Canine Cognitive Dysfunction (CCD) is a naturally occurring neurodegenerative syndrome of aging dogs that shares important clinical, neuropathological, and molecular characteristics with Alzheimer’s disease. Consequently, domestic dogs have become one of the most informative comparative models for investigating mechanisms of human cognitive aging and neurodegeneration. Surprisingly, far less attention has been devoted to their closest living relative, the gray wolf (Canis lupus), despite the unique evolutionary perspective that this species offers. Here, we propose the hypothesis that domestication has modified the environmental determinants of neural resilience by altering the lifelong ecological conditions and patterns of ecological exposure experienced by the canine brain. Rather than suggesting that wolves are intrinsically protected against neurodegeneration, we propose that wolves and domestic dogs may follow different trajectories of brain aging because of long-term differences in physical activity, cognitive demands, social organization, metabolic regulation, and environmental predictability. Current evidence is indirect but biologically coherent. Nevertheless, converging observations from comparative neurobiology, veterinary neurology, environmental enrichment, cognitive reserve theory, and evolutionary medicine provide a biologically plausible framework for its formulation. We integrate these independent lines of evidence into a conceptual model linking domestication, lifelong environmental complexity, neural resilience, and cognitive aging. The hypothesis generates explicit and experimentally testable predictions involving comparative behavioral studies, neuropathology, biomarkers, neuroimaging, and One Health approaches. If supported, this framework would expand the current understanding of domestication beyond its recognized effects on morphology and behavior, identifying it as a potential evolutionary modifier of brain aging. Comparative investigation of wolves and domestic dogs may therefore provide novel insights into the mechanisms governing neural resilience and age-related neurodegeneration across mammalian species, including humans.
Temperature-sensitive auditory neuropathy (TSAN) is a rare and clinically distinct subtype of auditory neuropathy. TSAN is characterized by reversible deterioration of auditory neural function during hyperthermic states despite well-preserved cochlear outer hair cell activity. Although several case reports, familial studies, and experimental investigations have described this disorder, the available evidence remains inconclusive. This scoping review integrates clinical, genetic, and neurobiological evidence on TSAN, sheds light on its underlying mechanisms, and explores genotype-phenotype correlations. A comprehensive search of PubMed, PMC, Scopus, Web of Science, and Google Scholar was conducted up to December 2025. Studies reporting temperature-dependent auditory dysfunction consistent with TSAN were included regardless of their study design. Eligible publications comprised case reports, case series, familial cohorts, genetic studies, and mechanistic investigations. We narratively synthesized the extracted study data because of their methodological heterogeneity. Thirteen studies met the inclusion criteria and were grouped into clinical, genetic, and mechanistic studies. Clinically, TSAN is characterized by preserved otoacoustic emissions and/or cochlear microphonics with absent or severely abnormal auditory brainstem responses during hyperthermia. Hearing thresholds and speech perception typically deteriorate during febrile episodes and often improve following temperature normalization. Genetic evidence supports an autosomal recessive OTOF-related basis in reported TSAN cases, with temperature-sensitive phenotypes more frequently reported in genotypes containing certain non-truncating variants. Mechanistic evidence across molecular, synaptic, cortical, and translational levels supports a model of temperature-dependent presynaptic dysfunction, including impaired otoferlin-mediated synaptic vesicle release and altered neural synchrony. TSAN represents a temperature-dependent presynaptic synaptopathy in which thermal vulnerability of synaptic proteins, particularly otoferlin, may contribute to reversible neural dysfunction. Integration of clinical, genetic, and experimental data supports a coherent neurobiological framework with important consequences for diagnosis, genetic counseling, and translational auditory neuroscience.
Histological heterogeneity and complex imaging patterns make brain tumour diagnosis difficult. In order to make timely clinical decisions and plan personalised treatment, MRI multi-class brain tumour classification must be accurate. Expert evaluation in conventional image interpretation increases diagnostic burden and inter-observer variability. While current AI-based tumour classification methods have improved, learning discriminative spatial-contextual representations and giving clinically relevant model interpretability remain challenges. This article offers Convolutional Recurrent Attention Network (CRANet) for multi-class brain tumour classification using T1-weighted MRI data to overcome these issues. Convolutional Neural Networks (CNNs) extract hierarchical spatial features, Recurrent Neural Networks (RNNs) model contextual dependencies among deep feature representations, and a Channel-Spatial Attention Module emphasises diagnostically informative features during classification in the proposed architecture. Cross-validation evaluates generalisation performance, whereas noise reduction, intensity normalisation, and data augmentation improve data quality and model resilience. Experiments show that CRANet outperforms state-of-the-art deep learning methods in conventional diagnostic measures. Attention activation maps improve model transparency and clinician interpretation by visualising picture areas contributing to classification decisions, without localising tumours.
Following COVID, some individuals have developed Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We assessed whether a salivary biomarker of fatigue could identify young adults with ME/CFS following COVID. We examined the ratio of the concentrations of 2 peptide fragments in saliva, referred to as the Fatigue Biomarker Index (FBI), in participants from our study diagnosed with severe ME/CFS, moderate ME/CFS, and recovered controls. Participants classified with severe ME/CFS exhibited higher FBI values than participants with moderate ME/CFS and recovered controls. These findings are exploratory and require replication in larger, adequately powered studies.
Encephalitis can cause persistent motor, cognitive, behavioral, and participation restrictions. This narrative review synthesizes the available rehabilitation literature and develops a clinically oriented, phase-specific conceptual framework for post-encephalitis physical therapy. The framework supports individualized decision-making and future prospective validation; it is not presented as a validated clinical protocol. PubMed, Scopus, and Web of Science were searched for English-language publications from January 2010 to October 2025. Encephalitis concepts were combined with rehabilitation, physical therapy, motor recovery, functional outcome, gait, balance, and task-oriented training using AND and OR. Eligible clinical evidence comprised randomized and non-randomized studies, observational cohorts, case series, and case reports reporting motor or functional outcomes. Reviews and other publications were retained separately as contextual sources. We synthesized the evidence descriptively and used it to inform framework development. Eighteen clinical reports meeting the physical therapy-specific eligibility criteria and reporting measurable motor or functional outcomes were included in the descriptive clinical evidence set: 4 cohort studies, 4 case series, and 10 case reports. Five reports identified during full-text screening as primarily cognitive rehabilitation, dysphagia/swallowing rehabilitation, or general clinical-outcome reports without a sufficiently characterized physical therapy intervention were not included in the physical therapy evidence set. Reports without rehabilitation exposure, reports concerning encephalopathy rather than encephalitis, and conference abstracts were also excluded from the intervention evidence set. No randomized controlled trial specifically evaluating physical therapy after encephalitis was identified. We retained additional reviews and broader neurorehabilitation sources only for contextualization and framework development. Four studies provided sufficiently explicit admission-to-discharge data for a limited semi-quantitative summary; heterogeneity precluded pooling. The available evidence suggests that early, individualized, task-oriented physical therapy may contribute to motor and functional recovery after encephalitis when integrated within multidisciplinary rehabilitation. Because the evidence is heterogeneous and largely observational, the proposed framework should be regarded as hypothesis-generating and clinically informative rather than as evidence of established efficacy. Prospective studies are needed to evaluate its feasibility, safety, and effectiveness.
