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Background Cartilage conduction hearing aids (CCHAs) were newly devised and spread fast in Japan since their launch in 2017. However, little knowledge is available for this new device. Purpose The aim of this study was to establish the knowledge of CCHAs and suggest their indication. Research Design Correlational study. Study Sample A total 256 patients were registered. Data Collection and Analysis The fitting of CCHAs was surveyed in nine institutions. The outcomes were assessed by audiometric tests. The patients were classified into seven groups, depending on the ear conditions. The clinical characteristics, assessment results, and purchase rates were compared among the groups. The assessment results of CCHAs were also compared with those of previously used hearing aids. Results Most patients who used CCHAs were classified into the bilateral closed (aural atresia or severe stenosis) ear (n=65) or unilateral closed ear (n=124) groups. The patients in these groups achieved good benefits that resulted in a high purchase rate. The bilateral continuous otorrhea group also supported a high purchase rate, although the benefits of CCHAs were not always excellent. In contrast, the purchase rate was poor in the patients who could use air conduction hearing aids (ACHAs) without absolute problems. As for using a CCHA as a contralateral routing of signals hearing aid, the benefits depended on the patients. Conclusions CCHAs are considered as a great option not only to the patients with closed ears but also to those who had difficulties in ACHAs usage. [ABSTRACT FROM AUTHOR]

Aim To evaluate the long-term effectiveness of modified brief assertiveness training (with cognitive techniques) for nurses. Background Most assertiveness training takes a long time to conduct; thus, briefer training is required for universal on-the-job training in the workplace. Methods In this single-group study, nurses received two 90-min training sessions with a 1-month interval between sessions. The degree of assertiveness was assessed by using the Rathus Assertiveness Schedule as the primary outcome, at four time points: pre- and post-training, 3-month follow-up and 6-month follow-up. Results A total of 33 nurses received the training, and the mean Rathus Assertiveness Schedule score improved from −14.2 ( SD = 16.5) pre-training to −10.5 ( SD = 18.0) post-training ( p < .05). These improvements were maintained until the 6-month follow-up. The pre-post effect size of 0.22 (indicating small effect) was larger than the effect sizes ranging from −0.56 to 0.17 (no effect) reported in previous studies that used brief training. Conclusions Modified brief assertiveness training seems feasible and may achieve long-term favourable outcomes in improving assertiveness among nurses. Implications for Nursing Management The ease of implementation of assertiveness training is important because creating an open environment for communication leads to improved job satisfaction, improved nursing care and increased patient safety. [ABSTRACT FROM AUTHOR]

Background Individuals with Williams syndrome (WS) exhibit atypical attentional characteristics when viewing faces. Although atypical configural processing of faces has been reported in WS, the relative strengths of configural and local feature information to capture visual attention in WS remains unclear. We previously demonstrated that attentional capture by target-unrelated upright faces differs depending on what response is measured. Whereas eye movements reflected subtle atypical attentional properties at the late stage of visual search, manual responses could not capture the atypical attentional profiles towards target-unrelated upright faces in individuals with WS. Here we used the same experimental paradigm to assess whether sensitivity to configural facial information is necessary for capturing attention in WS. Methods We measured both eye movements and manual responses from 17 individuals with WS and 34 typically developing children and adults while they were actively involved in a visual search task with an inverted face distractor. Task measures (reaction time and performance accuracy) and gaze behaviour (initial direction of attention and fixation duration) were analysed for each stimulus. Results When the target and the inverted face were displayed in the same search array, reaction times and accuracies in individuals with WS showed similar tendencies as typical controls. Analysis of task and gaze measures revealed that attentional orienting towards inverted faces was not atypical. Conclusion Although individuals with WS exhibited atypical gaze behaviour towards upright faces in our previous study, this unusual behaviour disappears if the faces are upside down. These findings suggest that local feature information alone (e.g. eyes) does not contribute to the heightened attention to faces, but configural information appears necessary for drawing attention to faces in individuals with WS, at least in the current experimental paradigm. [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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Objective: This study assessed the development of stress from polymerization of light-cured dental resin composites for 24 hours after irradiation. Materials and Methods: Initial cracks were made near the edge of a cylindrical hole in glass, and crack lengths were measured. Revolution Formula 2, Kalore and Venus Diamond were polymerized in the hole. Crack lengths were measured at several intervals after irradiation up to 24 hours. Stresses at the composite-glass interface were calculated using the crack lengths. Elastic moduli of the composites were measured at the same time intervals. Results: Interfacial stress and elastic modulus were significantly related to material and time. Stress continued to increase up to 12 hours after irradiation. Significantly lower stresses were measured in Kalore and Venus Diamond than Revolution Formula 2 throughout 24 hours. Stress at 24 hours was two times greater than the stress at 30 minutes. The increase in elastic modulus from 30 minutes to 24 hours ranged from 8 to 24%, which was less than the increase in stress over the same time period. Conclusions: Interfacial stress and elastic modulus of the composites demonstrated the average increases of 155% and 14%, respectively, from 30 minutes to 24 hours after irradiation. [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]

Summary: Patients with rheumatoid arthritis showed greater response to 18-month administration of daily teriparatide especially in the increase of bone formation markers at 1 month and femoral neck bone mineral density at 18 months compared to postmenopausal osteoporosis patients. Introduction: The aim of this study was to evaluate the effects of 18-month administration of daily teriparatide (TPTD) in osteoporosis patients with rheumatoid arthritis (RA) by comparing that of postmenopausal osteoporosis patients (Porosis). Methods: The effects of TPTD were examined between RA ( n = 70; age 68.4 years; disease activity score assessing 28 joints with CRP [DAS28-CRP] 2.8; rheumatoid factor [RF] positivity 75.5 %) with 77.1 % of prior bisphosphonate (BP), 84.3 % of oral prednisolone (PSL) (4.4 mg/day at baseline), 25.7 % of biologics, and Porosis ( n = 62; age 71.3 years) with 77.4 % of prior BP. Results: Femoral neck (FN) bone mineral density (BMD) increase at 18 months was significantly greater in RA compared to Porosis (4.7 vs. 0.7 %, P = 0.038), whereas it was 9.7 versus 7.9 % ( P = 0.736) in the lumbar spine (LS). The increase of bone formation markers (bone alkaline phosphatase [bone ALP] and N-terminal type I procollagen propeptide [PINP]) at 1 month were all significantly greater in RA compared to Porosis. A multivariate logistic regression analysis revealed that the significant indicator of 18-month BMD increase in RA was a 3-month increase of under-carboxylated osteocalcin (ucOC) for LS ( β = 0.446, P = 0.005) and baseline ucOC for FN ( β = 0.554, P = 0.001), in which both showed significant negative correlation with baseline PSL dose. Conclusions: RA showed greater response to daily TPTD administration, especially in the increase of bone formation markers at 1 month and FN BMD increase at 18 months compared to Porosis. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to compare the levels of bone and cartilage metabolism markers in the synovial fluid of the hip joint between patients with secondary OA due to osteonecrosis of the femoral head (ONFH), rapidly destructive arthrosis (RDA) and developmental dysplasia of the hip (DDH).Methods. We studied 70 synovial fluid samples obtained from 57 patients with ONFH (mean age 46 years, 34 males, 23 females), 21 samples obtained from 21 patients with RDA (mean age 70 years, 2 males, 19 females) and 20 samples obtained from 20 patients with DDH (mean age 56 years, 2 males, 18 females). The levels of bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), as bone metabolism markers, and matrix metalloproteinase 3 (MMP-3) and keratan sulphate (KS), as cartilage metabolism markers, were analysed.Results. The levels of BAP, MMP-3 and KS were significantly higher in the ONFH group than in the RDA and DDH groups. The levels of TRACP-5b were highest in the RDA group. The levels of BAP in the ONFH group after the development of osteoarthritic changes were significantly lower than those observed in earlier stages. In comparisons between the samples obtained from each group with a terminal condition, the ONFH samples exhibited significantly higher MMP-3 and KS levels, while the TRACP-5 levels were highest in the RDA group.Conclusion. The ONFH patients showed a relatively bone formative condition before the osteoarthritic stage and maintained a higher rate of cartilage turnover throughout several stages compared with the RDA and DDH patients. RDA patients were characterized by a significantly high osteoclast activity. [ABSTRACT FROM PUBLISHER]

Objective. Interstitial pneumonia (IP) is a chronic progressive interstitial lung disease associated with high mortality and poor prognosis. However, the pathogenesis of IP remains to be elucidated. The aim of this study was to clarify the role of CD161+ Vδ1+ γδ T cells in SSc patients with IP.Methods. The proportion of CD161+ Vδ1+ γδ T cells in peripheral blood mononuclear cells (PBMCs) and serum sialylated carbohydrate antigen (KL-6) levels were determined. GeneChip analysis was performed with CD161− and CD161+ Vδ1+ γδ T cells. Cytokine and chemokine expression from CD161+ Vδ1+ γδ T cells was measured and used to evaluate the effect of culture supernatant on fibroblast proliferation.Results. The proportion of CD161+ Vδ1+ γδ T cells was significantly higher in SSc than healthy controls (HCs) and correlated negatively with serum KL-6 levels in IP-positive SSc patients. The gene and mRNA expression level of chemokine ligand 3 (CCL3) was markedly higher in CD161+ Vδ1+ γδ T cells than in CD161− Vδ1+ γδ T cells. CD161+ Vδ1+ γδ T cells in IP-positive SSc patients showed higher production of CCL3 and lower production of IFN-γ than in HCs. Culture supernatant derived from IP-negative and IP-positive SSc patients promoted fibroblast proliferation, whereas that from HCs did not.Conclusion. The small proportion and the altered cell functions of CD161+ Vδ1+ γδ T cells among PBMCs in SSc patients play a role in the pathogenesis of IP. These findings suggest that CD161+ Vδ1+ γδ T cells may play a regulatory role in the pathogenesis of IP in SSc patients via IFN-γ production. [ABSTRACT FROM PUBLISHER]

A posterior cross-bite is defined as an abnormal bucco-lingual relationship between opposing molars, pre-molars or both in centric occlusion. Although it has been reported that patients with unilateral posterior cross-bite often show unique chewing patterns, the relationship between the form of cross-bite and masticatory jaw movement remains unclear in adult patients. The objective of this study was to investigate masticatory jaw movement among different forms of cross-bite. One hundred and one adults were recruited in this study: 27 had unilateral first molar cross-bite ( MC group); 28, unilateral pre-molar cross-bite ( PC group); 23, anterior cross-bite ( AC group); and 23, normal occlusion (control group). Masticatory jaw movement of the lower incisor point was recorded with six degrees of freedom jaw-tracking system during unilateral mastication. Our results showed that the reverse chewing ratio during deliberate unilateral mastication was significantly larger in the MC group than in the PA ( P < 0·001), AC ( P < 0·001) and control ( P < 0·001) groups. These findings suggest that compared to the anterior or pre-molar cross-bite, the first molar cross-bite is more closely associated with a higher prevalence of a reverse chewing cycle. [ABSTRACT FROM AUTHOR]

Incomplete Cure of TIC with Rate Control Background It is uncertain whether rate or rhythm control is more favorable for patients experiencing tachycardia-induced cardiomyopathy (TIC) secondary to rapid atrial fibrillation (AF). Methods and Results We compared the electrophysiological and hemodynamic properties and outcome after AF ablation in 20 patients with a history of decompensated TIC who maintained sinus rhythm or had paroxysmal AF (group 1), 32 with a history of decompensated TIC who had persistent or longstanding persistent AF (group 2), 377 without TIC who had paroxysmal AF (group 3), and 225 without TIC who had persistent or longstanding persistent AF (group 4). The corrected sinus node recovery time was more prolonged in group 2 than in groups 1, 3, or 4 (1,066 ± 946 vs. 416 ± 188, 450 ± 322 and 590 ± 329 milliseconds; P < 0.001, respectively). The mean left atrial pressure in group 2 was greater than that in groups 1, 3, or 4 (13.9 ± 6.5 vs. 7.5 ± 3.1, 8.2 ± 4.1 and 10.8 ± 4.2 mmHg; P < 0.001, respectively). The left ventricular ejection fraction assessed after the recovery from the decompensation was more decreased in group 2 than in group 1; however, it almost returned to normal if sinus rhythm was maintained after the AF ablation in group 2. The presence of a history of TIC did not predict an AF recurrence after the ablation. Conclusions Heart rate control during AF without sinus conversion may result in an incomplete cure of TIC, suggesting the advantages of rhythm control with ablation in patients with TIC. [ABSTRACT FROM AUTHOR]

Objective Streptococcus mutans, a major dental caries pathogen, has shown to be associated with the aggravation of cerebral hemorrhage and inflammatory bowel diseases. In this study, we evaluated the effects of S. mutans on the development of non-alcoholic steatohepatitis ( NASH) in a mouse model. Materials and methods Streptococcus mutans oral strain MT8148 (serotype c) and a blood isolate TW871 ( k) were used. C57BL/6J mice (6 weeks old) were fed a high-fat diet for 4 weeks; the test strains or phosphate-buffered saline was then intravenously administered. Mice were euthanized after 8 or 12 weeks. Whole body, extirpated liver, and visceral fat weights were determined, and histopathological evaluations of the liver specimens were performed. Results Mice infected with TW871 showed significantly greater body and liver weights than those administered MT8148 or phosphate-buffered saline. Histopathological analyses revealed prominent infiltration of inflammatory cells and adipocellular deposition in livers extirpated 8 weeks after an infection with TW871; fibrosis was also observed in livers extirpated after 12 weeks. Conclusion These results suggest that a specific strain of S. mutans could induce NASH. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to determine the significance of miR-126 and miR-20b in colorectal carcinogenesis. Methods: We analyzed the expressions of miR-126 and miR-20b in 136 colorectal tumors from 39 microsatellite stable (MSS) tumors, 23 high microsatellite instability (MSI-H) tumors, 16 Lynch syndrome, and 58 familial adenomatous polyposis (FAP) tumors including adenoma, intramucosal carcinoma, and invasive carcinoma. Results: All four kinds of tumors showed underexpression of both miR-126 and miR-20b. The frequency of miR-126 downregulation was 100.0% in FAP adenomas, 85.7% in FAP intramucosal carcinomas, 78.9% in invasive carcinomas, 81.3% in Lynch syndrome tumors, 68.4% in MSS tumors, and 65.4% in MSI-H tumors. The frequency of miR-20b downregulation was 64.0% in FAP adenomas, 50.0% in FAP intramucosal carcinomas, 73.3% in invasive carcinomas, 62.5% in Lynch syndrome tumors, 79.5% in MSS tumors, and 91.3% in MSI-H tumors. The current study demonstrated underexpression of miR-126 and miR-20b in various types of colorectal cancer. These findings support the hypothesis that angiogenesis results from underexpressions of miR-126 and miR-20b and occurs as an early event in colorectal carcinogenesis. Conclusions: Underexpression of miR-126 and miR-20b was observed in various types of colorectal cancer, and occurs as an early event of colorectal carcinogenesis in FAP tumors. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective. The mechanisms of ectopic calcification in inflammatory diseases are poorly understood. We investigated the effects of inflammatory cytokines on the mechanisms of calcification in human adipose tissue-derived mesenchymal stem cells (hADSCs).Methods. The effects of inflammatory cytokines were evaluated using hADSCs cultured in osteoblast induction medium. mRNA expression was measured by real-time PCR and protein levels were measured by western blotting. Cell mineralization was evaluated by Alizarin Red S staining.Results. In hADSCs, administration of IL-6/soluble IL-6 receptor (sIL-6R), TNF or IL-1β accelerated calcification through enhanced expression of an osteoblast differentiation marker, runt-related transcription factor 2 (RUNX2). IL-6/sIL-6R had the greatest effect. The transcription of mRNA for receptor tyrosine kinase-like orphan receptor 2 (ROR2), involved in the non-canonical wingless-type (WNT) MMTV integration site pathway, was increased, while β-catenin expression, an essential factor in the canonical WNT signalling pathway for osteoblast differentiation, did not change. Suppression of signal transducer and activator of transcription 3 (STAT3), but not STAT1, by small interfering RNA (siRNA) exerted a strong inhibitory effect on RUNX2 and ROR2 expression, and inhibited accelerated calcification.Conclusion. IL-6/sIL-6R stimulation accelerated the ROR2/WNT5A pathway in hADSCs in a STAT3-dependent manner, resulting in augmented calcification. These results suggest that the mechanisms of ectopic calcification accelerated by IL-6 in hADSCs may be involved in chronic inflammatory tissues and that IL-6 inhibitors may be beneficial in the treatment of ectopic calcification in inflammatory diseases. [ABSTRACT FROM PUBLISHER]

6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a bioactive ingredient of wasabi (Wasabia japonica), which is a popular spice in Japan. 6-MSITC has been reported to inhibit the proliferation of breast cancer and melanoma cell lines. We inoculated 30 female Balb-nu/nu mice with MDA-MB-231 or -453 cells, and orally administered varying concentrations of 6-MSITC for 12 days following tumor growth. The tumor volumes and tumor weights from mice inoculated with MDA-MB-231 cells, and the tumor volumes of MDA-MB-453 cells were significantly inhibited by 6-MSITC on Days 9 and 11 after drug administration. DNA fragmentation, DNA ladder, and caspase 3/7 activity performed in vitro revealed that 6-MSITC induced apoptosis of MDA-MB-231, MDA-MB-453, and MCF-7 cells. Furthermore, nuclear factor-κB (NF-κB) expression in the nuclei and phosphorylation of inhibitor κBα (IκBα) was downregulated by 6-MSITC in a concentration-dependent manner; however, this activity was not observed in MCF-7 cells. Moreover, this downregulation of phosphorylated IκBα by 6-MSITC in MDA-MB-231 and -453 cells supports its inhibitory effects on NF-κB activity. The expression of phosphorylated AKT (pAKT) reduced by 6-MSITC was confirmed in MDA-MB-231 cells. Thus, we conclude that 6-MITC promotes apoptosis of breast cancer cells by inhibiting NF-kB and therefore releasing its control of the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to characterize arthropathies of the hands associated with anti-aminoacyl tRNA synthetase (ARS) autoantibodies.Methods. Fifty-six patients with anti-ARS antibodies were selected from consecutive patients who visited Keio University Hospital between1983 and 2011, based on their joint symptoms and the availability of hand X-rays. Their clinical characteristics, anti-CCP antibodies, RF, and hand X-ray findings were retrospectively examined.Results. Based on characteristic hand X-ray findings, the anti-ARS-positive patients with joint symptoms could largely be categorized into three groups. The predominant group (64%) was patients with no significant X-ray findings. The remaining patients with destructive changes were classified into two distinct groups. One group had mainly erosions in the PIP and MCP joints and/or ankylosis of the wrists with anti-CCP and RF, which is consistent with the features of RA. The other group showed subluxation of the thumbs and periarticular calcification that was independent of anti-CCP or RF, which is exclusively found in anti-Jo-1-positive patients.Conclusion. Autoantibody profiles, including anti-CCP, RF and individual anti-ARS specificities, are useful in classifying anti-ARS-associated arthropathies of the hands into RA or anti-Jo-1-related disorders. [ABSTRACT FROM PUBLISHER]

Aim To examine the associations between the pre-pregnancy body mass index ( BMI) and gestational weight gain ( GWG) with pregnancy outcomes in Japanese women. Methods The medical records of 1883 Japanese women who delivered singleton infants from January 2010 to January 2013 at Osaka- Minami Medical Center were retrospectively reviewed. We use the BMI classification which the World Health Organization defined for Asian populations and the GWG classified based on the current 2009 Institute of Medicine ( IOM) recommendations. The odds ratio ( OR) of each of the groups for the different pregnancy outcomes were compared to the recommended group using a logistic regression analysis adjusted by age, gestational weeks, parity, weight gain, mode of delivery, pregnancy induced hypertension ( PIH) and gestational diabetes mellitus. Results Women who were obese ( BMI, ≥25 kg/m2) and overweight ( BMI, 23-24.9 kg/m2) had a higher rate of developing PIH (adjusted OR, 6.68 and 3.21 [95% confidence interval [ CI], 3.31-13.3 and 1.29-7.24]). In contrast, GWG exhibited a correlation with the weight of the infant. The inadequate GWG group had a higher rate of small-for-gestational age ( SGA) infants (adjusted OR, 1.72 [95% CI, 1.22-2.46]). The rate of emergency cesarean section was not significantly different between the groups. Conclusion A pre-pregnancy BMI less than 23 kg/m2 is desirable to prevent Japanese women from developing PIH. GWG within the IOM recommendations also reduced the risk of PIH and SGA. [ABSTRACT FROM AUTHOR]

Objective Thymidine phosphorylase (TP) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) is induced by tumor necrosis factor α (TNFα) and other cytokines that have been reported to be major inflammation mediators in RA. We previously demonstrated that TP plays an important role in angiogenesis and tumor growth, invasion, and metastasis. The aim of this study was to investigate whether the role of TP in the pathogenesis of RA is similar to its role in tumors. Methods In FLS obtained from 2 patients with RA, the expression of TP, interferon-γ (IFNγ)-inducible protein 10 (CXCL10), and other cytokines was measured by quantitative real-time polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assays. Microarray analysis was performed using FLS transfected with TYMP complementary DNA and treated with a TP inhibitor. Results The expression of TP in FLS was up-regulated by TNFα, interleukin-1β (IL-1β), IL-17, IFNγ, and lipopolysaccharide. Microarray analysis of FLS overexpressing TP identified CXCL10 as a thymidine phosphorylase-related gene. The expression of CXCL10 was induced by TNFα, and this induction was suppressed by TYMP small interfering RNA and TP inhibitor. Furthermore, the combination of TNFα and IFNγ synergistically augmented the expression of TP and CXCL10. TP-induced CXCL10 expression was suppressed by the antioxidant EUK-8. In the synovial tissue of patients with RA, TP levels were significantly correlated with CXCL10 expression. Conclusion The combination of TNFα and IFNγ strongly induced the expression of thymidine phosphorylase in RA FLS. The induction of thymidine phosphorylase enhanced the expression of CXCL10, which may contribute to the Th1 phenotype and bone destruction observed in RA. [ABSTRACT FROM AUTHOR]

Purpose. To compare the postoperative changes of the retinal nerve fiber layer (RNFL) thickness in patients with macular holes (MHs) treated with vitrectomy with indocyanine green- (ICG-), brilliant blue G- (BBG-), or triamcinolone acetonide- (TA-)assisted internal limiting membrane (ILM) peeling. Methods. Sixty-one eyes of 61 consecutive patients with MHs were studied. Each eye was randomly selected to undergo either ICG- (n = 18), BBG- (n = 21), or TA-assisted (n = 22) ILM peeling. The circumferential retinal nerve fiber layer (RNFL) thickness was determined by spectral-domain optical coherence tomography (SD-OCT) before and 1, 3, 6, 9, and 12 months postoperatively. The mean overall and the sectoral thicknesses of the RNFL were obtained for each group. Results. A transient increase of the RNFL thickness was seen in the mean overall and sectoral thicknesses except for the nasal/inferior sector at 1 month after surgery for the three groups. Then, the thickness gradually decreased and returned to the baseline level in all sectors except for the nasal/inferior sector. The differences in the RNFL thickness among the groups were not significant for at least 12 months postoperatively. Conclusions. The degree of change of the RNFL thickness was not significantly related to the type of vital stain used during MH surgery. [ABSTRACT FROM AUTHOR]

CartoSound Merge Using Left Atrial Posterior Wall Background CartoSound™ (CS) module is useful in integrating 3-dimensional (3D) left atrial (LA) image with CT image. Integration method, however, has not been established. We reported the accuracy of LA electroanatomical (EA) and CT image integration by registering LA roof (LAR) and posterior wall (LAPW). Methods The consecutive 56 atrial fibrillation patients undergoing pulmonary vein isolation were studied. In the initial 29 patients, before the transseptal puncture, 3D CS LAR and LAPW image was created by registering a mean of 10 contour lines between the right and left pulmonary veins. After transseptally inserting a mapping catheter into LA, 3D EA image of LAR and LAPW was obtained by sampling a mean of 40 points. LA CT image was taken at the full-inspiratory position and 0% of R-R interval. After visual alignment of CS or EA and LA CT image, the 2 images were integrated with surface registration program. In the latter 27 patients, both CT and CS images were taken while matching the respiratory phase at the end-tidal position and cardiac cycle at 50% of R-R interval. Results In the initial 29 patients, the mean distances between EA and CT images and between CS and CT images were 1.53 ± 0.27 and 1.59 ± 0.23 mm, respectively (P = NS). In the latter 27, the mean distance was decreased to 1.08 ± 0.14 mm (P < 0.0001). Conclusions CS system is useful in image integration with 3D CT. Matching both respiratory phase and cardiac cycle between CS and CT image acquisition improves the image integration accuracy. [ABSTRACT FROM AUTHOR]

Serum albumin levels are a practical marker of general health status in the elderly and have been used to determine the severity of underlying diseases and the risk for death. This longitudinal study evaluated the relationship between serum albumin concentrations and tooth loss over 10 years in elderly subjects, after controlling for confounding factors. A sample of 554 dentate subjects among enrolled subjects ( n = 600) was involved in this planned longitudinal study with follow-up examinations after 5 and 10 years. At the 5-year follow-up, 373 (67·3%), subjects were available for re-examination. In addition, 331 (59·7%) were available at the 10-year follow-up. Multiple Poisson regression analysis was conducted to evaluate the relationship between the number of missing teeth over 5 or 10 years and serum albumin levels at baseline after adjusting for 10 variables: gender, serum markers levels at baseline, dental status, smoking habits and educational years and oral health behaviour. The number of missing teeth over 5 or 10 years was significantly negatively associated with serum albumin levels at baseline [incidence rate ratios ( IRR) = 0·373, P < 0·0001 for 5 years; IRR = 0·570, P < 0·0001 for 10 years]. We conclude that elderly subjects with hypoalbuminemia are at high risk for 5- and 10-year tooth loss. [ABSTRACT FROM AUTHOR]

Aim The associations among changes in dietary intake, maternal bodyweight, and fetal growth during the course of pregnancy were investigated in a prospective cohort study carried out on 135 Japanese women. Material and Methods Dietary intake was analyzed using digital photos of meals taken over 3 consecutive days, in the first, second and third trimester, and was compared with maternal bodyweight, estimated fetal bodyweight by ultrasound examination, and birthweight. Results Surprisingly, the mean total calorie intake remained below 1600 kcal/day during pregnancy, much lower than the value recommended in the 2010 edition of ' Dietary Reference Intakes for Japanese'. Dietary intake was similar throughout despite the recommendation of extra intake in late pregnancy. Maternal dietary intake did not correlate with fetal growth, although maternal bodyweight in the second trimester positively correlated with estimated fetal bodyweight in the third trimester. Maternal bodyweight before pregnancy positively correlated with birthweight. Conclusions Maternal bodyweight as well as eating habits established before pregnancy may have a considerable effect on fetal growth. There is an urgent need to improve the diet of Japanese women of child-bearing age, especially during pregnancy. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression and function of Mohawk (MKX) in human adult anterior cruciate ligament (ACL) tissue and ligament cells from normal and osteoarthritis (OA)-affected knees. Methods Knee joints were obtained at autopsy (within 24-48 hours postmortem) from 13 donors with normal knees (mean ± SD age 36.9 ± 11.0 years), 16 donors with knee OA (age 79.7 ± 11.4 years), and 8 aging donors without knee OA (age 76.9 ± 12.9 years). All cartilage surfaces were graded macroscopically. MKX expression was analyzed by immunohistochemistry and quantitative polymerase chain reaction. ACL-derived cells were used to study regulation of MKX expression by interleukin-1β (IL-1β). MKX was knocked down with small interfering RNA (siRNA) to analyze the function of MKX in extracellular matrix (ECM) production and differentiation in ACL-derived cells. Results The expression of MKX was significantly decreased in ACL-derived cells from OA knees compared with normal knees. Consistent with this finding, immunohistochemistry analysis showed that MKX-positive cells were significantly reduced in ACL tissue from OA donors, in particular in cells located in disorientated fibers. In ACL-derived cells, IL-1β strongly suppressed MKX expression and reduced expression of the ligament ECM genes COL1A1 and TNXB. In contrast, SOX9, a chondrocyte master transcription factor, was up-regulated by IL-1β treatment. Importantly, knockdown of MKX expression with siRNA up-regulated SOX9 expression in ACL-derived cells, whereas the expression of COL1A1 and TNXB was reduced. Conclusion Reduced expression of MKX is a feature of degenerated ACL in OA-affected joints, and this may be mediated in part by IL-1β. MKX appears necessary to maintain the tissue-specific cellular differentiation status and ECM production in adult human tendons and ligaments. [ABSTRACT FROM AUTHOR]

Purpose: Elevated circulating activities of alanine aminotransferase (ALT), a marker for liver injury, and the lifestyle of a higher rate of eating in healthy and preclinical subjects are associated with increased risk of obesity and diabetes. In this study, we examined the associations between self-reported rate of eating and circulating ALT activity in middle-aged apparently healthy Japanese men. Methods: We conducted a cross-sectional study of 3,929 apparently healthy men aged 40-59 years (mean ± SD age, 49.2 ± 5.8 years; BMI, 23.5 ± 2.8 kg/m) who participated in health checkups in Japan. We analyzed their clinical serum parameters and lifestyle factors, including self-reported rate of eating. Associations between self-reported rate of eating and liver injury markers [ALT, γ-glutamyl transpeptidase (GTP), and aspartate aminotransferase (AST)], other clinical parameters or lifestyle factors were determined using analysis of variance followed by Tukey's test. Multivariate logistic regression analyses (MLRA) were performed with ALT activity as the dependent variable and independent variables that included self-reported rate of eating. Results: MLRA showed that ALT activity showed trends for higher self-reported rate of eating after adjustment for age, energy intake, and smoking status. The association between ALT activity and self-reported rate of eating disappeared after adjustment for BMI. Conclusion: The results of this study show that ALT activity is positively associated with self-reported rate of eating in middle-aged apparently healthy Japanese men. [ABSTRACT FROM AUTHOR]

Background: Both combination therapies of an an-giotensin II receptor blocker (ARB) with the thiazide diuretic hydrochlorothiazide (HCTZ) and an ARB with a calcium channel blocker (CCB) are recommended to achieve blood pressure (BP) goals in antihy-pertensive treatment. However, although HCTZ is known to have unfavorable effects on lipid metabolism, the effects of HCTZ in the ARB + HCTZ combination on lipid metabolism have not been fully elucidated. Objective: The aim of this study was to compare the effects on lipid metabolism of combination treatment with the ARB losartan + HCTZ and losartan + the CCB amlodipine and to assess the efficacy in BP lowering of these 2 combination therapies. The metabolism of glucose, uric acid (UA), and high-sensitivity C- reactive protein (hs-CRP), an inflammation marker of atherosclerosis, were also assessed in association with lipid metabolism. Methods: This 48-week, prospective, randomized, open-label trial was conducted at 2 clinics and 2 hospitals in Tokorozawa City (Saitama, Japan) and Shin-juku- ku Ward (Tokyo, Japan). Eligible patients had a systolic BP (SBP) >140 mm Hg and/or diastolic BP (DBP) >90 mm Hg despite a > 1-month history of monotherapy with an ARB. Patients were randomly assigned to receive losartan 50 mg/d + HCTZ 12.5 mg/d (LOS + HCTZ) or losartan 50 mg/d + amlodipine 5 mg/d (LOS + CCB) for 48 weeks. Follow-up visits were scheduled at 4, 8, 12, 24, and 48 weeks. Biochemical measurements were centrally measured at a single institute. Tolerability and treatment compliance were assessed by physicians every 4 weeks. Results: A total of 112 patients were enrolled; 26 were excluded from the final analysis, leaving 42 and 44 patients in the LOS + HCTZ and LOS + CCB groups, respectively, included in the final analysis. At 48 weeks, SBP and DBP were significantly decreased in the 2 treatment groups (both, P < 0.0001). The decrease in SBP was significantly greater in the LOS + HCTZ group than in the LOS + CCB group (P < 0.001). The difference in the decrease in DBP between the 2 groups was nonsignificant. There were no significant differences in the changes from baseline (Δ) in any of the lipid parameters between the 2 groups. The decreases at 8 and 12 weeks in LDL-C, TC, and apolipo-protein (apo) B were significantly greater in the LOS + CCB group compared with those in the LOS + HCTZ group. The between-group differences in ΔTG, ΔHDL-C, ΔapoA- 1, and AapoE throughout the study were nonsignificant. Changes in fasting plasma glucose (FPG), hemoglobin A1c, and hs-CRP were not significantly different between the 2 groups. The between-group difference in ΔUA in men was not significant, but a significant difference was found in women (LOS + HCTZ, 0.74 mg/dL; LOS + CCB, 0.28 mg/dL [P = 0.0017]). No clinically significant adverse events were reported with either treatment throughout the study. Conclusions: The findings from the present study suggest that LOS + HCTZ was more efficacious in decreasing SBP than was LOS + CCB in the management of hypertension refractory to ARB monotherapy. Unfavorable effects on lipid metabolism were not observed with either combination therapy. [ABSTRACT FROM AUTHOR]

Background: Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved patient outcomes. The Japanese Ministry of Health and Welfare (JMHW) and the International Society on Thrombosis and Haemostasis (ISTH) criteria are the most specific for diagnosis of septic DIC. The revised Japanese Association for Acute Medicine (JAAM) criteria are able to diagnose sepsis-induced DIC in the early stage. Recombinant human soluble thrombomodulin (rhTM) has recently been used for treating DIC. Previous studies have shown a benefit of using rhTM for DIC diagnosed by the JMHW or ISTH criteria, but not the JAAM criteria. The purpose of this study was to sequentially evaluate coagulation biomarkers and the DIC score after giving rhTM treatment to patients with sepsis-induced DIC diagnosed according to the JAAM criteria. Methods: We performed a retrospective cohort study. Critically ill patients were included if diagnosed with sepsisinduced DIC according to the JAAM criteria. They were either treated without rhTM (control group) or with rhTM (treatment group). The primary outcome was the DIC score on day 7. The secondary outcome was 28-day mortality from the start of DIC treatment. Changes in the results of coagulation tests were assessed over time from the start of treatment to day 7. Results: Twelve and 23 patients were assigned to the treatment and control groups, respectively. The DIC score on day 7 was significantly higher in the treatment group (3.3 ± 1.4) than in the control group (4.9 ± 1.8, p < 0.05). Estimated survival showed lower in treatment group than control group. There was significant difference between the control group and the treatment group (p < 0.05). The D-dimer level on day 7 was significantly lower in the treatment group (7.5 ± 4.1 μg/mL) than in the control group (30.9 ± 33.6 μg/mL, p < 0.05). Life-threatening bleeding did not occur. Our results indicated that rhTM improved sepsis-induced DIC and mortality. Conclusions: Recombinant human soluble thrombomodulin may improve sepsis-induced DIC diagnosed according to the JAAM criteria without an increased bleeding risk. [ABSTRACT FROM AUTHOR]

Although many previous studies reported that honey promotes wound healing, no study has examined the effects of Japanese honey. The aim of this study was to investigate the effects of three types of Japanese honey, Acacia, Buckwheat flour, and Chinese milk vetch honey, on wound healing in comparison with hydrocolloid dressing. Circular full-thickness skin wounds were produced on male mice. Japanese honey or hydrocolloid dressing was applied daily to the mice for 14 days. The ratio of wound area for the hydrocolloid dressing group increased initially in the inflammatory and early proliferative phases and then decreased rapidly to heal with scarring. However, the ratios of wound area for the Japanese honey groups decreased in the inflammatory phase, increased in the proliferative phase, and decreased in the proliferative phase, and some wounds were not completely covered with new epithelium. These findings indicate that using Japanese honey alone has limited benefit, but since it reduces wound size in the inflammatory phase, it is possible to apply a combined treatment in which Japanese honey is applied only in the inflammatory phase, followed by hydrocolloid dressing from the proliferative phase, which would effectively contract the wound. [ABSTRACT FROM AUTHOR]

We investigated the SMF effects on hemodynamics in the caudal artery-ligated rat as an in vivo ischemia model using noninvasive near-infrared spectroscopy (NIRS) combined with power spectral analysis by fast Fourier transform. Male Wistar rats in the growth stage (10 weeks old) were randomly assigned into four groups: (i) intact and nonoperated cage control (n = 20); (ii) ligated alone (n = 20); (iii) ligated and implanted with a nonmagnetized rod (sham magnet; n = 22); and (vi) ligated and implanted with a magnetized rod (n = 22). After caudal artery ligation, a magnetized or unmagnetized rod (maximum magnetic flux density of 160mT) was implanted transcortically into the middle diaphysis of the fifth caudal vertebra. During the experimental period of 7 weeks, NIRS measurements were performed in 3- , 5- , and 7-week sessions and the vasomotion amplitude and frequency were analyzed by fast Fourier transform. Exposure for 3.7 weeks to the SMF significantly contracted the increased vasomotion amplitude in the ischemic area. These results suggest that SMF may have a regulatory effect on rhythmic vasomotion in the ischemic area by smoothing the vasomotion amplitude in the early stage of the wound healing process. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to determine the correlation between non-reassuring fetal heart rate (NRFHR) patterns and poor neonatal outcome in placental abruption. Material and Methods: A retrospective study was performed involving 83 placental abruptions with a live fetus at one tertiary and one secondary hospital in Miyazaki prefecture, Japan. We examined the correlation among NRFHR, umbilical arterial blood gas status, and neonatal poor outcomes, including neonatal death (ND) and cerebral palsy (CP). Results: A total of 83 cases were divided into bradycardia ( n = 27), recurrent late deceleration (rLD, n = 29), severe variable deceleration or prolonged deceleration (sVD/PD, n = 8), and other cases ( n = 19). In the bradycardia group, the incidence of low umbilical artery (UA) pH (<7.0) was 59% and the average UA pH was 6.96 ± 0.22. Among these cases, 10 showed severe bradycardia (less than 80 b.p.m.) and an average UA pH of 6.85 ± 0.24, and four cases resulted in poor outcome (three CP and one ND). In the rLD group, the incidence of low UA pH (<7.0) was 7% and the average UA pH was 7.24 ± 0.12. In this group, a 40-week-old fetus with umbilical phlebitis had a lower UA pH (6.92) and developed CP. In the sVD/PD group, there were no cases of a low UA pH (<7.0) and the average UA pH was 7.30 ± 0.04. In this group, a 31-week-old boy with a UA pH of 7.36 developed CP (PVL). The remaining 19 cases had no CP. Conclusion: Poor neonatal outcome of placental abruption is closely related to NRFHR, especially the degree of bradycardia. In the rLD and sVD/PD groups, risk factors, such as prematurity and fetal inflammation, co-existed. [ABSTRACT FROM AUTHOR]

Aim Lipopolysaccharide is a bacterial virulence factor implicated in chronic periodontitis, which may penetrate the junctional epithelial barrier and basement membrane to insult underlying stroma. We sought to identify lipopolysaccharide-induced global gene expression changes responsible for signalling between stroma and epithelium during disease onset. Materials and Methods Using a rat lipopolysaccharide periodontitis model, junctional epithelium and underlying stromal tissue were separately collected from healthy and diseased animals by laser-capture microdissection and subject to gene expression microarray analysis. Key gene products identified were validated in gingival epithelial and fibroblast cell cultures. Results Global gene expression patterns distinguishing health versus disease were found in and between both tissue types. In stroma, the most significantly altered gene ontology function group ( Z ≥ 4.00) was cytokines, containing most significantly (±2-fold; p < 0.05) upregulated genes amphiregulin, IL1-β and Fas ligand, all positive, diffusible modulators of the epithelial growth factor receptor pathway. In epithelium, the most significant changes were in downregulated FOS-related antigen-1 gene, somatostatin receptor-2 gene and mucin-4 gene, all negative modulators of the epithelial growth factor receptor pathway. Conclusion These results establish a periodontitis model for studying gene product interactions and suggests that the onset of junctional epithelial disease hyperproliferation involves a concerted stromal-epithelial signalling axis. [ABSTRACT FROM AUTHOR]

Aim Trehalose, which is a disaccharide formed by a 1,1 linkage of two glucose molecules, was suggested to have a suppressive effect on bone resorption. In this study, we examined the effects of topical application of trehalose on osteoclast differentiation in a rat periodontitis model. Material and Methods Rats were divided into four groups. One group received no treatment. In the other groups, experimental periodontitis was induced by ligature placement. These rats with experimental periodontitis received topical application of pure water (vehicle group), 30 mg/ml trehalose solution (30 mg/ml trehalose group) or 60 mg/ml trehalose solution (60 mg/ml trehalose group) to the gingival sulcus respectively. Results The vehicle group showed higher numbers of polymorphonuclear leucocytes, receptor activator of nuclear factor kappa B ligand (RANKL)-positive cells and osteoclasts compared with the no treatment group respectively. Trehalose-applied groups exhibited lower numbers of these cells compared with the vehicle group. Gene expressions of tumour necrosis factor-α, RANKL and toll-like receptor 4 were suppressed by trehalose. In addition, protein expressions of RANKL inducing pathway were less activated by trehalose. Conclusion Topical application of trehalose could suppress osteoclast differentiation by inactivation of RANKL inducing pathway in the rat periodontitis model. [ABSTRACT FROM AUTHOR]

Aim Postural tachycardia syndrome ( POTS) is one of the most frequent forms of chronic orthostatic intolerance in children and adolescents. The aim of the present study was to examine the influence of a genetic background on POTS. Methods A total of 96 children and adolescents with orthostatic dysregulation were studied. The polymorphism of the G protein β3 subunit ( GNB3) C825T and G protein α subunit ( GNAS1) T131C of genes encoding components of the autonomic nervous system were determined and compared with circulatory responses to active standing. Results In the GNB3 gene C825T polymorphism, the CT and TT genotype had a significant lower supine heart rate and a larger increase of heart rate by standing than the CC, associated with evaluated power of the high-frequency component of heart rate variability. According to the criteria of the Japanese clinical guidelines, 48 children were diagnosed as POTS and 30 were as normal responder with somatoform disorder (SD). In GNB3 C825T polymorphism, the TT genotype was more frequently found in the POTS group (45.8%) than in the SD group (25.0%; P = 0.036). In the GNAS1 T393C, the genotype frequencies for the T393C polymorphisms of GNA1 did not differ significantly between the groups. Conclusion The gene polymorphisms GNB3 C825T might be a risk factor for POTS through the enhanced vagal withdrawal of the heart in children and adolescents. [ABSTRACT FROM AUTHOR]

Objective. In RA, response to TNF blockers may be associated with a profile of cytokine production unique to each patient. This study sought to predict the response to biologic agents by examining pro-inflammatory cytokine synthesis in stimulated whole blood cultures (WBCs).Methods. We measured the concentration of TNF-α, IL-1β and IL-6 in supernatants of lipopolysaccharide (LPS)-stimulated WBCs obtained from RA patients (n = 41) before anti-TNF therapy (infliximab, 13; etanercept, 26; and adalimumab, 2) and from healthy controls (n = 12). At 24 weeks after biologics, whole bloods were again drawn from 14 of 41 patients. Response was defined by the European League Against Rheumatism response criteria after 24 weeks of therapy.Results. Among 41 patients, 32 were responders (good 14/moderate 18), while 9 were non-responders. All cytokines measured were significantly lower in RA patients than in controls. In RA, IL-1β production was lower in non-responders than in responders [median (interquartile range): 3.5 (1.5–9.4) vs 10.0 (5.1–93.1) pg/ml, P = 0.048]. The area under the curve from a receiver operating characteristic curve analysis for the prediction of response using IL-1β was 0.717 (95% CI 0.520, 0.914). The sensitivity and specificity of IL-1β (cut-off value 4.84 pg/ml) was 78.1 and 77.8%, respectively. All cytokines were significantly higher 6 months later compared with their respective baseline.Conclusion. IL-1β measurement in LPS-stimulated WBC is useful to predict responsiveness to anti-TNF agents. Cytokine production capacities in LPS-stimulated WBCs are up-regulated by biologics. [ABSTRACT FROM PUBLISHER]

Background: Prehypertension is defined as blood pressure (BP) ≥90th percentile, or ≥120/80 mmHg, but <95th percentile for age, sex, and height. Since the definition is made by conventional BP measurements and office BP can be quite variable, we studied whether prehypertension could be differentiated by ambulatory BP monitoring from normotension or hypertension (HTN) in children and adolescents. Methods: One hundred and fifty-eight children (84 boys and 74 girls, aged 6-17 years, median 12) were studied. According to the office BP values, they were divided into normotension (80), prehypertension (20), and HTN (58). Results: Systolic BP index and systolic daytime ambulatory BP (ABP) were significantly higher in prehypertensive patients than in normotensives and lower than hypertensives. When daytime ABP was used to diagnose HTN, four normotensive (5.0%), four prehypertensive (20.0%), and 27 hypertensive (46.6%) patients had HTN. Thus, in patients with prehypertension, the prevalence of masked HTN is significantly higher than in those with normotension. On the other hand, the prevalence of daytime ambulatory HTN is significantly lower, i.e., white-coat effect is more frequent, compared with hypertensive patients. Conclusion: Prehypertension lies between normotension and HTN in ABP values as well and is a good candidate for identifying masked HTN. Our data emphasize the importance of identifying prehypertension in children and adolescents. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of an anti-platelet drug (clopidogrel) on the prevention of steroid-induced osteonecrosis (ON) in rabbits.Methods. Adult male Japanese white rabbits were divided into two groups and treated as follows: one group received daily clopidogrel mixed in normal saline (AP; n = 35), the other received only normal saline (NS; n = 30). One week after the administration, all rabbits were injected once intramuscularly with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. Three weeks after, both the femora and humeri were examined histopathologically for the presence of ON. The platelet aggregation assay and hematological examinations were performed before and after the steroid injection.Results. The incidence of ON in the AP group (48.5%) was significantly lower than that observed in the NS group (73.3%). The platelet aggregations in the AP group were significantly inhibited by the administration of clopidogrel. The levels of total cholesterol and triglycerides showed no significant differences between the AP and NS group.Conclusion. The present experimental study demonstrated that the administration of an anti-platelet drug prevented steroid-induced ON in rabbits and that platelet aggregation seems to be one of the possible factors involved in the pathogenesis of steroid-induced ON. [ABSTRACT FROM PUBLISHER]

Summary The aim of this study was to investigate the influence of chewing force on salivary stress markers (alpha-amylase activity, salivary cortisol level and secretory immunoglobulin A secretion rate) as indicators of mental stress. Participants comprised 20 healthy men. The first set of saliva specimens (S1) was collected at immediately after a 20-min rest to evaluate stress markers. As stress loading, the participants were required to perform arithmetic calculations for 20 min, after which the second set of saliva specimens (S2) was collected. Each participant was then required to chew a piece of tasteless gum for 10 min, after which the third set of saliva specimens (S3) was collected. After a 20-min rest, the fourth set of saliva specimens (S4) was collected. Weak, habitual and strong chewing forces were assigned. Change rates of stress markers between S2 and S3, and S2 and S4 were calculated. A significant difference was observed in the change rate of cortisol levels between S2 and S3. Cortisol level decreased more under strong chewing than under weak chewing. No significant differences were observed in the change rate of amylase activity or s-IgA secretion rate among the three chewing forces. The results suggest that differences in chewing force influence the salivary cortisol level of the three stress markers, and that a strong chewing force induces a greater reduction in mental stress than a weak one. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the independent relationship between masticatory and physical performance in community-living oldest old people (mean age ± standard deviation 87.8 ± 2.2, range 85-102). Design Cross-sectional analysis . Setting University research center or home-based examination. Participants Four hundred eighty-nine community-living individuals (219 men, 270 women) aged 85 and older. Measurements Maximum occlusal force ( MOF) was measured using an occlusal force measuring device. Sociodemographic and functional factors, oral health, comorbidities, blood chemistry, lower extremity performance, and handgrip strength were assessed. Blood chemistry analyses included serum albumin, C-reactive protein, interleukin ( IL)-6, and total and free testosterone. Results MOF was significantly associated with age, body mass index, and cognitive impairment in men but not in women. Comorbidities and blood chemistry were not associated with MOF except for a significant association with IL-6 concentration in women. In a multivariate model adjusted for various confounders, lower MOF was associated with greater risk for poor performance on the timed up and go ( TUG) test in men and women (men: odds ratio ( OR)=2.34, 95% confidence interval ( CI)=1.02-5.38; women: OR=2.44, 95% CI=1.12-5.33). MOF was similarly associated with performance in chair standing, one-leg standing, and handgrip strength only in men. These associations remained after adjustment for number of natural teeth. Conclusion MOF was strongly and independently associated with all measures of physical performance in men and with the TUG test in women after adjustment for various confounders, suggesting that age-related declines in masticatory and skeletal muscle functions share common mechanistic pathways in older age, particularly in men. [ABSTRACT FROM AUTHOR]

Summary The purposes of this study were to determine whether a response shift was observable after partial denture treatment and to identify the predictors that influenced the response shift magnitude and direction. A total of 173 consecutive patients with no more than eight missing teeth who received implant-supported, fixed or removable partial dentures at Okayama University Dental Hospital were asked to complete a full-version Oral Health-Related Quality of Life (OHRQoL) questionnaire before (pre-test) and after treatment (post-test). Additionally, a short form (then-test) consisting of seven questions selected from the full version had its reliability verified and was utilised to retrospectively assess the pre-treatment OHRQoL status. The difference between the summary scores of the then-test and the pre-test determined the response shift magnitude and direction. The then-test mean score (22·9 ± 6·6) was significantly lower (worse OHRQoL) than that of the pre-test (26·4 ± 5·2). The response shift effect size was of moderate magnitude and negative direction ( d = −0·78). A multiple regression analysis showed that age (younger patients) ( P < 0·01), number of replaced teeth (fewer) ( P < 0·01) and pre-test scores (lower) ( P < 0·01) were the significant predictors for response shift. In conclusion, a response shift phenomenon with negative and moderate effect size was observed after partial denture treatment. The significant predictor variables were young age, fewer numbers of replaced teeth and lower pre-test scores [ABSTRACT FROM AUTHOR]

It is important to identify premature infants with prenatal inflammation as it contributes to short- and long-term complications. Our object was to study how prenatal inflammation affects the urinary β-microglobulin (β-MG) level. Preterm neonates were divided based on the presence of chorioamnionitis (CAM) into the CAM ( n = 100) and non-CAM groups ( n = 117). These were further subdivided into five groups each: 30 preterm neonates of 23-26; 42 neonates of 27-28; 54 neonates of 29-30; 51 neonates of 31-32; and 40 neonates of 33-34 weeks' gestation. The urinary β-MG level within 48 h of birth was significantly higher in the CAM group than in the non-CAM group among the neonates of 23-26 weeks' gestation (18.3 ± 6.9 vs 10.0 ± 5.6 × 10 μg/gCr, p = 0.0018) and the neonates of 27-28 weeks' gestation (16.2 ± 10.8 vs 8.8 ± 3.3 × 10 μg/gCr, p = 0.0101). However, there was no difference in urinary β-MG level between the CAM and the non-CAM group among the neonates ≥ 29 weeks 'gestation. Moreover, the elevated urinary β-MG level in the neonates ≤ 28 weeks ' gestation with CAM had disappeared by 1 week after birth. The reasons for the increase in urinary β-MG level within 48 h of birth in very preterm neonates (≤ 28 weeks' gestation) with CAM are believed to be not only prematurity, but also prenatal inflammation. It is suggested that the urinary β-MG level during the early postnatal period can identify prenatal inflammation. [ABSTRACT FROM AUTHOR]