Toxins

Background: Post-stroke spasticity (PSS) is a common complication in stroke survivors, significantly impairing functional recovery and quality of life. Despite its prevalence, Italy lacks national guidelines or structured good clinical practice documents, resulting in heterogeneous clinical management. Methods: An Italian Delphi study was conducted to establish expert-based recommendations for PSS management. A panel of 93 rehabilitation medicine specialists and neurologists, each with over 5 years of experience in PSS management with botulinum toxin A (BoNT-A), participated in two rounds of voting on 47 statements drafted and approved by seven Key Opinion Leaders (KOLs), recognized for their national and international expertise. Consensus was defined as ≥75% of respondents answering ‘strongly agree’ or ‘somewhat agree’. Results: In Round 1, consensus was reached for 90% of statements; five items did not achieve the threshold. After revision and a second round, consensus was achieved for all items, including consideration of lesion site in clinical management and the role of adjuvant post-injection interventions. The panel’s heterogeneity ensured broad representativeness. Conclusion: This Delphi study provides the first structured Italian expert recommendations for PSS management. Full consensus was reached in all 47 statements and in the Symptoms domain, particularly regarding pain, stiffness and heaviness, which highlights the importance of a structured framework to support consistent, individualized care. By standardizing patient assessment, treatment planning, and follow-up strategies, these findings provide a practical reference for clinicians.

Extreme weather impacts the ecological niches of fungi, altering mycotoxin risks in wildlife. We analyzed mycotoxin carry-over into European fallow deer (Dama dama) milk across seasons and assessed how drought influences the shift from Fusarium to Aspergillus mycotoxins and affects physiological resilience. Samples were collected during 2021/2022 and a drought-stricken 2022/2023 from South Transdanubia and Northeastern Hungary. Aflatoxin B1/M1 (AFB1/AFM1), Fumonisin B1 (FB1), Deoxynivalenol (DON), Zearalenone (ZEN), and Body Condition Scores (BCS) were measured to evaluate the impact of exposure on health status. The severe drought significantly altered the mycotoxin profile: ZEN levels declined significantly (from a median of 0.28 to 0.00 ng/mL), consistent with the moisture requirements of Fusarium graminearum, whereas DON concentrations increased. Concurrently, AFM1 persisted, exhibiting increased variance and extreme outliers in the maize-dominated South Transdanubian region. Distinct pharmacokinetic patterns were observed, and positive correlations were observed between milk and feces for lipophilic toxins, validating milk as a possible biomarker. Hydrophilic DON showed no correlation despite its accumulation. Emergence of “Poor” BCS group carrying loads supports “condition-dependent foraging” hypothesis, as stressed individuals are forced to consume contaminated resources, exacerbating oxidative stress and metabolic deficits.

Chronic exposure to the cyanotoxin microcystin-LR is an emerging environmental driver of non-alcoholic fatty liver disease (NAFLD); however, the initiating molecular events at sub-lethal, environmentally relevant concentrations remain elusive. Current safety guidelines focus primarily on acute injury, potentially overlooking silent metabolic disruption. The present study investigates the early metabolic toxicity of chronic low-dose microcystin-LR (10 µg/L) in a 7-week rat model, specifically focusing on pre-symptomatic perturbations in lipid homeostasis. By integrating biochemical profiling with multivariate systems toxicology (LASSO and PLS-DA), we identified a specific phenotype of “Silent Hepatic Total Cholesterol Accumulation” (T-CHOL +16%, p = 0.01) occurring in the absence of systemic dyslipidemia or overt liver injury. Mechanistic analysis revealed a specific dual failure of cholesterol homeostasis, characterized by the paradoxical upregulation of the influx transporter Ldlr (LASSO coef +0.661) and the suppression of the efflux transporter Abcg1 (PLS1 loading −0.358). Crucially, Ldlr upregulation occurred despite the concomitant transcriptional downregulation of Srebp2 (Spearman ρ = −0.585), indicating a regulatory uncoupling mechanism. We propose that microcystin-LR-induced protein phosphatase 2A (PP2A) inhibition likely drives this uncoupling via a post-transcriptional override—possibly involving ERK/RSK-mediated Ldlr mRNA stabilization. Concurrently, this inhibition appears to block LXR-mediated Abcg1 expression through sustained AMPK hyperactivation resulting from the loss of dephosphorylation. These findings indicate liver-specific cholesterol accumulation as the critical first step of environmental NAFLD pathogenesis, suggesting that current WHO guidelines (1 µg/L) may require re-evaluation regarding metabolic safety. We propose the hepatic Ldlr/Abcg1 ratio as a potential early biomarker for revised risk assessment.