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Background: There has been a significant increase in scientific investigations of the hearing‐dementia association among the research on potentially modifiable risk factors for cognitive impairment. We tested two clinical questions. Analysis 1: does persistent hearing aid (HA) use decrease the decline in cognitive function caused by ageing? Analysis 2: does cognitive function at the time of HA fitting predict future persistent HA use? Methods: This case–control study performed at two referral centres reported data obtained over a 4.5‐year period. We recruited a group of patients with cognitive decline, aged 65 or older with or without hearing loss. The intervention consisted of the use of HAs. The primary outcome measures were adherence to continuous HA use and cognitive function measured using the Japanese version of the Mini‐Mental State Examination Test and the Reading Cognitive Test Kyoto. Results: Eighteen HA users and 18 controls were included in the first analysis. HA use was associated with a deceleration of cognitive decline 12 months later. In the second analysis, 11 participants with good adherence to HA use were compared with 12 participants who showed poor adherence to HA use. Among the variables employed in this study, cognitive function measured using the Reading Cognitive Test Kyoto was significantly lower in participants with poor adherence to HA. Conclusions: HA use in cognitively impaired individuals with hearing loss can slow age‐related cognitive decline. Cognitively impaired people with hearing loss who fail to commit to HA use tend to have lower cognitive measurement scores before HA fitting. HA use is generally more challenging as people age and their cognitive abilities decline. Therefore, it is desirable that HAs be used when hearing loss and dementia are in their early stages. [ABSTRACT FROM AUTHOR]

Aim: The gut microbiota has emerged as a new intervention target for sarcopenia. Prior studies in humans have focused on the association between gut microbiota and skeletal muscle quantity, while the evidence on muscle function and quality is lacking. This study aimed to identify gut microbiota genera associated with skeletal muscle function, quantity, and quality in a general population of Japanese adults. Methods: This cross‐sectional study included 164 participants aged 35–80 years, women and men recruited from urban areas of Japan. Fecal samples were collected and analyzed using 16S rRNA gene amplicon sequencing. Skeletal muscle function was measured using handgrip strength and leg extension power (LEP), while skeletal muscle mass was estimated using bioelectrical impedance analysis. Phase angle was used as a measure of skeletal muscle quality. Multivariate linear regression analysis stratified by age group was used to examine the association between the dominant genera of the gut microbiota and skeletal muscle variables. Results: A significant association was found between Bacteroides and Prevotella 9 with LEP only in the ≥60 years group. When both Bacteroides and Prevotella 9 were included in the same regression model, only Bacteroides remained consistently and significantly associated with LEP. No significant associations were observed between skeletal muscle mass, handgrip strength, and phase angle and major gut microbiota genera. Conclusions: In this study, we observed a significant positive association between Bacteroides and leg muscle function in older adults. Further studies are required to elucidate the underlying mechanisms linking Bacteroides to lower‐extremity muscle function. Geriatr Gerontol Int 2024; 24: 53–60. [ABSTRACT FROM AUTHOR]

Background: Problematic Internet use (PIU) remains a significant social concern in Japan and across the globe. Numerous studies have been conducted to examine the prevalence of PIU, and its association with lifestyle habits and mental health status. To the best of our knowledge, few studies have examined the association between parental attachment and PIU in Japan. Furthermore, preventive measures in Japan have primarily targeted adolescents via education. Therefore, in this study we explored the association between PIU and attachment styles among adolescents to seek a new approach for the development of appropriate, effective measures. Methods: A self‐administered survey was conducted at one private (in 2018) and two public junior high schools (in 2020) in Kagawa Prefecture, western Japan. We used the Internet Addiction Test (IAT), the Experiences in Close Relationships–Relationship Structures (ECR–RS) questionnaire, and the Birleson Depression Self‐Rating Scale for Children (DSRS‐C). Multiple regression analysis was performed to examine the association between IAT scores and attachment styles. Results: Of 1,413 participants (grades 7–9; 700 boys and 713 girls), 39% of the students showed possible PIU and 3% showed PIU. Students with PIU tended to sleep for shorter durations, access the Internet for long hours, and have a poor mental health status (p < 0.01). PIU was significantly associated with insecure attachment (p < 0.0001). Conclusions: The findings of our study imply that improving attachment styles and developing secure attachment between the child and parent might help mitigate and/or prevent PIU. [ABSTRACT FROM AUTHOR]

Aim: This observational study aimed to describe the rate and degree of difficult experiences with COVID‐19 pandemic‐related changes (DE) during pregnancy, clarify the relationship between DE and self‐compassion of women postnatally, and investigate the influence of compassion from a partner (CP) and compassion from the woman's mother (CM) on this relationship. Methods: Data from 46 1‐month postnatal women in Japan were collected through a self‐report questionnaire from October to December 2020. Self‐compassion was measured using the Japanese version of the Self‐Compassion Scale; DE, CP, and CM were measured using original questions based on prior studies. Results: Almost all participants (97.8%) experienced more than one DE during pregnancy. Data analyses revealed that DE in maternity hospitals (d = 0.76), DE in social support (d = 0.53), and CM (d = 0.64) were associated with self‐compassion. A two‐way analysis of variance suggested that CM moderated the relationship between self‐compassion and DE in preparation for the baby (η2 = 0.11) and the birth plan (η2 = 0.11), whereas CP moderated the relationship between self‐compassion and DE in social support (η2 = 0.07). Conclusions: Our findings suggest that self‐compassion negatively correlates with DE in maternity hospitals and social support. Additionally, CM may buffer the influence of DE in preparation for the baby and the birth plan on self‐compassion; moreover, CP may buffer the influence of DE in social support on self‐compassion. This study highlights the importance of supporting perinatal women to adapt to COVID‐19‐related changes through cooperation with their families, which may increase self‐compassion. [ABSTRACT FROM AUTHOR]

Advances in patient care for pressure injuries (PIs) have reduced the prevalence of PIs in Japan, although not in recent years. Several single‐nucleotide polymorphisms (SNPs) have been identified in genes potentially associated with PIs. However, individual variance among PI risks require targeted investigations that may lead to the identification of PI susceptibilities or preventive care options that directly influence PI development pathways. This cross‐sectional study examined the association between PIs and SNPs in genes related to tissue tolerance in patients in a long‐term care hospital in Japan. A total of 178 participants (130 control, 20 with superficial PI history, and 28 with deep PI history) were enrolled in this study of eight SNPs in hypoxia inducible factor 1 subunit alpha (HIF1A), vascular endothelial growth factor C (VEGFC), heat shock protein 90 alpha family class A member 1 (HSP90AA1), myostatin (MSTN), and vitamin D receptor (VDR). The primary outcome was a history of superficial and deep PIs in the last 6 months. SNPs were examined by real‐time polymerase chain reaction, followed by multivariate logistic regression analyses of the associations between the SNPs and PI history. The results showed a significant association between VEGFC rs1485766 and the history of superficial PIs (odds ratio = 2.95; 95% confidence interval = 1.07–8.11; p = 0.04). Stratified analysis using the Braden Scale (≤14) indicated a significant association between HIF1A rs11549465 and deep PIs (p = 0.04). Our study demonstrated that VEGFC rs1485766 and HIF1A rs11549465 were associated with superficial and deep PI susceptibilities, respectively. [ABSTRACT FROM AUTHOR]

Aim: To examine factors of a hypothetical model related to stressors, burnout and turnover in nurses from developed and developing countries—Canada, Japan, the United States, Malaysia and Thailand. Design: A cross‐sectional questionnaire‐based study. Methods: Conducted between April 2016 and October 2017, the Maslach Burnout Inventory, Intention to Leave Scale, and Nursing Stress Scale collected data from acute care hospital nurses in Canada (n = 309), Japan (n = 319), Malaysia (n = 242), Thailand (n = 211) and the United States (n = 194). Results: Compared to other countries, burnout "exhaustion" was the highest in Japan and "cynicism" and intention to leave the job were the highest in Malaysia. Thailand had lower burnouts and turnover than other countries and higher professional efficacy than Japan and Malaysia. In all countries, reducing stressors is important for reducing burnout and intention to leave jobs, especially as they relate to "lack of support." [ABSTRACT FROM AUTHOR]

Aims: To evaluate how a structured interactive two‐day education programme for clinical nurses on end‐of‐life (EOL) care for older people affects nurses' attitudes and knowledge. Design: Non‐randomised controlled trial. Methods: Nurses were recruited separately for intervention and control groups. The intervention group assisted older patients with EOL care and recruited patients for the programme. To prevent sampling bias, control group nurses were recruited from a facility with numerous EOL care opportunities. The intervention was a two‐day educational programme. Using valid and reliable scales, we evaluated the attitudes (total score range: 26–130) and knowledge (total score range: 0–51) of the intervention group four times (pretraining, post‐training, 3 months, 6 months) and the control group three times (baseline, 3 months, 6 months) between January 2016 and April 2017. Analysis of covariance examined both groups' score changes at 3 and 6 months while adjusting for confounding factors. Results: Participants were 338 nurses caring primarily for older people (intervention group: 164; control group: 174); 142 responded at all measurement points. The change in mean value of the attitude scale from baseline to 3 months (differences in the groups' attitude scores = 7.33; 95% CI = 2.43–12.24; p =.004) and 6 months (differences in groups' attitude scores = 5.77; 95% CI = 0.17–11.37; p =.044) was greater in the intervention group. Moreover, the mean knowledge scale score change from baseline to 3 months was greater in the intervention group (differences in groups' knowledge scores = 5.74; 95% CI = 4.07 to 7.39; p <.001). There was no evidence of a change in this score between baseline and 6 months. Conclusion: The programme improved nurses' medium‐ to long‐term attitudes and knowledge. Thus, it may help nurses enhance the quality of care they provide. Implications for practice: A two‐day educational program improves nurses' medium‐ to long‐term attitudes and knowledge on end‐oflife care. For quality end‐of‐life care for older people, a structured and evidence‐based educational program should be provided to nursing staff. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to develop a scale that can comprehensively measure public health nurses'(PHNs) career development and to verify the validity and reliability of that scale. Design and samples: This study is a cross‐sectional investigation. The participants were 1,009 PHNs working in a government facility in Japan. A total of 586 participants who had been working for more than 3 years as PHNs were analyzed. Measurements: Anonymous self‐response questionnaires included items on professional awareness, practical competency, and job satisfaction. We conducted exploratory factor analysis and confirmatory factor analysis to clarify the construct validity of the scale. The reliability was examined by the Cronbach's α coefficient. The validity was examined by an external reference relevant validity and the known‐group method. Results: The scale was structured with 32 items covering three factors: "community activities, policy, and management," "PHN identity," and "foundations as a PHN." The Cronbach's α coefficients were all greater than 0.9. In confirmatory factor analysis, the scale showed acceptable goodness of fit. Conclusions: The comprehensive career development scale for PHNs proved its reliability and validity. This scale may be useful to promote PHN identity and competency comprehensively in basic education and in‐charge education. [ABSTRACT FROM AUTHOR]

Background Thrombocytopenia during intoxication, rebound thrombocytosis during 1 to 3 weeks of abstinence, and subsequent normalization of the platelet count are common in alcoholics. Methods We evaluated 989 Japanese alcoholic men to identify the effects of genetic polymorphisms of alcohol dehydrogenase-1B ( ADH1B; rs1229984) and aldehyde dehydrogenase-2 ( ALDH2; rs671) on platelet counts during an 8-week in-hospital abstinence period. Results Thrombocytopenia (<15 × 104/ μl) was observed in 25.9% of the subjects upon admission. The platelet counts increased from 21.4 ± 0.3 × 104/ μl (mean ± SE) to 27.6 ± 0.3 × 104/ μl, and a rebound platelet increase of ≥10 × 104/ μl was observed in 28.6% of the patients during the first 2 weeks after admission. By 4 weeks, the mean platelet counts had returned to intermediate levels and remained stable thereafter. The reversible suppression and rebound increase in the platelet counts were more prominent in the slow-metabolizing ADH1B*1/*1 group than in the fast-metabolizing ADH1B*2 group. Throughout the 8 weeks, the mean platelet counts of the active ALDH2*1/*1 group were consistently lower than those in the inactive ALDH2*1/*2 group. Cirrhosis was a strong determinant of a lower platelet count. After adjustments for nongenetic factors including cirrhosis, multiple linear regression analyses showed that the ADH1B*1/*1 genotype was associated with a lower platelet count (partial regression coefficient = −1.3 × 104/ μl) on the admission day , but subsequently had a positive effect on the platelet count at 1 and 2 weeks after admission (+1.5 and +3.8 × 104/ μl, respectively). The ALDH2*1/*1 genotype was associated with a lower platelet count (−2.1 to −3.9 × 104/ μl) consistently throughout the 8 weeks. Multiple logistic regression analyses showed that the ADH1B*1/*1 genotype increased the risk of thrombocytopenia upon admission (odds ratio [95% confidence interval] = 1.61 [1.14 to 2.27]) and of a rebound platelet increase during the first 2 weeks (3.86 [2.79 to 5.34]). The ALDH2*1/*1 genotype increased the risk of thrombocytopenia upon admission (1.73 [1.06 to 2.82]). Conclusions In alcoholics, the ADH1B*1/*1 genotype increased the risk of thrombocytopenia upon admission and of a rebound platelet increase 2 weeks thereafter, while the ALDH2*1/*1 genotype was associated with lower platelet counts throughout the 8-week hospital stay. [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 Diabetes is often associated with increased prevalence and severity of periodontal disease. We hypothesized that gingival epithelial cells modify periodontal disease progression and predicted that hyperglycemia would activate an inflammatory response in human gingival epithelial cells ( HGECs). Materials and Methods We tested our hypothesis in immortalized HGECs (epi 4 cells) isolated from periodontal tissue and transfected with the simian virus 40 T antigen. The epi 4 cells were cultured in high (25 mM, HG) and normal (6 mM, NG) glucose conditions. Results The epi 4 cells showed increased interleukin-8 ( IL-8) protein secretion and mRNA expression when cultured in HG, compared with in NG. These effects were not associated with increased cell proliferation and were not observed in a hyperosmolar control group (normal glucose with 19 mM mannitol). Increased IL-8 secretion in HG was inhibited by pretreatment with an antioxidant, N-acetylcysteine, or a protein kinase C inhibitor, Ro31-8220. Hyperglycemia did not affect IL-8 secretion by gingival fibroblasts or periodontal ligament cells. In epi 4 cells, hyperglycemia also induced expression of toll-like receptor 2 ( TLR2) but not TLR4. Conclusion These findings suggest a potential participation of epithelial cells in periodontal disease during diabetes by evoking an excessive host inflammatory response. [ABSTRACT FROM AUTHOR]

The 'Skippu-Mama' peer support program was developed to improve quality of life and reduce parental stress in mothers of children with autism spectrum disorders. The program was designed to improve these variables by refreshing and healing participants' minds and bodies. Twenty-four mothers of 26 children diagnosed with ASD in Japan were included in the study and completed measures of quality of life and parental stress before, during, and after participation in the Skippu-Mama program. Our results demonstrated that time was a significant main effect. Further, multiple comparisons with Bonferroni corrections indicated a significant increase in World Health Organization Quality of Life 26 scores three months into the program and at its conclusion six months after commencement. Overall, the Skippu-Mama program improved the quality of life of mothers of children with ASD, and we believe that the intervention's focus on both individual and family variables may be especially effective in this population. [ABSTRACT FROM AUTHOR]

While more women with breast cancer survive because of advances in cancer treatment including hormonal therapy, they are at a risk of menopausal symptoms, which can threaten their psychological wellbeing. We examined the effect of menopausal symptoms on women's psychological wellbeing during three different phases of breast cancer: short-term (0-1 years since diagnosis), medium-term (2-5 years), and long-term (more than 5 years). In this cross-sectional study, 425 survivors treated with hormonal therapy were recruited from a convenience sample in Japan and completed an anonymous self-administered questionnaire. Multiple regression analysis revealed that menopausal symptoms significantly contributed to psychological wellbeing in all phases. In long-term survivors, menopausal symptoms were significantly milder; however, the negative effect was prolonged. One in three to four survivors was suspected to have poor psychological wellbeing, irrespective of time. Although the effect of menopausal symptoms on psychological wellbeing has been described in short-term survivors, little is known about the long-term effect. This study examines the effect of menopausal symptoms on psychological wellbeing, thereby providing useful information regarding long-term quality of life. [ABSTRACT FROM AUTHOR]

Background Infant flow biphasic nasal continuous positive airway pressure (Bi-NCPAP) and regular NCPAP (Re-NCPAP) are equally useful with respect to the rate of successful weaning from mechanical ventilation. It remains unclear, however, whether Bi-NCPAP or Re-NCPAP is more effective for reducing apnea of prematurity (AOP). Methods A multicenter randomized controlled study was conducted of 66 infants assigned to receive Bi-NCPAP and 66 assigned to receive Re-NCPAP for respiratory support after extubation. Primary outcome was the number of AOP events during the 48 h observation period after successful extubation, defined as no reintubation and no adverse events associated with the use of NCPAP during the observation period. The secondary outcome was successful extubation. Reintubation was at the discretion of the attending physician. Results Baseline characteristics were similar between the two groups. The number of AOP events during the 48 h observation period was significantly lower in infants with Bi-NCPAP than in those with Re-NCPAP (5.2 ± 6.5 vs 10.3 ± 10.9 per infant, respectively; P = 0.002). The rate of successful extubation tended to be greater in those with Bi-NCPAP than in those with Re-NCPAP (92.4%, 61/66 vs 80.3%, 53/66, respectively; P = 0.074). Adverse events occurred in only one of 132 infants: erosive dermatitis developed on the nose after application of Re-NCPAP. The risk of reintubation did not differ significantly between the two groups (7.6%, 5/66 for Bi-NCPAP vs 18.2%, 12/66 for Re-NCPAP; P = 0.117). Conclusions Bi-NCPAP was superior to Re-NCPAP for reduction of AOP following extubation. [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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Background The domesticated legume, Canavalia gladiata (commonly called the sword bean), is known to contain canavanine. The fruit is used in Chinese and Japanese herbal medicine for treating the discharge of pus, but its pharmacological mechanisms are still unclear. Objectives This study examined the effect of sword bean extract ( SBE) on (i) oral bacteria and human oral epithelial cells in vitro, and (ii) the initiation and progression of experimental Porphyromonas gingivalis-induced alveolar bone resorption in rats. Material and Methods A high-performance liquid chromatography/ ultraviolet method was applied to quantitate canavanine in SBE. By assessing oral bacterial growth, we estimated the minimum inhibitory concentration and minimum bactericidal concentration of SBE, canavanine, chlorhexidine gluconate ( CHX) solution. The cytotoxicity of SBE, canavanine, CHX, leupeptin and cystatin for KB cells was determined using a trypan blue assay. The effects of SBE, canavanine, leupeptin and cystatin on Arg-gingipain (Rgp) and Lys-gingipain (Kgp) were evaluated by colorimetric assay using synthetic substrates. To examine its effects on P. gingivalis-associated periodontal tissue breakdown, SBE was orally administered to P. gingivalis-infected rats. Result Sword bean extract contained 6.4% canavanine. SBE and canavanine inhibited the growth of P. gingivalis and Fusobacterium nucleatum. The cytotoxicity of SBE, canavanine and cystatin on KB cells was significantly lower than that of CHX. Inhibition of Rgp with SBE was comparable to that with leupeptin, a known Rgp inhibitor, and inhibition of Kgp with SBE was significantly higher than that with leupeptin at 500 μg/ mL ( p < 0.05). P. gingivalis-induced alveolar bone resorption was significantly suppressed by administration of SBE, with bone levels remaining comparable to non-infected animals ( p < 0.05). Conclusion The present study suggests that SBE might be effective against P. gingivalis-associated alveolar bone resorption. [ABSTRACT FROM AUTHOR]

Background and Objective Keratinization of the oral mucosa, such as the gingiva, has been shown to be important for periodontal health. Caspase-14 is a protease that plays a role in keratinization of the epidermis. The objective of this study was to investigate whether the expression of caspase-14 is intimately linked with keratinization and to examine the effect of the main component of green tea on the improvement of keratinization in rat oral mucosal preparations. Material and Methods Histological and immunohistochemical analyses and quantitative mRNA measurements of caspase-14 and its substrate filaggrin were performed using different types of rat epithelial tissue and organotypic reconstruction culture models derived from epithelial cells and fibroblasts taken from the rat oral mucosa. Results In the skin, palate, buccal mucosa and esophagus, the degree of keratinization appeared to be associated with expression of cytokeratin 10. The relative protein and mRNA expression levels of caspase-14 and filaggrin were consistent with the degree of keratinization in the following order: skin > palate > buccal mucosa > esophagus. The culture models of palatal and buccal mucosa retained a stratified epithelial structure. Expression of caspase-14 appeared to be stronger in the palatal model than in the buccal model. Remarkably, epigallocatechin-3-gallate (EGCG) improved the localization of cytokeratins and increased the expression of caspase-14 and filaggrin. This expression was more intense in the palatal model than in the buccal model, indicating that both models maintain the intrinsic properties of keratinization of the mucosa from where the cultured cells were derived. Conclusions These results suggest that keratinization is closely associated with expression of caspase-14 and filaggrin. Our reconstruction models are promising tools for drug evaluation and show that EGCG is beneficial for improving both keratinization and expression of the linked protease in the oral mucosa. [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]

Background and Objective Antibiotics at below minimal inhibitory concentrations ( MICs) may induce various biological responses in bacteria. In this study, we hypothesized that subinhibitory concentrations (sub ICs) of tetracycline and doxycycline induce the shedding of lipopolysaccharide ( LPS) by Porphyromonas gingivalis and, as a consequence, may contribute to enhancing the host inflammatory response associated with periodontitis. Material and Methods A polymyxin-based enzyme-linked immunosorbent assay was used to quantify LPS shedding by P. gingivalis grown in the presence of sub ICs of tetracycline and doxycycline. A macrophage model was used to show that tetracycline- and doxycycline-mediated LPS shedding by P. gingivalis can induce cytokine secretion. The secretion of interleukin (IL)-1β, IL-8, and tumor necrosis factor-α was quantified by enzyme-linked immunosorbent assay. Results LPS was shed spontaneously in a time-dependent way by P. gingivalis during growth. LPS shedding was significantly increased by growth in the presence of subICs of tetracycline and doxycycline corresponding to 1/20 of their MICs (0.025 μg/mL for tetracycline and 0.0125 μg/mL for doxycycline). This shedding was not associated with an increased rate of bacterial cell lysis. Stimulating macrophages with a P. gingivalis culture supernatant induced the secretion of IL-1β, IL-8 and tumor necrosis factor-α when the bacteria were grown in the presence of 1/20 MIC of the antibiotics. Conclusion Our study showed that growing P. gingivalis in the presence of sub ICs of either tetracycline or doxycycline induces LPS shedding. Shed LPS may in turn increase cytokine secretion in a macrophage model. [ABSTRACT FROM AUTHOR]

Aim Falling is the leading cause of injury-related deaths in older adults, and a loss of balance is often the precursor to a fall. However, little is known about the rate at which balance declines with age. The objective of the present study was to determine whether there is an age-associated decline in static ( SB) and/or dynamic ( DB) balance in community-dwelling older women. Method SB and DB were determined in 971 older women. Intraclass correlation coefficients ( ICC) were used to determine test-retest reliability. Sway velocity was used to measure SB standing on a platform and foam with eyes open and closed. DB was characterized by limits of stability ( LOS) that measured end-point excursion ( EXE) and maximum excursion ( MXE) of the body's center of pressure. Results ICC for EXE and MXE for the LOS test were excellent ( EPE = 0.96, MXE = 0.96). ICC for SB tests, except for the eyes open firm surface condition ( ICC = 0.10), showed a high level of reproducibility ( ICC = 0.88 and 0.90). Relationships existed between age and SB ( r = 0.31, P < 0.001), and between age and DB ( r = −0.46-−0.48, P < 0.001). The rate of decline for both DB and SB was approximately 1% per year. Age was significantly associated with all balance measures. DB got significantly lower with advancing age until 80 years, and then plateaued. SB did not decline with age until 80 years, and then decreased significantly thereafter. Conclusion Although large individual variation was found with balance ability, an age-related decline was found with both dynamic and static balance for Japanese older women. Geriatr Gerontol Int 2014; 14: 556-560. [ABSTRACT FROM AUTHOR]

This study aimed to develop a reliable and valid measure of functional health literacy in a Japanese clinical setting. Test development consisted of three phases: generation of an item pool, consultation with experts to assess content validity, and comparison with external criteria (the Japanese Health Knowledge Test) to assess criterion validity. A trial version of the test was administered to 535 Japanese outpatients. Internal consistency reliability, calculated by Cronbach's alpha, was 0.81, and concurrent validity was moderate. Receiver Operating Characteristics and Item Response Theory were used to classify patients as having adequate, marginal, or inadequate functional health literacy. Both inadequate and marginal functional health literacy were associated with older age, lower income, lower educational attainment, and poor health knowledge. The time required to complete the test was 10-15 min. This test should enable health workers to better identify patients with inadequate health literacy. [ABSTRACT FROM AUTHOR]

Background Frequency of alcohol drinking is known to influence cardiovascular risk. However, little is known regarding the relationship between frequency of drinking and metabolic syndrome (MetS). The aim of this study was to determine how frequency of heavy drinking modifies the prevalence of MetS. Methods The subjects were middle-aged male nondrinkers and occasional or regular heavy drinkers (ethanol intake: ≥66 g per drinking day). Odds ratios ( ORs) for MetS and each component comprising MetS were calculated with adjustment for age and histories of smoking and regular exercise. Results ORs versus nondrinkers for MetS defined by the criteria of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) or the International Diabetes Federation ( IDF) were significantly higher than the reference level of 1.00 in occasional heavy drinkers ( NCEP- ATP III, 1.94 [confidence interval (CI): 1.54 to 2.45]; IDF, 1.97 [ CI: 1.56 to 2.49]) and regular heavy drinkers ( NCEP- ATP III, 1.48 [ CI: 1.19 to 1.84]; IDF, 1.50 [ CI: 1.20 to 1.86]). When compared with the reference level, OR versus nondrinkers for large waist circumference was significantly higher in occasional heavy drinkers (1.96 [ CI: 1.63 to 2.35]), but not in regular heavy drinkers (1.12 [ CI: 0.96 to 1.32]), while OR versus nondrinkers for hyperglycemia was significantly lower in regular heavy drinkers (0.66 [ CI: 0.46 to 0.95]), but not in occasional heavy drinkers (0.86 [ CI: 0.60 to 1.24]). Conclusions There is a positive association between heavy drinking and MetS, which is stronger in occasional drinkers than in regular drinkers. This difference may be explained by a positive association between occasional heavy drinking and central obesity and an inverse association between regular heavy drinking and hyperglycemia. The results suggest that heavy drinking, even if occasionally, is a cardiovascular risk factor. [ABSTRACT FROM AUTHOR]

Background Adiponectin secreted from adipose tissue is assumed to mediate protective effects on development of metabolic syndrome (MetS) and MetS-related diseases such as cardiovascular diseases and cancer. Relationship between alcohol intake and circulating adiponectin levels is not consistent among the several previous studies. In the present study, we investigated effects of alcohol intake and the alcohol-related polymorphisms on serum adiponectin levels among Japanese male workers. Methods We conducted a cross-sectional design study with 541 male workers aged 51.5 ± 5.9 (mean ± SD) years in a Japanese plant. Information on alcohol intake and other lifestyles was obtained by a self-administered questionnaire. Serum total adiponectin (T-Ad), high-molecular-weight adiponectin ( HMW-Ad), medium-molecular-weight adiponectin ( MMW-Ad), and low-molecular-weight adiponectin ( LMW-Ad) levels were measured by the enzyme-linked immune assay system kit. Two genotypes in the alcohol dehydrogenase-1B ( ADH1B) and aldehyde dehydrogenase-2 ( ALDH2) genes were determined using blood sample. In multivariate regression analyses, we adjusted for age, body mass index, smoking, and physical exercise. Results Among all subjects, high alcohol consumption of 12 units (1 unit contains 22.9 g of ethanol) a week or more was negatively associated with T-Ad levels in the multivariate model, although not significant. When we performed analyses separately for each genotype, high alcohol consumption was negatively associated with T-Ad, HMW-Ad, and LMW-Ad levels only in those with ADH1B *2/*2. Such relationships were not observed in each ALDH2 genotype group. Conclusions High alcohol consumption was inversely associated with T-Ad, HMW-Ad, and LMW-Ad levels in those with ADH1B *2/*2 genotype, but not in those with the other ADH1B genotypes. To our knowledge, this is the first study that reports combined effects of the alcohol-related polymorphisms and alcohol intake on serum adiponectin levels. Additional studies are required to confirm the present finding. [ABSTRACT FROM AUTHOR]

Background and Objective The transplantation of cell sheets of mesenchymal stem cells ( MSCs) is expected to be the next generation of periodontal regenerative therapy. An adequate method of multilayering MSCs has yet to be established. When cell sheets proliferate, they usually contract and detach from culture dishes and then the proliferation of cells in the contracted areas is arrested. ROCK-mediated contractile force causes cell contraction. Although multilayer formation medium ( MFM) stimulated the proliferation of growth-arrested confluent MSCs, MSCs detached from the culture dish. Therefore, we investigated the effects of ROCK inhibitor Y-27632 on the proliferation and detachment of confluent MSCs, and examined the ability of cells to differentiate within the cell sheets. Material and Methods Confluent MSCs were cultured in MFM containing transforming growth factor-β1, ascorbic acid and fetal bovine serum either with or without Y-27632. Cell proliferation was examined by bromodeoxyuridine incorporation assays and total DNA measurement. Sheet contractions were examined by light microscopy and stereomicroscopy. Multilayer formations and focal adhesion assembly were observed with confocal microscopy. Characteristic of cells were examined by flow cytometric analysis. Osteoblast lineage differentiation was observed with alkaline phosphatase and alizarin red S staining. Adipocyte lineage differentiation was observed with oil red O staining. Results The addition of Y-27632 to MFM prevented the cell sheets from detaching and did not inhibit MSC growth. The cell numbers cultured with MFM/ Y-27632 were significantly higher than that obtained with MFM-only on day 4. Cell sheets detached from the culture dish on day 4, and the number of bromodeoxyuridine-positive cells in the detached area decreased. Cells in the cell sheets had similar characteristics to primary MSCs, and differentiated into osteoblast and adipocyte lineages. Conclusion Y-27632 both prevented the MSC sheets from detaching and maintained the multilayered proliferation of confluent MSCs by MFM, and then cells in the sheets had differentiation potency. [ABSTRACT FROM AUTHOR]

Background and Objective T-helper type 17 ( Th17) cells produce interleukin-17 ( IL-17) and help to protect against inflammation and infection in periodontal disease. Furthermore, while follicular dendritic cell-secreted protein ( FDC- SP) may be involved in the inflammation of periodontal tissue, the biological role of FDP- SP in periodontal disease is still unknown. The purpose of the present study was to clarify the expression of IL-17 and FDC- SP in experimental periodontitis in rats. Material and Methods Seven-week-old male Wistar rats were divided into baseline control, sham and test groups. Experimental periodontitis was induced by placing a ligature in the mesiopalatal area, and untreated rats served as a baseline control group. Morphological changes in alveolar bone were investigated 7, 14 and 28 d after treatment. Expression of the Rankl, osteoprotegerin ( Opg) and Il17 genes was analyzed 5 and 7 d after the induction of experimental periodontitis. Results Alveolar bone resorption progressed in the test group for 7 d, but not thereafter. At 5 d after the induction of periodontitis, the Rankl/ Opg mRNA ratio and the expression of IL-17 in the test group were significantly increased compared with the respective values in the baseline control group; however, there were no significant differences between the test and control groups at 7 d. The expression of FDC- SP was significantly decreased in the test group compared with the baseline control group at 5 and 7 d after the induction of periodontitis, and this value had returned to normal levels at 14 and 28 d. Conclusion These results suggest that both IL-17 and FDC- SP could be involved in the inflammatory response, and FDC- SP in the junctional epithelium might play an important role in the Th17 cell-related immune response. [ABSTRACT FROM AUTHOR]

Background and Objective Occlusal trauma is an important factor that influences the progression of periodontitis, but it is unclear whether occlusal trauma influences periodontal destruction at the onset of periodontitis. We established an experimental periodontitis model with both site-specific loss of attachment and alveolar bone resorption. The purpose of the present study was to investigate the effects of occlusal trauma on periodontal destruction, particularly loss of attachment, at the onset of experimental periodontitis. Material and Methods Sixty rats were used in the present study. Forty-eight rats immunized with lipopolysaccharide ( LPS) intraperitoneally were divided into four groups. In the trauma ( T) group, occlusal trauma was induced by placing an excessively high metal wire in the occlusal surface of the mandibular right first molar. In the inflammation ( I) group, periodontal inflammation was induced by topical application of LPS into the palatal gingival sulcus of maxillary right first molars. In the trauma + inflammation ( T+ I) group, both trauma and periodontal inflammation were simultaneously induced. The PBS group was administered phosphate-buffered saline only. Another 12 nonimmunized rats (the n−( T+ I) group) were treated as described for the T+ I group. All rats were killed after 5 or 10 d, and their maxillary first molars with surrounding tissues were observed histopathologically. Loss of attachment and osteoclasts on the alveolar bone crest were investigated histopathologically. To detect immune complexes, immunohistological staining for C1q B was performed. Collagen fibers were also observed using the picrosirius red-polarization method. Results There were significant increases in loss of attachment and in the number of osteoclasts in the T+ I group compared with the other groups. Moreover, widespread distribution of immune complexes was observed in the T + I group, and collagen fibers oriented from the root surface to the alveolar bone crest had partially disappeared in the T, T+ I and n−( T+ I) groups. Conclusion When inflammation was combined with occlusal trauma, immune complexes were confirmed in more expanding areas than in the area of the I group without occlusal trauma, and loss of attachment at the onset of experimental periodontitis was increased. Damage of collagen fibers by occlusal trauma may elevate the permeability of the antigen through the tissue and result in expansion of the area of immune-complex formation and accelerating inflammatory reaction. The periodontal tissue destruction was thus greater in the T+ I group than in the I group. [ABSTRACT FROM AUTHOR]

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]

Aim Nursing and healthcare-associated pneumonia ( NHCAP) is a modified category of healthcare-associated pneumonia adjusted for the healthcare system of Japan. The clinical characteristics and risk factors for mortality have not been well characterized in elderly patients with NHCAP. Methods We retrospectively investigated 960 consecutive patients aged ≥65 years admitted for pneumonia. Baseline characteristics, severity, pathogen distribution, outcomes and risk factors for mortality were compared between patients with community-acquired pneumonia ( CAP) and those with NHCAP. The applicability of age, dehydration, respiratory failure, orientation disturbance, and low BP (A-DROP) score, a standard severity index for CAP in Japan, was also evaluated in NHCAP. Results The study participants consisted of 373 patients (38.8%) with CAP and 587 (61.2%) with NHCAP. The patients with NHCAP were older and had poorer performance status ( PS) and more comorbidities than those with CAP. The frequency of potentially drug-resistant ( PDR) pathogens and in-hospital mortality were found in 10 (2.7%) and 17 patients (4.6%) with CAP, and 60 (10.2%) and 83 patients (14.1%) with NHCAP, respectively ( P < 0.0001). The incidences of PDR pathogens and mortality were not significantly different among the criteria for NHCAP. The higher mortality was associated with PS, comorbidity with Charlson Comorbidity Index ≥3, and the coexistence of congestive heart failure, chronic kidney disease and malignancy. A-DROP score was poor at predicting mortality in most patients with NHCAP. Conclusion The current criteria for NHCAP seem to be appropriate for differentiating patients with poor outcomes from community-acquired pneumonia patients. It is essential to assess individual underlying conditions, such as PS and comorbidity, when caring for patients with NHCAP. Geriatr Gerontol Int 2013; 14: 362-371. [ABSTRACT FROM AUTHOR]

Aim To evaluate the effectiveness of a strength and balance enhancing exercise intervention as a means of preventing falls in community-dwelling elderly Japanese women with a history of falls, while comparing functional fitness, fall and fracture rate in excluded subjects. Methods A 1-year follow-up trial was carried out on 105 participants over the age of 70 years, who were randomly assigned to the exercise or education group, and also on 91 women excluded based on the exclusion criteria. The exercise group attended a 60-min exercise class twice a week for 3 months. Falls, injuries, fractures, and functional fitness assessments were measured at baseline, post-intervention and 1-year follow up. Results During the follow up, fall rates were 19.6% in the exercise group, 40.4% in the education group and 40.8% in excluded subjects (χ2 = 7.069, P = 0.029). Compared with the exercise group, the odds ratio ( OR) for falls was greater in the education group ( OR 2.78, 95% confidence interval ( CI) 1.17-6.96) and excluded participants ( OR 2.83, 95% CI 1.25-6.80). The OR for fractures was over fourfold greater in excluded participants (OR 4.30, 95% CI 1.02-9.70) than the exercise group. Conclusions The exercise intervention for participants with fall history effectively decreased incidences of falls and fractures. However, fall and fracture rates in excluded people were high. Further research focusing on feasible countermeasures for falls in excluded people who are at high risk of fractures is required. Geriatr Gerontol Int 2013; 14: 285-292. [ABSTRACT FROM AUTHOR]

Aims Our objective was to evaluate the level of pregnant women's exposure to tobacco smoke by urinary cotinine testing at prenatal examinations, and to examine the effects of disclosing the results of urinary cotinine tests to pregnant women and their families on their smoking activities. Methods A prospective cohort study was conducted, enrolling 420 pregnant women who attended prenatal examinations at five private clinics in Japan. Urinary cotinine testing and a questionnaire survey regarding smoking status were conducted in early, middle, and late pregnancy. Urinary cotinine values were measured semiquantitatively using NicCheck I test strips. The results of each urinary cotinine test were handed to the pregnant woman and shared with her family. Results The percentages of urinary cotinine-positive subjects in middle and late pregnancy were significantly decreased compared with early pregnancy ( P < 0.001 each). Among the active smokers, there were no significant differences in the urinary cotinine-positive rates and the numbers of cigarettes among the three stages. In contrast, the urinary cotinine-positive rates in the passive smokers in late pregnancy were significantly lower than in early pregnancy ( P = 0.045) and those in non-smokers in middle and late pregnancy were also lower than in early pregnancy ( P = 0.001, P < 0.001). The numbers of cigarettes smoked by persons close to the passive smokers in middle and late pregnancy were significantly lower than in early pregnancy ( P < 0.001). Conclusions The feedback of the urinary cotinine test results at prenatal examinations decreased the level of exposure of pregnant passive smokers and non-smokers to tobacco smoke. [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]

ABSTRACT Objective We examined the existence of nonfat-phobic anorexia nervosa (NFP-AN) and fat-phobic AN, with no evidence of distortions related to body shape and weight (AN-NED), in a Japanese sample and studied eating disorder pathology and psychopathology in NFP-AN and AN-NED. Method The study participants were 200 (52.2%) women with typical AN, 86 (22.5%) women with NFP-AN, and 97 (25.3%) women with AN-NED. Diagnosis of the three types of AN was made by structured clinical interviews. The Eating Attitudes Test (EAT) and the Eating Disorder Inventory (EDI) were administered to all the participants. Results There were significant differences among the three groups in terms of duration of illness, maximum and minimum BMIs and AN subtypes. There was no transition from the NFP-AN and AN-NED groups to the typical AN group during the 2- to 7-year follow-up period. There were significant differences among the three groups in scores of the EAT, the EDI total, and all the subscales of the EDI. Discussion Besides typical AN, there were two types of atypical AN in terms of fat phobia and body image disturbance in this Japanese sample. The findings of the current study suggest that there may be significant differences among the three groups in terms of eating disorder pathology and psychopathology. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:130-137) [ABSTRACT FROM AUTHOR]