Neurological intractable diseases are progressive, and as the disease advances, symptoms can include not only motor impairments but also autonomic nervous system disorders and higher brain dysfunction, with a wide range of pathologies. Patients face a variety of difficulties in daily life, and various issues were identified even in a survey targeting home care support service provider that create care plans on-site. The role of rehabilitation is to provide a stable home life and to maintain ADL (activities of daily living) and QOL (quality of life), which are crucial points. In home settings, there are issues such as staff lacking knowledge of rehabilitation for intractable diseases, not knowing which rehabilitation content is more appropriate, a shortage of human resources for rehabilitation, and insufficient teamwork. Consideration is being given to creating rehabilitation pamphlets to assist in rehabilitation guidance. Additionally, there have been reports on the development of rehabilitation using new devices [external stimulation, VR (virtual reality), tDCS (transcranial direct current stimulation)], indicating progress in clinical research.

Non-seizure issues (NSIs), including cognition, behavior/psychiatric symptoms, adaptive and social functioning, sleep, autonomic, and motor impairments, often shape day-to-day outcomes in Lennox-Gastaut syndrome (LGS) more than seizures, yet clinicians lack LGS-specific, feasible assessment pathways. An expert panel synthesized evidence and clinical experience to propose a lifespan, clinic-ready framework that pairs clinician-administered measures with caregiver/teacher reports and uses brief global impressions from both clinicians and caregivers to detect meaningful change. The framework emphasizes continuous, structured conversations about NSIs at every visit, with standardized tools deployed less frequently in line with the properties of instrument re-administration and local resources. As a pragmatic guide, behavior/sleep are typically reviewed every 6-12 months, and cognition/adaptive skills are reviewed annually. Rather than prescribing a universal "minimum battery" the approach prioritizes personalization to developmental stage, comorbidities, disability level, and family context. The Discussion also integrates therapeutic considerations: Early data suggest fenfluramine and cannabidiol may benefit alertness, behavior, sleep, and communication beyond seizure reduction, while acknowledging that LGS-specific evidence remains preliminary. Key gaps include the limited validation of instruments in LGS, the scarcity of adult-focused measures (e.g., biopsychosocial frailty), and tools that are insufficiently sensitive to small but meaningful changes. We outline a research agenda for co-designed clinical outcome assessments that combine quantitative scales with qualitative insights from patients, caregivers, and teachers. Centering NSIs and feasible follow-up, this work offers a practical route to move LGS care beyond seizure counts toward participation, resilience, and quality of life for patients and families. PLAIN LANGUAGE SUMMARY: People with Lennox-Gastaut syndrome often struggle with problems beyond seizures, such as learning, behavior, sleep, movement, and daily living skills. These non-seizure issues can affect quality of life even more than seizure counts. We propose a practical, clinic-ready approach to check these issues across all ages using brief clinician assessments plus caregiver and teacher input. Regular conversations at each visit, with targeted questionnaires every 6-12 months or yearly, can help detect meaningful changes and guide care.

Sexual dysfunction (SD) is a prevalent but frequently overlooked complication of Type 2 Diabetes Mellitus, with a particularly high burden in South Asia, a region experiencing a rapid rise in diabetes prevalence. Despite its significant effects on quality of life, interpersonal relationships, and psychological well-being, SD is often insufficiently addressed in routine clinical care. This gap is largely influenced by sociocultural barriers, limited openness in patient-physician communication, and inadequate access to specialized services. In men, erectile dysfunction (ED) represents the most common clinical manifestation and may occur before overt cardiovascular disease, reflecting underlying endothelial and vascular abnormalities. In contrast, sexual dysfunction in women is more heterogeneous, encompassing reduced sexual desire, impaired lubrication, difficulty achieving orgasm, and pain during intercourse. These issues often carry profound personal and relational implications within South Asian sociocultural settings. The underlying mechanisms are complex and multifaceted, involving vascular compromise, autonomic neuropathy, hormonal imbalance, as well as psychological and sociocultural influences. Comprehensive evaluation includes the use of validated assessment instruments, focused clinical examination, and appropriate laboratory investigations. Management requires a holistic and culturally appropriate strategy, integrating optimal glycaemic control, management of cardiovascular risk factors, psychosocial support, and involvement of partners when appropriate. In addition, condition-specific pharmacological and non-pharmacological interventions should be tailored to individual needs. This review consolidates current evidence with an emphasis on the South Asian context, identifies significant gaps in regional and gender-specific data, and explores the potential implications of emerging glucose-lowering therapies on sexual health outcomes.

Ischemic stroke frequently results in sympathetic overactivity and blood pressure dysregulation, primarily due to impaired central autonomic regulation within the rostral ventrolateral medulla (RVLM) in the brainstem. However, the molecular mechanisms underlying this dysfunction remain insufficiently defined. In this study, we examined the regulatory interplay between the renin-angiotensin system (RAS), autophagy, and iron metabolism in the RVLM in a transient middle cerebral artery occlusion model (MCAO) of ischemic stroke in Sprague-Dawley rats. Our results revealed that stroke induced an imbalance in RAS pressor and depressor signaling, disrupted autophagic flux, and altered iron storage protein expression. These molecular abnormalities were accompanied by elevated blood pressure and suggest a mechanistic link to sympathetic dysregulation. Notably, transcranial direct current stimulation (tDCS) mitigated these stroke-induced abnormalities by downregulating RAS pressor signaling, restoring impaired autophagic activity-including autophagic ferritin degradation-and consequently reducing iron accumulation-associated oxidative stress in the RVLM. Collectively, our findings propose a putative molecular cascade contributing to post-stroke sympathetic overactivity and highlight non-invasive tDCS as a potential neuromodulatory intervention to restore neurochemical homeostasis in the RVLM.

Hearts change their wall thickness (concentric growth) and chamber size (eccentric growth) as they adapt to circulatory demands and the intrinsic function of their contractile cells. Factors associated with wall thickening include variants of sarcomeric proteins that enhance contractility, mitochondrial dysfunction, and hypertension. Chambers can dilate due to many factors including sarcomeric variants that depress contractility and aortic and / or mitral valve insufficiency. Despite intensive study, the mechanisms that regulate cardiac growth remain unclear. It is also uncertain whether inherited variants induce growth via the same mechanisms as more common clinical pathologies, such as hypertension. Here we show that computer simulations of a beating left ventricle reproduce both variant and non-variant-related growth patterns when myocytes grow concentrically to regulate intracellular ATP concentration and eccentrically to maintain titin-based intracellular stress. The simulations support the hypothesis that cardiac growth reflects homeostatic feedback through three interacting systems whereby myocytes add or remove mitochondria and sarcomeres (1) in parallel to match ATP generation to myocardial energy demand, and (2) in series to regulate passive tension, while (3) the autonomic nervous system regulates cardiac power, and thus myocardial ATPase, via baroreflex control. The new framework provides a mechanistic basis for the patterns of eccentric and concentric growth induced by a wide range of clinically-relevant conditions and could facilitate in silico testing of potential therapies for cardiac disease.

Sexual dysfunction is a common but insufficiently addressed non-motor symptom in movement disorders. While Parkinson's disease (PD) is the condition most frequently investigated, sexual dysfunction is also reported in Huntington's disease, dystonia, and other movement disorders. Clinical presentations are heterogeneous, encompassing reduced desire, erectile dysfunction, ejaculatory and orgasmic disorders, lubrication difficulties, dyspareunia, and hypersexuality. In PD, prevalence estimates vary widely across studies, largely because of differences in disease stage, cultural context, and assessment methodology. The most consistent associated factors include depression, anxiety, age, autonomic dysfunction, and motor disability. Dopaminergic treatment has a bidirectional influence, with potential benefit on hypoactive sexual symptoms but an increased risk of hypersexuality, especially with dopamine agonists. Evidence for treatment remains limited, with the strongest support for phosphodiesterase-5 inhibitors in erectile dysfunction and dopaminergic treatment adjustment in hypersexuality. Sexual dysfunction remains underrecognized in routine practice despite its major impact on quality of life and intimate relationships. Routine screening and multidisciplinary management should be encouraged in the care of patients with movement disorders.

Taurine is the most abundant free amino acid in heart and is important in tissue volume regulation. β-alanine, a common dietary amino acid, decreases cardiac taurine flux in fish and negatively impacts their responses to stress. Brook char (Salvelinus fontinalis) fed a β-alanine enriched diet to induce taurine deficiency (TD) have lower heart rates and less pronounced decreases in heart rate (bradycardia) under hypoxia, but impacts on blood flow in vivo have not been examined. We aimed to determine if changes in taurine flux constrain cardiac output under hypoxia and to characterize the role of autonomic control in this response. We measured rates of oxygen consumption (ṀO2) and cardiorespiratory parameters in brook char acutely exposed to hypoxia (partial pressure of oxygen of 8.33 kPa). Resting heart rate and the magnitude of the bradycardia were lower in TD fish, as was the effect of hypoxia on ṀO2. Diet did not influence stroke volume, but cardiac output was consistently lower in TD brook char. Heart rate variability was higher in TD fish due to subtle changes in cholinergic and adrenergic tones on the heart. A lack of lactate accumulation indicated that the hypoxic stress was insufficient to challenge fluid volume regulation, but resting heart function and its response to hypoxia were still altered by dietary β-alanine. The influence of diet on cardiorespiratory function is poorly understood in fish and the nutritional landscape of aquatic ecosystems is changing; our results illustrate potential mechanisms by which diet can impact stress tolerance in fish.

Postural stability reflects the integrated function of autonomic, neuromuscular, and postural control systems and deteriorates with aging and reduced physical activity. Although electrocardiography(ECG), electromyography(EMG), and center of pressure(COP) measures have each been used to characterize functional changes, their relative measurement sensitivity across different task conditions remains insufficiently understood when multiple physiological modalities are evaluated within the same cohort. This study compared the relative measurement sensitivity of ECG-, EMG-, and COP-derived physiological features for signal-based assessment of postural stability across static and dynamic task conditions. A total of 110 women were classified into young(YG, n=30), active older(AOG, n=57), and non-active older(NOG, n=23) groups. Resting ECG, grip-force EMG during maximal voluntary contractions, and COP signals during side-by-side stance, semitandem stance, and the five-times sit-to-stand(FTSS) task were collected. Time-and frequency-domain features were extracted from each modality. Group differences were evaluated using statistical analyses. Machine-learning models were employed as analytical tools to quantify the relative measurement sensitivity of modality-and task-specific feature sets, rather than as diagnostic classifiers. Physiological features derived from all three modalities demonstrated significant group-related differences(p < 0.001). COP-derived features exhibited pronounced task dependency, with substantially greater sensitivity during the dynamic FTSS task compared with static stance conditions. When measurement sensitivity was quantified using machinelearning-based discriminative capacity, COP features obtained during FTSS showed the highest sensitivity, followed by COP features during semi-tandem stance, ECG-derived HRV features, and EMG frequency-domain features.The measurement sensitivity of signal-based postural stability assessment is strongly influenced by both physiological signal selection and task design. COP-derived features, particularly those obtained during dynamic functional tasks such as FTSS, provide the highest sensitivity to functional variation, while ECG-and EMG-derived features offer complementary information on autonomic and neuromuscular contributions. These findings support a measurement-oriented framework for selecting appropriate physiological signals and task conditions for quantitative postural stability assessment in aging populations.