Genetic transformation of novel isolates of chicken Lactobacillus bearing probiotic features for expression of heterologous proteins: a tool to develop live oral vaccines

BACKGROUND: The use of lactic acid bacteria as vehicles to delivery antigens to immunize animals is a promising issue. When genetically modified, these bacteria can induce a specific local and systemic immune response against selected pathogens. Gastric acid and bile salts tolerance, production of antagonistic substances against pathogenic microorganisms, and adhesive ability to gut epithelium are other important characteristics that make these bacteria useful for oral immunization. RESULTS: Bacteria isolated on de Man, Rogosa and Sharpe medium (MRS) from different gastrointestinal portions of broiler chicks were evaluated for their resistance to artificial gastric acid and bile salts, production of hydrogen peroxide, and cell surface hydrophobicity. Thirty-eight isolates were first typed at species level by PCR amplification of 16S-23S rRNA intergenic spacers using universal primers that anneal within 16S and 23S genes, followed by restriction digestion analyses of PCR amplicons (PCR-ARDRA). An expression cassette was assembled onto the pCR2.1-Topo vector by cloning the promoter, leader peptide, cell wall anchor and terminator sequences derived from the laminin binding S-layer protein gene of L. crispatus strain F5.7 (lbs gene). A sequence encoding the green fluorescent protein (GFP) was inserted as reporter gene, and an erythromycin resistance gene was added as selective marker. All constructs were able to express GFP in the cloning host E. coli XL1-Blue and different Lactobacillus strains as verified by FACS and laser scanning confocal microscopy. CONCLUSION: Lactobacillus isolated from gastrointestinal tract of broiler chickens and selected for probiotic characteristics can be genetically modified by introducing an expression cassette into the lbs locus. The transformed bacteria expressed on its cell wall surface different fluorescent proteins used as reporters of promoter function. It is possible then that similar bacterial model expressing pathogen antigens can be used as live oral vaccines to immunize broilers against infectious diseases

Risco de câncer de pulmão, laringe e esôfago atribuível ao fumo

OBJECTIVE:Lung, laryngeal and esophageal cancers have smoking as one of their main risk factors. The objective of this study was to evaluate the population attributed risk (PAR) of smoking for these forms of cancer. METHODS: The study was based in three case-control studies conducted in medium size cities in Brazil. Incident cases of lung cancer, laryngeal cancer and esophageal cancer seen at a hospital setting and diagnosed through biopsy were analyzed; controls were hospitalized patients with another diagnoses. Smoking was the exposure factor measured at three levels: non-smokers, former smokers and smokers, which were defined using a questionnaire applied by trained interviewers. For effect measure, odds ratio was used and the populational attributed risk for smoking was then calculated for a 95% CI. RESULTS: A total of 122 lung cancer cases and 244 controls, 50 cases of laryngeal cancer and 48 cases of esophageal cancer, and 96 controls for both of them were studied. The prevalence of smoking exposure was 34%, which is the overall prevalence of smoking in this city's adult population. Odds ratios (OR) for the PAR analysis were the adjusted OR for confounding variables from each study. Lung cancer PAR was 63% (95% IC, 0.58-0.68) for former smokers and 71% (95%IC, 0.65-0.77) for smokers. Larynx cancer PAR was 74% (95% IC, 0.70-0.78) and 86% (95%IC, 0.81-0.85) for former smokers and smokers, respectively. Esophageal cancer PAR was 54% (95%IC, 0.46-0.62) for smokers. CONCLUSION: Smoking is an avoidable risk factor and smoking cessation could be responsible for significant reductions in the incidence of these three forms of cancer.OBJETIVO: Os tipos de câncer de pulmão, laringe e esôfago têm como um de seus principais fatores de risco o fumo. O objetivo do estudo foi avaliar o risco populacional atribuível ao fumo nesses tipos de câncer. MÉTODOS: A pesquisa baseou-se em três estudos de caso-controle em cidade de médio porte do Brasil. Analisaram-se casos incidentes hospitalares de câncer de pulmão, de laringe e de esôfago diagnosticados por biópsias; os controles foram pacientes hospitalizados por outros motivos, sem ser câncer ou doenças altamente relacionadas ao fumo. O fator de exposição foi o tabagismo medido em três níveis: não-fumantes, ex-fumantes e fumantes atuais, definidos por meio de questionários aplicados por entrevistadores treinados. Para a medida de efeito, foi utilizado o odds ratio obtendo-se, dessa forma, o "risco populacional atribuível" ao fumo com IC de 95%. RESULTADOS: Foram estudados 122 casos e 244 controles de câncer de pulmão, 50 casos de câncer de laringe e 48 casos de câncer de esôfago, com um grupo de 96 controles comum a ambos. A prevalência da exposição ao fumo utilizada para a análise foi de 34%, que corresponde à prevalência de fumo na população adulta da cidade. Os odds ratios para o cálculo do risco populacional atribuível foram obtidos por análises ajustadas para os fatores de confusão de cada um dos estudos. Para ex-fumantes com câncer de pulmão, o risco populacional atribuível foi de 63% (IC95%, 0,58-0,68) e, para fumantes, de 71% (IC95%, 0,65-0,77). Para câncer de laringe, o RPA foi de 74% (IC95%, 0,70-0,78) para ex-fumantes e de 86% (IC95%, 0,81-0,85) para fumantes. O câncer de esôfago mostrou um risco de 54% (IC95%, 0,46-0,62) para fumantes. CONCLUSÃO: Conclui-se que o fumo é um importante fator de risco e que a cessação do mesmo contribuiria para reduções significativas na incidência de câncer nesses três sítios

ExoClock Project. III. 450 New Exoplanet Ephemerides from Ground and Space Observations

The ExoClock project has been created to increase the efficiency of the Ariel mission. It will achieve this by continuously monitoring and updating the ephemerides of Ariel candidates, in order to produce a consistent catalog of reliable and precise ephemerides. This work presents a homogenous catalog of updated ephemerides for 450 planets, generated by the integration of ∼18,000 data points from multiple sources. These sources include observations from ground-based telescopes (the ExoClock network and the Exoplanet Transit Database), midtime values from the literature, and light curves from space telescopes (Kepler, K2, and TESS). With all the above, we manage to collect observations for half of the postdiscovery years (median), with data that have a median uncertainty less than 1 minute. In comparison with the literature, the ephemerides generated by the project are more precise and less biased. More than 40% of the initial literature ephemerides had to be updated to reach the goals of the project, as they were either of low precision or drifting. Moreover, the integrated approach of the project enables both the monitoring of the majority of the Ariel candidates (95%), and also the identification of missing data. These results highlight the need for continuous monitoring to increase the observing coverage of the candidate planets. Finally, the extended observing coverage of planets allows us to detect trends (transit-timing variations) for a sample of 19 planets. All the products, data, and codes used in this work are open and accessible to the wider scientific community

ExoClock Project III: 450 new exoplanet ephemerides from ground and space observations

The ExoClock project has been created with the aim of increasing the efficiency of the Ariel mission. It will achieve this by continuously monitoring and updating the ephemerides of Ariel candidates over an extended period, in order to produce a consistent catalogue of reliable and precise ephemerides. This work presents a homogenous catalogue of updated ephemerides for 450 planets, generated by the integration of $\sim$18000 data points from multiple sources. These sources include observations from ground-based telescopes (ExoClock network and ETD), mid-time values from the literature and light-curves from space telescopes (Kepler/K2 and TESS). With all the above, we manage to collect observations for half of the post-discovery years (median), with data that have a median uncertainty less than one minute. In comparison with literature, the ephemerides generated by the project are more precise and less biased. More than 40\% of the initial literature ephemerides had to be updated to reach the goals of the project, as they were either of low precision or drifting. Moreover, the integrated approach of the project enables both the monitoring of the majority of the Ariel candidates (95\%), and also the identification of missing data. The dedicated ExoClock network effectively supports this task by contributing additional observations when a gap in the data is identified. These results highlight the need for continuous monitoring to increase the observing coverage of the candidate planets. Finally, the extended observing coverage of planets allows us to detect trends (TTVs - Transit Timing Variations) for a sample of 19 planets. All products, data, and codes used in this work are open and accessible to the wider scientific community.Comment: Recommended for publication to ApJS (reviewer's comments implemented). Main body: 13 pages, total: 77 pages, 7 figures, 7 tables. Data available at http://doi.org/10.17605/OSF.IO/P298

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

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