Dhvar5 antimicrobial peptide (AMP) chemoselective covalent immobilization results on higher antiadherence effect than simple physical adsorption

Bacterial colonization and subsequent biofilm formation is still one of the major problems associated with medical devices. Antimicrobial peptides (AMP) immobilization onto biomaterials surface is a promising strategy to avoid bacterial colonization. However, a correct peptide orientation and exposure from the surface is essential to maintain AMP antimicrobial activity. This work aims to evaluate the effect of the immobilization on antibacterial activity of Dhvar5 (LLLFLLKKRKKRKY), an AMP with a head-to-tail amphipathicity. Dhvar5 was linked to thin chitosan coatings in i) a controlled orientation and exposure, testing covalent immobilization of its N- or C-terminus and using spacers with different lengths and flexibilities or in ii) a random orientation by physical adsorption. Chitosan coating was chosen due to its antimicrobial properties and readiness to be functionalized. Surface characterization demonstrated the chemoselective immobilization of the peptide with different spacers in a similar concentration (∼2 ng/cm2). Efficacy assays demonstrated that covalent immobilization of Dhvar5 exposing its cationic end, improves the chitosan coating antimicrobial effect by decreasing Methicillin-resistant Staphylococcus aureus (MRSA) colonization. This effect was enhanced when longer spacers were used independently of their flexibility. In opposite, immobilized Dhvar5 exposing its hydrophobic end has no effect on bacterial adhesion to chitosan, and when adsorbed in a random orientation even induces bacterial adhesion to chitosan coating.This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) and by Portuguese funds through FCT (Fundacao para a Ciencia e a Tecnologia) in the framework of the projects: PTDC/CTM/101484/2008; PEst-C/SAU/LA0002/2013; Pest-C/QUI/UI0081/2013. Fabiola Costa acknowledges FCT for the PhD grant SFRH/BD/72471/2010

Carbon Dioxide Utilisation -The Formate Route

UIDB/50006/2020 CEEC-Individual 2017 Program Contract.The relentless rise of atmospheric CO2 is causing large and unpredictable impacts on the Earth climate, due to the CO2 significant greenhouse effect, besides being responsible for the ocean acidification, with consequent huge impacts in our daily lives and in all forms of life. To stop spiral of destruction, we must actively reduce the CO2 emissions and develop new and more efficient “CO2 sinks”. We should be focused on the opportunities provided by exploiting this novel and huge carbon feedstock to produce de novo fuels and added-value compounds. The conversion of CO2 into formate offers key advantages for carbon recycling, and formate dehydrogenase (FDH) enzymes are at the centre of intense research, due to the “green” advantages the bioconversion can offer, namely substrate and product selectivity and specificity, in reactions run at ambient temperature and pressure and neutral pH. In this chapter, we describe the remarkable recent progress towards efficient and selective FDH-catalysed CO2 reduction to formate. We focus on the enzymes, discussing their structure and mechanism of action. Selected promising studies and successful proof of concepts of FDH-dependent CO2 reduction to formate and beyond are discussed, to highlight the power of FDHs and the challenges this CO2 bioconversion still faces.publishersversionpublishe

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future

Global, regional, and national mortality among young people aged 10–24 years, 1950–2019: a systematic analysis for the Global Burden of Disease Study 2019

Summary: Background Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10–24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We report trends in estimated total numbers of deaths and mortality rate per 100 000 population in young people aged 10–24 years by age group (10–14 years, 15–19 years, and 20–24 years) and sex in 204 countries and territories between 1950 and 2019 for all causes, and between 1980 and 2019 by cause of death. We analyse variation in outcomes by region, age group, and sex, and compare annual rate of change in mortality in young people aged 10–24 years with that in children aged 0–9 years from 1990 to 2019. We then analyse the association between mortality in people aged 10–24 years and socioeconomic development using the GBD Socio-demographic Index (SDI), a composite measure based on average national educational attainment in people older than 15 years, total fertility rate in people younger than 25 years, and income per capita. We assess the association between SDI and all-cause mortality in 2019, and analyse the ratio of observed to expected mortality by SDI using the most recent available data release (2017). Findings In 2019 there were 1·49 million deaths (95% uncertainty interval 1·39–1·59) worldwide in people aged 10–24 years, of which 61% occurred in males. 32·7% of all adolescent deaths were due to transport injuries, unintentional injuries, or interpersonal violence and conflict; 32·1% were due to communicable, nutritional, or maternal causes; 27·0% were due to non-communicable diseases; and 8·2% were due to self-harm. Since 1950, deaths in this age group decreased by 30·0% in females and 15·3% in males, and sex-based differences in mortality rate have widened in most regions of the world. Geographical variation has also increased, particularly in people aged 10–14 years. Since 1980, communicable and maternal causes of death have decreased sharply as a proportion of total deaths in most GBD super-regions, but remain some of the most common causes in sub-Saharan Africa and south Asia, where more than half of all adolescent deaths occur. Annual percentage decrease in all-cause mortality rate since 1990 in adolescents aged 15–19 years was 1·3% in males and 1·6% in females, almost half that of males aged 1–4 years (2·4%), and around a third less than in females aged 1–4 years (2·5%). The proportion of global deaths in people aged 0–24 years that occurred in people aged 10–24 years more than doubled between 1950 and 2019, from 9·5% to 21·6%. Interpretation Variation in adolescent mortality between countries and by sex is widening, driven by poor progress in reducing deaths in males and older adolescents. Improving global adolescent mortality will require action to address the specific vulnerabilities of this age group, which are being overlooked. Furthermore, indirect effects of the COVID-19 pandemic are likely to jeopardise efforts to improve health outcomes including mortality in young people aged 10–24 years. There is an urgent need to respond to the changing global burden of adolescent mortality, address inequities where they occur, and improve the availability and quality of primary mortality data in this age group

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings The global TFR decreased from 2.72 (95% uncertainty interval [UI] 2.66-2.79) in 2000 to 2.31 (2.17-2.46) in 2019. Global annual livebirths increased from 134.5 million (131.5-137.8) in 2000 to a peak of 139.6 million (133.0-146.9) in 2016. Global livebirths then declined to 135.3 million (127.2-144.1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2.1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27.1% (95% UI 26.4-27.8) of global livebirths. Global life expectancy at birth increased from 67.2 years (95% UI 66.8-67.6) in 2000 to 73.5 years (72.8-74.3) in 2019. The total number of deaths increased from 50.7 million (49.5-51.9) in 2000 to 56.5 million (53.7-59.2) in 2019. Under-5 deaths declined from 9.6 million (9.1-10.3) in 2000 to 5.0 million (4.3-6.0) in 2019. Global population increased by 25.7%, from 6.2 billion (6.0-6.3) in 2000 to 7.7 billion (7.5-8.0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58.6 years (56.1-60.8) in 2000 to 63.5 years (60.8-66.1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112