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Purpose: Many women experience pain around the low back and pelvic girdle during/after pregnancy. These pains have different risk factors and require independent management strategies. Therefore, an epidemiological database is required to understand when each type of pain occurs, and how serious it could be. Thus, the history of pain in the lumbopelvic region throughout the perinatal period was investigated. Methods: The information of 170 women recruited at the obstetrics and gynecology clinics in Japan was collected at 12, 24, 30, and 36 weeks of pregnancy, in the early days after childbirth, and one month after childbirth. The presence and severity of sacroiliac joint pain, pubic pain, groin pain, and low back pain were assessed using a numerical rating scale. Descriptive statistics were used to determine changes in the prevalence of pain. In addition, the change in the severity of each type of pain was observed through descriptive statistics, by including only those who had pain. Results: The sacroiliac joint pain showed a twofold increase from 12 to 24 weeks, while the pubic pain suddenly increased after 24 weeks. The severity of pubic and groin pain increased sharply during pregnancy. Regarding low back pain, the change in the severity was lesser than the other pains. The sacroiliac joint pain was the highest among the four pains during pregnancy. Conclusion: Each type of pain had a different incidence rate and a different time of onset and aggravation. These results help women and health professionals to manage, and prevent these harmful symptoms. [ABSTRACT FROM AUTHOR]

Autologous nerve grafting is the gold standard method for peripheral nerve injury with defects. Artificial nerve conduits have been developed to prevent morbidity at the harvest site. However, the artificial conduit regeneration capacity is not sufficient. A Bio 3D printer is technology that creates three-dimensional tissue using only cells. Using this technology, a three-dimensional nerve conduit (Bio 3D nerve conduit) was created from several cell spheroids. We reported the first application of the Bio 3D nerve conduit for peripheral nerve injury. A Bio 3D nerve conduit that was created from several cells promotes peripheral nerve regeneration. The Bio 3D nerve conduit may be useful clinically to treat peripheral nerve defects. [ABSTRACT FROM AUTHOR]

Early detection of knee osteoarthritis (KOA) can improve treatment outcomes and prevent its progression. The aim of this systematic review was to identify the functional changes in early KOA. Electronic journal databases and platforms, including PubMed, the Physiotherapy Evidence Database, the Cochrane Central Register of Controlled Trials, and Scopus were searched. The inclusion criteria were as follows: (1) studies comparing patients with early KOA with an age-matched control group and (2) studies with objectively measured functional changes as outcomes. Studies that included individuals with Kellgren and Lawrence (K/L) grades > 2- were excluded. A random-effects model was constructed to calculate pooled standardized mean differences (SMDs). A total of nine articles were included in this systematic review. Seven studies used classification criteria to define early KOA, including knee pain; a K/L grade of 0, 1, or 2- (osteophytes only) for the medial compartment; and the presence of two out of four MRI criteria. The remaining two studies included K/L grade 1 confirmed by radiography. Early KOA participants had a significantly longer timed up-and-go test (TUG) time (pooled SMD: 0.57; 95% confidence interval: 0.15, 0.98). The two groups had similar knee extension muscle strength at 90° knee flexion. The quality of evidence for each measured outcome was "very low." In this review, longer TUG was identified as a functional manifestation of early KOA. Further studies involving functional assessments are needed to develop a screening method to detect early KOA. Key Points • There is a need for diagnostic criteria that include functional changes in patients with early knee osteoarthritis, since radiographic facilities are not available everywhere. • In this review, a long timed up-and-go test time was identified as a functional manifestation of early knee osteoarthritis. • If the findings of this study can be replicated, measurement of TUG may allow for earlier detection of knee osteoarthritis outside the hospital and in routine clinical practice without the use of MRI or X-rays. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the association between hip extensor muscle weakness and performance of activities of daily living (ADL) including stair ambulation, sit-to-stand (STS), and walking in patients with early-stage knee osteoarthritis (OA). Methods: Community-dwelling older individuals (age ≥ 65 years and Kellgren–Lawrence grade 1–2) were recruited in this cross-sectional study. The ability to perform stair ambulation, STS, and walking was measured using the Japanese Knee Osteoarthritis Measure. The maximum isometric knee extensor and hip extensor muscle strengths were evaluated. To investigate the association between hip extensor muscle strength and performance on ADL, a multivariate logistic analysis was conducted, adjusting for age, sex, and knee extensor muscle strength. Results: A total of 161 participants were included in this study. Multivariate logistic analysis revealed a significant association between lower hip extensor muscle strength and higher presence of difficulty in stair ambulation [odds ratio (OR), 0.33; 95% confidence interval (CI), 0.11. 0.98; p < 0.05] and STS (OR, 0.32; 95% CI, 0.11. 0.92; p < 0.05). No significant association between hip extensor muscle strength and difficulty in walking was observed (OR, 0.47; 95% CI, 0.14. 1.62; p = 0.23). Conclusions: Hip extensor muscle weakness was associated with difficulty during stair ambulation and STS in patients with early-stage knee OA, after adjusting for knee extensor muscle strength. The results suggest that hip extensor muscle strength may be important to improve or maintain ADL in patients with early-stage knee OA. [ABSTRACT FROM AUTHOR]

Although autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects, harvesting autologous nerves is highly invasive and leads to functional loss of the ablated part. In response, artificial nerve conduits made of artificial materials have been reported, but the efficacy of the nerve regeneration still needs improvement. The purpose of this study is to investigate the efficacy and mechanism of the Bio three-dimensional (3D) conduit composed of xeno-free human induced pluripotent stem cell–derived mesenchymal stem cells (iMSCs). The 5-mm nerve gap of the sciatic nerve in immunodeficient rats was bridged with the Bio 3D conduit or silicone tube. Functional and histological recovery were assessed at 8 weeks after surgery. The regenerated nerve in the Bio 3D group was significantly superior to that in the silicone group based on morphology, kinematics, electrophysiology, and wet muscle weight. Gene expression analyses demonstrated neurotrophic and angiogenic factors. Macroscopic observation revealed neovascularization both inside and on the surface of the Bio 3D conduit. Upon their subcutaneous implantation, iMSCs could induce angiogenesis. The Bio 3D conduit fabricated from iMSCs are an effective strategy for nerve regeneration in animal model. This technology will be useful in future clinical situations. [ABSTRACT FROM AUTHOR]

This study aimed to examine the effect of transcutaneous electrical nerve stimulation (TENS) on stair climbing capacity in individuals with pre-radiographic to mild knee osteoarthritis (OA). This is a secondary analysis of data from a single, participant-blinded, randomized controlled trial with a pre-post design. Participants with pre-radiographic to mild knee OA (mean age, 59.1 years; 72.9% women) were randomly assigned into two groups, a TENS (n = 30) and a sham-TENS groups (n = 29). TENS or sham-TENS treatments were applied to all participants by using the prototype TENS device with pre-specified parameters. The primary outcome measures included valid and reliable functional measures for stair climbing (stair-climb test [SCT]), visual analog scale for knee pain during the SCT, and quadriceps muscle strength. TENS improved SCT time by 0.41 s (95% confidence interval [CI]: 0.07, 0.75). The time reduction in the transition phase explains the TENS therapeutic effect. Post-hoc correlation analyses revealed a non-significant but positive relationship between the pain relief effect and improved 11-step SCT time in the TENS group but not in the sham-TENS group. These results indicate that the TENS intervention may be an option for reducing the burden of early-stage knee OA. [ABSTRACT FROM AUTHOR]

Objective: The association between pain catastrophizing and ability to perform activities of daily living (ADL) requiring weight bearing, in particular stair climbing, standing from a seated position, and walking, in individuals with knee osteoarthritis (OA) is unclear. This study aimed to investigate the association between pain catastrophizing and ability to perform these ADLs by this population. Method: This cross-sectional study included individuals with knee OA (Kellgren and Lawrence grades 1–4). The ability to perform ADL was evaluated using the knee OA-related health domain measure (Japanese Knee Osteoarthritis Measure). Pain catastrophizing was evaluated using the Pain Catastrophizing Scale. The association between pain catastrophizing and ability to perform ADL, in particular stair climbing, standing from a seated position, and walking, was evaluated using the logistic regression analysis. Three types of sensitivity analysis were performed to validate the results of the logistic regression analysis. Results: A total of 151 participants were included in the final analysis. When adjusted for covariates, those with pain catastrophizing showed significantly decreased stair climbing ability (odds ratio 8.84; 95% confidence interval 1.37 to 56.92). Moreover, the results did not change even with sensitivity analysis. By contrast, when adjusted for covariates, those with pain catastrophizing did not show significantly decreased ability to stand from a seated position and walk. Conclusion: Pain catastrophizing in knee OA patients showed significantly decreased stair climbing ability. There is a need to consider the effect of pain catastrophizing in rehabilitation of knee OA patients with decreased ability to climb stairs. Key Points • Pain catastrophizing in knee OA patients showed significantly decreased stair climbing ability. • Ability to stand from a seated position and walk were not affected by pain catastrophizing. • There is a need to consider the effect of pain catastrophizing in rehabilitation of knee OA patients with decreased ability to climb stairs. [ABSTRACT FROM AUTHOR]

Introduction/objectives: This study aimed to investigate the association between hip abductor muscle strength and knee pain in patients with early-stage knee osteoarthritis (OA) while ascending and descending stairs. Method: This cross-sectional study included individuals with early-stage knee OA (Kellgren/Lawrence grades 1 or 2). Knee pain while ascending and descending stairs was evaluated using a knee OA-related health domain measure (Japanese Knee Osteoarthritis Measure). Knee extension and hip abductor muscle strength were also evaluated. The association between hip abductor muscle strength and knee pain while ascending and descending stairs was evaluated using multiple regression analysis. Results: A total of 157 participants were included in the final analysis. After the adjustment for age, sex, and knee extension strength, those with knee pain while descending stairs showed significantly decreased hip abductor muscle strength (β, − 0.09; 95% confidence interval [CI], − 0.19 to − 0.003). In contrast, after the adjustment for age, sex, and knee extension muscle strength, those with knee pain while ascending stairs did not have significantly decreased hip abductor muscle strength (β, − 0.06; 95% CI, − 0.15 to 0.02). Conclusions: Patients with early-stage knee OA and knee pain while descending stairs had significantly reduced hip abductor muscle strength. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to examine the interaction effect between ambulatory physical activity (PA) and varus thrust on knee pain in individuals with knee osteoarthritis (OA). Method: Subjects (n = 207; mean age: 73.1 years, 71.5% women) in orthopedic clinics with diagnosed knee OA (Kellgren/Lawrence grade ≥ 1) were enrolled in this 12-month observational cohort study. Participants underwent gait observation for varus thrust assessment and pedometer-based ambulatory PA measurements at baseline and 12-month follow-up. Knee pain intensity was assessed using the Japanese Knee Osteoarthritis Measure pain subscale as a primary outcome measure. Multiple linear regression analyses were performed to evaluate ambulatory PA–thrust interaction on knee pain intensity. Results: Ninety-two subjects (mean age, 73.4 years; 68.5% women) completed the 12-month follow-up assessment. Baseline ambulatory PA–thrust interaction was significant (P = 0.017) in the cross-sectional analysis, adjusting for covariates, which yielded R2 = 0.310. Subgroup analysis showed that varus thrust was significantly associated with worse knee pain in subjects walking ≥ 5000 steps/day adjusting for covariates (beta: 7.94; 95% CI: 3.82, 12.1; P < 0.001) with a higher predictive ability (R2 = 0.664). In contrast, ambulatory PA–thrust interaction in the longitudinal analysis showed no significant association with knee pain changes. Conclusions: Ambulatory PA interacted with varus thrust in the association with knee pain, as coexisting high ambulatory PA and varus thrust had the strongest association with higher knee pain. Maximal pain relief effects might be achieved when both ambulatory PA and varus thrust are treated simultaneously, rather than treating each separately. [ABSTRACT FROM AUTHOR]

To compare the efficacy and adherence rates of two parallel home exercise therapy programs—multiple exercise (training and stretching the knee and hip muscles) and control (training the quadriceps muscles)—on knee pain, physical function, and knee extension strength in community-dwelling elderly individuals with pre-radiographic knee osteoarthritis (OA). One hundred patients with medial knee pain were randomly allocated to one of two 4-week home exercise programs. Individuals with a Kellgren/Lawrence (K/L) grade 0 or 1 OA (pre-radiographic knee OA) in the medial compartment were enrolled. Primary outcomes were knee pain (visual analog scale), self-reported physical function (Japanese Knee Osteoarthritis Measure [JKOM]), and isometric maximum muscle strength of the knee extensor measured using a hand-held dynamometer. A total of 52 patients (28 [53.8%] in the multiple exercise group, 24 [46.2%] in the control group) completed the trial. The JKOM activities of daily living and general health conditions outcomes improved significantly in the multiple exercise group compared to the control group (JKOM activities of daily living, beta = − 0.76; 95% confidence interval [CI], − 1.39 to − 0.13; p = 0.01; JKOM general health conditions, beta = − 0.25; 95% CI, − 0.48 to − 0.01; p = 0.03). The home exercise compliance rates of the multiple exercise and control groups were 96.6 and 100%, respectively. When targeting pre-radiographic knee OA in community-dwelling elderly, it is important to implement home exercise programs that aim to improve muscle strength and joint flexibility rather than knee extension muscle power only. [ABSTRACT FROM AUTHOR]

This study aimed to develop a self-questionnaire index relevant to lower limb functional assessment reflecting clinical symptoms and activity restrictions associated with activities of daily living (ADL) for patients with knee osteoarthritis. This cross-sectional study enrolled patients with knee osteoarthritis (Kellgren/Lawrence grade ≥ 1). Participants evaluated clinical symptoms and activity restrictions using self-reported questionnaires. Radiographic evaluation, knee joint range of motion (ROM), and lower limb muscle strength were assessed. Associations between clinical symptoms, activity restrictions, and knee and hip joint function were evaluated using multiple and logistic regression analysis. Overall, 142 participants were included in the final analysis. Patients with knee pain while rising from a chair had lower knee and hip extension strength (knee extension β = − 0.28; 95% confidence interval (CI), − 0.41 to − 0.14; P < 0.0001; hip extension β = − 0.26; 95% CI, − 0.42 to − 0.08; P = 0.0034), and restricted knee extension ROM (odds ratio [OR] = 2.17; 95% CI, 1.02-4.63; P = 0.041). Patients with knee pain during stair climbing, turning or who were unable to stand on one leg without external support had reduced hip abduction muscle strength (β = − 0.17; 95% CI, − 0.27 to − 0.07; P = 0.0008). Patients with knee pain while rising from a chair or stepping showed more severe knee joint degeneration on radiographic evaluation (OR = 3.26; 95% CI, 1.11-10.91; P = 0.03). The self-questionnaire index reflected clinical symptoms and activity restrictions associated with ADL and was significantly associated with lower limb function in individuals with knee osteoarthritis. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Background: The association between subjective cognitive decline and falls has not been clearly determined.Aims: Our aim was to explore the effect of subjective cognitive decline on falls in community-dwelling older adults with or without objective cognitive decline.Methods: We included 470 older adults (mean age 73.6 ± 5.2; 329 women) living in the community and obtained data on fall history directly from the participants. Subjective cognitive decline was assessed using a self-administered question. Objective cognitive function was measured using the Mini-Mental State Examination. Statistical analyses were carried out separately for participants with objective cognitive decline and those without.Results: A multiple logistic regression analysis showed that, among participants without objective cognitive decline, subjective cognitive decline was positively associated with falls [OR 1.91; 95% confidence interval (CI) 1.17-3.12; p = 0.01). Conversely, among participants with objective cognitive decline, subjective cognitive decline was negatively associated with falls (OR 0.07; 95% CI 0.01-0.85, p = 0.04).Discussion: The result suggests that the objective-subjective disparity may affect falls in community-dwelling older adults.Conclusions: The presence of subjective cognitive decline was significantly positively associated with falls among cognitively intact older adults. However, among their cognitively impaired peers, the absence of subjective cognitive decline was positively associated with falls. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether knee pain during various activities of daily living (ADLs) is associated with physical activity in patients with early and severe knee osteoarthritis (OA). We hypothesized that the painful ADLs associated with decreased physical activity differ according to disease severity. This cross-sectional study enrolled 270 patients with medial knee OA, assigned to either the early (Kellgren Lawrence [K/L] grade 1-2) or the severe group (K/L grade 3-4). Physical activity was assessed using a pedometer. Knee pain during six ADLs (waking up in the morning, walking on a flat surface, ascending stairs, etc.) was evaluated using a questionnaire. We performed multiple regression and quantile regression analysis to investigate whether knee pain during each ADL was associated with physical activity. In the early group, the more knee pain they experienced while ascending stairs, the lower their physical activity was (75th regression coefficient = −1033.70, P = 0.018). In the severe group, the more knee pain they experienced while walking on a flat surface or bending to the floor or standing up, the lower their physical activity was (unstandardized coefficients = −1850.87, P = 0.026; unstandardized coefficients = −2640.35, P = 0.010). Knee pain while ascending stairs and while walking on a flat surface or bending to the floor or standing up was a probable limiting factor for physical activity in early and severe knee OA, respectively. These findings suggested that a reduction in task-specific knee pain according to disease severity could improve physical activity levels. [ABSTRACT FROM AUTHOR]

Background: The shuttle walking test (SWT) is a simple, widely used method for assessing endurance performance in the elderly. Despite widespread community use, its associated factors are unclear. Aims: We aim to identify previously undefined SWT association factors in community-dwelling elderly people. Methods: Herein, 149 healthy elderly Japanese subjects performed the SWT, and were assessed for height, weight, smoking history, 10-m walk time, Timed Up and Go (TUG) scores, handgrip strength, skeletal mass index (SMI), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV), cardio-ankle vascular index, and ankle brachial index. We divided men and women into higher and lower SWT score groups, compared between-group parameters, and performed stepwise multivariate logistic regression analysis to identify factors independently associated with SWT scores. Results: Age, BMI, 10-m walk time, TUG score, SMI, FVC (L; %-predicted), and FEV (L; %-predicted) were significantly different between SWT score groups for men, while in women, significant differences were observed in age, TUG score, handgrip strength, FVC (L; %-predicted), and FEV (L; %-predicted) ( p < 0.05). In the multivariate logistic regression model, 10-m walk time, and FEV showed significant associations with SWT results in men; among women, age was the only significantly associated factor ( p < 0.05). Conclusions: Results indicate that better lung function and shorter walk time independently associate with SWT results in community-dwelling men; in women, age is the only association. Our findings may offer insight when considering the focus of community exercise programs among the elderly. [ABSTRACT FROM AUTHOR]

Background and aims: The aim of this study was to investigate the physiological characteristics of community-dwelling elderly subjects, aged ≥65 years, with airflow limitation in the Japanese community. Methods: Subjects were recruited through local press advertisement, and 180 individuals were enrolled. Data on age, body mass index (BMI), gender, smoking history, and past medical history were obtained, as were pulmonary function parameters, skeletal muscle mass index, and physical activity. Results: The final study population comprised 161 participants from whom we obtained valid spirometry results. The mean age of this population was 73.4 ± 4.4 years, and 78 participants (48.4 %) were men. The prevalence of airflow limitation was 29.2 % ( n = 47). Subjects with airflow limitation were significantly older ( P = 0.01) and had poorer pulmonary function ( P < 0.01), lower BMI ( P < 0.01), and lower skeletal muscle mass index ( P = 0.03) than healthy elderly subjects. Furthermore, skeletal muscle mass index was significantly correlated with the percentage of predicted forced vital capacity ( r = 0.45, P < 0.05) and forced expiratory volume in 1 s ( r = 0.50, P < 0.05) only in men with airflow limitation. Conclusions: We found that the skeletal muscle mass index was significantly reduced in community-dwelling elderly with airflow limitation, and the skeletal muscle mass index was correlated with pulmonary function only in men with airflow limitation. [ABSTRACT FROM AUTHOR]

A disturbance in gait pattern is a serious problem in patients with rheumatoid arthritis (RA). The aim of the present study was to examine the utility of the smartphone gait analysis application in patients with RA. The smartphone gait analysis application was used to assess 39 patients with RA (age 65.9 ± 10.0 years, disease duration 11.9 ± 9.4 years) and age-matched control individuals (mean age, 69.1 ± 5.8 years). For all RA patients, the following data were obtained: disease activity score (DAS) 28, modified health assessment questionnaire (mHAQ), and assessment of walking ability. Patients walked 20 m at their preferred speed, and trunk acceleration was measured using a Smartphone. After signal processing, we calculated the following gait parameters for each measurement terminal: peak frequency (PF), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. The gait parameters of RA and control groups were compared to examine the comparability of the 2 groups. Criterion-related validity was determined by evaluating the correlation between gait parameters and clinical parameters using Spearman's correlation coefficient. The RA group showed significantly lower scores for the walking speed, AC, and CV than the control group. There were no significant differences in PF. PF (gait cycle) was mildly associated with gait speed ( P < 0.05). AC (gait balance) was moderately associated with the DAS, mHAQ, gait ability, and gait speed ( P < 0.05). CV (gait variability) was moderately associated with the DAS, gait ability, and gait speed ( P < 0.05). This is the first study to examine the use of a smartphone device for gait pattern measurement. The results suggest that some gait parameters recorded using the smartphone represent an acceptable assessment tool for gait in patients with RA. [ABSTRACT FROM AUTHOR]

Background and aims: Increased fear of falling is associated with greater muscular coactivation during standing postural control. Excessive muscular coactivation reduces the performance of agonist muscles. Although several recent studies have observed increased muscular coactivation during walking in older adults, little is known about the relationship between fear of falling and muscular coactivation during walking. The purpose of this study was to compare muscular coactivation during walking between older adults with fear of falling and older adults without fear of falling. Methods: Thirty-eight healthy older adults (82.3±6.8 years) participated in this study. Walking speed and step length were measured. Electromyography (EMG) data were collected from the tibialis anterior and soleus during walking to calculate the co-contraction index (CI). Subjects were divided into those with fear of falling and those without fear of falling, on the basis of a modified Falls Efficacy Scale (FES). Stepwise multiple regression analysis was used, with CI as the dependent variable, and fear of falling, experience of falling (during the past year), walking speed, step length, and age as independent variables. Results: Mean values of CI during walking, walking speed, and step length were 51.9+11.7%, 0.90±0.40 m/s, and 0.43±0.11 m, respectively. Eight subjects (21.1 %) had fallen within the past year, and 19 subjects (50.0%) had fear of falling. All subjects without fear of falling had FES scores of 10 (maximum score). Subjects with fear of falling had a median FES score of 17 (interquartile range, 13 to 25). Stepwise multiple regression analysis revealed that fear of falling remained significantly associated with CI (p<0.01): CIs for subjects with fear and those without fear were 59.5±12.2% and 46.7 ±8.5%, respectively. Conclusion: Individuals with a fear of falling have increased muscular co-activation at the ankle joint during walking, at least in a certain subgroup of older adults. Further research is needed to clarify negative and positive effects of muscular coactivation during walking in fearful subjects. [ABSTRACT FROM AUTHOR]

Background and aims: A close relationship exists between dual-task (DT)-related gait changes and the risk of falling in the elderly. However, the impact of DT training on the incidence of falls in the elderly remains unclear. We aimed to evaluate the effects of a seated stepping exercise in DT conditions to improve walking ability in community-dwelling elderly. Methods: This was a randomized controlled trial (RCT) in community-dwelling elderly in Japan. Fifty-three participants were randomly assigned to a DT group (stepping exercise in DT conditions, n=26) and a single- task (ST) group (stepping exercise in ST conditions, n=27). All participants received 50 min group training sessions, once a week for 24 weeks. Outcome measures were based on differences in walking ability in single- task (ST), cognitive-task (CT), and manual-task (MT) conditions between DT and ST groups. Results: Participants in the DT group showed significantly greater improvement in outcome measures, including 10-m gait speed, walking cadence, and cost during cognitive and manual tasks. The number of enumerated figures during CT, as well as the numbers of steps taken and of enumerated figures during stepping with MT demonstrated significant Group x Time interactions (p<0.05). Conclusions: This RCT suggests that the seated stepping exercise is more effective at improving ambulatory function in DT conditions than in ST conditions. [ABSTRACT FROM AUTHOR]

Background and aims: The aim of the present study is to compare the gaze behavior be-tween falters and non-fallers during obstacle avoidance in dual-task conditions. Methods: Nine older adults who had no experience of falling (mean age 79.9±5.4) and 9 older adults with known experience of falling (83.4±3.6) participated in the study. We examined their gaze behavior during obstacle avoidance in single-task (ST) and dual-task (DT) conditions. Results: In the ST condition, compared with the faller group, the non-faller group showed no significant difference in timing of gaze transfer from the obstacle (faller: gaze transfer from obstacle when 1.6±1.1 steps before; non-faller: 1.9±0.7 steps before, p=0.493). In the DT condition, the faller group chose a transfer of gaze strategy significantly earlier than the non-faller group (faller: 2.7±1.4 steps before; non-faller: 1.6±0.5 steps before, p=0.008). Conclusion: Our findings suggest that fallers chose an early transfer of gaze strategy when challenged with an obstacle in DT conditions. [ABSTRACT FROM AUTHOR]

Genome-wide expression profiling revealed overexpression of the gene encoding frizzled homologue 10 (FZD10), a cell-surface receptor for molecules in the Wnt pathway, as a potential contributor to synovial sarcomas (SS). Northern blotting and immunohistochemical staining confirmed that expression levels of FZD10 were very high in nearly all SS tumors and cell lines examined but absent in most normal organs or in some cancers arising in other tissues. Treatment of human SS cells with small-interfering RNA (siRNA) to FZD10 decreased the amount of its product and suppressed growth of SS cells. Moreover, a polyclonal antibody specifically recognizing the extracellular domain (ECD) of FZD10 was markedly effective in mediating ADCC against FZD10-overexpressing synovial sarcoma cells in vitro. Injection of the antibody into SS xenografts in nude mice attenuated tumor growth, and TUNEL assays revealed clusters of apoptotic cells in antibody-treated xenografts. Taken together, these findings suggest that a humanized antibody against FZD10 might be a promising treatment for patients with tumors that overexpress FZD10; minimal or no adverse reactions would be expected because FZD10 protein is not abundant in vital organs.Oncogene (2005) 24, 6201–6212. doi:10.1038/sj.onc.1208780; published online 27 June 2005 [ABSTRACT FROM AUTHOR]

We report here that the Id2 (inhibitor of DNA binding 2) gene is a novel target of transcriptional activation by EWS–FLI1 and EWS–ERG, two fusion proteins that characterize Ewing family tumors (EFTs). To identify downstream targets of these EWS–ETS fusion proteins, we introduced EWS–ETS fusion constructs into a human fibrosarcoma cell line by retroviral transduction. cDNA microarray analysis revealed that Id2 expression was up-regulated by introducing the EWS–ETS fusion gene but not by the normal full-length ETS gene. An Id2 promoter-luciferase reporter assay showed that transactivation by EWS–ETS involves the minimal Id2 promoter and may function in cooperation with c-Myc within the full-length regulatory region. A chromatin immunoprecipitation assay revealed direct interaction between the Id2 promoter and EWS-FLI1 fusion protein in vivo. Significantly higher expression of Id2 and c-Myc was observed in all of the six EFT cell lines examined compared to six other sarcoma cell lines. Moreover, high levels of Id2 expression were also observed in five of the six primary tumors examined. Id2 is generally thought to affect the balance between cell differentiation and proliferation in development and is highly expressed in several cancer types. Considering these previous studies, our data suggest that the oncogenic effect of EWS–ETS may be mediated in part by up-regulating Id2 expression.Oncogene (2002) 21, 8302–8309. doi:10.1038/sj.onc.1206025 [ABSTRACT FROM AUTHOR]

Post-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA. [ABSTRACT FROM AUTHOR]

Cell-based therapies are attracting attention as alternative therapeutic options for brain damage. In this study, we investigated the therapeutic effect of a combined therapy of cell transplantation and locomotor training by evaluating the neuronal connectivity. We transplanted neural cells derived from the frontal cortex of E14.5 GFP-expressing mice into the frontal lobe of 3-week-old rats with brain injury, followed by treadmill training (TMT) for 14 days. In the TMT(−) group, graft-derived neurites were observed only in the striatum and internal capsule. In contrast, in the TMT(+) group, they were observed in the striatum, internal capsule, and the cerebral peduncle and spinal cord. The length of the longest neurite was significantly longer in the TMT(+) group than in the TMT(−) group. In the TMT(+) group, Synaptophysin+ vesicles on the neuronal fibers around the ipsilateral red nucleus were found, suggesting that neuronal fibers from the grafted cells formed synapses with the host neurons. A functional analysis of motor recovery using the foot fault test showed that, 1 week after the transplantation, the recovery was significantly better in the cell transplantation and TMT group than the cell transplantation only group. The percentage of cells expressing C-FOS was increased in the grafts in the TMT(+) group. In conclusion, TMT promoted neurite extensions from the grafted neural cells, and the combined therapy of cell transplantation and locomotor training might have the potential to promote the functional recovery of rats with brain injury compared to cell transplantation alone. [ABSTRACT FROM AUTHOR]

This systematic review with a meta-analysis aimed to summarize the current evidence of the effectiveness of mesenchymal stem cell (MSC) treatment for knee osteoarthritis (OA) and to examine whether rehabilitation is an effect modifier of the effect estimate of MSC treatment. A literature search yielded 659 studies, of which 35 studies met the inclusion criteria (n = 2385 patients; mean age: 36.0–74.5 years). The meta-analysis results suggested that MSC treatment through intra-articular injection or arthroscopic implantation significantly improved knee pain (standardized mean difference [SMD]: −1.45, 95% confidence interval [CI]: −1.94, −0.96), self-reported physical function (SMD: 1.50, 95% CI: 1.09, 1.92), and cartilage quality (SMD: −1.99; 95% CI: −3.51, −0.47). However, the MSC treatment efficacy on cartilage volume was limited (SMD: 0.49; 95% CI: −0.19, 1.16). Minor adverse events (knee pain or swelling) were reported with a wide-ranging prevalence of 2–60%; however, no severe adverse events occurred. The evidence for these outcomes was "very low" to "low" according to the Grades of Recommendation, Assessment, Development and Evaluation system because of the poor study design, high risk of bias, large heterogeneity, and wide 95% CI of the effects estimate. Performing rehabilitation was significantly associated with better SMD for self-reported physical function (regression coefficient: 0.881, 95% CI: 0.049, 1.712; P = 0.039). We suggest that more high quality randomized controlled trials with consideration of the potential rehabilitation-driven clinical benefit would be needed to facilitate the foundation of effective MSC treatment and regenerative rehabilitation for patients with knee OA. [ABSTRACT FROM AUTHOR]