Monitoring of Potential Safety Events and Vital Signs during Active Mobilization of Patients Undergoing Continuous Renal Replacement Therapy in a Medical Intensive Care Unit.

BACKGROUND/AIMS: This study aims to evaluate potential safety events and vital sign changes during active mobilization physical therapy (PT) in critically ill patients undergoing continuous renal replacement therapy (CRRT). METHODS: A retrospective review was performed on 29 patients who were treated with CRRT and who underwent 81 PT sessions in a medical intensive care unit at a single referral hospital; 15 patients underwent 33 sessions with passive range of motion (PROM) and 17 patients underwent 48 active mobilization PT sessions. Three patients received both types of PT including 8 PROM and 5 active mobilization PT sessions. The occurrences of safety events and vital sign changes during active mobilization PT sessions were evaluated. RESULTS: The safety events did not develop during 33 sessions with PROM. However, there were 2 safety events (4.1%) during 48 active mobilization PT sessions including one session with mobilization in the bed and the other in a sitting position on the edge of the bed. These safety events exclusively developed during active mobilization PT sessions, in which concomitant extracorporeal membrane oxygenation (ECMO) support and CRRT were delivered. Regarding vital sign changes during PT sessions, there were no significant differences in systolic blood pressure (BP), diastolic BP, mean arterial pressure, heart rate, respiratory rate, or peripheral oxygen saturation before and after both PROM and active mobilization PT sessions. CONCLUSIONS: This study showed that active mobilization PT can be performed safely in patients who are being treated with CRRT without a significant hemodynamic change. However, the development of potential safety events in patients with ECMO needs to be monitored carefully.

Effects of Robot-assisted Gait Training Combined with Functional Electrical Stimulation on Recovery of Locomotor Mobility in Chronic Stroke Patients: A Randomized Controlled Trial.

[Purpose] The purpose of the present study was to investigate the effects of robot-assisted gait training combined with functional electrical stimulation on locomotor recovery in patients with chronic stroke. [Subjects] The 20 subjects were randomly assigned into either an experimental group (n = 10) that received a combination of robot-assisted gait training and functional electrical stimulation on the ankle dorsiflexor of the affected side or a control group (n = 10) that received robot-assisted gait training only. [Methods] Both groups received the respective therapies for 30 min/day, 3 days/week for 5 weeks. The outcome was measured using the Modified Motor Assessment Scale (MMAS), Timed Up-and-Go Test (TUG), Berg Balance Scale (BBS), and gait parameters through gait analysis (Vicon 370 motion analysis system, Oxford Metrics Ltd., Oxford, UK). All the variables were measured before and after training. [Results] Step length and maximal knee extension were significantly greater than those before training in the experimental group only. Maximal Knee flexion showed a significant difference between the experimental and control groups. The MMAS, BBS, and TUG scores improved significantly after training compared with before training in both groups. [Conclusion] We suggest that the combination of robot-assisted gait training and functional electrical stimulation encourages patients to actively participate in training because it facilitates locomotor recovery without the risk of adverse effects.

Abnormal Electroencephalogram Findings and Its Correlation With Clinical Features From Pediatric Patients in Psychiatric Clinic.

Objective: We aimed to evaluate the occurrence of electroencephalogram (EEG) abnormalities in pediatric patients attending an outpatient psychiatry clinic at a tertiary center. We examined the rates of abnormalities and specific findings based on demographics, specific diagnoses, and clinical severity. Methods: This study included pediatric patients who underwent EEG at the outpatient psychiatry clinic. Patient demographics, psychiatric diagnosis, intellectual disability, intelligent quotient (IQ) score, family history of psychiatric disorders, and Clinical Global Impression-Severity (CGI-S) score were obtained through retrospective electronic health record analysis. The rate of EEG abnormalities was calculated, and specific abnormal findings were reviewed. Relationships between the rate of EEG abnormalities and diagnosis, severity, IQ, and age at EEG examination were analyzed. Results: Of 319 patients who underwent EEG, 21.3% (68 patients) of patients exhibited abnormalities, including background abnormalities (14.7%, 47 patients), interictal epileptiform discharges (IEDs) (10.3%, 33 patients), and a slow posterior dominant rhythm (3.8%, 10 patients). The frontal region was the most commonly affected area. Neurodevelopmental disorders (NDDs) had the most frequent abnormalities (29.8%), followed by anxiety (16.7%), sleep (14.3%), mood (11.7%), psychotic (5%), and conduct disorders (0%). Disease severity did not correlate with the rate of EEG abnormalities. Adjusted for age, sex, severity, and family history, patients with EEG abnormalities exhibited lower IQ scores. Conclusion: EEG abnormalities were common in pediatric patients with psychiatric disorders, with background abnormalities detected as frequently as IEDs. Disease severity was not associated with EEG abnormality, while IQ scores showed a negative correlation.

Epilepsy phenotype and gene ontology analysis of the 129 genes in a large neurodevelopmental disorders cohort.

Objective: Although pediatric epilepsy is an independent disease entity, it is often observed in pediatric neurodevelopmental disorders (NDDs) as a major or minor clinical feature, which might provide diagnostic clues. This study aimed to identify the clinical and genetic characteristics of patients with epilepsy in an NDD cohort and demonstrate the importance of genetic testing. Methods: We retrospectively analyzed the detailed clinical differences of pediatric NDD patients with epilepsy according to their genetic etiology. Among 1,213 patients with NDDs, 477 were genetically diagnosed by exome sequencing, and 168 had epilepsy and causative variants in 129 genes. Causative genes were classified into two groups: (i) the "epilepsy-genes" group resulting in epilepsy as the main phenotype listed in OMIM, Epi25, and ClinGen (67 patients) and (ii) the "NDD-genes" group not included in the "epilepsy-genes" group (101 patients). Results: Patients in the "epilepsy-genes" group started having seizures, often characterized by epilepsy syndrome, at a younger age. However, overall clinical features, including treatment responses and all neurologic manifestations, showed no significant differences between the two groups. Gene ontology analysis revealed the close interactions of epilepsy genes associated with ion channels and neurotransmitters. Conclusion: We demonstrated a similar clinical presentation of different gene groups regarding biological/molecular processes in a large NDDs cohort with epilepsy. Phenotype-driven genetic analysis should cover a broad scope, and further studies are required to elucidate integrated pathomechanisms.

Broad spectrum of phenotype and genotype in Korean α-dystroglycan related muscular dystrophy presenting to a tertiary pediatric neuromuscular center.

α-Dystroglycanopathies are a clinically and genetically heterogeneous group of muscular dystrophies associated with the defective glycosylation of α-dystroglycan (α-DG). Eighteen genes associated with α-dystroglycanopathies have been identified, and the relative prevalence of genetic subtypes varies with ethnicity. Here, we investigated the clinical and genetic characteristics of α-DG-related muscular dystrophy in the Korean pediatric population. We analyzed the clinical characteristics and variant profiles of 42 patients with α-DG-related muscular dystrophies diagnosed by either reduced glycosylation of α-DG and/or genetic confirmation. Genotype-phenotype correlations were explored by a retrospective medical record review. The muscle-eye-brain disease/Fukuyama congenital muscular dystrophy was the most common phenotype (28/42, 66.7%). Homozygous or compound heterozygous variants were detected in 37 patients belonging to 34 unrelated families (37/42; 88.1%). Pathogenic variants were identified in FKTN (n = 24), POMGNT1 (n = 4), GMPPB (n = 4), FKRP (n = 2), POMT1 (n = 2), and ISPD (n = 1). Compound heterozygous retrotransposal insertions and deep-intronic variants in FKTN were the most common genotypes and were associated with severe phenotypes. This study suggests that α-DG-related muscular dystrophy has a wide range of genotypes and phenotypes according to ethnicity. A stratified genetic test according to ethnicity should be considered to diagnose α-DG-related muscular dystrophy.

The Korean undiagnosed diseases program phase I: expansion of the nationwide network and the development of long-term infrastructure.

BACKGROUND: Phase I of the Korean Undiagnosed Diseases Program (KUDP), performed for 3 years, has been completed. The Phase I program aimed to solve the problem of undiagnosed patients throughout the country and develop infrastructure, including a data management system and functional core laboratory, for long-term translational research. Herein, we share the clinical experiences of the Phase I program and introduce the activities of the functional core laboratory and data management system. RESULTS: During the program (2018-2020), 458 patients were enrolled and classified into 3 groups according to the following criteria: (I) those with a specific clinical assessment which can be verified by direct testing (32 patients); (II) those with a disease group with genetic and phenotypic heterogeneity (353 patients); and (III) those with atypical presentations or diseases unknown to date (73 patients). All patients underwent individualized diagnostic processes based on the decision of an expert consortium. Confirmative diagnoses were obtained for 242 patients (52.8%). The diagnostic yield was different for each group: 81.3% for Group I, 53.3% for Group II, and 38.4% for Group III. Diagnoses were made by next-generation sequencing for 204 patients (84.3%) and other genetic testing for 35 patients (14.5%). Three patients (1.2%) were diagnosed with nongenetic disorders. The KUDP functional core laboratory, with a group of experts, organized a streamlined research pipeline covering various resources, including animal models, stem cells, structural modeling and metabolic and biochemical approaches. Regular data review was performed to screen for candidate genes among undiagnosed patients, and six different genes were identified for functional research. We also developed a web-based database system that supports clinical cohort management and provides a matchmaker exchange protocol based on a matchbox, likely to reinforce the nationwide clinical network and further international collaboration. CONCLUSIONS: The KUDP evaluated the unmet needs of undiagnosed patients and established infrastructure for a data-sharing system and future functional research. The advancement of the KUDP may lead to sustainable bench-to-bedside research in Korea and contribute to ongoing international collaboration.

Treadmill exercise alleviates short-term memory impairments of pups born to old and obese mother rats.

Obesity causes atrophy of the brain, leading to deterioration in working memory, learning, and cognitive function. The status of short-term memory in rat pups born to older obese mother rats was verified, and the effect of treadmill exercise on short-term memory in rat pups was investigated. Step-down avoidance test for short-term memory, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining for apoptosis, and immunohistochemistry for Ki67 for new cell generation were done. The old female rats were fed with normal diet (5% of fat), and the old and obese female rats were fed with high-fat diet (60% of fat) for up to 50 weeks in age (for 44 weeks in experimental period). The newborn rats were divided into four groups according to the conditions of the mother rats as follows: the rat pups group born to old rats, the rat pups group born to old rats with exercise, the rat pups group born to old and obese rats, the rat pups group born to old and obese rats with exercise. Maternal exercise improved short-term memory, decreased TUNEL-positive cell number, and increased Ki67-positive cell number of the pups born to old and obese rats. Maternal exercise has been found to contribute to eliminating the health risks of fetuses born to old obese mothers.

Voluntary Wheel Running Exercise Improves Aging-Induced Sarcopenia via Activation of Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α/Fibronectin Type III Domain-Containing Protein 5/Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway.

PURPOSE: In this study, the protective effect of voluntary wheel running exercise on muscle loss and muscle weakness in gastrocnemius of old rats was investigated. The association of voluntary wheel exercise with the peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)/fibronectin type III domain-containing protein 5 (FNDC5)/adenosine monophosphate- activated protein kinase (AMPK) signaling pathway and vascular endothelial growth factor (VEGF) expression was also evaluated. METHODS: Six-month-old and 22-month-old male rats were used for this experiment. The rats in voluntary wheel running exercise groups were performed wheel running for 2 months. Weight bearing test for walking strength, rotarod test for motor coordination and balance, hematoxylin and eosin (H&E) staining for histological changes in the muscle tissues, Western blot analysis for PGC-1α, FNDC5, AMPK, immunofluorescence for VEGF were conducted. RESULTS: Decreased muscle mass, strength, and coordination due to aging were associated with a decrease in the PGC-1α/ FNDC5/AMPK signaling pathway in the gastrocnemius. Voluntary wheel running exercise enhanced VEGF expression by activating the PGC-1α/FNDC5/AMPK signaling pathway, then increased muscle mass, strength, and coordination. CONCLUSION: It has been suggested that voluntary wheel running exercise alleviates symptoms of urological diseases that are difficult to treat. Wheel running exercise is a good therapeutic strategy to prevent or treat aging-related sarcopenia.

Effect of exercise immersion experience on health promotion and lifelong physical education of high school students in sports club activities.

The purpose of this study was to investigate the impact of high school students' athletic commitment, health promotion education, and lifelong sports activities. To this end, the researcher searched for research subjects of 397 high school students residing in Seoul in 2019. As a result of the analysis, the following conclusions were drawn. First, the effect of exercise commitment on sports health promotion education was investigated. Looking at the activities of high school students, their commitment to behavior has had a profound impact on their health responsibilities and relationships. Second, the study also investigated the impact of athletic commitment to lifelong sports of sports activities in high school students and found that cognitive and behavioral commitment had a significant impact on lifelong sports. Finally, as a result of investigating the impact of health promotion education on lifelong sports of high school student sports activities, it was found that health responsibility and relationships have a great influence on lifelong sports.

Effects of Kinesio taping on blood fatigue factors after isokinetic exercise.

This study examined the effects of Kinesio taping on recovery from fatigue induced by an exercise of concentric contraction using an isokinetic machine. Eight healthy collegiate students participated in two experiments: the Kinesio taping application condition and the no Kinesio taping application condition. The fatigue was induced by concentric exercise at 60°/sec, 50 repetitions for one session, and repeated 3 sessions. Changes of blood ammonia, lactate, lactate dehydrogenase (LDH), and creatinine kinase (CK) were monitored. Blood was collected before exercise, immediately after exercise, 24 hr after exercise, and 72 hr after exercise. Blood ammonia tended to reduce during the recovery process, but no differences were found between conditions. Blood lactate tended to reduce during the recovery process, but no differences were found between conditions. In the blood LDH, no differences were found between conditions. Blood creatine kinase tended to reduce during the recovery process, but no differences were found between conditions. The present results showed that Kinesio taping did not affect the recovery phase of blood ammonia, lactate concentration, LDH, and CK.

Self-esteem and social development according to participation in school sports club.

The purpose of this study is to explore the meaning of the middle school sports club and to understand the impact on the self-esteem and social development of middle school students participating in the school sports club. To achieve the purpose of this study, a questionnaire survey was conducted on 450 students by selecting a middle school. Of the 420 collected questionnaires, 399 questionnaires were used as a valid sample. As a result of examining seven areas of self-esteem, self-esteem in five areas excluding domestic ego and personality ego was highest in the group that participated in the league. As a result of examining the difference in social development according to the type of participation in school sports clubs, the league participation group was higher in all five areas. As a result of examining the difference in self-esteem according to the period of participation in school sports clubs, the group participating in the league was high in six areas excluding physical ability, however, it was difficult to see a statistically significant difference. As for the factor related to physical ability, the group with the longest participation period of 13 months or longer was the highest, and there is a statistically significant difference. As a result of examining the difference in social development according to the period of participation in school sports clubs, the group under 6 months was the highest in four areas other than physical activity. Physical activity was highest in the group over 13 months.

Resistance exercise improves short-term memory through inactivation of NF-κB pathway in mice with Parkinson disease.

Dysfunctions of Parkinson disease (PD) are classified into motor dysfunction, autonomic nervous system dysfunction, and nonmotor dysfunction, and clinical symptoms such as muscle stiffness, tremors, speech disorders, balance disorders, and slow movements appear. Resistance exercise is a main compartment of exercise programs for PD patient. The effect of resistant exercise on short-term memory in PD mice was studied in relation to the activation of nuclear factor (NF)-κB pathway. PD was induced by subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. For resistance exercise, mice performed ladder climbing 5 days per week for 5 weeks. Step-down avoidance test for short-term memory, enzyme-linked immunoassay for tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, Western bot for NF-κB, NF-κB inhibitor (IκB)-α, B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), and Bcl-2, and immunohistochemistry for cleaved caspase-3 were done. Latency time was shortened, TNF-α, IL-6, and IL-1ß concentration was increased, NF-κB expression and IκB-α phosphorylation were increased, cleaved caspase-3 and Bax expression was enhanced, and Bcl-2 expression was suppressed by PD induction. Latency time was lengthened, TNF-α, IL-6, and IL-1ß concentration was decreased, NF-κB expression and IκB-α phosphorylation were suppressed, cleaved caspase-3 and Bax expression was decreased, and Bcl-2 expression was increased in PD mice by resistance exercise or levodopa treatment. Resistance exercise improved short-term memory by inhibiting secretion of proinflammatory cytokines and apoptosis through inactivation of NF-κB. These effects of resistance exercise were similar to levodopa treatment.

Treadmill Running Improves Spatial Learning Memory Through Inactivation of Nuclear Factor Kappa B/Mitogen-Activated Protein Kinase Signaling Pathway in Amyloid-ß-Induced Alzheimer Disease Rats.

PURPOSE: Exercise is known to reduce proinflammatory cytokines production and apoptosis. We investigated the effect of treadmill running on spatial learning memory in terms of activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway in Alzheimer disease (AD) rats. We also evaluated the effect of treadmill running on proinflammatory cytokine production and apoptosis. METHODS: Using the stereotaxic frame, amyloid-ß (Aß) was injected into the lateral ventricle of the brain. The rats belong to treadmill running groups were forced to run on a motorized treadmill for 30 minutes per a day during 4 weeks, starting 3 days after Aß injection. Morris water maze task was done for the determination of spatial learning memory. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry for cleaved caspase-3, and western blot for NF-κB, inhibitory protein of NF-κB (IκB), MAPK signaling pathway, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß were done. RESULTS: Induction of AD increased proinflammatory cytokine secretion by activating the NF-κB/MAPK signaling pathway. These changes induced apoptosis in the hippocampus and reduced spatial learning memory. In contrast, treadmill running inactivated the NF-κB/MAPK signaling pathway and suppressed proinflammatory cytokine production. These changes inhibited apoptosis and improved spatial learning memory. CONCLUSION: Current results showed that treadmill running promoted spatial learning memory through suppressing proinflammatory cytokine production and apoptosis via inactivation of NF-κB/MAPK signaling pathway. Treadmill exercise can be considered an effective intervention for symptom relieve of AD.

Treadmill exercise improves spatial learning ability by increasing cell proliferation in offspring born to maternal rats receiving stress during pregnancy.

Prenatal stress causes learning deficits by inhibiting neurogenesis in the hippocampus. We studied the effects of maternal treadmill running or offspring treadmill running on the spatial learning ability of adolescent offspring rats or adult offspring rats born to maternal rats that received stress during pregnancy. For this study, spatial learning ability was measured by radial 8-arm maze task. Immunohistochemistry for 5-bromo-2'-deoxyuridine and Western blot for brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) were also conducted. Stress was induced by exposing pregnant rats to hound in an enclosed room. Maternal treadmill running or treadmill running of offspring improved spatial learning ability of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring increased hippocampal cell proliferation of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring increased BDNF and TrkB expression in the hippocampus of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring inhibited Bax expression and increased Bcl-2 expression in the hippocampus of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Mother's exercise during pregnancy or child's exercise after childbirth can improve the spatial learning ability deteriorated due to stress during pregnancy.

Expanding the clinical phenotype and genetic spectrum of PURA-related neurodevelopmental disorders.

BACKGROUND: PURA-related neurodevelopmental disorders (PURA-NDDs) include 5q31.3 deletion syndrome and PURA syndrome. PURA-NDDs are characterized by neonatal hypotonia, moderate to severe global developmental delay/intellectual disability (GDD/ID), facial dysmorphism, epileptic seizures, nonepileptic movement disorders, and ophthalmological problems. PURA-NDDs have recently been identified and underestimated in neurodevelopmental cohorts, but their diagnosis is still challenging. METHODS: We retrospectively reviewed the clinical characteristics, genetic spectrum, and diagnostic journey of patients with PURA-NDDs. RESULTS: We report 2 patients with 5q31.3 microdeletion and 5 with PURA pathogenic variants. They demonstrated hypotonia (7/7, 100%), feeding difficulties (4/5, 80%), and respiratory problems (4/7, 57%) in the neonatal period. All of them had severe GDD/ID and could not achieve independent walking and verbal responses. Distinctive facial features of open-tented upper vermilion, long philtrum, and anteverted nares and poor visual fixation and tracking with or without nystagmus were most commonly found (5/7, 71.4%). There were no significant differences in clinical phenotypes between 5q31.3 microdeletion syndrome and PURA syndrome. PURA-NDDs need to be considered as a differential diagnosis in individuals who show severe hypotonia, including feeding difficulties since birth and severe developmental retardation with distinctive facial and ophthalmological features. CONCLUSIONS: Our data expands the phenotypic and genetic spectrum of PURA-NDD. Next-generation sequencing methods based on the detailed phenotypic evaluation would shorten the diagnostic delay and would help this rare disorder become a recognizable cause of neurodevelopmental delay.

The Role of Focal Epilepsy Features in Defining SCN1A Mutation-positive Dravet Syndrome as Generalized and Focal Epilepsy.

BACKGROUND AND PURPOSE: This study was aimed to describe focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients. METHODS: A total of 82 SCN1A mutation-positive patients were reviewed retrospectively (39 boys and 43 girls). Seizure type and electroencephalography (EEG) findings were investigated according to the stage, disease onset, and steady state (after age 2 years). Long-term video EEG data were used to classify the seizure type. RESULTS: Focal seizures at onset and the steady state were found in 54.9% (45/82) and 90% (63/70) of patients, respectively. Afebrile focal seizures were an initial seizure in about one fourth of the patients (22/82, 26.8%). Of 48 seizures captured during long-term video EEG monitoring of 30 patients, 19 seizures were classified as focal onset (39.6%). Of the 19 focal seizures, 12 were either focal motor or focal non-motor seizures, and seven were focal onset bilateral tonic-clonic seizure. Focal epileptiform discharges were more frequent than generalized epileptiform discharges at seizure onset and during the clinical course on conventional EEG (3.7% vs. 0%, 52.9% vs. 32.9%, respectively). CONCLUSIONS: Our study provides a comprehensive description of focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients. Recognizing these features as defining the clinical spectrum of Dravet syndrome may lead to earlier genetic diagnosis and tailored management.

Early-onset autosomal dominant GTP-cyclohydrolase I deficiency: Diagnostic delay and residual motor signs.

OBJECTIVE: Autosomal dominant (AD) guanosine triphosphate cyclohydrolase 1 (GCH1) deficiency is the most common cause of dopa-responsive dystonia (DRD). Patients with GCH1 deficiency are likely to experience diagnostic delay, but its consequences have not been described thoroughly in patients with early-onset disease. We describe the diagnostic delay and residual motor signs (RMS) observed in patients with early-onset (before 15 years of age) disease. METHODS: Twelve patients with early-onset AD GCH1 deficiency from a single center were included in the case series analysis. For the meta-analysis, the PubMed database was searched for articles on early-onset AD GCH1 deficiency published from 1995 to 2019. RESULTS: In the case series, the mean duration of diagnostic delay was 5.6 years. Two patients exhibited RMS, and four patients underwent orthopedic surgery. The literature search yielded 137 AD GCH1 deficiency cases for review; gait disturbance was reported in 92.7% of patients, diurnal fluctuation of symptoms in 91.9%, and RMS in 39%. The mean duration of diagnostic delay was 14.6 years overall: 12.0 years in RMS-negative patients and 21.2 years in RMS-positive patients. CONCLUSIONS: Diagnostic delay in early-onset AD GCH1 deficiency is more closely associated with later RMS. Early clinical suspicion, timely diagnosis, and levodopa treatment may reduce the occurrence of RMS in patients with early-onset AD GCH1 deficiency.

Voluntary Wheel Running Improves Spatial Learning Memory by Suppressing Inflammation and Apoptosis via Inactivation of Nuclear Factor Kappa B in Brain Inflammation Rats.

PURPOSE: Exercise has been shown to protect against diverse brain diseases. Voluntary exercise improves cognition and has a neuroprotective effect. The aim of this investigation is to study the effect of voluntary wheel running on brain inflammation in rats with regard to inflammation and apoptosis. METHODS: Brain inflammation was caused by intracranial injection of lipopolysaccharide using a stereotaxic instrument. Voluntary wheel running group were conducted during 21 consecutive days, staring 2 days after brain inflammation. RESULTS: Brain inflammation increased proinflammatory cytokine production and apoptosis cell death in the hippocampus. There changes in the hippocampus deteriorated spatial learning memory. However, voluntary wheel running suppressed the secretion of inflammatory cytokines and apoptotic neuronal cell death via inactivation of nuclear factor kappa B (NF-κB)/NF-κB inhibitor-α pathway. Voluntary wheel running also promoted the recovery of the spatial learning memory impairment. CONCLUSION: Voluntary wheel running after brain inflammation enhanced spatial learning memory by suppressing proinflammatory cytokine secretion and apoptosis cell death. Voluntary wheel running is also expected to be effective in inflammatory diseases of the urogenital system.

Treadmill exercise in obese maternal rats during pregnancy improves spatial memory through activation of phosphatidylinositol 3-kinase pathway in the hippocampus of rat pups.

Maternal nutrition is necessary for the growth of the fetus, and excessive intake of nutrients interferes with brain development in offspring. In the current study, the effect of treadmill running during pregnancy in obese maternal rats on spatial learning memory and spatial working memory in rat pups was investigated. Phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and extracellular signal-regulated kinase 1 and 2 (ERK1/2) was also identified in rat pups. Female rats were divided into the normal diet group and the high-fat diet group for 7 weeks, including pregnancy and lactation. Maternal treadmill running was performed for 4 weeks. The born rat pups were classified into a control group, a treadmill exercise group, a high-fat diet group, a high-fat diet and treadmill exercise group according to the status of maternal rats. Radial 8-arm maze task for spatial learning memory and Morris water maze task for spatial working memory were done. Western blot analysis was conducted to determine the expressions of PI3K, Akt, ERK1/2. In the current results, maternal treadmill running during pregnancy improved spatial learning memory and spatial working memory in rat pups born to obese maternal rats. This improving effect of memory was due to the enhanced phosphorylation of PI3K, Akt, and ERK1/2 by treadmill running.

Ankle exercise with functional electrical stimulation affects spasticity and balance in stroke patients.

Stroke patients have limited motor function due to ankle spasticity, and various interventions are applied to solve this problem. The purpose of this study was to investigate the effects of functional electrical stimulation (FES) with ankle exercise on spinal cord motor neuron excitability and balance in stroke patients. Twenty-five stroke patients were divided into the three groups. For the intervention, the control group applied general physiotherapy, the experimental group I applied a sham FES with ankle exercise, and the experimental group II applied a FES with ankle exercise. All groups applied the intervention for 30 min per session, 5 times a week, for a total of 8 weeks. The functional reaching test (FRT), Timed Up and Go test was used to measure balance ability, and H-reflex was used to measure spinal motor neuron excitability. All tests were measured before and after the intervention. In the ankle exercise with FES group, spinal motor neuron excitability significantly decreased (P<0.05), and FRT was significantly increased (P<0.05). Therefore, FES with ankle exercise for stroke patients could be suggested as an effective intervention for improving motor function.