Trunk postural reactions to the force perturbation intensity and frequency during sitting astride in children with cerebral palsy.

The purpose of this study was to examine kinematic and neuromuscular responses of the head and body to pelvis perturbations with different intensities and frequencies during sitting astride in children with CP. Sixteen children with spastic CP (mean age 7.4 ± 2.4 years old) were recruited in this study. A custom designed cable-driven robotic horse was used to apply controlled force perturbations to the pelvis during sitting astride. Each participant was tested in four force intensity conditions (i.e., 10%, 15%, 20%, and 25% of body weight (BW), frequency = 1 Hz), and six force frequency conditions (i.e., 0.5 Hz, 1 Hz, 1.5 Hz, 2 Hz, 2.5 Hz, and 3 Hz, intensity = 20% of BW). Each testing session lasted for one minute with a one-minute rest break inserted between two sessions. Kinematic data of the head, trunk, and legs were recorded using wearable sensors, and EMG signals of neck, trunk, and leg muscles were recorded. Children with CP showed direction-specific trunk and neck muscle activity in response to the pelvis perturbations during sitting astride. Greater EMG activities of trunk and neck muscles were observed for the greater intensities of force perturbations (P < .05). Participants also showed enhanced activation of antagonistic muscles rather than direction-specific trunk and neck muscle activities for the conditions of higher frequency perturbations (P < .05). Children with CP may modulate trunk and neck muscle activities in response to greater changes in intensity of pelvis perturbation during sitting astride. Perturbations with too high frequency may be less effective in inducing direction-specific trunk and neck muscle activities.

A high-fat diet catalyzes progression to hyperglycemia in mice with selective impairment of insulin action in Glut4-expressing tissues.

Insulin resistance impairs postprandial glucose uptake through glucose transporter type 4 (GLUT4) and is the primary defect preceding type 2 diabetes. We previously generated an insulin-resistant mouse model with human GLUT4 promoter-driven insulin receptor knockout (GIRKO) in the muscle, adipose, and neuronal subpopulations. However, the rate of diabetes in GIRKO mice remained low prior to 6 months of age on normal chow diet (NCD), suggesting that additional factors/mechanisms are responsible for adverse metabolic effects driving the ultimate progression of overt diabetes. In this study, we characterized the metabolic phenotypes of the adult GIRKO mice acutely switched to high-fat diet (HFD) feeding in order to identify additional metabolic challenges required for disease progression. Distinct from other diet-induced obesity (DIO) and genetic models (e.g., db/db mice), GIRKO mice remained leaner on HFD feeding, but developed other cardinal features of insulin resistance syndrome. GIRKO mice rapidly developed hyperglycemia despite compensatory increases in ß-cell mass and hyperinsulinemia. Furthermore, GIRKO mice also had impaired oral glucose tolerance and a limited glucose-lowering benefit from exendin-4, suggesting that the blunted incretin effect contributed to hyperglycemia. Secondly, GIRKO mice manifested severe dyslipidemia while on HFD due to elevated hepatic lipid secretion, serum triglyceride concentration, and lipid droplet accumulation in hepatocytes. Thirdly, GIRKO mice on HFD had increased inflammatory cues in the gut, which were associated with the HFD-induced microbiome alterations and increased serum lipopolysaccharide (LPS). In conclusion, our studies identified important gene/diet interactions contributing to diabetes progression, which might be leveraged to develop more efficacious therapies.

Overground walking with a constraint force on the nonparetic leg during swing improves weight shift toward the paretic side in people after stroke.

Targeting enhancing the use of the paretic leg during locomotor practice might improve motor function of the paretic leg. The purpose of this study was to determine whether application of constraint force to the nonparetic leg in the posterior direction during overground walking would enhance the use of the paretic leg in people with chronic stroke. Fifteen individuals after stroke participated in two experimental conditions, i.e., overground walking with a constraint force applied to the nonparetic leg and overground walking only. Each participant was tested in the following procedures that consisted of overground walking with either constraint force or no constraint force, instrumented split-belt treadmill walking, and pressure-sensitive gait mat walking before and after the overground walking. Overground walking practice with constraint force resulted in greater enhancement in lateral weight shift toward the paretic side (P < 0.01), muscle activity of the paretic hip abductors (P = 0.04), and propulsion force of the paretic leg (P = 0.05) compared with the results of the no-constraint condition. Overground walking practice with constraint force tended to induce greater increase in self-selected overground walking speed (P = 0.06) compared with the effect of the no-constraint condition. The increase in propulsion force from the paretic leg was positively correlated with the increase in self-selected walking speed (r = 0.6, P = 0.03). Overground walking with constraint force applied to the nonparetic leg during swing phase of gait may enhance use of the paretic leg, improve weight shifting toward the paretic side and propulsion of the paretic leg, and consequently increase walking speed.NEW & NOTEWORTHY Application of constraint force to the nonparetic leg during overground walking induced improved lateral weight shifts toward the paretic leg and enhanced muscle activity of the paretic leg during walking. In addition, one session of overground walking with constraint force might induce an increase in propulsive force of the paretic leg and an increase in self-selected overground walking speed, which might be partially due to the improvement in motor control of the paretic leg.

Alternating Magnetic Field-Promoted Nanoparticle Mixing: The On-Chip Immunocapture of Serum Neuronal Exosomes for Parkinson's Disease Diagnostics.

The analysis of cargo proteins in exosome subpopulations has considerable value in diagnostics but a translatable impact has been limited by lengthy or complex exosome extraction protocols. We describe herein a scalable, fast, and low-cost exosome extraction using an alternating (AC) magnetic field to support the dynamic mixing of antibody-coated magnetic beads (MBs) with serum samples within 3D-printed microfluidic chips. Zwitterionic polymer-coated MBs are, specifically, magnetically agitated and support ultraclean exosome capture efficiencies >70% from <50 µL of neat serum in 30 min. Applied herein to the immunocapture of neuronal exosomes using anti-L1CAM antibodies, prior to the array-based assaying of α-synuclein (α-syn) content by a standard duplex electrochemical sandwich ELISA, sub pg/mL detection was possible with an excellent coefficient of variation and a sample-to-answer time of ∼75 min. The high performance and semiautomation of this approach hold promise in underpinning low-cost Parkinson's disease diagnostics and is of value in exosomal biomarker analyses more generally.

Vertical-horizontal illusory effects with gaze restrictions do not change length estimations using the lower limb.

Gaze direction and use of visual feedback can affect illusory influences over perceptions and manual length size estimates of the vertical-horizontal (V-H) illusion, in which the vertical, bisecting segment of an inverted T (IT) appears longer than the horizontal, bisected segment. We questioned whether V-H illusory influences would also exist for the lower limb. Participants stepped forward in an attempt to make the toe-to-toe distance of their dominant foot equal to a short or long bisecting segment length of a vertically projected IT. Performances under three gaze conditions included: maintaining gaze on the IT intersection throughout a trial for target fixation (TF); viewing the intersection for 4 s then looking down and performing the step for movement fixation (MF); and viewing the intersection for 4 s then maintaining gaze on the remembered location of the intersection and performing the step for remembered target fixation (RTF). Variables included step displacement, peak velocity (PV), and normalized ground reaction force amplitude (GRFampN), as well as time to peak and peak amplitude of the center of pressure (COPtime and COPamp, respectively). Main effects of gaze on PV, GRFampN, COPtime, and COPamp revealed lower values for MF compared to TF and RTF, which did not exist for step displacement. No significant correlations existed between step displacement and other variables across participants. Together, we found evidence to suggest differences between movement planning and movement completion. Exploitation of deceptive visual cues can guide step planning and early step execution, but do not guide final step estimations.

A new filterless indoor air purifier for particulate matter and bioaerosol based on heterogeneous condensation.

Using an indoor air purifier is an important solution for improving indoor air quality and protecting people from the harmful effects of air pollution on their health. The filter air purifiers can remove particulate matter including bioaerosols, but their filter media can cause secondary pollution. To fulfill this need, a new filterless indoor air purifier, the Cloud-Air-Purifying (CAP) air purifier, is presented in this study. Using heterogeneous condensation and supergravity technology, the CAP air purifier grows and collects fine particles, while rapidly disinfecting bioaerosols with chemical disinfection and ultraviolet (UV) disinfection. Furthermore, the purifying performance of the CAP air purifier was tested in a simulated cabin. The results showed the clean air delivery rate (CADR) of the CAP air purifier was approximately 150 m3/h, and the effective coefficient was 0.93. The CAP air purifier was highly efficient in purifying fine particulate matter, 93% for PM10 and 91% for particle size of 0.5-1 µm in 60 min, which was 13-58 times more than natural decay. The reason for the efficient removal of fine particles is that they can condense and grow in water vapor supersaturated environment and be collected in a supergravity field. Moreover, the CAP air purifier has significant bactericidal effects on bioaerosols. It achieved a disinfection efficiency of 99.99997% by decreasing bioaerosols from 108 CFU/m3 to less than 30 CFU/m3 in only 20 min when particle purification in combination with UV disinfection and disinfectant (ClO2). Furthermore, ClO2 release concentrations, noise, and power consumption were investigated for application purposes, with results showing that they were within acceptable limits. The study presents an innovative idea and design for preventing airborne microorganisms and particulate matter through heterogeneous condensation technology.

Repeated adaptation and de-adaptation to the pelvis resistance force facilitate retention of motor learning in stroke survivors.

Locomotor adaptation to novel walking patterns induced by external perturbation has been tested to enhance motor learning for improving gait parameters in individuals poststroke. However, little is known regarding whether repeated adaptation and de-adaptation to the externally perturbed walking pattern may facilitate or degrade the retention of locomotor learning. In this study, we examined whether the intermittent adaptation to novel walking patterns elicited by external perturbation induces greater retention of the adapted locomotion in stroke survivors, compared with effects of the continuous adaptation. Fifteen individuals poststroke participated in two experimental conditions consisting of 1) treadmill walking with intermittent (i.e., interspersed 2 intervals of no perturbation) or continuous (no interval) adaptation to externally perturbed walking patterns and 2) overground walking before, immediately, and 10 min after treadmill walking. During the treadmill walking, we applied a laterally pulling force to the pelvis toward the nonparetic side during the stance phase of the paretic leg to disturb weight shifts toward the paretic side. Participants showed improved weight shift toward the paretic side and enhanced muscle activation of hip abductor/adductors immediately after the removal of the pelvis perturbation for both intermittent and continuous conditions (P < 0.05) and showed longer retention of the improved weight shift and enhanced muscle activation for the intermittent condition, which transferred from treadmill to overground walking (P < 0.05). In conclusion, repeated motor adaptation and de-adaptation to the pelvis resistance force during walking may promote the retention of error-based motor learning for improving weight shift toward the paretic side in individuals poststroke.NEW & NOTEWORTHY We examined whether the intermittent versus the continuous adaptation to external perturbation induces greater retention of the adapted locomotion in stroke survivors. We found that participants showed longer retention of the improved weight shift and enhanced muscle activation for the intermittent versus the continuous conditions, suggesting that repeated motor adaptation and de-adaptation to the pelvis perturbation may promote the retention of error-based motor learning for improving weight shift toward the paretic side in individuals poststroke.

The recombinant Newcastle disease virus Anhinga strain expressing human TRAIL exhibit antitumor effects on a glioma nude mice model.

Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. However, the potential oncolytic ability of the recombinant newcastle disease virus (NDV) Anhinga strain carried with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has not been fully explored at present. In the present study, the recombinant NDV/Anh-TRAIL that secretes soluble TRAIL was constructed and the experiment results suggested NDV/Anh-TRAIL as a promising candidate for glioma therapy. Growth kinetic and TRAIL secreted quantity of recombinant NDV/Anh-TRAIL virus were measured. Cytotoxic and cell apoptosis were analyzed for its anti-glioma therapy in vitro. Nude mice were used for the in vivo evaluation. Both tumor volume and mice behavior after injection were observed. The recombinant virus replicated with the same kinetics as the parental virus and the highest expression of TRAIL (77.8 ng/L) was found at 48 hours. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole and flow cytometry data revealed that the recombinant NDV/Anh-TRAIL (56.1 ± 8.2%) virus could induce a more severe apoptosis rate, when compared with the NDV wild type (37.2 ± 7.0%) and mock (7.0 ± 1.8%) groups (P < .01), in U251 cells. Furthermore, in the present animal study, the average tumor volume was smaller in the NDV/Anh-TRAIL group (97.21 mm3 ), when compared with the NDV wild type (205.03 mm3 , P < .05) and PBS (310.30 mm3 , P < .01) groups.

PP2A methylation controls sensitivity and resistance to ß-amyloid-induced cognitive and electrophysiological impairments.

Elevated levels of the ß-amyloid peptide (Aß) are thought to contribute to cognitive and behavioral impairments observed in Alzheimer's disease (AD). Protein phosphatase 2A (PP2A) participates in multiple molecular pathways implicated in AD, and its expression and activity are reduced in postmortem brains of AD patients. PP2A is regulated by protein methylation, and impaired PP2A methylation is thought to contribute to increased AD risk in hyperhomocysteinemic individuals. To examine further the link between PP2A and AD, we generated transgenic mice that overexpress the PP2A methylesterase, protein phosphatase methylesterase-1 (PME-1), or the PP2A methyltransferase, leucine carboxyl methyltransferase-1 (LCMT-1), and examined the sensitivity of these animals to behavioral and electrophysiological impairments caused by exogenous Aß exposure. We found that PME-1 overexpression enhanced these impairments, whereas LCMT-1 overexpression protected against Aß-induced impairments. Neither transgene affected Aß production or the electrophysiological response to low concentrations of Aß, suggesting that these manipulations selectively affect the pathological response to elevated Aß levels. Together these data identify a molecular mechanism linking PP2A to the development of AD-related cognitive impairments that might be therapeutically exploited to target selectively the pathological effects caused by elevated Aß levels in AD patients.

PINK1 signalling rescues amyloid pathology and mitochondrial dysfunction in Alzheimer's disease.

Mitochondrial dysfunction and synaptic damage are early pathological features of the Alzheimer's disease-affected brain. Memory impairment in Alzheimer's disease is a manifestation of brain pathologies such as accumulation of amyloid-ß peptide and mitochondrial damage. The underlying pathogenic mechanisms and effective disease-modifying therapies for Alzheimer's disease remain elusive. Here, we demonstrate for the first time that decreased PTEN-induced putative kinase 1 (PINK1) expression is associated with Alzheimer's disease pathology. Restoring neuronal PINK1 function strikingly reduces amyloid-ß levels, amyloid-associated pathology, oxidative stress, as well as mitochondrial and synaptic dysfunction. In contrast, PINK1-deficient mAPP mice augmented cerebral amyloid-ß accumulation, mitochondrial abnormalities, impairments in learning and memory, as well as synaptic plasticity at an earlier age than mAPP mice. Notably, gene therapy-mediated PINK1 overexpression promotes the clearance of damaged mitochondria by augmenting autophagy signalling via activation of autophagy receptors (OPTN and NDP52), thereby alleviating amyloid-ß-induced loss of synapses and cognitive decline in Alzheimer's disease mice. Loss of PINK1 activity or blockade of PINK1-mediated signalling (OPTN or NDP52) fails to reverse amyloid-ß-induced detrimental effects. Our findings highlight a novel mechanism by which PINK1-dependent signalling promotes the rescue of amyloid pathology and amyloid-ß-mediated mitochondrial and synaptic dysfunctions in a manner requiring activation of autophagy receptor OPTN or NDP52. Thus, activation of PINK1 may represent a new therapeutic avenue for combating Alzheimer's disease.

Increased neuronal PreP activity reduces Aß accumulation, attenuates neuroinflammation and improves mitochondrial and synaptic function in Alzheimer disease's mouse model.

Accumulation of amyloid-ß (Aß) in synaptic mitochondria is associated with mitochondrial and synaptic injury. The underlying mechanisms and strategies to eliminate Aß and rescue mitochondrial and synaptic defects remain elusive. Presequence protease (PreP), a mitochondrial peptidasome, is a novel mitochondrial Aß degrading enzyme. Here, we demonstrate for the first time that increased expression of active human PreP in cortical neurons attenuates Alzheimer disease's (AD)-like mitochondrial amyloid pathology and synaptic mitochondrial dysfunction, and suppresses mitochondrial oxidative stress. Notably, PreP-overexpressed AD mice show significant reduction in the production of proinflammatory mediators. Accordingly, increased neuronal PreP expression improves learning and memory and synaptic function in vivo AD mice, and alleviates Aß-mediated reduction of long-term potentiation (LTP). Our results provide in vivo evidence that PreP may play an important role in maintaining mitochondrial integrity and function by clearance and degradation of mitochondrial Aß along with the improvement in synaptic and behavioral function in AD mouse model. Thus, enhancing PreP activity/expression may be a new therapeutic avenue for treatment of AD.

NR2B-dependent cyclophilin D translocation suppresses the recovery of synaptic transmission after oxygen-glucose deprivation.

N-methyl d-aspartate receptor (NMDA) subunit 2B (NR2B)-containing NMDA receptors and mitochondrial protein cyclophilin D (CypD) are well characterized in mediating neuronal death after ischemia, respectively. However, whether and how NR2B and CypD work together in mediating synaptic injury after ischemia remains elusive. Using an ex vivo ischemia model of oxygen-glucose deprivation (OGD) in hippocampal slices, we identified a NR2B-dependent mechanism for CypD translocation onto the mitochondrial inner membrane. CypD depletion (CypD null mice) prevented OGD-induced impairment in synaptic transmission recovery. Overexpression of neuronal CypD mice (CypD+) exacerbated OGD-induced loss of synaptic transmission. Inhibition of CypD-dependent mitochondrial permeability transition pore (mPTP) opening by cyclosporine A (CSA) attenuated ischemia-induced synaptic perturbation in CypD+ and non-transgenic (non-Tg) mice. The treatment of antioxidant EUK134 to suppress mitochondrial oxidative stress rescued CypD-mediated synaptic dysfunction following OGD in CypD+ slices. Furthermore, OGD provoked the interaction of CypD with P53, which was enhanced in slices overexpressing CypD but was diminished in CypD-null slices. Inhibition of p53 using a specific inhibitor of p53 (pifithrin-µ) attenuated the CypD/p53 interaction following OGD, along with a restored synaptic transmission in both non-Tg and CypD+ hippocampal slices. Our results indicate that OGD-induced CypD translocation potentiates CypD/P53 interaction in a NR2B dependent manner, promoting oxidative stress and loss of synaptic transmission. We also evaluate a new ex vivo chronic OGD-induced ischemia model for studying the effect of oxidative stress on synaptic damage.

Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy.

Newcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical study and are currently approved for clinical trials. NDV Anhinga strain which is a mesogenic strain should be classified as lytic strain and has a therapeutic efficacy in hepatocellular cancer. In this study, we evaluated the capacity of NDV Anhinga strain to elicit immune reaction in vivo and the possibility for using as a vaccine vector for expressing tumor therapeutic factors. Interleukin-2 (IL-2) could boost the immune response against the tumor cells. Therefore, we use NDV Anhinga strain as backbone to construct a recombinant virus (NDV/Anh-IL-2) expressing IL-2. The virus growth curve showed that the production of recombinant NDV/Anh-IL-2 was slightly delayed compared to the wild type. The NDV/Anh-IL-2 strain could express soluble IL-2 and effectively inhibit the growth of hepatocellular carcinoma in vivo. 60 days post-treatment, mice which were completely cured by previous treatment were well protected when rechallenged with the same tumor cell. From the H&E-stained sections, intense infiltration of lymphocyte was observed in the NDV Anhinga strain treated group, especially in NDV/Anh-IL-2 group. The NDV Anhinga strain could not only kill the tumor directly, but could also elicit immune reaction and a potent immunological memory when killing tumor in vivo. In conclusion, the Anhinga strain could be an effective vector for tumor therapy; the recombinant NDV/Anh-IL-2 strain expressing soluble IL-2 is a promising candidate for hepatoma therapy.

Neuronally Derived Extracellular Vesicle α-Synuclein as a Serum Biomarker for Individuals at Risk of Developing Parkinson Disease.

IMPORTANCE: Nonmotor symptoms of Parkinson disease (PD) often predate the movement disorder by decades. Currently, there is no blood biomarker to define this prodromal phase. OBJECTIVE: To investigate whether α-synuclein in neuronally derived serum-extracellular vesicles identifies individuals at risk of developing PD and related dementia. DESIGN, SETTING, and PARTICIPANTS: This retrospective, cross-sectional multicenter study of serum samples included the Oxford Discovery, Marburg, Cologne, and Parkinson's Progression Markers Initiative cohorts. Participants were recruited from July 2013 through August 2023 and samples were analyzed from April 2022 through September 2023. The derivation group (n = 170) included participants with isolated rapid eye movement sleep behavior disorder (iRBD) and controls. Two validation groups were used: the first (n = 122) included participants with iRBD and controls and the second (n = 263) included nonmanifest GBA1N409S gene carriers, participants with iRBD or hyposmia, and available dopamine transporter single-photon emission computed tomography, healthy controls, and patients with sporadic PD. Overall the study included 199 participants with iRBD, 20 hyposmic participants with available dopamine transporter single-photon emission computed tomography, 146 nonmanifest GBA1N409S gene carriers, 21 GBA1N409S gene carrier patients with PD, 50 patients with sporadic PD, and 140 healthy controls. In the derivation group and validation group 1, participants with polysomnographically confirmed iRBD were included. In the validation group 2, at-risk participants with available Movement Disorder Society prodromal markers and serum samples were included. Among 580 potential participants, 4 were excluded due to alternative diagnoses. EXPOSURES: Clinical assessments, imaging, and serum collection. MAIN OUTCOME AND MEASURES: L1CAM-positive extracellular vesicles (L1EV) were immunocaptured from serum. α-Synuclein and syntenin-1 were measured by electrochemiluminescence. Area under the receiver operating characteristic (ROC) curve (AUC) with 95% CIs evaluated biomarker performance. Probable prodromal PD was determined using the updated Movement Disorder Society research criteria. Multiple linear regression models assessed the association between L1EV α-synuclein and prodromal markers. RESULTS: Among 576 participants included, the mean (SD) age was 64.30 (8.27) years, 394 were male (68.4%), and 182 were female (31.6%). A derived threshold of serum L1EV α-synuclein distinguished participants with iRBD from controls (AUC = 0.91; 95% CI, 0.86-0.96) and those with more than 80% probability of having prodromal PD from participants with less than 5% probability (AUC = 0.80; 95% CI, 0.71-0.89). Subgroup analyses revealed that specific combinations of prodromal markers were associated with increased L1EV α-synuclein levels. Across all cohorts, L1EV α-synuclein differentiated participants with more than 80% probability of having prodromal PD from current and historic healthy control populations (AUC = 0.90; 95% CI, 0.87-0.93), irrespective of initial diagnosis. L1EV α-synuclein was increased in at-risk participants with a positive cerebrospinal fluid seed amplification assay and was above the identified threshold in 80% of cases (n = 40) that phenoconverted to PD or related dementia. CONCLUSIONS AND RELEVANCE: L1EV α-synuclein in combination with prodromal markers should be considered in the stratification of those at high risk of developing PD and related Lewy body diseases.

Clinical outcomes and clinico-pathological correlations in children with MPO-ANCA-associated glomerulonephritis showing renal arteritis.

The aim of this study was to evaluate the clinical features, pathological characteristics, and prognosis in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) with renal arteritis. The study involved 97 children from five pediatric clinical centers with MPO-AAGN who exhibited distinct clinical features. The patients were divided into AAGN-A+ and AAGN-A-, based on the presence or absence of arteritis, and the disparities in clinical, histopathological characteristics, and prognosis between the two groups was evaluated. In contrast to the AAGN-A- group, the children in the AAGN-A+ group exhibited more pronounced clinical symptoms and renal pathological injury. Arteritis positively moderately correlated with the serum creatinine, interleukin-6, urinary neutrophil gelatinase-associated lipocalin, negatively moderately correlated with serum complement C3. The renal survival rate in the AAGN-A+ group was significantly poorer than AAGN-A- group (χ2 = 4.278, p = 0.039). Arteritis showed a good predictive value for end-stage kidney disease (ESKD), and C3 deposition, ANCA renal risk score and arteritis were independent risk factors for the development of ESKD in children with MPO-AAGN. Arteritis is a significant pathological change observed in children with MPO-AAGN, and the formation of arteritis may be related to the inflammatory response and activation of the complement system.

Is Traditional Chinese Medicine Effective in Treating Tic Disorders (Tourette Syndrome)? A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Traditional Chinese medicine (TCM) is a type of alternative medicine that has been widely utilized in the prevention and treatment of neuropsychiatric diseases such as schizophrenia, ADHD, Alzheimer disease, and Tourette syndrome (TS) in many countries. However, the results regarding TCM's effectiveness and safety in treating TS are conflicting. Therefore, the goal of the present study is to analyze and summarize the available literature related to the efficacy of TCM in the treatment of tic disorders, especially TS. METHODS: Relevant articles for the meta-analysis were searched using appropriate keywords from PubMed, MEDLINE, and CENTRAL databases. Event data for TCM for the treatment of TS in the control and intervention arms were determined from the randomized controlled trials, and diagnostic odds ratio (DOR) and risk of bias analysis were performed. Meta-analysis was performed using MedCalc software, and suitable parameters to assess heterogeneity were computed. RESULTS: Twelve randomized clinical trials with a total of 1,681 TS patients were included as per the inclusion criteria. The patients' clinical symptoms were improved to a greater extent, and the pooled DOR of 1.311 with a 95% confidence interval (CI) value ranging from 0.804 to 2.139 and I2 value of 72.04% were obtained. The pooled relative risk was 1.09, with a 95% CI value ranging from 0.97 to 1.268. The data heterogeneity was assessed, and we achieved a Q value of 33.54, a p value of 0.0004, and I2 value of 67.21% with a 95% CI value of 32.91-82.10. All these values are statistically significant, with p < 0.005, and confirmed the effectiveness of TCM for TS patients. CONCLUSION: The present meta-analysis on account of these statistically significant results highly recommends using TCM to treat TS.

Design and Implementation of a Portable Knee Actuator for the Improvement of Crouch Gait in Children with Cerebral Palsy.

Common manifestation of spastic Cerebral Palsy (CP) are abnormal gait pathologies. These conditions require greater energy expenditure to successfully ambulate and are linked with significant deterioration in joint health and childhood musculoskeletal development. Crouch gait presents with knee hyperflexion throughout stance due to extensor muscle weakness and spasticity in flexor muscles stemming from neurological damage. The goal of this study was to develop a wearable cable-driven robotic system that applies controlled perturbation to the knee joint during overground walking in children with CP. Two children with spastic CP were recruited in this pilot study. They were tested in two conditions, i.e., applying knee resistance vs. knee assistance during overground walking. Kinematic and EMG data were recorded during overground walking. Data indicated that it was feasible to apply controlled knee perturbation torque during overground walking in children with crouch and preliminary results showed an improvement in crouch gait pattern in children with CP after one session of walking with the robotic system.Clinical Relevance- This study might have a potential clinical significance modifying neuromuscular control of CP patients with Crouch Gait.

Improving Trunk Postural Control Facilitates Walking in Children With Cerebral Palsy: A Pilot Study.

OBJECTIVE: The aim of this study is to determine the effects of bilateral trunk support during walking on trunk and leg kinematics and neuromuscular responses in children with cerebral palsy. DESIGN: Fourteen children with spastic cerebral palsy (Gross Motor Function Classification System level I to III) participated in this study. Children walked on a treadmill under four different conditions, that is, without support (Baseline), with bilateral support applied to the upper trunk (upper trunk support), the lower trunk (lower trunk support), and combined upper and lower trunk (combined trunk support). The trunk and leg kinematics and muscle activity were recorded. RESULTS: Providing bilateral support to the trunk had a significant impact on the displacement of the pelvis and trunk ( P < 0.003) during walking. Children's weaker leg showed greater step length ( P = 0.032) and step height ( P = 0.012) in combined trunk support compared with baseline and greater step length in upper trunk support ( P = 0.02) and combined trunk support ( P = 0.022) compared with lower trunk support. Changes in soleus electromyographic activity during stance phase of gait mirrored the changes in step length across all conditions. CONCLUSIONS: Providing bilateral upper or combined upper and lower trunk support during walking may induce improvements in gait performance, which may be due to improved pelvis kinematics. Improving trunk postural control may facilitate walking in children with cerebral palsy.

PIEZO1-HaloTag hiPSCs: Bridging Molecular, Cellular and Tissue Imaging.

PIEZO1 channels play a critical role in numerous physiological processes by transducing diverse mechanical stimuli into electrical and chemical signals. Recent studies underscore the importance of endogenous PIEZO1 activity and localization in regulating mechanotransduction. To enable physiologically and clinically relevant human-based studies, we genetically engineered human induced pluripotent stem cells (hiPSCs) to express a HaloTag fused to endogenous PIEZO1. Combined with super-resolution imaging, our chemogenetic approach allows precise visualization of PIEZO1 in various cell types. Further, the PIEZO1-HaloTag hiPSC technology allows non-invasive monitoring of channel activity via Ca2+-sensitive HaloTag ligands, with temporal resolution approaching that of patch clamp electrophysiology. Using lightsheet imaging of hiPSC-derived neural organoids, we also achieve molecular scale PIEZO1 imaging in three-dimensional tissue samples. Our advances offer a novel platform for studying PIEZO1 mechanotransduction in human cells and tissues, with potential for elucidating disease mechanisms and development of targeted therapeutics.