A new sensitive molecular marker for Aspergillus’ Calmodulin gene detection in biological samples, used as a supplementary diagnosis for invasive Aspergillosis (IA)/ Um novo marcador molecular sensível para a detecção do gene Calmodulin em amostras biológicas do Aspergillus, utilizado como diagnóstico suplementar para a Aspergilose invasiva (IA)

Introduction: Aspergillosis is caused by the fungi of Aspergillus genus. After inhalation, Aspergillus’ conidia can invade the tracheal bronchus and lungs, resulting in airway colonization, inflammatory granuloma and invasive aspergillosis (IA), which is most likely to occur in neutropenic and immunosuppressed patients. Presently, IA has been associated with COVID-19 in patients admitted to intensive care units (ICU) for longer periods of time. Objective: The objective of this is to design a new molecular marker for detection of Aspergillus spp. in biological samples, in order to develop a new technique for IA diagnosis which is faster, more efficient and safer. Methodology: The primer was designed in silico using conserved sequences of the Calmodulin gene. After confirming the results in silico, in vitro evaluation was performed using the PCR technique. Results: The designed primer showed high specificity for the Aspergillus species. Conclusion: In this study the standardized PCR reaction with the designed marker proved to be safely utilized as a diagnostic method for IA.  The development of a test to aid in the diagnosis of IA is of great importance, since traditional methods are in turn time consuming and generally confused with other diseases. Early diagnosis contributes to faster treatment initiation and increasing the patient's chance of survival. We can conclude that the standardized PCR with the designed primer can be used safely in the development of a diagnostic test for IA, being of low cost, and accessible to patients treated by the public health system. A Patent application for this molecular marker has been submitted, with the number BR1020190281294

Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

Effective control of SARS-CoV-2 infection on primary exposure may reveal correlates of protective immunity to future variants, but we lack insights into immune responses before or at the time virus is first detected. We use blood transcriptomics, multiparameter flow cytometry, and T cell receptor (TCR) sequencing spanning the time of incident non-severe infection in unvaccinated virus-naive individuals to identify rapid type 1 interferon (IFN) responses common to other acute respiratory viruses and cell proliferation responses that discriminate SARS-CoV-2 from other viruses. These peak by the time the virus is first detected and sometimes precede virus detection. Cell proliferation is most evident in CD8 T cells and associated with specific expansion of SARS-CoV-2-reactive TCRs, in contrast to virus-specific antibodies, which lag by 1–2 weeks. Our data support a protective role for early type 1 IFN and CD8 T cell responses, with implications for development of universal T cell vaccines

Estudo espacial da mortalidade por acidentes de motocicleta em Pernambuco

OBJETIVO: Analisar a distribuição espacial da mortalidade por acidentes de motocicleta no estado de Pernambuco. MÉTODOS: Estudo ecológico de base populacional, usando os dados de mortalidade por acidentes de motocicletas ocorridos de 01/01/2000 a 31/12/2005. As unidades de análise foram municípios. Para a análise da distribuição espacial dos óbitos foram construídos coeficientes médios de mortalidade, tendo como numerador os óbitos por acidentes de motocicletas registrados no Sistema de Informações sobre Mortalidade e, como denominador, a população do centro do período. Utilizaram-se técnicas de análise espacial, suavização do coeficiente pelo método bayesiano empírico local e o diagrama de espalhamento de Moran, aplicados sobre a base cartográfica digital do estado. RESULTADOS: O coeficiente médio de mortalidade por acidentes de motocicletas em Pernambuco foi de 3,47/100 mil habitantes. Dos 185 municípios, 16 faziam parte de cinco conglomerados identificados com coeficientes de mortalidade que variaram de 5,66 a 11,66/100 mil habitantes, considerados áreas críticas. Três dessas áreas localizam-se na região de desenvolvimento sertão e duas no agreste. CONCLUSÕES: O risco de morrer por acidente de motocicleta é maior nas áreas de conglomerado em regiões fora do eixo metropolitano, sugerindo medidas de intervenção que considerem o contexto de desenvolvimento econômico, social e cultural

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Worldwide trends in underweight and obesity from 1990 to 2022 : a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

A list of authors and their affiliations appears online. A supplementary appendix is herewith attached.Background: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity.peer-reviewe

Evaluation of the length of adaptation period for changeover and crossover nutritional experiments with cattle fed tropical forage-based diets

It was evaluated the impact of the diet switch on nutritional characteristics and bacterial community composition in cattle fed tropical forage-based diet aiming to establish the minimal length of the adaptation period that could be applied to changeover or crossover design protocols. Twelve rumen-cannulated crossbreed (B. taurus × B. indicus) bovines were used in this experiment (four young bulls, four steers, and four heifers). The experiment lasted 60 days and two diet switches were done at d 21 and d 41. Four diet sequences were evaluated (one animal of each category per sequence): sugarcane-corn silage-sugarcane, corn silage-sugarcane-corn silage, high-low-high concentrate diets, and low-high-low concentrate diets. All diets were adjusted to 110 g crude protein/kg dry matter by using urea. Four groups of variables were evaluated along experimental days: voluntary intake characteristics, fecal excretion and composition, ruminal digesta compostion, and ruminal fermentation profile. The pattern of the groups along time was interpreted through a non-hierarchical clustering procedure and the stabilization of each group of characteristics was achieved within 9–13, 9–14, 6–13, and 4–11 days after diet switch, respectively. The diversity of the liquid-associated rumen bacterial community was also evaluated by using PCR-DGGE in the young bulls from 6 days before to 20 days after the second diet switch. The pattern of microbial diversity was evaluated through a clustering procedure using the unweight pair group method with arithmetic mean. The bacterial community in the liquid phase stabilized within 3–9 days after diet switch. From the results of this experiment, among all obtained times to adapt intake, fecal and digesta composition, and ruminal fermentation and microbial diversity, a 14-days adaptation period is recommended for changeover and crossover experiments with cattle fed tropical forage-based diets

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified