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Herein we report synthesis of bare cerium oxide nanoparticles from cerium hydroxide and NiS@CeO2 nanocomposite (NC) from nickel cinnamaldehyde thiosemicarbazone complex (single source molecular precursor) and CeO2 nanoparticles by solvothermal method using ethylene glycol as a capping agent. These materials were characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, high resolution transmission electron microscopy and energy dispersive X-ray techniques. The crystallite size of the composite nanoparticles calculated using XRD is 17.99 nm. TEM shows spherical shape morphology of NiS@CeO2 nanocomposite with average particle size less than 10 nm. Electrochemical properties of bare CeO2 and NiS@CeO2 NC electrodes were evaluated by cyclic voltammetry, galvanostatic charge/discharge and electrochemical impedance spectroscopy. The electrochemical measurements show that the capacitance value of NiS@CeO2 NC electrode is significantly higher (707.84 F g−1) compared to bare CeO2 electrode (80.91 F g−1) at current density 1 A g−1. This can be attributed to synergistic effect in nanocomposite. The cycle stability of NiS@CeO2 NC electrode was found to be 98.41 % even after 6000 charge–discharge cycles at 2 A g−1 current density.

This work reports one-pot solvothermal synthesis of CuFeS2 nanomaterial using Cu(NO3)2•6H2O and FeCl2(3-Cl-benztsczH)2, where benztsczH = benzaldehyde thiosemicarbazone as molecular precursors. The electrochemical performance of as-prepared chalcopyrite, CuFeS2 nanomaterial was studied in order to investigate its ability to work as a supercapacitor material for energy storage devices. The material obtained was characterized by various techniques. The XRD pattern of as-prepared chalcopyrite, CuFeS2 matches with tetragonal phase of the material (JCPDS card no. 037–0471). The crystallite size calculated using Scherrer's formula is found to be 41.5 nm. High resolution transmission electron microscopy (HRTEM) revealed the presence of nanomaterial having spherical morphology. The electrochemical properties of the as-prepared chalcopyrite, CuFeS2 electrode were investigated in aqueous electrolyte, 6 M KOH. Cyclic voltammetry (CV) and galvanostatic charge/discharge (GCD) curves show the pseudocapacitive behaviour of the CuFeS2 electrode. The material is found to have excellent specific capacitance of 206.3 C g−1 (589 F g−1) at 0.5 A g−1 current density with cycle stability of ∼82% after 2000 cycles (at current density of 4 A g−1).

Purpose We describe here a multicentric community-dwelling cohort of older adults (>60 years of age) established to estimate incidence, study risk factors, healthcare utilisation and economic burden associated with influenza and respiratory syncytial virus (RSV) in India.Participants The four sites of this cohort are in northern (Ballabgarh), southern (Chennai), eastern (Kolkata) and western (Pune) parts of India. We enrolled 5336 participants across 4220 households and began surveillance in July 2018 for viral respiratory infections with additional participants enrolled annually. Trained field workers collected data about individual-level and household-level risk factors at enrolment and quarterly assessed frailty and grip strength. Trained nurses surveilled weekly to identify acute respiratory infections (ARI) and clinically assessed individuals to diagnose acute lower respiratory infection (ALRI) as per protocol. Nasal and oropharyngeal swabs are collected from all ALRI cases and one-fifth of the other ARI cases for laboratory testing. Cost data of the episode are collected using the WHO approach for estimating the economic burden of seasonal influenza. Handheld tablets with Open Data Kit platform were used for data collection.Findings to date The attrition of 352 participants due to migration and deaths was offset by enrolling 680 new entrants in the second year. All four sites reported negligible influenza vaccination uptake (0.1%–0.4%), low health insurance coverage (0.4%–22%) and high tobacco use (19%–52%). Ballabgarh had the highest proportion (54.4%) of households in the richest wealth quintile, but reported high solid fuel use (92%). Frailty levels were highest in Kolkata (11.3%) and lowest in Pune (6.8%). The Chennai cohort had highest self-reported morbidity (90.1%).Future plans The findings of this cohort will be used to inform prioritisation of strategies for influenza and RSV control for older adults in India. We also plan to conduct epidemiological studies of SARS-CoV-2 using this platform.

BackgroundInfluenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years.Methods and findingsIn June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV (n = 1,015), IIV (n = 1,010), nasal placebo (n = 507), or IPV (n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years. Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year. In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was -46.2% (95% CI -88.9 to -13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI -19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted.ConclusionsIn this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children.Trial registrationClinical Trials Registry of India CTRI/2015/06/005902.

Abstract Background Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population. Methods 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m2; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38). Discussion This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD. Trial registration ClinicalTrials.gov: NCT02063776. The trial was prospectively registered on the 14 Feb 2014.

The synthesis and characterization of lead sulphide nanoparticles using complexes as single sources of both lead and sulphur are reported. A cubic phase of galena perfectly matched all synthesized nanoparticles confirming that no secondary product was generated. The complexes prepared from thiosemicarbazide materials and lead bromide reacted differently in oleylamine to produce PbS nanoparticles. Smaller cubic shapes and quantum dots with a blue-shifted absorption were yielded from cinnamaldehyde thiosemicarbazide and benzophenone thiosemicarbazide complexes due to larger ligands and the symmetrical position of the thiosemicarbazide group in benzophenone complex. Relatively larger particles were obtained from acetophenone thiosemicarbazide complex. The temperature of synthesis also affected the shape and size of PbS nanoparticles.

Purpose: To report here a case of uncontrolled glaucoma during third-trimester of pregnancy that was treated successfully with bilateral Xen gel stent insertion. Observations: A 35-year-old woman presented during the third trimester of pregnancy with bilateral uncontrolled primary open angle glaucoma. Her disc examination and visual fields were consistent with advanced glaucoma. After failed Selective Laser Trabeculoplasty and maximal medical treatment, including Acetazolamide, she was treated with bilateral consecutive Xen stent surgery with successful control of her intraocular pressure. Conclusions and Importance: The use of Xen implant may have advantages over traditional trabeculectomy, especially during pregnancy, as the procedure is shorter, with less dependence on on-table antimetabolite and being minimally invasive with sparing of the conjunctiva. Keywords: Xen gel stent, Glaucoma in pregnancy

High yield, low cost, environmentally friendly chemical bath synthesis process is used to produce submicron structures of ZnO and ZnO-carbon composites. Synthesis of ZnO rod structures (submicron sized) were confirmed using SEM images. To synthesis ZnO-carbon composites, well characterized carbon spheres produced using aerosol assisted CVD technique was used. Use of carbon spheres as a seed during synthesis of ZnO is observed to produce multipod structures of ZnO on to the surface of carbon spheres; the growth is explained by proposing suitable model. Room temperature photoluminescence spectra recorded for ZnO and ZnO-carbon composites synthesized show a systematic disappearance of a band-edge emission (sharp peak present at ∼380 nm observed for pure ZnO) with increased number of carbon spheres. Competent photo-catalytic activity of synthesized composite is confirmed by studying photo degradation investigation performed using a model dye molecule i.e. methyl orange. The work reveals possibility to use synthesized composites as a nontoxic and biocompatible catalyst for fragmentation of a methyl orange dye molecule. Photo-degradation mechanism of a methyl orange dye is proposed herewith considering the role of carbon spheres and ZnO in presence of UV photon.

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

The present work aims towards the design and development of extended release formulation of freely water-soluble drug diltiazem hydrochloride (DLTZ) based on osmotic technology by using controlled porosity approach. DLTZ is an ideal candidate for a zero-order drug delivery system because it is freely water-soluble and has a short half-life (2-3 h). Sodium chloride (Osmogen) was added to the core tablet to alter the solubility of DLTZ in an aqueous medium. Cellulose acetate (CA) and sorbitol were used as semipermeable membrane and pore former, respectively. The effect of different formulation variables namely concentration of osmogen in the core tablet, % pore former, % weight gain, pH of the dissolution medium and agitation intensity on the in vitro release was studied. DLTZ release was directly proportional to % pore former and inversely proportional to % weight gain. The optimized formulation (F8) delivered DLTZ independent of pH and agitation intensity for 12 h at the upper level concentration of % pore former (25% w/w) and middle level concentration of % weight gain (6% w/w). The comparative study of elementary osmotic pump (EOP) and controlled porosity osmotic pump revealed that it superior than conventional EOP and also easier and cost effective to formulate.

Influenza surveillance was carried out in a subset of patients with influenza-like illness (ILI) presenting at an Employee Health Clinic (EHS) at All India Institute of Medical Sciences (AIIMS), New Delhi (urban) and pediatric out patients department of civil hospital at Ballabhgarh (peri-urban), under the Comprehensive Rural Health Services Project (CRHSP) of AIIMS, in Delhi region from January 2007 to December 2010. Of the 3264 samples tested, 541 (17%) were positive for influenza viruses, of which 221 (41%) were pandemic Influenza A(H1N1)pdm09, 168 (31%) were seasonal influenza A, and 152 (28%) were influenza B. While the Influenza viruses were detected year-round, their types/subtypes varied remarkably. While there was an equal distribution of seasonal A(H1N1) and influenza B in 2007, predominance of influenza B was observed in 2008. At the beginning of 2009, circulation of influenza A(H3N2) viruses was observed, followed later by emergence of Influenza A(H1N1)pdm09 with co-circulation of influenza B viruses. Influenza B was dominant subtype in early 2010, with second wave of Influenza A(H1N1)pdm09 in August-September, 2010. With the exception of pandemic H1N1 emergence in 2009, the peaks of influenza activity coincided primarily with monsoon season, followed by minor peak in winter at both urban and rural sites. Age group analysis of influenza positivity revealed that the percent positivity of Influenza A(H1N1)pdm09 influenza virus was highest in >5-18 years age groups (OR 2.5; CI = 1.2-5.0; p = 0.009) when compared to seasonal influenza. Phylogenetic analysis of Influenza A(H1N1)pdm09 from urban and rural sites did not reveal any major divergence from other Indian strains or viruses circulating worldwide. Continued surveillance globally will help define regional differences in influenza seasonality, as well as, to determine optimal periods to implement influenza vaccination programs among priority populations.

Understanding microbial gene functions relies on the application of experimental genetics in cultured microorganisms. However, the vast majority of bacteria and archaea remain uncultured, precluding the application of traditional genetic methods to these organisms and their interactions. Here, we characterize and validate a generalizable strategy for editing the genomes of specific organisms in microbial communities. We apply environmental transformation sequencing (ET-seq), in which nontargeted transposon insertions are mapped and quantified following delivery to a microbial community, to identify genetically tractable constituents. Next, DNA-editing all-in-one RNA-guided CRISPR-Cas transposase (DART) systems for targeted DNA insertion into organisms identified as tractable by ET-seq are used to enable organism- and locus-specific genetic manipulation in a community context. Using a combination of ET-seq and DART in soil and infant gut microbiota, we conduct species- and site-specific edits in several bacteria, measure gene fitness in a nonmodel bacterium and enrich targeted species. These tools enable editing of microbial communities for understanding and control.

We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.

Many bacterial and archaeal organisms use clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) systems to defend themselves from mobile genetic elements. These CRISPR-Cas systems are classified into six types based on their composition and mechanism. CRISPR-Cas enzymes are widely used for genome editing and offer immense therapeutic opportunity to treat genetic diseases. To realize their full potential, it is important to control the timing, duration, efficiency and specificity of CRISPR-Cas enzyme activities. In this Review we discuss the mechanisms of natural CRISPR-Cas regulatory biomolecules and engineering strategies that enhance or inhibit CRISPR-Cas immunity by altering enzyme function. We also discuss the potential applications of these CRISPR regulators and highlight unanswered questions about their evolution and purpose in nature.

Anti-CRISPRs (Acrs) are small proteins that inhibit the RNA-guided DNA targeting activity of CRISPR-Cas enzymes. Encoded by bacteriophage and phage-derived bacterial genes, Acrs prevent CRISPR-mediated inhibition of phage infection and can also block CRISPR-Cas-mediated genome editing in eukaryotic cells. To identify Acrs capable of inhibiting Staphylococcus aureus Cas9 (SauCas9), an alternative to the most commonly used genome editing protein Streptococcus pyogenes Cas9 (SpyCas9), we used both self-targeting CRISPR screening and guilt-by-association genomic search strategies. Here we describe three potent inhibitors of SauCas9 that we name AcrIIA13, AcrIIA14, and AcrIIA15. These inhibitors share a conserved N-terminal sequence that is dispensable for DNA cleavage inhibition and have divergent C termini that are required in each case for inhibition of SauCas9-catalyzed DNA cleavage. In human cells, we observe robust inhibition of SauCas9-induced genome editing by AcrIIA13 and moderate inhibition by AcrIIA14 and AcrIIA15. We also find that the conserved N-terminal domain of AcrIIA13-AcrIIA15 binds to an inverted repeat sequence in the promoter of these Acr genes, consistent with its predicted helix-turn-helix DNA binding structure. These data demonstrate an effective strategy for Acr discovery and establish AcrIIA13-AcrIIA15 as unique bifunctional inhibitors of SauCas9.

Background and Objective: In areas with a large Deaf/hard‐of‐hearing (DHH) population, emergency medicine (EM) providers may benefit from cultural awareness training as this has been shown to foster delivery of more equitable care in other minority populations. Rochester, New York, has been touted to be the home to the largest per‐capita DHH population in the United States. Given the large local DHH community and DHH professionals working in Rochester, University of Rochester (UR) providers likely have higher exposure to DHH people than most other EM providers in the United States. All UR providers receive annual institutional cultural sensitivity e‐training that includes information about the DHH community. In addition to the e‐training, the UR EM residents also receive a workshop during intern year and recurrent DHH culture education throughout their residency. The purpose of this study was to measure impact of preexisting cultural sensitivity training and higher DHH person exposure on DHH cultural awareness in UR providers compared to non‐UR EM providers who may have lower DHH person exposure and culture training. Methods: In this cross‐sectional study, a survey on DHH cultural awareness was distributed to UR and Emergency Research Network in the Empire State (ERNIES) emergency departments. As surrogates for cultural awareness, the survey evaluated providers' exposure, knowledge, comfort, and attitudes to Deaf culture. Descriptive statistics were employed to characterize the sample. Bivariate analysis was performed to compare UR provider responses to others using chi‐square and Fisher's exact testing. Results: Of 83 recruited participants, 75 providers completed the survey, and 53/75 (71%) responders were from UR. While high percentages of UR and non‐UR participants reported seeing DHH patients recently (98% vs. 96%, respectively), one‐third (24/75) of all participants reported having no experience or training on Deaf culture. Compared to only 10% of other providers, one‐third of UR providers were better able to identify cultural nuances within the DHH community (p = 0.01). UR providers were significantly less comfortable communicating with Deaf patients via lipreading, which is typically an unreliable/unsafe mode of communication (11% vs. 69%, p = 0.002). When knowledge was assessed, UR providers better identified Deaf patient rights in a clinical setting (89% vs. 77%, p = 0.002). Also, all trainees had significantly higher scores on questions related to Deaf culture compared to all advance practice providers and attendings (mean scores 6.86 vs. 6.06 and 6, respectively, p = 0.03). Conclusions: EM providers with high exposure to DHH people and DHH culture training are more comfortable with and able to better identify nuances of Deaf culture. Additionally, EM providers with DHH culture training are less comfortable communicating using lipreading with DHH patients suggesting increased awareness of a common, yet ineffective and inaccurate, communication pitfall with this population. The study suggests that implementing Deaf culture education in areas with a large DHH population may enhance cultural awareness and comfort of future providers in caring for Deaf patients. [ABSTRACT FROM AUTHOR]