62 research outputs found
Vascular anomaly in bilateral ectopic kidney: a case report
Ectopic kidney occurs as a result of a halt in migration of kidneys to their normal locations during embryonal period. While kidneys ascend through pelvis, they receive new branches from vessels (iliac and aorta) close to them. When they reach the highest point, they receive new branches from aorta and the former branches degenerate. Renal vessels do not degenerate in the ectopic caudal kidney, more than one accessory and polar arteries may arise. In various studies, a possibility of association between presence of multiple renal arteries and hypertension, has been reported. We aimed to present a case with bilateral ectopic kidney and vascular anomaly associated with hypertension and renal dysfunction
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.
BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca
Interleukin 4: Its Role in Hypertension, Atherosclerosis, Valvular, and Nonvalvular Cardiovascular Diseases
Hypertension is one of the major physiological risk factors for cardiovascular diseases, and it affects more than 1 billion adults worldwide, killing 9 million people every year according to World Health Organization. Also, hypertension is associated with increased risk of kidney disease and stroke. Studying the risk factors that contribute to the pathogenesis of hypertension is key to preventing and controlling hypertension. Numerous laboratories around to globe are very active pursuing research studies to delineate the factors, such as the role of immune system, which could contribute to hypertension. There are studies that were conducted on immune-deficient mice for which experimentally induced hypertension has been ameliorated. Thus, there are possibilities that immune reactivity could be associated with the development of certain type of hypertension. Furthermore, interleukin 4 has been associated with the development of pulmonary hypertension, which could lead to right ventricular remodeling. Also, the immune system is involved in valvular and nonvalvular cardiac remodeling. It has been demonstrated that there is a causative relationship between different interleukins and cardiac fibrosis
Characterization of Juquitiba Virus in Oligoryzomys fornesi from Brazilian Cerrado
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Previous issue date: 2014Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hantaviroses e Rickettsioses. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hantaviroses e Rickettsioses. Rio de Janeiro, RJ, Brasil .Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hantaviroses e Rickettsioses. Rio de Janeiro, RJ, Brasil .Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hantaviroses e Rickettsioses. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia e Parasitologia de Mamíferos Silvestres de Reservatórios. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia e Parasitologia de Mamíferos Silvestres de Reservatórios. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia e Parasitologia de Mamíferos Silvestres de Reservatórios. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia e Parasitologia de Mamíferos Silvestres de Reservatórios. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Câncer. Programa de Genética. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Genética. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia e Parasitologia de Mamíferos Silvestres de Reservatórios. Rio de Janeiro, RJ, Brasil.The Juquitiba virus, an agent of Hantavirus Cardiopulmonary Syndrome,
is one of the most widely distributed hantavirus found in South America. It has been
detected in Oligoryzomys nigripes, Akodon montensis, Oxymycterus judex, Akodon
paranaensis in Brazil and in O. nigripes, Oryzomys sp. and Oligoryzomys fornesi rodents
in Argentine, Paraguay and Uruguay. Here, we report the genomic characterization of the
complete S segment from the Juquitiba strain, isolated from the lung tissues of O. fornesi,
the presumed rodent reservoir of Anajatuba virus in Brazilian Amazon, captured in the
Cerrado Biome, Brazil
Strategies in the development of vaccines to prevent infections with group A streptococcus
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