Psychopharmacological interaction of alcohol and posttraumatic stress disorder: Effective action of naringin.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are prevalently co-occurring, important risk factors for a broad array of neuropsychiatric diseases. To date, how these two contrastive concomitant pairs increase the risk of neuropsychiatric states, notably exacerbating PTSD-related symptoms, remains unknown. Moreover, pharmacological interventions with agents that could reverse PTSD-AUD comorbidity, however, remained limited. Hence, we investigated the neuroprotective actions of naringin in mice comorbidly exposed to PTSD followed by repeated ethanol (EtOH)-induced AUD. Following a 7-day single-prolong-stress (SPS)-induced PTSD in mice, binge/heavy drinking, notably related to AUD, was induced in the PTSD mice with every-other-day ethanol (2 g/kg, p.o.) administration, followed by daily treatments with naringin (25 and 50 mg/kg) or fluoxetine (10 mg/kg), from days 8-21. PTSD-AUD-related behavioral changes, alcohol preference, hypothalamic-pituitary-adrenal (HPA)-axis dysfunction-induced neurochemical alterations, oxidative/nitrergic stress, and inflammation were examined in the prefrontal-cortex, striatum, and hippocampus. PTSD-AUD mice showed aggravated anxiety, spatial-cognitive, social impairments and EtOH intake, which were abated by naringin, similar to fluoxetine. Our assays on the HPA-axis showed exacerbated increased corticosterone release and adrenal hypertrophy, accompanied by marked dopamine and serotonin increase, with depleted glutamic acid decarboxylase enzyme in the three brain regions, which naringin, however, reversed, respectively. PTSD-AUD mice also showed increased TNF-α, IL-6, malondialdehyde and nitrite levels, with decreased antioxidant elements in the prefrontal-cortex, striatum, and hippocampus compared to SPS-EtOH-mice, mainly exacerbating catalase and glutathione decrease in the hippocampus relative SPS-mice. These findings suggest that AUD exacerbates PTSD pathologies in different brain regions, notably comprising neurochemical dysregulations, oxidative/nitrergic and cytokine-mediated inflammation, with HPA dysfunction, which were, however, revocable by naringin.

Substance use-related problems in mild intellectual disability: A Swedish nationwide population-based cohort study with sibling comparison.

Background: Evidence for substance use-related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use-related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods: We conducted a population-based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use-related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use-related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol-related somatic disease, conviction for a substance-related crime, and substance-related death. Results: Individuals with mild intellectual disability had a higher risk of any substance use-related problem compared to the general population (HR, 1.81; 95% CI, 1.72-1.91), both in males (HR, 1.76; 95% CI, 1.65-1.89) and females (HR, 1.89; 95% CI, 1.74-2.05). The risks of substance use-related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21-8.24). The associations were attenuated in the sibling comparison models. Conclusions: Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use-related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use-related problems.

Prevalence of mental health symptoms in Austrian veterinarians and examination of influencing factors.

Although previous studies point to a high mental health burden in veterinarians, little is known about mental health in Austrian veterinarians as well as potential underlying factors of poor mental health. We assessed mental health in Austrian veterinarians, compared it to the mental health of the general population, and explored potential risk factors for poor mental health in veterinarians. A total of n = 440 veterinarians (72.0% women; mean age: 44.53 ± 11.25 years) took part in an online survey in 2022 in which validated screening tools for symptoms of depression (PHQ-9), anxiety (GAD-7), sleep disorders (ISI-2), perceived stress (PSS-4), and alcohol abuse (CAGE) were applied. Multivariable logistic regression revealed higher adjusted odds for exceeding cut-offs for clinically relevant depressive, anxiety, and insomnia symptoms in veterinarians (1.35-2.70) compared to the general population. Mental health symptoms in veterinarians were associated with female gender, physical inactivity, higher smartphone usage, higher working hours, less professional experience, and working with pets. In conclusion, it appears that veterinarians encounter mental health challenges that are more pronounced than those experienced in the general population. The teaching of strategies to improve mental hygiene as part of the curricula of veterinary education and targeted training and mentoring of employers and their team should be implemented to improve mental health in the veterinary profession.

Developmental trajectories of child and adolescent emotional problems: associations with early adult alcohol use behaviors.

BACKGROUND: Whether emotional problems during childhood and adolescence are longitudinally associated with adult alcohol use behaviors is unclear. This study examined associations between developmental trajectories of emotional problems and early adult alcohol use behaviors, while considering co-occurring conduct problems, developmental change/timing, sex differences, and potential confounds. METHODS: Participants were from the Twins Early Development Study (analytic N = 19,908 individuals). Emotional and conduct problems were measured by parent reports at child ages 4, 7, and 9 years and via self-reports at ages 9, 11, and 16 years on the Strengths and Difficulties Questionnaire. Alcohol use behaviors (alcohol consumption and alcohol-related problems) were self-reported by the twins on the Alcohol Use Disorders Identification Test at age 22 years. Piecewise latent growth curve models described nonlinear developmental trajectories of emotional and conduct problems from ages 4 to 16. At age 22, alcohol use was regressed on emotional and conduct problems' intercepts and slopes from piecewise latent growth curve model and sex differences in regression coefficients were tested. Using twin modeling, Cholesky decompositions and direct path models were compared to test whether significant phenotypic associations were best explained by direct phenotypic influences or correlated genetic and environmental influences. RESULTS: Emotional problems had different associations with alcohol-related problems versus alcohol consumption. After accounting for direct influences from conduct problems, emotional problems were not associated with alcohol-related problems, while emotional problems at age 9 were negatively associated with alcohol consumption in males. CONCLUSIONS: Overall, findings did not support emotional problems as prospective risk factors for severe alcohol use above and beyond risks associated with conduct problems. Sex- and age-specific links between emotional problems and alcohol consumption in early adulthood may be worthy of further exploration, particularly as twin analyses improved our confidence that such links may be underpinned by causal mechanisms.

The Relationship Between Intimate Partner Violence, Depression, Alcohol Abuse in Black and Hispanic Women.

The relationship between intimate partner violence (IPV), depression, and risky alcohol use is complex and multi-dimensional. Depression has been documented as a common consequence of experiencing IPV, where depressed individuals might turn to substances like alcohol as a coping mechanism. Thus, assessing the indirect effect of depression in the relationship between IPV and alcohol abuse in African American and Hispanic women is warranted. Cross-sectional data was collected from 152 African American and Hispanic women living in Miami, Florida. Descriptive statistics, correlation analysis, and Hayes' direct and indirect mediation analyses were conducted. A total of 77% reported IPV. The mean age was 42.84 (SD = 10.69). About 57% of participants identified as African American, and 62% identified as Hispanic/Latino. On average, participant depression scores (8.6, SD = 5.7) showed mild-to-moderate severity, and the average alcohol abuse score was 15.5 (±8.9), suggesting risky alcohol use. IPV was directly associated with alcohol abuse (ß = .50, 95% CI [.18, .82]; [R2 = .059, F(1, 150) = 9.37, p < .001), and with depression (ß = .48, 95% CI [.27, .69]; [R2 = .119, F(1, 150) = 20.43, p < .001). Depression modified the effect of IPV on alcohol abuse by about 19% (ß = .56, 95% CI [.33, .80]; [R2 = .185, F(2, 149) = 16.87, p < .0026). Results of this study suggest that depression is an important component to be considered when addressing alcohol abuse among women with experiences of IPV. This study highlights the importance of assessing women who report IPV for depressive symptoms when treating alcohol use disorders.

Pseudobulbar Affect in an Elderly Female With Small Vessel Ischemic Disease and Alcohol Abuse Disorder: A Case Report.

Pseudobulbar affect (PBA) is a neurological condition characterized by recurrent, inappropriate, and involuntary outbursts of emotion, primarily crying and laughter, which are dissociated from the individual's emotional experience. The precise underlying cause of PBA remains unknown; however, existing evidence suggests the involvement of dopaminergic, serotonergic, and glutamatergic neurotransmission within the corticopontine-cerebellar pathways responsible for regulating the motor expression of emotions. Additionally, PBA has been observed to co-occur with other neurocognitive and psychiatric disorders. Therefore, it is crucial to consider the possibility of a PBA diagnosis in patients with underlying neurological damage and disorders.

Treadmill Exercise Reshapes Cortical Astrocytic and Neuronal Activity to Improve Motor Learning Deficits Under Chronic Alcohol Exposure.

Alcohol abuse induces various neurological disorders including motor learning deficits, possibly by affecting neuronal and astrocytic activity. Physical exercise is one effective approach to remediate synaptic loss and motor deficits as shown by our previous works. In this study, we unrevealed the role of exercise training in the recovery of cortical neuronal and astrocytic functions. Using a chronic alcohol injection mouse model, we found the hyperreactivity of astrocytes along with dendritic spine loss plus lower neuronal activity in the primary motor cortex. Persistent treadmill exercise training, on the other hand, improved neural spine formation and inhibited reactive astrocytes, alleviating motor learning deficits induced by alcohol exposure. These data collectively support the potency of endurance exercise in the rehabilitation of motor functions under alcohol abuse.

Iatrogenic open humeral shaft fractures following functional bracing.

INTRODUCTION: The treatment of closed humeral shaft fractures tends to be successful with functional bracing. Treatment failure due to iatrogenic conversion to an open fracture has not been described in the literature. We present a case series of patients that experienced open humeral shaft fractures after initially being treated with functional bracing for closed humeral shaft fractures and describe what factors are associated with this complication. MATERIALS AND METHODS: This was a retrospective case series performed at three level 1 trauma centers across North America. All nonoperatively treated humeral shaft fractures were reviewed from 2001 to 2023. Patients were included if they sustained a humeral shaft fracture, > 18 years old, were initially treated non-operatively with functional bracing which subsequently converted to an open fracture. Eight patients met inclusion criteria. All included patients were eventually treated with irrigation, debridement, and open reduction and internal fixation. Outcomes assessed included mortality rate, time until the fracture converted from closed to open, need for further surgery, and bony union. Descriptive statistics were used in analysis. RESULTS: The eight included patients on average were 65 ± 21.4 years old and had a body mass index (BMI) of 25.6 ± 5.2. Six patients were initially injured due to a fall. Time until the fractures became open on average was 5.2 ± 3.6 weeks. Three patients (37.5%) died within 1.8 ± 0.6 years after initial injury. The average Charlson Comorbidity Index (CCI) score was 4.5 ± 3.4. Three patients (37.5%) had dementia. Common characteristics among this cohort included a history of visual disturbances (50.0%), cerebrovascular accident (50.0%), smoking (50.0%), and alcohol abuse (50.0%). CONCLUSION: Conversion from a closed to open humeral shaft fracture after functional bracing is a potentially devastating complication. Physicians should be especially cognizant of patients with a low BMI, history of falling or visual disturbance, dementia, age ≥ 65, decreased sensorimotor protection, and significant smoking or alcohol history when choosing to use functional bracing as the final treatment modality. LEVEL OF EVIDENCE: IV.

Hovenia dulcis Fruit Peduncle Polysaccharides Reduce Intestinal Dysbiosis and Hepatic Fatty Acid Metabolism Disorders in Alcohol-Exposed Mice.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) have the potential to alleviate alcoholic liver injury and play essential roles in treating alcohol-exposed liver disease; however, the hepatoprotective effects and mechanisms remain elusive. In this study, we investigated the hepatoprotective effects of HDPs and their potential mechanisms in alcohol-exposed mice through liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels, and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. When applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria, significant increases in Firmicutes at the phylum level, increased Lactobacillus abundance, and decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid and glycerophospholipid metabolism, and identified two important metabolites-C00157 (phosphatidylcholine, a glycerophospholipid plays a central role in energy production) and C04230 (1-Acyl-sn-glycero-3-phosphocholine, a lysophospholipid involved in the breakdown of phospholipids)-involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs have a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Clinical Indicators of Bone Deterioration in Alcoholic Liver Cirrhosis and Chronic Alcohol Abuse: Looking beyond Bone Fracture Occurrence.

Although previous studies indicated that chronic alcohol abuse (CAA) and alcoholic liver cirrhosis (ALC) are associated with increased bone fragility, understanding bone fragility determinants is still modest in these individuals. We used a comprehensive individualized clinical fracture risk assessment approach (vertebral osteodensitometry, femoral osteodensitometry and geometry, and serum bone turnover biomarkers) to compare adult male patients with ALC who have not previously had femoral or vertebral fractures (n = 39), patients with CAA (without liver cirrhosis, n = 78) who have not previously had femoral or vertebral fractures and healthy age- and sex-matched controls (n = 43). Our data suggested that intertrochanteric bone mineral density was significantly lower in ALC and CAA patients than in controls. Also, the trabecular bone score was considerably lower in ALC patients compared with CAA and control individuals. The most significant inter-group differences in femoral geometry were noted on the femoral shaft. Patients with ALC and CAA have a higher 10-year risk of major osteoporotic fractures compared to the controls. Analysis of bone turnover biomarkers showed increased osteoprotegerin and beta-C-terminal telopeptide serum concentrations and decreased insulin growth factor-1 concentrations in patients with ALC compared to CAA and control groups. Our data revealed that bone alterations are present in patients with ALC and CAA even if they did not sustain a nontraumatic bone fracture, but it is also indicative that current bone-assessing clinical methods are not entirely reliable. Thus, future studies should focus on developing a reliable integrative clinical tool that can be used to accurately predict and prevent bone fracture occurrences in patients with ALC and CAA.

Exploring in the classroom the relationship between alcohol intake and behavioral disorders through an animal model.

Alcohol consumption has profound effects on behavior, such as impaired judgment, addiction or even death. It is estimated that alcohol contributes to around three million deaths worldwide, 13.5% of them in young people with ages between 20 and 39 years. Consequently, it is necessary to raise awareness among college and high school students of the risk related to alcohol drinking. The small nematode Caenorhabditis elegans is an animal widely used as a model organism to study nearly all aspects of Biochemistry. It is a powerful tool to test the potential bioactivity and molecular mechanisms of natural compounds and drugs in vivo. Therefore, it is an interesting topic to include in an undergraduate course of Biotechnology, Biochemistry or Biology students among other scientific vocations. C. elegans is also used as a neurobiological model to evaluate substances´ neurotoxicity and behavioral effects. The proposed experiment introduces students to the handling of this preclinical model and to the evaluation of behavioral alterations induced by chemicals in scientific research. The effects of different doses of ethanol on C. elegans behavior are studied using a versatile chemotaxis assay. This laboratory experiment is suitable for an undergraduate course. The practical session can be used in the global strategies of information and awareness of educational centres to mitigate the impact of alcohol abuse among students, both in formal courses or in Science fairs or exhibitions.

Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable.

Hemochromatosis represents clinically one of the most important genetic storage diseases of the liver caused by iron overload, which is to be differentiated from hepatic iron overload due to excessive iron release from erythrocytes in patients with genetic hemolytic disorders. This disorder is under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), the gut microbiome, and alcohol abuse as a risk factor, which are all topics of this review article. Triggered by released intracellular free iron from ferritin via the autophagic process of ferritinophagy, ferroptosis is involved in hemochromatosis as a specific form of iron-dependent regulated cell death. This develops in the course of mitochondrial injury associated with additional iron accumulation, followed by excessive production of ROS and lipid peroxidation. A low fecal iron content during therapeutic iron depletion reduces colonic inflammation and oxidative stress. In clinical terms, iron is an essential trace element required for human health. Humans cannot synthesize iron and must take it up from iron-containing foods and beverages. Under physiological conditions, healthy individuals allow for iron homeostasis by restricting the extent of intestinal iron depending on realistic demand, avoiding uptake of iron in excess. For this condition, the human body has no chance to adequately compensate through removal. In patients with hemochromatosis, the molecular finetuning of intestinal iron uptake is set off due to mutations in the high-FE2+ (HFE) genes that lead to a lack of hepcidin or resistance on the part of ferroportin to hepcidin binding. This is the major mechanism for the increased iron stores in the body. Hepcidin is a liver-derived peptide, which impairs the release of iron from enterocytes and macrophages by interacting with ferroportin. As a result, iron accumulates in various organs including the liver, which is severely injured and causes the clinically important hemochromatosis. This diagnosis is difficult to establish due to uncharacteristic features. Among these are asthenia, joint pain, arthritis, chondrocalcinosis, diabetes mellitus, hypopituitarism, hypogonadotropic hypogonadism, and cardiopathy. Diagnosis is initially suspected by increased serum levels of ferritin, a non-specific parameter also elevated in inflammatory diseases that must be excluded to be on the safer diagnostic side. Diagnosis is facilitated if ferritin is combined with elevated fasting transferrin saturation, genetic testing, and family screening. Various diagnostic attempts were published as algorithms. However, none of these were based on evidence or quantitative results derived from scored key features as opposed to other known complex diseases. Among these are autoimmune hepatitis (AIH) or drug-induced liver injury (DILI). For both diseases, the scored diagnostic algorithms are used in line with artificial intelligence (AI) principles to ascertain the diagnosis. The first-line therapy of hemochromatosis involves regular and life-long phlebotomy to remove iron from the blood, which improves the prognosis and may prevent the development of end-stage liver disease such as cirrhosis and hepatocellular carcinoma. Liver transplantation is rarely performed, confined to acute liver failure. In conclusion, ferroptosis, ROS, the gut microbiome, and concomitant alcohol abuse play a major contributing role in the development and clinical course of genetic hemochromatosis, which requires early diagnosis and therapy initiation through phlebotomy as a first-line treatment.

[Qualitative and quantitative characteristics of structures of cerebral cortex structure in young people under conditions of chronic alcohol intoxication]. / Kachestvennaya i kolichestvennaya kharakteristika struktur kory golovnogo mozga u lits molodogo vozrasta v usloviyakh khronicheskoi alkogol'noi intoksikatsii.

OBJECTIVE: To study morphological changes of cerebral cortex in young people under the conditions of chronic alcohol intoxication (CAI). MATERIAL AND METHODS: Morphometric examination of cerebral cortex fragments obtained from 28 persons who died with a CAI diagnosis (average age was 38 years), and 25 subjects who died from other causes, which are not associated with alcohol consumption (average age was 39 years), was carried out. RESULTS: It was shown that neurons of pathological shapes, including hypo- and hyperchromic, pyknotic and «shadow-like¼, were dominant in group of CAI. There was an increase in the glial index and a greater intensity of perivascular and pericellular edema compared to the control group. CONCLUSION: Morphological changes of cerebral cortex under the conditions of CAI are non-specific and largely similar to neurodegenerative alterations in other pathological conditions, senile dementia. Clearer histological criteria for alcoholic encephalopathy are needed, including with the use of immunohistochemical methods.

Diosgenin alleviates alcohol-mediated escalation of social defeat stress and the neurobiological sequalae.

RATIONALE: Emerging evidence indicates that persistent alcohol consumption escalates psychosocial trauma achieved by social defeat stress (SDS)-induced neurobiological changes and behavioral outcomes. Treatment with compounds with neuroprotective functions is believed to reverse ethanol (EtOH)-aggravated SDS-induced behavioral impairments. OBJECTIVES: We investigated the outcomes of diosgenin treatment, a phytosteroidal sapogenin in mice co-exposed to repeated SDS and EtOH administration. METHODS: During a period of 14 days, SDS male mice were repeatedly administered EtOH (20%, 10 mL/kg) orally from days 8-14 (n = 9). Within days 1-14, SDS mice fed with EtOH were simultaneously treated with diosgenin (25 and 50 mg/kg) or fluoxetine (10 mg/kg) by oral gavage. Locomotor, cognitive-, depressive-, and anxiety-like behaviors were assessed. Adrenal weight, serum glucose, and corticosterone levels were assayed. Brain markers of oxido-inflammatory, neurochemical levels, monoamine oxidase-B, and acetylcholinesterase activities were measured in the striatum, prefrontal cortex, and hippocampus. RESULTS: The anxiety-like behavior, depression, low stress resilience, social, and spatial/non-spatial memory decline exhibited by SDS mice exposed to repeated EtOH administration were alleviated by diosgenin (25 and 50 mg/kg) and fluoxetine, illustrated by increased dopamine and serotonin concentrations and reduced monoamine oxidase-B and acetylcholinesterase activities in the prefrontal cortex, hippocampus, and striatum. Diosgenin attenuated SDS + EtOH interaction induced corticosterone release and adrenal hypertrophy, accompanied by reduced TNF-α, IL-6, malondialdehyde, and nitrite levels in the striatum, prefrontal cortex, and hippocampus. Diosgenin increased glutathione, superoxide dismutase, and catalase levels in SDS + EtOH-exposed mice. CONCLUSIONS: Our data suggest that diosgenin reverses SDS + EtOH interaction-induced behavioral changes via normalization of hypothalamic-pituitary-adrenal axis, neurochemical neurotransmissions, and inhibition of oxidative and inflammatory mediators in mice brains.

No Association of Blood Alcohol Concentration on Burn Patient Outcomes.

INTRODUCTION: Alcohol abuse is common among burn patients. Burn patients under the influence of alcohol are at risk for developing organ failure, prolonged hospital duration, and increased intensive care unit (ICU) resources. Our study aims to analyze the association between presenting alcohol levels and the outcomes of burn patients. METHODS: A retrospective analysis of admitted burn patients was performed from 2016 to 2021. Patients were divided into two groups based on blood alcohol content (BAC), low (<80), and high (≥80) mg/dL. Data included demographics, comorbidities, and outcomes. Univariate analyses were performed, and a P value <0.05 was significant. RESULTS: A total of 197 patients were included (32.5% females, mean age 47.2 ± 15.2, 26.9% smokers, 28.4% illegal drug abuse, and 56.3% no comorbidities). Mortality was 7.6%, morbidity 20.8%, 39.1% required burn ICU admission, and 25.9% were intubated. When comparing BAC groups, we found no differences in demographics, comorbidities, inhalational injury incidence, carbon monoxide level, intubation, or burn ICU admission rates. The high-BAC group had longer ventilator days (high BAC 16.7 ± 19.3 versus low BAC 7.5 ± 9.1, P = 0.026) and longer stays in the ICU (18.6 ± 21.8 versus 10.7 ± 15.4, P = 0.075). The low-BAC group had more 3rd-degree burn percentage (5.0 ± 15.3 versus 15.4 ± 27.5, P = 0.024). Both morbidity and in-house mortality rates were similar for both groups (23.8% versus 16.0%, P = 0.192, and 6.6% versus 9.3%, P = 0.476, respectively). CONCLUSIONS: Burn patients with higher BAC had significantly longer mechanical ventilator days. However, higher alcohol concentrations had no association with regard to mortality, overall length of stay, or complication rates.

Alcohol Promotes Lipogenesis in Sebocytes-Implications for Acne.

The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect-the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris.

Recommendations on the measurement and use of the alcohol consumption biomarker CDT. A position paper from the IFCC Working Group on CDT standardisation.

BACKGROUND: Carbohydrate deficient transferrin (CDT) is a biomarker for excessive alcohol consumption utilized in clinical and forensic medicine and workplace testing. Previously, many different analytical methods for CDT were used and the measurand varied considerably, making direct comparison of test results difficult. To end this confusion, the IFCC established a working group on CDT standardisation (WG-CDT) which completed its tasks in 2017. METHODS: This IFCC position paper by the WG-CDT summarizes state of the art information about the measurand and the analytical methods and gives concise recommendations for its utilization. RESULTS: The results achieved by the CDT standardisation process led to accuracy improvements in national external quality assessment schemes over the years. A brief review of ROC based comparison studies with the traditional biomarkers (GGT, MCV, ALT and AST) discusses the bias resulting from inadequate study populations. In large groups of the general population the superior diagnostic performance of CDT is confirmed. CONCLUSION: The relationship between alcohol intake versus resulting CDT is discussed as well as the cutoff and measurement uncertainty. Concerning the application in practice, potential pitfalls are considered and recommendations handling both analytical and preanalytical caveats are given. Finally, some examples of serious misunderstandings in publications about CDT are addressed.

War, forced displacement, and alcohol abuse: experiences and perceptions of war-affected south Sudanese refugee youth living in Bidibidi refugee settlement in northern Uganda.

Refugees are at high risk of alcohol abuse due to their experiences of structural, physical, sexual, and psychological violence in their countries of origin, during flight, and within host communities. Given the prolonged civil war in their country, South Sudanese have continued to flee profound forms of violence and now constitute the largest population of refugees in Uganda. However, little is known about their displacement experiences, as well as the reality of alcohol use and abuse within refugee settlements. Drawing upon the direct voices of a sample of war-affected South Sudanese young people, this article explores their experiences of forced displacement and their links to alcohol abuse, as well as their perceptions regarding appropriate alcohol treatment interventions for refugees in the camp. A total of 22 semi-structured qualitative interviews were conducted with 14 refugee youth (aged 18-25) alongside eight adult key informants who work with the youth (religious leaders, sports coaches, educators, social workers, and settlement administrators). Using thematic analysis, the study revealed a series of key themes influencing and shaping the high incidence of alcohol abuse among the youth. These included traumatic wartime and migration experiences, family separation, poor prospects, and the ubiquitous availability of alcohol in the settlement. In addition, we show how alcohol operates as a strategic tool for survival for the youth, as well as highlight how these perceptions can help to inform alcohol treatment interventions in the Bidibidi refugee settlement. To our knowledge, this is the first in-depth study of alcohol abuse among war-affected South Sudanese refugee youth in Uganda, addressing a significant gap in the current literature on war-affected youth, forced displacement, and alcohol abuse. We contend that involving youth in the design of interventions can be helpful for culturally sensitive and relevant prevention, treatment, and care in refugee settings. In addition, providing employment opportunities and meaningful engagement for growth through social participation can help to address harmful alcohol use among youth in the camps.

Comparative analysis between CDT in serum and Ethyl glucuronide in hair to define the best reliable tool for the diagnosis of alcohol abuse.

The increase in alcohol consumption in society has not only led to a number of medical issues but has also become a matter of considerable legal importance. Thus, there is both scientific interest and the necessity to diagnose alcohol abuse in the application of the provisions of the law through laboratory tests that ensure maximum objectivity. The purpose of this work is to study and compare the diagnostic performance of two of the main markers of alcohol abuse, serum carbohydrate-deficient transferrin (CDT) and Ethyl glucuronide (EtG) in a group of 336 driving under the influence (DUI) of alcohol offenders. Thus, it is possible to establish the best marker of alcohol consumption in order to assess the fitness to drive of DUI subjects.EtG was detected in 55 hair samples, while CDT was detected in 5 blood samples. Of the EtG-positive subjects 96,4% had CDT values below the cut-off. While CDT refers to an alcohol consumption of approximately the previous 10 days, EtG allows to detect an excessive alcohol consumption of the last few months. Because of these two different time-windows, EtG proves to be more reliable, since it is more difficult for subjects to change their drinking practice to test negative to toxicological analysis. The determination of Ethyl glucuronide on hair matrix is a valuable tool for the diagnosis of alcohol abuse, with high sensitivity and specificity and certainly greater reliability than traditional markers such as CDT, being a direct marker of alcohol consumption.

Potential role of inducible nitric oxide synthase (iNOS) activity in testicular dysfunction following co-administration of alcohol and combination antiretroviral therapy (cART) in diabetic rats: an immunohistochemistry study.

Diabetes, alcohol abuse, and combination antiretroviral therapy (cART) use have been reported to cause multi-organ complications via induction of oxidative stress and inflammation. Moreover, these are the most common factors implicated in male reproductive dysfunctions. This study evaluated testicular oxidative stress, inflammation, apoptosis, and germ cell proliferation in diabetic rats receiving alcohol or cART and their combination. Thirty adult male Sprague Dawley rats were divided into five groups, each consisting of six rats; control, diabetic only (DM), diabetic treated with alcohol (DM + A), diabetic treated with cART (DM + cART), and diabetic treated with both alcohol and cART (DM + A + cART). After 90 days of treatment, the rats were terminated, and the testes were extracted and processed for immunohistochemistry analysis for oxidative stress, inflammatory cytokines, apoptosis, and cell proliferation marker. In comparison to the control, oxidative stress markers, inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHDG) increased significantly in all treated groups. Expression of testicular proinflammatory cytokines, interleukin-1ß, and tumor necrosis factor-α was upregulated in all treated groups, but interleukin-6 was upregulated in DM, DM + cART, and DM + A + cART treated groups and was downregulated in the DM + A treated group. All treated animal groups showed an upregulation of apoptotic marker (caspase 3) and a downregulation of proliferation marker (Ki-67). However, Ki-67 staining intensity significantly increased in treated animals compared to the control. These findings suggest that diabetes, alcohol abuse, cART use, and their combination via iNOS activity upregulation can induce inflammation and oxidative stress in testicular tissue, stimulating germ cell apoptosis and proliferation inhibition leading to failure of spermatogenesis.