Therapeutic Effects of an Anti-Gravity Treadmill (AlterG) Training on Neuromuscular Abnormalities Associated with Spasticity in Children with Cerebral Palsy.

We aimed to characterize the therapeutic effects of Anti-Gravity Treadmill (AlterG) Training on neuromuscular abnormalities associated with spasticity in children with cerebral palsy (CP). Eighteen subjects were divided into two groups; AlterG and control. All subjects received up to 40 minutes of training 3 times a week for 8 weeks. The control group received conventional occupational therapy. The advanced parallel-cascade system identification technique was used to characterize the neuromuscular abnormalities associated with spasticity and separated its intrinsic and reflex components. Reflex stiffness gain (GR) and intrinsic stiffness gain (K) were used to track the therapeutic effects of training on neural and muscular abnormalities. Both K and GR were strongly positioned dependent; they varied linearly with the ankle angle at dorsiflexion. Their position dependence was quantified by fitting a linear model to K and GR over dorsiflexion positions. The evaluations were performed at four-time points; i.e. the baseline (before starting the training), 1 and 2 months after starting the training, and 1 month after the completion of the training to assess the persistent effects. We determined the changes in K and GR intercept and slope parameters over these 3 months to evaluate the therapeutic effects of training on neuromuscular abnormalities. The results revealed that all K and GR parameters decreased substantially following using AlterG training and these changes were greater than those observed in the control. The results also showed that these therapeutic effects were persistent to a high extent, particularly in the AlterG group. Our findings suggested that AlterG training could be considered as a robust therapeutic intervention to reduce neuromuscular abnormalities and manage spasticity.

The Therapeutic Effects of Low-Amplitude, High-Frequency Perturbations on Neuromuscular Abnormalities Associated with Spasticity in Children with Cerebral Palsy.

We aimed to investigate the impact of ankle joint therapy with low-amplitude, high-frequency perturbation training on neuromuscular abnormalities associated with spasticity in children with Cerebral Palsy (CP). Four spastic CP children (2 males and 2 females) received a 10-session training of high-frequency and low-amplitude perturbations superimposed on passive stretches over the range of motion of their ankle as well as local perturbations at dorsiflexion position. The associated passive parameters, including total passive range of motions, passive range of motions toward dorsiflexion, stiffness, energy loss and torque dynamic gain were evaluated at the baseline and after a 10 session training. Our findings indicate that passive range of motion increased, and passive reflex stiffness, which usually increases in CP children, decreased following the completion of training. Our results demonstrate that intensive sessions of perturbation therapy could be considered an effective therapeutic mean for the management of spasticity and contracture, and eventually the enhancement of mobility of CP children.

Impact of anti-gravity locomotion (AlterG) training on structure and function of corticospinal tract and gait in children with cerebral palsy.

We aimed to characterize the impact of anti-gravity locomotion training on the structure and function of the corticospinal tract (CST) in cerebral palsy (CP). Fourteen CP children participated. Nine children were trained with an antigravity treadmill (Alter-G) and five children received occupational therapy (OT). Treatments were provided for 45 min each session, 3 sessions per week for 8 weeks. Diffusion tensor imaging (DTI) was used, and fractional anisotropy (FA), mean diffusivity (MD), radial (RD) and axial (AD) diffusivity was extracted to characterize the structure of the CST. Transcranial magnetic stimulation (TMS) was used and threshold, latency, and peak-peak amplitude of the MEP signal, elicited by the TMS, were used to quantify the function of the CST. Walking ability was evaluated by measuring gait speed, endurance, balance, and mobility. The evaluations were performed before and after the interventions. The results showed that FA improved in both sides of the brain for the AlterG group, but enhanced only in the less affected side of the OT group. MD, RD, and AD mostly improved in the more affected side of the AlterG group. The enhancement of the CST function was similar in both groups. Walking speed and endurance also enhanced in both groups, but the improvement was greater in the AlterG group. Our findings demonstrate that AlterG training can improve gait ability, and simultaneously result in brain neuroplasticity. The clinical implication is that AlterG training can be used as an effective rehabilitation approach to improve gait persistently.

Does repetitive Transcranial Magnetic Stimulation (rTMS) have therapeutic effects on Dynamic Balance of Children with Cerebral Palsy?

Our big goal in this research was to evaluate the therapeutic effects of repetitive Transcranial Magnetic Stimulation (rTMS) on cerebral palsy (CP) children with balance deficits. Four spastic hemiplegic CP children were participated; the experimental group received rTMS training 4 days a week for 3 weeks and then for the next 3 weeks they received typical occupational therapy just after rTMS therapy. The control group received placebo rTMS instead of real one accordingly. Their dynamic balance was evaluated before the start of the treatment and 6 weeks after it. Center of pressure (COP) and center of mass (COM) features were regarded as dynamic balance parameters. Our results showed that the peak to peak of COP, COM, COM-COP, COM-COP inclination angles all improved for both experimental (15-86%) and control group patients, though there was less improvement about 8-46% in features of the control patients. Our results demonstrate that intensive sessions of the rTMS training could have the potential to enhance the therapeutic effects of typical occupational therapy that can produce dynamic balance improvements in CP children compared to using the occupational therapy by itself.

The Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Balance Control in Children with Cerebral Palsy.

Cerebral palsy (CP) is a neurological disorder which can result in balance and mobility impairments. Four children with spastic CP participated and randomly assigned to experimental and control groups. The experimental group received 1-Hz repetitive Transcranial Magnetic Stimulation (rTMS) four times a week for 3 weeks, and the control group received sham rTMS using the similar experimental protocol. Each rTMS session lasted for 20 minutes. Postural balance was quantified by analyzing the center of pressure (COP) signal of a force plate according to the Romberg test. The balance was also evaluated using the Berg Balance Scale (BBS). The evaluations were done before and after the treatment. COP signal features showed up to 70% improvement following rTMS treatment, whereas there was no notable improvements in the control group. Similarly the BBS assessment presented balance enhancement only in the experimental group. These results, particularly under closed eye foam condition may imply an improvement in proprioception system.Our findings suggested that rTMS has a potential to be used as a therapeutic method to improve postural balance in children with CP.

The Effects of Low Frequency Repetitive Transcranial Magnetic Stimulation on White Matter Structural Connectivity in Children with Cerebral Palsy.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment technique for recovery of movement disorders by altering cortical plasticity. In this research, we studied the effects of low-frequency rTMS on white matter (WM) structural connectivity and clinical parameters in children with cerebral palsy (CP).,Four spastic hemiplegic CP children were randomly divided into experimental and control groups. In the experimental group, at first, 1Hz rTMS treatment was performed 4 days/week for 3 weeks on two hemiplegia patients over a contralesional primary motor cortex (M1). Then, 1Hz rTMS treatment was performed 4 days/week for 3 weeks followed by a 30min occupational therapy (OT). In the control group, two CP children received sham rTMS for 3 weeks and then sham rTMS combined with OT for 3 weeks in the same schedule as the experimental group. Evaluations performed using diffusion tensor imaging (DTI), and clinical measurements of gait performance before and after the treatment. Graph theoretical analysis was used to characterize topological changes of structural connectivity. Our findings demonstrate the 1Hz rTMS is effective in improving motor activity in spastic hemiplegic CP children, and is more effective when combined with OT.

The impact of AlterG training on balance and structure of vestibulospinal tract in cerebral palsy children.

We aimed to investigate the effects of an antigravity treadmill (AlterG) on the balance and structure of the vestibulospinal tract. The AlterG can reduce the weightbearing of patients and hence can facilitate their locomotion. Three children with cerebral palsy (CP) received AlterG training three days per week for eight weeks with each session lasting 45 minutes. The balance of children was evaluated using the Berg balance test and the Timed Up and Go (TUG) test. The diffusion tensor imaging (DTI) method was employed to quantify changes of the structure of the vestibulospinal tract. Evaluations were performed before and after the 8-week training. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were measured to evaluate the vestibulospinal tract structure. The results showed that the mean FA of the vestibulospinal tract increased and other metrics decreased for all subjects. Our findings indicated that the balance and structure of the vestibulospinal tract were improved up to 30% for all children following the 8-week AlterG training. This indicates that the balance improvement of the CP children following the AlterG training was accompanied with persistent neuroplasticity in their brain. The clinical implication is that the AlterG training has a potential to be used as an effective therapeutic tool for the treatment of balance impairment in CP children.

Therapeutic effects of anti-gravity treadmill (AlterG) training on reflex hyper-excitability, corticospinal tract activities, and muscle stiffness in children with cerebral palsy.

We aimed to study therapeutic effects of antigravity treadmill (AlterG) training on reflex hyper-excitability, muscle stiffness, and corticospinal tract (CST) function in children with spastic hemiplegic cerebral palsy (CP). Three children received AlterG training 3 days per week for 8 weeks as experimental group. Each session lasted 45 minutes. One child as control group received typical occupational therapy for the same amount of time. We evaluated hyper-excitability of lower limb muscles by H-reflex response. We quantified muscle stiffness by sonoelastography images of the affected muscles. We quantified CST activity by transcranial magnetic stimulation (TMS). We performed the evaluations before and after training for both groups. H response latency and maximum M-wave amplitude were improved in experimental group after training compared to control group. Two children of experimental group had TMS response. Major parameters of TMS (i.e. peak-to-peak amplitude of motor evoked potential (MEP), latency of MEP, cortical silent period, and intensity of pulse) improved for both of them. Three parameters of texture analysis of sonoelastography images were improved for experimental group (i.e. contrast, entropy, and shear wave velocity). These findings indicate that AlterG training can improve reflexes, muscle stiffness, and CST activity in children with spastic hemiplegic CP and can be considered as a therapeutic tool to improve neuromuscular abnormalities occurring secondary to CP.

Comparison of QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) for diagnosis of latent tuberculosis in haemodialysis (HD) patients: a meta-analysis of κ estimates.

Diagnosis of latent tuberculosis infection (LTBI) is a concern in haemodialysis (HD) patients. Many studies have compared QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) for detecting LTBI and reported the κ statistic of agreement between QFT-GIT and TST in HD patients. The present study aimed to systematically review this literature and conduct meta-analysis of individual studies that estimated the κ between QFT-GIT with TST among HD patients. All relevant published studies that were available as full-text were obtained by searching Medline (1950), Web of Sciences (1945), Scopus (1973) through May 2016. The κ was re-estimated from the individual studies and pooled using random effect meta-analysis. Subgroup analysis and meta-regression were applied to evaluate the effect of Bacillus Calmette-Guérin (BCG) vaccination, TST cut-off points, quality of studies, sample size and age on variation of κ estimate. Eight studies involving 901 HD patients were included in meta-analysis. The pooled κ estimate was 0·28 (I 2 = 18·4%, P = 0·239, 95% confidence intervals 0·22-0·34). The discordance of TST-/QFT-GIT+ was more than TST+/QFT-GIT-. History of BCG vaccination, TST cut-off points and age are related to variation of κ estimates. TST and QFT-GIT are not comparable in detecting LTBI in HD patients. The higher TST-/QFT-GIT+ ratio compared with TST+/QFT-GIT- ratio, may indicate the superiority of QFT-GIT over TST for detection LTBI in HD patients.

Dynamic Sequence Evolution of a Sex-Associated B Chromosome in Lake Malawi Cichlid Fish.

B chromosomes are extra chromosomes found in many species of plants, animals, and fungi. B chromosomes often manipulate common cellular processes to increase their frequency, sometimes to the detriment of organismal fitness. Here, we characterize B chromosomes in several species of Lake Malawi cichlid fish. Whole genome sequencing of Metriaclima zebra "Boadzulu" individuals revealed blocks of sequence with unusually high sequence coverage, indicative of increased copy number of those sequences. These regions of high sequence coverage were found only in females. SNPs unique to the high copy number sequences permitted the design of specific amplification primers. These primers amplified fragments only in Metriaclima lombardoi individuals that carried a cytologically identified B chromosome (B-carriers), indicating these extra copies are located on the B chromosome. These same primers were used to identify B-carrying individuals in additional species from Lake Malawi. Across 7 species, a total of 43 B-carriers were identified among 323 females. B-carriers were exclusively female; no B chromosomes were observed in the 317 males surveyed from these species. Quantitative analysis of the copy number variation of B-specific sequence blocks suggests that B-carriers possess a single B chromosome, consistent with previous karyotyping of M. lombardoi A single B chromosome in B-carriers is consistent with 2 potential drive mechanisms: one involving nondisjunction and preferential segregation in a mitotic division prior to the germ-line, and the other involving preferential segregation during meiosis I.

Tuberculin and QuantiFERON-TB-Gold tests for latent tuberculosis: a meta-analysis.

BACKGROUND: Up to now, there has been no universal consensus on the agreement between the tuberculin skin test (TST) and the QuantiFERON-TB-Gold test (QFT) in the detection of latent tuberculosis infection (LTBI) among high-risk populations. AIMS: To estimate the agreement between TST and QFT among health care workers (HCWs). METHODS: A meta-analysis in which all major electronic databases, including Medline, Scopus, Web of Sciences and Ovid, were searched until June 2014. All cross-sectional and cohort studies addressing the agreement between TST and the QFT were included. The extracted data were analysed and the results were reported using random effect models. RESULTS: The overall kappa statistic between TST and the QFT was 0.27 [95% confidence interval (CI) 0.22, 0.32] and the adjusted kappa statistic for prevalence and bias was 0.41 (95% CI 0.32, 0.50). The kappa for subjects with and without bacillus Calmette-Guérin (BCG) vaccination was 0.27 (95% CI 0.18, 0.36) and 0.31 (95% CI 0.15, 0.46) respectively. The figures were 0.30 (95% CI 0.16, 0.43) and 0.82 (95% CI 0.74, 0.90) for prevalence-adjusted and bias-adjusted kappa, respectively. CONCLUSIONS: The overall agreement between TST and QFT in the detection of LTBI among HCWs was poor. After adjusting for the prevalence and bias indices, kappa statistics reached fair agreement. The utility of each of these two tests is dependent on the prevalence and burden of tuberculosis as well as the BCG vaccination status.

Pendulum test measure correlates with gait parameters in children with cerebral palsy.

Individuals with cerebral palsy (CP) usually suffer from different impairments including gait impairment and spasticity. Spastic hypertonia is a defining feature of spasticity and manifests as a mechanical abnormality. The objective of this study was to determine the relationship between spastic hypertonia and gait impairments in spastic children with CP, addressing an important controversial issue. Spastic hypertonia was quantified using the pendulum test. The gait impairments were evaluated using the motion capture system in a gait laboratory. Our results showed significant correlations among gait parameters; i.e. walking speed, step length, and the pendulum test measures. This indicates that neuromuscular abnormalities are associated with spasticity and may contribute to gait impairments. The clinical implication is that the impaired gait in children with CP may be improved with the treatment of neuromuscular abnormalities.

Development and field testing of a novel patient-reported outcome measure of dysphagia in patients with eosinophilic esophagitis.

BACKGROUND: Dysphagia is the hallmark of eosinophilic esophagitis (EoE), but no validated dysphagia instruments in this population exist. AIM: To develop and field test a patient-reported outcome (PRO) for dysphagia in subjects with EoE. METHODS: This was a multi-centre/multi-phase prospective study. The first phase developed a dysphagia questionnaire using qualitative methods. The second phase was a 30-day field trial to test the instrument and assess content validity. Adolescents and adults with EoE, active symptoms of dysphagia and oesophageal eosinophilia (≥15 eosinophils per high-power field) were enrolled. Solid-food-avoidance days, dysphagia days and actions taken to get relief were recorded. A dysphagia score was calculated and compared to the Straumann Dysphagia Instrument (SDI). RESULTS: Ten adolescents and 10 adults were included in the first phase and the Dysphagia Symptom Questionnaire (DSQ), a three-item daily electronic diary, was developed. In the second phase, 35 subjects finished the field trial (18 adults, 17 adolescents, mean age 24, 54% male, 95% white, 54% currently on topical corticosteroids). The median number of dysphagia days per week was 2 for adolescents vs. 4 for adults (P < 0.001), and 2 for those on topical steroids vs. 4 for those not on topical steroids (P < 0.001). The DSQ score strongly correlated with the number of dysphagia days (R = 0.96; P < 0.001) and the SDI (R = 0.77; P < 0.001). CONCLUSIONS: The DSQ, a three-question patient-reported outcome, was successfully developed and field tested. The DSQ had content validity and the score accurately measured dysphagia frequency and intensity. The Dysphagia Symptom Questionnaire is suitable for use in clinical trials of EoE patients with dysphagia.

Solitary fibrous tumour presenting as a pedunculated lung mass with associated lung atresia: report of a case.

This case report describes a solitary fibrous tumour presenting as a pedunculated mass arising from an almost completely atretic right middle lobe of lung. The intraoperative findings and pathologic diagnostic criteria used are described. To our knowledge, this is the first case report of a solitary fibrous tumour associated with partial lung atresia.

Construction of knowledge, attitude and practice questionnaire for assessing plagiarism.

BACKGROUND: This study was conducted to develop a questionnaire in order to evaluate knowledge, attitude and practice (KAP) of the faculty members and students toward plagiarism. METHODS: A KAP study was conducted from June to October 2011 enrolling 390 volunteers anonymously (response rate 96%). The questionnaire included the following four parts: (a) general characteristics like gender, academic degree and education level; (b) nine questions regarding knowledge (Min=0, Max=9); (c) nine questions regarding attitude (Min=9, Max=27); and (d) eight questions regarding practice (Min=0, Max=8). A pilot study was conducted to assess reliability of the questions regarding knowledge and attitude. Cronbach's alpha coefficient for the knowledge and attitude questions was 0.70 and 0.74 respectively. RESULTS: The overall prevalence of at least once plagiarism commission was 38% (SD=0.035). The overall mean score of knowledge, attitude and practice was 5.94 (SD=1.66), 24.12 (SD=2.99), and 0.66 (SD=1.15) respectively. Knowledge of plagiarism was significantly higher among higher academic degrees and females. Their negative attitude toward plagiarism was stronger too. No statistically significant difference regarding plagiarism commission was observed among different academic degrees in both sexes. According to linear regression analysis, plagiarism commission decreased 13% per one unit increase in score of knowledge (P=0.005) and 16% per one unit increase in score of attitude (P<0.001). CONCLUSIONS: This knowledge, attitude, and practice (KAP) questionnaire was developed as a standard tool in order to assess perception of subjects toward plagiarism and to estimate the prevalence and the type of plagiarism commission.

Pharmacological inhibition of the lateral habenula improves depressive-like behavior in an animal model of treatment resistant depression.

Identifying new treatment approaches for treatment resistant depression (TRD) is an important topic for translational psychiatry. Functional inhibition of the lateral habenula (LHb) has recently been claimed to offer such an option for TRD. Rats which are bred for high susceptibility to develop learned helplessness provide a genetic model for TRD. We used the gamma-aminobutyric acid agonist muscimol to inhibit the LHb in Sprague-Dawley rats with congenital learned helplessness (cLH). Stereotactic pharmacological inhibition of the LHb exerted antidepressive effects in treatment resistant cLH rats.