Background. The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)—associated tuberculous meningitis is unknown. Methods. We conducted a randomized, ...double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, perprotocol, and prespecified subgroup analyses. Results. A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio HR, 1.12; 95% confidence interval CI,.81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI,.87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions. Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis.
Rabies is a fatal viral disease that causes an estimated 59,000 human deaths each year. The majority of these deaths occur in developing countries in Asia. Canine rabies is endemic to Vietnam, which ...is, however, moving towards the disease's elimination. Many countries, such as Vietnam, have invested tremendous resources in controlling rabies, highlighting the goal of regional and global elimination of this neglected disease. In Vietnam, rabies is recognised as one of five high-priority, zoonotic diseases by the Ministry of Health and the Ministry of Agriculture and Rural Development. Investment by the government and by international partners for rabies prevention and control has played a substantial role in reducing human rabies deaths from 404 cases in 1992 to 74 cases in 2017. The catalyst for this effort was the Prime Minister's creation of the National Rabies Program in 1996, which led to increased support and resources for rabies prevention and control. Interventions carried out since then include the expansion of post-exposure prophylaxis centres throughout the country, the introduction or revision of key legislation and guidelines, and improved multisectoral One Health collaboration. In addition, support from international partners, such as the World Organisation for Animal Health (OIE), the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), and the Centers for Disease Control and Prevention (CDC), has helped to increase awareness, manage dog populations more effectively, and improve Vietnam's surveillance and diagnostic capabilities. To pursue the goal of eliminating dog-mediated rabies in Vietnam, political commitment is crucial. Resources must be made available to enforce the regulations and guidelines that will enable Vietnam to achieve greater canine rabies vaccination coverage. In this paper, the authors provide an overview of the animal and human health systems in Vietnam, as well as past, current and future directions of rabies prevention and control.
Reactive oxygen species (ROS) play an essential role in the progression of many chronic diseases like atherosclerosis and rheumatoid arthritis. For decades, antioxidant compounds have always been ...considered as potential treatments for these ROS-related diseases. Concomitantly, noninvasive imaging systems such as magnetic resonance imaging (MRI) have also been widely used in the diagnosis of diseases, especially atherosclerosis. In this study, we investigated the feasibility to develop chitosan nanococktails containing both nanoceria and superparamagnetic iron oxide nanoparticles for ROS-related theranostics. Nanoceria utilized as therapeutic modules capable of ROS scavenging and iron-oxide nanoparticles utilized as imaging agents for MRI have been synthesized separately. Subsequently, two versions of theranostic chitosan nanococktails containing both nanoceria and iron oxide nanoparticles (Chit-IOCO and Chit-TPP-IOCO) were successfully synthesized via two different mechanisms, electrostatic self-assembly, and ionic gelation. In vitro studies such as cytotoxicity, MRI, and ROS scavenging were performed. These theranostic nanococktails demonstrated effective ROS scavenging and MRI contrast as a potential platform for treatment and diagnosis of ROS-related diseases. Results indicated that both Chit-IOCO and Chit-TPP-IOCO can reduce the ROS level of the lipopolysaccharide-stimulated macrophage J774A.1 to the baseline level. Chit-IOCO was less toxic to the cells than Chit-TPP-IOCO. In addition, Chit-IOCO exhibited higher MRI relaxivity than Chi-TPP-IOCO (308 and 150 mM–1 s–1, respectively), indicating that Chi-IOCO was more effective than Chit-TPP-IOCO as an MRI contrast agent in macrophages. Taken together, Chit-IOCO nanococktail demonstrates outstanding potential for treatment and diagnosis of ROS-related diseases. Potentially, this nanococktail can be easily modified to include new modules, allowing future application of personalized medicine.
The goal of the RENEB inter-laboratory comparison 2021 exercise was to simulate a large-scale radiation accident involving a network of biodosimetry labs. Labs were required to perform their analyses ...using different biodosimetric assays in triage mode scoring and to rapidly report estimated radiation doses to the organizing institution. This article reports the results obtained with the cytokinesis-block micronucleus assay. Three test samples were exposed to blinded doses of 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 13 mA, ∼75 keV, 1 Gy/min). These doses belong to 3 triage categories of clinical relevance: a low dose category, for no exposure or exposures inferior to 1 Gy, requiring no direct treatment of subjects; a medium dose category, with doses ranging from 1 to 2 Gy, and a high dose category, after exposure to doses higher than 2 Gy, with the two latter requiring increasing medical attention. After irradiation the test samples (no. 1, no. 2 and no. 3) were sent by the organizing laboratory to 14 centers participating in the micronucleus assay exercise. Laboratories were asked to setup micronucleus cultures and to perform the micronucleus assay in triage mode, scoring 500 binucleated cells manually, or 1,000 binucleated cells in automated/semi-automated mode. One laboratory received no blood samples, but scored pictures from another lab. Based on their calibration curves, laboratories had to provide estimates of the administered doses. The accuracy of the reported dose estimates was further analyzed by the micronucleus assay lead. The micronucleus assay allowed classification of samples in the corresponding clinical triage categories (low, medium, high dose category) in 88% of cases (manual scoring, 88%; semi-automated scoring, 100%; automated scoring, 73%). Agreement between scoring laboratories, assessed by calculating the Fleiss' kappa, was excellent (100%) for semi-automated scoring, good (83%) for manual scoring and poor (53%) for fully automated scoring. Correct classification into triage scoring dose intervals (reference dose ±0.5 Gy for doses ≤2.5 Gy, or reference dose ±1 Gy for doses >2.5 Gy), recommended for triage biodosimetry, was obtained in 79% of cases (manual scoring, 73%; semi-automated scoring, 100%; automated scoring, 67%). The percentage of dose estimates whose 95% confidence intervals included the reference dose was 58% (manual scoring, 48%; semiautomated scoring, 72%; automated scoring, 60%). For the irradiated samples no. 2 and no. 3, a systematic shift towards higher dose estimations was observed. This was also noticed with the other cytogenetic assays in this intercomparison exercise. Accuracy of the rapid triage modality could be maintained when the number of manually scored cells was scaled down to 200 binucleated cells. In conclusion, the micronucleus assay, preferably performed in a semi-automated or manual scoring mode, is a reliable technique to perform rapid biodosimetry analysis in large-scale radiation emergencies.
•hASCs have V1a receptors and are responsive to AVP during adipogenesis.•AVP signaling is via the Gq-PLC-IP3 pathway which increases intracellular Ca2+.•Ca2+ influx and release by the endoplasmic ...reticulum are the Ca2+ sources.•AVP inhibits adipocyte differentiation.
Intracellular Ca2+ signaling is important for stem cell differentiation and there is evidence it may coordinate the process. Arginine vasopressin (AVP) is a neuropeptide hormone secreted mostly from the posterior pituitary gland and increases Ca2+ signals mainly via V1 receptors. However, the role of AVP in adipogenesis of human adipose-derived stem cells (hASCs) is unknown. In this study, we identified the V1a receptor gene in hASCs and demonstrated that AVP stimulation increased intracellular Ca2+ concentration during adipogenesis. This effect was mediated via V1a receptors, Gq-proteins and the PLC-IP3 pathway. These Ca2+ signals were due to endoplasmic reticulum release and influx from the extracellular space. Furthermore, AVP supplementation to the adipogenic medium decreased the number of adipocytes and adipocyte marker genes during differentiation. The effect of AVP on adipocyte formation was reversed by the V1a receptor blocker V2255. These findings suggested that AVP may function to inhibit adipocyte differentiation.
This study presents a 3‐dimensional (3D) network structure of cellulose scaffold (CS), which was in situ decorated with silver nanoparticles (AgNPs). The scaffold was then infiltrated with epoxy ...matrix and cured at elevated temperature to sinter the AgNPs; finally, highly thermoconductive epoxy composites (Ag@CS/epoxy) was obtained. The resultant Ag@CS20/epoxy composite reached a thermal conductivity of 2.52 W·m−1·K−1 at 2.2 vol% of filler loading, which shows an enhancement of over 11‐folds in the thermal conductivity compared to the neat epoxy. The superb electrical conductivity value of over 53,691 S·m−1 of the Ag@CS20/epoxy was achieved, which led to exceptional EMI SE values of 69.1 dB. Furthermore, surface temperatures during heating and cooling were also investigated to demonstrate the superior heat dissipating capacity of the Ag@CS/epoxy composite, which can be potentially put an application as thermal dissipating material in the next generation of electronics.
The 3D structure of sintered silver based polymer composites for thermoconductive EMI shielding materials.
In this study, lead (Pb) and cadmium (Cd) were used as chemical stressors. Healthy A. testudineus were exposed to Pb (20, 30, and 40 mg/L) and Cd (3, 5, and 10 mg/L) for 7, 14, 21, and 28 days to ...assess the response of A. testudineus elicited by these metals. The tendency of Pb and Cd accumulation in the tissues of A. testudineus was as follows: gill >> liver > muscle for Pb and liver >> gill > muscle for Cd. Endocrine stress response was characterized by varying the levels of cortisol and glucose plasma. Exposure to both Pb and Cd caused significantly increase levels of plasma cortisol (p < 0.05), while blood glucose levels slightly increased at the beginning and then decreased sharply. Based on the erratic changes in levels of plasma cortisol and blood glucose, it can be concluded that exposure to high concentrations of Pb and Cd does not cause death; however, it adversely affects the interrenal and pancreatic activities of A. testudineus. Biochemical changes can be used as biomarkers for stress assessment and management in fish.
Staphylococcus aureus
is the Gram-positive, immobile, round-shaped bacterium usually existing on wounds, marine environments, and contaminated food. α-Hemolysin (also called
-toxin), a common ...pore-forming toxin that presents in most
S. aureus
strains with the ability to penetrate the host cell membrane, leading to osmotic swelling and cell death, appears to be a potential biomarker for detection. Based on a sandwich format, this study developed a lateral flow immunoassay (LFIA) targeting
-toxin to detect
S. aureus
. Silver enhancement method was applied to enhance the test line’s signal and, therefore, improve the limit of detection (LOD). This method relies on the accumulation on AuNP surface of silver atoms which come from silver nitrate salt after being reduced by reducing agent. The developed LFIA could detect the target antigen within approximately 20 min with no cross-reactivity. The LOD was increased 10-fold after the silver enhancement, from 10
5
to 10
4
CFU/mL of bacteria suspensions. The results indicated that
-toxin is a promising target to detect
S. aureus
. Targeting
-toxin not only can be a potential detection approach but also a tool for measuring toxicity.
PDF
