Hypovolemic shock (dengue shock syndrome (DSS)) is the most common life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and ...2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, Pmeta = 4.41 × 10−11, per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, Pmeta = 3.08 × 10−10, per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
•Ag/GO was successfully synthesized by co-precipitation.•LAA was used as a reducing agent, which is easy to find, and eco-friendly.•AgNPs with size 17.65 ± 4.76 nm were decorated on GO.•Concentration ...and contact time significantly affect the antibacterial activity.•The antibacterial activity of Ag/GO increased when pH value was decreased.
Herein, silver/graphene oxide (Ag/GO) nanocomposite was fabricated by co-precipitation with green reducing agent and then was characterized with modern analytical techniques. The antibacterial activities were conducted via the effects of Ag/GO concentration, time, and pH. Results show that silver nanoparticles were uniformly distributed on the GO sheets nanosized of 17.65 ± 4.76 nm. The antibacterial performance was optimized at pH 5.6, eradicating P. aeruginosa in 180 min at 50 µg/mL Ag/GO concentration and S. aureus in 480 min at 300 µg/mL Ag/GO. This demonstrates the potential of Ag/GO as an antibacterial nanocomposite material.
This study challenges the long-standing deficit discourse of international students. Applying agency theories, it explores six Vietnamese doctoral students' narratives of their candidature in an ...Australian research-intensive university using data drawn from semi-structured interviews. The findings confirm the high level of agency that international students displayed in previous research and show new nuances. Needs-response agency is displayed in the way the students dealt with language for research purposes. Agency as struggle and resistance is manifest in the soft strategies, which may be culturally invisible through the Western lens. Agency for becoming shows the transformation into a more confident and autonomous self. Pervading the other forms of agency, relational agency refers to the way these candidates effectively mobilised their families and communities, and maturated networks. The study expands understanding of international doctoral students' abilities to successfully navigate their candidature. The findings have important implications for supervisors to further develop their expertise.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Lower Mekong Delta Coastal Zone (LMDCZ) is emblematic of the coastal erosion problem facing many tropical deltas. Over the last 3500 years, large river sediment fluxes expanded the delta seaward, ...and waves and currents formed the Ca Mau Peninsula to the southwest. Since the middle of the 20th century, the LMDCZ is affected by various human activities that include reduction of river fluxes due to damming and sand mining, land subsidence due to groundwater extraction, and reduction of protective coastal mangroves in favor of agriculture and aquaculture. Coastal erosion is observed along many sections of the delta, with a rate of up to 50 m per year in some areas. However, the role of human activities remains difficult to assess because of its complexity. The present modeling study is designed to sort out the contribution of natural hydrodynamic redistribution of sediments from man-induced erosion. The modeling system used is based on CROCO, forced by global reanalyses at the boundaries and at the surface, including wave statistics (required by the sediment transport model). Tides and realistic river forcing are also included. Calibration and validation relies on a combination of in situ and remotely-sensed observations, and laboratory experiments. Once validated, coastal dynamics are investigated by performing sensitivity experiments for both the hydro- and sediment dynamics. The results suggest that while wind is the main factor driving the coastal currents, the sediment dynamics is essentially the result of re-suspension due to wave-induced bed shear stress. The suspended sediments are then redistributed by coastal currents that are not limited to the nearshore zone. Strong seasonality of the process is observed with the northeast winter monsoon being the season of strongest re-suspension and sediment redistribution. The annual sediment budget is characterized by important local disequilibrium, with alongshore patterns that are in agreement with the observed shoreline evolution. The effect of a decrease in river sediment supply is difficult to evaluate because the estuarine zone is still in accretion, apart from the particular case of Go Cong shores. Far from the estuarine zone, subsidence is an additional strong candidate to explain erosion in areas that should naturally be accreting. Synthesizing these results, the study proposes a first attempt at a “taxonomy and geography” of processes along the coastal Mekong delta that can explain the recent observations of shoreline changes and help design protection measures.
Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an ...inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever. Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576.
Dengue is the most prevalent arboviral disease of humans. The host and virus variables associated with dengue virus (DENV) transmission from symptomatic dengue cases (n = 208) to Aedes aegypti ...mosquitoes during 407 independent exposure events was defined. The 50% mosquito infectious dose for each of DENV-1-4 ranged from 6.29 to 7.52 log10 RNA copies/mL of plasma. Increasing day of illness, declining viremia, and rising antibody titers were independently associated with reduced risk of DENV transmission. High early DENV plasma viremia levels in patients were a marker of the duration of human infectiousness, and blood meals containing high concentrations of DENV were positively associated with the prevalence of infectious mosquitoes 14 d after blood feeding. Ambulatory dengue cases had lower viremia levels compared with hospitalized dengue cases but nonetheless at levels predicted to be infectious to mosquitoes. These data define serotype-specific viremia levels that vaccines or drugs must inhibit to prevent DENV transmission.
Since the 1960s the membrane‐bound enzyme alkaline phosphatase (ALP) has been utilized in drug delivery. As it cleaves phosphate substructures from drugs, auxiliary agents, and even from the surface ...of nanocarriers, this enzyme enables the design of drug delivery systems that can alter their properties in the body on demand. Anionic nanocarriers exhibiting bioinert properties can alter their surface to interactive once having reached the target site as due to an ALP‐triggered cleavage of anionic phosphate groups from their surface charge converts to cationic improving for instance cellular uptake. Moreover, features such as the accumulation of nanocarriers at the target site or a targeted drug release triggered by ALP can be introduced. In addition, ALP is utilized to improve the potential of numerous diagnostic systems. Within this review, one provides an overview about the activity, selectivity, and distribution of this enzyme, as well as the great variety of applications in drug delivery and diagnostics making use of it.
Alkaline phosphatase has been an endogenous partner for phosphate prodrugs for decades. More recently, it has been utilized as a reliable partner for enzyme‐responsive drug nanocarriers and diagnostic systems constructed from novel phosphate‐functionalized biomaterials.
To prepare new polycationic pullulan derivatives exhibiting highly mucoadhesive and sustained drug release properties.
Hydroxy groups of pullulan were activated with mesyl chloride followed by ...conjugation with low-molecular weight polyamines. Pullulan-tris(2-aminoethyl)amine (Pul-TAEA) and pullulan-polyethyleneimine (Pul-PEI) were evaluated regarding swelling behaviour, mucoadhesive properties and potential to control drug release.
Pul-TAEA and Pul-PEI exhibited excellent swelling properties at pH 6.8 showing 240- and 370-fold increase in weight. Compared to unmodified pullulan, Pul-TAEA and Pul-PEI displayed 5- and 13.3-fold increased dynamic viscosity in mucus. Mucoadhesion studies of Pul-TAEA and Pul-PEI on intestinal mucosa showed a 6- and 37.8-fold increase in tensile strength, and a 72- and 120-fold increase in mucoadhesion time compared to unmodified pullulan, respectively. Due to additional ionic interactions between cationic groups on polyaminated pullulans and an anionic model drug, a sustained drug release was achieved.
Polyaminated pullulans are promising novel mucoadhesive excipients for mucosal drug delivery.
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Dengue is a public health problem in many countries. Rapid diagnosis of dengue can assist patient triage and management. Detection of the dengue viral protein, NS1, represents a new approach to ...dengue diagnosis.
The sensitivity and specificity of the Platelia NS1 ELISA assay and an NS1 lateral flow rapid test (LFRT) were compared against a gold standard reference diagnostic algorithm in 138 Vietnamese children and adults. Overall, the Platelia NS1 ELISA was modestly more sensitive (82%) than the NS1 LFRT (72%) in confirmed dengue cases. Both ELISA and LFRT assays were more sensitive for primary than secondary dengue, and for specimens collected within 3 days of illness onset relative to later time points. The presence of measurable DENV-reactive IgG and to a lesser extent IgM in the test sample was associated with a significantly lower rate of NS1 detection in both assays. NS1 positivity was associated with the underlying viraemia, as NS1-positive samples had a significantly higher viraemia than NS1-negative samples matched for duration of illness. The Platelia and NS1 LFRT were 100% specific, being negative in all febrile patients without evidence of recent dengue, as well as in patients with enteric fever, malaria, Japanese encephalitis and leptospirosis.
Collectively, these data suggest NS1 assays deserve inclusion in the diagnostic evaluation of dengue patients, but with due consideration for the limitations in patients who present late in their illness or have a concomitant humoral immune response.
•Ag/GO was successfully synthesized by the in situ method. Glucose was used as an eco-friendly reducing agent.•AgNPs with an average size of 17.68 ± 4.48 nm.•Ag/GO express the extremely high ...antibacterial capacity against S. aureus and S. enterica.•Placket–Burman and Box–Behnken model experimental design was used to optimize.
In this study, silver/graphene oxide (Ag/GO) nanocomposites were synthesized using the in situ method. Glucose was selected as an eco-friendly reducing agent for the reduction of Ag+ into silver nanoparticles (AgNPs). The characterization of GO and Ag/GO with Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, Raman spectroscopy, scanning electron microscopye, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. Results showed that Ag/GO was successfully synthesized. Silver nanoparticles (AgNPs) with an average size of 17.68 ± 4.48 nm were uniformly distributed onto GO sheets. The antibacterial activity of GO, AgNPs, and Ag/GO were tested against Staphylococcus aureus ATCC 25,923 (S. aureus) and Salmonella enterica ATCC 35,664 (S. enterica) bacteria by optical density and plate colony–counting methods. Test results showed that Ag/GO had higher antibacterial activity than its precursors (bare AgNPs and GO) with a bactericidal rate of more than 99.90 %. Thus, Ag/GO was selected for further experimentation. Simultaneous effects of the interaction time, Ag/GO concentration, pH, annealing temperature, and S. aureus density on the antibacterial activity of Ag/GO were also investigated with full factorial experimental design according to Placket–Burman and Box–Behnken designs. After 10 min of interaction time at 37 °C, the optimal values of these factors were determined to be: Ag/GO concentration of 48 μg/mL, pH 5, and S. aureus density 5.3 × 106 CFU/mL, corresponding to an antibacterial capacity of 99.95 % towards S. aureus. The presented experiment confirmed Ag/GO to be able of eliminating about 99.99 % of S. aureus. All results of the present study affirmed the potential applications of Ag/GO as an antibacterial agent in the medical field.
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