Home-based virtual reality-enhanced upper limb training system in children with brain injury: a randomized controlled trial.

Background: Rehabilitation of upper limb function can be challenging in children with brain lesion. Recent virtual reality (VR) rehabilitation may be an additional treatment option in pediatric rehabilitation. Objectives: To assess the feasibility and effectiveness of a home-based VR-enhanced rehabilitation program with wearable multi-inertial measurement unit (IMU) sensors on upper limb functions in children with brain injury. Methods: This multicenter single blind randomized controlled trial included 40 children with cerebral palsy (CP) or static brain injury. Subjects were randomized 1:1 to experimental and control group. Both the groups maintained the same therapeutic content and dose of occupational therapy during the intervention period. The experimental group performed additional training at home using the VR-enhanced program for at least 30 min/day, 5 days/week, for 6 weeks. VR training consisted of daily activities or games promoting wrist and forearm articular movements using wearable IMU sensors. The Melbourne Assessment of Unilateral Upper Limb Function-version 2 (MA2), Upper Limb Physician's Rating Scale (ULPRS), Pediatric Evaluation of Disability Inventory-computer adaptive test (PEDI-CAT), computerized 3D motion analysis, and user satisfaction survey were performed. Mann-Whitney U test was used to compare treatment effects between groups, and Friedman and Wilcoxon signed-rank tests were used to compare pre and post intervention. Results: Overall 35 children (15 in VR group and 20 in control group) completed the protocol. In the experimental group, an average VR training time was 855 min. The accuracy of motion measured by MA2, segmental movements by ULPRS, daily living capability and social cognitive function by PEDI-CAT, movement time and shoulder movement pattern by motion analysis showed significant improvements. However, there were no significant differences in any of the functional outcome measures compared to the control group. All the children and parents reported positive experiences. Conclusions: Home-based VR training though it had limited impact on improving upper limb function, it could help improve social cognitive function, movement pattern, and efficiency in children with brain injury and could be an effective means of extending clinical therapy to the home. Clinical Trial Registration: CRIS.nih.go.kr: identifier KCT0003172.

Dysregulation of Liver Regeneration by Hepatitis B Virus Infection: Impact on Development of Hepatocellular Carcinoma.

The liver is unique in its ability to regenerate in response to damage. The complex process of liver regeneration consists of multiple interactive pathways. About 2 billion people worldwide have been infected with hepatitis B virus (HBV), and HBV causes 686,000 deaths each year due to its complications. Long-term infection with HBV, which causes chronic inflammation, leads to serious liver-related diseases, including cirrhosis and hepatocellular carcinoma. HBV infection has been reported to interfere with the critical mechanisms required for liver regeneration. In this review, the studies on liver tissue characteristics and liver regeneration mechanisms are summarized. Moreover, the inhibitory mechanisms of HBV infection in liver regeneration are investigated. Finally, the association between interrupted liver regeneration and hepatocarcinogenesis, which are both triggered by HBV infection, is outlined. Understanding the fundamental and complex liver regeneration process is expected to provide significant therapeutic advantages for HBV-associated hepatocellular carcinoma.

Reliability of the Modified Ashworth and Modified Tardieu Scales with Standardized Movement Speeds in Children with Spastic Cerebral Palsy.

The Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS) are widely used to quantify spasticity. However, the reliability of their use for ankle plantar flexors has been questioned. In this study, we aimed to examine whether their reliabilities could be increased to acceptable levels for ankle plantar flexors using standardized movement speed in children with spastic cerebral palsy. The MAS and MTS scores for 92 limbs were assessed by two raters on two occasions, 1 week apart. A metronome was used to maintain the stretching velocity at 120 beats per minute. The intraclass correlation coefficients (ICCs) of the intra-rater reliabilities of the MAS and MTS and inter-rater reliability of the MAS were over 0.7. However, the ICCs for the inter-rater reliability of the MTS were <0.7 and >0.75 for the gastrocnemius and soleus muscles, respectively. The ICCs for the inter- and intra-rater reliabilities of the R1 angles ranged from 0.68 to 0.84, while those of the R2 angles ranged from 0.74 to 0.93. The reliabilities of the R2-R1 angles were not satisfactory. In conclusion, with a standardized movement speed, the reliability of the MAS for the ankle plantar flexors and the MTS for the soleus were satisfactory; however, that of the MTS for the gastrocnemius was not.

Gait Adaptation Is Different between the Affected and Unaffected Legs in Children with Spastic Hemiplegic Cerebral Palsy While Walking on a Changing Slope.

Walking on sloped surfaces requires additional effort; how individuals with spastic hemiplegic cerebral palsy (CP) manage their gait on slopes remains unknown. Herein, we analyzed the difference in gait adaptation between the affected and unaffected legs according to changes in the incline by measuring spatiotemporal and kinematic data in children with spastic hemiplegic CP. Seventeen children underwent instrumented three-dimensional gait analysis on a dynamic pitch treadmill at an incline of +10° to -10° (intervals of 5°). While the step length of the affected legs increased during uphill gait and decreased during downhill gait, the unaffected legs showed no significance. During uphill gait, the hip, knee, and ankle joints of the affected and unaffected legs showed increased flexion, while the unaffected leg showed increased knee flexion throughout most of the stance phase compared with the affected leg. During downhill gait, hip and knee flexion increased in the affected leg, and knee flexion increased in the unaffected leg during the early swing phase. However, the ankle plantar flexion increased during the stance phase only in the unaffected leg. Although alterations in temporospatial variables and joint kinematics occurred in both legs as the slope angle changed, they showed different adaptation mechanisms.

The Roles of Ubiquitination in Pathogenesis of Influenza Virus Infection.

The ubiquitin system denotes a potent post-translational modification machinery that is capable of activation or deactivation of target proteins through reversible linkage of a single ubiquitin or ubiquitin chains. Ubiquitination regulates major cellular functions such as protein degradation, trafficking and signaling pathways, innate immune response, antiviral defense, and virus replication. The RNA sensor RIG-I ubiquitination is specifically induced by influenza A virus (IAV) to activate type I IFN production. Influenza virus modulates the activity of major antiviral proteins in the host cell to complete its full life cycle. Its structural and non-structural proteins, matrix proteins and the polymerase complex can regulate host immunity and antiviral response. The polymerase PB1-F2 of mutated 1918 IAV, adapts a novel IFN antagonist function by sending the DDX3 into proteasomal degradation. Ultimately the fate of virus is determined by the outcome of interplay between viral components and host antiviral proteins and ubiquitination has a central role in the encounter of virus and its host cell.

Spatial CRISPR genomics identifies regulators of the tumor microenvironment.

While CRISPR screens are helping uncover genes regulating many cell-intrinsic processes, existing approaches are suboptimal for identifying extracellular gene functions, particularly in the tissue context. Here, we developed an approach for spatial functional genomics called Perturb-map. We applied Perturb-map to knock out dozens of genes in parallel in a mouse model of lung cancer and simultaneously assessed how each knockout influenced tumor growth, histopathology, and immune composition. Moreover, we paired Perturb-map and spatial transcriptomics for unbiased analysis of CRISPR-edited tumors. We found that in Tgfbr2 knockout tumors, the tumor microenvironment (TME) was converted to a fibro-mucinous state, and T cells excluded, concomitant with upregulated TGFß and TGFß-mediated fibroblast activation, indicating that TGFß-receptor loss on cancer cells increased TGFß bioavailability and its immunosuppressive effects on the TME. These studies establish Perturb-map for functional genomics within the tissue at single-cell resolution with spatial architecture preserved and provide insight into how TGFß responsiveness of cancer cells can affect the TME.

Efficacy and safety of onabotulinumtoxinA with standardized physiotherapy for the treatment of pediatric lower limb spasticity: A randomized, placebo-controlled, phase III clinical trial.

BACKGROUND: Spasticity is common in cerebral palsy and can result in pain and diminished health-related quality of life. OBJECTIVE: To evaluate the safety and efficacy of onabotulinumtoxinA for lower limb spasticity treatment in children with cerebral palsy. METHODS: In this registrational phase 3, multinational, randomized, double-blind, placebo-controlled trial (NCT01603628), children (2-< 17 years) with cerebral palsy and ankle spasticity (Modified Ashworth Scale-Bohannon [MAS] score≥2) were randomized 1 : 1 : 1 to standardized physical therapy and onabotulinumtoxinA (4 or 8 U/kg), or placebo. Primary endpoint was average change from baseline at weeks 4 and 6 in MAS ankle score. Secondary endpoints included the Modified Tardieu Scale (MTS) and Global Attainment Scale (GAS). RESULTS: 381 participants were randomized. MAS scores averaged at weeks 4 and 6 were significantly reduced with both onabotulinumtoxinA doses (8 U/kg: -1.06, p = 0.010; 4 U/kg: -1.01, p = 0.033) versus placebo (-0.8). Significant improvements in average dynamic component of spasticity, measured by MTS, and in function, measured by GAS, were observed at several time points with both onabotulinumtoxinA doses versus placebo. Most adverse events were mild or moderate. CONCLUSIONS: OnabotulinumtoxinA was well tolerated and effective in reducing lower limb spasticity and improving functional outcomes versus placebo in children.

Spatiotemporal parameters from instrumented motion analysis represent clinical measurement of upper limb function in children with cerebral palsy.

BACKGROUND: There are various tools that measure upper limb function in children with cerebral palsy(CP) clinically, but these measurement methods are examiner-dependent and scale values are not proportional to the upper limb function which makes it difficult to quantify the function. RESEARCH QUESTION: The purpose of this study was to investigate whether the new parameters derived from 3D motion analysis reflect the upper limb function which measured by Melbourne Assessment 2 (MA2) in children with cerebral palsy (CP) compared to the clinical measurements. METHODS: Forty children with CP (24 boys, 16 girls; mean [SD] age, 6 years 11 months [3 years 5 months]) were recruited. Motion capture was conducted during phases T1-T4 of Reach and Grasp Cycles. New parameters (movement time, number of movement units, index of curvature) were derived from wrist marker data. Range of motion (ROM), accuracy, dexterity, and fluency of unilateral upper limb function were assessed using MA2. Spearman rank coefficients were determined to evaluate correlations between MA2 and the new parameters. RESULTS AND SIGNIFICANCE: Index of curvature correlated negatively with MA2 accuracy scores during T1 (rs -0.347, p < 0.05), T2 (rs -0.471, p < 0.01), and T3 (rs -0.660, p < 0.01). Number of movement units correlated negatively with MA2 ROM, accuracy, and fluency scores during T1 (ROM rs -0.334; accuracy rs -0.331; fluency rs -0.375; p < 0.05) and T3 (ROM rs -0.499; accuracy rs -0.531; fluency rs -0.515; p < 0.01). Index of curvature and number of movement units are objective, simple parameters showing fair to good correlation with MA2 accuracy and fluency of upper limb function.

Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients.

BACKGROUND AND AIM: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. METHODS: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. RESULTS: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). CONCLUSIONS: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.

Evaluation of sitting and standing postural balance in cerebral palsy by center-of-pressure measurement using force plates: comparison with clinical measurements.

BACKGROUND: Center-of-pressure (CoP) measurements have been studied for assessing balance control. While CoP measurements using force plates have been used to assess standing balance in children with cerebral palsy (CP), it has not been assessed in a sitting position, which specifically reflects trunk postural control. RESEARCH QUESTION: The purpose of this study was to compare CoP measurements using force plates during both standing and sitting trials with the Pediatric Balance Scale (PBS) in children with spastic CP. METHODS: We recruited 26 children with spastic CP (7.8 ±â€¯3.4 years, 4-13 years) and used the PBS, a validated evaluation tool that measures static and dynamic balance control. We took CoP measurements using force plates during sitting and standing. For both trials, subjects stayed still for 10 s with their eyes open or closed. We calculated the CoP velocity, mediolateral (ML) and anteroposterior (AP) velocity, and ML and AP displacements of CoP. RESULTS AND SIGNIFICANCE: During standing trials, static PBS standing scores negatively correlated with more AP displacement and velocity than ML displacement and velocity (p < 0.05). During sitting trials, dynamic PBS sitting scores negatively correlated with ML displacement and velocity (p < 0.05). CoP parameters in the ML direction of the sitting position and CoP parameters in the AP direction of the standing position may better reflect the balance control in children with spastic CP.

The Effects of Over-Ground Robot-Assisted Gait Training for Children with Ataxic Cerebral Palsy: A Case Report.

Poor balance and ataxic gait are major impediments to independent living in ataxic cerebral palsy (CP). Robot assisted-gait training (RAGT) has been shown to improve the postural balance and gait function in children with CP. However, there is no report on the application of RAGT for children with ataxic CP. Here, we report two cases of children with ataxic CP who underwent over-ground RAGT along with conventional therapy for 4 weeks. Outcome measures including the gross motor function measure (GMFM), pediatric balance scale, pediatric reach scale, one-minute walk test, and Timed Up and Go test were assessed before and after the 4-week intervention. Both cases were well adapted to the RAGT system without any significant adverse event. Improvements in the GMFM after RAGT, compared with that in the GMFM, after intensive conventional therapy have been reported previously. It is noteworthy that over-ground RAGT improved areas of the GMFM that did not improve with conventional therapy. In addition, over-ground RAGT with conventional therapy led to improvements in functional balance and walking capacity. These findings suggest that over-ground RAGT is feasible and may be a potential option for enhancing balance and functional walking capacity in children with ataxic CP.

Relationship between the more-affected upper limb function and daily activity performance in children with cerebral palsy: a cross-sectional study.

BACKGROUND: There are differences in roles between the more-affected and less-affected upper limb of children with cerebral palsy (CP). However, there is a lack of studies of the relationship between the more-affected limb function and activities of daily living (ADL) in children with CP. Thus, the aim of this prospective cross-sectional study was to investigate the relationship between more-affected upper limb function and ADL in children with CP. METHODS: Children with spastic CP (unilateral CP n = 28, bilateral CP n = 31; 34 males, 25 females; mean age ± SD, 6.8 ± 3.1y [range, 3-14y]) participated in this study. Function of the more-affected upper limb was measured using the Melbourne Assessment of Unilateral Upper limb Function, version 2 (MA2) and the Upper Limb Physician's Rating Scale (ULPRS). Performance of daily living activities was measured using the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT). RESULTS: The range, accuracy and fluency dimension of MA2 and ULPRS total scores were moderately correlated with the daily activity domain (r = 0.47, 0.47, 0.56 for MA2 and r = 0.50 for ULPRS, respectively; P < 0.001) rather than the mobility, social/cognitive, and responsibility domains of the PEDI-CAT. ULPRS scores for elbow extension, supination in extension, supination in flexion, and two-handed function were moderately correlated with the PEDI-CAT daily activity domain (r = 0.44, 0.43, 0.41, and 0.49, respectively; P < 0.01). Finger opening and thumb-in-palm deformity of the ULPRS did not correlate with any PEDI-CAT domain. CONCLUSIONS: The MA2 range, accuracy, and fluency domains (rather than dexterity) had the strongest correlations with the PEDI-CAT daily activity domain. Elbow extension, forearm supination, and two-handed function (rather than wrist and finger movements) of the ULPRS had the strongest correlations with the PEDI-CAT daily activity domain.

Effects of a Short Emotional Management Program on Inpatients with Schizophrenia: A Pilot Study.

The prevalence of schizophrenia is gradually increasing worldwide. Many patients with schizophrenia have a diminished ability to empathize and to detect their own emotions or those of others, deteriorating their social functioning and their quality of life. Nonetheless, emotional management training may improve patients' emotion recognition, emotional expression, and negative symptoms. Developing and applying a short but effective program that reflects the current medical environment, in which hospital stays are ever-diminishing, is warranted. This one-group, pretest-posttest, quasi-experimental pilot study aimed to examine the effects of a short emotional management program (EMP-S) on 17 patients with chronic schizophrenia. Participants were patients hospitalized in the National Center for Mental Health in Korea. After the completion of a twice-a-week, eight-session, four-week long EMP-S, participants showed improvements in emotion recognition, emotional expression, and negative symptoms. Our results suggest the applicability and potential effectiveness of the EMP-S, which takes the length of psychiatric hospital stay and the inpatient environment into consideration. To minimize any barriers to social functioning in the post-discharge lives of inpatients with chronic schizophrenia and enhance their social cognition-by improving their emotion recognition, emotional expression, and negative symptoms-we suggest the periodical administration of this EMP-S to these inpatients.

Overground Robot-Assisted Gait Training for Pediatric Cerebral Palsy.

The untethered exoskeletal robot provides patients with the freest and realistic walking experience by assisting them based on their intended movement. However, few previous studies have reported the effect of robot-assisted gait training (RAGT) using wearable exoskeleton in children with cerebral palsy (CP). This pilot study evaluated the effect of overground RAGT using an untethered torque-assisted exoskeletal wearable robot for children with CP. Three children with bilateral spastic CP were recruited. The robot generates assistive torques according to gait phases automatically detected by force sensors: flexion torque during the swing phase and extension torque during the stance phase at hip and knee joints. The overground RAGT was conducted for 17~20 sessions (60 min per session) in each child. The evaluation was performed without wearing a robot before and after the training to measure (1) the motor functions using the gross motor function measure and the pediatric balance scale and (2) the gait performance using instrumented gait analysis, the 6-min walk test, and oxygen consumption measurement. All three participants showed improvement in gross motor function measure after training. Spatiotemporal parameters of gait analysis improved in participant P1 (9-year-old girl, GMFCS II) and participant P2 (13-year-old boy, GMFCS III). In addition, they walked faster and farther with lower oxygen consumption during the 6-min walk test after the training. Although participant P3 (16-year-old girl, GMFCS IV) needed the continuous help of a therapist for stepping at baseline, she was able to walk with the platform walker independently after the training. Overground RAGT using a torque-assisted exoskeletal wearable robot seems to be promising for improving gross motor function, walking speed, gait endurance, and gait efficiency in children with CP. In addition, it was safe and feasible even for children with severe motor impairment (GMFCS IV).

Distinctive HBV Replication Capacity and Susceptibility to Tenofovir Induced by a Polymerase Point Mutation in Hepatoma Cell Lines and Primary Human Hepatocytes.

Tenofovir disoproxil fumarate (TDF) has been regarded as the most potent drug for treating patients with chronic hepatitis B (CHB). However recently, viral mutations associated with tenofovir have been reported. Here, we found a CHB patient with suboptimal response after more than 4 years of TDF treatment. Clonal analysis of hepatitis B virus (HBV) isolated from sequential sera of this patient identified the seven previously reported TDF-resistant mutations (CYELMVI). Interestingly, a threonine to alanine mutation at the 301 amino acid position of the reverse-transcriptase (RT) domain, (rtT301A), was commonly accompanied with CYELMVI at a high rate (72.7%). Since the rtT301A mutation has not been reported yet, we investigated the role of this naturally occurring mutation on the viral replication and susceptibility to tenofovir in various liver cells (hepatoma cells as well as primary human hepatocytes). A cell-based phenotypic assay revealed that the rtT301A mutation dramatically impaired the replication ability with meaningful reduction in sensitivity to tenofovir in hepatoma cell lines. However, attenuated viral replication by the rtT301A mutation was significantly restored in primary human hepatocytes (PHHs). Our findings suggest that the replication capability and drug sensitivity of HBV is different between hepatoma cell lines and PHHs. Therefore, our study emphasizes that validation studies should be performed not only in the liver cancer cell lines but also in the PHHs to understand the exact viral fitness under antiviral pressure in patients.

Virtual reality rehabilitation in children with brain injury: a randomized controlled trial.

AIM: To investigate the efficacy of a virtual reality rehabilitation system of wearable multi-inertial sensors to improve upper-limb function in children with brain injury. METHOD: Eighty children (39 males, 41 females) with brain injury including cerebral palsy aged 3 to 16 years (mean age 5y 8mo, SD 2y 10mo) were assessed as part of a multicentre, single-blind, randomized controlled trial. The intervention group received a 30-minute virtual reality intervention and a 30-minute session of conventional occupational therapy while the control group received 60 minutes of conventional occupational therapy per session, with 20 sessions over 4 weeks. The virtual reality rehabilitation system consisted of games promoting wrist and forearm articular movements using wearable inertial sensors. The Melbourne Assessment of Unilateral Upper Limb Function-2 (MA-2), Upper Limb Physician's Rating Scale, Pediatric Evaluation of Disability Inventory Computer Adaptive Test, and computerized three-dimensional motion analysis were performed. RESULTS: Both groups (virtual reality, n=40; control, n=38) significantly improved after treatment compared to baseline; however, the virtual reality group showed more significant improvements in upper-limb dexterity functions (MA-2, virtual reality group: Δ=10.09±10.50; control: Δ=3.65±6.92), performance of activities of daily living, and forearm supination by kinematic analysis (p<0.05). In the virtual reality group, children with more severe motor impairment showed significant improvements compared to those with less severe impairment. INTERPRETATION: The virtual reality rehabilitation system used in this study, which consists of wearable inertial sensors and offers intensive, interactive, and repetitive motor training, is effective in children with brain injury. WHAT THIS PAPER ADDS: Both virtual reality rehabilitation and conventional occupational therapy were effective for upper-limb training. Virtual reality training was superior in improving dexterity, performance of activities of daily living, and active forearm supination motion. The effect of virtual reality training was significant in children with more severe motor impairments.

Incidental Diagnosis of Pediatric Arytenoid Cartilage Dislocation During Videofluoroscopic Swallowing Study: A Case Report.

Arytenoid cartilage dislocation is one of the most common mechanical causes of vocal fold immobility. The most common etiologies are intubation and external trauma, but its incidence is lower than 0.1%. Its symptoms include dysphonia, vocal fatigue, loss of vocal control, breathiness, odynophagia, dysphagia, dyspnea, and cough. Although there are some reports of arytenoid cartilage dislocation in adults, there are only few reports on its occurrence in children. It is particularly difficult to detect the symptoms of arytenoid cartilage dislocation in uncooperative pediatric patients with brain lesions without verbal output or voluntary expression. We report a case of arytenoid cartilage dislocation with incidental findings in a videofluoroscopic swallowing study performed to evaluate the swallowing function.

Entecavir-resistant hepatitis B virus decreases surface antigenicity: A full genome and functional characterization.

BACKGROUND AND AIM: Since polymerase and surface genes overlap in hepatitis B virus (HBV), an antiviral-induced mutation in the polymerase gene may alter the surface antigenicity in patients with chronic hepatitis B (CHB), but this possibility has not been clearly confirmed. This study aimed to determine the drug susceptibility and surface antigenicity of the patient-derived mutants. PATIENTS AND METHODS: Full-length HBV genomes isolated from four entecavir-resistant CHB patients were cloned and sequenced. Around 10 clones of full-length HBV obtained from each patient were analysed and registered in the NCBI GenBank. Representative clones were further characterized by in vitro drug susceptibility and surface antigenicity assays. RESULTS: The rtL180M + rtM204V mutations were common among all the clones analysed. Additionally, the ETV resistance mutations rtT184A/L, rtS202G and rtM250V were found among three patients. Most of the ETV-resistant mutants had amino acid alterations within the known epitopes recognized by T- and B-cells in the HBV surface and core antigens. The in vitro drug susceptibility assay showed that all tested clones were resistant to ETV treatment. However, they were all susceptible to ADV and TDF. More importantly, the rtI169T mutation in the RT domain, led to the sF161L mutation in the overlapping S gene, which decreased in surface antigenicity. CONCLUSIONS: The ETV resistance mutations can affect the antigenicity of the HBsAg proteins due to changes in the overlapping sequence of this surface antigen. Thus, the apparent decline or disappearance of HBsAg needs to be interpreted cautiously in patients with previous or current antiviral resistance mutations.

Botulinum Toxin Type A Injections Impact Hamstring Muscles and Gait Parameters in Children with Flexed Knee Gait.

The aim of this study was to determine if botulinum toxin type A (BoNT-A) injection into the medial hamstring can improve gait kinematics and muscle-tendon length in spastic cerebral palsy (CP) with a flexed knee gait (FKG). Twenty-nine children with spastic CP (Gross Motor Function Classification System I-III) with FKG were recruited for this prospective study. BoNT-A was injected into the semitendinosus and semimembranosus (SM) muscles under ultrasonography guidance. Assessments included Gross Motor Function Measure (GMFM), Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS), 3-dimensional computerized gait analysis, calculated SM muscle-tendon length and lengthening velocity during gait using musculoskeletal modeling at baseline, 4 and 16 weeks after the injection. Compared to baseline data, significant improvements in GMFM, MAS, and MTS were demonstrated at weeks 4 and 16, and also a significant increase in maximum knee extension during the stance phase was observed at week 4. In addition, the mean lengthening velocity during the swing phase was increased at week 16 without a change in the SM muscle length. Furthermore, there was a significant increase in anterior pelvic tilt at week 4, compared to baseline data. The significant decrease in hip internal rotation after injection was observed only in children with excessive hip internal rotation at initial contact before injection. BoNT-A injection into hamstrings leads to a significant increase in knee extension and anterior pelvic tilt with an increase in lengthening velocity of SM in spastic CP with FKG.

Contra-Lateral Unintended Upper Arm Movement during Unimanual Tasks in Children with Cerebral Palsy.

PURPOSE: To characterize associated reactions (ARs) in the contralateral arm across multiple muscles during unimanual tasks and to identify factors related to ARs in children with cerebral palsy (CP). MATERIALS AND METHODS: This was a prospective, cross-sectional study of 35 children with CP. The extent of ARs of the contra-lateral, non-task hand was assessed while performing three unimanual tasks (opening and clenching the fist, a finger opposition task, and tapping fingers). The occurrence of ARs in each trial was evaluated separately for each task using a four-point scale (total scores ranged from 0 to 12). Surface electromyography (SEMG) was used to measure the firing activity of the muscles of the opposite arm during the task. The Manual Ability Classification System and Melbourne Assessment 2 (MA-2) were used to evaluate upper limb function. RESULTS: AR scores were higher in the more-affected limb than in the less-affected limb. SEMG data on the non-task hand showed motor overflow up to the elbow muscles in the more-affected limb. Root mean square ratios of EMG signals were significantly higher in children with ARs than in children without ARs. Multiple regression analysis showed both age and MA-2 to be significant factors related to ARs in the more-affected limb. CONCLUSION: Children with visible ARs showed motor overflow in the non-task limb during unimanual hand tasks. Age and upper limb function were significantly related to the extent of ARs in the more-affected limb of children with CP.