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Aim This study aimed to develop and test a causal model focused on assertiveness, stress coping, and workplace environment as factors affecting burnout among novice nurses. Design Cross‐sectional study was conducted with novice nurses of 17 hospitals. Methods The Novice Nurse Assertiveness Scale and the Japanese version of Maslach Burnout Inventory. Results Data from 645 female novice nurses were analysed. The mean age, Novice Nurse Assertiveness Scale and Maslach Burnout Inventory were 22.6 ± 3.0, 67.4 ± 10.3 and 13.7 ± 2.5. For the final model, the study adopted a model that includes indirect influences; inappropriate assertiveness and inappropriate coping affected the dissatisfaction with the job and then affected the burnout. The goodness of fit index was GFI = 0.94, AGFI = 0.91, RMSEA = 0.66, and R 2 was .86. The findings validated this as a causal model of assertiveness, stress coping, and the work environment as factors affecting burnout for novice nurses.

The migration of lung fibroblasts plays a pivotal role in wound repair and fibrotic processes in the lung. Although the receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of lung diseases, its role in lung fibroblast migration is unclear. The current study examined the effect of three different RAGE ligands, namely, high mobility group box 1 (HMGB1), S100A12, and N-epsilon-(carboxymethyl) lysine (CML), on human fibronectin-directed human fetal lung fibroblast (HFL-1) migration. HMGB1 augmented, whereas S100A12 inhibited, HFL-1 migration in a concentration-dependent manner. CML did not affect HFL-1 migration. The effect of HMGB1 was not through RAGE. However, the effect of S100A12 was mediated by RAGE, but not Toll-like receptor 4. S100A12 did not exert a chemoattractant effect, but inhibited HFL-1 chemotaxis and/or chemokinesis. Moreover, S100A12 mediated HFL-1 migration through p38 mitogen-activated protein kinase (MAPK) but not through nuclear factor-kappa B, protein kinase A, phosphatase and tensin homolog deleted on chromosome 10, or cyclooxygenase. In addition, western blot analysis showed that S100A12 augmented p38 MAPK activity in the presence of human fibronectin. In conclusion, S100A12 inhibits lung fibroblast migration via RAGE-p38 MAPK signaling. This pathway could represent a therapeutic target for pulmonary conditions characterized by abnormal tissue repair and remodeling.

The increase in the elderly population in need of healthcare services has led to a serious shortage in the nursing workforce. To retain a large nursing workforce, a strong work–life balance among nurses is needed along with a healthy work environment. This prospective study investigates the influence of work–life balance and sense of coherence on intention to leave among hospital nurses. A questionnaire survey was conducted with 2239 nurses as a baseline. The explanatory variables included striving for work–life balance behavior, a sense of coherence in terms of personal resources, and work-, organizational-, and individual-related factors. Using a cohort of 1368 valid responses, we measured intention to leave among 975 nurses with whom we were able to follow up 6 months after the baseline survey. We then performed multiple regression analysis. The behavior striving for work–life balance was shown to influence nurses’ intention to leave. Nurses who exhibited less striving for work–life balance behavior showed higher intentions to leave. The sense of coherence was not identified as a factor affecting intention to leave. Securing a comfortable work–life balance would reduce the nurses’ desire to quit the hospital. To reduce nurse turnover, nurse managers should develop support programs that can help nurses achieve a better work–life balance.

Rationale and Objectives Changes in the geometry of the chest wall due to lung hyperinflation occur in COPD. However, the quantitative assessment of impaired lung motions and its association with the clinical characteristics of COPD patients are unclear. This study aimed to investigate the respiratory kinetics of COPD patients by dynamic MRI. Materials and Methods This study enrolled 22 COPD patients and 10 normal participants who underwent dynamic MRI and pulmonary function testing (PFT). Changes in the areas of the lung and mediastinum during respiration were compared between the COPD patients and the normal controls. Relationships between MRI, CT parameters, and clinical measures that included PFT results also were evaluated. Results Asynchronous movements and decreased diaphragmatic motion were found in COPD patients. COPD patients had a larger ratio of MRI-measured lung areas at expiration to inspiration, a smaller magnitude of the peak area change ratio, and a smaller mediastinal-thoracic area ratio than the normal participants. The lung area ratio was associated with FEV1/FVC, predicted RV%, and CT lung volume/predicted total lung capacity (pTLC). The lung area ratio of the right lower and left lower lungs was significantly correlated with emphysema of each lower lobe. The expiratory mediastinal-thoracic area ratio was associated with FEV1% predicted and RV/TLC. Conclusion Changes in the lung areas of COPD patients as shown on MRI reflected the severity of airflow limitation, hyperinflation, and the extent of emphysema. Dynamic MRI provides essential information about respiratory kinetics in COPD.

Previous nationwide Japanese data suggested that pulmonary arterial hypertension (PAH) predominantly affects young women. However, the number of elderly patients diagnosed with PAH has been increasing in western countries. There have been no reports on elderly PAH patients in Asian countries. This study aimed to investigate the clinical characteristics of elderly PAH patients in a Japanese cohort. Idiopathic/heritable PAH (I/H-PAH) was included in the national research project on intractable diseases. The patients were required to submit a clinical research form completed by their attending physicians. We analyzed the characteristics of Japanese I/H-PAH using the newly registered forms in 2013 (Study 1, n = 148). Also, we did a retrospective, observational cohort study at Chiba University Hospital (Study 2, n = 42). We compared the characteristics of elderly PAH patients (≥65 years old) with younger patients (

Excessive release of neutrophil extracellular traps (NETs) has been implicated in several organ fibrosis, including pulmonary fibrosis. NETs constitute a phenomenon in which decorated nuclear chromatin with cytosolic proteins is released into the extracellular space. PAD4 (peptidylarginine deiminase 4) plays an important role in the formation of NETs. However, the role of NETs in the pathogenesis of pulmonary fibrosis remains undefined. Here, we identified NETs in the alveolar and interstitial lung space of mice undergoing bleomycin (BLM)-induced lung fibrosis, which was suppressed by a pan-PAD inhibitor, Cl-amidine. In vitro, BLM directly induced NETs in blood neutrophils, which was also inhibited by Cl-amidine. Furthermore, Padi4 gene knockout (PAD4-KO) in mice led to the alleviation of BLM-induced NETs and pulmonary fibrosis and to the expression of inflammatory and fibrotic genes. PAD4 deficiency prevented decreases in alveolar epithelial and pulmonary vascular endothelial cell numbers and increases in ACTA2-positive mesenchymal cells and S100A4-positive fibroblasts in the lung. Hematopoietic cell grafts from PAD4-KO mice, not wild-type mice, resolved BLM-induced lung fibrosis and fibrotic gene expression in wild-type and PAD4-KO mice, suggesting that expression of PAD4 in hematopoietic cells may be involved in the development of lung fibrosis. These data suggest that PAD4 deficiency could ameliorate BLM-induced formation of NETs and lung fibrosis, suggesting that this pathway could serve as a therapeutic target for pulmonary fibrosis treatment.

Background: Exacerbation causes deterioration of quality of life and worsens respiratory dysfunction, which leads to poor prognosis in patients with COPD. In an aging society, nutritional indices have been reported as significant prognostic factors in many diseases in recent years. However, the relationship between the nutritional indicators and the prognosis in elderly patients with COPD is unknown. Material and Methods: We enrolled Nighty-four subjects who performed spirometry, blood tests, and MDCT. The subjects were divided into two groups according to age: the subjects >75 (n=56) and the subjects Results: There was no significant correlation between PNI and FEV1%pred or the percentage of attenuation volume (LAV%). There were significant differences between the groups with/without exacerbation in PNI, serum albumin, and neutrophil-to-lymphocyte ratio(NLR) in patients with age >75. The multivariate analysis showed that FEV1%pred was a significant predictor in the patients age 75. Conclusion: In patients with age >75, prognostic nutritional index was significantly related to COPD exacerbation risk more than the severity of COPD. Nutritional status may be a potential prediction of clinical course in elderly patients with COPD.

It is important to select an appropriate surrogate matrix for preparing calibration standards and quality control samples while quantitatively assaying for endogenous substances, because a blank matrix that does not contain the endogenous substance cannot be derived from the species from which the target study samples are collected. This is because the assay results might be affected, depending on the characteristics of the analyte in the surrogate matrix. Our discussion group that participated in the Japan Bioanalysis Forum discussed the recommended selection strategies, focusing on large and small molecules in ligand binding assays and LC–MS, respectively. We established an efficient selection strategy for a surrogate matrix, with simple compositions as the first candidates stated in this article.

Objective: This study aimed to investigate the validity and reliability of the Japanese version of the Rathus assertiveness schedule (J-RAS) in psychiatric day care users with schizophrenia. Subjects and Methods: We examined 715 psychiatric day care users with schizophrenia by conducting the test twice between September 2007 and February 2008 using a questionnaire-based survey. We examined construct validity and used the internal reliability test, split-half method, and test–retest method to examine reliability. The questionnaires were distributed and collected by post via the director of each facility. Results: Of the 1272 psychiatric day care users, 715 users (56.2%) were enrolled in the study. Seven factors were extracted for construct validity. The cumulative contribution rate of these factors was 49.4% and the internal consistency of 30 items of the J-RAS was α = 0.72. The split-half method revealed a significant correlation between the total scores of the odd- and even-numbered items (r = 0.64, p < 0.01). The test–retest method revealed a significant difference between the total scores of the first and second tests of the 30 items of the J-RAS (r = 0.73, P < 0.01). Conclusion: We confirmed the validity and reliability of the J-RAS in psychiatric day care users with schizophrenia and demonstrated its efficacy in evaluating psychiatric day care users.

Background: Increased neutrophil percentage in bronchoalveolar lavage fluids (BALF) in idiopathic pulmonary fibrosis is associated with poor prognosis. Neutrophil extracellular traps (NETs) exhibit a neutrophil antimicrobial function and induce systemic tissue damage and chronic inflammation under normal and diseased conditions such as acute respiratory distress syndrome and organ fibrosis. The enzyme peptidyl arginine deiminase, type Ⅳ (PAD4) mainly regulates NET release. However, the role of NETs in pulmonary fibrosis is unclear. Objectives: To verify the role of NET in murine pulmonary fibrosis induced by bleomycin (BLM) instillation. Methods: Wild type (C57BL/6) and PAD4-knockout (Pad4-/-, C57BL/6 background) mice were used to evaluate NET levels in BALF and lungs 2, 7, and 21 days after single bronchial instillation of saline and BLM (5U/kg body weight). Fibrosis was evaluated by Masson’s trichrome staining and modified Ashcroft Scale. Lung collagen load was evaluated by Sircol Collagen Assay 21 days after instillation. Results: In the BLM group, immunohistochemistry (IHC) showed that NETs increased in lavage 2 days after instillation (p = 0.013) and decreased in BALF and lungs 7 and 21 days after instillation. Two days after instillation, NETs in BALF and lungs of PAD4-KO mice decreased compared to wild type mice. After 21 days, pulmonary fibrosis score of PAD4-KO mice was lower than that of wild type mice (p = 0.003). In the BLM group, collagen load of PAD4-KO mice tended to be lower than that of wild type mice (408.8 ± 0.0 vs 472.1 ± 20.4 µg/whole lung). Conclusion: NETs may contribute to developing pulmonary fibrosis induced by BLM instillation.

1. Esaxerenone (CS-3150) is a novel non-steroidal mineralocorticoid receptor antagonist. The pharmacokinetics, tissue distribution, excretion, and metabolism of esaxerenone were evaluated in rats and monkeys. 2. Following intravenous dosing of esaxerenone at 0.1-3 mg/kg, the total body clearance and the volume of distribution were 3.53-6.69 mL/min/kg and 1.47-2.49 L/kg, respectively, in rats, and 2.79-3.69 mL/min/kg and 1.34-1.54 L/kg, respectively, in monkeys. The absolute oral bioavailability was 61.0-127% in rats and 63.7-73.8% in monkeys. 3. After oral administration of [

Aim Burnout is a common feature among healthcare professionals; however, little systematic research exists on burnout among nurses who are raising children. The burnout-related factors among female nurses with children under the age of 3 years were identified in order to ascertain potential burnout prevention methods. Methods In total, 1681 nurses with children who worked at nine city hospitals in Kanagawa Prefecture, Japan, were sent the Maslach Burnout Inventory–Human Services Survey; 1173 nurses responded in June 2014. They were divided according to their sex and children's ages. A data analysis was undertaken for those female nurses with children who were aged under 3 years who provided valid responses (n = 158). Results A number of factors related to burnout in female nurses with children aged under 3 years was found via a multiple regression analysis: irritation at being unable to attend to their own affairs, over 4–6 h of overtime work per week, having a child aged under 3 years as the first or second child, little sense of work fulfillment, using a childcare facility outside the workplace, dissatisfaction with their salary, feeling ill-qualified as a parent, and a sense of inadequate support. Conclusions Child care occurs during a limited period and appropriate support is needed. A workplace environment with no overtime work, a childcare facility in the workplace, and mental health support to reduce “feelings of irritation” and “feeling ill-qualified as a parent” could help to prevent burnout in female nurses with toddlers and infants.

Aim This prospective cohort study aims to clarify the factors affecting burnout in female nurses who have preschool-age children. Methods The subjects were 2151 female nurses who have preschool-age children and work at 70 city hospitals across Japan. The questionnaires were completed by 1644 female nurses with preschool-age children in October 2010, and they were divided into a cohort to observe the incidence of burnout, which was investigated in October 2011. Results At the baseline, the authors obtained responses from 1802 subjects (83.8%) who had agreed to join the study. The subjects the authors were able to investigate totaled 523, of whom 117 (22.4%) had experienced burnout. Multiple logistic regression analysis showed that influencing or predictive factors in burnout were years at the present workplace, will to continue work, assertiveness, overtime work, and spanking children. Conclusion Female nurses who have preschool-age children tend to burnout easily if they have been at their present workplace for less than 3 years, wish to quit working, respond to a child's misbehavior with spanking, are “very low” in assertiveness, or work 4–6 h of overtime per week.

Aim This study aimed to clarify conditions of women experiencing post-partum anemia and identify factors that work against the alleviation of anemia. Methods This was a retrospective longitudinal study, involving 246 women giving birth at five participating institutions, diagnosed with anemia on day 3 post-partum, and given a blood sample at the medical examination 1 month after the birth. With answers about alleviation of anemia during the 1 month post-partum period as an objective variable, and explanatory variables, multiple logistic regression analysis was performed. The explanatory variables included demographic data of the participants, information about anemia, following the nutrition instruction advice for anemia alleviation, family structure and others assisting the participants, and self-management skills (measured by the Self-Management Skill [SMS] scale). Results The present authors collected 211 valid responses; the average age was 32.6 years. The mean hemoglobin values on the 3rd and 30th days post-partum were 9.6 and 12.0 g/dL, respectively. One fifth of the participants (21.3%) showed no anemia alleviation. The mean value on the SMS scale was 28.35, and the anemia alleviated group (30.78) was significantly higher than the non-alleviated group (19.38). Results of the multiple logistic regression analysis showed a strong relationship between anemia risk and self-management skills. The absence of anemia alleviation increased 2.51 times as the total score of the SMS decreased 1 point. Conclusion There is an urgent need to develop an intervention program to alleviate post-partum anemia focusing on the low score items because self-management skills strongly affect alleviation improvement.

Since it was recently reported that an antibody for proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces the risk of cardiovascular events in a clinical context, PCSK9 inhibition is thought to be an attractive therapy for dyslipidemia. In the present study, we created a novel small biologic alternative to PCSK9 antibodies called DS-9001a, comprising an albumin binding domain fused to an artificial lipocalin mutein (ABD-fused Anticalin protein), which can be produced by a microbial production system. DS-9001a strongly interfered with PCSK9 binding to low-density-lipoprotein receptor (LDL-R) and PCSK9-mediated degradation of LDL-R. In cynomolgus monkeys, single DS-9001a administration significantly reduced the serum LDL-C level up to 21 days (62.4% reduction at the maximum). Moreover, DS-9001a reduced plasma non-high-density-lipoprotein cholesterol and oxidized LDL levels, and their further reductions were observed when atorvastatin and DS-9001a were administered in combination in human cholesteryl ester transfer protein/ApoB double transgenic mice. Additionally, their reductions on the combination of atorvastatin and DS-9001a were more pronounced than those on the combination of atorvastatin and anacetrapib. Besides its favorable pharmacologic profile, DS-9001a has a lower molecular weight (about 22 kDa), yielding a high stoichiometric drug concentration that might result in a smaller administration volume than that in existing antibody therapy. Since bacterial production systems are viewed as more suited to mass production at low cost, DS-9001a may provide a new therapeutic option to treat patients with dyslipidemia. In addition, considering the growing demand for antibody-like drugs, ABD-fused Anticalin proteins could represent a promising new class of small biologic molecules.

Human in vitro and dog in vitro/in vivo researches indicate that the drug-drug interaction (DDI) of decreased plasma valproic acid (VPA) concentration by co-administration of carbapenem antibiotics is caused by inhibition of acylpeptide hydrolase (APEH)-mediated VPA acylglucuronide (VPA-G) hydrolysis by carbapenems. In this study, we investigated VPA disposition and APEH activities in TK-NOG chimeric mice, whose livers were highly replaced with human hepatocytes, to evaluate the utility of this animal model and the clinical relevance of the DDI mechanism.VPA and VPA-G concentrations in plasma, urinary excretion of VPA-G and APEH activity in humanized livers were measured after co-administration of VPA with meropenem (MEPM) to chimeric mice.After co-administration with MEPM to the chimeric mice, plasma VPA concentration more rapidly decreased than without the co-administration. An increase in plasma AUC and urinary excretion of VPA-G was also observed. APEH activity in humanized livers was strongly inhibited even at 24 h after co-administration of MEPM to the chimeric mice.The DDI of VPA with carbapenems was successfully observed in chimeric mice with humanized livers. The DDI was caused by long-lasting inhibition of hepatic APEH-mediated VPA-G hydrolysis by carbapenems, which strongly supports the APEH-mediated mechanism of the clinical DDI. This is the first example showing the usefulness of chimeric mice with humanized livers for evaluation of a DDI via non-cytochrome P450 enzyme.

Scedosporium prolificans (S. prolificans) is a type of mold, which rarely affects immunocompromised people. We treated a 71-year-old woman with acute myeloid leukemia (AML-M5a) with low-dose cytarabine, acralubicin, and filgrastim as the induction therapy. On day 7 after the initiation of chemotherapy, she became febrile and agranulocytic, and developed anal pain ; therefore, we discontinued the chemotherapy on day 8. Broad-spectrum antibiotics, micafungin, and then liposomal amphotericin B were ineffective. The serum concentration of β-D-glucan was 525 pg/mL. She died of multiple organ failure on day 17. S. prolificans was detected from the blood culture on day 13. Physicians should consider Scedosporium spp. infection when principal antifungal agents are ineffective and fungal infection is strongly suspected.

This study examined the physiological responses to cold stimulus during intermittent high-intensity exercise simulating on-snow alpine ski training. 7 male alpine skiers performed intermittent high-intensity exercises composed of 4 bouts of cycling exercise at 140% VO 2max intensity for 30 s with 10-min rests on a cycle ergometer in cold (1°C) and control (22°C) conditions. The subjects wore racing suits, middle layers and half pants designed for alpine skiers. Rectal temperature and mean skin temperature were lower in the cold condition than in the control condition (36.8 ± 0.5 vs. 37.1 ± 0.1°C and 28.4 ± 0.6 vs. 33.3 ± 0.6°C, respectively). Oxygen consumption during rests and the last 2 bouts of exercise was higher in the cold condition than in the control condition. Although plasma noradrenaline and serum triglyceride were higher in the cold condition than in the control condition, plasma glucose, adrenaline and serum glycerol were lower. Serum free fatty acid and plasma lactate concentrations did not differ significantly between the 2 conditions. These results indicate that a cold stimulus affects body temperature and energy metabolism and may lead to a decrease in exercise capacity in alpine skiers during on-snow training.

Burnout is a common feature among healthcare professionals; however, little systematic research exists on burnout among nurses who are raising children. The burnout-related factors among female nurses with children under the age of 3 years were identified in order to ascertain potential burnout prevention methods.In total, 1681 nurses with children who worked at nine city hospitals in Kanagawa Prefecture, Japan, were sent the Maslach Burnout Inventory-Human Services Survey; 1173 nurses responded in June 2014. They were divided according to their sex and children's ages. A data analysis was undertaken for those female nurses with children who were aged under 3 years who provided valid responses (n = 158).A number of factors related to burnout in female nurses with children aged under 3 years was found via a multiple regression analysis: irritation at being unable to attend to their own affairs, over 4-6 h of overtime work per week, having a child aged under 3 years as the first or second child, little sense of work fulfillment, using a childcare facility outside the workplace, dissatisfaction with their salary, feeling ill-qualified as a parent, and a sense of inadequate support.Child care occurs during a limited period and appropriate support is needed. A workplace environment with no overtime work, a childcare facility in the workplace, and mental health support to reduce "feelings of irritation" and "feeling ill-qualified as a parent" could help to prevent burnout in female nurses with toddlers and infants.

Few studies, each limited to a single major city, have investigated the prevalence and seasonal patterns of different viruses among children with low respiratory tract infections (LRTI) in Northeastern Brazil. The aim of this study was to determine the frequency of respiratory syncytial virus (RSV) and of 7 other viruses in children for LRTI in 4 capitals from this region, and investigate their association with several risk factors, including meteorological data. From April 2012 to March 2013, 507 children, aged up to 24 months and hospitalized with LRTI in one of the participating centers at Aracajú, Salvador, Recife, and Maceió, had a sample of nasopharyngeal aspirate collected and analyzed for the following viruses by reverse-transcription polymerase chain reaction followed by hybridization on low-density microarrays: RSV, influenza, parainfluenza, adenovirus, rhinovirus, metapneumovirus, bocavirus, and coronavirus. The result was positive in 66.5% of cases, RSV was the most common virus (40.2%). Except for rhinovirus (17%), all other virus had frequency rates lower than 6%. Viral coinfections were detected in 13.8% of samples. Possible related risk factors for RSV infection were low age upon entry, attendance of daycare, low gestational age, and low educational level of the father. The relative frequency of viral infections was associated with increasing temperature and decreasing humidity separately, but the results also suggested both associated with increased frequency of RSV. Some of these findings differ from those reported for other regions in Brazil and may be used to guide policies that address LRTI.

LRH-1 (liver receptor homologue-1), a transcription factor and member of the nuclear receptor superfamily, regulates the expression of its target genes, which are involved in bile acid and cholesterol homoeostasis. However, the molecular mechanisms of transcriptional control by LRH-1 are not completely understood. Previously, we identified Ku80 and Ku70 as LRH-1-binding proteins and reported that they function as co-repressors. In the present study, we identified an additional LRH-1-binding protein, ILF3 (interleukin enhancer-binding factor 3). ILF3 formed a complex with LRH-1 and the other two nuclear receptor co-activators PRMT1 (protein arginine methyltransferase 1) and PGC-1α (peroxisome proliferator-activated receptor γ co-activator-1α). We demonstrated that ILF3, PRMT1 and PGC-1α were recruited to the promoter region of the LRH-1-regulated SHP (small heterodimer partner) gene, encoding one of the nuclear receptors. ILF3 enhanced SHP gene expression in co-operation with PRMT1 and PGC-1α through the C-terminal region of ILF3. In addition, we found that the small interfering RNA-mediated down-regulation of ILF3 expression led to a reduction in the occupancy of PGC-1α at the SHP promoter and SHP expression. Taken together, our results suggest that ILF3 functions as a novel LRH-1 co-activator by acting synergistically with PRMT1 and PGC-1α, thereby promoting LRH-1-dependent gene expression.