Alcohol addiction is a chronic relapsing brain disorder characterized by significant neurobiological changes, particularly within the hippocampus, which mediates emotional regulation and reward-seeking behavior. Previous studies have shown that alcohol-induced neuronal injury contributes to withdrawal-associated anxiety and persistent alcohol preference. This study investigated the therapeutic effects of low-intensity focused ultrasound (LIFU) on the hippocampus in a mouse model of alcohol addiction. Twenty-six male C57BL/6 mice were allocated to an alcohol-exposed group (n = 20) and a control group (n = 6). Following a 28-day modeling period, the alcohol group was randomly subdivided into a therapy group and a sham group. The therapy group received LIFU treatment, while the sham group underwent an identical procedure with the ultrasound transducer powered off. After seven days of treatment, the therapy group exhibited less severe anxiety symptoms upon alcohol withdrawal and a reduced preference for alcohol compared to the sham group. The brain-derived neurotrophic factor (BDNF) concentration was significantly lower in the therapy group than in the sham group, but did not differ significantly from the control group. Hippocampal HE staining revealed more pronounced degeneration and apoptosis of granule cells in the dentate gyrus (DG) region in the sham group relative to the therapy group. These preliminary findings suggest that LIFU may modulate alcohol addiction by mitigating hippocampal neuronal injury.

Background and Objectives: Postoperative pain and intra-abdominal adhesions are common complications following surgery. Pain delays early mobilization, whereas adhesions can lead to bowel obstruction, chronic pain, or infertility. Current treatments, including systemic analgesics and physical barrier methods, are only partially effective. We hypothesized that combining these modalities would yield superior outcomes. Accordingly, we investigated whether a lidocaine-loaded alginate-carboxymethyl cellulose-polyethylene oxide (ACPE) electrospun film could more effectively reduce both postoperative pain and adhesion formation than either component alone. Materials and Methods: An electrospun nanofiber film composed of ACPE containing lidocaine was prepared. Its effects were evaluated in rats using an incisional pain and a peritoneal adhesion model. Four groups were compared: saline control, free lidocaine, drug-free ACPE film, and lidocaine-loaded ACPE film. Fifteen rats were allocated to each group. The primary outcome was the mechanical withdrawal threshold (MWT) after plantar incision, while secondary outcomes included histological changes and adhesion scores assessed by the Moreno system. Results: The lidocaine-ACPE film significantly increased MWT compared with all other groups, demonstrating a stronger and longer-lasting analgesic effect than free lidocaine. Adhesion scores were also lowest in the film group. Histological analysis confirmed a reduction in inflammatory cell infiltration and collagen deposition. Conclusions: A lidocaine-loaded ACPE nanofiber film effectively reduced both postoperative pain and adhesion formation in a rodent model. The combination of sustained local drug release and physical barrier function provides a promising strategy to address two major postoperative complications. Further preclinical studies are warranted before clinical application.

Plasma neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), tau protein and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are candidate biomarkers of alcohol withdrawal (AW)-associated brain toxicity, as they are biomarkers of axonal, neuronal or glial injury. The aim of this study was to investigate the changes of these biomarkers during AW in patients with severe alcohol use disorder (AUD). Plasma NFL, GFAP, tau and UCHL1 levels were measured, with SIMOA, at three times: on Day 1 (T1), on Day 3 or 4 (T2) and on Day 13, 14 or 15 (T3) of AW. They were analysed with a linear mixed model adjusted for age, sex and body mass index. Changes in these levels according to AW symptom severity were evaluated. Twenty-four inpatients with severe AUD were included: 20 men (83.3%), aged 47.4 years [±11.3], with symptoms requiring a median equivalent-diazepam dose of 0.81 mg/kg at T1. A significant increase was observed for NFL level from T1 to T2 (β = 0.349, p = 0.035), but not for GFAP, tau or UCHL1 levels. In AW symptom severity analyses, a significant positive association was found with equivalent-diazepam dose required × T1-T2 time interaction factor for NFL (β = 0.161, p = 0.028) and for GFAP (β = 0.400, p = 9.9 × 10-4). This longitudinal study provided preliminary indication that brain injury could occur within the first days of AW, especially in patients with severe pharmacological dependence. Plasma NFL and GFAP are promising biomarkers of AW-related brain pathology and should be investigated as biomarkers of therapeutic response to test innovative drug strategies for preventing this toxicity. Trial Registration: Clinical Trials: NCT05216705.

Alcohol use disorder (AUD) represents a critical public health challenge, with early-life adversity conferring heightened risk for compulsive drinking patterns. Alcohol has long been known to exert direct effects on developing neurotransmitter systems, targeting among others GABAergic, glutamatergic, and dopaminergic signaling. Recent evidence however indicates that early adversity also primes microglial activation and establishes chronic low-grade neuroinflammation, disrupting maturation of prefrontal-limbic-striatal circuits governing executive control and affect regulation. Hence, alcohol use may emerge in adolescents as a maladaptive coping mechanism, transiently alleviating stress-related dysphoria while exacerbating neuroimmune and neurocircuit dysfunction. While traditional neurocentric models convincingly depict how repeated withdrawal episodes may unmask this underlying vulnerability, precipitating relapse cycles that consolidate compulsive use, they inadequately explain the persistence and treatment resistance characteristic of adolescent-onset alcohol misuse because they fail to account for the peripheral biological systems that amplify central vulnerability. The gut-microbiota-brain axis represents one such amplifier: stress- and alcohol-related perturbations in barrier integrity and immunometabolic signaling increase peripheral inflammatory load reaching the brain, intensifying neuroimmune tuning of still-maturing control circuits. Integrating these central and peripheral processes reframes adolescent alcohol vulnerability as a systems-level phenomenon embedded within developmental and inflammatory biology, rather than a disorder of reward circuitry alone. This developmental framework suggests that adjunctive therapeutic strategies combining targeted neuroimmune modulation, behavioral intervention, and ecological stabilization during critical developmental windows may offer superior outcomes over conventional reward-focused pharmacotherapies. Realizing this potential will require biomarker-driven risk stratification, precision medicine approaches, and careful developmental consideration of intervention timing.

We report a case of a patient presenting with melena and dysphagia. His gastroscopy revealed an oesophageal mass and active duodenal papillary haemorrhage. Subsequent endoscopic retrograde cholangiopancreatography (ERCP) confirmed the presence of a haemorrhagic mediastinal pancreatic pseudocyst (MPP). Due to severe alcohol withdrawal syndrome, the patient declined surgical intervention. Conservative management and pancreatic tube placement under ERCP were performed, resulting in clinical stabilization. Follow-up imaging 2 months later demonstrated partial remission of the MPP. We further review the clinical characteristics and contemporary management strategies for MPP.

While binge drinking can significantly impact health negatively, it has become increasingly important to understand how sex differences contribute to this hazardous behavior, which may also serve as a risk factor for alcohol use disorder. We employed the binge drinking experimental model we developed previously to specifically analyze sex differences. Forty male and 40 female Long Evans rats were tested in the alcohol self-administration procedure, operationalized as alcohol responding in short daily session. We tested other parameters, including motivation, seeking, responses during cue omission sessions, withdrawal scores, and relapse after abstinence. We also conducted experiments to assess perseverance despite satiety. For the analysis we used first an unsupervised clustering approach using drinking speed and frequency of alcohol responses and then we analyzed our data by taking sex as the differentiating factor. Unbiased clustering analysis revealed four distinct groups: Fast Bingers, Bingers, Extreme Bingers and Low drinkers. Higher alcohol consumption and faster consumption speed correlated with elevated withdrawal scores. Sex-related differences were observed, with females outnumbering males in Extreme bingers. Females also exhibited higher alcohol-seeking behavior, relapse rates, and withdrawal scores. In addition, females exhibit lower sensitivity to devaluation in the satiety test. Our results suggest that females display greater vulnerability to cue-mediated alcohol-seeking behaviors and a more inflexible behavior. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research on binge drinking behaviors that is not only a hazardous behavior but may also be a critical factor in AUD vulnerability, particularly in females.

Alcohol use disorder (AUD) is characterized by problems controlling alcohol drinking despite adverse consequences, development of tolerance and/or withdrawal symptoms. Notably, sex differences in alcohol consumption patterns and susceptibility to relapse are well documented but remain poorly understood at the molecular level. In this study, we performed single-nuclei RNA sequencing (snRNA-seq) of the medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc) from male and female outbred RccHan Wistar rats exposed to the alcohol deprivation effect (ADE) paradigm, a well-established model of relapse-like drinking behaviour. Comparing high- to low-drinking rats, we found pronounced transcriptional changes across different cell types, with the highest number of differentially expressed genes observed in GABAergic medium spiny neurons (MSNs) of the NAcc and glutamatergic neurons of the mPFC associated with relapse. Importantly, we also identified sex- and region-dependent transcriptional alterations, including differential expression of dopamine receptors and phosphodiesterase family genes, which have previously been associated with AUD in humans, as well as alterations in the transcription of genes associated with synaptic plasticity and neuroimmune signalling. Finally, we found induction of immune-related genes in microglia and sex-dependent activation of immune- and myelination-related genes in astrocytes and oligodendrocytes. These findings highlight cell type-, region-, and sex-dependent molecular signatures associated with alcohol relapse drinking, which may provide new therapeutic targets for AUD.

Kratom and kratom products are increasingly used in Western countries for pain management, mood disorders, and opioid withdrawal. Despite perceptions of safety, kratom can cause hepatotoxicity and clinically relevant herb-drug interactions, particularly with medications metabolized by cytochrome P450 (CYP) enzymes. We report a 45-year-old male with stable psychiatric conditions on nortriptyline and lisdexamfetamine, who developed mild, reversible liver enzyme elevations and supratherapeutic nortriptyline levels during chronic kratom use (raw, dry leaf, two tablespoons daily for five to six years). Initial labs showed aspartate aminotransferase (AST) 33 U/L, alanine aminotransferase (ALT) 70 U/L, alkaline phosphatase (ALP) 136 U/L, gamma-glutamyl transferase (GGT) 141 U/L, and nortriptyline 350 mcg/L. Dose reduction of nortriptyline partially corrected serum levels, but liver enzyme elevations persisted. Kratom discontinuation led to normalization of both liver function tests and nortriptyline levels within three weeks. This case illustrates two clinically important considerations: kratom-induced liver injury (KILI) and a CYP-mediated herb-drug interaction. The patient's use of raw leaf contrasts with commercial products, which may include concentrated extracts, 7-hydroxymitragynine (7OHMG)-enriched formulations, or ethanol-based preparations, potentially increasing hepatotoxicity and interaction risk. Even mild liver enzyme elevations in patients using kratom warrant evaluation, particularly with concurrent CYP-metabolized medications. Clinicians should educate patients about product variability, monitor liver function and drug levels, and consider temporary kratom discontinuation to assess causality. This case reinforces the growing evidence of kratom's hepatotoxic potential and the importance of integrating pharmacokinetic considerations into patient care.