Efficacy of Motor Interventions on Functional Performance Among Preschool Children With Autism Spectrum Disorder: A Pilot Randomized Controlled Trial.

IMPORTANCE: Motor ability plays an important role in overall developmental profiles. Preschool children with autism spectrum disorder (ASD) are at risk of motor skills deficits and delays. However, evidence of the efficacy of different motor interventions for the identification of optimal treatment types is lacking, especially for preschool children with ASD. OBJECTIVE: To examine the efficacy of the Motor Skill Occupational Therapy Intervention ON ASD (MOTION-ASD) and Cognitive Orientation Exercise (CO-EXC) programs to improve motor skills performance, self-care performance, and adaptive behaviors among preschool children with ASD. DESIGN: Randomized controlled trial, two-group, triple-blinded, repeated-measures design Setting: University laboratory. PARTICIPANTS: Thirteen preschool children with ASD (M age = 4.91 yr). OUTCOMES AND MEASURES: The Bruininks-Oseretsky Test of Motor Proficiency-Second Edition, Brief Form, Assessment of Motor and Process Skills, and Vineland Adaptive Behavior Scales-Third Edition. RESULTS: Children in the MOTION-ASD group showed significantly greater improvements in manual coordination and overall gross and fine manual skills than those in the CO-EXC group immediately after the intervention. Significant improvements in fine manual control, body coordination, overall motor skills, and self-care performance were made throughout both interventions and were retained at the posttest and the 4-wk follow-up. CONCLUSIONS AND RELEVANCE: These findings provide supporting evidence that motor skills interventions involving fundamental skills and cognitive training may be a viable therapeutic option for treating children with ASD. The results also suggest that practitioners may consider providing structured and strategic motor skills interventions for preschool children with ASD. What This Article Adds: This study's rigorous tests of motor skills interventions support ways to manage motor difficulties in children with autism spectrum disorder (ASD). An intervention based on motor learning theory could benefit preschool children with ASD, especially in terms of manual coordination ability and overall gross and fine motor skills.

Does Botulinum Toxin Injection Exacerbate Sarcopenia and Bone Mass in Individuals With Cerebral Palsy?

BACKGROUND: Botulinum toxin (BoNT) causes sarcopenia and low bone mass in animal studies. Whether such effect exists in children and adolescents with spastic cerebral palsy (CP) is not clear yet. To investigate the influences of BoNT on grip strength (GS), skeletal muscle mass, and bone mineral density (BMD) in children and adolescents with spastic CP, we conducted this uncontrolled longitudinal study. METHODS: The body composition of individuals with spastic CP were measured by dual-energy X-ray absorptiometry at preinjection and at 12 and 24 weeks after BoNT intervention. Sarcopenia was defined as meeting both decreased GS and low muscle mass. Twenty-five participants were enrolled (mean age 8.5 years). RESULTS: Before BoNT intervention, four adolescents had sarcopenia and low bone mass. When the body composition was analyzed as four limbs, trunk, and head, the skeletal muscle mass of the injected limbs, appendicular skeletal muscle mass, and total body less head BMD increased significantly over 24-week follow-up period (P = 0.0117, 0.0032, 0.0229), whereas the GS remained unchanged. When the body composition was analyzed as segments derived from bilateral arms, forearms, hands, thighs, and lower legs, the skeletal muscle mass (P = 0.0113) but not BMD of the injected segments increased significantly over the 24 weeks. The prevalence of low muscle mass, decreased GS, sarcopenia, and low bone mass did not change over 24 weeks. CONCLUSIONS: The present study showed that BoNT does not exacerbate sarcopenia and low bone mass in individuals with spastic CP.

Cognitive Predictors of Social Interaction in Daily Contexts Among Children With Autism Spectrum Disorder.

IMPORTANCE: Theory of mind (ToM) and executive function (EF) are often used to explain social interaction deficits in children with autism spectrum disorder (ASD), but no behavioral studies have specifically examined their relationship. OBJECTIVE: To investigate the cognitive correlates of social interaction in daily contexts by ToM as well as cool and hot EFs among children with ASD. DESIGN: Cross-sectional study. SETTING: Teaching hospitals, clinics, and developmental centers. PARTICIPANTS: One hundred thirty-two children with ASD and their caregivers. OUTCOMES AND MEASURES: Measurements included the Vineland Adaptive Behavior Scales, Theory of Mind Task Battery, Dimensional Change Card Sort, and Children's Gambling Task, respectively, for children's daily social interaction, ToM, cool EF, and hot EF. Pearson's correlation analyses and three hierarchical regression models were conducted to identify the significant predictors of daily social interaction while controlling for verbal comprehension, measured using the Verbal Comprehension Index (VCI) of two Wechsler scales. RESULTS: ToM and cool EF were significant cognitive predictors of social interaction in daily contexts in children with ASD whose verbal comprehension was average or above average. CONCLUSIONS AND RELEVANCE: Our results suggest that ToM and cool EF are predictors of social interaction in daily contexts when considering children's verbal comprehension. Hot EF was not a significant predictor, contrary to our hypothesis. This behavioral study fills a research gap by enhancing the understanding of important cognitive correlates of social interaction in daily contexts for children with ASD to improve evaluation and intervention planning with this population. What This Article Adds: This study identified two cognitive predictors, ToM and cool EF, of social interaction in daily contexts for children with ASD. In addition to verbal comprehension, occupational therapy practitioners should assess ToM and cool EF to inform more comprehensive evaluation and intervention planning to improve social interaction in daily contexts for children with ASD.

A Touch-Observation and Task-Based Mirror Therapy Protocol to Improve Sensorimotor Control and Functional Capability of Hands for Patients With Peripheral Nerve Injury.

IMPORTANCE: To develop a practical program in the early phase after nerve repair for more rapid return of function. OBJECTIVE: To investigate the effects of touch-observation and task-based mirror therapy on the sensorimotor outcomes of patients with nerve repair. DESIGN: An assessor-blinded study with a randomized controlled design. SETTING: University hospital. PARTICIPANTS: We recruited 12 patients with median or ulnar nerve repair between the level of midpalm and elbow referred by the plastic surgeons. INTERVENTION: The patients were randomized into touch-observation and task-based mirror therapy or control groups, and both groups received training for 12 wk. OUTCOMES AND MEASURES: The Semmes-Weinstein monofilament (SWM) test, two-point discrimination test, Purdue Pegboard Test (PPT), Minnesota Manual Dexterity Test (MMDT), and pinch-holding-up activity test were assessed at pretreatment, immediately after treatment, and 12 wk after the last treatment. RESULTS: The experimental group showed greater improvements in the results of the pinch-holding-up activity test and the PPT Unilateral Pin Insertion, Bilateral Pin Insertion, and Assembly subtests. However, change on the SWM test revealed no significant difference between the two groups. CONCLUSIONS AND RELEVANCE: Touch-observation and task-based mirror therapy is an effective but low-cost treatment protocol to optimize sensorimotor control and functional capability of the upper limb in patients with peripheral nerve injury.

Effects of the Surface Texture and Weight of a Pinch Apparatus on the Reliability and Validity of a Hand Sensorimotor Control Assessment.

OBJECTIVES: To investigate the reliability and validity of a modified pinch apparatus devised with 3 surface textures and 2 different weights for clinical application. DESIGN: Case-controlled study. SETTING: A university hospital. PARTICIPANTS: The participants (N=32) included carpal tunnel syndrome (CTS) patients (n=16) with 20 sensory neuropathy hands, and an equal number of age-sex matched volunteers without CTS, as well as young volunteers without CTS (n=16 with 20 hands) used to analyze both the testing validity and reliability of the modified device. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Semmes-Weinstein monofilament (SWM) and two-point discrimination (2PD) tests were conducted, and the force ratio between the FPpeak (peak pinch force during lifting phase) and FLmax (maximum load force at maximum upward acceleration onset) detected from a pinch-holding-up activity (PHUA) under various testing conditions was obtained. RESULTS: The range of the intraclass correlation coefficient of this pinch device was 0.369-0.952. The CTS patients exhibited poorer force modulation ability according to the inertial change in a dynamic lifting task when compared to the controls under all testing conditions (P<.001). The area under the receiver operating characteristic force ratio curve was 0.841, revealing high accuracy of the test for diagnosing CTS neuropathic hands under the testing condition in which the 125-g coarse texture device was used. In addition, the weight factor was shown to have significant effects on the sensitivity and accuracy of the PHUA assessment. CONCLUSIONS: This study showed that the PHUA test via the modified pinch apparatus is a sensitive tool that can be used in clinical practice for detecting neuropathic CTS hands. In addition, changing the weight of the pinch device has a significant effect on the sensitivity and accuracy of the PHUA assessment.

Impacts of Sensation, Perception, and Motor Abilities of the Ipsilesional Upper Limb on Hand Functions in Unilateral Stroke: Quantifications From Biomechanical and Functional Perspectives.

BACKGROUND: The presence of subtle losses in hand dexterity after stroke affects the regaining of independence with regard to activities of daily living. Therefore, awareness of ipsilesional upper extremity (UE) function may be of importance when developing a comprehensive rehabilitation program. However, current hand function tests seem to be unable to identify asymptomatic UE impairments. OBJECTIVES: To assess the motor coordination as well as the sensory perception of an ipsilesional UE using biomechanical analysis of performance-oriented tasks and conducting a Manual Tactile Test (MTT). DESIGN: Case-controlled study. SETTING: A university hospital. PARTICIPANTS: A total of 21 patients with unilateral stroke, along with 21 matched healthy control subjects, were recruited. METHODS: Each participant was requested to perform a pinch-holding-up activity (PHUA) test, object-transport task, and reach-to-grasp task via motion capture, as well as the MTT. MAIN OUTCOME MEASUREMENTS: The kinetic data of the PHUA test, kinematics analysis of functional movements, and time requirement of MTT were analyzed. RESULTS: Patients with ipsilesional UE had an inferior ability to scale and produce pinch force precisely when conducting the PHUA test compared to the healthy controls (P < .05). The movement time was statistically longer and peak velocity was significantly lower (P < .05) in the performance-oriented tasks for the ipsilesional UE patients. The longer time requirement in 3 MTT subtests showed that the ipsilesional UE patients experienced degradation in sensory perception (P < .001). CONCLUSION: Comprehensive sensorimotor assessments based on functional perspectives are valid tools to determine deficits in the sensation-perception-motor system in the ipsilesional UE. Integration of sensorimotor training programs for ipsilesional UE in future neuro-rehabilitation strategies may provide more beneficial effects to regain patients' motor recovery and to promote daily living activity independence than focusing on paretic arm motor training alone. LEVEL OF EVIDENCE: III.

Determining the functional sensibility of the hand in patients with peripheral nerve repair: Feasibility of using a novel manual tactile test for monitoring the progression of nerve regeneration.

STUDY DESIGN: Case-controlled cohort study. INTRODUCTION: Sensory function is difficult to observe during nerve regeneration processes. Traditional sensory tests are limited to identifying the level of functioning hand sensation for sensory stimulus is given passively to the cutaneous surface of the hand. PURPOSE OF THE STUDY: To examine the outcome changes in the manual tactile test (MTT), Semmes-Weinstein monofilament (SWM) and 2-point discrimination (2PD) tests for patients with nerve repair and to investigate the concurrent validity of MTT by comparing it with the results of traditional tests. METHODS: Fifteen patients with nerve injury of the upper limbs were recruited, along with 15 matched healthy controls. The MTT, SWM, and 2PD tests were used to examine the sensory status of the subjects. RESULTS: Three subtests (barognosis, roughness differentiation, and stereognosis) in MTT showed that the patients improved with time. A moderate and mild correlation was found between the MTT and 2PD results and between the barognosis and SWM results. CONCLUSIONS: The MTT provides practical and functional perspectives on detecting nerve progression during the courses of degeneration and regeneration. LEVEL OF EVIDENCE: IV.

Manual Tactile Test Predicts Sensorimotor Control Capability of Hands for Patients With Peripheral Nerve Injury.

OBJECTIVES: To comprehend the merits of a Manual Tactile Test (MTT) in assessing hand sensorimotor functions by exploring the relations among 3 subtests along with the precision pinch performances for patients with peripheral nerve injuries (PNIs); and to understand the accuracy of the MTT by constructing the sensitivity and specificity of the test for patients with PNI. DESIGN: Case-control study. SETTING: Hospital and local community. PARTICIPANTS: Patients with PNI (n=28) were recruited along with age-, sex-, and handedness-matched healthy controls (n=28) (N=56). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Semmes-Weinstein monofilament, moving and static 2-point discrimination, roughness differentiation, stereognosis and barognosis subtests of the MTT, and precision pinch performance were used to examine the sensory and sensorimotor status of the hand. RESULTS: The worst results in all sensibility tests were found for the patients with PNI (P<.001) in comparison with the controls. Multiple linear regression analysis showed the MTT was a better indicator for predicting the sensorimotor capacity of hands in the patients with PNI (r(2)=.189, P=.003) than the traditional test (r(2)=.088, P=.051). The results of the receiver operating characteristic curve estimation show that the area under the curve was .968 and .959 for the roughness differentiation and stereognosis subtests, respectively, and .853 for the barognosis subtest, therefore revealing the accuracy of the MTT in assessing sensorimotor status for patients with PNI. CONCLUSIONS: This study indicates that the MTT is highly accurate and a significant predictor of sensorimotor performance in hands of patients with PNI. The MTT could therefore help clinicians obtain a better understanding of the sensorimotor and functional status of the hand with nerve injuries.

Downregulated CXCL12 expression in mesenchymal stem cells associated with severe aplastic anemia in children.

The mechanisms of idiopathic severe aplastic anemia (SAA) in children are not completely understood. Insufficiency of the bone marrow microenvironment, in which mesenchymal stem cells (MSCs) are an important element, can be a potential factor associated with hematopoietic impairment. In the current study, we studied whether aberrant gene expression could be found in MSCs from children with SAA. Using microarray analysis, two different patterns of global gene expression were detected in the SAA MSCs. Fourteen genes (POLE2, HGF, KIF20A, TK1, IL18R1, KITLG, FGF18, RRM2, TTK, CXCL12, DLG7, TOP2A, NUF2, and TYMS), which are related to DNA synthesis, cytokines, or growth factors, were significantly downregulated. Further, knockdown of gene expression was performed using the small hairpin RNA (shRNA)-containing lentivirus method. We found that knockdown of CXCL12, HGF, IL-18R1, FGF18, or RRM2 expression compelled MSCs from the controls to behave like those from the SAA children, with decreased survival and differentiation potential. Among them, inhibition of CXCL12 gene expression had the most profound effects on the behavior of MSCs. Further experiments regarding re-introduction of the CXCL12 gene could largely recover the survival and differentiation potential in MSCs with inhibition of CXCL12 expression. Our findings suggest that MSCs from children with SAA exhibit aberrant gene expression profiles and downregulation of CXCL12 gene may be associated with alterations in the bone marrow microenvironment.

Visual feedback and target size effects on reach-to-grasp tasks in children with autism.

This study explores the effects of visual condition and target size during four reach-to-grasp tasks between autistic children and healthy controls. Twenty children with autism and 20 healthy controls participated in the study. Qualisys motion capture system and kinematic measures were used to record movement. Autistic group showed significantly longer movement time, larger normalized jerk score, more movement unit than controls, especially in non-visual feedback and small target blocks. Autistic group also showed significantly larger maximal grip aperture and normalized maximal grip aperture in visual feedback condition than controls. Autistic children demonstrate motor coordination problems and also depend on more visual cuing in high accuracy tasks. Autistic children develop other compensatory skills while performing tasks.

Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects.

Dihydrodiol dehydrogenase (DDH) is frequently detected in cancer cells, and its overexpression correlates with drug resistance, the downregulation of DNA repair mechanisms, increased frequency of tumor recurrence, cancer cell metastasis and poor prognosis. The silencing of DDH expression using siRNA, on the other hand, reduces drug resistance and cancer cell mobility. These data suggest that DDH may be an oncogene-related protein. However, no specific DDH inhibitor has been identified to date. Thus, in this study, we used DDH as a target enzyme in a live-cell enzyme-linked immunosorbent assay to screen Chinese medicinal herb extracts (CMHEs) with the aim of identifying a DDH inhibitor. Using this method, we found 49 among 796 CMHEs that inhibited DDH expression. We selected three potential extracts, which had the highest activity against DDH, for further fractionation using high-performance liquid chromatography. The active ingredient was identified by immunoblot analysis. The function of the active ingredient was characterized by cell function analysis. Our results revealed that the CMHE-purified compounds targeted DDH, inducing autophagy and reducing DNA repair, which in turn enhanced the cytotoxic effects of the anticancer drugs and irradiation.

Expression of EBV-encoded oncogenes and EBV-like virions in multiple canine tumors.

Epstein-Barr virus (EBV) is a ubiquitous human oncovirus. Previous studies by us and others have indicated that pet dogs frequently encounter EBV or EBV-related viral infection. In this study, we explored whether EBV is involved in canine malignancies in dogs. EBV-specific BamHI W sequence was detected by polymerase chain reaction (PCR) in 10 of 12 canine tumor specimens, including 8 of 10 oral tumors. Using reverse transcription-PCR, gene expressions of latent membrane protein 1 (LMP 1) and BamHI H rightward reading frame 1 (BHRF1) were identified in 8 and 7 of 12 specimens, respectively. A novel LMP1 variant, T0905, was predominant in 5 canine tumor specimens and found to exist in EBV positive human BC-2 cells. Another LMP1 variant, T0902, was similar to human tumor variant JB7. The BHRF1 sequence identified from these canine tumors was identical to that of the B95-8 viral strain. LMP1 protein and EBV-encoded RNA (EBER) were detected by immunohistochemistry and fluorescent in situ hybridization, respectively, in several tumors, particularly in tumor nests of oral amelanotic melanomas. Furthermore, EBV-like virions adopting a herpesvirus egress pathway were detected in a canthal fibroblastic osteosarcoma and an oral amelanotic melanoma. In conclusion, we report the expressions of BHRF1 transcript (a viral anti-apoptotic protein), LMP1 (a viral oncoprotein) transcript and protein, EBER (a viral oncogenic RNA), and EBV-like virions in multiple canine tumors. The identity of BHRF1 and the resemblance of LMP1 variants between canine and human tumors indicate either a close evolutionary relationship between canine and human EBV, or the possibility of zoonotic transmission.