Global Comparison of Changes in the Number of Test-Positive Cases and Deaths by Coronavirus Infection (COVID-19) in the World

Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100-fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally

Oxidative stress induced inflammation initiates functional decline of tear production.

Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1) using a modified tetracycline system (Tet-On/Off system). This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b(560) large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC) in humans). The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease

Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion

Historical data in the 1950s suggests that 7%, 11%, 33%, and 87% of couples were infertile by ages 30, 35, 40 and 45, respectively. Up to 22.3% of infertile couples have unexplained infertility. Oxidative stress is associated with male and female infertility. However, there is insufficient evidence relating to the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. Recently, we have established Tet-mev-1 conditional transgenic mice, which can express the doxycycline-induced mutant SDHCV69E transgene and experience mitochondrial respiratory chain dysfunction leading to intracellular oxidative stress. In this report, we demonstrate that this kind of abnormal mitochondrial respiratory chain-induced chronic oxidative stress affects fertility, pregnancy and delivery rates as well as causes recurrent abortions, occasionally resulting in maternal death. Despite this, spermatogenesis and early embryogenesis are completely normal, indicating the mutation's effects to be rather subtle. Female Tet-mev-1 mice exhibit thrombocytosis and splenomegaly in both non-pregnant and pregnant mice as well as placental angiodysplasia with reduced Flt-1 protein leading to hypoxic conditions, which could contribute to placental inflammation and fetal abnormal angiogenesis. Collectively these data strongly suggest that chronic oxidative stress caused by mitochondrial mutations provokes spontaneous abortions and recurrent miscarriage resulting in age-related female infertility

<i>Tet-mev-1</i>/Dox(+) have dry eye disease.

<p>A, Aqueous tear production: Aqueous tear quantity values of <i>Tet-mev-1</i>/Dox(+) were significantly lower than those in the other types of mice (n≥6, ANOVA Tukey's test, p = 0.0024). B, <i>Tet-mev-1</i>/Dox(+) mice had more corneal fluorescein staining than in the other mice. C, The corneal fluorescein staining score of <i>Tet-mev-1</i>/Dox(+) was significantly worse than that in the other types of mice (all n = 8, ANOVA Tukey's test, p<0.00001).</p

Lacrimal gland in <i>Tet-mev-1 mice</i> with Dox has functional depression of mitochondria and excessive O₂⁻production.

<p>A, The activity of complexes I and II in WT/Dox(+) vs. <i>Tet-mev-1</i> mice/Dox(+). NADH-cytochrome c oxidoreductase was applied as an enzymatic indicator of complex I activity, and succinate-coenzyme Q oxidoreductase as an enzymatic indicator of complex II activity. Although there were no differences in the activity of complex I between these mice, complex II was significantly decreased in <i>Tet-mev-1 mice</i> with Dox. (WT: n = 5, <i>Tet-mev-1</i>: n = 3, NS, not significant; *P<0.01 [Student's t-test]). The vertical bars indicate the standard deviation of the separate experiments. B, Production of O₂⁻ in the lacrimal gland was significantly increased in <i>Tet-mev-1</i>/Dox(+) compared with that in the other types of mice. (n≥5, *P = 0.0014 [Kruskal-Wallis test]). The vertical bars indicate the standard deviation of the separate experiments. C, Carbonyl protein content of the lacrimal gland by ELISA. Each value shows the ratio of <i>Tet-mev-1</i> and WT for the relative amount of carbonyl protein in <i>Tet-mev-1 mice</i> with or without Dox (n = 4, *P = 0.004 [Student's t-test]). D, Immunohistochemical staining of 8-OHdG: <i>Tet-mev-1</i>/Dox(+) shows more positive nuclei (brown, indicated by the arrow) than the other types of mice.</p

Tofla virus : A newly identified Nairovirus of the Crimean-Congo hemorrhagic fever group isolated from ticks in Japan

Ixodid ticks transmit several important viral pathogens. We isolated a new virus (Tofla virus: TFLV) from Heamaphysalis flava and Heamaphysalis formsensis in Japan. The full-genome sequences revealed that TFLV belonged to the genus Nairovirus, family Bunyaviridae. Phylogenetic analyses and neutralization tests suggested that TFLV is closely related to the Hazara virus and that it is classified into the Crimean-Congo hemorrhagic fever group. TFLV caused lethal infection in IFNAR KO mice. The TFLV-infected mice exhibited a gastrointestinal disorder, and positron emission tomography-computed tomography images showed a significant uptake of 18F-fluorodeoxyglucose in the intestinal tract. TFLV was able to infect and propagate in cultured cells of African green monkey-derived Vero E6 cells and human-derived SK-N-SH, T98-G and HEK-293 cells. Although TFLV infections in humans and animals are currently unknown, our findings may provide clues to understand the potential infectivity and to develop of pre-emptive countermeasures against this new tick-borne Nairovirus