BackgroundAlthough meningitis is the most severe form of infection caused by Mycobacterium tuberculosis the immunopathogenesis of this disease is poorly understood. We tested the hypothesis that ...polymorphisms in Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP), an adaptor protein that mediates signals from Toll-like receptors activated by mycobacteria, are associated with susceptibility to tuberculosis (TB) MethodsWe used a case-population study design in Vietnam with cord-blood control samples (n=392) and case patients (n=358) who had either pulmonary (n=183) or meningeal (n=175) TB ResultsThe TIRAP single-nucleotide polymorphism (SNP) C558T was associated with increased susceptibility to TB, with a 558T allele frequency of 0.035 in control samples versus 0.074 in case patients (odds ratio OR, 2.25; P<.001). Subgroup analysis revealed that SNP 558T was more strongly associated with susceptibility to meningeal TB (OR, 3.02; P<.001) than to pulmonary TB (OR, 1.55; P=.22). In comparison to the 558CC genotype, the 558TT genotype was associated with decreased whole-blood interleukin-6 production, which suggests that TIRAP influences disease susceptibility by modulating the inflammatory response ConclusionsThese results provide the first evidence of an association of a TIRAP SNP with the risk of any disease and also suggest that the Toll-like receptor pathway influences susceptibility to meningeal and pulmonary TB by different immune mechanisms
Cellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted ...metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism.
We studied 1069 Indonesian and Vietnamese adults with TBM (26.6% HIV-positive), 54 non-infectious controls, 50 with bacterial meningitis, and 60 with cryptococcal meningitis. Tryptophan and downstream metabolites were measured in cerebrospinal fluid (CSF) and plasma using targeted liquid chromatography-mass spectrometry. Individual metabolite levels were associated with survival, clinical parameters, CSF bacterial load and 92 CSF inflammatory proteins.
CSF tryptophan was associated with 60-day mortality from TBM (hazard ratio HR = 1.16, 95% confidence interval CI = 1.10-1.24, for each doubling in CSF tryptophan) both in HIV-negative and -positive patients. CSF tryptophan concentrations did not correlate with CSF bacterial load nor CSF inflammation but were negatively correlated with CSF interferon-gamma concentrations. Unlike tryptophan, CSF concentrations of an intercorrelating cluster of downstream kynurenine metabolites did not predict mortality. These CSF kynurenine metabolites did however correlate with CSF inflammation and markers of blood-CSF leakage, and plasma kynurenine predicted death (HR 1.54, 95% CI = 1.22-1.93). These findings were mostly specific for TBM, although high CSF tryptophan was also associated with mortality from cryptococcal meningitis.
TBM patients with a high baseline CSF tryptophan or high systemic (plasma) kynurenine are at increased risk of death. These findings may reveal new targets for host-directed therapy.
This study was supported by National Institutes of Health (R01AI145781) and the Wellcome Trust (110179/Z/15/Z and 206724/Z/17/Z).
Nontyphoidal
(NTS), particularly
serovar Typhimurium, is among the leading etiologic agents of bacterial enterocolitis globally and a well-characterized cause of invasive disease (iNTS) in ...sub-Saharan Africa. In contrast,
Typhimurium is poorly defined in Southeast Asia, a known hot spot for zoonotic disease with a recently described burden of iNTS disease. Here, we aimed to add insight into the epidemiology and potential impact of zoonotic transfer and antimicrobial resistance (AMR) in
Typhimurium associated with iNTS and enterocolitis in Vietnam. We performed whole-genome sequencing and phylogenetic reconstruction on 85 human (enterocolitis, carriage, and iNTS) and 113 animal
Typhimurium isolates isolated in Vietnam. We found limited evidence for the zoonotic transmission of
Typhimurium. However, we describe a chain of events where a pandemic monophasic variant of
Typhimurium (serovar I:4,5,12:i:- sequence type 34 ST34) has been introduced into Vietnam, reacquired a phase 2 flagellum, and acquired an IncHI2 multidrug-resistant plasmid. Notably, these novel biphasic ST34
Typhimurium variants were significantly associated with iNTS in Vietnamese HIV-infected patients. Our study represents the first characterization of novel iNTS organisms isolated outside sub-Saharan Africa and outlines a new pathway for the emergence of alternative
variants into susceptible human populations.
Typhimurium is a major diarrheal pathogen and associated with invasive nontyphoid
(iNTS) disease in vulnerable populations. We present the first characterization of iNTS organisms in Southeast Asia and describe a different evolutionary trajectory from that of organisms causing iNTS in sub-Saharan Africa. In Vietnam, the globally distributed monophasic variant of
Typhimurium, the serovar I:4,5,12:i:- ST34 clone, has reacquired a phase 2 flagellum and gained a multidrug-resistant plasmid to become associated with iNTS disease in HIV-infected patients. We document distinct communities of
Typhimurium and I:4,5,12:i:- in animals and humans in Vietnam, despite the greater mixing of these host populations here. These data highlight the importance of whole-genome sequencing surveillance in a One Health context in understanding the evolution and spread of resistant bacterial infections.
U4/U6.U5 tri-snRNP is a 1.5-megadalton pre-assembled spliceosomal complex comprising U5 small nuclear RNA (snRNA), extensively base-paired U4/U6 snRNAs and more than 30 proteins, including the key ...components Prp8, Brr2 and Snu114. The tri-snRNP combines with a precursor messenger RNA substrate bound to U1 and U2 small nuclear ribonucleoprotein particles (snRNPs), and transforms into a catalytically active spliceosome after extensive compositional and conformational changes triggered by unwinding of the U4 and U6 (U4/U6) snRNAs. Here we use cryo-electron microscopy single-particle reconstruction of Saccharomyces cerevisiae tri-snRNP at 5.9 Å resolution to reveal the essentially complete organization of its RNA and protein components. The single-stranded region of U4 snRNA between its 3' stem-loop and the U4/U6 snRNA stem I is loaded into the Brr2 helicase active site ready for unwinding. Snu114 and the amino-terminal domain of Prp8 position U5 snRNA to insert its loop I, which aligns the exons for splicing, into the Prp8 active site cavity. The structure provides crucial insights into the activation process and the active site of the spliceosome.
We previously reported a new community-based mosquito control strategy that resulted in elimination of Aedes aegypti (Linn.) in 40 of 46 communes in northern and central Vietnam, and with annual ...recurrent total costs (direct and indirect) of only $0.28-$0.89 international dollars per person. This control strategy was extended to four provinces in southern Vietnam in Long An and Hau Giang (2004-2007) and to Long An, Ben Tre, and Vinh Long (2005-2010). In a total of 14 communes with 124,743 residents, the mean ± SD of adult female Ae. aegypti was reduced from 0.93 ± 0.62 to 0.06 ± 0.09, and the reduction of immature Ae. aegypti averaged 98.8%. By the final survey, no adults could be collected in 6 of 14 communes, and one commune, Binh Thanh, also had no immature forms. Although the community-based programs also involved community education and clean-up campaigns, the prevalence of Mesocyclops in large water storage containers > 50 liters increased from 12.77 ± 8.39 to 75.69 ± 9.17% over periods of 15-45 months. At the conclusion of the study, no confirmed dengue cases were detected in four of the five communes for which diagnostic serologic analysis was performed. The rate of progress was faster in communes that were added in stages to the program but the reason for this finding was unclear. At the completion of the formal project, sustainability funds were set up to provide each commune with the financial means to ensure that community-based dengue control activities continued.
The emergence and spread of resistance in Plasmodium falciparum malaria to artemisinin combination therapies in the Greater Mekong subregion poses a major threat to malaria control and elimination. ...The current study is part of a multi-country, open-label, randomised clinical trial (TRACII, 2015–18) evaluating the efficacy, safety, and tolerability of triple artemisinin combination therapies. A very high rate of treatment failure after treatment with dihydroartemisinin-piperaquine was observed in Thailand, Cambodia, and Vietnam. The immediate public health importance of our findings prompted us to report the efficacy data on dihydroartemisinin-piperaquine and its determinants ahead of the results of the overall trial, which will be published later this year.
Patients aged between 2 and 65 years presenting with uncomplicated P falciparum or mixed species malaria at seven sites in Thailand, Cambodia, and Vietnam were randomly assigned to receive dihydroartemisinin-piperaquine with or without mefloquine, as part of the TRACII trial. The primary outcome was the PCR-corrected efficacy at day 42. Next-generation sequencing was used to assess the prevalence of molecular markers associated with artemisinin resistance (kelch13 mutations, in particular Cys580Tyr) and piperaquine resistance (plasmepsin-2 and plasmepsin-3 amplifications and crt mutations). This study is registered with ClinicalTrials.gov, number NCT02453308.
Between Sept 28, 2015, and Jan 18, 2018, 539 patients with acute P falciparum malaria were screened for eligibility, 292 were enrolled, and 140 received dihydroartemisinin-piperaquine. The overall Kaplan-Meier estimate of PCR-corrected efficacy of dihydroartemisinin-piperaquine at day 42 was 50·0% (95% CI 41·1–58·3). PCR-corrected efficacies for individual sites were 12·7% (2·2–33·0) in northeastern Thailand, 38·2% (15·9–60·5) in western Cambodia, 73·4% (57·0–84·3) in Ratanakiri (northeastern Cambodia), and 47·1% (33·5–59·6) in Binh Phuoc (southwestern Vietnam). Treatment failure was associated independently with plasmepsin2/3 amplification status and four mutations in the crt gene (Thr93Ser, His97Tyr, Phe145Ile, and Ile218Phe). Compared with the results of our previous TRACI trial in 2011–13, the prevalence of molecular markers of artemisinin resistance (kelch13 Cys580Tyr mutations) and piperaquine resistance (plasmepsin2/3 amplifications and crt mutations) has increased substantially in the Greater Mekong subregion in the past decade.
Dihydroartemisinin-piperaquine is not treating malaria effectively across the eastern Greater Mekong subregion. A highly drug-resistant P falciparum co-lineage is evolving, acquiring new resistance mechanisms, and spreading. Accelerated elimination of P falciparum malaria in this region is needed urgently, to prevent further spread and avoid a potential global health emergency.
UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and National Institutes of Health.
Abstract
Background
Self-care behaviors during pregnancy significantly impacts mother and children's health. This study aimed to explore the self-care behaviors and the associations of these ...behaviors with the psychological well-being of women during pregnancy, as well as the mediating effects of different social support with these associations.
Methods
A cross-sectional data of 562 pregnant women at Hanoi Obstetrics & Gynecology Hospital and Ca Mau Obstetrics & Pediatrics in Vietnam were analyzed. Questions about self-care behaviors, pregnancy characteristics, social support, and psychological well-being were asked. Multivariate regression models were performed. Structural Equation Modeling (SEM) was employed to test the mediating effects of different social support with the association between self-care behaviors and psychological well-being.
Findings
Only 13% of pregnant women often or always did physical exercise at least three times a week, and 40% consumed enough fiber and five servings of vegetables a day. Only 78.7% always avoided alcohol drinking, and 53.9% of pregnant women avoided being exposed to second-hand smoking and 71,7% avoided using traditional medicine without physicians’ prescriptions. Around 66% of pregnant women always or often had prenatal care checkups as scheduled. Information sources, social support and childbirth expectation were major drivers for self-care practices. SEM model showed that social support mediated the relationship between maternal health behaviors and mental well-being.
Conclusion
This study highlighted the remarkable gaps in self-care practices among our pregnant women, which were significantly associated with their mental well-being. Social support-oriented consultancy and interventions should be warranted for improving behaviors and the mental well-being of pregnant women in Vietnam.
Several literature review studies have been conducted on cost-effectiveness threshold values. However, only a few are systematic literature reviews, and most did not investigate the different ...methods, especially in-depth reviews of directly eliciting WTP per QALY. Our study aimed to 1) describe the different direct approach methods to elicit WTP/QALY; 2) investigate factors that contribute the most to the level of WTP/QALY value; and 3) investigate the relation between the value of WTP/QALY and GDP per capita and give some recommendations on feasible methods for eliciting WTP/QALY in low- and middle-income countries (LMICs). A systematic review concerning select studies estimating WTP/QALY from a direct approach was carried out in seven databases, with a cut off date of 03/2022. The conversion of monetary values into 2021 international dollars (i$) was performed via CPI and PPP indexes. The influential factors were evaluated with Bayesian model averaging. Criteria for recommendation for feasible methods in LMICs are made based on empirical evidence from the systematic review and given the resource limitation in LMICs. A total of 12,196 records were identified; 64 articles were included for full-text review. The WTP/QALY method and values varied widely across countries with a median WTP/QALY value of i$16,647.6 and WTP/QALY per GDP per capita of 0.53. A total of 11 factors were most influential, in which the discrete-choice experiment method had a posterior probability of 100%. Methods for deriving WTP/QALY vary largely across studies. Eleven influential factors contribute most to the level of values of WTP/QALY, in which the discrete-choice experiment method was the greatest affected. We also found that in most countries, values for WTP/QALY were below 1 x GDP per capita. Some important principles are addressed related to what LMICs may be concerned with when conducting studies to estimate WTP/QALY.
Potassium-ion storage devices are attracting tremendous attention for wide-ranging applications on account of their low cost, fast charge transport in electrolytes, and large working voltage. ...However, developing cost-effective, high-energy electrodes with excellent structural stability to ensure long-term cycling performance is a major challenge. In this contribution, we have derived two different forms of carbon materials from almond shells using different chemical treatments. For instance, hard carbon (HC) and graphene-like activated carbon (AC) nanosheets are developed by employing simple carbonization and chemical activation routes, respectively. The resultant hard carbon (AS-HC) and activated carbon (AS-AC) exhibit outstanding electrochemical performance as negative and positive electrodes in a potassium-ion battery (KIB), respectively, through their tailor-made surface properties. These promising benefits pave a way to construct a biomass-derived carbon potassium-ion capacitor (KIC) by employing AS-HC as the negative electrode and AS-AC as the positive electrode in a K-based electrolyte. The as-fabricated KIC delivers a reasonable specific energy of 105 Wh/kg and excellent cycling life with negligible capacitance fading over 10 000 cycles. This “waste-to-wealth” approach can promote the development of sustainable KICs at low cost and inspire their use for fast-rate K-based energy storage applications.
Environmental factors contribute to over 70% of crop yield losses worldwide. Of these drought and salinity are the most significant causes of crop yield reduction. Rice is an important staple crop ...that feeds more than half of the world's population. However among the agronomically important cereals rice is the most sensitive to salinity. In the present study we show that exogenous expression of anti-apoptotic genes from diverse origins, AtBAG4 (Arabidopsis), Hsp70 (Citrus tristeza virus) and p35 (Baculovirus), significantly improves salinity tolerance in rice at the whole plant level. Physiological, biochemical and agronomical analyses of transgenic rice expressing each of the anti-apoptotic genes subjected to salinity treatment demonstrated traits associated with tolerant varieties including, improved photosynthesis, membrane integrity, ion and ROS maintenance systems, growth rate, and yield components. Moreover, FTIR analysis showed that the chemical composition of salinity-treated transgenic plants is reminiscent of non-treated, unstressed controls. In contrast, wild type and vector control plants displayed hallmark features of stress, including pectin degradation upon subjection to salinity treatment. Interestingly, despite their diverse origins, transgenic plants expressing the anti-apoptotic genes assessed in this study displayed similar physiological and biochemical characteristics during salinity treatment thus providing further evidence that cell death pathways are conserved across broad evolutionary kingdoms. Our results reveal that anti-apoptotic genes facilitate maintenance of metabolic activity at the whole plant level to create favorable conditions for cellular survival. It is these conditions that are crucial and conducive to the plants ability to tolerate/adapt to extreme environments.
PDF
