Severe fever with thrombocytopenia syndrome (SFTS), a tickborne viral disease, has been identified in China, South Korea, and Japan since 2009. We found retrospective evidence of SFTS virus (SFTSV) infection in Vietnam, which suggests that SFTSV infections also occur in Vietnam, where the virus has not been known to be endemic.

Inhibition of the bromodomain of the transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed in vivo chemical tool 1 (GNE-272) for the bromodomain of CBP that was moderately potent and selective over BRD4(1). In pursuit of a more potent and selective CBP inhibitor, we used structure-based design. Constraining the aniline of 1 into a tetrahydroquinoline motif maintained potency and increased selectivity 2-fold. Structure-activity relationship studies coupled with further structure-based design targeting the LPF shelf, BC loop, and KAc regions allowed us to significantly increase potency and selectivity, resulting in the identification of non-CNS penetrant 19 (GNE-781, TR-FRET IC = 0.94 nM, BRET IC = 6.2 nM; BRD4(1) IC = 5100 nΜ) that maintained good in vivo PK properties in multiple species. Compound 19 displays antitumor activity in an AML tumor model and was also shown to decrease Foxp3 transcript levels in a dose dependent manner.

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Scrub typhus, caused by the intracellular bacterium Orientia tsutsugamushi, is a major cause of febrile illness in the Asia/Pacific region. Here, we implemented a novel real-time PCR and determined the relation of DNA target gene concentration with serum cytokine levels. The limit of detection of the novel real-time PCR was 1,062 DNA copies per ml of EDTA whole blood. Specificity was excellent as determined on a panel of blood-and skin-borne bacteria, including Rickettsia spp. as well as healthy Vietnamese blood donors. Bacterial DNA concentrations after 9 to 12 days from symptoms onset were significantly higher than in earlier or later periods (P < 0.05). Significantly higher concentrations of gamma interferon (IFN-␥) and interleukin-10 (IL-10) occurred during the acute phase of disease (<10 days from onset) as opposed to the convalescent phase (P < 0.05). No significant differences were observed between the acute and the convalescent phases for tumor necrosis factor alpha (TNF-␣) and IL-1␤ concentrations. Regression analysis of DNA concentrations and cytokine levels identified a significant positive relationship for IL-10 (P < 0.0182) but not for IFN-␥, TNF-␣, and IL-1␤. In conclusion, proinflammatory cytokines and IL-10 were differentially related to human bacteremia. They may thus be induced by different constituents of O. tsutsugamushi. As a future prospect in a clinical diagnostic laboratory, quantitative real-time PCR may serve as a reliable tool to monitor therapy and to detect treatment failure.

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We conducted a meta-analysis to assess the association between tumor necrosis factor-alpha (TNF-alpha) gene TNFA -308 (G>A), TNFA -238 (G>A), TNFA -857 (C>T), TNFA -863 (C>A), TNFA -1031 (T>C), TNFA -1210 (A>T) polymorphisms and breast cancer(BC) susceptibility. We also performed subgroup analyses based on ethnicity (Caucasian, Asian, and African). An extensive search was performed to identify all case-control studies investigating such association. Thirteen eligible studies, including 10,236 BC patients and 13,143 controls, were identified. No significant association was observed in all genotypes in worldwide populations, but stratification by ethnicity indicated that the TNFA -308 A allele was associated with a decreased risk of BC compared with the G allele in Caucasian individuals (OR = 0.927, 95%CI = 0.879-0.978). Similar results were obtained when the A/A +A/G genotype was compared with the G/G genotype. In addition, meta-analysis results indicated that the A/A genotype of TNFA -308 was a risk factor for BC in African (A/A vs. G/G OR = 4.085 95%CI = 1.460-11.425; A/A vs. G/A OR = 4.861 95%CI = 1.746-13.527; A/A vs. G/A + G/G OR = 4.246 95%CI = 1.551-11.625), but not in Caucasian or Asian individuals. In conclusion, the results of this meta-analysis indicate that the TNFA -308 A allele may be an important protective factor for BC in European individuals, but it is not likely to confer susceptibility to BC in worldwide populations. In addition, the AA genotype of TNFA -308 may be a risk factor for BC in African individuals. Besides, other polymorphisms were not associated with BC susceptibility.

This article explores the impacts of floods on the economy, environment, and society and tries to clarify the rural community's coping mechanism to flood disasters in Central Viet Nam. It focuses on the social aspects of flood risk perception that shapes the responses to floods. The research findings revealed that flooding is an essential element for a coastal population, whose livelihood depend on productive functions of cyclical floods. The findings also revealed that floods, causing losses and damages, often inhibited economic development. The surveyed communities appeared to have evolved coping mechanisms to reduce the negative impacts of the floods, yet these coping mechanisms are under pressure due to environmental degradation. Integrated flood risk management is considered as a suitable paradigm for coping with flood disasters.