Central nervous system involvement in chronic lymphocytic leukemia: a case report and review of literature.

BACKGROUND: Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia. CASE PRESENTATION: It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy. CONCLUSION: Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood-brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia.

Reconstitution of human microglia and resident T cells in the brain of humanized DRAGA mice.

Humanized mouse models are valuable tools for investigating the human immune system in response to infection and injury. We have previously described the human immune system (HIS)-DRAGA mice (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD) generated by infusion of Human Leukocyte Antigen (HLA)-matched, human hematopoietic stem cells from umbilical cord blood. By reconstituting human cells, the HIS-DRAGA mouse model has been utilized as a "surrogate in vivo human model" for infectious diseases such as Human Immunodeficiency Virus (HIV), Influenza, Coronavirus Disease 2019 (COVID-19), scrub typhus, and malaria. This humanized mouse model bypasses ethical concerns about the use of fetal tissues for the humanization of laboratory animals. Here in, we demonstrate the presence of human microglia and T cells in the brain of HIS-DRAGA mice. Microglia are brain-resident macrophages that play pivotal roles against pathogens and cerebral damage, whereas the brain-resident T cells provide surveillance and defense against infections. Our findings suggest that the HIS-DRAGA mouse model offers unique advantages for studying the functions of human microglia and T cells in the brain during infections, degenerative disorders, tumors, and trauma, as well as for testing therapeutics in these pathological conditions.

Long-standing neuromyelitis optica with leukodystrophy-like asymptomatic MRI changes.

Patients with neuromyelitis optica (NMO) are unlikely to develop clinically silent lesions on brain magnetic resonance imaging (MRI), unlike patients with multiple sclerosis (MS). We encountered a patient with NMO who showed radiological progression and leukodystrophy-like changes on MRI during a long-standing, clinically asymptomatic period.

Autonomic Dysfunction in Amyotrophic Lateral Sclerosis - A Case-Control Study.

INTRODUCTION: This study aimed to explore autonomic nervous system involvement in amyotrophic lateral sclerosis (ALS) patients by evaluating sympathetic skin response (SSR). MATERIALS AND METHODS: The study included 35 sporadic (ALS) patients (cases), and 35 healthy age and sex-matched participants (controls) aged <60 years. SSR was recorded in the electrophysiology lab of the Neurology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Patients with diseases associated with peripheral or autonomic neuropathy were excluded. Prolonged latency (delayed SSR) or an absent response was considered abnormal SSR. RESULTS: SSR was found to be abnormal in 17 (48.6 %) ALS cases, with an absent response in the upper limbs of six cases (17.1%). Abnormal SSR was more prevalent in the lower limbs, with 33 (94.3%) and 20 (57.1%) cases having a delayed or absent response, respectively. In comparison, SSR was normal in all control participants (P-value <0.05). Abnormal SSR was significantly more common in the lower limbs of ALS cases with bulbar palsy than those without bulbar palsy (P-value=0.04). There was no association of SSR with disease severity and duration. CONCLUSION: ALS is significantly associated with abnormal SSR, indicating autonomic nervous system involvement. There could also be an association between bulbar palsy and abnormal SSR among ALS patients. Further studies should be carried out to determine the association of abnormal SSR with disease severity, duration, and type.

Diagnosis of pediatric central nervous system tumors using methylation profiling of cfDNA from cerebrospinal fluid.

Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.

Risk factors for falls among hospitalized medical patients - A systematic review and meta-analysis.

OBJECTIVE: To identify and quantify risk factors for in-hospital falls in medical patients. DATA SOURCES: Six databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and Google Scholar) were systematically screened until April 11, 2023, to identify relevant articles. STUDY SELECTION: All titles and abstracts of the retrieved articles were independently screened by two researchers who also read the full texts of the remaining articles. Quantitative studies that assessed risk factors for falls among adult patients acutely hospitalized were included in the review. Publications that did not capture internal medicine patients or focused on other specific populations were excluded. DATA EXTRACTION: Information on study characteristics and potential risk factors were systematically extracted. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. PRISMA and MOOSE guidelines were followed for reporting. DATA SYNTHESIS: The main outcome was any in-hospital falls. Using a random-effects meta-analysis model, association measures for each risk factor reported in five or more studies were pooled. Separate analyses according to effect measure and studies adjusted for sex and age at least were performed. Of 5,067 records retrieved, 119 original publications from 25 countries were included. In conclusion, 23 potential risk factors were meta-analyzed. Strong evidence with large effect sizes was found for a history of falls (OR 2.54; 95% CI 1.63- 3.96; I2 91%), antidepressants (pooled OR 2.25; 95% confidence interval [95% CI] 1.92-2.65; I2 0%), benzodiazepines (OR 1.97; 95% CI 1.68-2.31; I2 0%), hypnotics-sedatives (OR 1.90; 95% CI 1.53-2.36; I2 46%), and antipsychotics (OR 1.61; 95% CI 1.33-1.95; I2 0%). Furthermore, evidence of associations with male sex (OR 1.22, 95% CI 0.99-1.50, I2 65%) and age (OR 1.17, 95% CI 1.02-1.35, I2 72%) were found, but effect sizes were small. CONCLUSIONS: The comprehensive list of risk factors, which specifies the strength of evidence and effect sizes, could assist in the prioritization of preventive measures and interventions.

The neutrophil extracellular traps in neurological diseases: An update.

Neutrophil extracellular traps released by neutrophils are web-like DNA structures adhered to granulin proteins with bactericidal activity and can be an important mechanism for preventing pathogen dissemination or eliminating microorganisms. However, they also play important roles in diseases of other systems, such as the central nervous system. We tracked the latest advances and performed a review based on published original and review articles related to neutrophil extracellular traps and neurological diseases. Generally, neutrophils barely penetrate the blood-brain barrier into the brain parenchyma, but when pathological changes such as infection, trauma, or neurodegeneration occur, neutrophils rapidly infiltrate the central nervous system to exert their defensive effects. However, neutrophils may adversely affect the host when they uncontrollably release neutrophil extracellular traps upon persistent neuroinflammation. This review focused on recent advances in understanding the mechanisms and effects of neutrophil extracellular traps release in neurological diseases, and we also discuss the role of molecules that regulate neutrophil extracellular traps release in anticipation of clinical applications in neurological diseases.

Altered Heart Rate Variability During Mobile Game Playing and Watching Self-Mobile Gaming in Individuals with Problematic Mobile Game Use: Implications for Cardiac Health.

Introduction: The surge in mobile gaming, fueled by smartphone and internet accessibility, lacks a comprehensive understanding of physiological changes during gameplay. Methods: This study, involving 93 participants (average age 21.75 years), categorized them into Problematic Mobile Gaming (PMG) and non-problematic Mobile Gaming (nPMG) groups based on Problematic Mobile Gaming Questionnaire (PMGQ) scores. The PMGQ is a 12-item scale developed in Taiwan to assess symptoms of problematic mobile gaming. The research delved into heart rate variability (HRV) alterations during real-time mobile gaming and self-gaming video viewing. Results: Results showed that the PMG group significantly presents a lower root mean square of successive differences (RMSSD), and High Frequency (lnHF) than does the nPMG group (F=4.73, p=0.03; F=10.65, p=0.002, respectively) at the baseline. In addition, the PMG group significantly displayed elevated HF and low-frequency to high-frequency (LF/HF) in the mobile-gaming (F=7.59, p=0.007; F=9.31, p=0.003) condition as well as in the watching self-gaming videos (F=9.75, p=0.002; F=9.02, p=0.003) than did the nPMG. Conclusion: The study suggests targeted interventions to mitigate autonomic arousal, offering a potential avenue to address adverse effects associated with problematic mobile gaming behavior. The PMG group displayed increased craving scores after real-time mobile gaming and watching self-gaming video excerpts, unlike the nPMG group. Elevated LF/HF ratios in frequent gaming cases heightened autonomic arousal, presenting challenges in relaxation after mobile gaming. These findings contribute to a nuanced understanding of the complex interplay between mobile gaming activities, physiological responses, and potential intervention strategies.

Gut-directed therapy in Parkinson's disease.

Parkinson's disease (PD) is a common and slow-progressing neurodegenerative disorder characterized by motor and non-motor symptoms, including gastrointestinal (GI) dysfunctions. Over the last years, the microbiota-gut-brain (MGB) axis is emerging as a bacterial-neuro-immune ascending pathway that contributes to the progression of PD. Indeed, PD patients are characterized by changes in gut microbiota composition, alterations of intestinal epithelial barrier (IEB) and enteric neurogenic/inflammatory responses that, besides determining intestinal disturbances, contribute to brain pathology. In this context, despite the causal relationship between gut dysbiosis, impaired MGB axis and PD remains to be elucidated, emerging evidence shows that MGB axis modulation can represent a suitable therapeutical strategy for the treatment of PD. This review provides an overview of the available knowledge about the beneficial effects of gut-directed therapies, including dietary interventions, prebiotics, probiotics, synbiotics and fecal microbiota transplantation (FMT), in both PD patients and animal models. In this context, particular attention has been devoted to the mechanisms by which the modulation of MGB axis could halt or slow down PD pathology and, most importantly, how these approaches can be included in the clinical practice.

Predictors for the Differentiation between Glioblastoma, Primary Central Nervous System Lymphoma, and Metastasis in Patients with a Solitary Enhancing Intracranial Mass.

Introduction Differentiation between glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastasis is important in decision-making before surgery. However, these malignant brain tumors have overlapping features. This study aimed to identify predictors differentiating between GBM, PCNSL, and metastasis. Materials and Methods Patients with a solitary intracranial enhancing tumor and a histopathological diagnosis of GBM, PCNSL, or metastasis were investigated. All patients with intracranial lymphoma had PCNSL without extracranial involvement. Demographic, clinical, and radiographic data were analyzed to determine their associations with the tumor types. Results The predictors associated with GBM were functional impairment ( p = 0.001), large tumor size ( p < 0.001), irregular tumor margin ( p < 0.001), heterogeneous contrast enhancement ( p < 0.001), central necrosis ( p < 0.001), intratumoral hemorrhage ( p = 0.018), abnormal flow void ( p < 0.001), and hypodensity component on noncontrast cranial computed tomography (CT) scan ( p < 0.001). The predictors associated with PCNSL comprised functional impairment ( p = 0.005), deep-seated tumor location ( p = 0.006), homogeneous contrast enhancement ( p < 0.001), absence of cystic appearance ( p = 0.008), presence of hypointensity component on precontrast cranial T1-weighted magnetic resonance imaging (MRI; p = 0.027), and presence of isodensity component on noncontrast cranial CT ( p < 0.008). Finally, the predictors for metastasis were an infratentorial ( p < 0.001) or extra-axial tumor location ( p = 0.035), smooth tumor margin ( p < 0.001), and presence of isointensity component on cranial fluid-attenuated inversion recovery MRI ( p = 0.047). Conclusion These predictors may be used to differentiate between GBM, PCNSL, and metastasis, and they are useful in clinical management.

An extremely rare case of primary alveolar rhabdomyosarcoma in the central nervous system.

Background: Alveolar rhabdomyosarcoma (ARMS) shows a predilection for the peripheral extremities and is very rarely identified as a primary in the brain. Here, we report a case of ARMS with multiple lesions exclusively within the central nervous system (CNS). Case Description: A 20-year-old man presented to our hospital with a gradually increasing headache and disturbance of consciousness. Neuroimaging showed hydrocephalus and multiple tumor lesions, including in the brainstem and cerebellum, with uniform gadolinium enhancement on T1-weighted magnetic resonance imaging, as well as spinal cord seeding. Cerebrospinal fluid (CSF) analysis showed a slightly elevated cell count (6/µL; normal, <5/µL) and highly elevated protein (153 mg/dL). In addition, atypical cells were cytologically identified in the CSF. No other laboratory findings were abnormal. Emergency ventricular drainage was performed to control cerebral pressure, followed by a biopsy to confirm the diagnosis. Histological examination revealed a fascicular arrangement of oval cells with eosinophilic cytoplasm and tumor cells with pleomorphic nuclei and prominent nucleoli. Immunohistochemical studies showed negative results for glial fibrillary acidic protein and positive results for desmin and myogenin. In addition, molecular analysis revealed that this tumor had the H3F3A p.Lys28Met mutation and no paired box (PAX)3-forkhead box O1 (FOXO1) or PAX7-FOXO1 fusion genes. ARMS was, therefore, diagnosed. Chemotherapy and radiotherapy were subsequently initiated, but tumor growth could not be controlled, and the patient died 6 months after surgery. Conclusion: This report describes an extremely rare case of ARMS arising exclusively within the CNS.

Physiological Profiling of Agitation in Dementia: Insights From Wearable Sensor Data.

Background and Objectives: The number of people with dementia is expected to triple to 152 million in 2050, with 90% having accompanying behavioral and psychological symptoms (BPSD). Agitation is among the most critical BPSD and can lead to decreased quality of life for people with dementia and their caregivers. This study aims to explore objective quantification of agitation in people with dementia by analyzing the relationships between physiological and movement data from wearables and observational measures of agitation. Research Design and Methods: The data presented here is from 30 people with dementia, each included for 1 week, collected following our previously published multimodal data collection protocol. This observational protocol has a cross-sectional repeated measures design, encompassing data from both wearable and fixed sensors. Generalized linear mixed models were used to quantify the relationship between data from different wearable sensor modalities and agitation, as well as motor and verbal agitation specifically. Results: Several features from wearable data are significantly associated with agitation, at least the p < .05 level (absolute ß: 0.224-0.753). Additionally, different features are informative depending on the agitation type or the patient the data were collected from. Adding context with key confounding variables (time of day, movement, and temperature) allows for a clearer interpretation of feature differences when a person with dementia is agitated. Discussion and Implications: The features shown to be significantly different, across the study population, suggest possible autonomic nervous system activation when agitated. Differences when splitting the data by agitation type point toward a need for future detection models to tailor to the primary type of agitation expressed. Finally, patient-specific differences in features indicate a need for patient- or group-level model personalization. The findings reported in this study both reinforce and add to the fundamental understanding of and can be used to drive the objective quantification of agitation.

Three-Headed Biceps Brachii Muscle: A Rare Site of Proximal Median Nerve Entrapment.

The biceps brachii muscle is a highly variable muscle in the anterior compartment of the arm, and the most common variants include additional heads or slips. The median nerve courses with the brachial artery in the medial arm near the biceps brachii muscle, crosses the elbow, and enters the forearm deep to the bicipital aponeurosis. While entrapment of the median nerve in the carpal tunnel is one of the most common neuropathies, more proximal entrapments by the bicipital aponeurosis or other variants have been reported. In a 94-year-old embalmed female cadaver received through the Humanity Gift Registry of Pennsylvania, a biceps brachii muscle with an additional slip that arose from the coracoid process was found, which bridged over the median nerve and blended with the investing fascia of the forearm flexors via aponeurosis. Because of the course of this muscular slip in the arm and its relationship to the median nerve, this may be an additional site of proximal entrapment of the median nerve. It is important to consider these rare sites of nerve entrapment when diagnosing patients with median nerve neuropathy.

MRI-based radiomics signatures for preoperative prediction of Ki-67 index in primary central nervous system lymphoma.

PURPOSE: The aim of this study was to develop and validate radiomics signatures based on MRI for preoperative prediction of Ki-67 proliferative index (PI) expression in primary central nervous system lymphoma (PCNSL). METHODS: A total of 341 patients with PCNSL were retrospectively analyzed, including 286 patients in one center as the training set and 55 patients in another two centers as the external validation set. Radiomics features were extracted and selected from preoperative contrast-enhanced T1-weighted images, fluid attenuation inversion recovery to build radiomics signatures according to the Ki-67 PI. The predictive performances of the radiomics model were evaluated using four classifiers including random forest, K-Nearest Neighbors, Neural Network and Decision Tree. A combined model was built by incorporating radiomics signature, clinical variables and MRI radiological characteristics using multivariate logistic regression analysis, and a nomogram was established to predict the expression of Ki-67 individually. The predictive performances of the models were evaluated using area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: Radiomics signatures were independent predictors of the expression level of Ki-67 (OR: 2.523, P < 0.001). RF radiomics models had the highest accuracy (0.934 in the training set and 0.811 in the external validation set) and F1 Score (0.920 in the training set and 0.836 in the external validation set). The clinic-radiologic-radiomics nomogram showed better predictive performance with AUCs of 0.877(95 % CI: 0.837-0.918) in the training set and 0.866(95 % CI: 0.774-0.957) in the external validation set. The calibration curve and DCA demonstrated goodness-of-fit and improved benefits in clinical practice of the nomogram. CONCLUSIONS: Nomograms integrating MRI-based radiomics and clinical-radiological characteristics could effectively predict Ki-67 PI in primary PCNSL.

Favorable efficacy and reduced acute neurotoxicity by antisense oligonucleotides with 2',4'-BNA/LNA with 9-(aminoethoxy)phenoxazine.

An increasing number of antisense oligonucleotides (ASOs) have been approved for clinical use. However, improvements of both efficacy and safety in the central nervous system (CNS) are crucial for the treatment with CNS diseases. We aimed to overcome the crucial issues by our development of various gapmer ASOs with a novel nucleoside derivative including a 2',4'-BNA/LNA with 9-(aminoethoxy)phenoxazine (BNAP-AEO). The various gapmer ASOs with BNAP-AEO were evaluated for thermal stability, in vitro and in vivo efficacy, and acute CNS toxicity. Thermal stability analysis of the duplexes with their complementary RNAs showed that ASOs with BNAP-AEO had a higher binding affinity than those without BNAP-AEO. In vitro assays, when transfected into neuroblastoma cell lines, demonstrated that ASOs with BNAP-AEO, had a more efficient gene silencing effect than those without BNAP-AEO. In vivo assays, involving intracerebroventricular injections into mice, revealed ASOs with BNAP-AEO potently suppressed gene expression in the brain. Surprisingly, the acute CNS toxicity in mice, as assessed through open field tests and scoring systems, was significantly lower for ASOs with BNAP-AEO than for those without BNAP-AEO. This study underscores the efficient gene-silencing effect and low acute CNS toxicity of ASOs incorporating BNAP-AEO, indicating the potential for future therapeutic applications.

Clinical management of extra­adrenal myelolipoma in the central nervous system: A case report.

Extra-adrenal myelolipoma (EAM) is a rare benign tumor composed of mature adipose and hematopoietic tissues. Its etiology remains to be elucidated and there are few case reports describing the clinical features and treatment of EAMs in the central nervous system. The present study presented our experience and practice in the clinical management of a case of EAM in the right frontal region. A 56-year-old woman was found to have a space-occupying right frontal lesion on computed tomography (CT) of the head. Unenhanced magnetic resonance imaging (MRI) showed a lesion of ~1.5x1.2 cm. Enhanced whole abdominal CT showed a right presacral mass, 2.0 cm in diameter, with clear margins. The postoperative histopathological findings showed mainly mature adipose tissue mixed with extramedullary hematopoietic components. This confirmed the diagnosis of a (bone) marrow lipoma. Myelolipoma of the central nervous system is extremely rare. to the best of the authors' knowledge, only two cases of intracranial myelolipoma have been reported, and the present study introduced the first case in a Chinese patient reported in English. However, when CT shows high density and MRI shows mixed density in the tumor area even without enhancement, the possibility of myelolipoma should be considered in the differential diagnosis.

Napping and heart rate variability in elite athletes.

Sleep and autonomic nervous system (ANS) influence each other in a bidirectional fashion. Importantly, it has been proposed that sleep has a beneficial regulatory influence over cardiovascular activity, which is mostly controlled by autonomic regulation through the activity of sympathetic and parasympathetic pathways of the ANS. A well-established method to non-invasively assess cardiac autonomic activity is heart rate variability (HRV) analysis. We aimed to investigate the effect of a 40-min nap opportunity on HRV. Twelve professional basketball players randomly accomplished two conditions: 40-min nap (NAP) and control (CON). Nocturnal sleep and naps were monitored by actigraphic recording and sleep diaries. Total sleep time (TST), time in bed (TIB), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were analyzed. HRV was analyzed in 5-min segments during quiet wake before and after each condition with controlled breathing. Were analysed high (HF) and low frequency (LF) bands, the standard deviation of NN interval (SDNN), HRV index and stress index (SI). Wellness Hooper index and Epworth Sleepiness Scale (ESS) were assessed before and after both conditions. There was no significant difference in TIB, TST, SE, WASO, and VAS between NAP and CON. A significant increase in SDNN, HRV index, and LF and a significant decrease in HF, SI, ESS, and Hooper's stress and fatigue scores were observed from pre- to post-nap. In conclusion, napping reduces sleepiness, stress and fatigue, and might provide an advantage by preparing the body for a much-required sympathetic comeback following peaceful rest.

Functional neurological disorder, physical activity and exercise: What we know and what we can learn from comorbid disorders.

Functional neurological disorder (FND) is a common neurologic disorder associated with many comorbid symptoms including fatigue, pain, headache, and orthostasis. These concurrent symptoms lead patients to accumulate multiple diagnoses comorbid with FND, including fibromyalgia, chronic fatigue syndrome, postural orthostatic tachycardia syndrome, persistent post-concussive symptoms, and chronic pain. The role of physical activity and exercise has not been evaluated in FND populations, though has been studied in certain comorbid conditions. In this traditional narrative literature review, we highlight some existing literature on physical activity in FND, then look to comorbid disorders to highlight the therapeutic potential of physical activity. We then consider abnormalities in the autonomic nervous system (ANS) as a potential pathophysiological explanation for symptoms in FND and comorbid disorders and postulate how physical activity and exercise may provide benefit via autonomic regulation.

Poliovirus capsid protein VP3 can penetrate vascular endothelial cells.

The poliovirus (PV) enters the central nervous system (CNS) via the bloodstream, suggesting the existence of a mechanism to cross the blood-brain barrier. Here, we report that PV capsid proteins (VP1 and VP3) can penetrate cells, with VP3 being more invasive. Two independent parts of VP3 are responsible for this function. Both peptides can penetrate human umbilical cord vascular endothelial cells, and one peptide of VP3 could also penetrate peripheral blood mononuclear cells. In an in vitro blood-brain barrier model using rat-derived astrocytes, pericytes, and endothelial cells, both peptides were observed to traverse from the blood side to the brain side at 6 h after administration. These results provide insights into the molecular mechanisms underlying PV invasion into the CNS.

Sleep Apnea, Autonomic Disturbances, and Blood Pressure Variability.

Augmented blood pressure variability has emerged as a quantity predictive of adverse cardiovascular outcomes. Among the range of intrinsic and extrinsic factors shown to increase night-time, circadian, short-term, and long-term blood pressure variations, the presence and severity of obstructive sleep apnea have emerged as one of the most prevalent and potent. Obstructive sleep apnea alters acutely the normal nocturnal equilibrium between sympathetic and parasympathetic tone, magnifying nocturnal blood pressure oscillations, and induces sustained autonomic aftereffects with the capacity to amplify short-term and intersessional blood pressure variabilities. The object of this brief review is to synthesize the current understanding of the potential interrelations between obstructive sleep apnea, the acute and sustained autonomic disturbances that it elicits, and beat-to-beat blood pressure fluctuation during sleep, nocturnal dipping status, and day-to-day blood pressure variability and the consequences of these perturbations for cardiovascular risk.