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We have previously reported the draft genome sequences of 59 endospore-forming Gram-positive bacterial strains isolated from Vietnamese crop plants due to their ability to suppress plant pathogens. Based on their draft genome sequence, eleven of them were assigned to the Brevibacillus and one to the Lysinibacillus genus. Further analysis including full genome sequencing revealed that several of these strains represent novel genomospecies. In vitro and in vivo assays demonstrated their ability to promote plant growth, as well as the strong biocontrol potential of Brevibacilli directed against phytopathogenic bacteria, fungi, and nematodes. Genome mining identified 157 natural product biosynthesis gene clusters (BGCs), including 36 novel BGCs not present in the MIBiG data bank. Our findings indicate that plant-associated Brevibacilli are a rich source of putative antimicrobial compounds and might serve as a valuable starting point for the development of novel biocontrol agents.

Elimination of chemically synthesized pesticides, such as fungicides and nematicides, in agricultural products is a key to successful practice of the Vietnamese agriculture. We describe here the route for developing successful biostimulants based on members of the Bacillus subtilis species complex. A number of endospore-forming Gram-positive bacterial strains with antagonistic action against plant pathogens were isolated from Vietnamese crop plants. Based on their draft genome sequence, thirty of them were assigned to the Bacillus subtilis species complex. Most of them were assigned to the species Bacillus velezensis . Whole genome sequencing of strains BT2.4 and BP1.2A corroborated their close relatedness to B. velezensis FZB42, the model strain for Gram-positive plant growth-promoting bacteria. Genome mining revealed that at least 15 natural product biosynthesis gene clusters (BGCs) are well conserved in all B. velezensis strains. In total, 36 different BGCs were identified in the genomes of the strains representing B. velezensis, B. subtilis, Bacillus tequilensis , and Bacillus. altitudinis . In vitro and in vivo assays demonstrated the potential of the B. velezensis strains to enhance plant growth and to suppress phytopathogenic fungi and nematodes. Due to their promising potential to stimulate plant growth and to support plant health, the B. velezensis strains TL7 and S1 were selected as starting material for the development of novel biostimulants, and biocontrol agents efficient in protecting the important Vietnamese crop plants black pepper and coffee against phytopathogens. The results of the large-scale field trials performed in the Central Highlands in Vietnam corroborated that TL7 and S1 are efficient in stimulating plant growth and protecting plant health in large-scale applications. It was shown that treatment with both bioformulations resulted in prevention of the pathogenic pressure exerted by nematodes, fungi, and oomycetes, and increased harvest yield in coffee, and pepper.

Introduction: Linezolid (LZD) plays an important role in the treatment of severe infections caused by Gram-positive bacteria. Thrombocytopenia is regarded as one of the most common side effects of linezolid, which results from the destruction of platelets or myelosuppression. The study aimed to identify the risk factors associated with the development of thrombocytopenia in Vietnamese patients. Methodology: This retrospective, descriptive cross-sectional study was performed on adult patients who received parenteral LZD therapy (1,200 mg/day) in at least 3 days between January 2020 and June 2021 at a tertiary referral hospital in Vietnam. Thrombocytopenia was defined as either a final platelet count of less than 100 G/L or a 25% decrease in platelet count from baseline. Multivariate logistic regression analysis was applied to predict risk factors associated with LZD-induced thrombocytopenia. Results: In the 208 patients included in the study, the average age was 69 and males accounted for 73.1%. LZD-induced thrombocytopenia occurred in 37% of patients. LZD-induced thrombocytopenia was significantly associated with shock (HR = 8.26, 95% CI 3.82 – 17.84, p < 0.001), baseline creatinine clearance (HR = 1.02, 95% CI [1.01 – 1.03], p = 0.002), and duration of LZD treatment of at least 14 days (HR = 4.45, 95% CI [1.83 – 11.05], p = 0.001). Conclusions: The results showed that thrombocytopenia was fairly common in patients using linezolid. Shock, renal failure, and duration of linezolid therapy of at least 14 days were significant risk factors for the incidence of linezolid-induced thrombocytopenia.

Investigation in radioactive contaminant removal from aqueous solutions has been considered essential upon unexpected nuclear accidents. In this report, we have successfully prepared Prussian blue analogues (PBAs) with different substituted cations (A2[Fe(CN)6] (A: Cu2+, Co2+, and Ni2+)). The synthesized PBAs were characterized and employed for the removal of Cs+, Sr2+, and Co2+ as sorption models, which are commonly found in radioactive waste. Sorption examinations reveal that Cu2[Fe(CN)6] has the highest sorption capacity towards Cs+, Sr2+, and Co2+ compared with those of Co2[Fe(CN)6] and Ni2[Fe(CN)6]. This is mainly attributed to the cation-exchange ability of substituted metal within the framework of PBAs. The sorption mechanism is qualitatively and quantitatively supported by infrared spectroscopy (IR) and total reflection X-ray fluorescence spectroscopy analysis (TXRF). In addition, it was found that Cs+ is adsorbed most effectively by PBAs due to the size matching between Cs+ ions and the channel windows of PBAs. These findings are important for the design of sorbents with suitable ion-exchange capacity and selectivity toward targeted radioactive wastes.

This paper deals with the effect of input parameters of Powder Mixed Electric Discharge Machining (PMEDM) process on the surface roughness when processing cylindrical shaped parts. In this work, the workpiece material is 90CrSi alloy tool steel and the nanopowder is silicon carbide. Also, five input parameters including the pulse on time, the pulse off time, the powder concentration, the current and the server voltage were selected to investigate their influence on the surface roughness. Taguchi method and ANOVA analysis were used and the effect of input parameters on the surface roughness was presented. Moreover, optimum input parameters for minimum surface roughness was suggested.

Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Web-based app (https://thaole.shinyapps.io/tbmapp/). 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIV-infected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.

Background. Drug-resistant tuberculous meningitis (TBM) is difficult to diagnose and treat. Mortality is high and optimal treatment is unknown. We compared clinical outcomes of drug-resistant and -susceptible TBM treated with either standard or intensified antituberculosis treatment. Methods. We analyzed the influence of Mycobacterium tuberculosis drug resistance on the outcomes of patients with TBM enrolled into a randomized controlled trial comparing a standard, 9-month antituberculosis regimen (containing rifampicin 10 mg/kg/day) with an intensified regimen with higher-dose rifampicin (15 mg/kg/day) and levofloxacin (20 mg/kg/day) for the first 8 weeks. The primary endpoint of the trial was 9-month survival. In this subgroup analysis, resistance categories were predefined as multidrug resistant (MDR), isoniazid resistant, rifampicin susceptible (INH-R), and susceptible to rifampicin and isoniazid (INH-S + RIF-S). Outcome by resistance categories and response to intensified treatment were compared and estimated by Cox regression. Results. Of 817 randomized patients, 322 had a known drug resistance profile. INH-R was found in 86 (26.7%) patients, MDR in 15 (4.7%) patients, rifampicin monoresistance in 1 patient (0.3%), and INH-S + RIF-S in 220 (68.3%) patients. Multivariable regression showed that MDR (hazard ratio [HR], 5.91 [95% confidence interval {CI}, 3.00–11.6]), P < .001), was an independent predictor of death. INH-R had a significant association with the combined outcome of new neurological events or death (HR, 1.58 [95% CI, 1.11–2.23]). Adjusted Cox regression, corrected for treatment adjustments, showed that intensified treatment was significantly associated with improved survival (HR, 0.34 [95% CI, .15–.76], P = .01) in INH-R TBM. Conclusions. Early intensified treatment improved survival in patients with INH-R TBM. Targeted regimens for drug-resistant TBM should be further explored. Clinical Trials Registration. ISRCTN61649292.

Abstract Background Pretreatment predictors of death from tuberculous meningitis (TBM) are well established, but whether outcome can be predicted more accurately after the start of treatment by updated clinical variables is unknown. Hence, we developed and validated models that dynamically predict mortality using time-updated Glasgow Coma Scale (GCS) and plasma sodium measurements, together with patient baseline characteristics. Methods We included 1048 adults from 4 TBM studies conducted in southern Vietnam from 2004 to 2016. We used a landmarking approach to predict death within 120 days after treatment initiation using time-updated data during the first 30 days of treatment. Separate models were built for patients with and without human immunodeficiency virus (HIV) infection. We used the area under the receiver operating characteristic curve (AUC) to evaluate performance of the models at days 10, 20, and 30 of treatment to predict mortality by 60, 90, and 120 days. Our internal validation was corrected for overoptimism using bootstrap. We provide a web-based application that computes mortality risk within 120 days. Results Higher GCS indicated better prognosis in all patients. In HIV-infected patients, higher plasma sodium was uniformly associated with good prognosis, whereas in HIV-uninfected patients the association was heterogeneous over time. The bias-corrected AUC of the models ranged from 0.82 to 0.92 and 0.81 to 0.85 in HIV-uninfected and HIV-infected individuals, respectively. The models outperformed the previously published baseline models. Conclusions Time-updated GCS and plasma sodium measurements improved predictions based solely on information obtained at diagnosis. Our models may be used in practice to define those with poor prognosis during treatment. We used time-updated Glasgow Coma Scale and plasma sodium measurements, together with baseline patient characteristics, in a model to dynamically predict death in adults with tuberculous meningitis. Predictions can be made from any time point until day 30 of follow-up.

Background The optimal transfusion threshold for patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains uncertain. Methods We used data from OBLEX (ClinicalTrials.gov: NCT03714048), an international, prospective, observational study conducted across 12 centres in Australia, Europe, and North America between 2019 and 2022. The study collected information on patient demographics, bleeding risk factors, transfusion practices during the first seven days of ECMO, and in-hospital mortality. Using these data, we emulated a target trial comparing the effects of liberal transfusion practice (transfusion initiated at Hb ≥ 90 g/L) and restrictive transfusion practice (transfusion initiated at Hb ≤ 70 g/L) on hospital mortality within seven days of ECMO initiation. Sequential trials approach was used to estimate the causal contrast. Results A total of 534 patients were included, with 46% dying during hospitalisation. After accounting for potential confounders, the liberal transfusion practice demonstrated a modest survival benefit within the first two days of ECMO, with differences in survival probabilities of 12% (95% CI 3% to 21%) at day 2 and 13% (95% CI 2% to 25%) at day 3, corresponding to the number needed to treat (NNT) of 8 and 7 respectively. No differences in survival benefit were found after day 3. These results were consistent across sensitivity and exploratory analyses. Conclusion This target trial emulation study suggests that a liberal transfusion threshold may provide a modest survival benefit during the early course of VA-ECMO, but no benefit afterwards. Prospective studies are needed to confirm these findings, assess clinical adoption, and investigate underlying mechanism.

Importance Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals. Objective To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin. Design, Setting, and Participants This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023. Interventions Daily 100-mg enteric-coated aspirin or matching placebo. Main Outcomes and Measures Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records. Results Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04). Conclusions and Relevance This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma. Trial Registration ISRCTN.org Identifier:ISRCTN83772183