Hand, Foot, and Mouth Disease in Hunan Province, China, 2009-2014: Epidemiology and Death Risk Factors

<div><p>Hand, foot, and mouth disease (HFMD) is an arising public health problem in Asia, including China. Epidemiological data is necessary to enable judicious public health responses and interventions. We analyzed the epidemiological and laboratory data of 759,301 HFMD cases reported to the Hunan Provincial Center for Disease Control and Prevention from 1 January 2009 to 31 December 2014. Univariate and multivariable conditional logistic regression analyses were used to identify risk factors of fatality in HFMD. The incidence of HFMD was highest among children aged 1–3 years, compared with other age groups. Of the total HFMD cases, 7,222 (0.95%) were considered severe and 338 (0.04%) were fatal. Enterovirus-A71 was the major cause of severe and fatal cases (65.75% and 88.78%, respectively). For severe cases, the median time from symptom onset to diagnosis was 0.5 days (interquartile range [IQR] 0–1.5 days); the median time from diagnosis to severe illness was 2 days (IQR 1–3 days). For fatal cases, the median time from symptom onset to diagnosis was 0.5 days (IQR 0–1.5 days); the median time from diagnosis to death was 1.5 days (IQR 0.5–2.5 days). In multivariable analysis, the abuse of antibiotic, glucocorticoid and pyrazolone in village clinics at basic medical institutions were identified as independent risk factors for HFMD fatal cases. In conclusion, our results suggest that the future direction to control and respond to HFMD is intensive surveillance of enterovirus-A71 and improving the ability to diagnose disease and treat patients, especially in basic medical institutions.</p></div

Time interval of HFMD development in severe cases and fatal cases.

<p>(A) A:Symptom onset; B: diagnosis; C: start of severe illness; D: death. (B) The time 0 is symptom onset, and the mean in each block is in reference to the location of the previous block.</p

Adjusted odds ratio (OR) and 95% confidence interval (CI) derived from multiple conditional logistic regression model.

<p>Adjusted odds ratio (OR) and 95% confidence interval (CI) derived from multiple conditional logistic regression model.</p

Constituent ratios of enterovirus serotypes in laboratory-confirmed cases of HFMD by clinical severity in Hunan Province, 2009–2014.

<p>Constituent ratios of enterovirus serotypes in laboratory-confirmed cases of HFMD by clinical severity in Hunan Province, 2009–2014.</p

Distribution of case and control groups and univariate conditional logistic regression model.

<p>Distribution of case and control groups and univariate conditional logistic regression model.</p

The age-specific incidence rate (per million) in Hunan Province, China, 2009–2014.

<p>The age-specific incidence rate (per million) in Hunan Province, China, 2009–2014.</p

Diversity and Abundance of Arsenic Biotransformation Genes in Paddy Soils from Southern China

Microbe-mediated arsenic (As) biotransformation in paddy soils determines the fate of As in soils and its availability to rice plants, yet little is known about the microbial communities involved in As biotransformation. Here, we revealed wide distribution, high diversity, and abundance of arsenite (As­(III)) oxidase genes (<i>aioA</i>), respiratory arsenate (As­(V)) reductase genes (<i>arrA</i>), As­(V) reductase genes (<i>arsC</i>), and As­(III) <i>S</i>-adenosylmethionine methyltransferase genes (<i>arsM</i>) in 13 paddy soils collected across Southern China. Sequences grouped with As biotransformation genes are mainly from rice rhizosphere bacteria, such as some <i>Proteobacteria</i>, <i>Gemmatimonadales</i>, and <i>Firmicutes</i>. A significant correlation of gene abundance between <i>arsC</i> and <i>arsM</i> suggests that the two genes coexist well in the microbial As resistance system. Redundancy analysis (RDA) indicated that soil pH, EC, total C, N, As, and Fe, C/N ratio, SO₄^2–-S, NO₃^–-N, and NH₄⁺-N were the key factors driving diverse microbial community compositions. This study for the first time provides an overall picture of microbial communities involved in As biotransformation in paddy soils, and considering the wide distribution of paddy fields in the world, it also provides insights into the critical role of paddy fields in the As biogeochemical cycle

Case distribution and demographic characteristics of reported HFMD cases in Hunan Province, China, 2009–2014.

<p>Case distribution and demographic characteristics of reported HFMD cases in Hunan Province, China, 2009–2014.</p

Phosphorylation Weakens but Does Not Inhibit Membrane Binding and Clustering of K‑Ras4B

K-Ras4B is one of the most frequently mutated Ras isoforms in cancer. The signaling activity of K-Ras4B depends on its localization to the plasma membrane (PM), which is mainly mediated by its polybasic farnesylated C-terminus. On top of the constitutive cycles that maintain the PM enrichment of K-Ras4B, conditional phosphorylation at Ser181 located within this motif has been found to be involved in regulating K-Ras4B’s cell distribution and signaling activity. However, discordant observations have undermined our understanding of the role this phosphorylation plays. Here, we report an efficient strategy for producing K-Ras4B simultaneously bearing phosphate, farnesyl, and methyl modifications on a preparative scale, a very useful <i>in vitro</i> system when used in concert with model biomembranes. By using this system, we determined that phosphorylation at Ser181 does not fully inhibit membrane binding and clustering of K-Ras4B but reduces its membrane binding affinity, depending on membrane fluidity. In addition, phosphorylated K-Ras4B maintains tight association with its cytosolic shuttle protein PDEδ. After delivering K-Ras4B containing nonhydrolyzable phosphoserine mimetic into cells, the protein displayed a decreasing PM distribution compared with nonphosphorylable K-Ras4B, implying that phosphorylation might facilitate the dissociation of K-Ras4B from the PM. In addition, phosphorylation does not alter the localization of K-Ras4B in the liquid-disordered lipid subdomains of the membrane but slightly alters the thermotropic properties of K-Ras4B-incorporated membranes probably due to minor differences in membrane partitioning and dynamics. These results provide novel mechanistic insights into the role that phosphorylation at Ser181 plays in regulating K-Ras4B’s distribution and activity