Excessive Alcohol Research Articles

The effect of Transcendental Meditation on self-esteem, self-efficacy, and gratitude, for increasing empowerment of female youth in Uganda

This longitudinal study with female youth in the slums of Kampala, Uganda (n = 130), explored the impact of the Transcendental Meditation® (TM®) technique on self-esteem, the primary outcome measure, and self-efficacy, gratitude, hope, tiredness, and resilience as secondary outcomes. Quality-of-life behaviors were also assessed, including excessive alcohol use. After baseline testing participants learned TM over five consecutive days. Participants practiced TM at home for 20 min twice a day and attended two follow-up sessions. Post-testing occurred at five months. Significant improvements in self-esteem (p < .001), self-efficacy (p < .001), gratitude (p < .001), and tiredness (p = .05) were found. A decrease in excessive alcohol use was also observed (p = .02). At eight months a short answer questionnaire showed improved physical health, decreased stress and anxiety levels, and improved relationships in the family and community. Our findings have important implications for enhancing the well-being and empowerment of these vulnerable female youth.

Metabolic dysfunction-associated fatty liver disease and heavy alcohol consumption increase mortality:A nationwide study.

The effects of excessive alcohol consumption on the prognosis of metabolic dysfunction-associated fatty liver disease (MAFLD) remain unclear. We investigated all-cause and cause-specific mortality according to the amount of alcohol consumed by Asian individuals with MAFLD. This nationwide retrospective study included 996,508 adults aged 40-79years who underwent health check-ups between 2009 and 2012. Participants were categorized by the alcohol consumption-non-alcohol, moderate alcohol, and heavy alcohol group (≥ 30g/day for men, ≥ 20g/day for women) and by the combination of the presence or absence of MAFLD. Hepatic steatosis was defined as the fatty liver index ≥ 30. Cox analyses were used to analyze the association between alcohol consumption and MAFLD and all-cause and cause-specific mortality. MAFLD significantly increased all-cause, liver-, and cancer-related mortality. Individuals with both MAFLD and heavy alcohol consumption expressed the highest mortality risk in liver-related mortality compared to non-MAFLD and non-alcohol group (adjusted hazard ratio (HR), 9.8; 95% confidence interval (CI), 8.20-12.29). Regardless of MAFLD, heavy alcohol consumption increased the risk of liver- and cancer-related mortality. MAFLD and heavy alcohol consumption increased all-cause, liver-, and cancer-related mortality. Heavy alcohol consumption and MAFLD synergistically increase liver-related mortality.

Incidence of Chronic Kidney Failure and Alcohol Consumption: Meta Analysis

One of the main risk factors for chronic kidney disease (CKD) is excessive alcohol consumption. Alcohol consumption can damage the kidneys and disrupt their function because the kidneys filter toxins and waste products from the blood. This study aims to estimate the magnitude of the relationship between alcohol consumption and the incidence of chronic kidney failure. This research is a systematic review and meta analysis with PICO as follows, population: Adults. Intervention: alcohol consumption, Comparison: no alcohol consumption. Outcome: chronic failure events. The articles used in this research were obtained from three databases, namely Google Scholar, Pubmed, and Science Direct. Keywords to search for articles are "Alcohol" AND "Chronic Kidney Disease" OR CKD AND Multivariate. Articles used from 2018 – 2023. Article selection was carried out using the PRISMA flow diagram. Articles were analyzed using the Review Manager 5.3 application. A total of 6 cohort studies, namely Asia and Europe, were selected for systematic review and meta analysis. Cohort studies show that alcohol consumption influences the incidence of CKD. Patients who consume alcohol have a risk of experiencing CKD that is 1.05 times compared to those who do not consume alcohol, but the resulting increase in risk is not statistically significant (aHR= 1.04 95% CI= 0.85 to 1.27; p= 0.710). Forest Plot also shows heterogeneity of effect estimates between primary studies I2= 84%; p= 0.040, which means that the estimated effect between primary studies in this meta-analysis varies. Thus, the calculation of the average effect estimate was carried out using a random effect model approach.

Effects of idebenone and coenzyme Q10 on NLRP3/caspase-1/IL-1β pathway regulation on ethanol-induced hepatotoxicity in rats

Chronic and excessive alcohol consumption leads to liver toxicity. There is a need to investigate effective therapeutic strategies to alleviate alcohol-induced liver injury, which remains the leading cause of liver-related morbidity and mortality worldwide. Therefore here, we looked into and evaluated how ethanol-induced hepatotoxicity was affected by coenzyme Q10 (CoQ10) and its analog, idebenone (IDE), on the NLRP3/caspase-1/IL-1 pathway. Hepatotoxicity induced in rats through the oral administration of gradually increasing dosages of ethanol (from 2 to 6 g/kg/day) over 30 days and the effect of CoQ10 (10 or 20 mg/kg) and IDE (50 or 100 mg/kg) were evaluated. Serum hepatotoxicity markers (ALT, AST, GGT, ALP, and TBIL), tissue oxidative stress markers and the mRNA expressions of IL-1β, IL-18, TGF-β, NF-κB, NLRP3, and caspase-1 were evaluated. Masson’s trichrome staining was also used to visualize fibrosis in the liver tissue. The results indicated that ethanol exposure led to hepatotoxicity as well as considerable NLRP3/caspase-1/IL-1β pathway activation. Moreover, CoQ10 or IDE treatment reduced measured parameters in a dosage-dependent manner. Thus, by inhibiting the NLRP3/caspase-1/IL-1 pathway, CoQ10 and IDE can prevent the hepatotoxicity caused by ethanol, although CoQ10 is more effective than IDE. This study will provide insight into new therapeutic avenues that take advantage of the anti-inflammatory and antioxidant properties of CoQ10 and IDE in ethanol-induced liver diseases.

#430 Risk factors for major bleeding in patients with non-valvular atrial fibrillation and CKD G3-G5D on oral anticoagulants

Abstract Background and Aims We previously published a register-based cohort study comparing direct oral anticoagulants (DOAC) and warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) GFR category 3-5 (G3-G5) including patients on dialysis (G5D) (1). This study showed that DOAC was associated with lower risk of major bleeding but similar risk of ischemic stroke compared to warfarin. Bleedings were however more common than strokes, especially in advanced CKD (G5-G5D) where the risk of major bleeding was up to 10 times higher than the risk of stroke. Subsequently, the stroke- and bleeding risk in patients with AF and advanced CKD must be carefully evaluated when deciding on whether to prescribe oral anticoagulants (OAC) or not. Available stroke- and bleeding scoring systems do not perform well in CKD (2, 3). This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-G5D. Method Data was collected from high quality Swedish healthcare registers including Swedish Renal Registry and Auricula, a register for atrial fibrillation and oral anticoagulants and the National Patient Register. Patients with eGFR&amp;lt;60 ml/min/1.73m2 and non-valvular atrial fibrillation and either DOAC (apixaban, rivaroxaban, edoxaban and dabigatran) or warfarin treatment between 2009-2018 where included. DOAC treatment periods were collected from the Swedish Prescribed Drug Register (PDR), starting from dispense date covering assumed standard pill use and an additional 30 days grace period. Warfarin treatment periods were collected directly from Auricula. An undefined treatment was a period of no OAC or a period of warfarin from PDR not matching a treatment period in Auricula. All periods of OAC treatment with either DOAC or warfarin were evaluated in a multivariate Cox regression model regarding the risk of major bleeding requiring inpatient care. Time-dependent covariates adjusted for in the model were age, sex, years from study start, GFR category, congestive heart failure, diabetes mellitus, hypertension, excessive alcohol use, liver disease, vascular disease, previous gastrointestinal bleeding, intracranial bleeding, other bleeding, ischemic stroke/ transient ischemic attack (TIA), myocardial infarction, PCI and exposures (DOAC, warfarin and periods of undefined treatment). Results Of 2453 included patients, 59% had warfarin (time in therapeutic range, TTR, 67%) and 41% DOAC at inclusion, predominantly apixaban (81% of DOAC users). The mean age was 77 years, 28.3% had G3, 45.4% G4, 9.1% G5 and 17.3% G5D (Table 1). Mean follow up was 2.2 years. During follow up 424 major bleedings occurred yielding 8.9 (95% confidence interval 8.1-9.8) bleedings per 100 patient-years. Table 2 shows effect estimates of each covariate on the outcome major bleeding. Covariates, besides warfarin, associated with increased risk of major bleeding were GFR category, G5/5D versus G3, hazard ratio 1.92 (95% CI 1.43-2.56), previous GI bleeding, 1.77 (1.39-2.25) and previous other bleeding 1.33 (1.09-1.62). Other factors associated with major bleeding were congestive heart failure 1.36 (1.11-1.68), male sex 1.28 (1.03-1.60) and vascular disease, 1.35 (1.01-1.79). Conclusion Patients with non-valvular atrial fibrillation and CKD G3-G5D on OAC are at high risk of major bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding, this reiterates the results of many previous studies. The present study also shows an association between OAC-associated major bleeding in CKD and male sex, congestive heart failure and vascular disease. Similar associations have been showed in non-CKD cohorts previously but is inadequately studied in CKD. Knowledge about risk factors for major bleeding on OAC in advanced CKD is essential when deciding on when to anticoagulate or not.

Risk factors for prevalent and incident hypertension in rheumatoid arthritis: data from the Canadian Early Arthritis Cohort.

Hypertension (HTN) is a common comorbidity in RA. This study aimed to explore the prevalence and incidence of HTN and baseline factors associated with incident HTN in early RA (ERA). Data were from the Canadian Early Arthritis Cohort (CATCH), an inception cohort of ERA patients having <1 year of disease duration. HTN was determined by patient- or physician-reported diagnosis, the use of anti-hypertensives and/or blood pressure. Multivariable logistic regression was performed to determine baseline factors associated with prevalent and incident HTN in this population. The study sample included 2052 ERA patients [mean age 55 years (s.d. 14), 71% female). The prevalence of HTN at study enrolment was 26% (23% in females and 34% in males). In both sexes, prevalent HTN was associated with older age, diabetes and hyperlipidaemia. HTN was associated with being overweight or high alcohol consumption in females. Of the RA patients who did not have HTN at enrolment, 24% (364/1518) developed HTN during the median follow-up period of 5 years (range 1-8). Baseline factors significantly associated with incident HTN were older age, being overweight, excess alcohol consumption and having hyperlipidaemia. Incident HTN was associated with high alcohol consumption in males and with hyperlipidaemia in females. RA-associated disease factors and treatments were not significantly associated with prevalent or incident HTN. Early RA patients had a high incidence of hypertension with the highest risk in older patients with traditional cardiovascular risk factors.

Pathophysiological correction of stress in the context of cardiovascular risk

Cardiovascular diseases are the leading cause of death worldwide. Prevention of these diseases is one of the most important tasks of modern medicine. First of all, it is necessary to influence modifying risk factors, namely: tobacco use, poor nutrition, low physical activity, excessive alcohol consumption, uncontrolled high blood pressure and hyperlipidemia. One of the important additional risk factors is stress, which causes a number of changes in the heart and kidneys, provoking the development and progression of cardiovascular diseases. Timely impact on the psychological state of a patient who is under the influence of chronic stress is the key to effectively reducing the risk of cardiovascular disasters. For this purpose, it is possible to recommend nootropic drugs that contribute to the reduction of clinical manifestations of asthenic syndrome and chronic fatigue syndrome caused by chronic stress.

Landscape of extrachromosomal circular DNAs, transcriptome, and proteome analysis reveals insights into alcoholic liver cirrhosis

Alcoholic liver cirrhosis (ALC) is a result of excessive and chronic alcohol consumption. Because alchol can cause DNA damage, extrachromosomal circular DNA (eccDNA) was investigated in ALC liver due to it can be a result of DNA damage. Considering eccDNA has ability to lead to genomic instability as an enhancer of gene transcription, we utilized Circle-Seq to identify differences in eccDNA profiles and gene expression patterns in liver samples obtained from ALC patients (n = 3) and healthy controls (n = 3) to investigate the role of eccDNA in the development of ALC. The abundance of eccDNA in ALC (mean = 13,349) were higher than the healthy control (mean = 11,557) without significant difference (pvalue = 0.6530). We observed 1,032 eccDNA containing genes showed higher expression in ALC patients compared to healthy controls (p < 0.05, log2FC > 1). Notably, we discovered seven genes that exhibited a significant positive correlation between eccDNA abundance and gene expression levels. These genes include A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2), Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C), Protein TANC1 (TANC1), Integrin alpha-2 (ITGA2), EH domain-containing protein 4 (EHD4), Phosphofurin acidic cluster sorting protein 1 (PACS1), and Neuron navigator 2 (NAV2). Through mass spectrometry proteomics, ITGA2 were found to have significantly higher abbudance in ALC. Integrins are a family of proteins plays key roles in the fibrosis development of liver. Thus, our study opens a new perspective for liver fibrosis development.

Could Alcohol-Related Cognitive Decline Be the Result of Iron-Induced Neuroinflammation?

Excessive and prolonged alcohol use can have long-term severe neurological consequences. The mechanisms involved may be complicated; however, new evidence seems to indicate the involvement of iron accumulation and neuroinflammation. Prolonged alcohol consumption has been linked to the accumulation of iron in specific regions of the brain. Evidence suggests that excess iron in the brain can trigger microglia activation in response. This activation leads to the release of pro-inflammatory cytokines and reactive oxygen species, which can cause damage to neurons and surrounding brain tissue. Additionally, iron-induced oxidative stress and inflammation can disrupt the blood-brain barrier, allowing immune cells from the periphery to infiltrate the brain. This infiltration can lead to further neuroinflammatory responses. Inflammation in the brain subsequently disrupts neuronal networks, impairs synaptic plasticity, and accelerates neuronal cell death. Consequently, cognitive functions such as memory, attention, and decision-making are compromised. Additionally, chronic neuroinflammation can hasten the development and progression of neurodegenerative diseases, further exacerbating cognitive impairment. Therefore, alcohol could act as a trigger for iron-induced neuroinflammation and cognitive decline. Overall, the mechanisms at play here seem to strongly link alcohol with cognitive decline, with neuroinflammation resulting from alcohol-induced iron accumulation playing a pivotal role.

Application of Machine Learning Algorithms to Predict Osteoporotic Fractures in Women.

Predicting the risk of osteoporotic fractures is vital for prevention. Traditional methods such as the Fracture Risk Assessment Tool (FRAX) model use clinical factors. This study examined the predictive power of the FRAX score and machine-learning algorithms trained on FRAX parameters. We analyzed the data of 2,147 female participants from the Ansan cohort study. The FRAX parameters employed in this study included age, sex (female), height and weight, current smoking status, excessive alcohol consumption (>3 units/d of alcohol), and diagnosis of rheumatoid arthritis. Osteoporotic fracture was defined as one or more fractures of the hip, spine, or wrist during a 10-year observation period. Machine-learning algorithms, such as gradient boosting, random forest, decision tree, and logistic regression, were employed to predict osteoporotic fractures with a 70:30 training-to-test set ratio. We evaluated the area under the receiver operating characteristic curve (AUROC) scores to assess and compare the performance of these algorithms with the FRAX score. Of the 2,147 participants, 3.5% experienced osteoporotic fractures. Those with fractures were older, shorter in height, and had a higher prevalence of rheumatoid arthritis, as well as higher FRAX scores. The AUROC for the FRAX was 0.617. The machine-learning algorithms showed AUROC values of 0.662, 0.652, 0.648, and 0.637 for gradient boosting, logistic regression, decision tree, and random forest, respectively. This study highlighted the immense potential of machine-learning algorithms to improve osteoporotic fracture risk prediction in women when complete FRAX parameter information is unavailable.

Effectiveness of genetic feedback on alcohol metabolism to reduce alcohol consumption in young adults: an open-label randomized controlled trial

BackgroundIt is unclear whether brief interventions using the combined classification of alcohol-metabolizing enzymes aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) together with behavioral changes in alcohol use can reduce excessive alcohol consumption. This study aimed to examine the effects of a brief intervention based on the screening of ALDH2 and ADH1B gene polymorphisms on alcohol consumption in Japanese young adults.MethodsIn this open-label randomized controlled trial, we enrolled adults aged 20–30 years who had excessive drinking behavior (average amount of alcohol consumed: men, ≥ 4 drinks/per day and women, ≥ 2 drinks/per day; 1 drink = 10 g of pure alcohol equivalent). Participants were randomized into intervention or control group using a simple random number table. The intervention group underwent saliva-based genotyping of alcohol-metabolizing enzymes (ALDH2 and ADH1B), which were classified into five types. A 30-min in-person or online educational counseling was conducted approximately 1 month later based on genotyping test results and their own drinking records. The control group received traditional alcohol education. Average daily alcohol consumption was calculated based on the drinking diary, which was recorded at baseline and at 3 and 6 months of follow-up. The primary endpoint was average daily alcohol consumption, and the secondary endpoints were the alcohol-use disorder identification test for consumption (AUDIT-C) score and behavioral modification stages assessed using a transtheoretical model.ResultsParticipants were allocated to the intervention (n = 100) and control (n = 96) groups using simple randomization. Overall, 28 (29.2%) participants in the control group and 21 (21.0%) in the intervention group did not complete the follow-up. Average alcohol consumption decreased significantly from baseline to 3 and 6 months in the intervention group but not in the control group. The reduction from baseline alcohol consumption values and AUDIT-C score at 3 months were greater in the intervention group than in the control group (p < 0.001). In addition, the behavioral modification stages were significantly changed by the intervention (p < 0.001).ConclusionsGenetic testing for alcohol-metabolizing enzymes and health guidance on type-specific excessive drinking may be useful for reducing sustained average alcohol consumption associated with behavioral modification.Trial registrationR000050379, UMIN000044148, Registered on June 1, 2021.

Alcoholic Cardiomyopathy: a summary of current knowledge and possible future directions

Introduction and purpose: Ethanol is still one of the most frequently consumed drugs worldwide and is a strong risk factor for more than 60 illnesses including alcoholic cardiomyopathy which is a specific heart muscle disease caused by long-term excessive alcohol consumption. The review aims to gather available data and summarize it to give better understanding of the disease, to help select patients with the condition to implement proper treatment, and to present possible future directions as the incidence of the disease is projected to persist in the future. Brief description of the state of knowledge: Alcoholic cardiomyopathy (ACM) is characterized by dilation, increased mass of the left ventricle, and reduced ejection fraction leading to end-stage heart failure. It is caused by ethanol’s direct toxicity on myocytes disturbing many different metabolic pathways. The result is a decrease in both systolic and diastolic function of the heart. The ACM development depends on factors such as genetics, gender, dietary factors and the dosage of ethanol consumption. The goal of the treatment is total alcohol abstinence, but the reduction of ethanol intake may also be beneficial. Patients should obtain a complete pharmacological treatment for heart failure. Summary: Ethanol overconsumption remains an unresolved problem, with the incidence of ACM projected to persist in the future, especially among patients with alcohol use disorder (AUD). Efforts for prevention, early detection, and effective treatment of ACM need to be established. A primary focus should be on treating AUD because it is the most effective way to halt the progression of the disease. Further research should focus on both asymptomatic and symptomatic patients with AUD to better define clinical manifestations, diagnostic approaches, and the most effective treatments for ACM.

Spontaneous intracerebral hemorrhage: a review of the prevalence, trigger factors, therapeutic and surgical treatment

Spontaneous intracerebral hemorrhage is the second most common subtype of stroke and is a significant cause of mortality and morbidity worldwide. Trigger factors that “accelerate” disease onset may include hypertension, excessive alcohol consumption, constant smoking, hypocholesterolemia, medications, male sex, advanced age, living in an underdeveloped country, ethnicity, chronic kidney disease, cerebral amyloid angiopathy, and microhemorrhages. Therapeutic solutions for spontaneous intracerebral hemorrhage aimed at stopping the progression of hemorrhage, reducing the clot volume of intraventricular and parenchymal hematoma, combating perihematomal edema and inflammation, rapidly reducing blood pressure, and providing hemostatic therapy with transfusion of platelets and other coagulation complexes. Clinical trials on minimally invasive methods of surgical evacuation (endoscopic surgery, stereotactic aspiration, and invasive craniopuncture) are ongoing and may provide positive results because of the shorter operation time and use of local anesthesia. Minimally invasive surgery methods can theoretically improve the outcomes of open surgery by reducing damage to collateral tissues and reducing anesthesia time; however, they cannot be a full-fledged alternative.

The Clinical Sequelae of the COVID-19 Pandemic: Loneliness, Depression, Excessive Alcohol Use, Social Media Addiction, and Risk for Suicide Ideation

Background Depression, loneliness, and alcohol use disorder are associated with suicide ideation. The ongoing COVID-19 pandemic has challenged our social structures with social distancing and isolation policies implemented worldwide, severely restricting social interactions. Studies regarding the effects of the pandemic are starting to shed light on the harmful psychological effects of these policies. Aims This study aims to identify whether the increase in suicidal ideation among college students (mostly young adults) during the pandemic was due to the known risk factors of loneliness, depression, alcohol use disorder, social media addiction, and other background variables. Method Nine hundred and eleven college students completed self-report questionnaires assessing suicidal risk, depressive symptoms, loneliness, excessive alcohol use, and social media use. Results During the pandemic suicidal ideation was associated with loneliness (χ2 = 54.65, p < 0.001), depressive symptoms (χ2 = 110.82, p < 0.001), alcohol use disorder (χ2 = 10.02, P < 0.01) and social media addiction (χ2 = 13.73, P < 0.001). Being single [OR = 2.55; p < 0.01], and self-identifying as a non-heterosexual [OR = 2.55; p < 0.01] were found to constitute additional risk factors. Limitations The structural nature of quantitative self-report scales does not offer the flexibility of gaining a deeper understanding of causes, specific to particular circumstances that may lead participants to ideate on suicide, even briefly. Conclusions Social distancing and isolation policies during the COVID-19 pandemic constitute an additional factor in the risk for suicide ideation.

Effects of social housing on alcohol intake in mice depend on the non-social environment.

Excessive alcohol consumption leads to serious health problems. Mechanisms regulating the consumption of alcohol are insufficiently understood. Previous preclinical studies suggested that non-social environmental and social environmental complexities can regulate alcohol consumption in opposite directions. However, previous studies did not include all conditions and/or did not include female rodents. Therefore, in this study, we examined the effects of social versus single housing in standard versus non-standard housing conditions in male and female mice. Adult C57BL/6 J mice were housed in either standard shoebox cages or in automated Herdsman 2 (HM2) cages and exposed to a two-bottle choice procedure with 3% or 6% ethanol versus water for 5 days. The HM2 cages use radiotracking devices to measure the fluid consumption of individual mice in an undisturbed and automated manner. In both housing conditions, mice were housed either at one or at four per cage. In standard cages, group housing of animals decreased alcohol consumption and water consumption. In HM2 cages, group housing significantly increased ethanol preference and decreased water intake. There were no significant differences in these effects between male and female animals. These observations were similar for 3 and 6% ethanol solutions but were more pronounced for the latter. The effects of social environment on ethanol preference in HM2 cages were accompanied by an increase in the number of approaches to the ethanol solution and a decrease in the number of approaches to water. The differences in ethanol intake could not be explained by differences in locomotor or exploratory activity as socially housed mice showed fewer non-consummatory visits to the ethanol solutions than single-housed animals. In addition, we observed that significant changes in behaviors measuring the approach to the fluid were not always accompanied by significant changes in fluid consumption, and vice versa, suggesting that it is important to assess both measures of motivation to consume alcohol. Our results indicate that the direction of the effects of social environment on alcohol intake in mice depends on the non-social housing environment. Understanding mechanisms by which social and non-social housing conditions modulate alcohol intake could suggest approaches to counteract environmental factors enhancing hazardous alcohol consumption.

HPLC based Phytochemicals Analysis of Phyllanthus emblica (Indian Gooseberry/Amla): A mini Review

High-Pressure Liquid Chromatography (HPLC) is an analytical tool extensively used for the scientific analysis of components in a mixture. Several reports attribute its high analytical potential to bioactive components from different medicinal plants. Hepatic disorders, which have been a major threat to public health for decades, affect cells, tissues, structure, or liver function. The damage caused by this can be triggered by biological causes, autoimmune diseases, excessive alcohol consumption, or the action of different compounds, for instance, few medicines. Phyllanthus emblica Linn. is a therapeutic plant that has been used to treat liver disorders in Asia for many decades now. It is mentioned in the Ayurvedic scriptures for its medicinal value. This review focuses on the intricacies of HPLC-based extraction and analysis of medicinally important phytochemicals, notably for hepatic disorders from the P. emblica plant. This will be useful for future phytochemical analysts working with medicinal plants.

Investigation of the Efficacy of Zonisamide in Alcohol Induced Hepatotoxicity

Subject: This research aims to evaluate the histological changes in liver tissue induced by alcohol consumption and to assess the effectiveness of zonisamide in treating alcohol-related hepatotoxicity. Materials and Methods: The study utilized 40 adult Wistar albino rats, divided into four groups: a control (sham), an ethanol group, a zonisamide group, and a combination of ethanol and zonisamide (ethanol+zonisamide). Each group underwent a four-day binge drinking protocol to mimic excessive alcohol intake observed in humans. Zonisamide was administered at a dose of 100 mg/kg daily. Post-treatment, the liver tissues were collected, stained with hematoxylin and eosin, and examined for histopathological changes. Results: The control and zonisamide-only groups showed no abnormal liver or vascular alterations, indicating zonisamide's safety. In contrast, the ethanol group displayed significant liver damage, including vascular dilatation, congestion, and extensive cellular degeneration. Conversely, the ethanol+zonisamide group exhibited substantial histological improvements with noticeable reductions in vascular impairments and signs of hepatocyte regeneration, suggesting that zonisamide mitigates the detrimental effects of alcohol on the liver. Conclusion: The study concludes that zonisamide has a protective effect against alcohol-induced liver damage. It appears to preserve the structural integrity of hepatocytes and supports cellular survival, potentially through its anti-inflammatory and antioxidant properties. These promising results advocate for further exploration of zonisamide as a therapeutic option for managing liver injuries associated with alcohol abuse. This study contributes significant insights into the therapeutic potential of zonisamide, encouraging more comprehensive investigations into its clinical applications in hepatology. Keywords: Alcohol, Zonisamide, Hepatotoxicity

Multifocal Osteonecrosis in Spinal Cord Injury

Dear Editors, Necrosis of the bone marrow and trabecular portion as a result of limited blood flow is known as osteonecrosis (ON) [1]. Several causes have been proposed for the development of ON, including vascular occlusions, ischemia, intravascular coagulation in interosseous tissue, increased intracortical pressure, mechanical stress, precursor cell death, and suppression of angiogenesis. There are multiple risk factors and medical condition associated with ON, including infections, hematological and coagulation problems, connective tissue illnesses, kidney diseases, excessive alcohol and tobacco use, and the use of corticosteroids and cytotoxic drugs [2]. Multifocal osteonecrosis, defined as the presence of osteonecrosis in three or more bone sites, is a rare entity representing less than 3% of osteonecrosis patients [3]. Due to its potent anti-inflammatory properties, methyl prednisolone (MP), one of the most extensively used corticosteroids, has been used for a long time in the acute phase of spinal cord injury and brain edema due to its strong anti-inflammatory properties [4]. Although studies have reported cases of multifocal osteonecrosis (MFON) brought on by corticosteroid medication, this link has never been examined in a patient with a spinal cord injury. This letter aims to highlight MFON that occurred in a patient who underwent acute spinal cord injury and high-dose steroid therapy.

Computational identification of potential bioactive compounds from Triphala against alcoholic liver injury by targeting alcohol dehydrogenase.

Alcoholic liver injury resulting from excessive alcohol consumption is a significant social concern. Alcohol dehydrogenase (ADH) plays a critical role in the conversion of alcohol to acetaldehyde, leading to tissue damage. The management of alcoholic liver injury encompasses nutritional support and, in severe cases liver transplantation, but potential adverse effects exist, and effective medications are currently unavailable. Natural products with their potential benefits and historical use in traditional medicine emerge as promising alternatives. Triphala, a traditional polyherbal formula demonstrates beneficial effects in addressing diverse health concerns, with a notable impact on treating alcoholic liver damage through enhanced liver metabolism. The present study aims to identify potential active phytocompounds in Triphala targeting ADH to prevent alcoholic liver injury. Screening 119 phytocompounds from the Triphala formulation revealed 62 of them showing binding affinity to the active site of the ADH1B protein. Promising lipid-like molecule from Terminalia bellirica, (4aS, 6aR, 6aR, 6bR, 7R, 8aR, 9R, 10R, 11R, 12aR, 14bS)-7, 10, 11-trihydroxy-9-(hydroxymethyl)-2, 2, 6a, 6b, 9, 12a-hexamethyl-1, 3, 4, 5, 6, 6a, 7, 8, 8a, 10, 11, 12, 13, 14b-tetradecahydropicene-4a-carboxylic acid showed high binding efficiency to a competitive ADH inhibitor, 4-Methylpyrazole. Pharmacokinetic analysis further confirmed the drug-likeness and non-hepatotoxicity of the top-ranked compound. Molecular dynamics simulation and MM-PBSA studies revealed the stability of the docked complexes with minimal fluctuation and consistency of the hydrogen bonds throughout the simulation. Together, computational investigations suggest that (4aS, 6aR, 6aR, 6bR, 7R, 8aR, 9R, 10R, 11R, 12aR, 14bS)-7, 10, 11-trihydroxy-9-(hydroxymethyl)-2, 2, 6a, 6b, 9, 12a-hexamethyl-1, 3, 4, 5, 6, 6a, 7, 8, 8a, 10, 11, 12, 13, 14b-tetradecahydropicene-4a-carboxylic acid from the Triphala formulation holds promise as an ADH inhibitor, suggesting an alternative therapy for alcoholic liver injury.

The impact of the world’s first regulatory, multi-setting intervention on sedentary behaviour among children and adolescents (ENERGISE): a natural experiment evaluation

BackgroundRegulatory actions are increasingly used to tackle issues such as excessive alcohol or sugar intake, but such actions to reduce sedentary behaviour remain scarce. World Health Organization (WHO) guidelines on sedentary behaviour call for system-wide policies. The Chinese government introduced the world’s first nation-wide multi-setting regulation on multiple types of sedentary behaviour in children and adolescents in July 2021. This regulation restricts when (and for how long) online gaming businesses can provide access to pupils; the amount of homework teachers can assign to pupils according to their year groups; and when tutoring businesses can provide lessons to pupils. We evaluated the effect of this regulation on sedentary behaviour safeguarding pupils.MethodsWith a natural experiment evaluation design, we used representative surveillance data from 9- to 18-year-old pupils before and after the introduction of the regulation, for longitudinal (n = 7,054, matched individuals, primary analysis) and repeated cross-sectional (n = 99,947, exploratory analysis) analyses. We analysed pre-post differences for self-reported sedentary behaviour outcomes (total sedentary behaviour time, screen viewing time, electronic device use time, homework time, and out-of-campus learning time) using multilevel models, and explored differences by sex, education stage, residency, and baseline weight status.ResultsLongitudinal analyses indicated that pupils had reduced their mean total daily sedentary behaviour time by 13.8% (95% confidence interval [CI]: -15.9 to -11.7%, approximately 46 min) and were 1.20 times as likely to meet international daily screen time recommendations (95% CI: 1.01 to 1.32) one month after the introduction of the regulation compared to the reference group (before its introduction). They were on average 2.79 times as likely to meet the regulatory requirement on homework time (95% CI: 2.47 to 3.14) than the reference group and reduced their daily total screen-viewing time by 6.4% (95% CI: -9.6 to -3.3%, approximately 10 min). The positive effects were more pronounced among high-risk groups (secondary school and urban pupils who generally spend more time in sedentary behaviour) than in low-risk groups (primary school and rural pupils who generally spend less time in sedentary behaviour). The exploratory analyses showed comparable findings.ConclusionsThis regulatory intervention has been effective in reducing total and specific types of sedentary behaviour among Chinese children and adolescents, with the potential to reduce health inequalities. International researchers and policy makers may explore the feasibility and acceptability of implementing regulatory interventions on sedentary behaviour elsewhere.