UNASSIGNED: Patients with cirrhosis are susceptible to development of acute kidney injury (AKI), which leads to poor outcome. We conducted a study to evaluate the spectrum of AKI in patients with cirrhosis.
UNASSIGNED: This study was conducted in consecutive cirrhotic patients with AKI admitted in a tertiary care center of India from April 2020 to December 2022. Details including history, examination findings, and results of laboratory investigations were recorded.
UNASSIGNED: A total of 243 patients were enrolled in this study. The majority (91.3%) of the patients were males. The most common etiology of cirrhosis was alcohol in 58.4% (n = 142) followed by hepatitis B in 10.3% (n = 25) of patients. Pre-renal form of AKI was present in 54.4% (n = 132) of patients and hepatorenal syndrome (HRS) in 21.8% (n = 53) of patients. IgA nephropathy was the commonest (n = 6) glomerular pathology in nonresponders with intrinsic renal disease. Majority of the patients belonged to stage II (46.9%) and stage I AKI (37%), while only 16.1% had stage III AKI. Various stages of AKI showed a significant correlation (P < 0.05) with Child-Turcotte-Pugh (CTP) score and Model for End-stage Liver Disease (MELD)-Na score. The overall in-hospital mortality rate was found to be 18.5% (n = 45).
UNASSIGNED: Renal dysfunction is a frequent complication among cirrhotic patients. Pre-renal factors were the most common cause of AKI in cirrhotics. Stages of AKI showed significant correlation with liver prognostic scores. Renal biopsy should be considered in patients not responding to treatment, to guide further management.

BACKGROUND: Alcohol-based handrub (ABHR) is the gold standard for hand hygiene (HH) and is a cornerstone of infection prevention and control (IPC) strategies. However, several factors influence the efficient use of ABHR by health workers. This study evaluated the tolerability and acceptability of a locally produced ABHR product and HH behaviour among health workers.
METHODS: A longitudinal hospital-based intervention study was conducted in accordance with the WHO\'s standardized protocol for evaluating ABHR tolerability and acceptability (Method 1). Sixty health workers across 4 hospitals in Sierra Leone were observed over a 30-day period at three separate visits (days 1, 3-5, and 30) by trained observers. The outcomes of interest included skin tolerability and product acceptabilityevaluated using subjective and objective measures.
RESULTS: Objective and subjective evaluations demonstrated strong skin tolerability and high acceptability with the product. At all three visits, the skin tolerability score assessed by trained observers was < 2 in ≥ 97% of participants, exceeding the WHO benchmark score (BMS = < 2 in ≥ 75%). Participants\' self-evaluations of overall skin integrity were 97% (visit 2) and 98% (visit 3) for scores > 4 (BMS = > 4 in ≥ 75%). The primary acceptability criteria increased up to 95% (colour) and 88% (smell) at visit 3 (BMS = > 4 in ≥ 50%). Despite high acceptability, the product\'s drying effect remained low at 52% and 58% during visits 2 and 3, respectively (BMS = > 4 in ≥ 75%). There were positive HH behaviours (n = 53, 88%), with more than half (n = 38, 63%) of them exhibiting HH at almost every HH moment. The mean ABHR was notably high (76.1 ml, SD ± 35), especially among nurses (mean = 80.1 ml) and doctors (mean = 74.0 ml).
CONCLUSIONS: The WHO-formulated, locally produced ABHR was well tolerated and accepted by health workers. These findings support the continuous utilization of evidence-based, cost-effective hand hygiene interventions in resource-limited settings. High handrub consumption and frequent HH practices were noticeable HH behaviours. Further research is recommended to optimize product formulations for skin dryness and investigate the association between ABHR consumption and hand hygiene compliance.

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.

Propolis is widely used as a supplementary food product for its health benefits. The aim of this study was to determine the effects of commercial propolis extracts on the liver and kidney. Propolis extracts (250 mg/kgbw/day) were administered orally to adult male Wistar albino rats in solvents of ethanol, propylene glycol, water, and olive oil. Liver enzyme levels were determined biochemically in blood samples, and histopathological examinations were performed on the liver. Damage rate in both kidney tissue in the propolis-ethanol extract group increased significantly compared with the other groups after 30 and 90 days of application (p < .05). According to the results, ethanol, used as a common solvent in propolis products, may adversely affect the liver in long-term use. The data indicate that propolis-olive oil extract may be an essential alternative due to its effective and reliable properties.

OBJECTIVE: Binge drinking (i.e., consuming enough alcohol to achieve a blood ethanol concentration of 80 mg/dL, approximately 4-5 drinks within 2 hours), particularly in early adolescence, can promote progressive increases in alcohol drinking and alcohol-related problems that develop into compulsive use in the chronic relapsing disease, alcohol use disorder (AUD). Over the past decade, neuroimmune signaling has been discovered to contribute to alcohol-induced changes in drinking, mood, and neurodegeneration. This review presents a mechanistic hypothesis supporting high mobility group box protein 1 (HMGB1) and Toll-like receptor (TLR) signaling as key elements of alcohol-induced neuroimmune signaling across glia and neurons, which shifts gene transcription and synapses, altering neuronal networks that contribute to the development of AUD. This hypothesis may help guide further research on prevention and treatment.
METHODS: The authors used the search terms \"HMGB1 protein,\" \"alcohol,\" and \"brain\" across PubMed, Scopus, and Embase to find articles published between 1991 and 2023.
UNASSIGNED: The database search found 54 references in PubMed, 47 in Scopus, and 105 in Embase. A total of about 100 articles were included.
CONCLUSIONS: In the brain, immune signaling molecules play a role in normal development that differs from their functions in inflammation and the immune response, although cellular receptors and signaling are shared. In adults, pro-inflammatory signals have emerged as contributing to brain adaptation in stress, depression, AUD, and neurodegenerative diseases. HMGB1, a cytokine-like signaling protein released from activated cells, including neurons, is hypothesized to activate pro-inflammatory signals through TLRs that contribute to adaptations to binge and chronic heavy drinking. HMGB1 alone and in heteromers with other molecules activates TLRs and other immune receptors that spread signaling across neurons and glia. Both blood and brain levels of HMGB1 increase with ethanol exposure. In rats, an adolescent intermittent ethanol (AIE) binge drinking model persistently increases brain HMGB1 and its receptors; alters microglia, forebrain cholinergic neurons, and neuronal networks; and increases alcohol drinking and anxiety while disrupting cognition. Studies of human postmortem AUD brain have found elevated levels of HMGB1 and TLRs. These signals reduce cholinergic neurons, whereas microglia, the brain\'s immune cells, are activated by binge drinking. Microglia regulate synapses through complement proteins that can change networks affected by AIE that increase drinking, contributing to risks for AUD. Anti-inflammatory drugs, exercise, cholinesterase inhibitors, and histone deacetylase epigenetic inhibitors prevent and reverse the AIE-induced pathology. Further, HMGB1 antagonists and other anti-inflammatory treatments may provide new therapies for alcohol misuse and AUD. Collectively, these findings suggest that restoring the innate immune signaling balance is central to recovering from alcohol-related pathology.

Chronic and continuous alcohol consumption increases the risk of cognitive decline and may lead to alcohol-related dementia. We investigated the potential of Heracleum moellendorffii Hance root extract (HME) for treating alcohol-related cognitive impairment. Behavioral tests evaluated the effects of HME on cognitive function and depression. Changes in hippocampus and liver tissues were evaluated by Western blotting and H&E staining. The group treated with HME 200 mg/kg showed a significant increase in spontaneous alternation in Y-maze and a decrease in immobility in a forced swimming test (FST) compared to the vehicle-treated group. These results suggest that HME can restore memory deficits and reverse depressive symptoms caused by chronic alcohol consumption. The HME-treated group also upregulated brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated cAMP response element-binding protein (CREB) in the hippocampus. Additionally, it reduced lipid vacuolation in the liver and increased the expression of aldehyde dehydrogenase 1 (ADH1). The administration of HME improves cognitive impairment and reverses depressive symptoms due to alcohol consumption, restoring neural plasticity in the hippocampus and alcohol metabolism in the liver. These findings suggest that HME is a promising treatment for alcohol-related brain disorders. Molecular mechanisms underlying the therapeutic effects of HME and its active ingredients should be investigated further.

Alcoholic liver disease (ALD) is a form of hepatic inflammation. ALD is mediated by gut leakiness. This study evaluates the anti-inflammatory effects of ASCs overexpressing interferon-beta (ASC-IFN-β) on binge alcohol-induced liver injury and intestinal permeability. In vitro, ASCs were transfected with a non-viral vector carrying the human IFN-β gene, which promoted hepatocyte growth factor (HGF) secretion in the cells. To assess the potential effects of ASC-IFN-β, C57BL/6 mice were treated with three oral doses of binge alcohol and were administered intraperitoneal injections of ASC-IFN-β. Mice treated with binge alcohol and administered ASC-IFN-β showed reduced liver injury and inflammation compared to those administered a control ASC. Analysis of intestinal tissue from ethanol-treated mice administered ASC-IFN-β also indicated decreased inflammation. Additionally, fecal albumin, blood endotoxin, and bacterial colony levels were reduced, indicating less gut leakiness in the binge alcohol-exposed mice. Treatment with HGF, but not IFN-β or TRAIL, mitigated the ethanol-induced down-regulation of cell death and permeability in Caco-2 cells. These results demonstrate that ASCs transfected with a non-viral vector to induce IFN-β overexpression have protective effects against binge alcohol-mediated liver injury and gut leakiness via HGF.

Understanding the role of iron in ethanol-derived hepatic stress could help elucidate the efficacy of dietary or clinical interventions designed to minimize liver damage from chronic alcohol consumption. We hypothesized that normal levels of iron are involved in ethanol-derived liver damage and reduced dietary iron intake would lower the damage caused by ethanol. We used a pair-fed mouse model utilizing basal Lieber-DeCarli liquid diets for 22 weeks to test this hypothesis. In our mouse model, chronic ethanol exposure led to mild hepatic stress possibly characteristic of early-stage alcoholic liver disease, seen as increases in liver-to-body weight ratios. Dietary iron restriction caused a slight decrease in non-heme iron and ferritin (FeRL) expression while it increased transferrin receptor 1 (TfR1) expression without changing ferroportin 1 (FPN1) expression. It also elevated protein lysine acetylation to a more significant level than in ethanol-fed mice under normal dietary iron conditions. Interestingly, iron restriction led to an additional reduction in nicotinamide adenine dinucleotide (NAD+) and NADH levels. Consistent with this observation, the major mitochondrial NAD+-dependent deacetylase, NAD-dependent deacetylase sirtuin-3 (SIRT3), expression was significantly reduced causing increased protein lysine acetylation in ethanol-fed mice at normal and low-iron conditions. In addition, the detection of superoxide dismutase 1 and 2 levels (SOD1 and SOD2) and oxidative phosphorylation (OXPHOS) complex activities allowed us to evaluate the changes in antioxidant and energy metabolism regulated by ethanol consumption at normal and low-iron conditions. We observed that the ethanol-fed mice had mild liver damage associated with reduced energy and antioxidant metabolism. On the other hand, iron restriction may exacerbate certain activities of ethanol further, such as increased protein lysine acetylation and reduced antioxidant metabolism. This metabolic change may prove a barrier to the effectiveness of dietary reduction of iron intake as a preventative measure in chronic alcohol consumption.

Ethanol sensors have found extensive applications across various industries, including the chemical, environmental, transportation, and healthcare sectors. With increasing demands for enhanced performance and reduced energy consumption, there is a growing need for developing new ethanol sensors. Micro-electromechanical system (MEMS) devices offer promising prospects in gas sensor applications due to their compact size, low power requirements, and seamless integration capabilities. In this study, SnO2-TiO2 nanocomposites with varying molar ratios of SnO2 and TiO2 were synthesized via ball milling and then printed on MEMS chips for ethanol sensing using electrohydrodynamic (EHD) printing. The study indicates that the two metal oxides dispersed evenly, resulting in a well-formed gas-sensitive film. The SnO2-TiO2 composite exhibits the best performance at a molar ratio of 1:1, with a response value of 25.6 to 50 ppm ethanol at 288 °C. This value is 7.2 times and 1.8 times higher than that of single SnO2 and TiO2 gas sensors, respectively. The enhanced gas sensitivity can be attributed to the increased surface reactive oxygen species and optimized material resistance resulting from the chemical and electronic effects of the composite.

Microbiota analyses are key to understanding the bacterial communities within dairy cattle, but the impact of different storage conditions on these analyses remains unclear. This study sought to examine the effects of freezing at -80°C immediately after collection, refrigeration at 4°C for three days and seven days and absolute ethanol preservation on the microbiota diversity of pooled fecal samples from dairy cattle. Examining 16S rRNA gene sequences, alpha (Shannon, Pielou evenness, observed features and Faith PD indices) and beta (Bray-Curtis, βw and Weighted UniFrac) diversity were assessed. The effects of storage conditions on these metrics were evaluated using linear mixed models and PERMANOVA, incorporating the farm as a random effect. Our findings reveal that 7d and E significantly altered the Shannon index, suggesting a change in community composition. Changes in Pielou evenness for 3d and 7d storage when compared to 0d were found, indicating a shift in species evenness. Ethanol preservation impacted both observed features and Faith PD indices. Storage conditions significantly influenced Bray-Curtis, βw, and Weighted UniFrac metrics, indicating changes in community structure. PERMANOVA analysis showed that these storage conditions significantly contributed to microbiota differences compared to immediate freezing. In conclusion, our results demonstrate that while refrigeration for three days had minimal impact, seven days of refrigeration and ethanol preservation significantly altered microbiota analyses. These findings highlight the importance of sample storage considerations in microbiota research.