Exploring How Antibody Format Drives Clearance from the Brain.

Monoclonal antibodies (mAbs) have high binding specificity and affinity, making them attractive for treating brain diseases. However, their effectiveness is limited by poor blood-brain barrier (BBB) penetration and rapid central nervous system (CNS) clearance. Our group identified blood-brain barrier modulator (BBBM) peptides that improved mAb penetration across the BBB into the brain. In this study, we investigated the pharmacokinetics of a mAb delivered to the brain using BBBMs after intravenous (IV) administration and explored the impact of antibody format (size, neonatal Fc receptor (FcRn) binding, hyaluronic acid binding) on brain clearance following direct injection into the central nervous system (CNS) via intracerebroventricular (ICV) injection. IRDye800CW-labeled antibodies were administered into C57BL/6 mice via ICV or IV injection, and organ concentrations were measured after various time points. When a mAb was coadministered with a BBBM peptide, the permeation of mAb across the BBB was increased compared to mAb alone at early time points; however, the mAb was cleared within 2 h from the brain. ICV experiments revealed that an antibody Fab fragment had a higher brain exposure than a mAb, and that a Fab fused to a hyaluronic acid binding domain (Fab-VG1) showed remarkable improvement in brain exposure. These findings suggest that BBBMs and antibody format optimization may be promising strategies for enhancing brain retention of therapeutic antibodies.

Diffuse lymphoma involvement of the spinal cord showed on [18F]FDG PET/MRI.

A 61-year-old woman with diffuse large B-cell lymphoma received a fluorine-18-deoxyglucose positron emission tomography/computed tomography ([¹8F]FDG PET/CT) for staging. Because of the obvious uptake of [¹8F]FDG in the spinal cord and brain, a positron emission tomography/magnetic resonance imaging (PET/MRI) was performed after the positron emission tomography/computed tomography (PET/CT). The images showed diffuse [¹8F]FDG uptake of the spinal cord and increased T2 signal intensity on MRI, which was suspected to be lymphoma involvement. The patient was diagnosed with diffuse large B-cell lymphoma involving the right maxillofacial region, right cervical lymph nodes, cervix, brain and spinal cord (stage IV of non-germinal center B-cell origin). After chemotherapy, the spinal [¹8F]FDG uptake level decreased significantly, which was considered to be a partial metabolic response. Our case was different from prior, which indicated the pattern of spinal cord involvement by lymphoma was focal.

Autonomic and Enteric Profiling May Help Predict Response to Diverse Obesity Therapies.

PURPOSE: Changes in autonomic (ANS) and enteric nervous systems (ENS) may be involved in pathogenesis of obesity. We hypothesized that baseline autonomic and enteric parameters may predict outcomes of diverse obesity therapies. MATERIAL AND METHODS: We studied ANS and ENS physiology in 37 patients (8 male, 29 female, age 45 years, weight 129.7 kg) at 4 centers in patients undergoing medical (9: low-calorie diet) versus invasive (22: 16 sleeve, 6 bypass) and semi-invasive (6: 2 band, 2 high energy stimulation, 2 aspiration) weight loss therapies. Weight loss was reported as percent weight loss from baseline to latest values at 1 year and in some up to 5 years; classified as < or > /= 20% for each group. ANS testing included sympathetic adrenergic function by measuring reflex vasoconstriction and postural adjustment ratio. ENS was measured non-invasively using cutaneous low-resolution electrogastrogram. RESULTS: Percent weight loss was greater with the invasive (28.5%) than semi-invasive (9.1%) or non-invasive low-calorie diet (4.4%) (p < .001). Percent weight loss at 1 year (and up to 5 years) corresponded to the adrenergic measure of postural adjustment ratio (r = .42, p = .012), total pulse amplitude at rest (r = .56, p < .001), and electrogastrogram standing-to-rest difference (r = .33, p = .056). CONCLUSION: Baseline autonomic and enteric function measures correspond to percentage with loss in this pilot study using diverse weight loss methods. Autonomic and enteric profiling has potential clinical use for evaluation and treatment of obesity but needed larger controlled trials.

Para table tennis improves psychological/mental and cardiovascular health in individuals with spinal cord injury.

BACKGROUND: Although rehabilitation exercise is known to be beneficial for cardiovascular and mental health, it remains a daunting challenge for patients with spinal cord injury (SCI) who rely on wheelchairs for mobility. OBJECTIVE: This study aimed to examine the effectiveness of a 4-week para table tennis program in enhancing self-efficacy and health outcomes in adults with SCI. METHODS: A total of 39 SCI patients were included and divided into the experimental group (n = 18, a 4-week para table tennis training program) and the control group (n = 21). Frequency domain indices of heart rate variability (HRV) were used to evaluate the function of the autonomic nervous system. RESULTS: Following para table tennis training, there was a significant reduction in the physical stress index (PSI, P < 0.001), accompanied by shifts in autonomic regulation of vagal dominance. Additionally, the para table tennis training led to significant improvements in vessel state, differential pulse wave index, atrial elasticity, eccentric constriction power, remaining blood volume, and self-efficacy (all P < 0.05). CONCLUSION: Para table tennis training results in favorable changes in sympathetic tone, enhanced self-efficacy, improved cardiovascular well-being, and an overall positive transformation in HRV.

Optogenetic modulation of cardiac autonomic nervous system.

The following is a narrative review of the fundamentals of optogenetics. It focuses on the advantages and constraints of manipulating the autonomic nervous system by modifying the pathophysiological characteristics that arise in different diseases. Although the use of this technique is currently experimental, we will discuss improvements that have been implemented and identify the necessary measures for potential preclinical translation in the control of the cardiac autonomic nervous system.

Exploratory Dual PET imaging of [18F] fluorodeoxyglucose and [11C]acetoacetate in type 2 diabetic nonhuman primates.

Despite recent advancements in imaging (amyloid-PET & tau-PET) and fluid (Aß42/Aß40 & Aß42/ptau) biomarkers, the current standard for in vivo assessment of AD, diagnosis and prediction of Alzheimer's disease (AD) remains challenging. We demonstrated in nonhuman primates (NHP) that increased plasma and cerebrospinal fluid (CSF) glucose correlated with decreased CSF Aß42 and CSF Aß40, a hallmark of plaque promoting pathogenesis. Together, our findings demonstrate that altered glucose homeostasis and insulin resistance are associated with Aß and amyloid in rodent and NHP models. This warranted further exploration into the dynamics of altered brain metabolism in the NHP model of T2D, cross referenced with CSF and blood-based AD markers. Preliminary dual PET ([11C]acetoacetate ([11C]AcAc) and [18F]fluorodeoxyglucose ([18F]FDG) imaging studies were conducted in an aged cohort of NHPs classified as T2D (n = 5) and pre-diabetic (n = 1) along with corresponding plasma and CSF samples for metabolite analysis. [11C]AcAc and [18F]FDG PET brain standard uptake values (SUV) were highly positively associated (r = 0.88, p = 0.02) in the T2D and pre-diabetic NHPs. Age was not significantly associated with brain SUV (age range 16.5-23.5 years old). Metabolic measures were positively correlated with brain [18F]FDG and CSF Aß42:40 was positively correlated to fasting glucose values. Although our findings suggest moderate correlations, this study further elucidates that peripheral insulin resistance and poor glycemia control alter AD-related pathology, illustrating how T2D is a risk factor for AD.

Hjernetegn.dk-The Danish Central Nervous System Tumor Awareness Initiative Digital Decision Support Tool: Design and Implementation Report.

BACKGROUND: Childhood tumors in the central nervous system (CNS) have longer diagnostic delays than other pediatric tumors. Vague presenting symptoms pose a challenge in the diagnostic process; it has been indicated that patients and parents may be hesitant to seek help, and health care professionals (HCPs) may lack awareness and knowledge about clinical presentation. To raise awareness among HCPs, the Danish CNS tumor awareness initiative hjernetegn.dk was launched. OBJECTIVE: This study aims to present the learnings from designing and implementing a decision support tool for HCPs to reduce diagnostic delay in childhood CNS tumors. The aims also include decisions regarding strategies for dissemination and use of social media, and an evaluation of the digital impact 6 months after launch. METHODS: The phases of developing and implementing the tool include participatory co-creation workshops, designing the website and digital platforms, and implementing a press and media strategy. The digital impact of hjernetegn.dk was evaluated through website analytics and social media engagement. IMPLEMENTATION (RESULTS): hjernetegn.dk was launched in August 2023. The results after 6 months exceeded key performance indicators. The analysis showed a high number of website visitors and engagement, with a plateau reached 3 months after the initial launch. The LinkedIn campaign and Google Search strategy also generated a high number of impressions and clicks. CONCLUSIONS: The findings suggest that the initiative has been successfully integrated, raising awareness and providing a valuable tool for HCPs in diagnosing childhood CNS tumors. The study highlights the importance of interdisciplinary collaboration, co-creation, and ongoing community management, as well as broad dissemination strategies when introducing a digital support tool.

Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy.

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Therefore, interrupting the vicious cycle within neuron-microglia interactions by promoting neuroprotective effects or inhibiting the neurotoxic effects of the CX3CL1-CX3CR1 signaling axis may be a therapeutic goal in DE by limiting the inflammatory response. However, the optimal approach to prevent DE is simply tight glycemic control, because the elimination of dysglycemic states in the CNS abolishes the fundamental mechanisms that induce this vicious cycle.

Blood pressure and heart rate variability to assess autonomic response to an acute bout of high intensity interval exercise in healthy young adults.

Autonomic nervous system (ANS) activity causes acute variations in blood pressure (BP) and heart rate (HR). These systems are challenged during high intensity interval exercise (HIIE). However, BP variability (BPV) and HR variability (HRV) response to HIIE is unknown. We characterized BPV and HRV during an acute HIIE bout using spectral low frequency [LF] and high frequency [HF] domains. We hypothesized that BPV would increase and HRV would decrease during high-intensity and active-recovery of HIIE compared to baseline [BL] and BPV would reduce and HRV would increase during cool down, post-HIIE, and 30 min post-HIIE compared to BL. HIIE involved 10 min of alternating high-intensity and active-recovery (approximately 70% and 10% of Wattmax) on a recumbent stepper. We did a secondary analysis on 23 datasets. The participants were 25 ± 1.5 years, 48% females. Our results showed high-intensity BPV LF was not significantly different from BL while HF increased. HRV LF and HF decreased compared to BL. During active-recovery, LF and HF for BPV and HRV increased greater than high-intensity. HRV LF and HF returned to BL after 30 min of recovery, whereas BPV HF was higher compared to BL. The rapid switching during HIIE uniquely modulates cardiovascular and ANS.

Motor and sensory impairment in survivors of childhood central nervous system (CNS) tumors in the St. Jude Lifetime Cohort (SJLIFE).

BACKGROUND: Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. METHODS: Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0-53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0-70.0] years, 55.7% female) completed in-person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form-36 physical/mental summary scores, social attainment). RESULTS: Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%-29.4%) than controls (2.9%, CI 1.4-4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06-18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19-72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01-1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68-11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10-0.84, Sensory: OR 0.35, CI 0.13-0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22-5.72). CONCLUSIONS: In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL.

The Biological Roles of microRNAs in Drosophila Development.

Drosophila is a well-established insect model system for studying various physiological phenomena and developmental processes, with a focus on gene regulation. Drosophila development is controlled by programmed regulatory mechanisms specific to individual tissues. When key developmental processes are shared among various insects, the associated regulatory networks are believed to be conserved across insects. Thus, studies of developmental regulation in Drosophila have substantially contributed to our understanding of insect development. Over the past two decades, studies on microRNAs (miRNAs) in Drosophila have revealed their crucial regulatory roles in various developmental processes. This review focuses on the biological roles of miRNAs in specific tissues and processes associated with Drosophila development. Additionally, as a future direction, we discuss sequencing technologies that can analyze the interactions between miRNAs and their target genes, with the aim of enhancing miRNA studies in Drosophila development.

Immediate Increase in the Root Mean Square of Successive Differences after Three Bouts of Remote Ischemic Preconditioning: A Randomized Controlled Trial.

(1) Background: Remote ischemic preconditioning (RIPC) is an intervention involving the application of brief episodes of ischemia and reperfusion to distant tissues to activate protective pathways in the heart. There is evidence suggesting the involvement of the autonomic nervous system (ANS) in RIPC-induced cardioprotection. This study aimed to investigate the immediate effects of RIPC on the ANS using a randomized controlled trial. (2) Methods: From March 2018 to November 2018, we conducted a single-blinded randomized controlled study involving 51 healthy volunteers (29 female, 24.9 [23.8, 26.4] years). Participants were placed in a supine position and heart rate variability was measured over 260 consecutive beats before they were randomized into either the intervention or the SHAM group. The intervention group underwent an RIPC protocol (3 cycles of 5 min of 200 mmHg ischemia followed by 5 min reperfusion) at the upper thigh. The SHAM group followed the same protocol but on the right upper arm, with just 40 mmHg of pressure inflation, resulting in no ischemic stimulus. Heart rate variability measures were reassessed afterward. (3) Results: The intervention group showed a significant increase in RMSSD, the possible marker of the parasympathetic nervous system (IG: 14.5 [5.4, 27.5] ms vs. CG: 7.0 [-4.3, 23.1 ms], p = 0.027), as well as a significant improvement in Alpha 1 levels compared to the control group (IG: -0.1 [-0.2, 0.1] vs. CG: 0.0 [-0.1, 0.2], p = 0.001). (4) Conclusions: Our results hint that RIPC increases the RMSSD and Alpha 1 parameters showing possible immediate parasympathetic modulations. RIPC could be favorable in promoting cardioprotective or/and cardiovascular effects by ameliorating ANS modulations.

Impact of Obstructive Sleep Apnea and Sympathetic Nervous System on Cardiac Health: A Comprehensive Review.

A prevalent condition linked to an elevated risk of cardiovascular disease is sleep apnea. This review examines the connections between cardiac risk, the sympathetic nervous system, and sleep apnea. The increased risk of hypertension, arrhythmias, myocardial infarction, and heart failure was highlighted in the pathophysiology of sleep apnea and its effect on sympathetic activation. It is also important to consider potential processes such as oxidative stress, inflammation, endothelial dysfunction, and autonomic imbalance that may relate sleep apnea-induced sympathetic activation to cardiac risk. With implications for creating innovative diagnostic and treatment approaches to lessen the cardiovascular effects of sleep apnea, the goal of this investigation is to improve the understanding of the intricate link between sympathetic activity, cardiac risk, and sleep apnea. This study aimed to clarify the complex relationship between cardiovascular health and sleep apnea by synthesizing the available research and highlighting the crucial role played by the sympathetic nervous system in moderating this relationship. Our thorough investigation may have important therapeutic ramifications that will direct the creation of focused therapies to enhance cardiovascular outcomes in sleep apnea sufferers.

Anesthetic approach to pregnant patients with malaria: a narrative review of the literature.

INTRODUCTION: Anesthesiologists play an important role in the management of labor and delivery during acute malaria infection. The peripartum anesthesia considerations for such cases remain unclear. FINDINGS: Important peripartum considerations include the severity of thrombocytopenia and coagulopathy, hemodynamic status and cardiac disease, and the likelihood of central nervous system (CNS) involvement. Several antimalarial drugs may interact with perioperative medications, causing hypoglycemia, methemoglobinemia, or QT prolongation. Labor should usually not be induced. Patient volume status should be optimized pre-induction, but fluids should be administered with caution given the risk of cerebral edema. In case of CNS involvement intracranial pressure should be maintained. Case reports describe the successful use of neuraxial anesthesia but this approach requires further confirmation of safety. Despite the risks accompanying airway management in pregnancy, in some cases, general anesthesia was preferred due to the chance of CNS infection and disease complications. Tight postoperative assessments of neurological and bleeding status are indicated regardless of the mode of delivery. CONCLUSIONS: Despite the prevalence of malaria, the perioperative risk and preferred mode of anesthesia for pregnant patients with acute malaria remain under-researched and outcome data are limited.

Post-Progression Analysis of EGFR-Mutant NSCLC Following Osimertinib Therapy in Real-World Settings.

BACKGROUND: Platinum-based chemotherapy is the current standard treatment option in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this setting. METHODS: Patients with EGFR-mutant NSCLC who were candidates to receive osimertinib in the metastatic setting at our Center from 2015 to 2022 were retrospectively evaluated to identify patients who received standard platinum-based chemotherapy post-osimertinib. Data were collected on treatment outcomes, with a focus on brain metastases and progression patterns. RESULTS: A total of 220 patients received indication for osimertinib in the study period; n = 176 had adequate follow-up data. Overall, n = 117 patients experienced disease progression on osimertinib. The median time to osimertinib progressive disease (PD) was 15 months (95% confidence interval CI 13-18). Of them, 51 patients (45%) had no access to further treatments. Of the remaining patients, n = 8 received experimental treatments, and n = 55 received standard platinum-based chemotherapy and were considered for this study. Median duration of chemotherapy was 3 months (95% CI 2-5); the best responses among 53 evaluable patients were observed as follows: 15% partial response/complete response (PR/CR), 40% stable disease (SD), 45% PD. Median progression-free survival (PFS) and overall survival (OS) were 3 (95% CI 2-5) and 10 (95% CI 6-15) months, respectively. All patients had baseline and follow-up brain radiologic assessments, and n = 23 had brain metastases at the start of chemotherapy. With a median follow-up of 13 months, intracranial PD occurred in 47% patients, being the first site of PD in 59% of cases. The median time for intracranial (IC) PD was 2 months (95% CI 2-7). IC PD occurred as oligometastatic in 29%, whereas in 71% of cases, it was associated with systemic PD. CONCLUSIONS: Access to subsequent treatments and CNS progression are confirmed unmet needs in EGFR-mutant NSCLC patients. Clinical and CNS-specific outcomes in patients receiving standard chemotherapy after the failure of osimertinib are dismal. Novel upfront treatment options with demonstrated prolonged PFS and better CNS outcomes may help address this important issue.

Fosfomycin-Containing Regimens for the Treatment of Central Nervous System Infections in a Neonatal Intensive Care Unit: A Case Series Study.

Central nervous system infections are among the most severe infectious conditions in the neonatal period and are still burdened by significant mortality, especially in preterm infants and those with a low birth weight or other comorbidities. In this study, we examined the role of fosfomycin-containing antibiotic regimens in neonates with central nervous system infections. We included six neonates over a period of five years: four with meningitis and two with cerebral abscesses. All patients underwent fosfomycin therapy after failing first-line antibiotic regimens. Of the six neonates, two died; two developed neurological and psychomotor deficits and two recovered uneventfully. None of the neonates experienced adverse reactions to fosfomycin, confirming the safety of the molecule in this population. In conclusion, the deep penetration in the central nervous system, the unique mechanism of action, the synergy with other antibiotic therapies, and the excellent safety profile all make fosfomycin an attractive drug for the treatment of neonatal central nervous system infections.

Effects of Acute Mental Stress on Choroidal Thickness.

Purpose: Previous studies have indicated an association between education and myopia, suggesting that numerous stress events during the educational process may influence eye health. This study aimed to investigate the impact of mental stress induced by mental arithmetic (MA) on choroidal thickness (CT). Methods: This study included 33 participants aged between 19 and 29 years. Swept-source optical coherence tomography (SS-OCT) was used to capture images of the posterior segment of the left eye during baseline and MA to assess changes in the CT. After denoising and compensation, the baseline images and MA images that had been rigidly registered and resampled to the baseline images were segmented using a deep learning-based method. Based on the segmentation results, the CT within the regions of 1 mm and 3 mm diameter centered at the lowest point of the fovea was calculated. Results: Significant increases were observed in both CT1mm and CT3mm during MA, with mean changes of 2.742 ± 7.098 µm (p = 0.034) and 3.326 ± 6.143 µm (p < 0.001), respectively. Conclusions: Thickening of the choroid has been observed during acute mental stress. We speculate that long-term or chronic mental stress could have a potential adverse impact on myopia progression.

Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.

The Central Nervous System (CNS) is vulnerable to a range of diseases, including neurodegenerative and oncological conditions, which present significant treatment challenges. The blood-brain barrier (BBB) restricts molecule penetration, complicating the achievement of therapeutic concentrations in the CNS following systemic administration. Gene therapy using recombinant adeno-associated virus (rAAV) vectors emerges as a promising strategy for treating CNS diseases, demonstrated by the registration of six gene therapy products in the past six years and 87 ongoing clinical trials. This review explores the implementation of rAAV vectors in CNS disease treatment, emphasizing AAV biology and vector engineering. Various administration methods-such as intravenous, intrathecal, and intraparenchymal routes-and experimental approaches like intranasal and intramuscular administration are evaluated, discussing their advantages and limitations in different CNS contexts. Additionally, the review underscores the importance of optimizing therapeutic efficacy through the pharmacokinetics (PK) and pharmacodynamics (PD) of rAAV vectors. A comprehensive analysis of clinical trials reveals successes and challenges, including barriers to commercialization. This review provides insights into therapeutic strategies using rAAV vectors in neurological diseases and identifies areas requiring further research, particularly in optimizing rAAV PK/PD.

The Clinical Significance and Application of Heart Rate Variability in Dialysis Patients: A Narrative Review.

Autonomic nervous system (ANS) dysfunction is prevalent in end-stage kidney disease (ESKD) patients, carrying significant risks for morbidity and mortality. Heart rate variability (HRV) is a simple and non-invasive method to evaluate ANS functions and predict prognoses in specific patient populations. Since there is a lack of a clear understanding of the clinical significance of HRV in predicting prognoses in ESKD patients, an updated review on this topic is urgently warranted. The clinical significance of HRV in dialysis patients includes its associations with metabolic syndrome, nutritional status, intradialytic hypotension, vascular access failure, major adverse cardiovascular events, and mortality. These findings underscore the essential role of the autonomic reserve, which might denote the elevation of ANS activity as a response to external stimulus. Patients with a higher level of sympathetic activity at the resting stage, but who are unable to adequately elevate their sympathetic activity under stress might be susceptible to a worse outcome in critical circumstances. Further applications of HRV include HRV biofeedback, risk classification, and real-time HRV monitoring. Overall, HRV is an optimal tool for predicting prognoses in dialysis patients. Further study is encouraged in order to gain a clearer understanding of the clinical significance and application of HRV, and thereby enhance the care of ESKD patients.

Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by heterogeneous symptoms, which lack specific biomarkers for its diagnosis. This study aimed to investigate plasma neurofilament light chain (NfL) levels as a potential biomarker for ME/CFS and explore associations with cognitive, autonomic, and neuropathic symptoms. Here, 67 ME/CFS patients and 43 healthy controls (HCs) underwent comprehensive assessments, including neuropsychological evaluation, autonomic nervous system (ANS) testing, and plasma NfL level analysis. ME/CFS patients exhibited significantly higher plasma NfL levels compared to HC (F = 4.30, p < 0.05). Correlations were observed between NfL levels and cognitive impairment, particularly in visuospatial perception (r = -0.42; p ≤ 0.001), verbal memory (r = -0.35, p ≤ 0.005), and visual memory (r = -0.26; p < 0.05) in ME/CFS. Additionally, higher NfL levels were associated with worsened autonomic dysfunction in these patients, specifically in parasympathetic function (F = 9.48, p ≤ 0.003). In ME/CFS patients, NfL levels explained up to 17.2% of the results in cognitive tests. Unlike ME/CFS, in HC, NfL levels did not predict cognitive performance. Elevated plasma NfL levels in ME/CFS patients reflect neuroaxonal damage, contributing to cognitive dysfunction and autonomic impairment. These findings support the potential role of NfL as a biomarker for neurological dysfunction in ME/CFS. Further research is warranted to elucidate underlying mechanisms and clinical implications.