Immediate sciatic nerve reconstruction using an ipsilateral common peroneal nerve graft at the time of sarcoma resection.

BACKGROUND: Concomitant resection of the sciatic nerve along with a malignant tumor is no longer a contraindication for limb-sparing surgery, as most of these patients remain ambulatory. However, sciatic nerve reconstruction after sarcoma resection is not commonly performed. Restoration of nerve function can improve patient quality of life. We describe our experience with four patients who underwent sciatic nerve reconstruction using an ipsilateral common peroneal nerve graft at the time of sarcoma resection. METHODS: Because of the low chance of peroneal nerve recovery, the ipsilateral peroneal trunk was used as a graft to reconstruct the tibial trunk of the sciatic nerve. Two patients were men and two were women. Mean age was 45.3 years (range, 15-62). Mean sciatic nerve defect length was 9.4 cm (range, 8.5-12.0). Proximal thigh defects (three patients) were reconstructed with a double cable; the one patient with a distal thigh defect underwent single cable reconstruction. Mean operation time was 492 min (range, 428-682). RESULTS: Mean length of the harvested peroneal trunks was 21 cm (range, 11-26). Mean graft length was 11.9 cm (range, 11-13). Postoperative course was uneventful in all four patients. One patient died of sarcoma lung metastasis and could not be evaluated. Three patients were followed for more than 2 years. Two patients achieved British Medical Research Council grade 4 plantar flexion; the remaining patient achieved grade 5 plantar flexion and grade 4 toe flexion. Semmes-Weinstein monofilament sensory testing showed loss of protective sensation on the plantar surface in all three. Musculoskeletal Tumor Society scores at last follow-up were 60.0%, 70.0%, and 43.3%, respectively. CONCLUSIONS: Immediate sciatic nerve reconstruction using an ipsilateral common peroneal nerve graft avoids reconstruction delay and scar tissue formation, which is advantageous for nerve recovery. This technique may be considered when sciatic nerve resection is anticipated during sarcoma resection.

In-vitro fertilisation-embryo-transfer complicates the antenatal diagnosis of placenta accreta spectrum using MRI: a retrospective analysis.

AIM: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for the antenatal diagnosis of placenta accreta spectrum (PAS). MATERIALS AND METHODS: Data from 95 patients with placenta previa or low-lying placenta who underwent MRI at Osaka University Hospital for the antenatal diagnosis of PAS between January 2013 and December 2018 were reviewed retrospectively. The antenatal MRI signs suggesting PAS were assessed. Patients were divided into two groups depending on whether they were diagnosed with PAS. Factors that affected PAS diagnosis were identified using multivariate analysis. RESULTS: The diagnostic accuracy of MRI for detecting PAS was as follows: 71.4% sensitivity, 96.4% specificity, and area under the curve (AUC) of 0.839 (95% confidence interval [CI]: 0.73-0.91). The diagnostic accuracy was lower in patients with in-vitro fertilisation with embryo transfer (IVF-ET): 22.2% sensitivity, 93.3% specificity, and AUC=0.578 (95% CI: 0.417-0.724). On multivariate analysis, only IVF-ET showed a significant association with false-positive or -negative MRI diagnosis of PAS (adjusted odds ratio: 26.5; 95% CI: 2.42-289.4; p=0.007). CONCLUSION: IVF-ET affects the antenatal diagnosis of PAS using MRI.

New physician specialty training system impact on distribution of trainees in Japan.

OBJECTIVES: The problem of uneven distribution of medical services and inequitable distribution of physicians is drawing much attention worldwide. Revealing how changes in the specialty training system in Japan have affected the distribution of doctors could help us understand this problem. In 2018, a new and standardized specialty training system was implemented by the Japanese Medical Specialty Board, which is recognized by the Ministry of Health, Labor and Welfare. The purpose of this study was to investigate how this new system has affected the geographical distribution of doctors commencing specialty training (trainees) and choice of specialty in Japan. STUDY DESIGN: Retrospective observational study. METHODS: The change in the number of trainees between the control period (2012-2014) and 2018 was investigated, taking into account the prefecture and specialty selected. Population, the proportion of residents aged 65 years or older (aging rate), and the total number of overall doctors in each prefecture were considered as the background characteristics of each prefecture. We created a Lorenz curve and calculated the Gini coefficient for the distribution of trainees. RESULTS: In 2018, the number of trainees per 100,000 population increased to 6.6 nationwide compared with 5.5 during the control period. The number of trainees per 100,000 population in 2018 increased in prefectures with a large population of ≧ 2,000,000, a low aging rate (<27%), and a high doctor density (≧ 250 doctors per 100,000 population). The Gini coefficient showed an increase to 0.226 in 2018 compared with only 0.160 during the control period. CONCLUSIONS: After the implementation of the new training system, there was an increase in the number of doctors enrolling in specialty programs, and the specialties other than internal medicine and surgery have attracted more trainees. Inequality in the distribution of doctors between urban and rural prefectures worsened. This indicates the need to explore new ways of balancing distribution while maintaining optimal opportunities for specialist training.

A tuberculosis outbreak at an insecure, temporary housing facility, manga café, Tokyo, Japan, 2016-2017.

In November 2016, a woman in her 30s who stayed at an insecure, temporary housing facility, a manga café in Tokyo, Japan, for a year was diagnosed with sputum smear-positive tuberculosis (TB). Since the café had 31 staff members and provided with accommodation to many people, the local health office initiated a contact investigation. This study aims to characterise the cases found in the outbreak. A TB case was defined as a person tested bacteriologically positive for TB, or was determined to have TB by a physician. A latent TB infection case was defined as a person tested positive by interferon-γ release assay. From January 2016 through November 2017, there were 31 staff members at the manga café, of which, six developed TB disease (one smear-negative, culture-positive and five smear- and culture-negative) in addition to seven LTBI. Another long-term customer was found having sputum smear-positive TB. Variable numbers tandem repeat (VNTR) test revealed that the index patient and the long-term customer had the identical type of VNTR; however, one staff member had a different VNTR. Local health authorities should intensify screening long-term customers of such facilities for TB regularly as well as once a TB outbreak occurs.

Angiopoietin-like protein 2 promotes chondrogenic differentiation during bone growth as a cartilage matrix factor.

OBJECTIVE: Chondrocyte differentiation is crucial for long bone growth. Many cartilage extracellular matrix (ECM) proteins reportedly contribute to chondrocyte differentiation, indicating that mechanisms underlying chondrocyte differentiation are likely more complex than previously appreciated. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor normally abundantly produced in mesenchymal lineage cells such as adipocytes and fibroblasts, but its loss contributes to the pathogenesis of lifestyle- or aging-related diseases. However, the function of ANGPTL2 in chondrocytes, which are also differentiated from mesenchymal stem cells, remains unclear. Here, we investigate whether ANGPTL2 is expressed in or functions in chondrocytes. METHODS: First, we evaluated Angptl2 expression during chondrocyte differentiation using chondrogenic ATDC5 cells and wild-type epiphyseal cartilage of newborn mice. We next assessed ANGPTL2 function in chondrogenic differentiation and associated signaling using Angptl2 knockdown ATDC5 cells and Angptl2 knockout mice. RESULTS: ANGPTL2 is expressed in chondrocytes, particularly those located in resting and proliferative zones, and accumulates in ECM surrounding chondrocytes. Interestingly, long bone growth was retarded in Angptl2 knockout mice from neonatal to adult stages via attenuation of chondrocyte differentiation. Both in vivo and in vitro experiments show that changes in ANGPTL2 expression can also alter p38 mitogen-activated protein kinase (MAPK) activity mediated by integrin α5ß1. CONCLUSION: ANGPTL2 contributes to chondrocyte differentiation and subsequent endochondral ossification through α5ß1 integrin and p38 MAPK signaling during bone growth. Our findings provide insight into molecular mechanisms governing communication between chondrocytes and surrounding ECM components in bone growth activities.

Silver-modified octahedral anatase particles as plasmonic photocatalyst.

Octahedral anatase particles (OAPs) were modified with silver nanoparticles (NPs) by photodeposition method. The properties of OAPs influenced the properties of silver deposits, and thus the photocatalytic activity of the obtained silver-modified OAPs. Photocatalytic activities were tested under UV and vis irradiation for oxidative decomposition of acetic acid and oxidation of 2-propanol, respectively. The properties of silver-modified OAPs were investigated by XRD, STEM, DRS, XPS and time-resolved microwave conductivity (TRMC) method. It was found that electron traps (ETs) worked as nucleation sites for silver, resulting in formation of smaller silver NPs on smaller OAPs with larger content of ETs. The modification with silver resulted in enhanced photocatalytic activity under both UV and vis irradiation. It was found that larger crystallite size of silver NPs, and thus larger polydispersity of silver deposits resulted in broad and intense plasmon resonance peak causing enhanced visible activity. The correlation between photocatalytic activity and TRMC data, e.g., slower decay of TRMC signal for more active samples, allowed discussion on property-governed photocatalytic activities of silver-modified titania.

Noble metal-modified octahedral anatase titania particles with enhanced activity for decomposition of chemical and microbiological pollutants.

Octahedral anatase particles (OAPs) were prepared by hydrothermal (HT) reaction of titanate nanowires (TNWs). OAPs were modified with noble metals (Au, Ag, Cu and Pt) by two photodeposition methods: in the absence and in the initial presence of oxygen in the system. Photocatalytic activities for oxidative decomposition of acetic acid and anaerobic dehydrogenation of methanol under UV/vis irradiation and for oxidation of 2-propanol under visible light irradiation were investigated. Antibacterial activities for bacteria (Escherichia coli) and fungi (Candida albicans) were investigated in the dark and under UV irradiation and/or visible light irradiation. It was found that the kind of metal deposition significantly influenced the properties of photocatalysts obtained and thus their photocatalytic and antimicrobial activities. Modification of OAPs with metallic deposits resulted in enhanced photocatalytic activities for all tested systems. Pt-modified OAPs showed the highest activity for dehydrogenation of methanol due to their highest work function and lowest activation overpotential of hydrogen evolution. Cu-modified OAPs exhibited the highest activity for oxidative decomposition of acetic acid under UV/vis irradiation, probably due to the heterojunction between Cu oxides and TiO2. On the other hand, Au-modified OAPs showed the highest photocatalytic activity under visible light irradiation due to their plasmonic properties. Bare OAPs, prepared with various durations of the HT reaction, did not have any antibacterial properties in the dark, while their activity under UV/vis irradiation was correlated with their photocatalytic activities for dehydrogenation of methanol and decomposition of acetic acid. Antimicrobial activity of modified OAPs in the dark and under visible light irradiation was the highest for Ag-modified OAPs. Under UV irradiation, Cu-modified OAPs showed the highest activity for inactivation of both bacteria and fungi.

Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways.

BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. RESULTS: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

A phase II study of SB939, a novel pan-histone deacetylase inhibitor, in patients with translocation-associated recurrent/metastatic sarcomas-NCIC-CTG IND 200†.

BACKGROUND: A subgroup of sarcomas is characterized by defining chromosomal translocations, creating fusion transcription factor oncogenes. Resultant fusion oncoproteins associate with chromatin-modifying complexes containing histone deacetylases (HDAC), and lead to epigenetic transcriptional dysregulation. HDAC inhibitors were shown to be effective in vitro, reversing gene repression by these complexes, restoring PTEN expression and apoptosis via the PI3K/Akt/mTOR pathway. PATIENTS AND METHODS: SB939 is an oral inhibitor of classes 1 and 2 HDAC. Eligible patients with recurrent or metastatic translocation-associated sarcoma (TAS) by local pathology were treated with 60 mg/day every other day for 3 of 4 weeks. Central pathology review was conducted with fusion oncogenes characterized, and HDAC2 expression correlated with efficacy in pre-specified methods. RESULTS: Twenty-two patients were treated with a median of 2 cycles. Fourteen patients were assessable for response with confirmed specific chromosomal translocations; 8 had a best response of stable disease (SD) (median duration 5.4 months) with no confirmed objective responses. The 3-month progression-free survival (PFS) rate was 49%. Among those with HDAC2 score ≥5, 7/10 had SD, versus 0/3 with HDAC2 score <5. SB939 was considered as well tolerated with <10% patients experienced ≥grade 3 toxicity. CONCLUSION: This study was stopped prematurely due to prolonged unavailability of SB939. No objective responses were seen. Although the observed SD in HDAC2 high patients was interesting, due to the small sample size, no definitive conclusion can be drawn about the efficacy of SB939 in this patient population. CLINICAL TRIAL: NCT01112384.

Risk factors of recurrent sickness absence due to depression: a two-year cohort study among Japanese employees.

PURPOSE: Depression has a high recurrence rate among employees. There have been few studies investigating risk factors for recurrent sickness absence due to depression after return to work (RTW). The objective of this study was to identify potential risk factors. METHODS: Subjects were 540 full-time employees at the biggest telecommunication company in Japan who returned to work from April 2002 to March 2008 after their first leave of absence due to depression. The Cox proportional hazard model was employed to find risk factors for recurrent sickness absence by analyzing variables including demographic, work-related and work environmental factors. RESULTS: Of 540 study subjects, 200 employees (37.0 %) experienced recurrent sickness absence due to depression after RTW within the follow-up period. Higher organizational job demand evaluated by the Brief Job Stress Questionnaire (BJSQ) was found to be a risk factor (OR 1.46, 95 % CI 1.01-2.10) for recurrent sickness absence due to depression adjusted for confounding factors. CONCLUSIONS: High organizational job demand (evaluated by BJSQ) is a risk factor for recurrent sickness absence due to depression after RTW.

Mutant allele frequency predicts the efficacy of EGFR-TKIs in lung adenocarcinoma harboring the L858R mutation.

BACKGROUND: Whether the mutant allele frequency (MAF) may also have predictive implications for tyrosine kinase inhibitor (TKI) therapy in patients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (AELAd) remains unknown. PATIENTS AND METHODS: Based on a biobanking system in conjunction with our institution, we assessed EGFR mutation status using pyrosequencing (Py) and by outsourcing laboratory tests, such as the Cycleave (Cy) and the Scorpion ARMS (A). RESULTS: Out of 705 patients enrolled in the Shizuoka Lung Cancer Mutation Study between July 2011 and March 2013, 102 AELAd patients were identified as carrying the L858R mutation (L858Rm) using Py to analyze histological specimens. Of these 102 patients, the EGFR mutation status was assessed using both Py and Cy in 48 patients: the median MAF of L858R (MAFLR) was 18.5% (range: 8%-82%), and 45 patients (94%) were identified as having an L858Rm using both Py and Cy. Three patients (6%) with discrepant L858Rm findings were only identified using Py. The plotting of a receiver operating characteristic curve to identify the discordance in L858Rm findings showed that the area under the curve for MAFLR was 0.967 (95% confidence interval: 0.91-1) and that an MAFLR of 9% resulted in high sensitivity (100%) and specificity (99%). Also, 29 patients with AELAd, excluding those with postoperative recurrences, had their L858R status assessed using Cy or A. The median age, 69 years (range: 47-84 years); male/female, 14 (48%)/15 (52%); smokers/never-smokers 13 (45%)/16 (55%); ECOG PS 0-1/2-3, 26 (90%)/3 (10%); stage IIIB/IV, 4 (14%)/25 (86%); median MAFLR, 18% (range: 8%-63%). Patients with an MAFLR of ≤9% had a significantly shorter progression-free survival (PFS) period after TKI therapy than those with an MAFLR of >9% (mPFS: 92 versus 284 days, P = 0.0027). CONCLUSION: The MAF may be a potential predictive factor of TKI treatment efficacy in patients with AELAd carrying the L858Rm.

Well-ordered monolayers of alkali-doped coronene and picene: molecular arrangements and electronic structures.

Adsorptions of alkali metals (such as K and Li) on monolayers of coronene and picene realize the formation of ordered phases, which serve as well-defined model systems for metal-intercalated aromatic superconductors. Upon alkali-doping of the monolayers of coronene and picene, scanning tunneling microscopy and X-ray absorption spectroscopy revealed the rearrangement of the entire molecular layer. The K-induced reconstruction of both monolayers resulted in the formation of a structure with a herringbone-like arrangement of molecules, suggesting the intercalation of alkali metals between molecular planes. Upon reconstruction, a shift in both the vacuum level and core levels of coronene was observed as a result of a charge transfer from alkali metals to coronene. In addition, a new density of states near the Fermi level was formed in both the doped coronene and the doped picene monolayers. This characteristic electronic feature of the ordered monolayer has been also reported in the multilayer picene films, ensuring that the present monolayer can model the properties of the metal-intercalated aromatic hydrocarbons. It is suggested that the electronic structure near the Fermi level is sensitive to the molecular arrangement, and that both the strict control and determinations of the molecular structure in the doped phase should be important for the determination of the electronic structure of these materials.

Individual-level data on the relationships of progression-free survival, post-progression survival, and tumor response with overall survival in patients with advanced non-squamous non-small cell lung cancer.

The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), or tumor response could be valid surrogate endpoints for OS after first-line chemotherapies in advanced NSCLC by using individual-level data, given the lack of research in this area. Between April 2009 and June 2011, 50 patients with advanced non-squamous NSCLC treated with cisplatin and pemetrexed as first-line chemotherapy were analyzed. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.89, P < 0.05, R2 = 0.79), PFS was moderately correlated with OS (r = 0.67, P < 0.05, R2 = 0.39), and tumor shrinkage was weakly correlated with OS (r = 0.36, P < 0.05, R2 = 0.14). Performance status at the beginning of second-line treatment, the best response to second-line treatment, and number of regimens used after progression following first-line chemotherapy were significantly associated with PPS (P < 0.05). Analysis of individual-level data suggested that PPS could be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS. These results should be validated in other larger populations.

Application of glucosylceramide-based liposomes increased the ceramide content in a three-dimensional cultured skin epidermis.

Ceramide is an intercellular lipid of the stratum corneum and is one of the most important components of the epidermal permeability barrier. Glucosylceramide (GlcCer), a ceramide precursor, was applied to three-dimensional skin culture to regulate ceramide. GlcCer/dimyristoylphosphatidylcholine (DMPC) = 4/4 (molar ratio and GlcCer/DMPC/dimyristoylphosphatidylglycerol (DMPG) = 4/4/1(molar ratio) liposomes were prepared by the thin-layer method. The particle diameters of GlcCer/DMPC and GlcCer/DMPC/DMPG liposomes were 124.0 ± 0.6 and 119.3 ± 18.9 nm, and the zeta potentials were 1.3 ± 0.3 and -19.9 ± 0.3 mV, respectively. Stability of these GlcCer liposomes was measured by transmission light scattering. Transmission light scattering of neutrally charged GlcCer (GlcCer/DMPC) liposomes increased in a time dependent manner. In contrast, negatively charged GlcCer (GlcCer/DMPC/DMPG) liposomes were not changed. ß-Glucocerebrosidase activity was measured in a cultured human skin model. Results confirmed that the cultured human skin model has ß-glucocerebrosidase activity. GlcCer/DMPC/DMPG liposomes were applied to the three-dimensional cultured human skin model, and ceramide NS, NP, AS, and AP were extracted from it. The various extracted ceramides were separated by high-performance thin-layer chromatography and quantified by a densitometer. The amount of ceramide AS only in the cultured skin model was significantly higher with the application of GlcCer-based liposomes than that of the nonapplication group, and was also dose dependent. Thus, GlcCer-based liposomes are useful for enriching the ceramide AS levels in a three-dimensional cultured skin model.

Effect of estradiol during culture of bovine oocyte-granulosa cell complexes on the mitochondrial DNA copies of oocytes and telomere length of granulosa cells.

During the development of oocytes from early antral follicles (EAFs) to antral follicles (AFs), the mitochondrial DNA copy number (Mt DNA number) increases, and granulosa cells markedly proliferate. This study examined the effect of supplementation of culture medium with estradiol-17ß (E2) on the in vitro growth of oocytes, and increases in the Mt DNA number, and telomere length during the in vitro culture of oocytes derived from EAFs (0.4-0.7 mm in diameter). The E2 supplementation improved antrum formation and the ratio of oocytes reaching the metaphase II (MII) stage, and there was a significant difference in these values between addition E2 concentrations of 10 µg/ml and 0.1 µg/ml. When the oocytes were cultured in the medium containing 10 µg/ml E2, the Mt DNA number determined by real-time polymerase chain reaction (PCR) significantly increased, and the ratio of the Mt DNA number at the end of culture to the Mt DNA number at the beginning of the culture was greatly different among cows, and could be predicted by the degree of the difference between the Mt DNA number of oocytes derived from EAFs and that of oocytes derived from AFs (3-6 mm in diameter). When oocytes were cultured for 16 days in a medium containing 10 µg/ml E2 or 0.1 µg/ml E2, the Mt DNA number of oocytes grown in vitro did not differ, but the telomere length of the granulosa cells was significantly greater in the 10 µg/ml E2 group than in the 0.1 µg/ml group. In conclusion, E2 supplementation in culture medium improved the growth of oocytes derived from EAFs, and a high E2 concentration increased the telomere length of the granulosa cells.

Age-associated changes in bovine oocytes and granulosa cell complexes collected from early antral follicles.

PURPOSE: To assess the age-associated changes in oocytes and granulosa cells derived from early antral follicles (EAFs). METHOD: Gene expression analysis of granulosa cells of the EAFs using a genome analyzer (Illumina) and in vitro culture of oocyte-granulosa cell complexes (OGCs) of EAFs (400-700 µm in diameter) collected from ovaries of aged (>120 months) and young (<50 months) cows. RESULTS: Gene expression profiles in granulosa cells of EAFs of aged cows, which included changes in genes that encode chaperone proteins and antioxidants. In vivo development of EAFs, as determined by oocyte diameter of EAFs and AFs (3-6 mm in diameter), appeared to be impaired in aged cows and the OGCs of aged cows contained low GSH compared to younger counterparts. When the OGCs were cultured in a medium containing low estradiol (E2, 0.1 µg/mL), the ratio of antrum formation was higher for OGCs from aged animals than that from young animals, while higher abnormal fertilization rate and lower total cell number of the blastocysts were observed in the OGCs of aged cows compared with those of young cows. On the contrary, when the OGCs were cultured in a medium containing 10 µg/mL E2, the ratio of antrum formation and fertilization outcome was comparable between the two age groups, whereas the total cell number of the blastocysts was still low in the aged group. CONCLUSION: Aging affects the gene expression profiles of the granulosa cells, and impairs in vitro developmental ability of OGCs collected from EAFs.

Heavy overtime work and depressive disorder among male workers.

BACKGROUND: The association between overtime and depression is unclear and very few studies have examined the association between heavy overtime work, i.e. working more than 60 h per week, and depression. AIMS: To examine the association between heavy overtime work and the onset of depressive disorder among male workers. METHODS: A 1-year follow-up cohort study of male workers in a manufacturing company in Japan, between 2008 and 2009. Working hours, depressive disorder, assessed by the Center for Epidemiologic Studies Depression (CES-D) Scale (score ≥16 points), and covariates were measured at baseline and at follow-up. Participants who had depressive disorder at baseline were excluded. RESULTS: At follow-up, 1194 participants aged between 18 and 71 years were analysed. Multiple logistic regression analysis revealed that the odds ratio for the new onset of depressive disorder was 4.5 (95% CI 1.8-11.1) times higher for employees working >60 h per week than for those working ≤50 h per week, when adjusted for age, lifestyle factors, work-related characteristics and socio-demographic characteristics at baseline and working hours at follow-up. However, the correlation between working 50.1 to 60 h per week and depressive disorder was not significant. The trend test of depressive disorder among groups by working hours was significant (P < 0.01). CONCLUSIONS: Heavy overtime work is a risk factor for the new onset of depressive disorder in this population of male workers. Working >60 h per week may be the cut-off to screen for high-risk groups who need preventive action against depressive disorder.

Coexistence effect of UVA absorbers to increase their solubility and stability of supersaturation.

OBJECTIVE: Sunscreens containing UVA absorbers in high concentrations are expected to be developed, since recent studies have suggested the possibility of involvement of UVA ray in skin cancer and early skin aging. Solubility and stability of supersaturation of UVA absorbers in UVB absorber were determined in the absence and the presence of cosmetic oil. Coexistence effect of UVA absorbers was analyzed to dissolve them in high concentrations. METHODS: Two UVA absorbers, diethylamino hydroxybenzoyl hexyl benzoate (DHHB) and butyl methoxydibenzoylmethane (BMDM), a UVB absorber, 2-ethylhexyl methoxycinnamate (EHMC), and a cosmetic oil, 2-ethylhexyl ester of oligomer of hydroxystearic acid (EH-O-HSA), were used. Their solutions were prepared at 80°C and cooled to 5°C. The solid DHHB and/or BMDM were added to it, and the time evolution of concentrations of the UVA absorbers in the solution phase was monitored. RESULTS: At the saturation in the absence of EH-O-HSA at 5°C, weight ratio of DHHB and BMDM to EHMC was 0.39/1.00 and 0.22/1.00, respectively. Addition of EH-O-HSA slightly changed the solubility of DHHB and BMDM. When the weight ratio of EH-O-HSA to EHMC was 0.20/1.00, weight ratio of DHHB and BMDM to EHMC was 0.35/1.00 and 0.25/1.00, respectively at the saturation at 5°C. In the presence of EH-O-HSA, a strong coexistence effect of DHHB and BMDM was found on their solubility. A thermodynamically stable saturated solution at 5°C having the composition that DHHB: BMDM: EHMC: EH-O-HSA = 0.47: 0.46: 1.00: 0.20 was obtained by the simultaneous addition of solid DHHB and BMDM into the initial solution. CONCLUSION: The solution type composite having the highest concentrations of DHHB and BMDM prepared in this study exhibited critical wavelength at 368 nm that was just below the border for sunscreens being qualified as 'Broad Spectrum' protection under the new rule launched by US FDA.

Influence of losartan intake on the circadian rhythm of melatonin secretion in humans.

It has been reported that losartan, an angiotensin II receptor blocker, alters the circadian rhythm of melatonin secretion and significantly reduces melatonin production. However, this finding has been confirmed at the animal experiment level only, and there are no reports of studies in humans. Therefore, we performed this study to confirm the reproducibility of the aforementioned findings of animal experiments in humans. Ten male subjects who were in good general health and free from any medical condition were recruited for this study. After a preliminary observation period of 7 days, the subjects received oral losartan treatment, 50 mg daily for 7 days. Blood samplings for measurement of the plasma melatonin concentrations were performed on day 7 of the preliminary observation period and day 7 of the losartan treatment period. The circadian rhythm of melatonin secretion after the 7-day treatment with losartan showed no significant difference from that recorded before the losartan administration. The significant decrease of the home blood pressure was observed on the afternoons. The blood samples showed significant decrease of the serum sodium and uric acid levels, along with a significant increase of the serum potassium level. The pharmacological actions of losartan at the ordinarily used clinical dose level were confirmed in humans, however, no significant inhibitory effect of the drug on melatonin secretion could be confirmed. These results are expected to be useful for guiding the proper use of angiotensin II receptor blockers.

Estradiol supports in vitro development of bovine early antral follicles.

Antrum formation and estradiol (E(2)) secretion are specific features of oocyte and granulosa cell complexes (OGCs). This study investigates the effect of E(2) on the in vitro development of bovine OGCs derived from early antral follicles as well as on the expression of genes in granulosa cells (GCs). The supplementation of culture medium with either E(2) or androstenedione (A(4)) improved the in vitro development of OGCs and the nuclear maturation of enclosed oocytes. When OGCs were cultured in medium containing A(4), developmentally competent OGCs secreted more E(2) than OGCs that were not competent. In addition, fulvestrant inhibited the effect of both E(2) and A(4) on OGCs development. Comprehensive gene expression analysis using next-generation sequence technology was conducted for the following three types of GCs: i) GCs of OGCs cultured for 4 days with E(2) (1 µg/ml; E(2)(+)), ii) GCs of OGCs cultured for 4 days without E(2) (E(2)(-)) or iii) OGCs that formed clear antrum after 8 days of in vitro culture in medium containing E(2) (1 µg/ml; AF group). GCs of the E(2)(+) group had a similar gene expression profile to the profile reported previously for the in vivo development of large follicles. This genetic profile included factors implicated in the up-regulation of E(2) biosynthesis and down-regulation of cytoskeleton and extracellular matrices. In addition, a novel gene expression profile was found in the AF group. In conclusion, E(2) impacts the gene expression profile of GCs to support the in vitro development of OGCs.