The effects of neurofeedback training for children with cerebral palsy and co-occurring attention deficits: A pilot study.

BACKGROUND: Limited research exists regarding the effectiveness of electroencephalogram (EEG) neurofeedback training for children with cerebral palsy (CP) and co-occurring attention deficits (ADs), despite the increasing prevalence of these dual conditions. This study aimed to fill this gap by examining the impact of neurofeedback training on the attention levels of children with CP and AD. METHODS: Nineteen children with both CP and co-occurring ADs were randomly assigned to either a neurofeedback or control group. The neurofeedback group received 20 sessions of training, lasting approximately 1 h per day, twice a week. Theta/beta ratios of the quantitative electroencephalography (QEEG) recordings were measured pre-training and post-training in the resting state. The Continuous Performance Test (CPT), the Test of Visual Perceptual Skills-3rd Version (TVPS-3) and the Conners' Parent Rating Scale (CPRS) were measured at pre- and post-training. RESULTS: The neurofeedback group showed both decreased theta/beta ratios compared with control group (p = 0.04) at post-training and a within-group improvement during training (p = 0.02). Additionally, the neurofeedback group had a trend of decreased omission rates of the CPT (p = 0.08) and the visual sequential memory and the visual closure subscores in the TVPS-3, compared with the control group (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: The results suggested that children with CP and co-occurring AD may benefit from neurofeedback training in their attention level. Further research is needed to explore long-term effects and expand its application in this population.

Sexual Crossing, Chromosome-Level Genome Sequences, and Comparative Genomic Analyses for the Medicinal Mushroom Taiwanofungus Camphoratus (Syn. Antrodia Cinnamomea, Antrodia Camphorata).

Taiwanofungus camphoratus mushrooms are a complementary and alternative medicine for hangovers, cancer, hypertension, obesity, diabetes, and inflammation. Though Taiwanofungus camphoratus has attracted considerable biotechnological and pharmacological attention, neither classical genetic nor genomic approaches have been properly established for it. We isolated four sexually competent monokaryons from two T. camphoratus dikaryons used for the commercial cultivation of orange-red (HC1) and milky-white (SN1) mushrooms, respectively. We also sequenced, annotated, and comparatively analyzed high-quality and chromosome-level genome sequences of these four monokaryons. These genomic resources represent a valuable basis for understanding the biology, evolution, and secondary metabolite biosynthesis of this economically important mushrooms. We demonstrate that T. camphoratus has a tetrapolar mating system and that HC1 and SN1 represent two intraspecies isolates displaying karyotypic variation. Compared with several edible mushroom model organisms, T. camphoratus underwent a significant contraction in the gene family and individual gene numbers, most notably for plant, fungal, and bacterial cell-wall-degrading enzymes, explaining why T. camphoratus mushrooms are rare in natural environments, are difficult and time-consuming to artificially cultivate, and are susceptible to fungal and bacterial infections. Our results lay the foundation for an in-depth T. camphoratus study, including precise genetic manipulation, improvements to mushroom fruiting, and synthetic biology applications for producing natural medicinal products. IMPORTANCETaiwanofungus camphoratus (Tc) is a basidiomycete fungus that causes brown heart rot of the aromatic tree Cinnamomum kanehirae. The Tc fruiting bodies have been used to treat hangovers, abdominal pain, diarrhea, hypertension, and other diseases first by aboriginal Taiwanese and later by people in many countries. To establish classical genetic and genomic approaches for this economically important medicinal mushroom, we first isolated and characterized four sexually competent monokaryons from two dikaryons wildly used for commercial production of Tc mushrooms. We applied PacBio single molecule, real-time sequencing technology to determine the near-completed genome sequences of four monokaryons. These telomere-to-telomere and gapless haploid genome sequences reveal all genomic variants needed to be studied and discovered, including centromeres, telomeres, retrotransposons, mating type loci, biosynthetic, and metabolic gene clusters. Substantial interspecies diversities are also discovered between Tc and several other mushroom model organisms, including Agrocybe aegerita, Coprinopsis cinerea, and Schizophyllum commune, and Ganoderma lucidum.

Association of age in motor function outcomes after multilevel myofascial release in children with cerebral palsy.

BACKGROUND: Many recommend deferring orthopedic surgery for cerebral palsy-related disorders in young children. However, age is correlated with musculoskeletal deterioration, and deferral may affect surgical outcomes. We aimed to clarify the relationships among age, degree of musculoskeletal disorder, and postoperative motor function change in children with cerebral palsy. METHODS: We prospectively evaluated children with cerebral palsy and a knee flexion gait disorder who underwent multilevel myofascial release between June 2010 and July 2014. The children were divided into younger (<10 years of age) and older (>10 years of age) groups. Outcome measures included the Gross Motor Function Measure (GMFM), range of motion, spasticity, and physical capacity. Preoperative factors and postoperative changes were compared between the groups using the chi-squared, independent t-, and Mann-Whitney tests. Significant factors were plotted by participant age to identify the relationships between age and other variables. RESULTS: We analyzed 20 patients who underwent multilevel myofascial release (12 and 8 in the younger and older groups, respectively). Whereas most preoperative factors were comparable between the two groups, the older group had a higher range of motion limitation score (44.4 vs. 36.1, p < 0.05). The older group also showed less improvement in the GMFM (-0.3 vs. +3.0, p < 0.05) and physical capacity (+0 vs. +1, p < 0.05) scores after 6 months of postoperative rehabilitation. CONCLUSIONS: Age was positively correlated with the range of motion limitation and negatively correlated with postoperative GMFM improvement. The less favored postoperative rehabilitation course in older children needs to be considered for parents whose children are amenable to surgeries.

Effects of action observation therapy and mirror therapy after stroke on rehabilitation outcomes and neural mechanisms by MEG: study protocol for a randomized controlled trial.

BACKGROUND: Loss of upper-extremity motor function is one of the most debilitating deficits following stroke. Two promising treatment approaches, action observation therapy (AOT) and mirror therapy (MT), aim to enhance motor learning and promote neural reorganization in patients through different afferent inputs and patterns of visual feedback. Both approaches involve different patterns of motor observation, imitation, and execution but share some similar neural bases of the mirror neuron system. AOT and MT used in stroke rehabilitation may confer differential benefits and neural activities that remain to be determined. This clinical trial aims to investigate and compare treatment effects and neural activity changes of AOT and MT with those of the control intervention in patients with subacute stroke. METHODS/DESIGN: An estimated total of 90 patients with subacute stroke will be recruited for this study. All participants will be randomly assigned to receive AOT, MT, or control intervention for a 3-week training period (15 sessions). Outcome measurements will be taken at baseline, immediately after treatment, and at the 3-month follow-up. For the magnetoencephalography (MEG) study, we anticipate that we will recruit 12 to 15 patients per group. The primary outcome will be the Fugl-Meyer Assessment score. Secondary outcomes will include the modified Rankin Scale, the Box and Block Test, the ABILHAND questionnaire, the Questionnaire Upon Mental Imagery, the Functional Independence Measure, activity monitors, the Stroke Impact Scale version 3.0, and MEG signals. DISCUSSION: This clinical trial will provide scientific evidence of treatment effects on motor, functional outcomes, and neural activity mechanisms after AOT and MT in patients with subacute stroke. Further application and use of AOT and MT may include telerehabilitation or home-based rehabilitation through web-based or video teaching. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02871700 . Registered on 1 August 2016.

Therapeutic effect of berberine on TDP-43-related pathogenesis in FTLD and ALS.

BACKGROUND: In the central nervous system regions of the sporadic and familial FTLD and ALS patients, TDP-43 has been identified as the major component of UBIs inclusions which is abnormally hyperphosphorylated, ubiquitinated, and cleaved into C-terminal fragments to form detergent-insoluble aggregates. So far, the effective drugs for FTLD and ALS neurodegenerative diseases are yet to be developed. Autophagy has been demonstrated as the major metabolism route of the pathological TDP-43 inclusions, hence activation of autophagy is a potential therapeutic strategy for TDP-43 pathogenesis in FTLD and ALS. Berberine, a traditional herbal medicine, is an inhibitor of mTOR signal and an activator for autophagy. Berberine has been implicated in several kinds of diseases, including the neuronal-related pathogenesis, such as Parkinson's, Huntington's and Alzheimer's diseases. However, the therapeutic effect of berberine on FTLD or ALS pathology has never been investigated. RESULTS: Here we studied the molecular mechanism of berberine in cell culture model with TDP-43 proteinopathies, and found that berberine is able to reverse the processing of insoluble TDP-43 aggregates formation through deregulation of mTOR/p70S6K signal and activation of autophagic degradation pathway. And inhibition of autophagy by specific autophagosome inhibitor, 3-MA, reverses the effect of berberine on reducing the accumulation of insoluble TDP-43 and aggregates formation. These results gave us the notion that inhibition of autophagy by 3-MA reverses the effect of berberine on TDP-43 pathogenesis, and activation of mTOR-regulated autophagy plays an important role in berberine-mediated therapeutic effect on TDP-43 proteinopathies. CONCLUSION: We supported an important notion that the traditional herb berberine is a potential alternative therapy for TDP-43-related neuropathology. Here we demonstrated that berberine is able to reverse the processing of insoluble TDP-43 aggregates formation through deregulation of mTOR/p70S6K signal and activation of autophagic degradation pathway. mTOR-autophagy signals plays an important role in berberine-mediated autophagic clearance of TDP-43 aggregates. Exploring the detailed mechanism of berberine on TDP-43 proteinopathy provides a better understanding for the therapeutic development in FTLD and ALS.

IFN-γ Induces Mimic Extracellular Trap Cell Death in Lung Epithelial Cells Through Autophagy-Regulated DNA Damage.

Treatment of interferon-γ (IFN-γ) causes cell growth inhibition and cytotoxicity in lung epithelial malignancies. Regarding the induction of autophagy related to IFN-γ signaling, this study investigated the link between autophagy and IFN-γ cytotoxicity. In A549 human lung cancer cells, IFN-γ treatment induced concurrent apoptotic and nonapoptotic events. Unexpectedly, the nonapoptotic cells present mimic extracellular trap cell death (ETosis), which was regulated by caspase-3 and by autophagy induction through immunity-related GTPase family M protein 1 and activating transcription factor 6. Furthermore, IFN-γ signaling controlled mimic ETosis through a mechanism involving an autophagy- and Fas-associated protein with death domain-controlled caspase-8/-3 activation. Following caspase-mediated lamin degradation, IFN-γ caused DNA damage-associated ataxia telangiectasia and Rad3-related protein (ATR)/ataxia telangiectasia mutated (ATM)-regulated mimic ETosis. Upon ATR/ATM signaling, peptidyl arginine deiminase 4 (PAD4)-mediated histone 3 citrullination promoted mimic ETosis. Such IFN-γ-induced effects were defective in PC14PE6/AS2 human lung cancer cells, which were unsusceptible to IFN-γ-induced autophagy. Due to autophagy-based caspase cascade activation, IFN-γ triggers unconventional caspase-mediated DNA damage, followed by ATR/ATM-regulated PAD4-mediated histone citrullination during mimic ETosis in lung epithelial malignancy.

Combining Afferent Stimulation and Mirror Therapy for Improving Muscular, Sensorimotor, and Daily Functions After Chronic Stroke: A Randomized, Placebo-Controlled Study.

OBJECTIVE: Mirror therapy (MT) combined with mesh glove (MG) afferent stimulation (MT + MG) has been suggested as an effective intervention for motor recovery in patients with stroke. This study aimed to further determine the treatment effects of the MT + MG approach on muscular properties, sensorimotor functions, and daily function. DESIGN: This was a single-blind, randomized, placebo-controlled study. Forty-eight participants with chronic stroke were recruited from medical centers and were randomly assigned to the MT, MT + MG, and MT with sham MG stimulation (MT + sham) groups. The intervention consisted of 1.5 hrs/day, 5 days/wk for 4 wks. Primary outcomes were the Fugl-Meyer Assessment and muscular properties (muscle tone and stiffness). Secondary outcomes included measures of sensorimotor and daily functions. RESULTS: Compared with the MT and MT + sham groups, the MT + MG group demonstrated improved muscular properties. The MT + MG and MT + sham groups showed greater improvement in manual dexterity and daily function than the MT group did. No beneficial effects on the Fugl-Meyer Assessment and other sensorimotor outcomes were found for the MT + MG group. CONCLUSIONS: Although no significant group differences were found in the Fugl-Meyer Assessment, MT + MG induced distinctive effects on muscular properties, manual dexterity, and daily function.

Pediatric aquatic therapy on motor function and enjoyment in children diagnosed with cerebral palsy of various motor severities.

This study investigates the effects of pediatric aquatic therapy on motor function, enjoyment, activities of daily living, and health-related quality of life for children with spastic cerebral palsy of various motor severities. Children with spastic cerebral palsy were assigned to a pediatric aquatic therapy group (n = 11; mean age = 85.0 ± 33.1 months; male : female = 4 : 7) or a control group (n = 13; mean age = 87.6 ± 34.0 months; male : female = 9 : 4). The statistic results indicate that the pediatric aquatic therapy group had greater average 66-item Gross Motor Function Measure following intervention than the control group (η(2) = 0.308, P = .007), even for children with Gross Motor Function Classification System level IV (5.0 vs 1.3). The pediatric aquatic therapy group had higher Physical Activity Enjoyment Scale scores than the control group at post-treatment (P = .015). These findings demonstrate that pediatric aquatic therapy can be an effective and alternative therapy for children with cerebral palsy even with poor Gross Motor Function Classification System level.

Efficacy of constraint-induced therapy on functional performance and health-related quality of life for children with cerebral palsy: a randomized controlled trial.

To better generalize training effects to the context of daily living, home-based constraint-induced therapy has been proposed. Therapeutic success of constraint-induced therapy is limited as to whether the improvements in functional performance can be transferred to quality of life. This randomized controlled trial aimed to investigate the efficacy of home-based constraint-induced therapy on functional performance and health-related quality of life. Twenty-two children with spastic unilateral cerebral palsy (6-8 years, 10 boys) were randomly assigned to receive constraint-induced therapy or traditional rehabilitation. Home-based constraint-induced therapy had immediate and maintaining effects on motor efficacy and functional performance and induced greater gains in health-related quality of life in the long run than in the short term. The home-based constraint-induced therapy protocol (relatively moderate intensity and shortened constraint time), which might balance the effectiveness and compliance of participants and caregivers, may be an effective alternative to conventional constraint-induced therapy.

Influence of magnetic knee wraps on joint proprioception in individuals with osteoarthritis: a randomized controlled pilot trial.

OBJECTIVE: To determine the effects of magnetic knee wraps (MKWs) on joint position sense (JPS) in individuals with mild-to-moderate knee osteoarthritis. DESIGN: Randomized, double-blind, placebo-controlled pilot trial. SETTING: Rehabilitation clinic of a tertiary hospital. SUBJECTS: Fifty volunteers with mild-to-moderate knee osteoarthritis participated and 33 (66%) completed the trial; only one (2%) withdrew due to study-related adverse effects. INTERVENTIONS: Knee wraps with a static magnetic field (35 mT) were compared with control knee wraps for 12 weeks. MAIN MEASURES: The main outcome measure was JPS at first, fourth, and twelfth week while applying of the knee wrap, quantified as the ability to replicate target knee joint angles. The secondary outcome was the Comprehensive Osteoarthritis Test (COAT) total score. RESULTS: In the intention-to-treat analysis with an alpha-level of 0.05, 12-week application of the MKWs did not significantly reduce the mean absolute error (MAE) of JPS (n = 18; P = 0.627); contrarily, the MAE was found to decrease significantly after wearing the sham MKWs (n = 20; P = 0.01). The COAT total score gradually improved in both groups (P < 0.05). When comparing the improvement of MAE and COAT total score at each follow-up between two groups, no significant differences were found; the maximal difference in the improvement of MAE between two groups was noted at week 12 (mean difference: 1.2°; 95% confidence interval -0.4 to 2.9; P = 0.144). In the per-protocol analysis, the study group showed better improvement in the COAT total score at week 12 (P = 0.033). CONCLUSION: The 35-mT MKWs could not significantly influence knee JPS in individuals with mild-to-moderate knee osteoarthritis.

Free radical scavenging activity and antiproliferative potential of Polygonum cuspidatum root extracts.

Polygonum cuspidatum is widely used as a medicinal herb in Asia. In this study, ethanol and ethyl acetate extracts of P. cuspidatum root were assayed for their 1,1-diphenyl-2-hydrazyl (DPPH) and hydroxyl free radical scavenging activities, total phenolics content, protective effect against DNA damage, and antiproliferative activity on human lung cancer cells. The ethanol and ethyl acetate (lipophilic phase) extracts of P. cuspidatum had significant scavenging effects on DPPH and hydroxyl radicals. Total phenolics content of ethanol and ethyl acetate (lipophilic phase) extracts of P. cuspidatum were 276.78 +/- 39.31 and 231.73 +/- 5.04 mg/ml, respectively; both extracts protected against hydroxyl radical-induced DNA strand scission. Furthermore, the extracts of P. cuspidatum induced apoptosis and inhibited cell growth in A549 and H1650 cell lines, suggesting that P. cuspidatum root extracts exhibit an antiproliferative effect on human lung cancer cells.

The effects of bilateral arm training on motor control and functional performance in chronic stroke: a randomized controlled study.

BACKGROUND: Most studies of bilateral arm training (BAT) did not employ a randomized controlled trial design and involved very limited functional training tasks. OBJECTIVE: Compare the effects of BAT with control intervention (CI) on motor control and motor performance of the upper extremity and also functional gains in patients with chronic stroke. METHODS: . This 2-group randomized controlled trial with pretreatment and posttreatment measures enrolled 33 stroke patients (mean age = 53.85 years) 6 to 67 months after onset of a first stroke. They received either a BAT program concentrating on both upper extremities moving simultaneously in functional tasks by symmetric patterns or CI (control treatment) for 2 hours on weekdays for 3 weeks. Outcome measures included kinematic analyses assessing motor control strategies for unilateral and bimanual reaching and clinical measures involving the Fugl-Meyer Assessment (FMA) of motor-impairment severity and the Functional Independence Measure (FIM) and the Motor Activity Log (MAL) evaluating functional ability. RESULTS: After treatment, the BAT group showed better temporal and spatial efficiency during unilateral and bilateral tasks and less online error correction only during the bilateral task than the control group. The BAT group showed a significantly greater improvement in the FMA than the control group but not in the FIM and MAL. CONCLUSIONS: Relative to CI, BAT improved the spatiotemporal control of the affected arm in both bilateral and unilateral tasks, decreased online corrections to perform bilateral tasks, and reduced motor impairment. These findings support the use of BAT to improve motor control and motor function of the affected upper limb in stroke patients.

The heterogeneous integration of single-walled carbon nanotubes onto complementary metal oxide semiconductor circuitry for sensing applications.

A simple methodology for integrating single-walled carbon nanotubes (SWNTs) onto complementary metal oxide semiconductor (CMOS) circuitry is presented. The SWNTs were incorporated onto the CMOS chip as the feedback resistor of a two-stage Miller compensated operational amplifier utilizing dielectrophoretic assembly. The measured electrical properties from the integrated SWNTs yield ohmic behavior with a two-terminal resistance of approximately 37.5 kOmega and the measured small signal ac gain (-2) from the inverting amplifier confirmed successful integration of carbon nanotubes onto the CMOS circuitry. Furthermore, the temperature response of the SWNTs integrated onto CMOS circuitry has been measured and had a thermal coefficient of resistance (TCR) of -0.4% degrees C(-1). This methodology, demonstrated for the integration of SWNTs onto CMOS technology, is versatile, high yield and paves the way for the realization of novel miniature carbon-nanotube-based sensor systems.

Effect of magnetic knee wrap on quadriceps strength in patients with symptomatic knee osteoarthritis.

OBJECTIVE: To determine the effects of magnetic knee wrap on isokinetic quadriceps strength in patients with painful knee osteoarthritis (OA). DESIGN: Randomized, double-blinded, placebo-controlled and before-after trial. SETTING: Rehabilitation clinic in a tertiary hospital. PARTICIPANTS: Eligible patients (N=50) (mean age+/-SD, 66.0+/-8.6 y) with mild to moderate knee OA were recruited from the outpatient department and 37 (74%) completed the trial. Only 3 (6%) withdrew due to study-related adverse effects. INTERVENTIONS: Wearing the active (n=24) or sham (n=26) magnetic knee wrap for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was isokinetic quadriceps strength. Secondary outcome measures included the Health Assessment Questionnaire Disability Index (HAQ-DI) and the Health Assessment Questionnaire (HAQ) Pain Scale. RESULTS: Using intention-to-treat analyses, the peak isokinetic quadriceps strength increased significantly in the treated leg at 30 degrees/s (P=.007) and 60 degrees/s (P=.022) after wearing the magnetic knee wrap. Compared with baseline, the median strength increase for the treated leg in the study group significantly exceeded that in the control group at week 4 (.05 Nm/kg vs -.09 Nm/kg at 60 degrees/s, P=.038) and week 12 (30 degrees/s, .09 Nm/kg vs .04 Nm/kg, P=.044; 60 degrees/s, .17 Nm/kg vs .02 Nm/kg, P=.031). The HAQ-DI and HAQ Pain Scales improved significantly in both groups. Compared with baseline, the improvement at week 12 in terms of the HAQ-DI in the study group significantly exceeded that in the control group. CONCLUSIONS: Magnetic knee wrap may significantly facilitate isokinetic quadriceps strength in patients with mild to moderate knee OA.

Effect of neuromuscular electrical stimulation on cough capacity and pulmonary function in patients with acute cervical cord injury.

OBJECTIVE: To assess the effectiveness of neuromuscular electrical stimulation (NMES) on cough capacity and prevention of pulmonary complication in patients with acute cervical cord injury. DESIGN: A randomized controlled trial. SUBJECTS: Twenty-six tetraplegic patients with cervical spinal cord injury, 13 in the NMES therapy group and 13 in the control group. METHODS: NMES was applied to the clavicular portion of the pectoralis major and abdominal muscle. Pulmonary function tests were performed before and after therapy, and at 3 months and 6 months follow-up. The pulmonary complications in this 6-month follow-up period were also recorded. RESULTS: After the 4-week therapy, and at 3 months and 6 months follow-up testing, patients in the NMES therapy group displayed significant improvement in their peak expiratory flow, forced expiratory volume in 1 second, forced vital capacity, maximal expiratory pressure and maximal inspiratory pressure, compared with those in the control group (p<0.05). Patients in the NMES therapy group also had fewer pulmonary complications in the follow-up period. CONCLUSION: NMES over the pectoralis and abdominal muscles might improve cough capacity and pulmonary function in cervical spinal cord injury with tetraplegia. This improvement might last for 6 months. With this improvement, pulmonary complications were reduced.