Population health and regional variations of disease burden in Japan, 1990–2015:a systematic subnational analysis for the Global Burden of Disease Study 2015

BackgroundJapan has entered the era of super-ageing and advanced health transition, which is increasingly putting pressure on the sustainability of its health system. The level and pace of this health transition might vary across regions within Japan and concern is growing about increasing regional variations in disease burden. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides a comprehensive, comparable framework. We used data from GBD 2015 with the aim to quantify the burden of disease and injuries, and to attribute risk factors in Japan at a subnational, prefecture-level.MethodsWe used data from GBD 2015 for 315 causes and 79 risk factors of death, disease, and injury incidence and prevalence to measure the burden of diseases and injuries in Japan and in the 47 Japanese prefectures from 1990 to 2015. We extracted data from GBD 2015 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy, and healthy life expectancy (HALE) in Japan and its 47 prefectures. We split extracted data by prefecture and applied GBD methods to generate estimates of burden, and attributable burden due to known risk factors. We examined the prefecture-level relationships of common health system inputs (eg, health expenditure and workforces) to the GBD outputs in 2015 to address underlying determinants of regional health variations.FindingsLife expectancy at birth in Japan increased by 4·2 years from 79·0 years (95% uncertainty interval [UI] 79·0 to 79·0) to 83·2 years (83·1 to 83·2) between 1990 and 2015. However, the gaps between prefectures with the lowest and highest life expectancies and HALE have widened, from 2·5 to 3·1 years and from 2·3 to 2·7 years, respectively, from 1990 to 2015. Although overall age-standardised death rates decreased by 29·0% (28·7 to 29·3) from 1990 to 2015, the rates of mortality decline in this period substantially varied across the prefectures, ranging from -32·4% (-34·8 to -30·0) to -22·0% (-20·4 to -20·1). During the same time period, the rate of age-standardised DALYs was reduced overall by 19·8% (17·9 to 22·0). The reduction in rates of age-standardised YLDs was very small by 3·5% (2·6 to 4·3). The pace of reduction in mortality and DALYs in many leading causes has largely levelled off since 2005. Known risk factors accounted for 34·5% (32·4 to 36·9) of DALYs; the two leading behavioural risk factors were unhealthy diets and tobacco smoking in 2015. The common health system inputs were not associated with age-standardised death and DALY rates in 2015.InterpretationJapan has been successful overall in reducing mortality and disability from most major diseases. However, progress has slowed down and health variations between prefectures is growing. In view of the limited association between the prefecture-level health system inputs and health outcomes, the potential sources of regional variations, including subnational health system performance, urgently need assessment.FundingBill & Melinda Gates Foundation, Japan Ministry of Education, Science, Sports and Culture, Japan Ministry of Health, Labour and Welfare, AXA CR Fixed Income Fund and AXA Research Fund

自発的高運動ラットの安静時遺伝子発現パターンと野生型ラット運動時遺伝子発現パターンの違い

The Spontaneously-Running Tokushima Shikoku (SPORTS) strain is an original line derived from Wistar rats, which spontaneously runs >6 km/day on wheels, and has better glucose tolerance and less fat than Wistar rats. However, the molecular mechanism that contributes to the increased metabolic activity in SPORTS rats is unknown. The present study aimed to characterize the gene expression profiles of skeletal muscles in SPORTS rats housed under sedentary (SED) conditions. We found that the expression levels of genes encoding mitochondrial respiratory chain enzymes such as ATP synthase 6 (mt-Atp6) and cytochrome c oxidase subunit 6c (Cox 6c), were higher in the soleus (SOL) muscles of SED SPORTS than in SED Wistar rats. The ratio of type IIa myofibers was higher and glucose tolerance was better in SED SPORTS than in Wistar rats that were sedentary and trained daily on treadmills, respectively. We then investigated candidate genes that might contribute to the better glucose tolerance of SED SPORTS rats using DNA microarray analysis. Among 116 upregulated genes in the SOL muscles of SED SPORTS rats, only 19 were also increased in trained Wistar rats. We focused on v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (Erbb3), which was associated with glucose transport in myocytes, and found higher expression levels in the SOL muscles of SED SPORTS than in SED Wistar rats. The SOL muscles of SED SPORTS rats also contained more activity of β-hydroxy-acylCoA dehydrogenase, a key enzyme of β-oxidation, indicating enhanced lipid oxidation. These findings suggest that increased metabolic activity in skeletal muscle (especially the SOL muscle) of SPORTS rats is congenital and that gene expression profiles of SPORTS rats and Trained Wistar rats are different

Generation of three induced pluripotent stem cell lines from postmortem tissue derived following sudden death of a young patient with STXBP1 mutation

We established three iPSC lines from postmortem-cultured fibroblasts derived following the sudden unexpected death of an 8-year-old girl with Lennox-Gastaut syndrome, who turned out to have the R551H-mutant STXBP1 gene. These iPSC clones showed pluripotent characteristics while retaining the genotype and demonstrated trilineage differentiation capability, indicating their utility in disease-modeling studies, i.e., STXBP1-encephalopathy. This is the first report on the establishment of iPSCs from a sudden death child, suggesting the possible use of postmortem-iPSC technologies as an epoch-making approach for precise identification of the cause of sudden death

Spatial heterogeneities in tectonic stress in Kyushu, Japan and their relation to a major shear zone Seismology

We investigated the spatial variation in the stress fields of Kyushu Island, southwestern Japan. Kyushu Island is characterized by active volcanoes (Aso, Unzen, Kirishima, and Sakurajima) and a shear zone (western extension of the median tectonic line). Shallow earthquakes frequently occur not only along active faults but also in the central region of the island, which is characterized by active volcanoes. We evaluated the focal mechanisms of the shallow earthquakes on Kyushu Island to determine the relative deviatoric stress field. Generally, the stress field was estimated by using the method proposed by Hardebeck and Michael (2006) for the strike-slip regime in this area. The minimum principal compression stress (σ3), with its near north-south trend, is dominant throughout the entire region. However, the σ 3 axes around the shear zone are rotated normal to the zone. This result is indicative of shear stress reduction at the zone and is consistent with the right-lateral fault behavior along the zone detected by a strain-rate field analysis with global positioning system data. Conversely, the stress field of the normal fault is dominant in the Beppu-Shimabara area, which is located in the central part of the island. This result and the direction of σ3 are consistent with the formation of a graben structure in the area

Improvement of Psoriasis by Alteration of the Gut Environment by Oral Administration of Fucoidan from Cladosiphon Okamuranus

Psoriasis is a chronic autoimmune inflammatory disease for which there is no cure; it results in skin lesions and has a strong negative impact on patients’ quality of life. Fucoidan from Cladosiphon okamuranus is a dietary seaweed fiber with immunostimulatory effects. The present study reports that the administration of fucoidan provided symptomatic relief of facial itching and altered the gut environment in the TNF receptor-associated factor 3-interacting protein 2 (Traf3ip2) mutant mice (m-Traf3ip2 mice); the Traf3ip2 mutation was responsible for psoriasis in the mouse model used in this study. A fucoidan diet ameliorated symptoms of psoriasis and decreased facial scratching. In fecal microbiota analysis, the fucoidan diet drastically altered the presence of major intestinal opportunistic microbiota. At the same time, the fucoidan diet increased mucin volume in ileum and feces, and IgA contents in cecum. These results suggest that dietary fucoidan may play a significant role in the prevention of dysfunctional immune diseases by improving the intestinal environment and increasing the production of substances that protect the immune system

Surface Capping-Assisted Hydrothermal Growth of Gadolinium-Doped CeO₂ Nanocrystals Dispersible in Aqueous Solutions

Nanocrystals of 20 mol % Gd³⁺-doped CeO₂ dispersible in basic aqueous solutions were grown via hydrothermal treatment of anionic Ce­(IV) and Gd­(III) carbonate complexes at 125–150 °C for 6–24 h with N­(CH₃)₄⁺ as a capping agent. The nanocrystals were characterized in detail using dynamic light scattering (DLS), ζ-potential measurements, X-ray diffraction (XRD), specific surface area measurements based on the Brunauer–Emmett–Teller theory (SSA_BET), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy, and Raman spectroscopy. DLS analysis revealed that the highly transparent product solution consisted of nanocrystals approximately 10–20 nm of hydrodynamic diameter with a very narrow size distribution, while the ζ-potential analysis results strongly suggested that the N­(CH₃)₄⁺ capped negatively charged sites on the nanocrystals’ surface and provided sufficient repulsive steric effect to prevent agglomeration. Moreover, the crystallite size (<i>d</i>_XRD) estimated from the XRD patterns and the equivalent particle size (<i>d</i>_BET) estimated from the SSA_BET data were in the range between 5–6 and 4–4.5 nm, respectively, and nearly constant independent of reaction time, indicating suppressed Ostwald ripening due to capping. Good agreement between the values obtained from the <i>d</i>_XRD and <i>d</i>_BET analyses with the size of the primary nanocrystals observed in the TEM image also confirmed that the primary nanocrystals were single crystals and nearly free from aggregation. Furthermore, the gadolinium content in the as-prepared nanocrystals was determined to be very close to 20 mol % and remained unchanged after HCl treatment, indicating successful doping of stoichiometric amount of Gd³⁺ into CeO₂ lattices. Finally, the Raman analysis suggested that only a slightly Gd³⁺-rich phase was present in the nanocrystals grown for shorter reaction times. By increasing the reaction time, even at 125 °C, the Gd³⁺ was homogeneously distributed into the CeO₂ lattices via solid state diffusion

Significant nutrient consumption in the dark subsurface layer during adiatom bloom : a case study on Funka Bay, Hokkaido, Japan

We conducted repetitive observations in Funka Bay, Hokkaido, Japan, on 15 February, 4 and 15 March, and 14 April 2019. The diatom spring bloom peaked on 4 March and started declining on 15 March. Funka Bay winter water remained below 30 m depth, which was below the surface mixed-layer and dark-layer depth (0.1 % of the surface photosynthetically active radiation, PAR, depth) on 4 and 15 March. In the subsurface layer at depths of 30-50 m, concentrations of NO3-, PO43-, and Si(OH)(4) decreased by half between these dates, even in the dark. Incubation experiments using the diatom Thalassiosira nordenskioeldii showed that this diatom could consume added nutrients in the dark at substantial rates after pre-culturing to deplete nutrients. Incubation experiments using natural seawater collected in the growing phase of the bloom on 8 March 2022 also showed that nutrient-depleted phytoplankton could consume added nutrients in the dark. We excluded three physical process - water mixing, diffusive transport, and subduction - as possible main reasons for the decrease in nutrients in the subsurface layer. We conclude that the nutrient reduction in the subsurface layer (30-50 m) between 4 and 15 March 2019 could be explained by nutrient consumption by diatoms in the dark in that layer

Isoprene production in the water column and sediment in Funka Bay, Hokkaido, Japan

We conducted shipboard observations in Funka Bay, Hokkaido, Japan, in 2015, 2016 and 2019 to observe temporal variations of isoprene (C5H8) concentration in water and sediment. We found increases in C5H8 concentrations below and within the euphotic zone, which were associated with chl-a peaks and changes in nutrient and dissolved oxygen (DO). We found a C5H8 peak in the subsurface layer within the euphotic zone at 20-30 m depth in May-June 2019 that coincided with a decrease in DO, suggesting that there was net oxygen consumption. We hypothesize that the rapid cycle of regenerated production in the subsurface layer in early summer resulted in C5H8 production (1.00-1.75 pmol (mu g chl-a) d(-1) at 30 m), decreased DO, relatively high chl-a levels, and nutrient depletion. We propose that C5H8 can be used as a new chemical parameter reflecting primary production, in addition to the common parameters of chlorophyll-a, nutrients, and oxygen. We attributed a C5H8 peak at the surface in May-June 2019 to photosynthetic production of C5H8 associated with new production, likely stimulated by the sporadic input of nutrients to the sea surface. In addition, this is the first study to report the presence of C5H8 in seafloor sediments. We found very high C5H8 concentrations in the sediment from the surface to 5 cm depth. We propose that C5H8 production and degradation by the bacterial community in coastal marine sediments are approximately in balance