Rotavirus group A (RVA) is the most common cause of severe childhood diarrhea worldwide. The introduction of rotavirus vaccination programs has contributed to a reduction in hospitalizations and ...mortality caused by RVA. From 2016 to 2021, we conducted surveillance to monitor RVA prevalence and genotype distribution in Nam Dinh and Thua Thien Hue (TT Hue) provinces where a pilot Rotavin-M1 vaccine (Vietnam) implementation took place from 2017 to 2020. Out of 6626 stool samples, RVA was detected in 2164 (32.6%) by ELISA. RT-PCR using type-specific primers were used to determine the G and P genotypes of RVA-positive specimens. Whole genome sequences of a subset of 52 specimens randomly selected from 2016 to 2021 were mapped using next-generation sequencing. From 2016 to 2021, the G9, G3 and G8 strains dominated, with detected frequencies of 39%, 23%, and 19%, respectively; of which, the most common genotypes identified were G9P8, G3P8 and G8P8. G1 strains re-emerged in Nam Dinh and TT Hue (29.5% and 11.9%, respectively) from 2020 to 2021. G3 prevalence decreased from 74% to 20% in TT Hue and from 21% to 13% in Nam Dinh province between 2017 and 2021. The G3 strains consisted of 52% human typical G3 (hG3) and 47% equine-like G3 (eG3). Full genome analysis showed substantial diversity among the circulating G3 strains with different backgrounds relating to equine and feline viruses. G9 prevalence decreased sharply from 2016 to 2021 in both provinces. G8 strains peaked during 2019–2020 in Nam Dinh and TT Hue provinces (68% and 46%, respectively). Most G8 and G9 strains had no genetic differences over the surveillance period with very high nucleotide similarities of 99.2–99.9% and 99.1–99.7%, respectively. The G1 strains were not derived from the RVA vaccine. Changes in the genotype distribution and substantial diversity among circulating strains were detected throughout the surveillance period and differed between the two provinces. Determining vaccine effectiveness against circulating strains over time will be important to ensure that observed changes are due to natural secular variation and not from vaccine pressure.
•In Vietnam from 2016 to 2021, the G9 RVA genotype was the most frequently detected, followed by G3 (23.9%) and G8 (18.8%)•The circulating G3P8 genotypes were phylogenetically diverse with human and equine-like strains equally distributed.•The antigenic epitopes present on VP7 protein of G1, G3 and G9 strains differed considerably with vaccine strains.
Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B ...deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking.
In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile.
The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval CI, -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group.
Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).
Tris(4‐carbazoyl‐9‐ylphenyl)amine (TCTA) is a commonly used host material for organic light‐emitting diodes (OLEDs). TCTA has poor solubility and hence to improve solubility the authors have ...synthesized first‐ and second‐generation TCTA‐based dendrimers with n‐propyl surface groups. These dendrimeric TCTA hosts have improved solubility and similar photophysical properties to TCTA. The hole mobility of solution‐processed TCTA is found to be an order of magnitude less than films formed by evaporation and similar to that of the two dendronized TCTAs (mobilities in the order of 10−5 cm2 V−1 s−1). The hole mobility in the films is found to decrease when a green emissive first‐generation light‐emitting dendrimer is blended with the host materials due to charge trapping on the emissive guest. In the case of the second‐generation host, there is evidence of a degree of phase separation in the film. Organic light‐emitting diodes are fabricated at guest concentrations corresponding to the maximum observed photoluminescence quantum yield (PLQY) and lowest hole mobility. It is found that the external quantum efficiency (EQE) does not always scale with the PLQY, leading to devices that have EQEs higher than expected based on the PLQY and outcoupling of light from a bottom emitting device.
Energy transfer, photoluminescence quantum yield (PLQY), charge mobility, and organic light‐emitting diode (OLED) performance are found to be dependent on the generation of the dendrimer host. OLED performance of the TCTA‐based host materials blended with a soluble phosphorescent light‐emitting dendrimer is found to depend on the maximum film PLQY, with good external quantum efficiencies achieved despite low charge mobilities.
Bacterial leaf blight (BLB) is a common disease that affects rice development and yield. The effects of major nutrients, especially nitrogen, on rice BLB susceptibility have been considered when ...devising rational fertilization strategies. However, the defense mechanism of rice against BLB under phosphate (Pi)-deficient conditions remains uncertain. Jasmonic acid (JA) is a phytohormone produced by rice plants to respond to abiotic and biotic stresses. Here, the involvement of the JA pathway in rice response to Xanthomonas oryzae pv. oryzae (Xoo) under low Pi was investigated in two contrasting rice cultivars G299 and G22. Expressions of JA-related genes under low Pi and Pi-related genes under JA treatment were assessed. The resistant capacity of G299 and G22 against Xoo infection was also investigated. In the JA-sensitive and Pi-sensitive cv. G299, JA-related genes were highly expressed under low Pi, and low Pi-responsive genes were strongly upregulated under JA treatment. Neither JA nor Pi pathways were activated in the JA-tolerant and low Pi-tolerant cv. G22. Low Pi strongly enhanced rice resistance to Xoo in cv. G299. Our study demonstrated that Pi deficiency confers rice resistance to Xoo. The JA pathway modulates the response to low Pi, depending on the cultivar. Pi-response genes are involved in Pi stress and may participate in the regulation of overall plant growth under various abiotic stresses. These findings provide new insights into the interaction between phosphate deficiency and the JA pathway and the subsequent effect on plant disease resistance.
Fac-tris2-phenylpyridinato-C2,Niridium(III) Ir(ppy)3 is a well-known phosphorescent material for organic light-emitting diodes (OLEDs) and while uniform thin films can be formed using evaporation ...under high vacuum, it is not sufficiently soluble to enable it to be processed from solution. Ir(ppy)3-cored dendrimers with solubilizing surface groups can be processed from solution to form good quality neat or guest:host blends, even when the host has relatively poor solubility. In this manuscript, we report the effect of adding different solubilizing surface groups, namely 2-ethylhexyloxy, n-propyl or t-butyl to first generation dendrons attached to the Ir(ppy)3 core on the optoelectronic properties of neat and blend films with tris(4-carbazoyl-9-ylphenyl)amine (TCTA). The different dendrons were found to have minimal effect on the photoluminescence spectra and efficiency of energy transfer from the host to the guest in the blend films. The hole mobility of neat films of the solution-processed Ir(ppy)3-cored dendrimer films was around 10−6 cm2 V−1 s−1, which was an order of magnitude less than Ir(ppy)3 films formed by evaporation. Blending the dendrimers with TCTA at a concentration of 11 mol% (the concentration of the highest film photoluminescence quantum yield) led to an order of magnitude decrease in the hole mobility compared to the neat films. However, despite the relatively low mobilities, simple two-layer OLEDs composed of a blend light-emitting layer and an electron transporting layer were found to reach a maximum EQE of 11.1% at a luminance of 1000 cd m−2 for a film with a PLQY of 60%.
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•Ir(ppy)3-cored dendrimers with solubilising surface groups are solution processed.•Good quality guest:host blend films formed with poorly soluble TCTA host.•Dendron type was found to have minimal effect on the host to guest energy transfer.•Charge mobility in dendrimer:TCTA blends less than in neat film.•Simple two-layer OLEDs had maximum EQEs of 11.1% at a luminance of 1000 cd m-2.
Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium ...hydroxide adjuvant.
We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients.
For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 CI95%: 51·12–71·55, 49·11 41·26–58·46, 57·18 48·4-67·5 compared to 7·10 6·32-13·92 of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 52·2–152·3, 80·0 50·8–125.9 and 95·1 63·1–143·6, compared to 55·1 33·4-91·0 of the convalescent group.
Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses.
This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.
Emerging studies indicate that cooperation between neurons and immune cells regulates antimicrobial immunity, inflammation and tissue homeostasis. For example, a neuronal rheostat provides excitatory ...or inhibitory signals that control the functions of tissue-resident group 2 innate lymphoid cells (ILC2s) at mucosal barrier surfaces
. ILC2s express NMUR1, a receptor for neuromedin U (NMU), which is a prominent cholinergic neuropeptide that promotes ILC2 responses
. However, many functions of ILC2s are shared with adaptive lymphocytes, including the production of type 2 cytokines
and the release of tissue-protective amphiregulin (AREG)
. Consequently, there is controversy regarding whether innate lymphoid cells and adaptive lymphocytes perform redundant or non-redundant functions
. Here we generate a new genetic tool to target ILC2s for depletion or gene deletion in the presence of an intact adaptive immune system. Transgenic expression of iCre recombinase under the control of the mouse Nmur1 promoter enabled ILC2-specific deletion of AREG. This revealed that ILC2-derived AREG promotes non-redundant functions in the context of antiparasite immunity and tissue protection following intestinal damage and inflammation. Notably, NMU expression levels increased in inflamed intestinal tissues from both mice and humans, and NMU induced AREG production in mouse and human ILC2s. These results indicate that neuropeptide-mediated regulation of non-redundant functions of ILC2s is an evolutionarily conserved mechanism that integrates immunity and tissue protection.
We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D).
In 5,230 Chinese patients ...(47.6% men) with T2D (mean ± SD age: 56.5 ± 13.9 years; median diabetes duration: 6 interquartile range 1, 12 years), enrolled consecutively in 1996-2012 and prospectively observed until 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes.
At baseline, 28.6% (n = 1,494) had low CP (<200 pmol/L) and 4.9% (n = 257) had positive GADA (GADA+). In the low-CP group, 8.0% had GADA+, and, in the GADA+ group, 46.3% had low CP. The GADA+ group had an adjusted hazard ratio (aHR) of 1.46 (95% CI 1.15-1.84, P = 0.002) for insulin initiation versus the GADA- group, while the low-CP group had an aHR of 0.88 (0.77-1.00, P = 0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (-1.9% at month 6; -1.5% at month 12 vs. -1% in the other three groups). The aHR of severe hypoglycemia was 1.29 (95% CI 1.10-1.52, P = 0.002) in the low-CP group and 1.38 (95% CI 1.04-1.83, P = 0.024) in the GADA+ group.
There is considerable heterogeneity in autoimmunity and β-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation, while GADA+ and low CP, increased the risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.
Chemoimmunotherapy is an effective therapy for an individual with nonsmall-cell lung cancer (NSCLC) without anaplastic lymphoma kinase or epidermal growth factor receptor mutations. However, it can ...also be related to adverse cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with high morbidities and mortality rates. We present a case of a 65-year-old male with NSCLC who underwent first-line chemotherapy with paclitaxel, carboplatin, and pembrolizumab, which was later followed by a second cycle of the same therapies. The patient developed a fever and rash 12 days after the second cycle. Pembrolizumab was strongly suspected as the culprit medication because cutaneous reactions to this drug have been frequently reported and threw other medications used as less likely candidates. This is the first case reported in Vietnam of SJS/TEN related to pembrolizumab and contributes to our knowledge of severe skin reactions associated with immune checkpoint inhibitors.
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