Combined effect of anti-high-mobility group box-1 monoclonal antibody and peramivir against influenza A virus-induced pneumonia in mice.

Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post-infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti-HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti-HMGB1 with conventional anti-influenza therapy might be useful against severe influenza virus infection.

[Prognostic significance of chimeric fusion gene analysis in pediatric acute megakaryoblastic leukemia].

Acute megakaryoblastic leukemia in children without Down syndrome (non-DS AMKL) is considered to be a poor prognostic subtype in acute myeloid leukemia. Recently, some chimeric fusion genes were found in pediatric non-DS AMKL; therefore, we attempted to detect chimeric fusion genes RBM15-MKL1, CBFA2T3-GLIS2, and NUP98-KDM5A from 10 pediatric non-DS AMKL diagnostic samples using polymerase chain reaction and Sanger sequencing methods. Two samples were positive for RBM15-MKL1, four had CBFA2T3-GLIS2, and only one case had NUP98-KDM5A. Both RBM15-MKL1-positive patients showed long-term remission after chemotherapy. The eight RBM15-MKL1-negative patients received hematopoietic stem cell transplantation (HSCT). In four CBFA2T3-GLIS2-positive patients, three had HSCT without complete remission and two of themdied. Additional treatment stratification depending on chimeric fusion genes and development of new therapeutic drugs are required for non-DS AMKL.

Anti-high mobility group box-1 monoclonal antibody treatment of brain edema induced by influenza infection and lipopolysaccharide.

Encephalopathy is a major cause of influenza-associated child death and severe neurological sequelae in Japan, highlighting the urgent need for new therapeutic strategies. In this study, we evaluated the effects of anti-high mobility group box-1 monoclonal antibody (α-HMGB1) treatment on brain edema induced by influenza A virus (IAV) and lipopolysaccharide in 4-week-old BALB/c female mice. The results showed that administration of 7.5 mg/kg α-HMGB1 1 h after IAV (A/Puerto Rico/8/34) inoculation significantly alleviated brain edema at 48 h after IAV inoculation, as confirmed by the suppression of Evans Blue dye leakage and matrix metallopeptidase-9 mRNA expression in the brain. Moreover, we also observed suppression of oxidative stress and different cytokines in IAV-inoculated mice. The expression of plasminogen activator inhibitor-1 was also attenuated following treatment with α-HMGB1. Notably, α-HMGB1 treatment had no effect on virus propagation in the lung. In summary, anti-HMGB1 treatment may improve the prognosis in cases with influenza-associated encephalopathy by attenuating brain edema and reducing the inflammatory responses induced by HMGB1.

Bidet toilet seats with warm-water tanks: residual chlorine, microbial community, and structural analyses.

Despite the reported health-related advantages of the use of warm water in bidets, there are health-related disadvantages associated with the use of these toilet seats, and the bacterial research is sparse. We conducted a survey on the hygienic conditions of 127 warm-water bidet toilet seats in restrooms on a university campus. The spray water from the toilet seats had less residual chlorine than their tap water sources. However, the total viable microbial count was below the water-quality standard for tap water. In addition, the heat of the toilet seats' warm-water tanks caused heterotrophic bacteria in the source tap water to proliferate inside the nozzle pipes and the warm-water tanks. Escherichia coli was detected on the spray nozzles of about 5% of the toilet seats, indicating that the self-cleaning mechanism of the spray nozzles was largely functioning properly. However, Pseudomonas aeruginosa was detected on about 2% of the toilet seats. P. aeruginosa was found to remain for long durations in biofilms that formed inside warm-water tanks. Infection-prevention measures aimed at P. aeruginosa should receive full consideration when managing warm-water bidet toilet seats in hospitals in order to prevent opportunistic infections in intensive care units, hematology wards, and other hospital locations.

Transient myeloproliferative disorder with partial trisomy 21.

Myeloid malignancy with Down syndrome (ML-DS) is estimated to have a step-wise leukemogenesis including GATA1 mutation. Trisomy 21 is essential for ML-DS; however, we do not know exactly which gene or genes located on chromosome 21 are necessary for the ML-DS. We report a female infant with transient myeloproliferative disorder (TMD) and partial trisomy 21. SNP array analysis showed 10 Mb amplification of 21q22.12-21q22.3, which included DYRK1A, ERG, and ETS but not the RUNX1 gene. With two other reported TMD cases having partial trisomy 21, DYRK1A, ERG, and ETS were the most likely genes involved in collaboration with the GATA1 mutation.

Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice.

INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.

Inhibitory Effects of Edaravone, a Free Radical Scavenger, on Cytokine-induced Hyperpermeability of Human Pulmonary Microvascular Endothelial Cells:A Comparison with Dexamethasone and Nitric Oxide Synthase Inhibitor.

Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α＋IL-1ß markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS.

Detection of RBM15-MKL1 fusion was useful for diagnosis and monitoring of minimal residual disease in infant acute megakaryoblastic leukemia.

Acute megakaryocytic leukemia (AMKL) with t(1;22)(p13;q13) is a distinct category of myeloid leukemia by WHO classification and mainly reported in infants and young children. Accurate diagnosis of this type of AMKL can be difficult, because a subset of patients have a bone marrow (BM) blast percentage of less than 20% due to BM fibrosis. Therefore, it is possible that past studies have underestimated this type of AMKL. We present here the case of a 4-month-old female AMKL patient who was diagnosed by presence of the RBM15-MKL1 (OTT-MAL) fusion transcript by RT-PCR. In addition, we monitored RBM15-MKL1 fusion at several time points as a marker of minimal residual disease (MRD), and found that it was continuously negative after the first induction chemotherapy even by nested RT-PCR. Detection of the RBM15-MKL1 fusion transcript thus seems to be useful for accurate diagnosis of AMKL with t(1;22)(p13;q13). We recommend that the RBM15-MKL1 fusion transcript be analyzed for all suspected AMKL in infants and young children. Furthermore, monitoring of MRD using this fusion transcript would be useful in treatment of AMKL with t(1;22)(p13;q13).

Redox-active protein thioredoxin-1 administration ameliorates influenza A virus (H1N1)-induced acute lung injury in mice.

OBJECTIVES: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice. DESIGN: Prospective animal trial. SETTING: Research laboratory. SUBJECTS: Nine-week-old male C57BL/6 mice inoculated with H1N1. INTERVENTION: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days -1, 1, and 3. MEASUREMENTS AND MAIN RESULTS: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice. CONCLUSIONS: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans.

Higher serum dehydroepiandrosterone sulfate levels are protectively associated with depressive symptoms in men, but not in women: a community-based cohort study of older Japanese.

OBJECTIVE: Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but evidence from prospective cohort studies is sparse. Therefore, we examined the association between serum DHEAS levels and depressive symptoms in older community-dwelling Japanese. DESIGN: A community-based cohort study. SETTING: Kurabuchi Town, Gunma Prefecture, Japan. PARTICIPANTS: A total of 554 residents (248 men and 306 women) age 65 years or older without depressive symptoms at baseline. MEASUREMENTS: We performed a baseline examination of the subjects between 2005 and 2006 to determine serum DHEAS levels. The subjects were categorized into three groups based on age strata- and sex-specific tertiles of DHEAS. Depressive symptoms were assessed with the Geriatric Depression Scale 15-item version (GDS-15) in face-to-face home visit interviews carried out once in 2007 and once in 2008. The association of DHEAS with depressive symptoms (GDS-15 ≥ 6) was analyzed with the use of logistic regression models. RESULTS: The incidence of depressive symptoms was 12.1% in men and 19.6% in women. In men, the multiadjusted odds ratio of depressive symptoms was 0.24 (95% confidence interval: 0.06-0.94, Wald χ2 = 4.20, degrees of freedom = 1, p = 0.04) for the highest tertile compared with the lowest. The association observed for the highest versus the lowest remained significant even after adjustment for physical performance and cognitive function. In women, DHEAS was not associated with depressive symptoms. CONCLUSIONS: In this study, higher serum DHEAS levels were found to be protectively and independently associated with the risk of developing depressive symptoms in men, but not in women.

Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy.

BACKGROUND: Acute encephalitis/encephalopathy (AEE) is a devastating cause of severe neurodevelopmental sequelae or death in children. Assessing ongoing brain injury and predicting outcomes using bedside point-of-care testing is expected to be extremely valuable. METHODS: For this study, three brain injury markers, S-100B, glial fibrillary acidic protein (GFAP), and tau protein, were measured in early cerebrospinal fluid samples of children with AEE. Subjects comprised three groups: Group 1 (non-AEE control, n = 27); Group 2 (AEE with normal resolution or mild sequelae, n = 13); and Group 3 (AEE with severe sequelae or death, i.e. "poor outcome," n = 10). RESULTS: All marker levels were significantly higher in Group 3 than in Group 1 or 2. In Group 3, only S-100B was significantly higher in non-survivors than in survivors. For scoring assessment (range: 0-3 points), the predictive accuracies of 3 points for poor outcomes in children with AEE (i.e. Group 2 and 3, n = 23) were 91% (21/23) for S-100B, 74% (17/23) for GFAP, and 78% (18/23) for tau. When the scores were summed up for S-100B, GFAP, and tau (range: 0-9 points), and for S-100B and tau (range: 0-6 points), the patients with poor outcomes were identified more accurately using the respective thresholds of 6 points and 4 points (96% [22/23] and 100% [23/23], respectively). CONCLUSION: Our findings suggest that combined measurement and scoring assessment of the markers, especially S-100B and tau, show promise as predictors of clinical outcomes in children with AEE.

Thioredoxin-1 and oxidative stress status in pregnant women at early third trimester of pregnancy: relation to maternal and neonatal characteristics.

This study examined the clinical and biological importance of thioredoxin-1, a redox-active defensive protein that controls multiple biological functions, in pregnant women. We measured serum concentrations of thioredoxin-1, total hydroperoxides, and redox potential in 60 pregnant women at the early third trimester: gestational age of 27-29 weeks. The thioredoxin-1 concentration (mean ± SD) was 90 ± 42 ng/ml. Total hydroperoxides was 471 ± 105 U.CARR (1 U.CARR = 0.08 mg/dl H(2)O(2)). Redox potential was 2142 ± 273 µmol/l. The total hydroperoxides: redox potential ratio (oxidative stress index) was 0.23 ± 0.08. Thioredoxin-1, total hydroperoxides, and oxidative stress index were higher and redox potential was lower than in blood of healthy adults. Total hydroperoxides and redox potential were mutually correlated significantly and negatively. Thioredoxin-1 correlated significantly and negatively and redox potential correlated significantly and positively with body weight and body mass index. Thioredoxin-1 and redox potential correlated significantly and positively with uric acid and albumin, respectively. Thioredoxin-1 and oxidative stress index correlated significantly and negatively and redox potential significantly and positively with neonatal birth weight. These results suggest that high concentrations of thioredoxin-1 are linked to high oxidative stress status in pregnant women and that neonatal birth weight is affected by the maternal oxidative condition during later pregnancy.

Prevalence and risk factors of dry eye disease in Japan: Koumi study.

OBJECTIVE: To estimate the prevalence and risk factors of dry eye disease (DED) in a rural setting in Japan. DESIGN: Cross-sectional study. PARTICIPANTS: We included 3294 subjects, aged ≥ 40 years who were in the residential registry for Koumi town. INTERVENTION: Subjects in a rural mountain area, Koumi town, completed questionnaires designed to detect dry eye diagnosis and risk factors. MAIN OUTCOME MEASURES: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by ophthalmologists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, gender, educational history, smoking history, alcohol drinking history, height and weight, visual display terminal (VDT) use, and contact lens (CL) wear, and past/current history of certain common systemic diseases were the main outcome measures. We used logistic regression analysis to examine associations between DED and other demographic factors. RESULTS: Of the 3294 eligible residents, 2791 residents (85%) completed the questionnaire. The percentage of women with a composite outcome of clinically diagnosed DED or severe symptoms (21.6%; 95% confidence interval [CI], 19.5-23.9) was higher than that of men (12.5%; 95% CI, 10.7-14.5; P<0.001). A low body mass index (BMI; odds ratio [OR], 2.07; 95% CI, 0.98-4.39), CL use (OR, 3.84; 95% CI, 1.46-10.10), and hypertension (HT) (OR, 1.39; 95% CI, 0.94-2.06) were risk factors for DED in men. Use of a VDT (OR, 2.33; 95% CI, 1.12-4.85), CL use (OR, 3.61; 95% CI, 2.13-6.10), and myocardial infarction or angina were the risk factors (OR, 2.64; 95% CI, 1.51-4.62), whereas high BMI was a preventive factor (OR, 0.69; 95% CI, 0.48-1.01) for DED in women. CONCLUSIONS: Among a Japanese cohort, DED leading to a clinical diagnosis or severe symptoms is prevalent. Use of CLs was a common dry eye risk factor in both genders. The condition is more prevalent in men with low BMI, HT, and in women with myocardial infarction or angina and VDT use. Relevant measures directed against the modifiable risks may provide a positive impact on public health and quality of life of Japanese. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Knee pain and future self-reliance in older adults: evidence from a community-based 3-year cohort study in Japan.

BACKGROUND: Although knee pain is common in older persons and can cause ambulatory limitation, its impact on self-reliance has rarely been examined in Japan, particularly in a community setting. The aim of this 3-year cohort study was to investigate the association of knee pain with dependence in activities of daily living (ADL) and mortality in community-dwelling older Japanese adults. METHODS: In 2005, presence of knee pain was assessed by a home visit survey of 1391 older adults aged 65 years or older (participation proportion = 97.3%). A total of 1265 participants who were ADL-independent at baseline were followed for 3 years, and information on outcomes, namely death and dependence in ADL, was collected. RESULTS: Participants who always had knee pain were more likely to become dependent in ADL than those who reported no knee pain (multivariate-adjusted OR, 1.98; 95% CI, 1.03-3.83); however, always having knee pain was not associated with mortality or a composite outcome of ADL dependence and death. Further analyses of each component of ADL dependence revealed that knee pain was associated with a need for assistance at home (long-term care eligibility, bathing, dressing, and transferring), but not with institutionalization. CONCLUSIONS: The participants were highly representative of the target population and the rate of follow-up was almost perfect (99.4%). The results suggest that knee pain is associated with future dependence in ADL, particularly a need for assistance at home.

Corrigendum to "Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion".

[This corrects the article DOI: 10.1155/2018/2380179.].

Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion.

Procalcitonin (PCT) is used as a biomarker in severe infections. Here, we retrospectively investigated levels of serum PCT, C-reactive protein (CRP), and inflammatory cytokines (IL-6, TNF-α, and IFN-γ) in the second phase of patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Nine AESD pediatric patients (4 men, 5 women; AESD group) admitted to Okayama University Hospital from 2010 to 2016 were compared with 10 control patients with febrile seizures (FS) (3 men, 7 women; FS group). Mean PCT concentrations (ng/mL) in the AESD and FS groups were significantly different, at 9.8 ± 6.7 and 0.8 ± 0.9, respectively (p = 0.0011). CRP (mg/dL) were 0.79 ± 0.89 and 1.4 ± 1.0 (p = 0.21), respectively; IL-6 (pg/mL) were 449.7 ± 705.0 and 118.3 ± 145.4 (p = 0.20), respectively; TNF-α (pg/mL) were 18.6 ± 12.5 and 16.6 ± 6.0 (p = 0.67), respectively; and IFN-γ (pg/mL) were 79.6 ± 158.5 and 41.9 ± 63.7 (p = 0.56), respectively. Ratios of PCT to CRP were 27.5 ± 34.2 and 3.2 ± 6.8 (p < 0.0001), respectively. The sensitivity and specificity in the diagnosis of AESD using a cutoff of PCT/CRP ratio of 1.0 were 100% and 80%, respectively. These results suggest that PCT and the PCT/CRP ratio are useful in auxiliary diagnosis of the second stage of AESD, and in AESD, PCT is likely to increase through a different mechanism.

Local and Systemic Immune Responses to Influenza A Virus Infection in Pneumonia and Encephalitis Mouse Models.

OBJECTIVE: To compare local and systemic profiles between different disease pathologies (pneumonia and encephalitis) induced by influenza A virus (IAV). METHODS: An IAV pneumonia model was created by intranasal inoculation of C57BL/6 mice with influenza A/WSN/33 (H1N1) virus. Lung lavage and blood collection were performed on day 3 after IAV inoculation. Similarly, an IAV encephalitis mouse model was created by direct intracranial IAV inoculation. Cerebrospinal fluid (CSF) and blood collection were conducted according to the same schedule. Cytokine/chemokine profiles were produced for each collected sample. Then the data were compared visually using radar charts. RESULTS: Serum cytokine profiles were similar in pneumonia and encephalitis models, but local responses between the bronchoalveolar lavage fluid (BALF) in the pneumonia model and CSF in the encephalitis model differed. Moreover, to varying degrees, the profiles of local cytokines/chemokines differed from those of serum in both the pneumonia and encephalitis models. CONCLUSION: Investigating local samples such as BALF and CSF is important for evaluating local immune responses, providing insight into pathology at the primary loci of infection. Serum data alone might be insufficient to elucidate local immune responses and might not enable clinicians to devise the most appropriate treatment strategies.

Effect of bidet toilet use on preterm birth and vaginal flora in pregnant women.

OBJECTIVE: To estimate the association between bidet toilet use and preterm birth, as well as the effect of bidet toilet use on bacterial vaginosis, in pregnant women. METHODS: Questionnaires about bidet toilet usage were sent to 2,545 women who gave birth between 2006 and 2010 in Tokyo. Crude and multivariable adjusted odds ratios (ORs) for the incidence of preterm birth (delivery at less than 37 completed weeks of gestation) and the prevalence of bacterial vaginosis between users and nonusers of the bidet toilet were calculated using data from the questionnaire and delivery records. Bacterial vaginosis was estimated by the balance of lactobacilli and nonlactobacillus microbes based on routine prenatal microbiologic test results. RESULTS: Of 1,293 women who responded to the questionnaire, 63.3% were users of the bidet toilet. The incidence of preterm birth was 15.8% among bidet users and 16.0% among nonusers (adjusted OR 1.04, 95% confidence interval [CI] 0.72-1.48). Additionally, no association was found between bidet toilet use and bacterial vaginosis (adjusted OR 0.96, 95% CI 0.70-1.33). CONCLUSION: Normal use of the bidet toilet by pregnant women poses no clinical health risk for preterm birth and bacterial vaginosis.

Self-reported hearing loss in older adults is associated with future decline in instrumental activities of daily living but not in social participation.

OBJECTIVES: To investigate whether self-reported hearing loss in older adults is associated with a decline in their ability to perform instrumental activities of daily living (IADL) or a decline in social participation. DESIGN: Prospective follow-up. SETTING: Community. PARTICIPANTS: One thousand two hundred fifty-four adults aged 65 to 98. MEASUREMENTS: Self-reported hearing loss, IADL, and social participation were evaluated through home-visit surveys. Self-reported hearing loss was measured according to responses to the question, "Do you have difficulty hearing and understanding what a person says to you in a quiet room if they speak normally to you, even when wearing your hearing aid?" Levels of IADL and social participation were measured using the subscales of the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). RESULTS: Of the 921 participants with a perfect baseline IADL score and valid follow-up scores, 105 also self-reported hearing loss at baseline. Of this group, 44.8% (total n = 105) reported a decline in their IADL score over the 3-year follow-up period. After adjusting for major confounders, a statistically significant difference in experiencing an IADL decline over the 3-year period was found between those with hearing loss at baseline and those without (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.12-2.87). Self-reported hearing loss at baseline did not have a statistically significant effect on decline in social participation (OR = 1.05, 95% CI = 0.63-1.76) over the 3-year follow-up period. CONCLUSION: Self-reported hearing loss was associated with a decline in IADL, but not with social participation.

Impact of hearing difficulty on dependence in activities of daily living (ADL) and mortality: a 3-year cohort study of community-dwelling Japanese older adults.

Studies have associated hearing impairment with adverse health outcomes, but the actual impact of hearing difficulty has been barely investigated. We investigated among older adults (i) the prevalence of hearing difficulty, (ii) the association of hearing difficulty with a composite outcome of dependence in activities of daily living (ADL) and death, and (iii) the population attributable risk fraction (PAF) of hearing difficulty. In 2005, a home-visit survey of 1364 Japanese older adults aged ≥65 (participation proportion=95.5%) was conducted to evaluate self-reports of hearing difficulty. Over 3 years, 99.4% of the initial sample was followed. Outcomes were measured by incidence of death or dependence in ADL. In the sample, the prevalence of hearing difficulty was 17.7% (age ≥65) and 25.7% (age ≥75). Hearing difficulty at high levels was associated with a composite outcome of dependence in ADL and mortality (adjusted odds ratio=OR and 95% confidence interval=95% CI=6.19 (1.92-19.92)) as well as with each outcome independently. Improving the hearing difficulty from high to moderate or no difficulty would reduce the composite outcome in 4.3% (age ≥65) and in 6.3% (age ≥75) of the target population. In conclusion, hearing difficulty was common, was associated with and had substantial impact on adverse health outcomes.