Search Results (376)

(1) Background: To report two cases of severe tick-borne encephalitis (TBE) in elderly patients presenting with a previously undescribed subarachnoid T2/FLAIR hyperintensity on repeated MRI examinations, which may serve as an early imaging biomarker of disease severity. (2) Methods: Two unvaccinated 82-year-old patients (one male and one female) presented with acute encephalitis and required intensive care. Serial brain MRI, EEG, CSF analysis, and neurophysiological assessments were performed. (3) Results: Both patients showed rapid progressive neurological deterioration in the context of TBE, confirmed by elevated serum and CSF IgM and IgG titers. Early follow-up MRI revealed striking sulcal hyperintensities on T2/FLAIR sequences, interpreted as protein-rich subarachnoid inflammatory changes. These changes paralleled clinical worsening and resolved on follow-up imaging. The male patient developed meningoencephalomyeloradiculitis, remained comatose, and died from respiratory failure (the brain and spinal cord were examined postmortem). The female patient had meningoencephaloradiculitis with severe dysphagia and was discharged with a modified Rankin Scale score of four. Both patients demonstrated epileptiform EEG activity. The CSF analysis revealed markedly elevated total protein, lactate, tau protein, and CXCL13, as evidence of blood–brain barrier disruption and inflammatory neurodegeneration. (4) Conclusions: We describe acute subarachnoid T2/FLAIR hyperintensity in TBE as an imaging feature that may correlate with severe systemic inflammation and a poor prognosis. This radiological finding could serve as a potential early prognostic marker in TBE. Full article

Background/Objectives: Tau protein, a central player in Alzheimer’s disease (AD) pathology, is classically known for its role in microtubule stabilisation. However, accumulating evidence indicates that tau also localises to the neuronal nucleus, particularly the nucleolus, where it may regulate chromatin organisation and transcription. In this study, we investigated whether different phosphorylation states of nuclear tau display age- and disease-dependent patterns, with a specific focus on the AT8 epitope (phospho-Ser202/Thr205). Methods: We analysed nuclear tau epitopes (Tau-1, AT8, PHF1, T181, and S262) by indirect immunofluorescence in SK-N-BE neuroblastoma cells under proliferative and retinoic acid-induced differentiated conditions and in post-mortem hippocampal CA1 neurons from foetal, young, aged, and AD brains. Other functional markers (UBTF, Ki67, fibrillarin and acetylated histone H4) were used to assess nuclear organisation and function. Results: Compared with the other epitopes, AT8 was unique in showing dynamic nuclear localisation: absent in proliferating cells but present after differentiation, abundant in young neurons, and significantly reduced in aged and AD samples. Nuclear AT8 co-localised with Ki67, and its decline was associated with neuronal cell cycle re-entry and nucleolar disorganisation. Conclusions: Among multiple nuclear tau epitopes, AT8 was the only one displaying age- and disease-related changes, and its reduction during ageing and AD correlates with nuclear stress, aberrant cell cycle activity, and neuronal vulnerability. Loss of nuclear AT8 may therefore represent an early marker of dysfunction in ageing and AD brains. Full article

Postmortem diagnosis of sudden cardiac death (SCD) may escape detection due to the absence of thrombi and slow development of structural and immunohistochemical changes. Therefore, this study explores the possibility of analyzing relevant clinical chemistry biomarkers in myocardial homogenates and serum. Following an initial pilot study, myocardial samples from 113 autopsy cases were homogenized with distilled water, T-PER or 2 M urea. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK-MB), lactate dehydrogenase (LDH), orosomucoid and total protein were analyzed with an IndikoPlus and a subset was also analyzed with a Roche Cobas 8000 c701 analyzer, which also provided results for cardiac Troponin T, myoglobin and NT-proBNP. Although the yields varied with different extraction buffers depending on the analyte, distilled water was often as effective as T-PER and 2 M urea extraction for most analytes. Biomarker levels were consistently higher in the myocardial homogenates than in serum. Proteomic profiling on a subset confirmed higher concentrations of the cardiac markers in the tissue samples than in serum. Finally, we investigated whether selected markers could support the diagnosis of acute cardiac disease by classifying cases as sudden cardiac death (SCD) or controls. There was no significant difference in serum concentrations of the selected biomarkers between SCD cases and controls, whereas a significant loss of several markers was observed in SCD myocardial samples as compared to controls. Hence, our results suggest that analysis of tissue homogenates is likely better for detecting early ischemia, and we show that an in-house benchtop multi-analyzer can provide rapid results to assist the pathologist’s decision-making during autopsy. Full article

Starvation in horses presents critical welfare, economic, and management challenges with underlying molecular mechanisms of metabolic modification and recovery left poorly defined. Prolonged caloric deprivation induces significant systemic shifts in carbohydrate, protein, and lipid metabolism, reflected in coordinated changes in tissue-specific gene expression. This review synthesizes current knowledge on equine metabolic responses to starvation, emphasizing pathways found through RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction (RT-qPCR) studies. Molecular investigations using RNA-seq and RT-qPCR have provided insight into transcriptional reprogramming during starvation and subsequent refeeding. Shifts in gene expression reflect the metabolic transition from carbohydrate dependence to lipid use, suppression of anabolic signaling, and activation of proteolytic pathways. However, interpretation of these data requires caution, as factors such as post-mortem interval, tissue handling, and euthanasia methods particularly the use of sodium barbiturates can influence transcript stability and abundance, potentially confounding results. The literature shows that starvation-induced molecular changes are not uniform across tissues, with skeletal muscle, liver, and adipose tissue showing distinct transcriptional signatures and variable recovery patterns during refeeding. Cross-species comparisons with hibernation, caloric restriction, and cachexia models provide context for understanding these changes, though equine-specific studies remain limited. Identified gaps include the scarcity of longitudinal data, inconsistent tissue sampling protocols, and lack of standardized reference genes for transcriptomic analyses in horses. Addressing these limitations will improve the accuracy of molecular evaluations and enhance our ability to predict recovery trajectories. A more comprehensive understanding of systemic and tissue-specific responses to starvation will inform evidence-based rehabilitation strategies, reduce the risk of refeeding syndrome, and improve survival and welfare outcomes for affected horses. Full article

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive pest in tea plantations, leading to significant economic losses through defoliation. Existing control strategies, including chemical insecticides and biological agents, are often limited by environmental concerns, resistance, and variable efficacy. Recent evidence suggests that bacteria influence insect physiology and could be leveraged for pest management, but the postmortem microbial ecology of E. grisescens remains uncharacterized. In this study, we employed 16S rRNA sequencing to investigate temporal changes in the bacterial communities of E. grisescens cadavers at 0, 7, and 21 days following cryogenic mortality. Our results indicate a time-dependent decline in microbial diversity, while species richness initially increased before subsequent reduction. The dominant endosymbiont Wolbachia gradually diminished after host death, whereas Enterobacter remained abundant. Notably, non-dominant genera including Lysinibacillus and Sporosarcina exhibited a transient increase in abundance at day 7 before reverting to control levels by day 21. This study presents the first comprehensive analysis of postmortem microbial succession in a lepidopteran system, highlighting dynamic shifts in bacterial composition and offering potential avenues for microbiome-based pest management strategies. Full article

The adrenal glands are central to the stress response in cetaceans, yet their morphological and molecular changes under chronic stress remain poorly described. We investigated adrenal histology and protein composition in stranded common dolphins (Delphinus delphis) to assess whether post-mortem material can provide insights into stress physiology. Adrenal glands from 58 dolphins recovered along the Irish coast during a period of reported nutritional stress in the species were analyzed for adrenal mass, cortex-to-medulla (C:M) ratios, and cortical cell density. Additionally, two archival formalin-fixed, paraffin-embedded (FFPE) tissues were included in a pilot trial to assess the feasibility of protein extraction and mass spectrometry analysis. While adrenal mass did not differ significantly between stress types, chronically stressed dolphins exhibited significantly higher C:M ratios and cortical mass, consistent with cortical hypertrophy. Protein extraction from FFPE tissues was feasible, with the in-gel digestion method yielding more proteins (136) than the filter-aided sample preparation method (22). These findings demonstrate that histological and proteomic approaches can detect stress-related signatures in dolphins and highlight the potential of archival tissues for retrospective biomarker discovery. Full article

This work provides a comparison of two commercial carbon fiber reinforced plastic (CFRP) materials: HexPly^® M18 1/G939 and RTM6/G939. Differences due to the additional thermoplastic in one CFRP are investigated for the two otherwise nearly identical, aromatic epoxy-based composites with respect to thermal degradation. The scenario chosen for testing is based on real incidents of repeated overheating by hot gases between roughly 200 and 320 °C, leading to moderate thermal damage. A special test setup is designed to continuously and alternately load CFRP with hot air in a rapid change. Post-mortem analysis is performed by mass loss, ultrasonic, and mechanical testing. Polymer degradation is analyzed by infrared spectroscopy. Even if the temperature-resistant thermoplastic polyetherimide (PEI) in the M18-1 matrix is enriched between the plies and a compensation of thermal strain during rapid temperature changes is expected, only a weak improvement is observed for residual strength in the presence of PEI, for continuous as well as alternating thermal loading. Thermally induced delaminations are even more pronounced in M18-1/G939. Deep insight is gained into degradation after repeated overheating of CFRP within the chosen scenario. Multivariate data analyses based on infrared spectroscopy allow for the determination of thermal history and residual strength, valuable for failure analysis. Full article

Several genetic diseases affecting the human nervous system are incurable and insufficiently understood. Among them, nine rare diseases form the polyglutamine (polyQ) family: Huntington’s disease (HD), spinocerebellar ataxia types 1, 2, 3, 6, 7, and 17, dentatorubral pallidoluysian atrophy, and spinal and bulbar muscular atrophy. In most patients, these diseases progress over decades to cause severe movement incoordination and neurodegeneration. Although their inherited genes with tandem-repeat elongations and the encoded polyQ-containing proteins have been extensively studied, the neuronal-type-specific pathologies and their long pre-symptomatic latency await further investigations. However, recent advances in detecting the single-nucleus transcriptome, alongside the length of tandem repeats in HD post-mortem brains, have enabled the identification of very high CAG repeat sizes that trigger transcriptional dysregulation and cell death in specific projection neurons. One challenge is to better understand the complexity of movement coordination circuits, including the basal ganglia and cerebellum neurons, which are most vulnerable to the high CAG expansion in each disease. Another challenge is to detect dynamic changes in CAG repeat length and their effects in vulnerable neurons at single-cell resolution. This will offer a platform for identifying pathological events in vulnerable long projection neurons and developing targeted therapies for all tandem-repeat expansions affecting the CNS projection neurons. Full article

Background: The willingness to donate organs after death remains low in many populations, often due to informational and psychological barriers. This study assessed the impact of an educational lecture on knowledge and attitudes toward postmortem organ donation among university students in Kazakhstan. Methods: A total of 129 students completed a pre-lecture questionnaire on donation attitudes, knowledge, and barriers; 97 also completed the post-lecture assessment. Changes were analyzed using paired t-tests, repeated-measures ANOVA, and logistic regression. Participants were grouped by attitudinal changes to identify predictors of consent. Results: Knowledge about organ donation increased significantly after the lecture (p < 0.001), with larger gains among females and non-medical students. The number of participants who were willing to donate rose from 27 to 56 (p < 0.001). About 37% showed a positive shift, while 3% shifted toward refusal. In the initially ambivalent group (n = 49), female gender (AOR = 35.6), greater knowledge gain (AOR = 3.03), and lower perceived barriers (AOR = 0.05) predicted a change towards consent. Uncertainty about how to express consent was the only significantly differing barrier (p = 0.036). Conclusion: A brief educational lecture effectively increased knowledge and willingness to donate. Targeted information on procedural aspects may reduce indecision and promote informed donor registration. Full article

Background/Objectives: Epigenetics refers to heritable modifications in gene expression that do not involve changes to the DNA sequence. Among these, DNA methylation, histone modifications, and non-coding RNAs play a key role in regulating gene activity and are influenced by environmental factors, including exposure to psychoactive substances. In recent years, it has been hypothesized that such alterations may serve as molecular markers with forensic relevance. This systematic review aims to evaluate whether current evidence supports the use of drug-induced epigenetic changes as potential toxicological fingerprints in human subjects. Methods: A systematic literature search was conducted following PRISMA guidelines, including articles published on PubMed between 1 January, 2010, and 31 December, 2025. Only studies conducted on human samples and published in English were considered; animal studies and articles lacking epigenetic data were excluded. Results: Forty-two studies met the inclusion criteria. The most commonly investigated substances (alcohol, cocaine, methamphetamine, cannabis, and opioids) were found to induce specific and, in some cases, persistent epigenetic changes. These include alterations in CpG methylation in promoter regions, variations in miRNA expression, and modulation of epigenetic enzymes. Such changes were observed in brain tissue, blood cells, and semen, with evidence of persistence even after drug cessation. Conclusions: Current evidence confirms that psychoactive substance use is associated with specific epigenetic modifications. However, forensic application remains limited due to confounding factors such as age, co-exposures, and post-mortem interval. Further standardized research is necessary to validate their use as forensic biomarkers. Full article

Metals are essential for the physiological and biochemical processes in the human brain. However, their accumulation can cause neurotoxic effects, including the generation of reactive oxygen species and structural changes in biomolecules. This study aimed to assess the presence and distribution of metals in the human globus pallidus internus using Particle-Induced X-ray Emission (PIXE) and Scanning Electron Microscopy with Energy-Dispersive X-ray (SEM-EDX). Post-mortem brain tissue samples from six individuals without clinical neuropathological findings were analysed. PIXE analysis revealed the presence of Fe, Cr, Al, Zn, Pb, and Ca. SEM-EDX analysis provided the qualitative elemental composition of an observed aggregate, revealing C, N, O, Na, Ca, Al, Si, S, K, Mg, Cl, Fe, Ni, and Cr. Our findings suggest that metal accumulation in the brain can result from environmental pollution and protein aggregation, as well as biomineralisation processes that sequester metal ions to mitigate their harmful effects. A deeper understanding of these accumulation pathways could contribute to improved therapeutic strategies for neurological diseases associated with metal toxicity. Full article

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease affecting approximately 1 million people in the United States. Despite extensive research into the mechanisms of disease development, many aspects of the biological changes during MS progression and the varying symptoms among patients remain unclear. In the era of high-throughput sequencing, transcriptome databases are flooded with data. However, bulk RNA sequencing (RNA-seq) data are typically used only for differential gene expression analysis. Alternative splicing, a key process that alters the transcriptome, can also be identified from bulk data. Here, we accessed 11 studies with bulk RNA-seq data of postmortem MS patients’ brain samples via NCBI’s Gene Expression Omnibus (GEO). We extracted additional information from these data by identifying exclusively alternatively spliced genes via replicate multivariate analysis of transcript splicing (rMATS) analysis. Our analyses revealed that changes in RNA splicing mediate distinct biological signals compared to those driven by differential gene expression. Gene ontology and protein do-main analyses of genes exclusively regulated by alternative splicing revealed distinct molecular differences between progressive and relapsing–remitting MS as well as among lesions from different brain regions and between white and gray matter. These findings highlight the critical role of alternative splicing and its associated pathways in MS disease development and progression. Full article

Hydroxyethyl starch (HES) 130/0.4 is commonly used for volume replacement, yet its hepatic effects in the context of acute haemorrhage remain unclear. This study aimed to evaluate hepatic histopathological changes related to HES 130/0.4 administration when compared to Ringer’s lactate (RL) in healthy pigs subjected to acute bleeding under general anaesthesia. Eighteen pigs were randomised into three groups: RL (n = 6), HES 130/0.4 (n = 6), and a non-bleeding control (n = 6). Liver tissue was collected postmortem and analysed using haematoxylin–eosin staining, cytochrome c immunohistochemistry, the TUNEL assay, and M30 immunofluorescence. No statistically significant differences were observed in general histopathological changes, TUNEL, or cytochrome c expression (p > 0.050). However, the pigs that received HES 130/0.4 for volume replacement showed significantly higher intensity of the liver M30 immunostaining in the Q-score (p < 0.010), H-score (p < 0.010), and c indexc index (p < 0.050) when compared to animals that received Ringer’s lactate solution or animals in the control group. These findings suggest that HES 130/0.4 induces increased early hepatocellular apoptosis when compared to RL in this model, raising concerns about its hepatic safety profile under haemorrhagic conditions. Full article

Background: The phenomenon of pink teeth represents a notable observation in forensic science, although its interpretation remains complex and not directly attributable to a specific cause of death. Methods: This systematic review provides an updated and comprehensive overview of the morphological and histological mechanisms associated with this finding, with a focus on hemoglobin diffusion and pigment accumulation during putrefaction rather than on detailed biochemical pathways. Results: Environmental conditions, especially high humidity and moderate temperatures, are identified as key facilitators. The synthesis of the available evidence, including case reports, observational series, and experimental studies, confirms that pink discoloration is primarily linked to postmortem hemoglobin diffusion following erythrocyte breakdown and release of heme groups into dentinal structures. This process occurs more frequently under conditions that preserve hemoglobin and facilitate its migration into dental tissues. Importantly, pink teeth have been documented across a wide spectrum of postmortem scenarios, such as hanging, drowning, carbon monoxide poisoning, and prolonged exposure to humid environments, indicating that their presence is neither pathognomonic nor exclusively associated with a specific cause of death. Assessment methods include semi-quantitative visual scoring systems (e.g., SPTC and SPTR), spectrophotometric assays, and histochemical analyses for hemoglobin derivatives. Recent advances in digital forensics, particularly micro-computed tomography and artificial intelligence–based segmentation, may further support the objective evaluation of chromatic dental changes. Conclusions: This review underscores the need for standardized approaches to the identification, classification, and analysis, both qualitative and quantitative, of pink teeth in medico-legal practice. Although not diagnostic in isolation, their systematic study enhances our understanding of decomposition processes and contributes supplementary interpretive data in forensic investigations. Full article

Currently regulated per- and polyfluoroalkyl substances (PFAS) have been associated with immune, endocrine, and neurotoxicity following gestational exposures. As a result, industries have effectively replaced them with next-generation PFAS, including perfluorohexanoic acid (PFHxA). PFHxA is increasingly found in the serum of pregnant women and in breast milk, and adult human post-mortem studies indicate that PFHxA is found in the brain, with the highest concentrations in the cerebellum and hypothalamus. Despite evidence of gestational, lactational, and nervous system exposure to PFHxA, developmental neurotoxicity (DNT) testing in mammals has not been conducted. For DNT evaluation, we exposed pregnant C57Bl/6J mice daily from gestational day 0 through postnatal day (P) 21 to two PFHxA exposure levels (a lower (0.32 mg/kg of body weight (bw), or higher (50 mg/kg of bw) dose of PFHxA)) or ddH₂O using treat-based administration. Given the high PFHxA levels in the cerebellum in post-mortem studies and the cerebellum’s protracted developmental window, we assessed acute transcriptional dysregulation and cellular morphology in this brain region on the last day of exposure at P21. Using bulk-RNA sequencing, we found that PFHxA exposure had subtle effects on transcripts related to neurons and glia, with females having a greater number of dysregulated transcripts than males. Using immunohistochemistry, we found that Purkinje cell linear frequency was increased in specific lobules in the higher-exposure group and that microglial morphology underwent subtle changes in specific cerebellar layers in the lower-exposure group in both sexes. Together these data suggest that PFHxA exposure may have lobule-specific impacts on the development of both neurons and glia in the cerebellum, highlighting the importance of studying the neurotoxicity of PFHxA in both sexes. Full article