Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis in rats

Effects of a novel elastase inhibitor, ONO-5046, on nephrotoxic serum nephritis in rats. ONO-5046 is a potent, specific and intravenously active inhibitor of neutrophil elastase. To examine the role of elastase in glomerulonephritis, we tested the effects of ONO-5046 on nephrotoxic serum (NTS) nephritis in a rat model of the disease in humans. Rats were administered ONO-5046 or phosphate-buffered saline (PBS) intraperitoneally 24hours prior to injection of NTS, and they were then given equal doses of ONO-5046 or PBS three hours and 1, 2, 3, 4, 5 and 6days later. Compared with the control groups, ONO-5046 significantly reduced proteinuria and hematuria, and suppressed the formation of crescentic glomeruli in a dose-dependent manner. Our results suggest that neutrophil elastase participates in NTS nephritis by degrading glomerular basement membrane proteins, and that the elastase inhibitor, ONO-5046, suppresses crescentic formation and glomerular injury caused by elastase

Effectiveness of mHealth consultation services for preventing postpartum depressive symptoms: a randomized clinical trial

妊娠中・産後にオンライン健康医療相談が利用できることで産後うつリスクが3分の2に低下. 京都大学プレスリリース. 2023-08-03.[Background] Although many conventional healthcare services to prevent postpartum depression are provided face-to-face, physical and psychosocial barriers remain. These barriers may be overcome by using mobile health services (mHealth). To examine the effectiveness of mHealth professional consultation services in preventing postpartum depressive symptoms in real-world settings, we conducted this randomized controlled trial in Japan, where universal free face-to-face perinatal care is available. [Methods] This study included 734 pregnant women living in Yokohama city who could communicate in Japanese, recruited at public offices and childcare support facilities. The participants were randomized to the mHealth group (intervention, n = 365), where they could use a free app-based mHealth consultation service with gynecologists/obstetricians, pediatricians, and midwives whenever and as many times as they wanted between 6 p.m. and 10 p.m. on weekdays throughout their pregnancy and postpartum periods (funded by the City of Yokohama government) or the usual care group (control, n = 369). The primary outcome was the risk of elevated postpartum depressive symptoms, defined as Edinburgh Postnatal Depression Scale score ≥ 9. Secondary outcomes were self-efficacy, loneliness, perceived barriers to healthcare access, number of clinic visits, and ambulance usage. All outcomes were collected three months post-delivery. We also conducted subgroup analyses assessing the differences in the treatment effect by sociodemographic status. [Results] Most women completed all questionnaires (n = 639 of 734, response rate: 87%). The mean baseline age was 32.9 ± 4.2 years, and 62% were primipara. Three months post-delivery, women in the mHealth group had a lower risk of elevated postpartum depressive symptoms (47/310 [15.2%]) compared to the usual care group (75/329 [22.8%], risk ratio: 0.67 [95% confidence interval: 0.48–0.93]). Compared with the usual care group, women in the mHealth group had higher self-efficacy, less loneliness, and fewer perceived barriers to healthcare access. No differences were observed in the frequency of clinic visits or ambulance usage. Furthermore, in the subgroup analyses, we did not find differences in the treatment effect by sociodemographic status. [Conclusions] Local government-funded mHealth consultation services have a preventive effect on postpartum depressive symptoms, removing physical and psychological barriers to healthcare access in real-world settings

Characterization of Quasispecies of Pandemic 2009 Influenza A Virus (A/H1N1/2009) by De Novo Sequencing Using a Next-Generation DNA Sequencer

Pandemic 2009 influenza A virus (A/H1N1/2009) has emerged globally. In this study, we performed a comprehensive detection of potential pathogens by de novo sequencing using a next-generation DNA sequencer on total RNAs extracted from an autopsy lung of a patient who died of viral pneumonia with A/H1N1/2009. Among a total of 9.4×106 40-mer short reads, more than 98% appeared to be human, while 0.85% were identified as A/H1N1/2009 (A/Nagano/RC1-L/2009(H1N1)). Suspected bacterial reads such as Streptococcus pneumoniae and other oral bacteria flora were very low at 0.005%, and a significant bacterial infection was not histologically observed. De novo assembly and read mapping analysis of A/Nagano/RC1-L/2009(H1N1) showed more than ×200 coverage on average, and revealed nucleotide heterogeneity on hemagglutinin as quasispecies, specifically at two amino acids (Gly172Glu and Gly239Asn of HA) located on the Sa and Ca2 antigenic sites, respectively. Gly239 and Asn239 on antigenic site Ca2 appeared to be minor amino acids compared with the highly distributed Asp239 in H1N1 HAs. This study demonstrated that de novo sequencing can comprehensively detect pathogens, and such in-depth investigation facilitates the identification of influenza A viral heterogeneity. To better characterize the A/H1N1/2009 virus, unbiased comprehensive techniques will be indispensable for the primary investigations of emerging infectious diseases

Diurnal Characteristics of Rainfall over the Contiguous United States and Northern Mexico in the Dynamically Downscaled Reanalysis Dataset (US10)

The diurnal characteristics of summer rainfall in the contiguous United States and northern Mexico were examined with the United States reanalysis for 5 years in 10-km horizontal resolution (US10), which is dynamically downscaled from the National Centers for Environmental Prediction National Center for Atmospheric Research (NCEP-NCAR) Global Reanalysis 1 using the Regional Spectral Model (RSM). The hourly precipitation outputs demonstrate a realistic structure in the temporal evolution of the observed rainfall episodes and their magnitudes across the United States without any prescriptions of the observed rainfall to the global reanalysis and the downscaled regional reanalysis. Nighttime rainfall over the Great Plains associated with eastward-propagating, mesoscale convective systems originating from the Rocky Mountains is also represented realistically in US 10, while the original reanalysis and most general circulation models (GCMs) have difficulties in capturing the series of nocturnal precipitation events in summer over the Plains. The results suggest an important role of the horizontal resolution of the model in resolving small-scale, propagating convective systems to improve the diurnal cycle of summer rainfall.open3

Role of PERK in mitochondrial function

Mitochondria play a central role in the function of brown adipocytes (BAs). Although mitochondrial biogenesis, which is indispensable for thermogenesis, is regulated by coordination between nuclear DNA transcription and mitochondrial DNA transcription, the molecular mechanisms of mitochondrial development during BA differentiation are largely unknown. Here, we show the importance of the ER-resident sensor PKR-like ER kinase (PERK) in the mitochondrial thermogenesis of brown adipose tissue. During BA differentiation, PERK is physiologically phosphorylated independently of the ER stress. This PERK phosphorylation induces transcriptional activation by GA-binding protein transcription factor α subunit (GABPα), which is required for mitochondrial inner membrane protein biogenesis, and this novel role of PERK is involved in maintaining the body temperatures of mice during cold exposure. Our findings demonstrate that mitochondrial development regulated by the PERK–GABPα axis is indispensable for thermogenesis in brown adipose tissue

Clinical application of removable partial dentures using thermoplastic resin—Part I: Definition and indication of non-metal clasp dentures

AbstractThis position paper proposes a definition and naming standard for removable partial dentures (RPDs) using thermoplastic resin, and presents a guideline for clinical application. A panel of 14 experts having broad experience with clinical application of RPDs using thermoplastic resin was selected from members of the Japan Prosthodontic Society. At a meeting of the panel, “non-metal clasp denture” was referred as the generic name of RPDs with retentive elements (resin clasps) made of thermoplastic resin. The panel classified non-metal clasp dentures into two types: one with a flexible structure that lacks a metal framework and the other having a rigid structure that includes a metal framework. According to current prosthetic principles, flexible non-metal clasp dentures are not recommended as definitive dentures, except for limited cases such as patients with a metal allergy. Rigid non-metal clasp dentures are recommended in cases where patients will not accept metal clasps for esthetic reasons. Non-metal clasp dentures should follow the same design principles as conventional RPDs using metal clasps

Clinical application of removable partial dentures using thermoplastic resin. Part II: Material properties and clinical features of non-metal clasp dentures

This position paper reviews physical and mechanical properties of thermoplastic resin usedfor non-metal clasp dentures, and describes feature of each thermoplastic resin in clinicalapplication of non-metal clasp dentures and complications based on clinical experience ofexpert panels. Since products of thermoplastic resin have great variability in physical andmechanical properties, clinicians should utilize them with careful consideration of thespecific properties of each product. In general, thermoplastic resin has lower color-stabilityand higher risk for fracture than polymethyl methacrylate. Additionally, the surface ofthermoplastic resin becomes roughened more easily than polymethyl methacrylate. Studiesrelated to material properties of thermoplastic resin, treatment efficacy and follow-up areinsufficient to provide definitive conclusions at this time. Therefore, this position papershould be revised based on future studies and a clinical guideline should be provided