Poison centers (PCs) in Germany are medical facilities that serve as points of contact for cases of poisoning or suspected poisoning and are available by phone 24 h a day. Consultations are provided by physicians who have completed specialized training in toxicology. Members of the public, healthcare professionals, and institutions with questions regarding toxicology can seek advice from the PCs. Over-the-counter medicines play an important role when contacting the PCs. These include pseudoephedrine (PSE), an indirect sympathomimetic, which is used in Germany as a combination preparation for the treatment of cold and flu symptoms and for the symptomatic treatment of allergic rhinitis. In Germany, PSE is combined with acetylsalicylic acid, acetaminophen, or ibuprofen, as well as with first- and second-generation H1 receptor antagonists. PSE has a decongestant effect on the mucous membranes of the nose and sinuses but also has stimulating effects and causes a feeling of alertness. This study includes an analysis of PSE poisoning cases reported to German PCs. They were asked to provide information on documented cases of PSE poisoning. Three of the seven centers surveyed provided their data (Erfurt 136 cases, Göttingen 175 cases, and Munich 210 cases, overall n = 521). The individual cases were then analyzed in terms of various aspects. The patient cases analyzed revealed age-related differences, with a higher incidence in childhood, particularly among children under 6 years of age. There were also indications of gender-specific differences. At the PC Erfurt, cardiovascular and neurological events predominate, with a male dominance. In Munich, neurological and gastrointestinal symptoms predominated. However, a high proportion of cases with unknown gender made gender-specific classification difficult. In Germany, young children up to the age of six are more severely affected despite contraindications and account for a significant proportion of inquiries to PCs. In recent years, PCs in Germany have reported an increase in cases of poisoning involving PSE combination preparations. A variety of symptoms have been observed in connection with PSE poisoning. As a preventive measure, it would be advisable for physicians-particularly pediatricians-and pharmacists to provide better patient education to raise awareness of the risks. Public platforms could also be used to conduct more educational outreach. Overall, the clinical relevance of PSE poisoning is evident from the present findings, which therefore require increased attention. PCs play an important role in this regard by providing acute consultation and systematically collecting data. However, the present findings should be interpreted in light of the limited data available to PCs.

Label-free quantitative detection of chemically diverse molecules is of critical importance across fields spanning medical diagnostics, food safety, and law enforcement. Surface-enhanced Raman spectroscopy (SERS) provides powerful molecular identification through fingerprint spectra, capable of achieving single-molecule detection limits when analytes are positioned directly at the plasmonic hotspots of Au/Ag substrates. Yet conventional contact-mode SERS, which relies on the direct adsorption of analytes onto bare metal surfaces, is limited by poor reproducibility and signal heterogeneity arising from random molecular orientations and competitive binding. Here, we present a proof-of-concept noncontact mode SERS platform that routinely delivers reproducible, predictable, and quantitative spectra readout, including discrimination of subtle enantiomeric differences. This platform utilizes fluorenylmethoxycarbonyl-lysine (Fmoc-Lys) scaffolds confined within 1-2 nm channels of nanoporous gold nanospheres. The Fmoc core captures target analytes through hydrophobic interactions, while the chiral center regulates the adsorption configuration/strength. This design fixes analyte distance and orientation relative to the metal surface, thereby minimizing stochastic spectral variation. We applied this platform to quantitatively analyzed methamphetamine (METH), a globally prevalent abused drug, in complex human urine samples and achieved accuracy comparable to mass spectrometry without requiring analyte-specific reference spectra. Our results highlight noncontact SERS as a general strategy for reliable, ultrasensitive molecular analysis, especially for targets lacking standard spectral libraries.

Polychlorinated Biphenyls (PCBs) are persistent organic pollutants in the environment. With high lipophilicity, PCBs are easily accumulated in the brain, finally leading to neurotoxicity. The underlying neurotoxicity mechanism of PCBs remains poorly understood and requires urgent investigation. The neurotransmitter system has been identified as a potential target of PCB-involved neurotoxicity. Current research on the neurotoxicity mechanism of PCBs predominantly focuses on single target. Due to the high complexity of the brain, the disorder of synaptic transmission triggered by environmental pollutants is highly complicated, and the corresponding mechanisms are likely to involve multi-targets. Here, we focused on two highly correlated components of the dopaminergic system-the dopamine transporter (DAT) and dopamine receptor (DR), to investigate whether there is a synergetic effect between them. By combining multiple computational methods and experimental assays, this study elucidated that DAT was a potential target of neurotoxicity for PCBs in the dopaminergic system, whereas it was highly unlikely for DR to bind PCBs. The computational results indicated that the affinity of the pentachloro biphenyl was higher than the tetrachloro biphenyl. The Van der Waals and π-π interactions were the main driving forces for PCBs binding to DAT. The decomposition energy confirmed that the key residues involved in the ligand binding were converged to Val120, Tyr124, and Phe325 for most of the tested PCBs. Our findings not only provide a detailed and plausible molecular mechanism of PCBs' neurotoxicity, but also are useful for the rational drug design to fight diverse CNS disorders and other diseases involving DAT.

Microcystin-LR (MC-LR) is a potent neurotoxin released by cyanobacterial blooms, posing significant threats to aquatic ecosystems and human health. However, the molecular mechanisms driving its dopaminergic neurodegeneration remain elusive. Herein, we demonstrated that chronic MC-LR exposure (60 days, 10 μg/L) to zebrafish exhibited motor deficits and anxiety-like behaviors. MC-LR also disrupted Nissl body integrity, reduced dopamine (DA) and its metabolites (HVA, DOPA), and suppressed key dopaminergic markers (TH, DAT and DRD1). These changes collectively impaired DA synthesis, transport and signaling cascades. Pathologically, MC-LR triggered robust neuroinflammation, evidenced by neuronal phagocytosis, microglial proliferation and elevated pro-inflammatory cytokines (TNF-α and IL-1β). Transcriptomic profiling, combined with computer simulation and CESTA, identified MyD88 as a master regulator of MC-LR-induced neuroinflammation. This finding was validated using both in vitro co-culture models (HMC3 microglia/SH-SY5Y neurons) and in vivo myd88 knockdown experiments. Notably, MC-LR promoted microglial M1 polarization via the MyD88/NFκB pathway, directly damaging dopaminergic neurons. Crucially, echinacoside (ECH) exerted potent neuroprotection by suppressing microglia activation, inhibiting MyD88/NFκB signaling, and restoring DA levels to controls. Together, these findings unveil a previously unrecognized pathway linking MC-LR exposure to inflammation-driven neurodegeneration, positioning MyD88 as a novel therapeutic target and ECH as a promising candidate against cyanotoxin-induced neurotoxicity.

The prevalence of methamphetamine use disorder has risen across the United States and many other countries, which has led to a concomitant rise in methamphetamine-induced psychosis (MIP). A promising and novel approach to address MIP can be found in 'chill packs', a psychiatric harm reduction intervention for people using methamphetamine. Chill packs consist of several low-dose olanzapine tablets (an antipsychotic medication) that can be self-administered in the event of methamphetamine-induced insomnia, anxiety, paranoia, delusions, or other dysphoric symptoms. One recent study assessed the effectiveness of an implementation of chill packs by the San Francisco Department of Health and found that repeat psychiatric emergency visits dropped by 32% after two-months and 13% after six-months from receipt of a chill pack. While these findings are promising, more research is needed to evaluate the efficacy and generalizability of this intervention. Here we provide a narrative review which synthesizes indirect evidence and contextual information relevant to this intervention, including: the epidemiology of MIP, clinical data supporting the use of olanzapine versus other antipsychotics for MIP, evidence for as-needed outpatient antipsychotic use, as well as qualitative and other data describing the potential for misuse of olanzapine and other antipsychotics. Overall, the literature supports that the prevalence of MIP is rising sharply, causing increased psychiatric burden. This is also linked to overdose risk among patients that use illicit fentanyl or other sedatives to "come down" after periods of heavy methamphetamine use. Olanzapine has demonstrated comparable efficacy for treating MIP compared to other antipsychotics with enhanced short-term sedative effects, despite a higher burden of long-term metabolic side effects. Olanzapine has very little documented misuse risk, although other agents in its class, especially quetiapine, have higher street value. Qualitative research highlights that some groups already self-administer olanzapine as a 'trip killer' to manage distressing psychiatric side effects from illicit drug use. Overall, we find substantial contextual evidence supporting further trials to evaluate chill packs as a harm-reduction intervention for MIP and provide recommendations for research needed to fill gaps in the evidence for this promising emerging intervention.

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant with disproportionate exposure burdens in infants and toddlers, yet its potential to programme later-life neurodegenerative susceptibility remains unclear. We exposed zebrafish embryos to TPhP (20-1000 μg/L, 2-120 hpf) and conducted life-course assessments after depuration at larval (7 dpf), juvenile (30 dpf), and adult (3 mpf) stages. Developmental TPhP exposure reduced whole-brain monoaminergic terminal signals in Tg (vmat2: GFP) larvae, increased acridine orange/propidium iodide (AO/PI)-defined neural cell death, impaired cerebrovascular growth, and produced a hypoactive locomotor profile. Co-exposure with apomorphine partially mitigated larval hypolocomotion at 20 μg/L. Persistent behavioral disturbances emerged with maturation, including hypolocomotion, abnormal light-dark preference, and adult deficits in spatial learning/memory and social interaction. Adult brains showed Parkinson's disease (PD)-relevant injury signatures, including reduced tyrosine hydroxylase immunoreactivity, dopamine depletion, and pronounced α-synuclein accumulation. Transcriptomic profiling implicated sustained remodelling of protein-folding programs, mitochondrial redox homeostasis, and ferroptosis-related pathways, which was functionally supported by reduced mitochondrial complex I activity, elevated oxidative DNA and lipid damage (8-OHdG, 4-HNE), and impaired antioxidant defenses (slc7a11, park7, GPX4). Molecular docking suggested structurally plausible interactions of TPhP with tyrosine hydroxylase (TH)and D2-type dopamine receptors (DRD2a/b). Collectively, transient developmental TPhP exposure extends beyond early neurotoxicity and is associated with persistent dopaminergic vulnerability and PD-like phenotypes across the life course.

PURPOSE OF REVIEW: This review evaluates structural neuroimaging research on substance-related psychosis to determine if these conditions share common neurobiological pathways with primary psychotic disorders, such as schizophrenia, or exhibit unique signatures. RECENT FINDINGS: Research indicates that methamphetamine, cannabis, and cocaine induce significant structural changes, including cortical thinning and grey matter loss. Methamphetamine-induced psychosis is associated with frontal lobe reductions and smaller hippocampal and amygdalar volumes. Cannabis use is linked to alterations in the cingulate cortex and cerebellar networks, particularly when use begins early in life. While many neuroimaging patterns overlap with schizophrenia substance-specific variations exist. For instance, methamphetamine users show more pronounced amygdalar reduction than those with primary psychosis. Generally, structural deficits are more severe and widespread in schizophrenia than in purely substance-induced cases. Substance-induced psychoses exhibit neuroanatomical signatures largely similar to primary psychoses, though distinct regional variations suggest partially divergent mechanisms. Future longitudinal and multimodal research is essential to identify definitive biomarkers for clinical differentiation.

Labetalol is widely prescribed as a first-line antihypertensive in pregnancy; however, rare but potentially severe idiosyncratic hepatotoxicity has been reported, with a disproportionately strong reporting signal for liver injury relative to other β-blockers. In this report, a fatal case is described in which mild initial symptoms rapidly progressed to fulminant hepatocellular injury and acute liver failure within days, underscoring the importance of early recognition of drug-induced liver injury and prompt discontinuation of labetalol. A PRISMA-guided systematic review of MEDLINE, Embase, CINAHL, Cochrane Library, PubMed, and Google Scholar (from inception to December 2025) identified 27 published case reports. Patients were predominantly female (≈80%), and one-third were pregnant or postpartum. Latency ranged from 7 to 365 days (median ≈60 days). The injury phenotype was consistently hepatocellular, often with autoimmune-like serologic or histologic features. Outcomes included full recovery in most (≈75%), but also liver transplantation and death. In the FDA Adverse Event Reporting System (2020Q1-2025Q1), labetalol showed strong disproportionality signals for DILI (PRR 22.7, 95% CI 15.6-33.1; ROR 23.7, 95% CI 16.0-35.1; IC025 2.5) and autoimmune hepatitis (PRR 59.8, 95% CI 34.1-104.8; ROR 60.9, 95% CI 34.4-108.1; IC025 2.8), which persisted when restricted to other β-blockers as comparators. Signals for acute hepatic failure and hyperbilirubinemia were elevated but less statistically robust. The available evidence is consistent with a clinically meaningful and biologically plausible association between labetalol and idiosyncratic hepatotoxicity, supporting heightened clinical awareness and further mechanistic and population-based study.

The spread of new psychoactive substances (NPS), particularly synthetic cathinones, poses growing challenges for forensic toxicology. Among them, metaphedrone (3-methylmethcathinone, 3-MMC) is a potent psychostimulant structurally related to mephedrone (4-MMC), acting as a monoamine transporter substrate with predominant dopaminergic and noradrenergic effects. Despite international control measures, 3-MMC remains widely available on illicit online markets and it is increasingly associated with severe intoxications and deaths. We report a fatal case of isolated 3-MMC intoxication investigated at the Section of Legal Medicine and Forensic Toxicology of our University. Postmortem examination revealed nonspecific macroscopic and histological findings, including pulmonary edema, polyvisceral congestion, and myocardial alterations. Toxicological analysis identified 3-MMC as the sole detected substance, with concentrations of 966 ng/mL in peripheral blood and 25,549 ng/mL in urine, consistent with previously reported fatal cases. Standard immunochemical screening was negative, highlighting the limitations of routine toxicology panels and the need for targeted GC-MS/MS methodologies in NPS detection. This case underscores the diagnostic challenges posed by 3-MMC-related deaths and reinforces the critical role of advanced analytical techniques in forensic investigations, emphasizing the need for continuous updating of toxicological protocols to address the evolving NPS landscape.