer insights on behaviour under research.Motivation for research: The research was prompted by a quest to gain understanding of thought processes (motivation to control behaviour) when alcohol is involved. By focusing on awareness, it was possible to interpret behaviour. The research is a basis for future studies and can contribute to discussions related to alcohol testing in the workplace.Research approach/design and method: A qualitative approach was followed to gain insights into the topic under research. Eight alcohol-consuming individuals who performed jobs considered high-risk consented to participate in semi-structured, face-to-face interviews. The data were analysed through interpretative phenomenological analysis (IPA).Main findings: The findings revealed excessive alcohol consumption and intoxication in spite of awareness of breathalyser testing. Individuals prone to external inducements were more likely to abuse alcohol. Behaviour therefore tends to be unstable and impulsive when alcohol is involved.Practical implications: Reporting for work after excessive drinking of alcohol is not an indication of total soberness. Individuals may physically be present in the workplace without making any contribution to work processes because of effects of alcohol.Contribution/value-add: The research highlights behavioural insights that can contribute to studies related to locus of control and control over alcohol in relation to testing to workplace testing.