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Objective: To evaluate the immediate effects of traditional local thermal therapy with indirect moxibustion on renal hemodynamics in patients with chronic kidney disease (CKD) by using Doppler ultrasonography (US). Design: Examiner-blinded crossover study. Participants: Forty-three participants with CKD (mean age ± standard deviation [SD], 44 ± 15 years; estimated glomerular filtration rate, 69.5 ± 25.5 mL/min per 1.73 m2; 20 men and 23 women). Intervention: Participants received three successive treatment sessions of indirect moxibustion bilaterally at BL 23, a crucial acupuncture point, in the session. In the control session, the examiner was blinded by using smoke and aroma produced by moxibustion performed in an ashtray placed near the patient's body. Outcome measures: The main outcome measure was resistive index (RI) in the renal segmental arteries. Blood flow parameters, including RI, were measured for six renal segmental arteries by using Doppler US at rest (baseline), immediately after completion of moxibustion (post 1), and 10 minutes later (post 2). Adverse events were monitored during intervention. Results: In the control session, RI at post 1 (median [first, third quartile]: 0.587 [0.562, 0.626]) and post 2 (0.583 [0.567, 0.629]) did not change significantly compared with baseline (0.592 [0.563, 0.636]), while in the treatment session, RI at post 1 (0.565 [0.530, 0.618]) and post 2 (0.561 [0.533, 0.614]) decreased significantly compared with baseline (0.590 [0.550, 0.652]) ( p < 0.001 and p < 0.001, respectively). The reduction in RI from baseline to post 2 in treatment session was significantly greater than in control session (mean ± SD, −0.026 ± 0.028 versus −0.003 ± 0.028; mean difference, −0.023 [95% confidence interval, −0.036 to −0.010]; p = 0.001]. No adverse events, such as burns, were observed during the study period. Conclusion: Renal vascular resistance was decreased after indirect moxibustion therapy in patients with CKD. [ABSTRACT FROM AUTHOR]

Background: There was no evidence of satisfying the standard to decide the efficacies of glucosamine and chondroitin in middle-aged and older Japanese adults with knee pain and/or stiffness. Aim: To investigate the effects of 24 week oral N-acetyl glucosamine and chondroitin sulfate supplementation on knee pain, self-reported knee function, physical activity, and physical performance. Methods: We randomly assigned 11 men and 39 women (aged 52-87 years) to receive 100 mg of N-acetyl glucosamine and 180 mg of chondroitin sulfate daily (Glu/Cho group) or a placebo (control, C group) for 24 weeks. The primary outcomes were a 100 mm visual analog pain scale (VAS) and the Japanese Knee Osteoarthritis Measure (JKOM) score. The secondary outcomes were physical activity and physical performance. Results: We observed a significant group × time interaction on the JKOM score. According to the post hoc test, it significantly decreased (i.e., improved knee function) from the 4- to 12-week follow-up in the Glu/Cho group and the Glu/Cho group score was significantly lower than the C group at the 12-week follow-up. We found a significant interaction on household physical activity. There was no significant interaction on VAS or physical performance tests. Discussion: The results of the present study were consistent with previous studies mainly conducted in European and American countries. Conclusion: These results suggest that consumption of N-acetyl glucosamine and chondroitin sulfate for 12 weeks or longer has a positive effect on self-reported knee function and household physical activity in middle-aged and older Japanese adults with knee pain and/or stiffness. [ABSTRACT FROM AUTHOR]

Background Roughly 40% of East Asians have inactive aldehyde dehydrogenase-2 ( ALDH2) encoded by the ALDH2*2 allele, and 90% have highly active alcohol dehydrogenase-1B ( ADH1B) encoded by the ADH1B*2 allele. Macrocytosis and macrocytic anemia in alcoholics have been associated with ADH1B and ALDH2 gene variants which increase acetaldehyde (AcH) levels. Methods We investigated the relationship between ADH1B*2, ALDH2*2, and leukocyte counts of Japanese alcoholic men ( N = 1,661). Results After adjusting for age, drinking habits, smoking habits, body mass index, presence of liver cirrhosis, and serum levels of C-reactive protein, we found that total and differential leukocyte counts were lower in the presence of the ALDH2*1/*2 genotype (vs. ALDH2*1/*1 genotype). ALDH2*2/*2 carriers were not found in our study population. Leukocyte, granulocyte, and monocyte counts were also lower in the presence of ADH1B*2 (vs. ADH1B*1/*1 genotype), but the lymphocyte count was higher. The ALDH2*1/*2 genotype was associated with leukocytopenia (<4,000/ μl; adjusted odds ratio [95% confidence interval] = 1.89 [1.27 to 2.80]), granulocytopenia (<2,000/ μl; 1.86 [1.22 to 2.82]), monocytopenia (<250/ μl; 2.22 [1.49 to 3.29]), and lymphocytopenia (<1,000/ μl; 1.93 [1.32 to 2.83]). In contrast, the ADH1B*2 had the opposite effect on lymphocytopenia (0.65 [0.46 to 0.93]). Considering genotype effects under conditions of immune stimulation, we observed suppressive effects of ADH1B*2 allele on leukocytosis (≥9,000/ μl; 0.69 [0.50 to 0.97]), granulocytosis (≥6,500/ μl; 0.66 [0.47 to 0.93]), and monocytosis (≥750/ μl; 0.56 [0.39 to 0.79]). The ADH1B*2 plus ALDH2*1/*2 combination had the greatest suppressive effects on the leukocyte, granulocyte, and monocyte counts. Conclusions The total and differential blood leukocyte counts of Japanese alcoholics were strongly affected by their ADH1B and ALDH2 gene variants. High AcH exposure levels probably play a critical role in the suppression of blood leukocyte counts in alcoholics. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the time series relationships between the peak musculotendon length and electromyography (EMG) activation during overground sprinting to clarify the risk of muscle strain injury incidence in each hamstring muscle. Full-body kinematics and EMG of the right biceps femoris long head (BFlh) and semitendinosus (ST) muscles were recorded in 13 male sprinters during overground sprinting at maximum effort. The hamstring musculotendon lengths during sprinting were computed using a three-dimensional musculoskeletal model. The time of the peak musculotendon length, in terms of the percentage of the running gait cycle, was measured and compared with that of the peak EMG activity. The maximum length of the hamstring muscles was noted during the late swing phase of sprinting. The peak musculotendon length was synchronous with the peak EMG activation in the BFlh muscle, while the time of peak musculotendon length in the ST muscle occurred significantly later than the peak level of EMG activation (p < 0.05). These results suggest that the BFlh muscle is exposed to an instantaneous high tensile force during the late swing phase of sprinting, indicating a higher risk for muscle strain injury. [ABSTRACT FROM AUTHOR]

Background: The Self-Directed Learning Readiness Scale for Nursing Education (SDLRSNE) assesses the extent to which an individual has the characteristics, capabilities, and attitudes required for self-directed learning. This study aimed to validate the Japanese version of the SDLRSNE with graduate-level nursing students. Method: Confirmatory factor analyses, using data from a cross-sectional online survey of 376 nursing students, were conducted to examine construct validity. Relationships with potential related factors were analyzed to evaluate construct validity. Reliability was evaluated with item analysis and Cronbach's alpha. Results: Factor analyses revealed that three-factor and individual subscale models had a moderate-to-poor fit. No meaningful relationship with potential related factors was noted. Reliability measurements indicated a moderate fit to data. Conclusion: This study could not confirm that the Japanese version of the SDLRSNE had acceptable levels of reliability and validity when tested with graduatelevel nursing students. Further research is needed to examine the psychometric properties of the Japanese version of the SDLRSNE with other adult nursing learners or with graduate-level nursing students in other countries. [ABSTRACT FROM AUTHOR]

This study focused on age-related changes in visual short-term memory using visual stimuli that did not allow verbal encoding. Experiment 1 examined the effects of age and the length of the stimulus presentation period on visual short-term memory function. Experiment 2 examined the effects of age, gender, and the length of the stimulus presentation period on visual short-term memory function. The worst memory performance and the largest performance difference between the age groups were observed in the shortest stimulus presentation period conditions. The performance difference between the age groups became smaller as the stimulus presentation period became longer; however, it did not completely disappear. Although gender did not have a significant effect ond’regardless of the presentation period in the young group, a significant gender-based difference was observed for stimulus presentation periods of 500 ms and 1,000 ms in the older group. This study indicates that the decline in visual short-term memory observed in the older group is due to the interaction of several factors. [ABSTRACT FROM AUTHOR]

Objective Progranulin is a growth factor that is active in wound repair and is an antagonist of tumor necrosis factor (TNF) receptors, regulating fibroblast activation, angiogenesis, and inflammation. Because long-standing activation of gene programs related to wound healing is a hallmark of systemic sclerosis (SSc), we sought to investigate the role of progranulin in SSc. Methods Progranulin expression levels in human and murine skin samples were determined by immunohistochemical analysis and quantitative reverse transcription-polymerase chain reaction. The role of progranulin in fibroblast activation was examined using a gene-silencing technique. Progranulin levels in serum obtained from 60 patients with SSc and 16 healthy control subjects were determined by enzyme-linked immunosorbent assay. Results Progranulin expression was increased in SSc dermal fibroblasts compared with normal dermal fibroblasts, both in vivo and in vitro. Transcription factor Fli-1, a deficiency of which is involved in the activation of SSc dermal fibroblasts, served as a potent repressor of the progranulin gene, and Fli-1+/− mice and bleomycin-treated wild-type mice exhibited up-regulated expression of progranulin in dermal fibroblasts. SSc dermal fibroblasts were resistant to the antifibrotic effect of TNF, but this resistance was reversed by gene silencing of progranulin. Serum progranulin levels were elevated in patients with early diffuse cutaneous SSc (dcSSc), especially in those with inflammatory skin symptoms, and were positively correlated with the C-reactive protein level. Conclusion Progranulin overproduction due to Fli-1 deficiency may contribute to the constitutive activation of SSc dermal fibroblasts by antagonizing the antifibrotic effect of TNF. Progranulin may also be involved in the inflammatory process associated with progressive skin sclerosis in early dcSSc. [ABSTRACT FROM AUTHOR]

Sit-to-stand exercise (STS) is a common activity of daily living. The objectives of the present study were: 1) to assess the validity of aerobic fitness measurements based on anaerobic thresholds (ATs), during incremental sit-to-stand exercise (ISTS) with and without arm support compared with an incremental cycle-ergometer (CE) test; and 2) to examine the reproducibility of the AT measured during the ISTSs. Twenty-six healthy individuals randomly performed the ISTS and CE test. Oxygen uptakes at the AT (AT-VO2) and heart rate at the AT (AT-HR) were determined during the ISTSs and CE test, and repeated-measures analyses of variance and Tukey's post-hoc test were used to evaluate the differences between these variables. Pearson correlation coefficients were used to assess the strength of the relationship between AT-VO2 and AT-HR during the ISTSs and CE test. Data analysis yielded the following correlations: AT-VO2 during the ISTS with arm support and the CE test, r = 0.77 (p < 0.05); AT-VO2 during the ISTS without arm support and the CE test, r = 0.70 (p < 0.05); AT-HR during the ISTS with arm support and the CE test, r = 0.80 (p < 0.05); and AT-HR during the ISTS without arm support and the CE test, r = 0.66 (p < 0.05). The AT-VO2 values during the ISTS with arm support (18.5 ± 1.9 mL⋅min-⋅kg-) and the CE test (18.4 ± 1.8 mL⋅min-⋅kg-) were significantly higher than those during the ISTS without arm support (16.6 ± 1.8 mL-min"1-kg"1; p < 0.05). The AT-HR values during the ISTS with arm support (126 ± 10 bpm) and the CE test (126 ±13 bpm) were significantly higher than those during the ISTS without arm support (119 ± 9 bpm; p < 0.05). The ISTS with arm support may provide a cardiopulmonary function load equivalent to the CE test; therefore, it is a potentially valid test for evaluating AT-VO2 and AT-HR in healthy, young adults. [ABSTRACT FROM AUTHOR]

Stabilisation splint therapy has long been thought to be effective for the management of temporomandibular disorders (TMD). However, the superiority of stabilisation splint therapy compared to other TMD treatments remains controversial. The aim of this study was to determine the efficacy of stabilisation splint therapy combined with non-splint multimodal therapy for TMD. A total of 181 TMD participants were randomly allocated to a non-splint multimodal therapy (NS) group (n = 85) or a nonsplint multimodal therapy plus stabilisation splint (NS+S) group (n = 96). Non-splint multimodal therapy included self-exercise of the jaw, cognitive--behavioural therapy, self-management education and additional jaw manipulation. Three outcome measurements were used to assess treatment efficacy: mouth-opening limitation, oro-facial pain and temporomandibular joint sounds. A two-factor repeated-measures analysis of variance (ANOVA) was used to evaluate the efficacy of the two treatment modalities (NS vs. NS+S), and Scheffe's multiple comparison test was used to compare the treatment periods. Subgroup analyses were performed to disclose the splint effects for each TMD diagnostic group. All three parameters significantly decreased over time in both groups. However, there were no significant differences between the two treatment groups in the total comparison or subgroup analyses; an exception was the group with degenerative joint disease. No significant difference between the NS and NS+S treatment approaches was revealed in this study. Therefore, we conclude that the additional effects of stabilisation splint are not supported for patients with TMD during the application of multimodal therapy. [ABSTRACT FROM AUTHOR]

Background and Objective The periodontal ligament ( PDL) is characterized by rapid turnover, high remodeling capacity and high inherent regenerative potential compared with other connective tissues. Periostin, which is highly expressed in the fibroblasts in the PDL, has been widely discussed in relation to collagen fibrillogenesis in the PDL. Recently, several reports have indicated periostin in cell migration. The aim of this study was to examine whether human PDL fibroblasts ( hPDLFs) with high levels of periostin expression promote the migration of human bone marrow mesenchymal stem cells ( hMSCs). Material and Methods The migration of hMSCs was examined by transwell chamber migration assay under different conditions: medium alone, hPDLFs, human dermal fibroblasts, recombinant periostin, integrin αvβ3 blocking antibody (anti- CD51/61 antibody) and inhibitors of FAK ( PF431396) and PI3 K ( LY294002). Phosphorylation of FAK and Akt in hMSCs under stimulation of periostin was examined by western blotting. Results The migration assay revealed that the number of migrated hMSCs by hPDLFs was significantly larger than those by dermal fibroblasts, periostin small interfering RNA hPDLFs and medium alone. Furthermore, recombinant periostin also strongly induced hMSC migration. The addition of anti- CD51/61 antibody, PF431396 and LY294002 caused a significant reduction in the number of migrated hMSCs respectively. The anti- CD51/61 antibody inhibited both FAK and Akt phosphorylations under periostin stimulation. PF431396 inhibited both FAK and Akt phosphorylations. LY294002 inhibited only Akt phosphorylation, and FAK phosphorylation was not influenced under periostin stimulation. Conclusion Periostin expression in hPDLFs promotes the migration of hMSCs through the αvβ3 integrin/ FAK/ PI3 K/ Akt pathway in vitro. [ABSTRACT FROM AUTHOR]

Summary: This study evaluated changes in spinal alignment and quality of life (QOL) after corrective spinal surgery for patients with postmenopausal osteoporosis and spinal kyphosis. Spinal global alignment and QOL were significantly improved after corrective spinal surgery but did not reach the level of non-operated controls. Introduction: With the increased aging of society, the demand for corrective spinal instrumentation for spinal kyphosis in osteoporotic patients is increasing. However, previous studies have not focused on the improvement of quality of life (QOL) after corrective spinal surgery in patients with osteoporosis, compared to non-operated control patients. The purposes of this study were thus to evaluate changes in spinal alignment and QOL after corrective spinal instrumentation for patients with osteoporosis and spinal kyphosis and to compare these results with non-operated patients. Methods: Participants comprised 39 patients with postmenopausal osteoporosis ≥50 years old who underwent corrective spinal surgery using multilevel posterior lumbar interbody fusion (PLIF) for symptomatic thoracolumbar or lumbar kyphosis, and 82 age-matched patients with postmenopausal osteoporosis without prevalent vertebral fractures. Spinopelvic parameters were evaluated with standing lateral spine radiography, and QOL was evaluated with the Japanese Osteoporosis QOL Questionnaire (JOQOL), SF-36, and Roland-Morris Disability Questionnaire (RDQ). Results: Lumbar kyphosis angle, sagittal vertical axis, and pelvic tilt were significantly improved postoperatively. QOL evaluated with all three questionnaires also significantly improved after 6 months postoperatively, particularly in domain and subscale scores for pain and general/mental health. However, these radiographic parameters, total JOQOL score, SF-36 physical component summary score, and RDQ score were significantly inferior compared with non-operated controls. Conclusions: The results indicate that spinal global alignment and QOL were significantly improved after corrective spinal surgery using multilevel PLIF for patients with osteoporosis and spinal kyphosis but did not reach the level of non-operated controls. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to elucidate the association between plasma intestinal fatty acid-binding protein (I-FABP) level and actual pathological damage of intestinal mucosa and its reversibility. Methods: An intestinal ischemia-reperfusion model was created by temporary occlusion of the descending aorta in 9 pigs which were divided into 3 groups according to the duration of visceral ischemic insult: 15-minute ischemia (n=3), 30-minute ischemia (n=3) and 60-minute ischemia (n=3). Blood samples and short segments of the jejunum for pathological examinations, including immunohistochemical staining of I-FABP, Ki-67 and E-cadherin, were taken at the beginning of the operation (T1) and 15 minutes (T2), 30 minutes (T3), 45 minutes (T4) and 60 minutes (T5) after reperfusion. Results: Plasma I-FABP after 15 minutes of ischemia reached a peak of 1859±1089 pg/ml at T3, while the level after 30 minutes of ischemia achieved a peak level of 5053±1717 pg/ml at T5. The level after 60 minutes of ischemia demonstrated a rapid increment up to 10734±93 pg/ml at T3. There was a significant difference in the trend of plasma I-FABP levels between 30 minutes and 60 minutes of ischemia (p=0.01). The strongest immunohistochemical staining of the intestinal epithelium for I-FABP was observed at T4 after 30 minutes of ischemia, with the shedding of injured epithelium followed by re-epithelialisation, with sequential up-regulation of Ki67 and E-cadherin. However, the intestinal epithelium after 60 minutes of ischemia demonstrated the lack of I-FABP expression with irreversible damage. Conclusion: Plasma I-FABP levels may be a crucial marker to recognize the reversibility of damage of the intestinal epithelium after an ischemic insult and the level of 5000 pg/ml is considered to be the critical borderline for irreversibility, which might prevent diagnostic delay in the clinical setting. [ABSTRACT FROM AUTHOR]

Purpose. Macrophages serve as sweepers of microbes and inflammation-derived wastes and regulators of inflammation. Some traditional Japanese medicines are reported to have adjuvant effects by modifying macrophages. Our aim was to characterize the actions of jumihaidokuto (JHT) for treatment of skin inflammations including acne vulgaris, in which Propionibacterium acnes has pathogenic roles. Methods. Dermatitis was induced in rat ears by intradermal injection of P. acnes. JHT or prednisolone (PDN) was given orally, and ear thickness and histology were evaluated. The effects of constituents and metabolites of JHT on monocytes were tested by cell-based assays using the human monocytic THP-1 cell. Results. JHT and PDN suppressed the ear thickness induced by P. acnes injection. Histological examinations revealed that JHT, but not PDN, promoted macrophage accumulation at 24 h after the injection. PDN suppressed the macrophage chemokine MCP-1 in the inflamed ears, while JHT did not affect it. The JHT constituents liquiritigenin and isoliquiritin increased expression of CD86 (type-1 macrophage marker) and CD192 (MCP-1 receptor) and enhanced phagocytosis by THP-1. Conclusions. JHT suppressed dermatitis, probably by enhancing type-1 macrophage functions, with an action different from PDN. JHT may be a beneficial drug in treatment of skin inflammation induced by P. acnes. [ABSTRACT FROM AUTHOR]

Background Alcohol-dependent patients are known to be generally more unfairness sensitive. The ultimatum game ( UG) is an experimental task designed to provoke feelings of perceived unfairness. A previous study using the UG has reported more unfairness sensitivity in patients with alcohol dependence than in a nondependent control group; it has been speculated that this increased sensitivity might be due to a difficulty in impulse control. However, the mechanism of this relationship has not been clarified. Therefore, the relationship between unfairness sensitivity in interpersonal relationships and impulsivity was investigated using UG and delay discounting ( DD) paradigms. Methods Subjects were 32 individuals with alcohol dependency and 36 healthy control individuals; both groups performed UG and DD tasks. Results Participants with alcohol dependence rejected monetary offers deemed unfair at a significantly higher rate than did control participants. Moreover, the proportion of accepting unfairness was negatively correlated with impulsivity in patients with alcohol dependence. Conclusions Perceived unfairness is related to impulsivity in patients with alcohol dependence. These results provide insights concerning the psychopathology of alcohol dependence. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods. Patients in an orthopedic clinic (n5266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n5173), dynamic varus (n517), static varus (n550), and static varus1dynamic varus (n526).The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results. Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08-12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19- 320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion. Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. [ABSTRACT FROM AUTHOR]

Knowledge regarding accelerometer-derived physical activity (PA) and sedentary behavior (SED) levels is scarce for Japanese older adults. The aims of this study were therefore to 1) describe levels of PA and SED in Japanese community-dwelling older adults, using tri-axial accelerometer; 2) examine the variation of PA and SED with respect to sex, age, and body mass index (BMI). Participants of this study were from the baseline survey of the Sasaguri Genkimon Study, who were 65 years or older and not certified as those requiring long-term care. PA was assessed objectively for seven consecutive days using tri-axial accelerometer. A total of 1,739 participants (median age: 72 years, men: 38.0%) with valid PA data were included. Overall, participants in the present study spent 54.5% of their waking time being sedentary and 45.5% being active, of which 5.4% was moderate-to-vigorous physical activity (MVPA). Women accumulated more minutes of light physical activity (LPA) and MVPA compared with men. In contrast, men spent more time being sedentary. Mean steps per day did not differ between sexes. Furthermore, participants with higher BMI (BMI ≥25) had lower PA levels, and longer SED compared with those with lower BMI (BMI <25). PA levels were lower and SED was longer with age. The present study is the first to demonstrate that the levels of PA and SED differed by sex, age, and BMI in Japanese community-dwelling older adults. In particular, women were more active compared with men, providing unique insight into the current level of PA in older adults. Data presented in the study will enable further investigation of additional determinants of PA and SED in order to develop effective population- based intervention strategies to promote PA and reduce prolonged SED in the Japanese population and possibly other rapidly aging societies. [ABSTRACT FROM AUTHOR]

Although video feedback (VF) is shown to improve appraisals of social performance in socially anxious individuals, its impact on state anxiety during a social situation is mixed. The current study investigated the effect of combined video feedback and audience feedback (AF) on self-perceptions of performance and bodily sensations as well as state anxiety pertaining to a speech task. Forty-one socially anxious students were randomly allocated to combined video feedback with audience feedback (VF + AF), video feedback only (VF), audience feedback only (AF), or a control condition. Following a 3-min speech, participants in the VF + AF, VF, and AF conditions watched the videotape of their speech with cognitive preparation in the presence of three confederates who served as audience, and/or received feedback from the confederates, while the control group watched their videotaped speech without cognitive preparation. Both VF + AF and AF conditions improved distorted appraisal of performance and bodily sensations as well as state anxiety. The clinical implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although it is useful for COPD patients to relieve their dyspnea by bracing their arms, the relationships between the arm bracing posture and expiratory flow limitation (EFL) and lung volume are unknown. Whether arm bracing affects dyspnea, EFL, and lung volume in elderly COPD patients was investigated. METHODS: Sixteen elderly subjects (median [interquartile range] age 81 [77-85] y) with stable COPD (percent-of-predicted FEV, 50.9 [31.3-64.9] %) and 16 age-matched healthy subjects were studied. Breathing patterns, EFL, lung volume, ..., and heart rate during quiet breathing were randomly evaluated in 3 standing postures: erect, leaning forward, and arm bracing. Dyspnea was also assessed for each posture with a Borg dyspnea score at the end of the test. RESULTS: Lung volume was significantly higher with arm bracing than with the other postures in both groups (P < .05). Breathing patterns, ..., and pulse rate were not significantly different among the 3 postures in both groups. However, EFL and Borg dyspnea scores were significantly lower with arm bracing than with the other postures in COPD subjects (P < .01). CONCLUSIONS: The decreased EFL in the arm bracing position may be caused by breathing at a higher lung volume than in the erect position, which may be one of the factors relieving dyspnea in elderly COPD patients. [ABSTRACT FROM AUTHOR]

Objective Interleukin-17 (IL-17)-producing T cells (Th17 cells) play critical roles in the pathogenesis of immune-related diseases, including systemic lupus erythematosus. However, the fundamental mechanism regulating Th17 cell differentiation is not fully understood. Recently, we demonstrated that plasma levels of CD147/basigin (Bsg) in patients with lupus nephritis (LN) were closely associated with disease activity. but the molecular mechanism involving Bsg has been elusive. Here, we addressed the role of Bsg in the pathogenesis of LN. Methods Injections of pristane (2,6,10,14-tetramethylpentadecane [TMPD]) were administered to Bsg−/− or Bsg+/+ mice to induce LN. The mice were killed 6 months after being injected, for histologic and biochemical analyses of the kidneys and spleens. Results Pristane induced LN more strikingly in Bsg−/− mice than in Bsg+/+ mice, even though humoral autoimmunity was similarly increased in both genotypes. The increased number of Th17, but not Th1, Treg cells, was augmented in Bsg−/− mice. The expression of IL-17 was also increased in the kidneys of Bsg−/− mice, in proportion to LN disease activity. Furthermore, treatment with anti-IL-17 antibody reduced LN disease activity in Bsg−/− mice. Complementary to these phenotypes of Bsg−/− mice, Bsg expression was enhanced in activated CD4+ T cells in vivo and in vitro. Bsg deficiency selectively augmented in vitro differentiation of naive CD4+ T cells to Th17 cells and STAT-3 phosphorylation during this differentiation. Moreover, STAT-3 phosphorylation was suppressed by crosslinking of Bsg with its antibody. Conclusion Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway. [ABSTRACT FROM AUTHOR]

Aim To investigate the utility of recombinant activated Factor VII (rFVIIa) for severe post-partum hemorrhage (PPH) in Japan. Methods We studied 69 patients treated with rFVIIa for severe PPH; 44 patients were from the registry of Japan Society of Obstetrical, Gynecological and Neonatal Hematology, and 25 were identified by a survey of the Japan Society of Obstetrics and Gynecology. Results Overall, the mean and median blood loss were 11 835 mL and 8639 mL, respectively. Treatment before rFVIIa included transarterial embolization in 23 patients and hysterectomy in 38. Forty-two patients had a single dose, 17 had two doses, and four had three doses. The mean (± SD) single dose was 81.60 ± 16.25 µg/kg. Sixty-five patients survived, and four died. The cause of PPH in patients who died was uterine rupture plus amniotic fluid embolism in two patients, uterine cervical laceration in one, and placental abruption in one. The amount of blood loss in cases of death was 6428-43 810 mL. This suggested that whether a patient survives or not was more dependent on her general condition before and after rFVIIa treatment than on the amount of blood loss. Four patients had thromboembolic events after rFVIIa treatment (deep vein thrombosis; deep vein thrombosis plus pulmonary embolism; acute myocardial infarction; and pulmonary embolism); all of these patients recovered. Conclusion The present promising results may support the utility of rFVIIa for severe PPH in Japan. [ABSTRACT FROM AUTHOR]

Objective. B cells play an important role in the pathogenesis of autoimmune diseases. The role of Bruton's tyrosine kinase (Btk) in cytokine-induced human B cell differentiation and class-switch recombination remains incompletely defined. This study analysed the effect of Btk on human activated B cells. Methods. Purified B cells from healthy subjects were stimulated with B cell receptor (BCR) and other stimuli with or without a Btk inhibitor and gene expression was measured. The B cell line BJAB was used to assess Btk-associated signalling cascades. Phosphorylated Btk (p-Btk) in peripheral blood B cells obtained from 10 healthy subjects and 41 patients with RA was measured by flow cytometry and compared with patient backgrounds. Results. IL-21 signalling, in concert with BCR, CD40 and BAFF signals, led to robust expression of differentiation- and class-switch DNA recombination-related genes and IgG production in human B cells, all of which were significantly suppressed by the Btk inhibitor. Although phosphorylation of STAT1 and STAT3 was induced by co-stimulation with IL-21, BCR and CD40, STAT1 phosphorylation in the nucleus, but not in the cytoplasm, was exclusively impaired by Btk blockade. High levels of p-Btk were noted in B cells of RA patients compared with controls and they correlated significantly with titres of RF among RF-positive patients. Conclusion. The findings elucidate a model in which Btk not only plays a fundamental role in the regulation of BCR signalling, but may also mediate crosstalk with cytokine signalling pathways through regulation of IL-21-induced phosphorylation of STAT1 in the nuclei of human B cells. Btk appears to have pathological relevance in RA. [ABSTRACT FROM AUTHOR]

Background and Objective Various studies have reported the relationship between alcohol consumption and gingival condition. However, they focus on the direct effects of alcohol consumption or alcohol sensitivity on gingival condition, and it is unclear how oral health behaviors relate these relationships. The aims of this study were to assess the inter-relationships between gingival condition, tooth-brushing behavior after drinking alcohol and alcohol sensitivity in university students who drink more than once per week on average. Material and Methods A total of 808 students (541 males, 267 females) that habitually consume alcohol were analyzed. The disease activity of gingival condition was assessed as the percentage of bleeding on probing (% BOP). Additional information regarding alcohol sensitivity and oral health behaviors, including tooth-brushing behavior after drinking, were also collected. Results Thirteen percent of the current participants reported neglecting tooth-brushing after drinking, and their alcohol consumption was higher than those who did not neglect tooth-brushing. Logistic regression analysis showed that high % BOP (% BOP ≥ 20) was associated with male ( OR = 1.53; 95% CI, 1.01-2.33), neglect of tooth-brushing after drinking ( OR = 2.60; 95% CI, 1.20-5.61) and debris index ( OR = 8.38; 95% CI, 4.24-16.60) in participants with low alcohol sensitivity. In participants with high alcohol sensitivity, high % BOP was associated with debris index ( OR = 7.60; 95% CI, 3.12-18.51), but not with any oral health behaviors. Conclusions The study revealed that alcohol consumption was indirectly related to gingival disease activity through the neglect of tooth-brushing after drinking alcohol in university students with low alcohol sensitivity. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the effect of the daily practice of a yoga therapy program learnt during a single session of an integrated yoga intervention that was developed by us as a stress management tool for school employees. Subjects: Ninety school employees. Design: Case-control study. Three months after the intervention, the subjects were assigned to a daily practice group (case: n=43) and a nonconsecutive daily practice group (control: n=47) according to their daily practice level of the yoga therapy program. Interventions: The subjects participated in a stress management education program based on an integrated yoga therapy session. The program included psychological education and counseling about stress management and yoga theories, as well as the practices of asanas, pranayama, relaxation, and cognitive structure based on Indian philosophy. Outcome measures: Assessments were performed before and after the program using the Subjective Units of Distress for mind and body and the Two-Dimensional Mood Scale. The General Health Questionnaire 28 (GHQ28) was used to assess the mental health state before the intervention and at 3 months after the program. Results: The subjects showed significant increases in their levels of calmness, comfort, and cheerfulness ( p<0.001) and significant decreases in cognitive mind and body stress ( p<0.001) after participating in the integrated yoga program. A comparison of the total scores on the GHQ28 using a two-way analysis of variance showed significant differences between the two groups in terms of both interaction ( p=0.047) and the main effect ( p=0.026). Conclusions: The present results suggested that a single session of an integrated yoga program was effective for reducing stress and that the mental health of school employees was promoted by the daily practice of the yoga therapy program. [ABSTRACT FROM AUTHOR]

One distinctive trait of kendo, the Japanese martial art of fencing, is the execution of sustained, high-effort vocalizations during actions. The purpose of this study was to determine the effect of these vocalizations on respiratory functions. First, the intensity of 3 kendo exercises was quantified by measuring oxygen uptake (V . O2) and comparing it with V . O2max measured during treadmill tests of 8 university kendo athletes. Respiratory variables of these 8 athletes were then analyzed using a portable breath gas analyzer during the most intensive kendo exercise, kakari-keiko, with and without vocalization. Breathing frequency (fB) increased regardless of vocalization, but in trials with vocalization, fB and ventilation were significantly lower, and expiration time was significantly longer. Components of expired gases were also affected by vocalization. Although there was no significant difference in oxygen uptake, vocalization yielded a reduction in carbon dioxide output (V . CO2) and an increase in fraction of end-tidal carbon dioxide (FetCO2). We thus conclude that these vocalizations greatly affect expiration breathing patterns in kendo. Moreover, repetition of kakarikeiko caused a reduction in V . CO2 and an increase in FetCO2 and CO2 storage. We consider the possibility that the sustained high-effort vocalizations of kendo also increase cerebral blood flow. [ABSTRACT FROM AUTHOR]

One distinctive trait of kendo, the Japanese martial art of fencing, is the execution of sustained, high-effort vocalizations during actions. The purpose of this study was to determine the effect of these vocalizations on respiratory functions. First, the intensity of 3 kendo exercises was quantified by measuring oxygen uptake (V . O2) and comparing it with V . O2max measured during treadmill tests of 8 university kendo athletes. Respiratory variables of these 8 athletes were then analyzed using a portable breath gas analyzer during the most intensive kendo exercise, kakari-keiko, with and without vocalization. Breathing frequency (fB) increased regardless of vocalization, but in trials with vocalization, fB and ventilation were significantly lower, and expiration time was significantly longer. Components of expired gases were also affected by vocalization. Although there was no significant difference in oxygen uptake, vocalization yielded a reduction in carbon dioxide output (V . CO2) and an increase in fraction of end-tidal carbon dioxide (FetCO2). We thus conclude that these vocalizations greatly affect expiration breathing patterns in kendo. Moreover, repetition of kakarikeiko caused a reduction in V . CO2 and an increase in FetCO2 and CO2 storage. We consider the possibility that the sustained high-effort vocalizations of kendo also increase cerebral blood flow. [ABSTRACT FROM AUTHOR]

Purpose: Body weight in young growing and young adult animals was reduced by a high dietary density of whey protein concentrate; however, it is unclear whether dietary proteins similarly affect body weight in aging animals. Here, we examined whether whey protein or whey peptide ingestion suppressed body fat accumulation and affected protein expression and phosphorylation in skeletal muscle in aging mice. Methods: Twenty-six male senescence-accelerated mouse prone 6 (SAMP6) mice were assigned randomly to three dietary treatment groups: 18.7 % casein control (CON), 18.7 % whey protein (WPR), and 18.7 % whey peptide (WPE). After 28 weeks of treatment, skeletal tissues were dissected and weighed for analysis. Western blotting was performed to examine the expression of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and adipose triglyceride lipase (ATGL) in quadriceps muscles. Results: Body (CON: 47.6 ± 2.2 g, WPR: 48.2 ± 2.7 g, WPE: 38.3 ± 2.0 g) and relative white adipose tissue (CON: 38.5 ± 3.5 mg/g, WPR: 43.8 ± 4.0 mg/g, WPE: 21.1 ± 4.4 mg/g) weights were lower in the WPE group compared with the other two groups ( p < 0.05), and no significant differences were observed between the CON and WPR groups. The relative weights of tibialis anterior muscle (CON: 1.04 ± 0.04 mg/g, WPR: 0.97 ± 0.03 mg/g, 1.23 ± 0.05 mg/g) and gastrocnemius muscle (CON: 3.02 ± 0.12 mg/g, WPR: 2.92 ± 0.15 mg/g, WPE: 3.65 ± 0.18 mg/g) were higher in the WPE group compared with the other groups ( p < 0.05). The phosphorylation of AMPK (WPR: 1.03 ± 0.11, WPE: 1.36 ± 0.12; fold change from control) and ACC (WPR: 1.08 ± 0.07, WPE: 1.18 ± 0.05; fold change from control) in WPE was higher than in CON ( p < 0.05). There were no significant differences in the expression levels of ATGL among the three groups. Conclusions: These data suggest that a normal (or moderate excess) dietary density of whey peptide attenuates body fat accumulation via upregulation of fatty acid oxidation in skeletal muscle in aging mice. [ABSTRACT FROM AUTHOR]

LA Wall Thickness, LA Electrogram, and Dormant PV Conduction Introduction Atrial remodeling plays a key role in development of the substrate for atrial fibrillation (AF). Whether the wall thicknesses of the left atrium (LA) and pulmonary vein (PV)-LA junction affect remodeling and AF ablation is unknown. We investigated the relationship between wall thicknesses, electrogram characteristics, and adenosine triphosphate (ATP)-provoked dormant PV conduction as they pertain to AF. Methods In 50 patients with AF and 25 patients without AF, wall thicknesses of the LA and PV-LA junction were measured on 320-slice computed tomography images. For the AF patients, NavX-based voltage maps generated during sinus rhythm were obtained, and ATP-provoked dormant PV conduction after PV isolation was evaluated. Results Walls of the LA and PV-LA junction were significantly thicker in the AF patients than in the control patients (1.83 ± 0.29 mm vs. 1.59 ± 0.28 mm, respectively; P = 0.0010; and 0.88 ± 0.14 mm vs. 0.65 ± 0.11 mm, P<0.0001, respectively). Wall thickness at the PV-LA junction was independently associated with AF (β = 0.40, P = 0.0002). In AF patients, the walls of the PV-LA junction showed stepwise thickening across bipolar voltages indicative of severe (bipolar voltage <33rd percentile) to moderate (33rd-66th percentiles) to mild fibrosis/scarring (≥66th percentile). Walls of the PV-LA junction with dormant PV conduction were significantly thicker than those without it (0.94 ± 0.19 mm vs. 0.86 ± 0.21 mm, respectively; P = 0.0025). Conclusions Together, the association between thickened PV-LA junction walls and AF and the increased bipolar voltage suggests that such wall thickening increases PV electrical activities, leading to initiation and maintenance of AF and perhaps to ATP-provoked dormant PV conduction. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify the differences between adolescent and collegiate baseball pitchers in the kinematic and kinetic profiles of the trunk and lower limbs during the pitching motion. The subjects were thirty-two adolescent baseball pitchers aged 12-15 years (APG) and thirty collegiate baseball pitchers aged 18-22 years (CPG). Three-dimensional motion analysis with a comprehensive lower-extremity model was used to evaluate kinematic and kinetic parameters during baseball pitching. The ground reaction forces (GRFs) of the pivot and stride legs during pitching were determined using two multicomponent force plates. The joint torques of hip, knee, and ankle were calculated by the inverse-dynamics computation of musculoskeletal human models using motion-capture data. To eliminate any effect of variation in body size, kinetic and GRFs data were normalized by dividing them by body mass. The velocity of a pitched ball was significantly higher (p < 0.01) in CPG (35.2 ± 1.9 m⋅s-1) than in the APG (30.7 ± 2.7 m⋅s-1). Most kinematic parameters for the lower limbs were similar between the CPG and the APG. Maximum Fy (toward the throwing direction) on the pivot leg and Fy and resultant forces on the stride leg at ball release were significantly greater in the CPG than in the APG (p < 0.05). Hip and knee joint torques on the lower limbs were significantly greater in the CPG than in the APG (p < 0.05). The present study indicates that the kinematics of lower limbs during baseball pitching are similar between adolescent and collegiate pitchers, but the momentum of the lower limbs during pitching is lower in adolescent pitchers than in collegiate ones, even when the difference in body mass is considered. [ABSTRACT FROM AUTHOR]

Conservative therapies, mainly resting care for the damaged muscle, are generally used as a treatment for skeletal muscle injuries (such as muscle fragmentation). Several past studies reported that microcurrent electrical neuromuscular stimulation (MENS) facilitates a repair of injured soft tissues and shortens the recovery period. However, the effects of MENS on the regeneration in injured skeletal muscle are still unclear. The purpose of this study was to investigate the effect of MENS on the regenerative process of injured skeletal muscle and to elucidate whether satellite cells in injured skeletal muscle are activated by MENS by using animal models. Male C57BL/6J mice, aged 7 weeks old, were used (n = 30). Mice were randomly divided into two groups: (1) cardiotoxin (CTX)-injected (CX, n = 15) and (2) CTX-injected with MENS treatment (MX, n=15) groups. CTX was injected into tibialis anterior muscle (TA) of mice in CX and MX groups to initiate the necrosis-regeneration cycle of the muscle. TA was dissected 1, 2, and 3 weeks after the injection. Muscle weight, muscle protein content, the mean cross-sectional areas of muscle fibers, the relative percentage of fibers having central nuclei, and the number of muscle satellite cells were evaluated. MENS facilitated the recovery of the muscle dry weight and protein content relative to body weight, and the mean cross-sectional areas of muscle fibers in CTXinduced injured TA muscle. The number of Pax7-positive muscle satellite cells was increased by MENS during the regenerating period. Decrease in the percentages of fibers with central nuclei after CTX-injection was facilitated by MENS. MENS may facilitate the regeneration of injured skeletal muscles by activating the regenerative potential of skeletal muscles. [ABSTRACT FROM AUTHOR]

Background: Prevention of chronic kidney allograft injury (CAI) is a major goal in improving kidney allograft survival; however, the mechanisms of CAI are not clearly understood. The current study investigated whether alternatively activated M2-type macrophages are involved in the development of CAI. Methods: A retrospective study examined kidney allograft protocol biopsies (at 1 h and at years 1, 5, and 10-a total of 41 biopsies) obtained from 13 children undergoing transplantation between 1991 and 2008 who were diagnosed with CAI: interstitial fibrosis and tubular atrophy (IF/TA) not otherwise specified (IF/TA-NOS). Results: Immunostaining identified a significant increase in interstitial fibrosis with accumulation of CD68 + CD163+ M2-type macrophages. CD163+ cells were frequently localized to areas of interstitial fibrosis exhibiting collagen I deposition and accumulation of α-smooth muscle actin (SMA) + myofibroblasts. There was a significant correlation between interstitial CD163+ cells and the parameters of interstitial fibrosis ( p < 0.0001), and kidney function ( r =−0.82, p < 0.0001). The number of interstitial CD163+ cells at years 1 and 5 also correlated with parameters of interstitial fibrosis at years 5 and 10 respectively. Notably, urine CD163 levels correlated with interstitial CD163+ cells ( r = 0.79, p < 0.01) and parameters of interstitial fibrosis ( p < 0.0001). However, CD3+ T lymphocytic infiltration did not correlate with macrophage accumulation or fibrosis. In vitro, dexamethasone up-regulated expression of CD163 and cytokines (TGF-β1, FGF-2, CTGF) in human monocyte-derived macrophages, indicating a pro-fibrotic phenotype. Conclusions: Our findings identify a major population of M2-type macrophages in patients with CAI, and suggest that these M2-type macrophages might promote the development of interstitial fibrosis in IF/TA-NOS. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that treatment involving eccentric training was effective in the conservative management of chronic tendinosis. However, the mechanisms for these phenomena are unknown. The purpose of this study was to compare changes in blood circulation of the tendons after the repeated concentric and eccentric contractions. 11 healthy males volunteered for this study. Subjects performed the repeated concentric (CON) and eccentric (ECC) contractions (5 sets of 10 maximal voluntary contractions) of the plantar flexors. During and after repeated contractions, oxyhemoglobin (Oxy), deoxyhemoglobin (Deoxy), total hemoglobin (THb), and oxygen saturation (StO2) of the Achilles tendons were measured using red laser lights. Oxy and THb increased during and after ECC, but not CON. Deoxy decreased during both CON and ECC. Increase in StO2 during and after ECC was greater than that during and after CON. These results suggested that changes in blood circulation of the Achilles tendon during and after repeated eccentric contractions were more remarkable than those during and after repeated concentric contractions. [ABSTRACT FROM AUTHOR]

This study examined changes in toll-like receptor 4 (TLR-4)-expressing monocytes and lymphocyte subpopulations in response to continuous intensive exercise training in athletes, as well as the effect of coenzyme Q10 (CoQ10) supplementation on these changes. Eighteen male elite kendo athletes in Japan were randomly assigned to a CoQ10-supplementation group ( n = 9) or a placebo-supplementation group ( n = 9) using a double-blind method. Subjects in the CoQ10 group took 300 mg CoQ10 per day for 20 days. Subjects in the placebo group took the same dosage of placebo. All subjects practiced kendo 5.5 h per day for 6 consecutive days during the study period. Blood samples were collected 2 weeks before training, on the first day (day 1), third day (day 3), and fifth day of training (day 5), and 1 week after the training period (post-training) to ascertain TLR-4+/CD14+ monocyte and lymphocyte subpopulations (CD3+, CD4+, CD8+, CD28+/CD4+, CD28+/CD8+, and CD56+/CD3− cells) using flow cytometry analysis. The group × time interaction for TLR-4+/CD14+ cells did not reach significance ( p = 0.08). Within the CoQ10 group, the absolute number of TLR-4+/CD14+ cells was significantly higher only at day 5. The placebo group showed a significant increase in the absolute number of TLR-4+/CD14+ cells at day 3, day 5, and post-training ( p < 0.05). There was no significant group × time interaction for any lymphocyte subpopulation. CD3+, CD8+, and CD56+/CD3− cells were significantly reduced at day 3 in both groups ( p < 0.05). In conclusion, CoQ10 supplementation might downregulate the increase of TLR-4-expressing monocytes in response to continuous strenuous exercise training in kendo athletes. [ABSTRACT FROM AUTHOR]

Background and Objective Epithelial cells are recognized as the first line of defense against bacterial infection and environmental harmful stimuli such as cigarette smoke ( CS). Although previous studies explored the effects of nicotine on host cells, mechanisms by which CS affects cellular functions remain uncertain. The present study investigated the effects of CS condensate ( CSC) on in vitro wound closure of gingival epithelial cells and their potential interactions with a major periodontal pathogen, Porphyromonas gingivalis. Material and Methods Human gingival epithelial cells (Ca9-22) were treated with CSC for 24 h. Cell proliferation was determined using a WST-1 assay. Cell migration was assessed using a wound closure model. The expression of integrins was analyzed by confocal scanning laser microscopy and real-time PCR. Intracellular invasion of P. gingivalis was evaluated by confocal scanning laser microscopy and an antibiotic protection assay. Results Low concentrations (1-10 μg/mL) of CSC showed no significant effect on cell proliferation. CSC demonstrated dual effects on epithelial wound closure of Ca9-22 cells: high concentrations (i.e. 250 μg/mL) significantly inhibited the wound closure whereas low concentrations (i.e. 10 μg/mL) promoted it ( p < 0.01). CSC induced distinct changes in cytoskeleton. When CSC-exposed cells were infected with P. gingivalis for 2 h, a significant inhibition of wound closure was observed concurrent with a decrease in integrin α3 expression near the wound area. A significantly increased P. gingivalis invasion into Ca9-22 was observed when exposed to low concentrations of CSC. Conclusion Low concentrations of CSC increased invasion of human gingival epithelial cells by P. gingivalis and induced changes in cytoskeleton and integrin expression, thereby modulating the cell migration. [ABSTRACT FROM AUTHOR]

Objective It is generally accepted that blockade of endothelin receptors has potentially beneficial effects on vasculopathy associated with systemic sclerosis (SSc). The aim of this study was to clarify the molecular mechanism underlying these effects using endothelial cell-specific Fli-1-knockout (Fli-1 ECKO) mice, an animal model of SSc vasculopathy. Methods Levels of messenger RNA for target genes and the expression and phosphorylation levels of target proteins were determined in human and murine dermal microvascular endothelial cells by real-time quantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. The binding of Fli-1 to the target gene promoters was evaluated using chromatin immunoprecipitation. Expression levels of Fli-1 and α-smooth muscle actin in murine skin were evaluated using immunohistochemistry. Vascular structure and permeability were evaluated in mice injected with fluorescein isothiocyanate-dextran and Evans blue dye, respectively. Results In human dermal microvascular endothelial cells, endothelin 1 induced phosphorylation of Fli-1 at Thr312 through the sequential activation of c-Abl and protein kinase Cδ, leading to a decrease in Fli-1 protein levels as well as a decrease in binding of Fli-1 to the target gene promoters, whereas bosentan treatment reversed those effects. In Fli-1 ECKO mice, 4 weeks of treatment with bosentan increased endothelial Fli-1 expression, resulting in vascular stabilization and the restoration of impaired leaky vessels. Conclusion The vascular fragility of Fli-1 ECKO mice was improved by bosentan through the normalization of Fli-1 protein levels and activity in endothelial cells, which may explain, in part, the mechanism underlying the beneficial effects of endothelin receptor blockade on SSc vasculopathy. [ABSTRACT FROM AUTHOR]

Outdoor exercise often proceeds in rainy conditions. However, the cooling effects of rain on human physiological responses have not been systematically studied in hot conditions. The present study determined physiological and metabolic responses using a climatic chamber that can precisely simulate hot, rainy conditions. Eleven healthy men ran on a treadmill at an intensity of 70% VO2maxfor 30 min in the climatic chamber at an ambient temperature of 33°C in the presence (RAIN) or absence (CON) of 30 mm · h−1of precipitation and a headwind equal to the running velocity of 3.15 ± 0.19 m · s−1. Oesophageal temperature, mean skin temperature, heart rate, rating of perceived exertion, blood parameters, volume of expired air and sweat loss were measured. Oesophageal and mean skin temperatures were significantly lower from 5 to 30 min, and heart rate was significantly lower from 20 to 30 min in RAIN than in CON (P < 0.05 for all). Plasma lactate and epinephrine concentrations (30 min) and sweat loss were significantly lower (P < 0.05) in RAIN compared with CON. Rain appears to influence physiological and metabolic responses to exercise in heat such that heat-induced strain might be reduced. [ABSTRACT FROM AUTHOR]

Aims This study aimed to compare the findings of the quality of nursing doctoral education survey across seven countries and discuss the strategic directions for improving quality. Background No comparative evaluation of global quality of nursing doctoral education has been reported to date despite the rapid increase in the number of nursing doctoral programmes. Design A descriptive, cross-country, comparative design was employed. Methods Data were collected from 2007-2010 from nursing schools in seven countries: Australia, Japan, Korea, South Africa, Thailand, UK and USA. An online questionnaire was used to evaluate quality of nursing doctoral education except for Japan, where a paper version was used. Korea and South Africa used e-mails quality of nursing doctoral education was evaluated using four domains: Programme, Faculty (referring to academic staff), Resource and Evaluation. Descriptive statistics, correlational and ordinal logistic regression were employed. Results A total of 105 deans/schools, 414 faculty and 1149 students/graduates participated. The perceptions of faculty and students/graduates about the quality of nursing doctoral education across the seven countries were mostly favourable on all four domains. The faculty domain score had the largest estimated coefficient for relative importance. As the overall quality level of doctoral education rose from fair to good, the resource domain showed an increased effect. Conclusions Both faculty and students/graduates groups rated the overall quality of nursing doctoral education favourably. The faculty domain had the greatest importance for quality, followed by the programme domain. However, the importance of the resource domain gained significance as the overall quality of nursing doctoral education increased, indicating the needs for more attention to resources if the quality of nursing doctoral education is to improve. [ABSTRACT FROM AUTHOR]

Background: A recent survey of 79 countries showed that fertility knowledge was lower in Japan than in any other developed country. Given the fertility decline in Japan and the importance of fertility knowledge, we conducted an online survey to examine fertility knowledge and the related factors for effective public education. Methods: We studied people aged 18-59 years old, n = 4,328 (the “General” group), and also people who had been trying to conceive for at least six months, 18-50 years old, n = 618 (the “Triers” group). Fertility knowledge was assessed using the Japanese version of the 13-item Cardiff Fertility Knowledge Scale (CFKS-J). All participants provided socio-demographic and fertility information. Participants also completed a 14-item health literacy scale and an 11-item health numeracy scale. We asked participants who were aware of age-related decline in fertility when and where they first acquired that knowledge. Results: The average percentages of CFKS-J items answered correctly were 53.1% in the Triers group and 44.4% in the General group (p < 0.001). Multivariate linear regression models showed in the Triers group greater fertility knowledge was associated with greater health literacy and prior medical consultation regarding their fertility. In the General group greater fertility knowledge was associated with being female, younger, university educated, currently trying to conceive, non-smoking, having higher household income, having higher health literacy and having higher health numeracy. Of those who were aware of the age-related decline in fertility, around 3% first learned the fact “at school”, and around 65% first learned it “through mass media” or “via the Internet”. More than 30% of the respondents first learned it “less than 5 years before” the survey. Conclusions: Although fertility knowledge had improved since a previous study, possibly due to recent media coverage of age-related infertility, it was still low. Educational interventions, both in schools and in the community, may be needed to increase fertility knowledge in the general population because most people obtain fertility knowledge from mass media, which has been shown to often present distorted and inaccurate fertility information. [ABSTRACT FROM AUTHOR]

Muscle injury frequently occurs in the medial head of the gastrocnemius ( MG), and stretching is used for treatment. However, there are no studies based on anatomical considerations and biomechanics. This study therefore examined the macroscopic anatomical structure of the triceps surae muscle to design an effective and selective MG stretching method, before quantitatively verifying that method by ultrasonography. The macroscopic anatomy was analyzed in 16 Japanese cadavers (25 legs). Based on the anatomical findings and the arrangement of fascicles in the MG, we concluded that ankle inversion might be advantageous for selective stretching of the tendon fiber bundles into which the MG inserts. We devised a method in which the limb was initially positioned with the knee joint in extension and the ankle joint in plantar flexion. Then, the ankle was dorsiflexed and inverted. The proposed method was compared with standard stretching and verified by ultrasonography in eight healthy adult males. This method effectively and selectively stretched the MG, producing a significantly decreased pennation angle and increased muscle fiber length. This method may be beneficial for preventing future injuries and may enhance the effect of therapy on the MG. [ABSTRACT FROM AUTHOR]

Homozygosity for the common nonsense polymorphism R577X in the α-actinin-3 gene ( ACTN3) causes complete α-actinin-3 deficiency in fast-twitch skeletal muscle fibers. This study investigated whether the ACTN3 R577X polymorphism affects fitness status using a battery of tests in a large Japanese cohort. In the present study, 1227 subjects (age: 25-85 years) were genotyped for the ACTN3 R577X polymorphism (rs1815739) using a TaqMan SNP genotyping assay (Applied Biosystems). All subjects were divided into 2 groups based on their age (<55 years and ≥55 years). All subjects completed a questionnaire about exercise habits and were subjected to a battery of tests to assess their fitness status (including grip strength test, chair stand test, and 8-foot walking test). A significant association between the ACTN3 R577X genotype and chair stand test performance was observed in the group of men ≥55 using ANCOVA adjusted for age and exercise habits ( p = 0.036). The ACTN3 R577X genotype accounted for 2.5% of the variability in the results of the chair stand test among men in the ≥55 age group. Moreover, for the ≥55 age group, performance in the chair stand test was lower among those with the XX genotype than among those with the RR genotype ( p = 0.024) or RX genotype ( p = 0.005), unlike results for the <55 age group. No significant difference was noted for hand grip strength or 8-foot walking time. Thus, our results suggest that the ACTN3 R577X genotype is associated with lower-extremity muscle function in the Japanese population. [ABSTRACT FROM AUTHOR]

Purpose: Coffee and green tea consumption may be associated with circulating adipokines, but data are inconsistent, scarce or lacking. We examined the association of coffee and green tea consumption with serum adiponectin, leptin, visfatin, resistin and plasminogen activator inhibitor-1 (PAI-1) among a Japanese working population. Methods: The authors analyzed data ( n = 509) from a cross-sectional survey among Japanese workers aged 20-68 years. Serum adipokines were measured using a Luminex suspension bead-based multiplexed array. Coffee and green tea consumption was assessed using a validated diet history questionnaire, and caffeine consumption from these beverages was estimated. Multiple regression analysis was performed with adjustment for potential confounding variables. Results: Coffee consumption was significantly, inversely associated with leptin and PAI-1 ( P for trend = 0.007 and 0.02, respectively); compared with subjects consuming <1 cup per day, those consuming ≥4 cups per day had 13 and 10 % lower means of leptin and PAI-1, respectively. Similar associations were observed for caffeine consumption ( P for trend = 0.02 for both leptin and PAI-1). Additionally, we noted a significant positive association between coffee consumption and adiponectin in men ( P for trend = 0.046), but not in women ( P for trend = 0.43, P for interaction = 0.11). Moreover, there was a positive association between coffee consumption and resistin in current male smokers ( P for trend = 0.01), but not in male non-smokers ( P for trend = 0.35, P for interaction = 0.11). Green tea consumption was not associated with any adipokine. Conclusions: Higher consumption of coffee and caffeine but not green tea was associated with lower serum levels of leptin and PAI-1 in Japanese adults. [ABSTRACT FROM AUTHOR]

We sought to determine whether serial measurements of oxidative stress levels could serve as a predictive marker for cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI). Biological antioxidant potential (BAP) levels were measured at admission and at 6, 12, and 24 months in 69 patients with STEMI. The CV events abruptly increased 6 to 10 months after successful percutaneous coronary intervention in patients with STEMI, and the 6-month BAP levels were significantly lower in patients with CV events (2456 μmol/L [interquartile range: 2237-2615 μmol/L]) than in those without (2849 μmol/L [2575-2987 μmol/L], P < .001). A decreased 6-month BAP level was an independent and significant predictor of long-term CV events (hazard ratio = 2.45; 95% confidence intervals 1.10-5.78; P = .04). Our findings suggest that serial changes in antioxidant capacity, assessed by BAP levels, may serve as a predictive marker for CV events after STEMI. [ABSTRACT FROM AUTHOR]

Background: The anterior cruciate ligament (ACL) does not heal spontaneously after injury, and ACL patients of different ages respond differently to treatment. Although ACL-derived CD34-positive cells contribute to bone-tendon healing after ACL reconstruction, the relationship between the healing potential of ACL-derived cells and a patient's age is unknown. Hypothesis: ACL-derived cells from young patients will have a greater effect on the maturation of bone-tendon integration in an immunodeficient rat model of ACL reconstruction compared with cells derived from older patients. Study Design: Controlled laboratory study. Methods: Sixty 10-week-old female immunodeficient rats underwent ACL reconstruction (using the autologous flexor digitorum longus tendon as a graft) followed by intracapsular administration of ACL-derived cells from patients aged 10 to 19 years (younger group) or patients aged 30 to 39 years (older group), or they were given phosphate-buffered saline (PBS; PBS group). Histologic, radiographic, and biomechanical examinations were performed 2 to 8 weeks after surgery. In addition, intrinsic and human cell– derived angiogenesis and osteogenesis were examined by immunohistochemistry. Results: In the younger group, histologic assessment demonstrated early bone-tendon healing, which induced endochondral ossification-like integration. Micro–computed tomography showed a statistically significant reduction in the area of tibial bone tunnel in the younger group (week 4, 20.0% ± 11.2% reduction; week 8, 25.7% ± 5.6% reduction) compared with the older group (week 4, 1.8% ± 3.0% reduction; week 8, 4.0% ± 5.9% reduction) and the PBS group (week 4, -0.5% ± 3.2% reduction; week 8, 3.3% ± 5.2% reduction) (week 4, P<.05; week 8, P<.01). Failure loads during tensile testing demonstrated a significantly higher ultimate load to failure in the younger group (17.52 ± 4.01 N) compared with the older (8.05 ± 2.91 N) and PBS (7.01 ± 3.16 N) groups (P<.05), and isolectin B4 and rat osteocalcin immunostaining indicated enhanced intrinsic angiogenesis and osteogenesis in the younger group. There was no statistically significant difference in the results of radiographic and biomechanical examinations between the older and PBS groups. Double immunohistochemistry for human-specific endothelial cell and osteoblast markers demonstrated a greater ability of differentiation into endothelial cells and osteoblasts in the younger group. Conclusion: ACL-derived cells from younger patients enhanced early bone-tendon healing in an immunodeficient rat model of ACL reconstruction. Clinical Relevance: Surgeons should consider a patient's age when performing ACL reconstruction with remnant preservation or ruptured tissue incorporation, as this can predict healing ability. [ABSTRACT FROM AUTHOR]

Summary: The associations between mid-femoral cross-sectional geometry and exercise characteristics were investigated in female athletes. The effects on bone geometry for weight-bearing sports with low-to-high-impact were greater than those for non-impact weight-bearing sports, whereas low-impact or high-strain-magnitude/low-strain-rate sports had less of an effect on bone geometry compared with higher-impact sports. Introduction: Many previous studies have investigated tibial geometry in athletes; however, few studies have examined the associations between femoral cross-sectional geometry and exercise characteristics. The aim of this study was to investigate these relationships using magnetic resonance imaging (MRI) at the femoral mid-shaft. Methods: One hundred and fifty-three female elite athletes, aged 18-34 years, were classified into five groups based on the characteristics of their sports. Sports were considered non-impact ( n = 27), low- or moderate-impact ( n = 39), odd-impact ( n = 38), high-strain-magnitude/low-strain-rate ( n = 10), or high-impact ( n = 39). Bone geometrical parameters, including cortical area, periosteal perimeter, and moment of inertia (bone strength index), were determined using MRI images. Results: Higher-impact groups displayed bone expansion, with significantly greater periosteal perimeters, cortical areas (~37.3 %), and minimum moments of inertia ( I, ~92.3 %) at the mid-femur than non- and low-impact groups. After adjusting for age, height, and weight, the cortical area and I of the low-impact and high-strain-magnitude/low-strain-rate groups were also significantly greater than those of the non-impact group. Conclusions: Higher-impact sports with high strain rates stimulated periosteal bone formation and improved bone geometry and strength indices at the femoral mid-shaft. Although our results indicate that weight-bearing sports are beneficial even if they are low impact, the effects of lower-impact or high-strain-magnitude/low-strain-rate sports on bone geometry were less pronounced than the effects of higher-impact sports at the femoral mid-shaft. [ABSTRACT FROM AUTHOR]

Summary: Serum sclerostin levels could be closely associated with serum phosphate and fibroblast growth factor-23 levels in hemodialysis patients with low intact parathyroid hormone (PTH) levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low PTH levels without any vitamin D treatment. Introduction: Intact parathyroid hormone (iPTH) is involved in the interaction between sclerostin and phosphate/fibroblast growth factor-23 (FGF23) in animal models. However, their relationship in patients on hemodialysis (HD) is unclear. Methods: Data of 102 HD patients were collected regarding clinical and laboratory parameters and mineral bone disorder medications. The patients were divided into subgroups according to the iPTH level (A, <70 pg/mL; B, 70-150 pg/mL; C, 150-300 pg/mL; and D, ≥300 pg/mL). Results: The sclerostin level was significantly and positively correlated with phosphate and log of FGF23 levels in subgroups A, B, and combined A and B. Multiple linear regression analysis in the combined A and B subgroup revealed that male sex ( t = 3.24, P = 0.01; 95 % confidence interval [CI] 11.78 to 50.43) and phosphate level ( t = 2.13, P = 0.04; 95 % CI, 1.08 to 36.91) were independent factors for serum sclerostin level. The log of serum FGF23 level ( t = 1.90, P = 0.06, 95 % CI −1.85 to 63.50) appeared to be an important factor for serum sclerostin level. The frequency of patients using vitamin D treatment was not significantly different among subgroups A (93.1 %), B (88.0 %), C (85.2 %), and D (90.5 %). Conclusion: Serum sclerostin levels were associated with serum phosphate and FGF23 levels in patients with low iPTH levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low iPTH levels without vitamin D treatment. [ABSTRACT FROM AUTHOR]

The current study examines in depth how two types of form-focused instruction (FFI), which are FFI with and without corrective feedback (CF), can facilitate second language speech perception and production of /ɹ/ by 49 Japanese learners in English as a Foreign Langage settings. FFI effectiveness was assessed via three outcome measures (perception, controlled production, and spontaneous production) and also according to two lexical contexts (trained and untrained items). Two experimental groups received 4 hr of FFI treatment to notice and practice the target feature of /ɹ/ (but without any explicit instruction) in meaningful discourse. A control group (n = 14) received comparable instruction in the absence of FFI. During FFI, the instructors provided CF only to students in the FFI + CF group (n = 18) by recasting their mispronunciations of /ɹ/, while no CF was provided to those in the FFI-only group (n = 17). Analyses of pre- and posttests showed that FFI itself can sufficiently promote the development of speech perception and production of /ɹ/ and the acquisitional value of CF in second language speech learning remains unclear. The results suggest that the beginner learners without much phonetic knowledge on how to repair their mispronunciation of /ɹ/ should be encouraged to learn the target sound only through FFI in a receptive mode without much pressure for modified output. [ABSTRACT FROM PUBLISHER]

Aims: To investigate the effectiveness of brief intervention (BI) conducted in the workplace for heavy drinkers. Methods: A randomized controlled trial was conducted at six companies in Japan. Participants were heavy drinkers who met the inclusion criteria and were randomized into three groups: the BI group, BI with diary group and a control group. Outcomes (total drinks, binge drinking episodes and alcohol-free days) were evaluated at 3 and 12 months. Results: The 304 participants recruited were allocated to the three groups and 277 participated in all follow-up evaluations. Dropout rates in the respective groups were 7.0, 14.9 and 5.5%. Some improvements were observed in all the groups. In particular, alcohol-free days in the BI group were significantly increased by 93.0% at 12 months. Total drinks at 12 months were reduced by 41 g per week in the BI group compared with the control group, although the intergroup difference was not significant. Conclusion: BI in the workplace is effective for increasing the number of alcohol-free days. However, the effectiveness on decreasing alcohol consumption was unclear, which could be explained by alcohol screening itself causing a reduction in drinking. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to identify the period of the gait cycle during which the hamstring muscles were likely injured by estimating the magnitude of tensile force in each muscle during overground sprinting. We conducted three-dimensional motion analysis of 12 male athletes performing overground sprinting at their maximal speed and calculated the hamstring muscle-tendon length and joint angles of the right limb throughout a gait cycle during which the ground reaction force was measured. Electromyographic activity during sprinting was recorded for the biceps femoris long head, semitendinosus, and semimembranosus muscles of ipsilateral limb. We estimated the magnitude of tensile force in each muscle by using the length change occurred in the musculotendon and normalized electromyographic activity value. The study found a quick increase of estimated tensile force in the biceps femoris long head during the early stance phase of the gait cycle during which the increased hip flexion angle and ground reaction force occurred at the same time. This study provides quantitative data of tensile force in the hamstring muscles suggesting that the biceps femoris long head muscle is susceptible to a strain injury during [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare metabolic costs, rating of perceived exertion (RPE), and stride frequency during backward walking in water and on land. The walking speeds in water were set to be half of those on land. There was no significant difference in metabolic costs and RPE between backward walking in water with a current and on land, at slow and moderate speeds (P > 0.05). However, at the fast speed (i.e., 3.0 and 6.0 km · h–1 for water and land, respectively), the metabolic costs and RPE during backward walking on land were significantly higher than when walking backward in water with a current (P < 0.05). With regard to backward walking at faster speeds, if the walking speed in water with a current is set at half the speed on land, then the speed will be inadequate for inducing metabolic costs and RPE that are similar to those produced on land. [ABSTRACT FROM AUTHOR]

Aim To evaluate the effects of fibroblast growth factor ( FGF)-2 on the healing of surgical periodontal defects in rats with early, streptozotocin-induced diabetes. Materials and Methods Fifty Wistar rats were assigned to streptozotocin-induced diabetes or non-diabetes group. Periodontal defects were surgically created at maxillary first molars. Defects were treated with hydroxypropyl cellulose ( HPC) or FGF-2 with HPC. Defect fill was evaluated by microcomputed tomography. Histological and immunohistochemical analyses were performed. Results Compared to vehicle alone, FGF-2 treatment yielded significantly greater bone volume and trabecular thickness in diabetes group. Diabetes group displayed reduced new bone formation and significantly longer epithelial down-growth compared to non-diabetes group. In diabetes group, FGF-2 treatment increased PCNA-positive cells and new bone formation after 2 weeks and suppressed epithelial down-growth, but new cementum formation was minimal even after 4 weeks. In diabetes group, overexpression of vascular endothelial growth factor was evident in cells within connective tissue, and no significant enhancement was observed by FGF-2 treatment. FGF-2 increased the expression of α-smooth muscle actin in diabetes group. Conclusions Treatment of surgical periodontal defects in diabetic rats with the single application of FGF-2 provided beneficial effects primarily on new bone formation via increasing cell proliferation and regulating angiogenesis. [ABSTRACT FROM AUTHOR]

Background A recent survey of 79 countries showed that fertility knowledge was lower in Japan than in any other developed country. Given the fertility decline in Japan and the importance of fertility knowledge, we conducted an online survey to examine fertility knowledge and the related factors for effective public education. Methods We studied people aged 18-59 years old, n = 4,328 (the "General" group), and also people who had been trying to conceive for at least six months, 18-50 years old, n = 618 (the "Triers" group). Fertility knowledge was assessed using the Japanese version of the 13-item Cardiff Fertility Knowledge Scale (CFKS-J). All participants provided socio-demographic and fertility information. Participants also completed a 14-item health literacy scale and an 11-item health numeracy scale. We asked participants who were aware of age-related decline in fertility when and where they first acquired that knowledge. Results The average percentages of CFKS-J items answered correctly were 53.1% in the Triers group and 44.4% in the General group (p < 0.001). Multivariate linear regression models showed in the Triers group greater fertility knowledge was associated with greater health literacy and prior medical consultation regarding their fertility. In the General group greater fertility knowledge was associated with being female, younger, university educated, currently trying to conceive, non-smoking, having higher household income, having higher health literacy and having higher health numeracy. Of those who were aware of the age-related decline in fertility, around 3% first learned the fact "at school," and around 65% first learned it "through mass media" or "via the Internet." More than 30% of the respondents first learned it "less than 5 years before" the survey. Conclusions Although fertility knowledge had improved since a previous study, possibly due to recent media coverage of age-related infertility, it was still low. Educational interventions, both in schools and in the community, may be needed to increase fertility knowledge in the general population because most people obtain fertility knowledge from mass media, which has been shown to often present distorted and inaccurate fertility information. [ABSTRACT FROM AUTHOR]