Effect of Multicomponent Home-Based Training on Gait and Muscle Strength in Older Adults After Hip Fracture Surgery: A Single Site Randomized Trial.

OBJECTIVE: To investigate the effect of 16-week home-based physical therapy interventions on gait and muscle strength. DESIGN: A single-blinded randomized controlled trial. SETTING: General community. PARTICIPANTS: Thirty-four older adults (N=34) post hip fracture were randomly assigned to either experimental group (a specific multi-component intervention group [PUSH], n=17, 10 women, age=78.6±7.3 years, 112.1±39.8 days post-fracture) or active control (a non-specific multi-component intervention group [PULSE], n=17, 11 women, age=77.8±7.8 years, 118.2±37.5 days post-fracture). INTERVENTION: PUSH and PULSE groups received 32-40 sessions of specific or non-specific multi-component home-based physical therapy, respectively. Training in the PUSH group focused on lower extremity strength, endurance, balance, and function for community ambulation, while the PULSE group received active movement and transcutaneous electrical nerve stimulation on extremities. MAIN OUTCOME MEASURES: Gait characteristics, and ankle and knee muscle strength were measured at baseline and 16 weeks. Cognitive testing of Trail Making Test (Part A: TMT-A; Part-B: TMT-B) was measured at baseline. RESULTS: At 16 weeks, both groups demonstrated significant increases in usual (P<.05) and fast (P<.05) walking speed, while there was no significant difference in increases between the groups. There was only 1 significant change in lower limb muscle strength over time (non-fractured side) between the groups, such that PUSH did better (mean: 4.33%, 95% confidence interval:1.43%-7.23%). The increase in usual and fast walking speed correlated with the baseline Trail-making Test-B score (r=-0.371, P=.037) and improved muscle strength in the fractured limb (r=0.446, P=.001), respectively. CONCLUSION: Gait speed improved in both home-based multicomponent physical therapy programs in older adults after hip fracture surgery. Muscle strength of the non-fractured limb improved in the group receiving specific physical therapy training. Specific interventions targeting modifiable factors such as muscle strength and cognitive performance may assist gait recovery after hip fracture surgery.

Intensive In-Bed Sensorimotor Rehabilitation of Early Subacute Stroke Survivors With Severe Hemiplegia Using a Wearable Robot.

Rehabilitation for stroke survivors with severe motor impairment remains challenging. Early motor rehabilitation is critical for improving mobility function post stroke, but it is often delayed due to limited resources in clinical practice. The objectives of this study were to investigate the feasibility and effectiveness of early in-bed sensorimotor rehabilitation on acute stroke survivors with severe hemiplegia using a wearable ankle robot. Eighteen patients (9 in the study group and 9 in the control group) with severe hemiplegia and no active ankle movement were enrolled in acute/subacute phase post stroke. During a typical 3-week hospital stay, patients in the study group received ankle robot-guided in-bed training (50 minutes/session, 5 sessions/week), including motor relearning under real-time visual feedback of re-emerging motor output, strong passive stretching under intelligent control, and game-based active movement training with robotic assistance. Whereas the control group received passive ankle movement in the mid-range of motion and attempted active ankle movement without robotic assistance. After multi-session training, the study group achieved significantly greater improvements in Fugl-Meyer Lower Extremity motor score (p = 0.007), plantarflexor strength (p = 0.009), and active range of motion (p = 0.011) than controls. The study group showed earlier motor recovery for plantarflexion and dorsiflexion than the control group (p < 0.05). This study showed that in-bed sensorimotor rehabilitation guided by a wearable ankle robot through combining motor relearning in real-time feedback, strong passive stretching, and active movement training facilitated early motor recovery for stroke survivors with severe hemiplegia in the acute/subacute phase.

In-Bed Sensorimotor Rehabilitation in Early and Late Subacute Stroke Using a Wearable Elbow Robot: A Pilot Study.

Objects: To evaluate the feasibility and effectiveness of in-bed wearable elbow robot training for motor recovery in patients with early and late subacute stroke. Methods: Eleven in-patient stroke survivors (male/female: 7/4, age: 50.7 ± 10.6 years, post-stroke duration: 2.6 ± 1.9 months) received 15 sessions of training over about 4 weeks of hospital stay. During each hourly training, participants received passive stretching and active movement training with motivating games using a wearable elbow rehabilitation robot. Isometric maximum muscle strength (MVC) of elbow flexors and extensors was evaluated using the robot at the beginning and end of each training session. Clinical measures including Fugl-Meyer Assessment of upper extremity (FMA-UE), Motricity Index (MI) for upper extremities, Modified Ashworth Scale (MAS) were measured at baseline, after the 4-week training program, and at a 1-month follow-up. The muscle strength recovery curve over the training period was characterized as a logarithmic learning curve with three parameters (i.e., initial muscle strength, rate of improvement, and number of the training session). Results: At the baseline, participants had moderate to severe upper limb motor impairment {FMA-UE [median (interquartile range)]: 28 (18-45)} and mild spasticity in elbow flexors {MAS [median (interquartile range)]: 0 (0-1)}. After about 4 weeks of training, significant improvements were observed in FMA-UE (p = 0.003) and MI (p = 0.005), and the improvements were sustained at the follow-up. The elbow flexors MVC significantly increased by 1.93 Nm (95% CI: 0.93 to 2.93 Nm, p = 0.017) and the elbow extensor MVC increased by 0.68 Nm (95% CI: 0.05 to 1.98 Nm, p = 0.036). Muscle strength recovery curve showed that patients with severe upper limb motor impairment had a greater improvement rate in elbow flexor strength than those with moderate motor impairment. Conclusion: In-bed wearable elbow robotic rehabilitation is feasible and effective in improving biomechanical and clinical outcomes for early and late subacute stroke in-patients. Results from the pilot study suggested that patients with severe upper limb motor impairment may benefit more from the robot training compared to those with moderate impairment.

Physical exercise improves strength, balance, mobility, and endurance in people with cognitive impairment and dementia: a systematic review.

QUESTION: Does physical exercise training improve physical function and quality of life in people with cognitive impairment and dementia? Which training protocols improve physical function and quality of life? How do cognitive impairment and other patient characteristics influence the outcomes of exercise training? DESIGN: Systematic review with meta-analysis of randomised trials. PARTICIPANTS: People with mild cognitive impairment or dementia as the primary diagnosis. INTERVENTION: Physical exercise. OUTCOME MEASURES: Strength, flexibility, gait, balance, mobility, walking endurance, dual-task ability, activities of daily living, quality of life, and falls. RESULTS: Forty-three clinical trials (n=3988) were included. According to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system, the meta-analyses revealed strong evidence in support of using supervised exercise training to improve the results of 30-second sit-to-stand test (MD 2.1 repetitions, 95% CI 0.3 to 3.9), step length (MD 5cm, 95% CI 2 to 8), Berg Balance Scale (MD 3.6 points, 95% CI 0.3 to 7.0), functional reach (3.9cm, 95% CI 2.2 to 5.5), Timed Up and Go test (-1second, 95% CI -2 to 0), walking speed (0.13m/s, 95% CI 0.03 to 0.24), and 6-minute walk test (50m, 95% CI 18 to 81) in individuals with mild cognitive impairment or dementia. Weak evidence supported the use of exercise in improving flexibility and Barthel Index performance. Weak evidence suggested that non-specific exercise did not improve dual-tasking ability or activity level. Strong evidence indicated that exercise did not improve quality of life in this population. The effect of exercise on falls remained inconclusive. Poorer physical function was a determinant of better response to exercise training, but cognitive performance did not have an impact. CONCLUSION: People with various levels of cognitive impairment can benefit from supervised multi-modal exercise for about 60minutes a day, 2 to 3days a week to improve physical function. [Lam FMH , Huang MZ, Liao LR, Chung RCK, Kwok TCY, Pang MYC (2018) Physical exercise improves strength, balance, mobility, and endurance in people with cognitive impairment and dementia: a systematic review. Journal of Physiotherapy 64: 4-15].

Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma.

Prevalent mutations in the mitogen-activated protein kinase 1 (MAPK1)/extracellular signal-regulated kinase 2 (ERK2) pathway have been identified in cervical squamous cell carcinoma in a large-scale genome sequencing effort. Furthermore, mutations in the rat sarcoma viral oncogene homolog (RAS)/Raf/Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway have also been revealed to have important roles in the pathogenesis of human cancer. However, whether the potential hotspot mutations in ERK2 and other components of the RAS/RAF/MEK/ERK signaling pathway also exist in Chinese patients with cervical carcinoma remains to be elucidated. In the present study, a total of 260 patients with cervical carcinoma of distinct subtypes were analyzed for the presence of potential hotspot mutations in the RAS/RAF/MEK/ERK signaling pathway. No ERK2 mutations were detected in these samples; however, Kirsten RAS (KRAS) p.G12D (c.35G>A) mutation was identified in 2/26 (7.7%) cervical adenocarcinoma cases, including 1/20 cervical mucinous adenocarcinoma and 1/6 cervical endometrioid carcinoma cases. In addition, no mutations in the ERK1, neuroblastoma RAS, Harvey RAS or B-Raf proto-oncogene serine/threonine kinase genes were detected in the present study. These results indicated that ethnic differences may be a primary reason for the discrepancy in ERK2 mutation frequencies between the current study and previous studies. Furthermore, mutation in the KRAS gene, but not other genes in the RAS/RAF/MEK/ERK signaling pathway, may have an active role in the pathogenesis of cervical carcinoma.

Psychometric properties of dual-task balance and walking assessments for individuals with neurological conditions: A systematic review.

BACKGROUND: The ability of performing a balance or walking task in conjunction with a secondary cognitive or motor task, referred to as dual-task (DT) ability, is essential in daily living. While there is some evidence that DT performance is impaired in individuals with neurological conditions, using reliable and valid tools to measure DT performance is essential. This systematic review aimed to evaluate the psychometric properties of DT balance and walking assessments in individuals with different neurological conditions. METHODS: A systematic literature search was conducted using PubMed, CINAHL, MEDLINE, PsycINFO, SCOPUS, Web of Science, and Cochrane Library (last search done in April 2016). The methodological quality was rated using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. RESULTS: Twenty-three articles involving individuals with stroke, Parkinson's disease, mild cognitive impairment, dementia, Alzheimer's disease, and multiple sclerosis were included. Outcomes derived from the walking tasks under DT condition generally demonstrated good reliability (correlation coefficient ≥0.75) across different neurological disorders, but their usefulness in distinguishing fallers from non-fallers was inconclusive. The reliability of outcomes derived from the cognitive/motor tasks and from the dual-task effect (DTE) (i.e., DT performance minus single-task performance) seemed to be lower but was understudied. The reliability of static or dynamic sitting/standing balance outcomes in DT condition was not assessed in any of the selected studies. CONCLUSIONS: The reliability of the outcomes derived from walking tasks was good. The psychometric properties of other DT outcomes need to be further investigated.

Whole-Body Vibration Intensities in Chronic Stroke: A Randomized Controlled Trial.

PURPOSE: A single-blinded randomized controlled study was conducted to investigate the effects of different whole-body vibration (WBV) intensities on body functions/structures, activity, and participation in individuals with stroke. METHODS: Eighty-four individuals with chronic stroke (mean age = 61.2 yr, SD = 9.2) with mild to moderate motor impairment (Chedoke-McMaster Stroke Assessment lower limb motor score: median = 9 out of 14, interquartile range = 7-11.8) were randomly assigned to a low-intensity WBV, high-intensity WBV, or control group. The former two groups performed various leg exercises while receiving low-intensity and high-intensity WBV, respectively. Controls performed the same exercises without WBV. All individuals received 30 training sessions over an average period of 75.5 d (SD = 5.2). Outcome measurements included knee muscle strength (isokinetic dynamometry), knee and ankle joint spasticity (Modified Ashworth Scale), balance (Mini Balance Evaluation Systems Test), mobility (Timed-Up-and-Go test), walking endurance (6-Minute Walk Test), balance self-efficacy (Activities-specific Balance Confidence scale), participation in daily activities (Frenchay Activity Index), perceived environmental barriers to societal participation (Craig Hospital Inventory of Environmental Factors), and quality of life (Short-Form 12 Health Survey). Assessments were performed at baseline and postintervention. RESULTS: Intention-to-treat analysis revealed a significant time effect for muscle strength, Timed-Up-and-Go distance, and oxygen consumption rate achieved during the 6-Minute Walk Test, the Mini Balance Evaluation Systems Test, the Activities-specific Balance Confidence scale, and the Short-Form 12 Health Survey physical composite score domain (P < 0.05). However, the time-group interaction was not significant for any of the outcome measures (P > 0.05). CONCLUSION: The addition of the 30-session WBV paradigm to the leg exercise protocol was no more effective in enhancing body functions/structures, activity, and participation than leg exercises alone in chronic stroke patients with mild to moderate motor impairments.

A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.

A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co­occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC­115, the MAPK1­mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC­binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (DNMT3A), transformation/transcription domain­associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease.

Tanshinone IIA inhibits the proliferation, migration and invasion of ectopic endometrial stromal cells of adenomyosis via 14-3-3ζ downregulation.

BACKGROUND: Adenomyosis is a specific subtype of endometriosis and recent evidences have indicated that Tanshinone IIA (TSIIA) might be a potential therapeutic option for endometriosis. Meanwhile, endometrial stromal cells (ESCs) of adenomyosis might play crucial roles in the progression of this disease, emphasizing the importance of targeting ESCs in the treatment of adenomyosis. Furthermore, previous evidences also implicated that deregulated 14-3-3ζ expression might be associated with therapeutic effects of certain drugs. AIM OF THE STUDY: The aim of this study is to evaluate the potential involvement of 14-3-3ζ in the process of TSIIA-treated adenomyosis. MATERIALS AND METHODS: Ectopic endometrial stromal cells (EESCs) were isolated from a total of 3 patients with adenomyosis. Cells were treated with TSIIA and infected with 14-3-3ζ-overexpressing adenovirus, the expression level of 14-3-3ζ was determined by western blotting (WB), cell viability was detected by Cell Counting Kit-8 (CCK8), cell invasion and migration was evaluated by transwell assay, and cell apoptosis was detected by flow cytometry. RESULTS: TSIIA could decrease cell viability, induce cell apoptosis, and inhibit cell migration and invasion in EESCs. Mechanistically, TSIIA markedly reduced the expression of 14-3-3ζ in EESCs, and overexpression of 14-3-3ζ could restore the ability of cell viability, migration and invasion, but has no effect on cell apoptosis. CONCLUSIONS: TSIIA could be a promising novel therapeutic agent for adenomyosis, via inducing cell apoptosis, inhibiting cell viability, migration and invasion in EESCs. Furthermore, the effects of cell viability, migration and invasion were mediated in 14-3-3ζ-dependent manner while that of cell apoptosis was mediated in 14-3-3ζ-independent manner.

Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas.

Cancer is caused by multiple genetic alterations within cells. Recently, large-scale sequencing has identified frequent ribonuclease type III (DICER1), CCCTC-binding factor (CTCF), ribosomal protein L22 (RPL22), DNA (cytosine-5-)-methyltransferase 3α (DNMT3A), transformation/transcription domain-associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 hotspot mutations in diverse types of cancer. However, it remains largely unknown whether these mutations also exist in ovarian carcinomas. In the present study, a collection of 251 patients with distinct subtypes of ovarian carcinomas were recruited and sequenced for the presence of these hotspot mutations. However, no mutations in the seven genes were detected in the samples. These negative results, together with certain recent reports, indicate that the hotspot mutations in the CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 genes may not be actively involved in the carcinogenesis of ovarian carcinoma. Of note, the DICER1 mutation frequency in Sertoli-Leydig cell tumor in the present study was significantly lower compared to prior observation, and therefore, it is speculated that this discrepancy may be mainly due to the small sample size analyzed in the study. In addition, among these samples, frequent polymerase (DNA directed) ε, catalytic subunit (POLE1) and ring finger protein 43 (RNF43) mutations were identified in endometrioid and mucinous ovarian carcinomas, respectively; thus DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations may not play synergistic roles with POLE1 or RNF43 mutations in the carcinogenesis of endometrioid or mucinous ovarian carcinomas.

Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma.

The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively involved in other subtypes of ovarian carcinoma.

RNF43 mutations are recurrent in Chinese patients with mucinous ovarian carcinoma but absent in other subtypes of ovarian cancer.

Ring finger protein 43 (RNF43) is an E3 ubiquitin-protein ligase that accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and directly transfers the ubiquitin to targeted substrate proteins. Recently, large-scale sequencing efforts have identified prevalent RNF43 mutations in pancreatic and ovarian mucinous carcinomas. In the present study, we sequenced the entire coding sequences of RNF43 in 251 Chinese patients with distinct subtypes of ovarian cancers for the presence of RNF43 mutations. A total of 2 novel heterozygous nonsynonymous RNF43 mutations were identified in 2 out of 15 (13.3%) patients with mucinous ovarian carcinoma, these mutations were evolutionarily highly conserved; while no mutation was detected in other samples. In addition, none of the RNF43-mutated samples harbored DICER1 (dicer 1, ribonuclease type III), PPP2R1A (protein phosphatase 2, regulatory subunit A, alpha), TRRAP (transformation/transcription domain-associated protein) and DNMT3A (DNA (cytosine-5-)-methyltransferase 3 alpha) hot-spot mutations. Recurrent RNF43 mutations existed in mucinous ovarian carcinomas implicated that these mutations might play crucial roles in the tumorigenesis of these patients, while the absence of DICER1, PPP2R1A, TRRAP and DNMT3A hot-spot mutations suggested that these genetic alterations might not play synergistic roles with RNF43 mutations in these individuals. Additionally, the absence of RNF43 mutations in other subtypes of ovarian carcinoma implicated that RNF43 mutations might not be actively involved in the pathogenesis of these disorders.

[Randomized controlled trial on manipulation for the treatment of cervical vertigo of high flow velocity type].

OBJECTIVE: To explore the effects of manipulation and traction combined with Nimodipine on the blood flow velocity of vertebrobasilar artery (VBA) in cervical vertigo of high flow velocity,and to evaluate clinical therapeutic effects between two methods. METHODS: From March 2008 to Feburary 2009,70 patients who were diagnosed as high flow velocity of cervical vertigo were randomly divided into treatment group (35 cases) and control group (35 cases). Among 70 patients, 32 were male and 38 were female. The age ranged from 21 to 45 years with an average of 37.6 years. The disease course ranged from one day to two years with an average of 12.6 days. Patients of the treatment group were treated with manipulation for total three weeks, three times once week. The patients in the control group were treated with traction (weight ranged from 5 to 6 kg, 20 minutes each time, once every other day) and Nimodipine for total three weeks (three times each day, and with a dose of 40 mg each time). After three weeks, the changes of flow velacity of VBI and score before and after treatment were observed using transcranil Doppler (TCD) and Evaluation Scale for Cervical Vertigo. After six weeks, the therapeutic effects were assessed. RESULTS: The mean velocity in left vertebral artery (LVA), right vertebral artery (RVA) and basilar artery (BA) were obviously lower than those before treatment in two groups (P < 0.01). The LVA, RVA and BA of the treatment group was lower than those of control group after 3 weeks (P < 0.01). There was significant difference in vertigo score after treatment between the two groups. The improvement rate of double-sides sign in X-ray image and the therapeutic effects of treatment group was superior to that of control group (P < 0.01). CONCLUSION: The effect of manipulation on flow velocity of VBA is superior to that of traction combined with Nimodipine, and there are better therapeutic effects in treating cervical vertigo of high flow velocity in comparison with traction combined with Nimodipine. But there are more higher demands for manipulation's application.

[Development of high speed UV-Vis spectrophotometer].

A high speed spectrophotometer based on a linear CCD was developed. The function and structure of the hardware and the software for the instrument were discussed. The elementary performance was tested as follows: wavelength range 200-820 nm, full spectrum scan time < 0.1 s, spectral bandwidth 0.7 nm, wavelength accuracy +/-1 nm, photometric accuracy +/- 0.005 AU, baseline flatness < 0.001 AU (rms), and stray light < 0.1%. Results showed that this instrument is easy to use, fast and with high analytical performance. In addition, it has internet function of remote control and remote access. With the powerful data processing and spectrum analyzing software, it will provide a strong tool for routine analysis and the research on dynamic reaction in chemistry and biology fields.