Diabetic nephropathy is a leading cause of proteinuria, kidney fibrosis, and subsequent end-stage renal disease. The renal prognosis of diabetic patients with refractory proteinuria is extremely poor. Therefore, identification of novel therapeutic targets to combat this serious condition and improve renal prognosis is urgently necessary. In diabetic patients, in addition to blood glucose levels, serum levels of free fatty acids (FFAs) are chronically elevated, even during postprandial periods. Of the various types of FFAs, saturated FFAs are highly cytotoxic and their levels are elevated in the serum of patients with diabetes. Thus, an increase in saturated FFAs is currently thought to contribute to proximal tubular cell damage and podocyte injury in diabetic nephropathy. Therefore, protecting both types of kidney cells from saturated FFA-related lipotoxicity may become a novel therapeutic approach for diabetic patients with refractory proteinuria. Interestingly, accumulating evidence suggests that controlling intracellular nutrient signals and autophagy can ameliorate the FFA-related kidney damage. Here, we review the evidence indicating possible mechanisms underlying cell injury caused by saturated FFAs and cell protective roles of intracellular nutrient signals and autophagy in diabetic nephropathy.

In aging societies, sarcopenia is considered to be a significant threat for the elderly and for people with multimorbidities. Although several diagnostic algorithms are currently available, no guidelines are so far available for the prevention and intervention of sarcopenia. Therefore, we decided to publish clinical sarcopenia guidelines by collaboration with the Japanese Association on Sarcopenia and Frailty, the Japan Geriatrics Society, and the National Center for Geriatrics and Gerontology to provide tools for clinical practice. We published a Japanese version in December 2017 and an English version in May 2018. This article is a summary of these clinical sarcopenia guidelines. As the disease code of sarcopenia is available in Japan, these guidelines would be useful for many healthcare professionals and can be used for the prevention of disabilities in the elderly.

Patients with patulous Eustachian tubes (PET) suffer from annoying aural symptoms, such as voice or breath autophony, and aural fullness due to the ET's abnormal patency. It may lead to an enormous reduction in quality of life. Various treatment methods, including conservative and surgical therapy, have been reported. In most cases, conservative treatment is sufficient to relieve patients of aural symptoms. However, some chronic and severe cases are resistant to traditional conservative therapy. Recently performed prospective and multicenter trials revealed the efficacy and safety of a silicone plug (Kobayashi plug) insertion for patients with severe PET. Patulous Eustachian tube handicap inventory-10 (PHI-10), tubal obstruction procedures, sitting computed tomography (CT), and ET function tests (tubo-tympano-aerodynamic graphy (TTAG) and sonotubometry) are useful for diagnosis as well as selecting candidates for surgery in severe cases.

Introduction: The cause of the syphilis resurgence in Japan is still unknown. In this study, we hypothesized that the spread of mobile dating software for use on mobile phones might have contributed to it. We investigated possible contributing factors of the syphilis resurgence in Japan.

Methods: We retrieved the number of reported cases of syphilis, human immunodeficiency virus infection, carbapenem-resistant Enterobacteriaceae infection, invasive Streptococcus pneumoniae infection, general population, foreign national residents, international overnight guests, detachment-type sex trade shops, physician density, and smartphone penetration rate at the prefectural level in 2017. We also obtained the number of three major dating app users in each prefecture. Using them, we performed association analyses.

Results: The median of syphilis incidence per 100,000 prefectural population was 2.34 (range 0.72 to 12.90). The values of Spearman's rank correlation coefficients between syphilis incidence and app penetration rates were 0.59 (p < 0.001) for app 1, 0.57 (p < 0.001) for app 2, and 0.56 for app 3 (p < 0.001). The values of correlation coefficient between syphilis incidence and prefectural population (0.50, p < 0.001), foreign national residents per prefectural population (0.46, p = 0.001), and smartphone penetration rate (0.54, p < 0.001) were significant, while international overnight guests per prefectural population (0.19, p = 0.19), sex trade shops (0.24, p = 0.10), and physician density (0.10, p = 0.52) were not. In the multiple regression analyses, the contents of an optimized model included the following two factors: for app 1 penetration rate (0.39, p < 0.001) and the number of sex trade shops per prefectural population (0.18, p = 0.008) with the adjusted R-squared value 0.49 and F value 22.97 (p < 0.001).

Conclusions: Dating app penetration rate was significantly associated with syphilis incidence. The popularization of social media is a possible contributing factor in the syphilis resurgence in Japan. Information concerning the use of social media should be included in future studies on transmission and prevention of sexually transmitted infections.

Introduction: The paucity and maldistribution of physicians among various specialties are key issues facing the Japanese health care system. Studies have shown that young physicians place more emphasis on work-life balance while selecting their specialty and that they prefer controllable lifestyle (CL) specialties over noncontrollable lifestyle (NCL) specialties. As this may be a cause of maldistribution, we investigated the relationship between views on work-life balance and specialty selection among young physicians in Japan.

Methods: An online questionnaire was sent to 1451 residents (postgraduate years 1-5) at 60 Japanese Red Cross hospitals across Japan.

Results: In all, 226 physicians responded (response rate: 15%), with 21% in CL and 74% in NCL specialties. When compared with NCL specialties, CL specialties had less overtime (43% vs. 16%, p = 0.001), considered life to be more important than work (26% vs. 15%, p = 0.018), and were more likely to give precedence to work-life balance over medical interest while choosing their specialty (49% vs. 30%, p < 0.001). Furthermore, physicians were more likely to change their choice of specialty, contrary to their professional interest, because of social reasons (49% vs. 26%, p = 0.007).

Conclusions: Our study suggests that young physicians in CL specialties have better working hours and place more emphasis on work-life balance while choosing their specialty compared with those in NCL specialties. The increase in the number of physicians in CL specialties is likely attributable to the growing preference for an optimal work-life balance among young physicians; this seems to have increased the maldistribution of physicians among various specialties. Institutional mechanisms to support the lifestyle of physicians (especially in NCL specialties) are required to provide a balanced medical service in Japan.

Introduction: To clarify the usefulness of glucose challenge test (GCT), the rate of gestational diabetes mellitus (GDM) detection and perinatal outcomes were compared between the groups of random blood glucose level (RBG) and 50 g GCT in this study.

Methods: The first survey was conducted at 255 institutions registered by the Kanto Society of Obstetrics and Gynecology and clinical training institutions in the Kanto Area, followed by a second survey. The included women were broadly classified into the RBG and GCT groups, according to the mid-trimester blood glucose screening method, and the perinatal outcomes of the two groups were retrospectively compared. The primary outcomes were the proportion of infants weighing 3,500 g or more and birth weight ≥90^th-percentile infants.

Results: The rate of GDM diagnosis was significantly higher in the GCT group (7.6%) than that in the RBG group (4.8%). However, no significant differences were observed in perinatal outcomes, i.e., the proportion of infants weighing 3,500 g or more or birth weight ≥90^th percentile.

Conclusions: GCT is not superior for predicting infants weighing 3,500 g or more and birth weight ≥90^th percentile, as compared with RBG.

Introduction: Infrastructure and the capacity to conduct clinical research in pediatrics have not been fully established in Japan. To elucidate the physicians' perspectives on clinical research, level of experience, existing barriers, and requests for support, we conducted a survey at 34 children's hospitals in Japan.

Methods: In January 2016, an online survey with 13 questions was sent to approximately 2000 physicians working in 34 pediatric hospitals belonging to the Japanese Association of Children's Hospitals and Related Institutions.

Results: Of the 360 respondents, 318 (88.3%) had presentations at academic conferences, and 261 (72.5%) had publications in academic journals, in the previous year. The most common study designs of clinical research conducted were case reports and case series. The most requested supports were for statistical analysis, followed by study design, grant application, and English-language editing. Younger physicians were more likely to prefer educational lectures (p < 0.001), whereas experienced physicians were more likely to request support for conducting statistical analysis (p = 0.002). Whereas physicians who had ever led a clinical trial requested support for the development of study protocol (p =.013), those without this experience preferred support for literature review (p =.002) and consultation services for study design (p =.027).

Conclusions: The requests for supports were different, depending on the physicians' years after graduation and experience level in clinical research. In order to enhance clinical research in pediatrics, it is essential to provide appropriate types and levels of educational and support programs.

Introduction: To investigate the proportion of those having preferred place for end-of-life care among residents in a remote island and its association with family composition.

Methods: Cross-sectional questionnaire survey was conducted in Ajishima, an island 23 km away from the coast of Ishinomaki City, northeast of Japan. Between October 2017 and February 2018, the questionnaire was distributed to 288 eligible residents and 113 valid responses were analyzed. Primary outcome was whether the subjects had preferred place for end-of-life care. The explanatory variable was family composition defined as whether having family members inside or outside the island [none (In−/Out−), only inside the island (In+/Out−), only outside the island (In−/Out+), and both inside and outside (In+/Out+) ]. Poisson regression analysis was used to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs) of showing preferred place in each group.

Results: The proportion of those having preferred place for end-of-life care was 72.6% in total. This rate significantly differed across family composition groups: 67.6%, 40.0%, and 82.9% for In+/Out+, In+/Out−, and In−/Out+ groups, respectively. The PR (95%CI) of having preferred place was 0.66 (0.33, 1.36) and 1.26 (1.01, 1.56) for In+/Out− and In−/Out+ groups, respectively, compared with In+/Out+ group.

Conclusions: This study showed that significantly higher preference for place of end-of-life care was seen among residents who had family members only outside the island compared with those who had families both inside and outside. Health care professionals should consider family compositions when initiating end-of-life discussion to residents in remote areas.

Pharmaceutical expenditure has been rapidly increasing since 2000 in Japan mainly due to successive introduction and diffusion of high-priced new pharmaceuticals (thereafter, drugs). The share of drug expenditure in the national healthcare expenditure rose from 19.6% in 2000 to 22.3% in 2013, a 2.7% point rise in 13 years. In the same period, the share of healthcare personnel's income dropped 3.8% points from 50.2% to 46.4%. Further, in 2016 national healthcare expenditure rose for 3.8%, which is exceptionally high by Japanese standard (roughly 2%), and the main culprit was the rapid increase in drug expenditure due to successive introduction of extremely high-priced drugs.

Due to these changes, drugs have become the main target in current healthcare cost containment policy.

In this article, I briefly explain two debates relating to drug cost and cost control that occurred in 2016 and 2017, respectively, in Japan, based on my two articles that I wrote when I participated in these debates. Although two debates are independent, the first debate that was triggered by an introduction of extraordinary high-priced drug (Opdivo) substantially affected the second debate on how to introduce official cost-effectiveness appraisal of new drugs in Japan.