Disability Weights Measurement for 17 Diseases in Japan: A Survey Based on Medical Professionals

When judging a population’s health to determine disability-adjusted life years, disability weight is a tool for measuring the severity of disability caused by a disease. However, previous studies have pointed out that surveys targeting ordinary citizens produce unclear disability weight values. Therefore, in an attempt to obtain clearer estimations, we conduct a paper-based questionnaire survey of medical professionals—nurses with over ten years of experience—believed to have extensive knowledge of diseases and experience in patient care. We find that disability weight estimations based on the survey of medical professionals presents higher values than those based on a survey of ordinary citizens using the same estimation approach, especially for non-terminal-stage diseases. This suggests that medical-professionals-based surveys may correct the underestimated disability weights of non-terminal diseases (e.g., early stage of cancers and mellitus) found through ordinary-citizens-based surveys. Moreover, we illustrate that depressive disorder and early-stage cancers have almost the same health loss since their disability weights are similar. While regulating policy, it is recommended that more attention be paid to non-terminal diseases and depression

Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium

Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1α activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1α protein stabilization in endometrial stromal cells, and that CS-induced HIF-1α-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1α might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling

Inflammatory Cytokine-Induced HIF-1 Activation Promotes Epithelial–Mesenchymal Transition in Endometrial Epithelial Cells

The endometrium undergoes repeated proliferation and shedding during the menstrual cycle. Significant changes to this environment include fluctuations in the partial pressure of oxygen, exposure to a high-cytokine environment associated with intrauterine infection, and inflammation. Chronic endometritis is a condition wherein mild inflammation persists in the endometrium and is one of the causes of implantation failure and miscarriage in early pregnancy. It is thought that the invasion of embryos into the endometrium requires epithelial–mesenchymal transition (EMT)-associated changes in the endometrial epithelium. However, the effects of inflammation on the endometrium remain poorly understood. In this study, we investigated the effects of the intrauterine oxygen environment, hypoxia-inducible factor (HIF), and inflammation on the differentiation and function of endometrial epithelial cells. We elucidated the ways in which inflammatory cytokines affect HIF activity and EMT in an immortalized cell line (EM-E6/E7/TERT) derived from endometrial epithelium. Pro-inflammatory cytokines caused significant accumulation of HIF-1α protein, increased HIF-1α mRNA levels, and enhanced hypoxia-induced accumulation of HIF-1α protein. The combined effect of inflammatory cytokines and hypoxia increased the expression of EMT-inducing factors and upregulated cell migration. Our findings indicate that pro-inflammatory factors, including cytokines and LPS, work synergistically with hypoxia to activate HIF-1 and promote EMT in endometrial epithelial cells

Concentration of stromal cell‐derived factor‐1 (SDF‐1/CXCL12) in the follicular fluid is associated with blastocyst development

Abstract Purpose To study the association between stromal cell‐derived factor‐1 (SDF‐1/CXCL12) and vascular endothelial growth factor (VEGF) concentrations in individual human ovarian follicles and IVF outcomes. Methods Concentrations of SDF‐1 and VEGF in 261 follicular fluid samples were measured with enzyme‐linked immunosorbent assay. IVF outcome parameters were included in fertilization rate, cleavage rate, embryo morphology on day 3, and blastocyst morphology on day 5. Results The follicular concentration of SDF‐1 and VEGF was not significantly associated with fertilization and cleavage outcome, and embryo morphology. The rates of full blastocysts and good‐quality blastocysts were significantly higher in follicles with an SDF‐1 concentration of 275‐350 pg/mL than in the follicles with SDF‐1 concentrations of <200 and ≥350 pg/mL (P < 0.05). The follicular concentration of VEGF was not associated with the blastocyst morphology. Conclusion Our findings showed that follicular concentration of SDF‐1, and not VEGF, may be a valuable biochemical marker of blastocyst development

Synthesis, Properties, and Biodegradability of Thermoplastic Elastomers Made from 2-Methyl-1,3-propanediol, Glutaric Acid and Lactide

An innovative type of biodegradable thermoplastic elastomers with improved mechanical properties from very common and potentially renewable sources, poly(L-lactide)-b-poly(2-methyl-1,3-propylene glutarate)-b-poly(L-lactide) (PLA-b-PMPG-b-PLA)s, has been developed for the first time. PLA-b-PMPG-b-PLAs were synthesized by polycondensation of 2-methyl-1,3-propanediol and glutaric acid and successive ring-opening polymerization of L-lactide, where PMPG is an amorphous central block with low glass transition temperature and PLA is hard semicrystalline terminal blocks. The copolymers showed glass transition temperature at lower than −40 °C and melting temperature at 130–152 °C. The tensile tests of these copolymers were also performed to evaluate their mechanical properties. The degradation of the copolymers and PMPG by enzymes proteinase K and lipase PS were investigated. Microbial biodegradation in seawater was also performed at 27 °C. The triblock copolymers and PMPG homopolymer were found to show 9–15% biodegradation within 28 days, representing their relatively high biodegradability in seawater. The macromolecular structure of the triblock copolymers of PLA and PMPG can be controlled to tune their mechanical and biodegradation properties, demonstrating their potential use in various applications

Synthesis, Properties, and Biodegradability of Thermoplastic Elastomers Made from 2-Methyl-1,3-propanediol, Glutaric Acid and Lactide

An innovative type of biodegradable thermoplastic elastomers with improved mechanical properties from very common and potentially renewable sources, poly(L-lactide)-b-poly(2-methyl-1,3-propylene glutarate)-b-poly(L-lactide) (PLA-b-PMPG-b-PLA)s, has been developed for the first time. PLA-b-PMPG-b-PLAs were synthesized by polycondensation of 2-methyl-1,3-propanediol and glutaric acid and successive ring-opening polymerization of L-lactide, where PMPG is an amorphous central block with low glass transition temperature and PLA is hard semicrystalline terminal blocks. The copolymers showed glass transition temperature at lower than &minus;40 &deg;C and melting temperature at 130&ndash;152 &deg;C. The tensile tests of these copolymers were also performed to evaluate their mechanical properties. The degradation of the copolymers and PMPG by enzymes proteinase K and lipase PS were investigated. Microbial biodegradation in seawater was also performed at 27 &deg;C. The triblock copolymers and PMPG homopolymer were found to show 9&ndash;15% biodegradation within 28 days, representing their relatively high biodegradability in seawater. The macromolecular structure of the triblock copolymers of PLA and PMPG can be controlled to tune their mechanical and biodegradation properties, demonstrating their potential use in various applications

Host Immune Response and Novel Diagnostic Approach to NTM Infections

The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of immunocompromised conditions, such as the post-transplantation state. The importance of proper diagnosis and management of NTM infection has been recently recognized. Host immunological responses play integral roles in vulnerability to NTM infections, and may contribute to the onset of specific types of NTM infection. Furthermore, distinct NTM species are known to affect and attenuate these host immune responses in unique manners. Therefore, host immune responses must be understood with respect to each causative NTM species. Here, we review innate, cellular-mediated, and humoral immunity to NTM and provide perspectives on novel diagnostic approaches regarding each NTM species

Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates

The number of patients infected with H7N9 influenza virus has been increasing since 2013. We examined the efficacy of neuraminidase (NA) inhibitors and the efficacy of a vaccine against an H7N9 influenza virus, A/Anhui/1/2013 (H7N9), isolated from a patient in a cynomolgus macaque model. NA inhibitors (oseltamivir and peramivir) barely reduced the total virus amount because of the emergence of resistant variants with R289K or I219T in NA [residues 289 and 219 in N9 of A/Anhui/1/2013 (H7N9) correspond to 292 and 222 in N2, respectively] in three of the six treated macaques, whereas subcutaneous immunization of an inactivated vaccine derived from A/duck/Mongolia/119/2008 (H7N9) prevented propagation of A/Anhui/1/2013 (H7N9) in all vaccinated macaques. The percentage of macaques in which variant H7N9 viruses with low sensitivity to the NA inhibitors were detected was much higher than that of macaques in which variant H5N1 highly pathogenic influenza virus was detected after treatment with one of the NA inhibitors in our previous study. The virus with R289K in NA was reported in samples from human patients, whereas that with I219T in NA was identified for the first time in this study using macaques, though no variant H7N9 virus was reported in previous studies using mice. Therefore, the macaque model enables prediction of the frequency of emerging H7N9 virus resistant to NA inhibitors in vivo. Since H7N9 strains resistant to NA inhibitors might easily emerge compared to other influenza viruses, monitoring of the emergence of variants is required during treatment of H7N9 influenza virus infection with NA inhibitors