Why Are COVID-19 Mortality Rates by Country or Region So Different?: An Ecologic Study of Factors Associated with Mortality from Novel Coronavirus Infections by Country

[Background] In order to find out the factors associated with the large disparities in COVID-19 mortality rates by country, we conducted an ecological study by linking existing statistics. In Japan, a large variation was observed in between geographical areas when assessing mortality. We performed a regional correlation analysis to find factors related to regional mortality. [Methods] This study design was an ecologic study. A multiple regression analysis was performed with COVID-19 mortality rates of different countries as the dependent variable together with various health care and economic factors. We calculated the cumulative mortality rate as of June 30, 2020. For the regional correlation analysis of Japan, 47 prefectures were divided into nine regions. The factors examined were health care and tourism. Data for 33 Organization for Economic Co-operation and Development (OECD) countries were analyzed. In Japan’s regional analysis, the whole country was classified into nine regions. [Results] Factors related to mortality were the incidence of Kawasaki disease (KD), number of computed tomographies (CTs), and alcohol consumption. Mortality was low in countries with high incidence of KD and high number of CTs, as well as in countries with high alcohol consumption. In European countries, high smoking prevalence and a high Gini coefficient were positively related to high mortality. According to a regional analysis in Japan, mortality was related to proportion of population in the densely inhabited districts, the number of foreign visitors per capita, and the number of Chinese visitors per capita. [Conclusion] Low mortality in East Asia was associated with specific disease morbidity (KD), alcohol consumption, and CT numbers. It was suggested that the mortality gap in Japan was related to the number of foreign tourists and the proportion of population in the densely inhabited districts

Suicide rates during social crises: Changes in the suicide rate in Japan after the Great East Japan earthquake and during the COVID-19 pandemic

We aimed to observe the changes in suicide rates after the Great East Japan Earthquake and during the coronavirus (COVID-19) pandemic, as typical cases of social crises, in Japan. A descriptive epidemiological study was conducted using data on the number of deaths by suicide published by the National Police Agency. The suicide rate ratio during the crisis—the monthly suicide mortality rate in the year of the crisis divided by the average suicide mortality rate in the three years before the crisis—was used as the indicator. After the earthquake, in March 2011 the suicide rate was 18% lower than the average mortality rate for the previous three years. However, it increased by 18% in May and 8% in June; increased mortality was observed among women. The suicide rate began to decline after October 2011. During the COVID-19 pandemic, the suicide rate decreased from February to June 2020. The declines in April and May were significant at 20% and 18%, respectively. From July onwards, the suicide rate of women began to rise, and from October, the overall suicide also began to increase. The rise in female suicide rates was significant, especially in October, with an increase of 70%. Thus, during these crises, suicide rates fell temporarily but then rose, especially among women. The period of increase in suicide rates was longer during the COVID-19 pandemic than after the earthquake. Therefore, there is an urgent need to promote measures for suicide prevention currently, and during a future crisis

Differences in Ocular Complications Between Candida albicans and Non-albicans Candida Infection Analyzed by Epidemiology and a Mouse Ocular Candidiasis Model

Objectives:Candida species are a major cause of hospital infections, including ocular candidiasis, but few studies have examined the propensities of specific species to invade the eye or the unique immunological responses induced. This study examined the frequency and characteristics of species-specific Candida eye infections by epidemiology and experiments using a mouse ocular candidiasis model.Methods: We reviewed medical records of candidemia patients from January 2012 to March 2017. We also evaluated ocular fungal burden, inflammatory cytokine and chemokine profiles, and inflammatory cell profiles in mice infected with Candida albicans, Candida glabrata, or Candida parapsilosis.Results: During the study period, 20 ocular candidiasis cases were diagnosed among 99 candidemia patients examined by ophthalmologists. Although C. parapsilosis was the most frequent candidemia pathogen, only C. albicans infection was significantly associated with ocular candidiasis by multivariate analysis. In mice, ocular fungal burden and inflammatory mediators were significantly higher during C. albicans infection, and histopathological analysis revealed invading C. albicans surrounded by inflammatory cells. Ocular neutrophil and inflammatory monocyte numbers were significantly greater during C. albicans infection.Conclusion:Candida albicans is strongly associated with ocular candidiasis due to greater capacity for invasion, induction of inflammatory mediators, and recruitment of neutrophils and inflammatory monocytes

Trends in sleep problems and patterns among Japanese adolescents: 2004 to 2017

Background Sleep problems in adolescence, such as insomnia and short sleep duration, are associated with physical and mental health problems. However, little is known about the recent trends in sleep problems among adolescents. Therefore, this study examined trends in sleep problems among Japanese adolescents. Methods Using data from the Lifestyle Survey of Adolescents collected in 2004 (n = 102,451), 2008 (n = 95,680), 2010 (n = 98,867), 2012 (n = 101,134), 2014 (n = 85,931), and 2017 (n = 64,417), we calculated the trends of insomnia, shorter sleep duration, late bedtimes, and poor sleep quality. Multivariable logistic regression analysis models were used to examine the association of each sleep problem and survey years. Findings We analyzed data from 545,285 Japanese adolescents. Results indicated that, since 2004, the odds ratio for insomnia have decreased (Adjusted odds ratio [AOR] 0•85, 95% CI 0•82–0•87), as have the odds ratio for poor sleep quality (AOR 0•92, 95% CI 0•88–0•95). However, the odds ratio for shorter sleep duration (AOR 1•13, 95% CI 1•10–1•17) and late bedtimes tended to increase (AOR 1•06, 95% CI 1•03–1•08) during this period. Interpretation The prevalence of insomnia symptoms and poor sleep quality among adolescents decreased from 2004 to 2017. However, there were increasing trends toward shorter sleep duration and late bedtimes. These changes are both relieving and concerning. Teachers, parents, and health professionals should consider educating adolescents regarding sleep hygiene, adjusting schedules of extracurricular activities, and enhancing time management to improve their sleep quantity

Effectiveness of Screening and Brief Alcohol Intervention at the Workplace: A Study Protocol for a Randomized Controlled Trial at Five Japan-Based Companies

Background: Despite evidence regarding the effectiveness of screening and brief interventions for excessive alcohol use in primary care, these tools are not a part of routine practice. It has been suggested that using these tools at the workplace may be critical to alcohol-associated harm; however, evidence for this claim is unclear. The aim of this article is to develop a study protocol which evaluates the effect of brief alcohol intervention at the workplace to reduce harmful alcohol drinking. Methods: A randomized controlled trial involving employees (aged 20–74 years) of five Japan-based companies who were screened “positive” by Alcohol Use Disorder Identification Test (AUDIT) is on-going. Participants were randomized into “Patient Information Leaflet” (control group), “Brief Advice and Counselling,” and “Five-minute Brief Advice” groups. A self-administered questionnaire was used to assess alcohol consumption, lifestyle behavior, health status, work performance, and consequences of alcohol use. Data of laboratory markers were collected from routine health checkups.Results: A total of 351 participants were randomized into Patient Information Leaflet (n = 111), Brief Advice and Counselling (n = 128), and Five-minute Brief Advice (n = 112) groups. Participants were mostly men with a median age of 49 years. Median AUDIT score and weekly alcohol consumption were 11 points and 238 g/week, respectively. Two-thirds of the participants were manufacturing workers. Conclusion: This study protocol developed the first trial in Japan to investigate the effect of brief alcohol intervention combined with a recommended screening tool at the workplace. Our findings can provide evidence on the effectiveness and relevance of these tools to occupational health

Heat-not-burn tobacco, electronic cigarettes, and combustible cigarette use among Japanese adolescents: a nationwide population survey 2017

Background: From among the global public health concerns, smoking remains one of the most crucial challenges. Especially for adolescents, the increase in the use of electronic cigarettes is controversial, as its use may lead to established smoking. In Japan, where a unique tobacco regulation system exists, the heat-not-burn tobacco market has been growing. However, the prevalence and association of combustible cigarettes and new tobacco-related products have not yet been closely investigated among Japanese adolescents. This study aimed to clarify the prevalence of smoking among adolescents, including new types of tobacco-related products, and to compare the characteristics of their users. Methods: The 2017 Lifestyle Survey of Adolescents is a nationally-representative survey collected in Japan. From the national school directory, 98 junior high schools and 86 high schools were randomly sampled throughout Japan. The students completed an anonymous questionnaire at school. We calculated the prevalence of use for each type of tobacco product. Then, the use of a combination of products and the characteristics of different types of products were examined. Results: In total, 64,152 students from 48 junior high schools and 55 high schools were included the analysis (school response rate = 56%, Mage = 15.7 years, 53.9% boys). The age-adjusted rate of ever (current) use of electronic cigarettes was 2.1% (0.7%) in junior high school and 3.5% (1.0%) in high school; that of combustible cigarettes was 2.6% (0.6%) in junior high school and 5.1% (1.5%) in high school. The rate of heat-not-burn tobacco use was lower relative to other products: 1.1% (0.5%) in junior high school and 2.2% (0.9%) in high school. An examination of the combined use of the three products identified a high number of dual users. Comparisons between different types of users indicated different backgrounds for combustible cigarette users and new product users. Conclusions: The prevalence of new tobacco-alternative products is growing in popularity among Japanese adolescents. Dual use is common, and many adolescents use new products only. Moreover, e-cigarettes might attract a broader range of groups to smoking. Continuous monitoring and research are needed to investigate their influence as a possible gateway to tobacco smoking

Unique Interplay between Sugar and Lipid in Determining the Antigenic Potency of Bacterial Antigens for NKT Cells

Structural and biophysical studies reveal the induced-fit mechanism underlying the stringent specificity of invariant natural killer T cells for unique glycolipid antigens from the pathogen Streptococcus pneumoniae

Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H2O2-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS

Intestinal Resident Yeast Candida glabrata Requires Cyb2p-Mediated Lactate Assimilation to Adapt in Mouse Intestine

The intestinal resident Candida glabrata opportunistically infects humans. However few genetic factors for adaptation in the intestine are identified in this fungus. Here we describe the C. glabrata CYB2 gene encoding lactate dehydrogenase as an adaptation factor for survival in the intestine. CYB2 was identified as a virulence factor by a silkworm infection study. To determine the function of CYB2, we analysed in vitro phenotypes of the mutant Δcyb2. The Δcyb2 mutant grew well in glucose medium under aerobic and anaerobic conditions, was not supersensitive to nitric oxide which has fungicidal-effect in phagocytes, and had normal levels of general virulence factors protease, lipase and adherence activities. A previous report suggested that Cyb2p is responsible for lactate assimilation. Additionally, it was speculated that lactate assimilation was required for Candida virulence because Candida must synthesize glucose via gluconeogenesis under glucose-limited conditions such as in the host. Indeed, the Δcyb2 mutant could not grow on lactate medium in which lactate is the sole carbon source in the absence of glucose, indicating that Cyb2p plays a role in lactate assimilation. We hypothesized that Cyb2p-mediated lactate assimilation is necessary for proliferation in the intestinal tract, as the intestine is rich in lactate produced by bacteria flora, but not glucose. The Δcyb2 mutant showed 100-fold decreased adaptation and few cells of Saccharomyces cerevisiae can adapt in mouse ceca. Interestingly, C. glabrata could assimilate lactate under hypoxic conditions, dependent on CYB2, but not yeast S. cerevisiae. Because accessible oxygen is limited in the intestine, the ability for lactate assimilation in hypoxic conditions may provide an advantage for a pathogenic yeast. From those results, we conclude that Cyb2p-mediated lactate assimilation is an intestinal adaptation factor of C. glabrata