Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. ...We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients.
We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization.
A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08).
Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.).
Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with ...amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.
We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks.
A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval CI, 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (-0.42 log10 colony-forming units CFU per milliliter per day vs. -0.31 and -0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy.
Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.).
A global pandemic has been declared for coronavirus disease 2019 (COVID-19), which has serious impacts on human health and healthcare systems in the affected areas, including Vietnam. None of the ...previous studies have a framework to provide summary statistics of the virus variants and assess the severity associated with virus proteins and host cells in COVID-19 patients in Vietnam. In this paper, we comprehensively investigated SARS-CoV-2 variants and immune responses in COVID-19 patients. We provided summary statistics of target sequences of SARS-CoV-2 in Vietnam and other countries for data scientists to use in downstream analysis for therapeutic targets. For host cells, we proposed a predictive model of the severity of COVID-19 based on public datasets of hospitalization status in Vietnam, incorporating a polygenic risk score. This score uses immunogenic SNP biomarkers as indicators of COVID-19 severity. We identified that the Delta variant of SARS-CoV-2 is most prevalent in southern areas of Vietnam and it is different from other areas in the world using various data sources. Our predictive models of COVID-19 severity had high accuracy (Random Forest AUC = 0.81, Elastic Net AUC = 0.7, and SVM AUC = 0.69) and showed that the use of polygenic risk scores increased the models' predictive capabilities. We provided a comprehensive analysis for COVID-19 severity in Vietnam. This investigation is not only helpful for COVID-19 treatment in therapeutic target studies, but also could influence further research on the disease progression and personalized clinical outcomes.
In this paper, a label-free and reagentless microRNA sensor based on an interpenetrated network of carbon nanotubes and electroactive polymer is described. The nanostructured polymer film presents ...very well-defined electroactivity in neutral aqueous medium in the cathodic potential domain from the quinone group embedded in the polymer backbone. Addition of microRNA miR-141 target (prostate cancer biomarker) gives a “signal-on” response, i.e. a current increase due to enhancement of the polymer electroactivity. On the contrary, non-complementary miRNAs such as miR-103 and miR-29b-1 do not lead to any significant current change. A very low detection limit of ca. 8fM is achieved with this sensor.
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•MicroRNA detection.•Label-free and direct electrochemical detection.•Conducting polymer nanostructured by carbon nanotubes.•Prostate cancer biomarker miR-141.
Adjunctive dexamethasone reduces mortality from tuberculous meningitis, but how it produces this effect is not known. Matrix metalloproteinases (MMPs) are important in the immunopathology of many ...inflammatory CNS diseases thus we hypothesized that that their secretion is important in TBM and might be influenced by dexamethasone.
The kinetics of cerebrospinal fluid (CSF) MMP and tissue inhibitors of MMPs (TIMPs) concentrations were studied in a subset of HIV uninfected adults (n = 37) with TBM recruited to a randomized, placebo-controlled trial of adjuvant dexamethasone. Analysis followed a pre-defined plan. Dexamethasone significantly reduced CSF MMP-9 concentrations in early follow up samples (median 5 days (range 3-8) of treatment), but had no significant influence on other MMPs/TIMPs. Additionally CSF MMP-9 concentration was strongly correlated to concomitant CSF neutrophil count.
Dexamethasone decreased CSF MMP-9 concentrations early in treatment and this may represent one mechanism by which corticosteroids improve outcome in TBM. The strong correlation between CSF MMP-9 and neutrophil count suggests that polymorphonuclear leukocytes may play a central role in the early pathogenesis of TBM.
It is well recognized that filter media play a crucial role in constructed wetlands (CWs) for decontamination of phosphorus (P)-rich wastewater. This study investigates the suitability of raw white ...hard clam shells (WHC) and white hard clam shells thermally modified at 800 °C (WHC-M800) as potential media to enhance P treatment performance in CWs. The results indicated that both WHC and WHC-M800 displayed appropriate physicochemical properties, such as high porosity, excellent hydraulic conductivity, and rich Ca content. WHC-M800 exhibited a superior P adsorption capacity (38.7 mg/g) to WHC (12.8 mg/g). However, the practical utilization of WHC-M800 as filter media in CWs may be compromised, due to certain limitations, for example: extremely high pH values in the post-adsorption solutions; high weight losses during calcination and adsorption processes; low mechanical strength; and intensive energy consumption. In contrast, the WHC demonstrated significant advantages of reasonably high P adsorption capacity, locally abundant availability, low cost, and marginal side effects. The fractionation of inorganic P of WHC and WHC-M800 revealed that Ca-bounded P was the most dominant binding form, followed by loosely bound P, Fe-P, occluded P, and Al-P. The present study demonstrates that recycling of WHC shells as a potential substrate in CWs provides a feasible method for upgrading P removal in CWs. Additionally, it helps to reduce waste WHC shells in a simple, cheap, and eco-friendly way, thus can double environmental benefits.
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•WHC and WHC-M800 were studied as wetland filter media to control P pollution.•WHC-M800 exhibited a markedly higher qmax value (38.7 mg/g) than WHC (12.8 mg/g).•WHC-M800 was not a potential CWs filter material due to significant limitations.•P sorption by WHC fitted Langmuir isotherm and Pseudo-first-order kinetic models.•The P removal pathway of WHC was mainly chemisorption in the form of Ca-P binding.
In the course of bioassay-guided study for natural antidiabetic compounds from microorganisms, two steroids, i.e. compounds
1
and
2
, were isolated
in vitro
from biomass of antidiabetic
Streptomyces
...sp. strain TD-X10. Structures of the compounds 1 and 2 were elucidated on the basis of spectroscopic analysis of nuclear magnetic resonance and mass spectral data and comparison with reported literature data as β-sitosterol and β-sitosteryl ferulate, respectively. While compound
1
exhibited faintly inhibitory activity against protein tyrosine phosphatase 1B, a highly validated therapeutic target for diabetes mellitus, compound
2
displayed a moderate inhibitory effect to the enzyme with IC
50
value of 40.05 ± 2.46 µM. The results highlight the antidiabetic potential of natural products from actinobacteria, particularly
Streptomyces
species.
This study sought to monitor the presence of carbapenem-resistant Enterobacteriaceae (CRE) and the proportion New Delhi metallo-beta-lactamase 1 (NDM-1)-producing bacteria between August 2010 and ...December 2012 in a surgical hospital in Vietnam. We identified 47 CRE strains from a total of 4,096 Enterobacteriaceae isolates (1.1 %) that were NDM-1-positive from 45 patients admitted to 11 different departments, with the majority being from the urology department. The NDM-1 gene was found in seven different species. Genotyping revealed limited clonality of NDM-1-positive isolates. Most of the isolates carried the NDM-1 gene on a plasmid and 17.8 % (8/45) of those were readily transferable. We found five patients at admission and one patient at discharge with NDM-1-positive bacteria in their stool. From 200 screening environmental hospital samples, five were confirmed to be NDM-1-positive and included
Acinetobacter
species (
n
= 3) and
Enterobacter aerogenes
(
n
= 2). The results reveal that NDM-1-producing Enterobacteriaceae are commonly isolated in patients admitted to a Vietnamese surgical hospital and are also detected in the hospital environment.
Regardless of the overwhelming use of next-generation sequencing technologies, microarray-based genotyping combined with the imputation of untyped variants remains a cost-effective means to ...interrogate genetic variations across the human genome. This technology is widely used in genome-wide association studies (GWAS) at bio-bank scales, and more recently, in polygenic score (PGS) analysis to predict and stratify disease risk. Over the last decade, human genotyping arrays have undergone a tremendous growth in both number and content making a comprehensive evaluation of their performances became more important. Here, we performed a comprehensive performance assessment for 23 available human genotyping arrays in 6 ancestry groups using diverse public and in-house datasets. The analyses focus on performance estimation of derived imputation (in terms of accuracy and coverage) and PGS (in terms of concordance to PGS estimated from whole-genome sequencing data) in three different traits and diseases. We found that the arrays with a higher number of SNPs are not necessarily the ones with higher imputation performance, but the arrays that are well-optimized for the targeted population could provide very good imputation performance. In addition, PGS estimated by imputed SNP array data is highly correlated to PGS estimated by whole-genome sequencing data in most cases. When optimal arrays are used, the correlations of PGS between two types of data are higher than 0.97, but interestingly, arrays with high density can result in lower PGS performance. Our results suggest the importance of properly selecting a suitable genotyping array for PGS applications. Finally, we developed a web tool that provides interactive analyses of tag SNP contents and imputation performance based on population and genomic regions of interest. This study would act as a practical guide for researchers to design their genotyping arrays-based studies. The tool is available at: https://genome.vinbigdata.org/tools/saa/ .
Orbital ischemic syndrome is a rare entity. The clinical signs typically demonstrate acute loss of visual acuity, chemosis, proptosis, ptosis, and total ophthalmoparesis. We report a case of a man ...who suffered an acute internal carotid artery occlusion and developed orbital ischemic syndrome after a mechanical thrombectomy.
A 57-year-old Vietnamese (Kinh ethnicity) man was brought to the emergency room with complaints of a speech disturbance, facial palsy, and severe weakness of the left arm and leg, which had started 4 hours earlier, after waking up. The National Institutes of Health Stroke Scale 12 (NIHSS 12) revealed the neurological score at admission. A head computed tomography scan showed no intracranial bleeding and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 8 on the right brain. Computed tomography angiography showed an occlusion of the right internal carotid artery. After that, a mechanical thrombectomy was performed, and the internal carotid artery was completely reperfused. After 10 hours, he experienced orbital pain, proptosis, ptosis, chemosis, and ophthalmoplegia of the right orbit. He also had acute loss of visual acuity, and fundoscopic examination revealed papilledema, no retinal hemorrhage, and no bruit in orbital auscultation. Intraocular pressure in the right eye was measured at 50.5 mmHg. Computed tomography angiography showed no carotid-cavernous fistula, but slight enlargement of the right medial and lateral rectus muscles. He was treated with steroids and hyperosmolar agents and recovered 7 days later, but had persistent loss of visual acuity in the right eye.
Orbital ischemic syndrome is a rare complication after mechanical thrombectomy treatment in acute ischemic stroke that can lead to loss of visual acuity.
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