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2.
Sci Total Environ ; 927: 171153, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38460683

RESUMO

About 3 billion new tires are produced each year and about 800 million tires become waste annually. Global dependence upon tires produced from natural rubber and petroleum-based compounds represents a persistent and complex environmental problem with only partial and often-times, ineffective solutions. Tire emissions may be in the form of whole tires, tire particles, and chemical compounds, each of which is transported through various atmospheric, terrestrial, and aquatic routes in the natural and built environments. Production and use of tires generates multiple heavy metals, plastics, PAH's, and other compounds that can be toxic alone or as chemical cocktails. Used tires require storage space, are energy intensive to recycle, and generally have few post-wear uses that are not also potential sources of pollutants (e.g., crumb rubber, pavements, burning). Tire particles emitted during use are a major component of microplastics in urban runoff and a source of unique and highly potent toxic substances. Thus, tires represent a ubiquitous and complex pollutant that requires a comprehensive examination to develop effective management and remediation. We approach the issue of tire pollution holistically by examining the life cycle of tires across production, emissions, recycling, and disposal. In this paper, we synthesize recent research and data about the environmental and human health risks associated with the production, use, and disposal of tires and discuss gaps in our knowledge about fate and transport, as well as the toxicology of tire particles and chemical leachates. We examine potential management and remediation approaches for addressing exposure risks across the life cycle of tires. We consider tires as pollutants across three levels: tires in their whole state, as particulates, and as a mixture of chemical cocktails. Finally, we discuss information gaps in our understanding of tires as a pollutant and outline key questions to improve our knowledge and ability to manage and remediate tire pollution.

3.
Environ Sci Technol ; 58(5): 2224-2235, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38267018

RESUMO

Estuarine environments are critical to fish species and serve as nurseries for developing embryos and larvae. They also undergo daily fluctuations in salinity and act as filters for pollutants. Additionally, global climate change (GCC) is altering salinity regimes within estuarine systems through changes in precipitation and sea level rise. GCC is also likely to lead to an increased use of insecticides to prevent pests from damaging agricultural crops as their habitats and mating seasons change from increased temperatures. This underscores the importance of understanding how insecticide toxicity to fish changes under different salinity conditions. In this study, larval Inland Silversides (Menidia beryllina) were exposed to bifenthrin (1.1 ng/L), cyfluthrin (0.9 ng/L), or cyhalothrin (0.7 ng/L) at either 6 or 10 practical salinity units (PSU) for 96 h during hatching, with a subset assessed for end points relevant to neurotoxicity and endocrine disruption by testing behavior, gene expression of a select suite of genes, reproduction, and growth. At both salinities, directly exposed F0 larvae were hypoactive relative to the F0 controls; however, the indirectly exposed F1 larvae were hyperactive relative to the F1 control. This could be evidence of a compensatory response to environmentally relevant concentrations of pyrethroids in fish. Effects on development, gene expression, and growth were also observed. Overall, exposure to pyrethroids at 10 PSU resulted in fewer behavioral and endocrine disruptive effects relative to those observed in organisms at 6 PSU.


Assuntos
Inseticidas , Piretrinas , Poluentes Químicos da Água , Animais , Salinidade , Piretrinas/toxicidade , Inseticidas/toxicidade , Peixes/fisiologia , Larva , Poluentes Químicos da Água/toxicidade
4.
J Virol ; 97(11): e0092223, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37861334

RESUMO

IMPORTANCE: The Omicron subvariants have substantially evaded host-neutralizing antibodies and adopted an endosomal route of entry. The virus has acquired several mutations in the receptor binding domain and N-terminal domain of S1 subunit, but remarkably, also incorporated mutations in S2 which are fixed in Omicron sub-lineage. Here, we found that the mutations in the S2 subunit affect the structural and biological properties such as neutralization escape, entry route, fusogenicity, and protease requirement. In vivo, these mutations may have significant roles in tropism and replication. A detailed understanding of the effects of S2 mutations on Spike function, immune evasion, and viral entry would inform the vaccine design, as well as therapeutic interventions aiming to block the essential proteases for virus entry. Thus, our study has identified the crucial role of S2 mutations in stabilizing the Omicron spike and modulating neutralization resistance to antibodies targeting the S1 subunit.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Endopeptidases , Conformação Molecular , Mutação , Peptídeo Hidrolases , SARS-CoV-2/classificação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
5.
Sci Total Environ ; 857(Pt 3): 159398, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36257430

RESUMO

Pyrethroids, a class of commonly used insecticides, are frequently detected in aquatic environments, including estuaries. The influence that salinity has on organism physiology and the partitioning of hydrophobic chemicals, such as pyrethroids, has driven interest in how toxicity changes in saltwater compared to freshwater. Early life exposures in fish to pyrethroids cause toxicity at environmentally relevant concentrations, which can alter behavior. Behavior is a highly sensitive endpoint that influences overall organism fitness and can be used to detect toxicity of environmentally relevant concentrations of aquatic pollutants. Inland Silversides (Menidia beryllina), a commonly used euryhaline model fish species, were exposed from 5 days post fertilization (~1-day pre-hatch) for 96 h to six pyrethroids: bifenthrin, cyfluthrin, cyhalothrin, cypermethrin, esfenvalerate and permethrin. Exposures were conducted at three salinities relevant to brackish, estuarine habitat (0.5, 2, and 6 PSU) and across 3 concentrations, either 0.1, 1, 10, and/or 100 ng/L, plus a control. After exposure, Inland Silversides underwent a behavioral assay in which larval fish were subjected to a dark and light cycle stimuli to determine behavioral toxicity. Assessment of total distanced moved and thigmotaxis (wall hugging), used to measure hyper/hypoactivity and anxiety like behavior, respectively, demonstrate that even at the lowest concentration of 0.1 ng/L pyrethroids can induce behavioral changes at all salinities. We found that toxicity decreased as salinity increased for all pyrethroids except permethrin. Additionally, we found evidence to suggest that the relationship between log KOW and thigmotaxis is altered between the lower and highest salinities.


Assuntos
Inseticidas , Piretrinas , Poluentes Químicos da Água , Animais , Larva , Permetrina , Salinidade , Ecotoxicologia , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/química , Piretrinas/toxicidade , Piretrinas/química , Peixes/fisiologia , Inseticidas/toxicidade , Inseticidas/química
6.
Trials ; 23(1): 755, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068618

RESUMO

BACKGROUND: South Asians are at high risk of type 2 diabetes (T2D). Lifestyle modification is effective at preventing T2D amongst South Asians, but the approaches to screening and intervention are limited by high costs, poor scalability and thus low impact on T2D burden. An intensive family-based lifestyle modification programme for the prevention of T2D was developed. The aim of the iHealth-T2D trial is to compare the effectiveness of this programme with usual care. METHODS: The iHealth-T2D trial is designed as a cluster randomised controlled trial (RCT) conducted at 120 sites across India, Pakistan, Sri Lanka and the UK. A total of 3682 South Asian men and women with age between 40 and 70 years without T2D but at elevated risk for T2D [defined by central obesity (waist circumference ≥ 95 cm in Sri Lanka or ≥ 100 cm in India, Pakistan and the UK) and/or prediabetes (HbA1c ≥ 6.0%)] were included in the trial. Here, we describe in detail the statistical analysis plan (SAP), which was finalised before outcomes were available to the investigators. The primary outcome will be evaluated after 3 years of follow-up after enrolment to the study and is defined as T2D incidence in the intervention arm compared to usual care. Secondary outcomes are evaluated both after 1 and 3 years of follow-up and include biochemical measurements, anthropometric measurements, behavioural components and treatment compliance. DISCUSSION: The iHealth-T2D trial will provide evidence of whether an intensive family-based lifestyle modification programme for South Asians who are at high risk for T2D is effective in the prevention of T2D. The data from the trial will be analysed according to this pre-specified SAP. ETHICS AND DISSEMINATION: The trial was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations. TRIAL REGISTRATION: EudraCT 2016-001,350-18 . Registered on 14 April 2016. CLINICALTRIALS: gov NCT02949739 . Registered on 31 October 2016.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Idoso , Povo Asiático , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/prevenção & controle , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/terapia , Sri Lanka
7.
Eur Respir J ; 60(6)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35896203

RESUMO

BACKGROUND: There are few data to support accurate interpretation of spirometry data in South Asia, a major global region with a high reported burden of chronic respiratory disease. METHOD: We measured lung function in 7453 healthy men and women aged ≥18 years, from Bangladesh, North India, South India, Pakistan and Sri Lanka, as part of the South Asia Biobank study. First, we assessed the accuracy of existing equations for predicting normal forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. Then, we used our data to derive (n=5589) and internally validate (n=1864) new prediction equations among South Asians, with further external validation among 339 healthy South Asians living in Singapore. RESULTS: The Global Lung Initiative (GLI) and National Health and Nutrition Examination Survey consistently overestimated expiratory volumes (best fit GLI-African American, mean±sd z-score: FEV1 -0.94±1.05, FVC -0.91±1.10; n=7453). Age, height and weight were strong predictors of lung function in our participants (p<0.001), and sex-specific reference equations using these three variables were highly accurate in both internal validation (z-scores: FEV1 0.03±0.99, FVC 0.04±0.97, FEV1/FVC -0.03±0.99) and external validation (z-scores: FEV1 0.31±0.99, FVC 0.24±0.97, FEV1/FVC 0.16±0.91). Further adjustment for study regions improves the model fit, with highest accuracy for estimation of region-specific lung function in South Asia. CONCLUSION: We present improved equations for predicting lung function in South Asians. These offer the opportunity to enhance diagnosis and management of acute and chronic lung diseases in this major global population.


Assuntos
Povo Asiático , Pulmão , Masculino , Feminino , Humanos , Adolescente , Adulto , Inquéritos Nutricionais , Valores de Referência , Espirometria , Volume Expiratório Forçado , Índia , Capacidade Vital
9.
Nat Commun ; 13(1): 1726, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365648

RESUMO

Immunization is expected to confer protection against infection and severe disease for vaccines while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies of an observational cohort of healthcare workers, we show that during a Severe Acute Respiratory Syndrome -Coronavirus 2 Delta-variant outbreak in Delhi, 25.3% (95% Confidence Interval 16.9-35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare workers were infected within less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, Inter Quartile Range 374) and without (342 U/ml, Inter Quartile Range 497), as was the induction of neutralization activity to wildtype. This was not vaccine failure since vaccine effectiveness estimate based on infection rates in an unvaccinated cohort were about 70% and most infections were asymptomatic. We find that while ChAdOx1-nCoV19 vaccination remains effective in preventing severe infections, it is unlikely to be completely able to block transmission and provide herd immunity.


Assuntos
Infecções Assintomáticas , COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pessoal de Saúde , Humanos , Imunização , SARS-CoV-2 , Vacinação
10.
PLoS One ; 17(3): e0264785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35298502

RESUMO

The variability of clinical course and prognosis of COVID-19 highlights the necessity of patient sub-group risk stratification based on clinical data. In this study, clinical data from a cohort of Indian COVID-19 hospitalized patients is used to develop risk stratification and mortality prediction models. We analyzed a set of 70 clinical parameters including physiological and hematological for developing machine learning models to identify biomarkers. We also compared the Indian and Wuhan cohort, and analyzed the role of steroids. A bootstrap averaged ensemble of Bayesian networks was also learned to construct an explainable model for discovering actionable influences on mortality and days to outcome. We discovered blood parameters, diabetes, co-morbidity and SpO2 levels as important risk stratification features, whereas mortality prediction is dependent only on blood parameters. XGboost and logistic regression model yielded the best performance on risk stratification and mortality prediction, respectively (AUC score 0.83, AUC score 0.92). Blood coagulation parameters (ferritin, D-Dimer and INR), immune and inflammation parameters IL6, LDH and Neutrophil (%) are common features for both risk and mortality prediction. Compared with Wuhan patients, Indian patients with extreme blood parameters indicated higher survival rate. Analyses of medications suggest that a higher proportion of survivors and mild patients who were administered steroids had extreme neutrophil and lymphocyte percentages. The ensemble averaged Bayesian network structure revealed serum ferritin to be the most important predictor for mortality and Vitamin D to influence severity independent of days to outcome. The findings are important for effective triage during strains on healthcare infrastructure.


Assuntos
COVID-19/mortalidade , Hospitalização/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , COVID-19/epidemiologia , COVID-19/etiologia , Criança , China/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Medição de Risco/métodos , Fatores de Risco , Adulto Jovem
11.
Chemosphere ; 287(Pt 3): 132289, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34562710

RESUMO

Contaminants of emerging concern (CEC) are a broad suite of chemicals commonly found in the environment, aquatic organisms and even drinking water. They include pharmaceuticals, personal care products, industrial chemicals and compounds added to consumer products. The CEC ammonium 2,3,3,3-tetrafluoro-2-heptafluoropropoxy propanoic acid, which is more commonly known as generic name GenX, is a replacement of common processing aid longer chain perfluorinated compounds (PFAS) due to a manufacturing shift in 2002 following the EPA stewardship program of 2015/16 in USA (USEPA, 2006). However, recently reported in North Carolina drinking water, GenX raising concerns about its accumulation in aquatic organisms, both wild and cultured, which could be a pathway for human exposure. To examine GenX accumulation and potential for human exposure, tilapia (Oreochromis mossambicus) fingerlings were dosed with GenX for up to 96 h in fresh (0 ppt) or brackish (16 ppt) water to determine uptake and bioconcentration. Depuration values were also determined after a 96 h exposure followed by 96 h without exposure. Bioconcentration was in decreasing order of plasma > liver > carcass > muscle, with higher distribution to liver followed by carcass and muscle. Muscle was found to have the highest half-life (1278 h) followed by carcass (532 h), plasma (106 h), and liver (152 h). The rate of uptake and depuration was positively affected by the salinity. As bioconcentration in all tissues increased with increasing salinity, this may raise concern for marine organisms and human exposure.


Assuntos
Tilápia , Poluentes Químicos da Água , Animais , Organismos Aquáticos , Bioacumulação , Humanos , Cinética
12.
Trials ; 22(1): 928, 2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34922608

RESUMO

BACKGROUND: People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. HYPOTHESIS: Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. DESIGN: Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. ENTRY CRITERIA: South Asian, men or women, age 40-70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0-6.4% inclusive). EXCLUSION CRITERIA: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. ENDPOINTS: The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. INTERVENTION: Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. RESULTS: We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). CONCLUSION: The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB APPROVAL: 16/WM/0171 TRIAL REGISTRATION: EudraCT 2016-001350-18 . Registered on 14 April 2016. ClinicalTrials.gov NCT02949739 . Registered on 31 October 2016, First posted on 31/10/2016.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Idoso , Povo Asiático , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Front Immunol ; 12: 765211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956193

RESUMO

Saturation suppressor mutagenesis was used to generate thermostable mutants of the SARS-CoV-2 spike receptor-binding domain (RBD). A triple mutant with an increase in thermal melting temperature of ~7°C with respect to the wild-type B.1 RBD and was expressed in high yield in both mammalian cells and the microbial host, Pichia pastoris, was downselected for immunogenicity studies. An additional derivative with three additional mutations from the B.1.351 (beta) isolate was also introduced into this background. Lyophilized proteins were resistant to high-temperature exposure and could be stored for over a month at 37°C. In mice and hamsters, squalene-in-water emulsion (SWE) adjuvanted formulations of the B.1-stabilized RBD were considerably more immunogenic than RBD lacking the stabilizing mutations and elicited antibodies that neutralized all four current variants of concern with similar neutralization titers. However, sera from mice immunized with the stabilized B.1.351 derivative showed significantly decreased neutralization titers exclusively against the B.1.617.2 (delta) VOC. A cocktail comprising stabilized B.1 and B.1.351 RBDs elicited antibodies with qualitatively improved neutralization titers and breadth relative to those immunized solely with either immunogen. Immunized hamsters were protected from high-dose viral challenge. Such vaccine formulations can be rapidly and cheaply produced, lack extraneous tags or additional components, and can be stored at room temperature. They are a useful modality to combat COVID-19, especially in remote and low-resource settings.


Assuntos
Anticorpos Neutralizantes/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Antivirais/imunologia , Cricetinae , Imunogenicidade da Vacina/imunologia , Camundongos , Glicoproteína da Espícula de Coronavírus/genética
14.
BMJ Glob Health ; 6(11)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34725039

RESUMO

INTRODUCTION: South Asians are at high risk of type 2 diabetes (T2D). We assessed whether intensive family-based lifestyle intervention leads to significant weight loss, improved glycaemia and blood pressure in adults at elevated risk for T2D. METHODS: This cluster randomised controlled trial (iHealth-T2D) was conducted at 120 locations across India, Pakistan, Sri Lanka and the UK. We included 3684 South Asian men and women, aged 40-70 years, without T2D but with raised haemoglobin A1c (HbA1c) and/or waist circumference. Participants were randomly allocated either to the family-based lifestyle intervention or control group by location clusters. Participants in the intervention received 9 visits and 13 telephone contacts by community health workers over 1-year period, and the control group received usual care. Reductions in weight (aim >7% reduction), waist circumference (aim ≥5 cm reduction), blood pressure and HbA1C at 12 months of follow-up were assessed. Our linear mixed-effects regression analysis was based on intention-to-treat principle and adjusted for age, sex and baseline values. RESULTS: There were 1846 participants in the control and 1838 in the intervention group. Between baseline and 12 months, mean weight of participants in the intervention group reduced by 1.8 kg compared with 0.4 kg in the control group (adjusted mean difference -1.10 kg (95% CI -1.70 to -1.06), p<0.001). The adjusted mean difference for waist circumference was -1.9 cm (95% CI -2.5; to 1.3), p<0.001). No overall difference was observed for blood pressure or HbA1c. People who attended multiple intervention sessions had a dose-dependent effect on waist circumference, blood pressure and HbA1c, but not on weight. CONCLUSION: An intensive family-based lifestyle intervention adopting low-resource strategies led to effective reduction in weight and waist circumference at 12 months, which has potential long-term benefits for preventing T2D. A higher number of attended sessions increased the effect on waist circumference, blood pressure and HbA1c. TRIAL REGISTRATION NUMBER: EudraCT: 2016-001350-18; ClinicalTrials.gov: NCT02949739.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Povo Asiático , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Seguimentos , Humanos , Estilo de Vida , Masculino , Redução de Peso
15.
ACS Infect Dis ; 7(8): 2546-2564, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34260218

RESUMO

The receptor binding domain (RBD) of SARS-CoV-2 is the primary target of neutralizing antibodies. We designed a trimeric, highly thermotolerant glycan engineered RBD by fusion to a heterologous, poorly immunogenic disulfide linked trimerization domain derived from cartilage matrix protein. The protein expressed at a yield of ∼80-100 mg/L in transiently transfected Expi293 cells, as well as CHO and HEK293 stable cell lines and formed homogeneous disulfide-linked trimers. When lyophilized, these possessed remarkable functional stability to transient thermal stress of up to 100 °C and were stable to long-term storage of over 4 weeks at 37 °C unlike an alternative RBD-trimer with a different trimerization domain. Two intramuscular immunizations with a human-compatible SWE adjuvanted formulation elicited antibodies with pseudoviral neutralizing titers in guinea pigs and mice that were 25-250 fold higher than corresponding values in human convalescent sera. Against the beta (B.1.351) variant of concern (VOC), pseudoviral neutralization titers for RBD trimer were ∼3-fold lower than against wildtype B.1 virus. RBD was also displayed on a designed ferritin-like Msdps2 nanoparticle. This showed decreased yield and immunogenicity relative to trimeric RBD. Replicative virus neutralization assays using mouse sera demonstrated that antibodies induced by the trimers neutralized all four VOC to date, namely B.1.1.7, B.1.351, P.1, and B.1.617.2 without significant differences. Trimeric RBD immunized hamsters were protected from viral challenge. The excellent immunogenicity, thermotolerance, and high yield of these immunogens suggest that they are a promising modality to combat COVID-19, including all SARS-CoV-2 VOC to date.


Assuntos
COVID-19 , Termotolerância , Animais , Anticorpos Antivirais , COVID-19/terapia , Cobaias , Células HEK293 , Humanos , Imunização Passiva , Camundongos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Soroterapia para COVID-19
16.
Toxics ; 9(5)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065370

RESUMO

Changing salinity in estuaries due to sea level rise and altered rainfall patterns, as a result of climate change, has the potential to influence the interactions of aquatic pollutants as well as to alter their toxicity. From a chemical property point of view, ionic concentration can increase the octanol-water partition coefficient and thus decrease the water solubility of a compound. Biologically, organism physiology and enzyme metabolism are also altered at different salinities with implications for drug metabolism and toxic effects. This highlights the need to understand the influence of salinity on pesticide toxicity when assessing risk to estuarine and marine fishes, particularly considering that climate change is predicted to alter salinity regimes globally and many risk assessments and regulatory decisions are made using freshwater studies. Therefore, we exposed the Inland Silverside (Menidia beryllina) at an early life stage to seven commonly used pesticides at two salinities relevant to estuarine waters (5 PSU and 15 PSU). Triadimefon was the only compound to show a statistically significant increase in toxicity at the 15 PSU LC50. However, all compounds showed a decrease in LC50 values at the higher salinity, and all but one showed a decrease in the LC10 value. Many organisms rely on estuaries as nurseries and increased toxicity at higher salinities may mean that organisms in critical life stages of development are at risk of experiencing adverse, toxic effects. The differences in toxicity demonstrated here have important implications for organisms living within estuarine and marine ecosystems in the Anthropocene as climate change alters estuarine salinity regimes globally.

17.
Front Microbiol ; 12: 653399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122366

RESUMO

Co-infection with ancillary pathogens is a significant modulator of morbidity and mortality in infectious diseases. There have been limited reports of co-infections accompanying SARS-CoV-2 infections, albeit lacking India specific study. The present study has made an effort toward elucidating the prevalence, diversity and characterization of co-infecting respiratory pathogens in the nasopharyngeal tract of SARS-CoV-2 positive patients. Two complementary metagenomics based sequencing approaches, Respiratory Virus Oligo Panel (RVOP) and Holo-seq, were utilized for unbiased detection of co-infecting viruses and bacteria. The limited SARS-CoV-2 clade diversity along with differential clinical phenotype seems to be partially explained by the observed spectrum of co-infections. We found a total of 43 bacteria and 29 viruses amongst the patients, with 18 viruses commonly captured by both the approaches. In addition to SARS-CoV-2, Human Mastadenovirus, known to cause respiratory distress, was present in a majority of the samples. We also found significant differences of bacterial reads based on clinical phenotype. Of all the bacterial species identified, ∼60% have been known to be involved in respiratory distress. Among the co-pathogens present in our sample cohort, anaerobic bacteria accounted for a preponderance of bacterial diversity with possible role in respiratory distress. Clostridium botulinum, Bacillus cereus and Halomonas sp. are anaerobes found abundantly across the samples. Our findings highlight the significance of metagenomics based diagnosis and detection of SARS-CoV-2 and other respiratory co-infections in the current pandemic to enable efficient treatment administration and better clinical management. To our knowledge this is the first study from India with a focus on the role of co-infections in SARS-CoV-2 clinical sub-phenotype.

19.
SSM Popul Health ; 13: 100751, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33665333

RESUMO

BACKGROUND: South Asia has become a major epicentre of the COVID-19 pandemic. Understanding South Asians' awareness, attitudes and experiences of early measures for the prevention of COVID-19 is key to improving the effectiveness and mitigating the social and economic impacts of pandemic responses at a critical time for the Region. METHODS: We assessed the knowledge, behaviours, health and socio-economic circumstances of 29,809 adult men and women, at 93 locations across four South Asian countries. Data were collected during the national lockdowns implemented from March to July 2020, and compared with data collected prior to the pandemic as part of an ongoing prospective surveillance initiative. RESULTS: Participants were 61% female, mean age 45.1 years. Almost half had one or more chronic disease, including diabetes (16%), hypertension (23%) or obesity (16%). Knowledge of the primary COVID-19 symptoms and transmission routes was high, but access to hygiene and personal protection resources was low (running water 63%, hand sanitisers 53%, paper tissues 48%). Key preventive measures were not widely adopted. Knowledge, access to, and uptake of COVID-19 prevention measures were low amongst people from disadvantaged socio-economic groups. Fifteen percent of people receiving treatment for chronic diseases reported loss of access to long-term medications; 40% reported symptoms suggestive of anxiety or depression. The prevalence of unemployment rose from 9.3% to 39.4% (P < 0.001), and household income fell by 52% (P < 0.001) during the lockdown. Younger people and those from less affluent socio-economic groups were most severely impacted. Sedentary time increased by 32% and inadequate fruit and vegetable intake increased by 10% (P < 0.001 for both), while tobacco and alcohol consumption dropped by 41% and 80%, respectively (P < 0.001), during the lockdown. CONCLUSIONS: Our results identified important knowledge, access and uptake barriers to the prevention of COVID-19 in South Asia, and demonstrated major adverse impacts of the pandemic on chronic disease treatment, mental health, health-related behaviours, employment and household finances. We found important sociodemographic differences for impact, suggesting a widening of existing inequalities. Our findings underscore the need for immediate large-scale action to close gaps in knowledge and access to essential resources for prevention, along with measures to safeguard economic production and mitigate socio-economic impacts on the young and the poor.

20.
Indian Heart J ; 73(1): 74-76, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33714413

RESUMO

BACKGROUND: HCQ is a commonly recommended drug for the prophylaxis of COVID-19. One of its rare side-effect includes QTc prolongation. METHODS: This was a prospective, cross sectional and observational study conducted on Hydroxychloroquine (HCQ) among Healthcare Workers (HCWs) at Max Super Speciality Hospital, Saket, New Delhi, India. A 3-lead ECG (only limb leads, it does not require chest leads) was performed. The QTc cut offs were pre decided, QTC < 470 ms for males and <480 ms for females was considered within the normal limits and anything above this was regarded as QTc prolongation. RESULTS: There were 274 HCWs enrolled into the study, including 175 males and 99 females. Majority of the HCWs were young and had a mean age of 32.19 ± 9.29 years. Out of these, 218 were taking HCQ as per the Indian Council of Medical Research (ICMR) guidelines. The median cumulative dose being taken was 1600 mg and the median QTc of these participants was 390 ms in males and 391.5 ms in females. Subsequently, 33 participants were followed-up and found to have a median QTc of 389 ms and a cumulative dose of HCQ as 2000 mg. CONCLUSION: In conclusion, ours is a first study in the middle of the pandemic which showed that HCQ prophylaxis in young HCWs without comorbidities did not show any QTc prolongation.


Assuntos
Tratamento Farmacológico da COVID-19 , Pessoal de Saúde , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Pneumonia Viral/tratamento farmacológico , Adulto , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Estudos Prospectivos , SARS-CoV-2
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