Early mucosal events promote distinct mucosal and systemic antibody responses to live attenuated influenza vaccine

Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8+ and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data

Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction

We present two real-time reverse-transcription polymerase chain reaction assays for a novel human coronavirus (CoV), targeting regions upstream of the E gene (upE) or within open reading frame (ORF)1b, respectively. Sensitivity for upE is 3.4 copies per reaction (95% confidence interval (CI): 2.5-6.9 copies) or 291 copies/mL of sample. No cross-reactivity was observed with coronaviruses OC43, NL63, 229E, SARS-CoV, nor with 92 clinical specimens containing common human respiratory viruses. We recommend using upE for screening and ORF1b for confirmation

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

BackgroundThe ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur.AimWe aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available.MethodsHere we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology.ResultsThe workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive - Global (EVAg), a European Union infrastructure project.ConclusionThe present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks

A INCIDÊNCIA DA HEMORRAGIA DIGESTIVA ALTA EM PACIENTES PEDIÁTRICOS APÓS USO DE ANTI-INFLAMATÓRIOS NÃO ESTEROIDAIS

INTRODUCTION: Upper Gastrointestinal Bleeding (OGH) in children is a clinical condition in which its causes are rarely reported in the literature, but studies demonstrate a correlation between prolonged or continuous use of non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of cases in pediatrics. OBJECTIVES: The present study seeks to analyze, through a bibliographic review, more in-depth studies and analyzes on the prolonged use of NSAIDs and the incidence of HGA in underage patients. METHODOLOGY: Bibliographic review carried out from June to July 2023. Literature searches were carried out in the PubMed and Scientific Electronic Library Online (SciELO) databases. 238 articles were found and after applying inclusion and exclusion criteria, 18 articles were selected to form the collection. RESULTS: The different studies analyzed demonstrate that although NSAIDs are predictors of damage to the gastric mucosa, they tend to play an indirect role in causing Upper Gastrointestinal hemorrhage. In this sense, in the majority of cases studied, patients have another risk factor for this complication - given a pre-existing intestinal injury, correlated with self-medication, especially medication administration without the correct dosage by parents/guardians. CONCLUSION: The mechanism of injury caused by NSAIDs is already known, however, there are still disagreements on the subject in question. It is essential that parents or guardians pay attention to the ideal dosage prescribed by doctors, respecting the medication administration interval, thus avoiding its irregular use and, therefore, its more vigorous consequences on the NSAID and HGA correlation in children, since which are highly complex cases and may require urgent care and hospitalization.INTRODUÇÃO: Hemorragia Gastrointestinal Alta (HGA) em crianças é uma condição clínica na qual suas causas são pouco relatadas na literatura, porém estudos demonstram correlação entre uso prolongado ou contínuo de anti-inflamatórios não esteroidais (AINES) com a incidência de casos na pediatria. OBJETIVOS: O presente estudo busca analisar por meio de uma revisão bibliográfica estudos e análises mais aprofundados sobre o uso prolongado de AINES e a incidência de HGA em pacientes menores de idade. METODOLOGIA: Revisão Bibliográfica realizada no período de junho a julho de 2023. As buscas da literatura foram feitas nas bases de dados PubMed e Scientific Electronic Library Online (SciELO). Foram encontrados 238 artigos e após aplicação de critérios de inclusão e exclusão, 18 artigos foram selecionados para a composição da coletânea. RESULTADOS: Os diferentes estudos analisados demonstram que apesar dos AINES serem preditores de lesão na mucosa gástrica, tendem a exercer papel indireto na causa de hemorragia Gastrointestinal Alta. Nesse sentido, a maioria dos casos estudados os pacientes possuem outro fator de risco para referida complicação- haja vista uma lesão intestinal pré-existente, correlacionado a automedicação, sobretudo, a administração medicamentosa sem a posologia correta por pais/responsáveis. CONCLUSÃO: O mecanismo de lesão pelo de AINES já é conhecido, porém, ainda existem divergências sobre o assunto em questão. É imprescindível que os pais ou responsáveis atentem-se à posologia ideal prescrita por médicos, respeitando o intervalo de administração do medicamento, evitando assim o seu uso irregular e, portanto, suas consequências mais vigorosas sobre a correlação AINES e HGA em crianças, uma vez que são casos de alta complexidade podendo precisar de atendimento e internação de urgência

ANÁLISE COMPARATIVA DO EIXO INTESTINO-CÉREBRO: RELAÇÃO ENTRE DISBIOSE E DEPRESSÃO.

OBJECTIVE: The present study seeks to analyze the intestine-brain axis through scientific literature, focusing on the transition of nutritional patterns, seeking a relationship between dysbiosis and depression. METHODOLOGY: Bibliographic review carried out from June to July 2023. Literature searches were carried out in the PubMed and Scientific Electronic Library Online (SciELO) databases. 209 articles were found and, after the inclusion criteria, 21 studies were selected to be included. RESULTS: The different studies analyzed indicate that the microbiota can be affected by several factors, such as probiotics, diet, antibiotics and dietary factors. As a result, changes in the microbiota, known as dysbiosis, can lead to dysregulation of the gut-brain axis and cause changes in mood, as well as depression. Therefore, it is necessary to carry out studies to better understand the gut-brain axis, with an emphasis on the relationship between dysbiosis and depression, in order to provide a better quality of life for such patients. CONCLUSION: It is necessary to balance care in the face of daily hyperactivity, associated with a reduction in negligence regarding diet, sleep quality and regular exercise, in order to control bacterial proliferation. In this sense, there is evidence that the microbiota directly interferes with the CNS, both in the prevention of diseases such as colorectal cancer, but being a causal factor in chronic inflammatory diseases, ulcerative colitis and Crohn's disease. Thus, the microbiome is a system that is evolving and maturing through the different stratifications of life.OBJETIVO: O presente estudo busca analisar por meio da literatura científica o eixo intestino-cérebro, com foco na transição dos padrões nutricionais, buscando relação da disbiose e depressão. METODOLOGIA: Revisão Bibliográfica realizada no período de junho a julho de 2023. As buscas da literatura foram feitas nas bases de dados PubMed e Scientific Electronic Library Online (SciELO). Foram encontrados 209 artigos e selecionados, após os critérios de inclusão, 21  estudos para compor. RESULTADOS: Os diferentes estudos analisados apontam que a microbiota pode ser afetada por diversos fatores, tais como, probióticos, dieta, antibióticos e fatores alimentares. Com isso, a alteração da microbiota, a disbiose, pode levar à desregulação do eixo intestino-cérebro e causar mudanças no humor, além de quadros depressivos. Assim, é necessário que se tenha estudos para melhor compreender o eixo intestino-cérebro, com ênfase na relação da disbiose com a depressão, a fim de proporcionar uma melhor qualidade de vida a tais pacientes. CONCLUSÃO: Faz-se necessário, equilibrar o cuidado perante a hiperatividade diária, associando-se a diminuição das negligências com relação a dieta, qualidade do sono e prática de exercícios regulares, a fim de controlar a proliferação bacteriana. Nesse sentido, há evidencias que a microbióta interfere diretamente o SNC, tanto na prevenção de doenças como o Cancer colorretal, mas sendo fator causal nas Doenças Inflamatórias crônicas, Colite Ulcerativa e Doença de Crohn. Dessa forma, o microbioma é um sistema que está em evolução e amadurecimento por meio das diferentes estratificações da vida

Influenza and Respiratory Virus Surveillance, Vaccine Uptake, and Effectiveness at a Time of Cocirculating COVID-19: Protocol for the English Primary Care Sentinel System for 2020-2021

BackgroundThe Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) are commencing their 54th season of collaboration at a time when SARS-CoV-2 infections are likely to be cocirculating with the usual winter infections.ObjectiveThe aim of this study is to conduct surveillance of influenza and other monitored respiratory conditions and to report on vaccine uptake and effectiveness using nationally representative surveillance data extracted from primary care computerized medical records systems. We also aim to have general practices collect virology and serology specimens and to participate in trials and other interventional research.MethodsThe RCGP RSC network comprises over 1700 general practices in England and Wales. We will extract pseudonymized data twice weekly and are migrating to a system of daily extracts. First, we will collect pseudonymized, routine, coded clinical data for the surveillance of monitored and unexpected conditions; data on vaccine exposure and adverse events of interest; and data on approved research study outcomes. Second, we will provide dashboards to give general practices feedback about levels of care and data quality, as compared to other network practices. We will focus on collecting data on influenza-like illness, upper and lower respiratory tract infections, and suspected COVID-19. Third, approximately 300 practices will participate in the 2020-2021 virology and serology surveillance; this will include responsive surveillance and long-term follow-up of previous SARS-CoV-2 infections. Fourth, member practices will be able to recruit volunteer patients to trials, including early interventions to improve COVID-19 outcomes and point-of-care testing. Lastly, the legal basis for our surveillance with PHE is Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002; other studies require appropriate ethical approval.ResultsThe RCGP RSC network has tripled in size; there were previously 100 virology practices and 500 practices overall in the network and we now have 322 and 1724, respectively. The Oxford-RCGP Clinical Informatics Digital Hub (ORCHID) secure networks enable the daily analysis of the extended network; currently, 1076 practices are uploaded. We are implementing a central swab distribution system for patients self-swabbing at home in addition to in-practice sampling. We have converted all our primary care coding to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) coding. Throughout spring and summer 2020, the network has continued to collect specimens in preparation for the winter or for any second wave of COVID-19 cases. We have collected 5404 swabs and detected 623 cases of COVID-19 through extended virological sampling, and 19,341 samples have been collected for serology. This shows our preparedness for the winter season.ConclusionsThe COVID-19 pandemic has been associated with a groundswell of general practices joining our network. It has also created a permissive environment in which we have developed the capacity and capability of the national primary care surveillance systems and our unique public health institute, the RCGP and University of Oxford collaboration

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks