Abstract: Neurostimulation and electrotherapy universally employ the rectangular waveform (square) as their standard stimulation signal. This article demonstrates that this choice constitutes a fundamental error of physical, mathematical, and neurophysiological nature, perpetuated since the mid-twentieth cen-tury through three converging factors: insufficient signal theory training in medical and paramedical curricula; technological drift toward ever-steeper wavefronts perceived as progress; and inadequate spectral disclosure by medical device manufacturers. We recall that the founders of electrical neu-rophysiology – Du Bois-Reymond (1843) and Helmholtz (1850) – stimulated with smooth-envelope signals, involuntarily close to membrane physiological requirements. We analyse the technological stratigraphy that progressively established the square wave as the unquestioned norm, and identify two erroneous assertions in the French foundational literature (Dumoulin & de Bisschop, 1987; Crépon, 1994) as crystallisation points of the error in clinical practice. We present spectral and energetic calcu-lations demonstrating the inadequacy of the rectangular signal relative to the biological bandwidth of the excitable membrane: for a 600 µs rectangular pulse at 50 Hz, Fourier harmonics extend to 81,650 Hz, wavefront components exceed 5 MHz, and the calculated peak power reaches 7.75 × 10⁸ W, versus 6.1 × 10⁵ W for the equivalent sinusoidal signal. We propose an optimal biomimetic signal described by a parametric Bézier curve whose inflexion points correspond to the conformational time constants of voltage-gated ion channels as described by the Hodgkin-Huxley model (1952). This zero-mean signal respects the natural opening and inactivation kinetics of sodium and potassium channels, concentrating its energy within the physiologically relevant bandwidth. The waveform is described as a scalable family parameterized by pulse duration τ, bounded within the physiologically valid range 200 µs ≲ τ ≲ 1000 µs, preserving full clinical adaptability. We analyse the electrode-tissue electrochemical interface, distinguishing faradaic from capacitive charge injection regimes, and demonstrate that the rectangular waveform systematically drives the interface into the faradaic regime, generating oxidative species and chronic peri-electrode inflammation. We present a comparative energetic analysis of three electrode-waveform configurations, showing that a high-capacitance elec-trode (CNT/aPDMS or TiN) combined with the Bézier waveform incurs only +61% in initial energy relative to the faradaic-rectangular reference, an overhead that remains stable over time, unlike the progressive energy escalation imposed by rectangular-induced fibrosis. We discuss the documented clinical consequences of the fundamental error: peri-electrode fibrosis in deep brain stimulation (DBS), progressive impedance drift in cardiac pacemakers and cochlear implants, and the relative inefficacy of consumer TENS devices. We conclude with a prospective section that addresses the concrete benefits this corrected approach offers to patients, clinicians, and manufacturers. This work is published open access under Creative Commons CC-BY 4.0. All parameters of the optimal signal are fully described herein, establishing permanent publication priority and excluding subsequent patent filing on this concept.

Abstract: Chemosensory systems exhibit remarkable plasticity that supports adaptive perception, learning, and behavioral responses to changing environmental and physiological conditions. Although synaptic mechanisms have traditionally been regarded as the principal basis of chemosensory plasticity, accumulating evidence indicates that this view is incomplete. This review synthesizes experimental findings showing that adaptive changes in chemosensory circuits arise through coordinated interactions across multiple biological levels. It examines how cortical feedback reshapes circuit dynamics and sensory representations, how astrocytes and microglia regulate the synaptic, metabolic, and inflammatory environments that constrain or enable plasticity, and how neural stem cell–mediated neurogenesis contributes structural remodeling across longer timescales. By integrating these mechanisms, the review proposes a multiscale coupling framework of chemosensory plasticity in which circuit-level modulation, glial regulation, and neurogenic remodeling function as interconnected rather than isolated processes. This perspective provides a more comprehensive account of how olfactory and broader chemosensory systems adapt to experience, internal state, and environmental change, and offers a conceptual basis for understanding how disruption of these coordinated mechanisms may contribute to chemosensory dysfunction in aging, neurodegenerative, metabolic, and post-viral conditions.

Abstract: Manual medicine has long outgrown explanations resting solely on structural-biomechanical correction. While the techniques reliably alleviate musculoskeletal pain and functional complaints, durable benefit appears to depend far less on lasting mechanical realignment than on a distributed set of neurophysiological, autonomic, interoceptive, and contextual processes. A persistent translational gap nevertheless remains between abstract predictive models of bodily regulation and the tangible regional tissue dynamics that clinicians encounter in practice. We propose PULSE-V (Predictive Updating of Local Somatic Errors via Vasomotion) as a hypothesis-generating framework intended to narrow that gap. The central suggestion is that low-frequency vasomotor oscillations (~0.1 Hz) within angiosomes, when exhibiting optimal fractal complexity and multiscale organisation, may serve as a candidate biophysical substrate capable of structuring ascending interoceptive signals. When this complexity is disrupted—shifting microvascular dynamics towards either rigid periodicity or stochastic noise—the resulting afferent stream may become ambiguous and contribute to interoceptive prediction error. Chronic somatic dysfunction can then be understood as a maladaptive attractor state: a self-stabilising loop in which ambiguous peripheral input, impaired sensory attenuation, and entrenched top-down priors reinforce one another. PULSE-V is offered as a deliberately falsifiable program rather than a settled theory. It generates testable predictions concerning regional vasomotor patterns, multimodal biomarker signatures, and the differential contributions of vasomotor, affective-touch, and relational treatment elements. If supported, the model would offer a mechanistically grounded account of the frequently observed discrepancy between the modest mechanical effects of manual intervention and the substantial clinical outcomes that follow.

Abstract: Neuroinflammation is increasingly recognized as a key modulator of therapeutic response and adverse events in Alzheimer’s disease (AD), especially during anti-amyloid-β (Aβ) monoclonal antibody (Aβ-mAb) treatment. We applied longitudinal translocator protein (TSPO) positron emission tomography (PET) to evaluate microglial activation in response to chronic Aβ-mAb therapy and its modulation by the PPAR-γ agonist pioglitazone. AppNL-G-F knock-in mice underwent TSPO-PET and Aβ-PET imaging at 5, 7.5, and 10 months of age across four treatment arms: placebo, Aβ-mAb, pioglitazone, and combination therapy. TSPO-PET detected early and progressive neuroinflammatory responses to Aβ-mAb that were attenuated by pioglitazone co-treatment. Both mono- and combination therapy modulated the temporal and spatial dynamics of the TSPO-PET signal. In addition, we derived a microglial desynchronization index from TSPO-PET connectivity, which captured individual neuroimmune responses and correlated with cognitive performance. Together, TSPO-PET and its regional synchronicity can quantify longitudinal, region-specific treatment effects, which may help to differentiate harmful from adaptive neuroinflammatory responses. These findings highlight the potential of TSPO-PET as a stratification biomarker to optimize therapeutic interventions. In summary, TSPO-PET enables in vivo tracking of treatment-associated neuroinflammatory responses during anti-Aβ immunotherapy and provides a non-invasive framework for evaluating combination strategies targeting amyloid pathology and immune regulation in AD.

Abstract: Background/Objectives: Longer lifetime exposure to endogenous estradiol (LEE2) has been associated with lower risk of age-related cognitive decline and dementia. Complementary to cognitive decline, behavioural and functional decline are also predictive of dementia risk; however, the association between LEE2 and these domains is underexplored. We investigated whether LEE2 is linked to later-life changes in behaviour and function. Methods: Baseline data from 1166 females enrolled in the CAN-PROTECT study were analyzed. LEE2 was estimated based on length of the reproductive period (menopause age - menarche age) plus years pregnant and scaled in 5-year increments. Objective cognition was measured using the CAN-PROTECT neuropsychological battery, while subjective cognition, behaviour, and function were measured using the Revised Everyday Cognition (ECog-II) scale, Mild Behavioral Impairment Checklist (MBI-C), and Standard Assessment of Global Everyday Activities (SAGEA) scale, respectively. Linear regressions modeled the association between LEE2 and neuropsychological performance. Three separate negative binomial regression models examined the association between LEE2 and ECog-II, MBI-C, and SAGEA total scores. All models adjusted for menopause hormone therapy ever use, menopause type, age, education, and ethnocultural background. Results: Each five-year increase in LEE2 was associated with lower MBI-C score (count ratio [CR]= 0.91, 95% CI [0.84, 0.98]) and lower SAGEA score (CR=0.91, 95% CI [0.86, 0.98]). LEE2 was not significantly associated with any objective or subjective cognitive measures. Conclusions: Longer LEE2 may confer protection against later-life behavioural and functional changes in older women.

Abstract: Delirium is a common and serious condition among neurological patients, and the overlap between delirium symptoms and neurological disorders complicates both diagnosis and management. Despite its clinical impact, guidance for delirium management in neurological settings remains limited. This qualitative study aimed to investigate healthcare professionals’ perceptions of delirium management in a Danish neurological hospital setting. Focus group interviews were conducted with five multidisciplinary healthcare professional groups. Maximum variation sampling was used to capture diverse perspectives, and 24 healthcare professionals from the same neurological department participated. Data were analyzed using reflexive thematic analysis. Three themes were identified: (1) delirium care practices in an acute neurological setting; (2) multidisciplinary collaboration in delirium care; and (3) responsibility for delirium care. The findings highlight challenges related to prioritization, mono-professional practices, and organizational structures that shape how responsibility for delirium management is understood and enacted. Overall, the study illustrates the complexity of delirium management within multidisciplinary neurological teams and suggests the need for context-sensitive approaches that support collaboration and clarify responsibilities in clinical practice.

Abstract: Background: Surface electromyography (sEMG) and movement analysis are increasingly applied to characterize neuromuscular impairments and guide rehabilitation after stroke. Objectives: To synthesize recent literature on the application of sEMG and movement analysis in adult stroke rehabilitation, identify trends and gaps, and discuss implications for clinical practice and future research. Methods: A non-systematic scoping search was performed across PubMed, Scopus, Web of Science, and Google Scholar using combinations of “Movement analysis”, “Gait analysis”, “Electromyography”, and “Stroke.” The first 100 relevant articles (determined by title and abstract relevance) reaching data saturation were included. Data were extracted into a comparative table with fields for study descriptors, outcomes, main results, and clinical implications. Results: Publications increased from the 1990s with a concentration around 2017. Rehabilitation journals accounted for the largest share, followed by neuroscience and engineering. Motion analysis dominated study aims (62%); experimental designs were predominant (82%). Only a minority of studies used sEMG as a primary outcome measure. Most research focused on chronic stroke and lower-limb gait, though a substantial portion addressed upper-limb function. Limitations included methodological heterogeneity, underrepresentation of acute/subacute phases, and limited use of randomized designs. Conclusions: sEMG and movement analysis offer complementary, clinically relevant insights for personalized post-stroke rehabilitation, but broader, standardized adoption—particularly in acute/subacute settings and as routine outcome measures—is needed to translate advances into improved patient care.

Abstract: Fatigue is a frequent, disabling and difficult to treat symptom of multiple sclerosis (MS). Low grade inflammation and energetic dysfunction have been proposed as mechanisms underlying the pathogenesis of this symptom. Owing to its anti-inflammatory and metabolic properties, there is a rational for ketogenic diet (KD) application in this setting. We conducted a single arm open label interventional study on a strictly selected group of 16 non-obese patients with multiple sclerosis who were prescribed KD for three months. With respect to baseline, at 3 months we observed a significant reduction of fatigue severity scale (5.18 ± 1.02 vs. 4.16 ± 0.98; p = 0.042), Epworth Sleepiness Scale (5.64 ± 2.46 vs. 8.46 ± 3.05; p < 0.001), Pittsburgh Sleep Quality Index (5.64 ± 3.53 vs. 7.62 ± 2.59; p = 0.009), Depression Anxiety Stress Scales-21 depression (3.18 ± 2.93 vs. 6.15 ± 3.81; p = 0.036) and anxiety (5.15 ± 4.10 vs. 1.55 ± 1.92; p = 0.019) sub-scales, and an improvement in energy sub-scale of Multiple Sclerosis Quality of Life-54 (52.49 ± 12.83 vs. 37.43 ± 14.26; p = 0.042). These findings suggest that KD might be useful for the treatment of fatigue and they raise the interest for the use of KD in the treatment of other symptoms frequently encountered in multiple sclerosis.

Abstract: Background: Temporomandibular disorders (TMD) exhibit a marked female predominance, suggesting a potential role for estrogen in their pathophysiology. However, the evidence linking estrogen status to TMD risk and symptom severity remains inconsistent across studies. Objective: To systematically review and synthesize the available evidence on the association between estrogen status—including hormonal contraceptive use, menopausal status, menstrual cycle variation, pregnancy, and estrogen receptor gene polymorphisms—and the prevalence and clinical features of TMD in women. Methods: A comprehensive search of PubMed, Embase, Scopus, Web of Science, and Google Scholar was conducted through September 2025. Observational studies involving women diagnosed with TMD using validated diagnostic criteria (RDC/TMD, DC/TMD, or equivalent) and reporting estrogen-related exposures were included. Two independent reviewers conducted study selection, data extraction, and risk-of-bias assessment using the Newcastle-Ottawa Scale (NOS). Due to heterogeneity in exposure definitions and outcome measures, a narrative synthesis was performed. Meta-analysis was not conducted due to insufficient homogeneity across studies. Results: Seven studies met the inclusion criteria, comprising six clinical studies involving 2,735 participants and one mechanistic supportive study involving 18 participants. Two high-quality clinical studies—a prospective cohort and a cross-sectional study—reported quantitative effect estimates: hormonal contraceptive use was associated with an increased risk of first-onset TMD (OR 1.37, 95% CI 1.13–1.66) and concurrent TMD symptoms (OR 1.20, 95% CI 1.06–1.35), while climacteric status was associated with increased odds of TMJ palpation pain (OR 2.64, 95% CI 1.12–6.21), crepitus (OR 2.92, 95% CI 1.13–7.56), and degenerative joint disease (OR 2.27, 95% CI 1.05–4.91). Additional moderate-quality studies provided qualitative evidence supporting associations between menopausal status and TMD prevalence, menstrual cycle–related symptom variation, pregnancy-related symptom modulation, and estrogen receptor gene polymorphisms with TMD susceptibility. According to GRADE criteria, the certainty of evidence was rated as moderate for hormonal contraceptive use and menopausal/climacteric status, and low to very low for the remaining exposure categories due to inconsistency, indirectness, and imprecision. Conclusions: Current evidence suggests that hormonal factors, particularly hormonal contraceptive use and menopausal status, are associated with TMD risk and symptom presentation. However, the limited number of high-quality studies, heterogeneity in exposure definitions, and variability in diagnostic criteria constrain definitive conclusions. Further well-designed prospective cohort studies with standardized diagnostic protocols and biochemically validated hormonal assessments are needed to clarify causal relationships and inform clinical decision-making.

Abstract: Pediatric brain tumours are highly prevalent and remain one of the leading causes of cancer-related deaths in children. There are numerous different brain tumour types that are now well characterized by magnetic resonance imaging (MRI), patient clinical course, neuropathological and molecular genetic alterations. One of the challenges with treating pediatric brain tumours with systemic chemotherapy is the inability of several chemotherapeutic agents to cross the blood brain barrier (BBB) which serves as a protective mechanism for neuronal homeostasis. The BBB is primarily comprised of microvascular endothelial tight junctions. Controlling BBB permeability to allow for therapeutics to cross and combat brain tumors is now possible using MR-guided Focused Ultrasound (MRgFUS). In this approach, microbubbles are administered intra-venously prior to MRgFUS BBB disruption at the targeted tumour site in the brain. In the presence of MRgFUS, the microbubbles in the brain capillaries oscillate, and temporarily disrupt the BBB enabling systemically administered chemotherapy drugs to cross at the targeted site. In this review, we provide evidence supporting the use of MRgFUS BBB disruption to treat brain tumours in animal models, and in on-going human clinical drug trials. We conclude with efforts to harness the potency of the immune system using MRgFUS against pediatric brain tumours.

Abstract: Background: Age-related hearing loss (HL) is a significant independent risk factor for Alzheimer's disease (AD), yet the molecular mechanisms underlying this comorbidity and the comparative efficacy of hearing interventions on cognitive outcomes remain unclear. This study aims to integrate clinical evidence and molecular data to address these gaps. Objective:To conduct a systematic review and network meta-analysis (NMA) to: 1) compare the effects of hearing interventions on cognitive function in AD patients; 2) identify and rank key microRNAs (miRNAs) associated with AD-HL comorbidity; 3) explore heterogeneity sources; and 4) cross-validate findings with independent clinical sequencing data. Methods: We systematically searched PubMed, Web of Science, Embase, and Cochrane Library up to May 2025. Included studies involved AD patients with/without HL, re-porting cognitive scores (MoCA, MMSE, AVLT) or miRNA expression data. A NMA was performed to rank interventions (cochlear implants-CI, hearing aids-HA, no in-tervention-NI) and miRNAs using surface under the cumulative ranking (SUCRA) curves. Heterogeneity was assessed via subgroup analysis and meta-regression. Pooled miRNA expression results were cross-validated against an independent clinical se-quencing dataset (LC-P20240110033, n=16) using intraclass correlation coefficient (ICC) and Bland-Altman plots. Results: Twelve studies (2,137 patients) were included. HL was significantly associated with worse cognitive function (MoCA: SMD = -0.82, 95% CI: -1.15 to -0.49; AVLT delayed recall: SMD = -1.12, 95% CI: -1.56 to -0.68). NMA revealed CI (SUCRA=0.89) was superior to HA (SUCRA=0.62) and NI (SUCRA=0.09) for preserving MoCA scores. Among nine differentially expressed miRNAs, hsa-miR-6875-5p was the most consistent biomarker (pooled FC = 1.52, 95% CI: 1.04–2.23), showing excellent agreement with sequencing data (FC = 3.29; ICC = 0.82, 95% CI: 0.67–0.91). Heterogeneity was significantly influenced by miRNA detection platform (p=0.04) and HL severity (p=0.03).Conclusion: This study demonstrates that HL exacerbates cognitive decline in AD in a dose-dependent manner. Cochlear implants may offer superior cognitive protection compared to hearing aids. The consistently dysregulated hsa-miR-6875-5p emerges as a promising cross-modal biomarker, bridging clinical observation and molecular pathology in AD-HL comor-bidity.

Abstract: A PIEZO2 variant was shown recently to protect against Alzheimer’s disease in the Hispanic population. This analysis implicates the potentially critical role of Piezo2 in Alzheimer’s disease pathophysiology. Another recent research mimicked acquired Piezo1 channelopathy by PIEZO1 manipulation. This study also showed that phosphatidylinositol 4,5-bisphosphate (PIP2) administration ameliorated brain capillary endothelial Piezo1 channelopathy in a mouse model of Alzheimer’s disease. However, the initiating microdamage is suggested to be in the prefrontal cortex further upstream of pathophysiology, namely an irreversible Piezo2 channelopathy of glutamatergic terminals that should fine modulate oxytocin release along stressful ultradian events. Implication of Piezo2 in the defensive arousal response reveals an underlying body-wide Piezo2 system of which the proposed prefrontal Piezo2 channelopathy posits a critical locus. PIP2 is emerging as a potential treatment method of Piezo channelopathy in Alzheimer’s disease, however the challenge remains how it could be administered more precisely to affected brain areas.

Abstract: Low-dose radiation (LDR) has emerged as a promising therapeutic modality for Alzheimer’s Disease (AD). Although different irradiation protocols have been explored, the optimal parameters for maximizing therapeutic efficacy remain unclear. Radiation energy has been shown to influence radiobiological responses, with more pronounced effects at lower energy ranges. We therefore investigated whether kilovoltage LDR (KLDR) provides superior therapeutic efficacy compared with megavoltage LDR (MLDR) in an AD mouse model (3xTg-AD). To this end, we directly compared the efficacy of MLDR and KLDR in AD mice to identify an optimal irradiation strategy for LDR treatment with potential relevance to clinical translation in AD. X-rays with 110-kV or 6-MV energy were applied to the brain of early-stage AD mice (3xTg-AD, 26-28 weeks age) (0.6 Gy × 5 fractions for 2.5 weeks). After LDR treatment, cognitive function was assessed in AD mice using passive avoidance (PA) test and novel object recognition (NOR) test. In addition, different molecular markers associated with inflammation, amyloid-beta (Aβ) plaques, tau burden, and neuronal and synaptic degeneration, were analyzed in the brain of AD mice. KLDR (110 kV) significantly inhibited cognitive decline in AD mice, as demonstrated by both the PA and NOR tests. In addition, KLDR significantly reduced hippocampal levels of GFAP, Iba-1, and pro-inflammatory cytokines (TNF-α and IL-1β), along with marked decreases in Aβ and tau levels. Furthermore, the expression levels of Aβ40 and Aβ42 were quantified by ELISA following KLDR and MLDR treatment, revealing a statistically significant reduction in the KLDR group. The degeneration of neurons and synapses was significantly suppressed also at the kilovoltage energy level. Conversely, MLDR (6 MV) exerted minimal effects and did not produce statistically significant improvements. Taken together, our findings demonstrate that radiation energy level is a key determinant of LDR therapeutic efficacy in AD mice, with KLDR showing significantly greater effectiveness in improving AD-related pathological features than MLDR. Therefore, KLDR may be recommended as a novel radiation protocol for AD treatment.

Abstract: Neuroinflammation has emerged as a central mechanism in the pathogenesis of epilepsy, particularly in drug-resistant epilepsy (DRE), where conventional antiseizure medications fail to achieve adequate control. Accumulating evidence indicates that inflammatory processes within the central nervous system contribute not only to seizure initiation but also to their perpetuation and pharmacoresistance. Among the key cellular mediators that play a pivotal role in neuroinflammation is microglia, which are the resident immune cells of the brain. In response to neuronal injury, infection, or recurrent seizures, microglia undergo activation and adopt diverse phenotypes ranging from pro-inflammatory to neuroprotective states. However, sustained or dysregulated microglial activation promotes the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species, thereby exacerbating neuronal hyperexcitability, disrupting synaptic function, and facilitating epileptogenesis. Recent researches have increasingly focused on targeting microglial activation as a therapeutic strategy in DRE. Preclinical and clinical studies have explored a range of anti-inflammatory interventions, including cytokine inhibitors, modulators of microglial signaling pathways such as Toll-like receptor and NF-κB pathways, and repurposed agents like minocycline and corticosteroids. Additionally, emerging therapies aimed at selectively modulating microglial phenotypes, shifting from pro-inflammatory to neuroprotective states, offer promising avenues for intervention. Despite these advances, challenges remain in translating these strategies into routine clinical practice, including issues of specificity, timing of intervention, and potential systemic side effects. Therapeutically, targeting microglial activation holds significant promise for addressing the unmet needs in DRE by not only reducing seizure frequency but also potentially modifying disease progression. A deeper understanding of microglial biology and its interaction with neuronal networks may facilitate the development of precision therapies tailored to inflammatory profiles in epilepsy. This review highlights the evolving landscape of microglia-targeted therapies and underscores their potential as a novel and complementary approach in the management of drug-resistant epilepsy.

Abstract: Background: The Testamentary Capacity Assessment Tool (ΤCAT) is a brief instrument with good psychometric properties, specifically designed for the assessment of testamentary capacity (TC) in individuals with dementia. It assesses memory, perception of financial matters and judgment, as well as cognitive functions, such as theory of mind, not measured by other traditional tools. Additionally, it does not require collateral sources of financial information. Aim of the present study was to provide an updated report on the use of the TCAT in research and systematic review studies. Methods: This narrative review includes studies that have used the TCAT for clinical use, validation in different culture, and comparison with the two other specialized TC assessment tools. The Pubmed database was searched using the keyword “Testamentary Capacity Assessment Tool”. Results: The TCAT has been validated in healthy Italian population and was found to be a useful adjunct instrument for TC assessment in older adults. Another study demonstrated its clinical utility in patients with acute ischemic stroke. A systematic review compared the TCAT to the other two existing specialized TC assessment tools, namely the Testamentary Capacity Instrument (TCI) and the Testamentary Definition Statement (TDS) and highlighted the superiority of the TCAT in clinical practice. Conclusions: TCAT is a useful, specialized screening tool that is easily applicable in clinical practice by both experts and non-experts. Further studies are recommended across different cultures, in both healthy and cognitively impaired adults, to support its standardized use in forensic and clinical settings.

Abstract: The DMD gene is well known for its product dystrophin, a large rod-shaped protein that plays a critical role in muscular membrane strength and integrity. Mutations affecting dystrophin lead to Duchenne muscular dystrophy, a fatal X-linked disease characterized by muscular weakness and breakdown. In addition to the full-length dystrophin product that is most often associated with disease, the DMD gene also encodes for multiple shorter isoforms of dystrophin with diverse functions. One isoform in particular, Dp71, has been increasingly found to play a wide variety of roles throughout the body. In this review, we consolidate the numerous studies on Dp71 to provide a comprehensive foundation for future work. We outline and summarize the current state of knowledge on the role of Dp71 in the brain, the retina, and skeletal muscles. We also explore Dp71-based therapies currently being tested in the pre-clinical landscape.

Abstract: Background: We investigated whether combining sural nerve sensory conduction study (s-SCS) and tibial nerve SEPs (t-SEPs) improves diagnostic accuracy for peripheral sensory neuropathy. Methods: We retrospectively reviewed 74 consecutive cases (114 lower limbs) of patients suspected of having neuropathy or radiculoneuropathy who underwent s-SCS and t-SEPs between July 2021 and December 2024. Abnormal s-SCS was defined as an amplitude <3.8 µV or a conduction velocity <39.3 m/s. Abnormal t-SEPs were defined as the failure to evoke N20, N20 latency >24.37 ms, the failure to evoke P37, or P37 latency >44.35 ms. Results: No cases showed s-SCS abnormalities with normal t-SEPs. Group 1 (G1) had normal s-SCS and normal t-SEPs, which were observed in 31 limbs (27.2%). Group 2 (G2) had normal s-SCSs and abnormal t-SEPs, which were found in 45 limbs (39.5%). Subgroups of G2 included normal N20 with abnormal P37, abnormal N20 with normal P37 and N20/P37 abnormalities. Group 3 (G3) had abnormal s-SCSs with abnormal t-SEPs, which was seen in 38 limbs (33.3%). Conclusions: Electrophysiological testing reveals normal distal and proximal sensory nerves in G1, suggesting preserved sensory nerve function. The distal sensory nerves are normal in G2. However, abnormal N20/P37 and abnormal N20 with nP37 indicate proximal sensory nerve involvement. Normal N20 with abnormal P37 indicates posterior column dysfunction. In G3, both the distal and proximal sensory nerve segments are abnormal. Therefore, adding t-SEPs to s-SCSs allows us to evaluate the full length of the peripheral nerves, which is useful for diagnosis and assessing treatment efficacy.

Abstract: Background: Post-stroke cognitive impairment (PSCI) is a common complication affecting a substantial proportion of stroke survivors and is associated with reduced functional independence, poorer rehabilitation outcomes, and increased caregiver burden. Early identification of patients at risk remains challenging. Neurofilament Light Chain (NfL), a marker of neuroaxonal injury, has emerged as a potential blood-based biomarker in neurological disorders.Objective: To systematically evaluate prospective evidence on NfL as a predictor of cognitive impairment following ischemic or hemorrhagic stroke.Methods: A systematic review was conducted in accordance with PRISMA Guidelines. PubMed, Cochrane Library, and ScienceDirect were searched for prospective cohort studies assessing plasma or serum NfL levels and subsequent cognitive outcomes in adult stroke patients. Eligible studies evaluated cognitive outcomes using validated assessment tools during follow-up. Due to methodological heterogeneity across studies, findings were synthesized narratively due to methodological heterogeneity.Results: Seven prospective cohort studies involving 2,907 stroke patients were included. Most studies measured NfL within 24-48 hours after stroke onset and assessed cognitive outcomes between 3 and 12 months. Across studies, elevated baseline NfL levels were consistently associated with an increased risk of PSCI and lower cognitive scores. In multivariable analyses, NfL remained independently predictive after adjustment for age, stroke severity, and infarct volume. Reported discriminative performance ranged from AUC 0.672 to 0.865, indicating moderate to good predictive ability.Conclusion: Blood-based NfL measurement is consistently associated with post-stroke cognitive impairment. These findings support circulating Nfl as a promising biomarker for early risk stratification of PSCI in stroke survivors.

Abstract: Interdisciplinary research is needed on the biomechanical and structural pathways that might explain why people with connective tissue disorders like hypermobile Ehlers-Danlos Syndrome (hEDS) are particularly susceptible to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and ME/CFS-like presentations of Long COVID. In particular, research is needed on the role that disordered fascia and lymphatic system dysfunction might play in the pathophysiology of ME/CFS and Long COVID. Research is also needed on the role that spinal conditions like craniocervical instability and Chiari Malformation might play in obstructing outflow from the glymphatic system.

Abstract: The review explores the development of non-implantable vestibular devices designed to address postural instability, particularly in aging populations and patients with vestibular hypofunction. It establishes that balance relies on complex sensory integration and that the functional decline of this system creates a significant medical need. Three principal technological strategies are examined: sensory substitution devices, galvanic vestibular stimulation (GVS), and immersive visual feedback systems. Sensory substitution devices, which convert balance data into auditory, tactile, or electrotactile cues, demonstrate significant promise. Examples like vibrotactile belts provide feedback that reduces postural sway, enhancing stability and patient confidence. Parallel to this, GVS—using electrical currents applied to the mastoids—emerges as a potent non-invasive method to modulate vestibular pathways, improving balance control and even inducing neuroplastic changes, especially with stochastic “noisy” signals. Most recently develop devices include augmented and virtual reality technologies offer innovative visual feedback, creating enriched rehabilitation environments that accelerate recovery by promoting sensory reweighting and neural adaptation. The review concludes that while implantable prostheses are advancing, non-invasive devices offer versatile, affordable and complementary solutions for balance restoration. Future success of non-invasive alternatives hinges on developing more sophisticated stimulation protocols that account for the complexity of natural movement and individual patient contexts, ultimately expanding therapeutic options for vestibular disorders.