In Vitro Antibacterial Activity of Propyl-Propane-Thiosulfinate and Propyl-Propane-Thiosulfonate Derived from Allium spp. against Gram-Negative and Gram-Positive Multidrug-Resistant Bacteria Isolated from Human Samples

Background: The aim of this study was to compare the in vitro antibacterial activity of two compounds derived from Alliaceae, PTS (propyl-propane-thiosulfinate), and PTSO (propyl-propane-thiosulfonate), with that of other antibiotics commonly used against bacteria isolated from humans. Materials and methods: A total of 212 gram-negative bacilli and 267 gram-positive cocci isolated from human clinical samples and resistant to at least one group of antibiotics were selected. In order to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) to various antibiotics as well as PTS and PTSO, all isolates underwent broth microdilution assay. Results: PTS showed moderate activity against Enterobacteriaceae with MIC50 (and MBC50) and MIC90 (and MBC90) values of 256-512 mg/L, while PTSO showed greater activity with MIC50 and MIC90 values of 64-128 mg/L and MBC50 and MBC90 values of 128-512 mg/L. These data show the bactericidal activity of both compounds and indicate that PTSO was more active than PTS against this group of bacteria. Both compounds showed lower activity against P. aeruginosa (MIC50 = 1024 mg/L, MIC90 = 2048 mg/L, MBC50 = 2048 mg/L, and MBC90 = 2048 mg/L, for PTS; MIC50 = 512 mg/L, MIC90 = 1024 mg/L, MBC50 = 512 mg/L, and MBC90 = 2048 mg/L, for PTSO) compared to those obtained in others nonfermenting gram-negative bacilli (MIC50 = 128 mg/L, MIC90 = 512 mg/L, MBC50 = 128 mg/L, and MBC90 = 512 mg/L, for PTS; MIC50 = 64 mg/L, MIC90 = 256 mg/L, MBC50 = 64 mg/L, and MBC90 = 256 mg/L, for PTSO) and also indicate the bactericidal activity of both compounds against these groups of bacteria. Finally, the activity against S. aureus, E. faecalis, and S. agalactiae was higher than that observed against enterobacteria, especially in the case of PTSO (MIC50 = 8 mg/L, MIC90 = 8 mg/L, MBC50 = 32 mg/L, and MBC90 = 64 mg/L, in S. aureus; MIC50 = 4 mg/L, MIC90 = 8 mg/L, MBC50 = 8 mg/L, and MBC90 = 16 mg/L, in E. faecalis and S. agalactiae). Conclusion: PTS and PTSO have a significant broad spectrum antibacterial activity against multiresistant bacteria isolated from human clinical samples. Preliminary results in present work provide basic and useful information for development and potential use of these compounds in the treatment of human infections

Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an

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

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

Caracterización de los mecanismos de resistencia a fosfomicina y nitrofurantoína en aislados clínicos de Klebsiella pneumoniae y Escherichia coli

Fosfomicina y nitrofurantoína son dos de los antibióticos de elección para el tratamiento por vía oral de las infecciones del tracto urinario (ITU) no complicadas debido a que permanecen con tasas de actividad elevada frente a bacterias resistentes a otros antibióticos. Sin embargo, recientes estudios de vigilancia epidemiológica han detectado una reducción de la sensibilidad bacteriana a estos fármacos. El objetivo fundamental del presente trabajo fue determinar los mecanismos de resistencia a estos antibióticos en aislados clínicos de Escherichia coli y Klebsiella pneumoniae productores de ITUs. Para ello, se seleccionaron 29 aislados clínicos de E. coli y 41 de K. pneumoniae resistentes a cualquiera de estos dos antibióticos y se realizaron pruebas fenotípicas para la detección de la actividad glutatión-S-transferasa, así como de la capacidad de crecimiento bacteriano en presencia de una sola fuente de carbono, G3P o G6P, como medida de la actividad transportadora de las proteínas GlpT y UhpT, respectivamente. Posteriormente, se amplificaron y secuenciaron, en todos los aislados, los genes cromosómicos relacionados con resistencia a fosfomicina (murA, glpT, uhpT, uhpA, ptsI y cyaA) y nitrofurantoína (nfsA, nfsB, ribE y ribH) buscando modificaciones que se pudiesen relacionar con la resistencia antibiótica expresada. También se comprobó la presencia de los genes plasmídicos fosAKP, fosA3, fosA4, fosA5, fosA6 y fosC2 relacionados con resistencia a fosfomicina, y oqxA y oqxB relacionados con resistencia a nitrofurantoína. De los 29 aislados de E. coli, 22 fueron resistentes a fosfomicina debido a la deleción de los genes uhpT y/o uhpA, lo que altera la permeabilidad bacteriana al antibiótico como consecuencia de la ausencia de expresión del transportador UhpT. Además, en 2 de estos 22 aislados también se demostró la presencia del gen fosA3, responsable de la presencia de enzimas glutatión-S-transferasas que modifican e inactivan la molécula de fosfomicina. Por su parte, 15 de los 29 aislados clínicos de E. coli fueron resistentes a nitrofurantoína. Algunas modificaciones detectadas en secuencias de las proteínas NfsA (His11Tyr, Ser33Arg, Gln67Leu, Cys80Arg, Gly126Arg, Gly154Glu, Arg203Cys), NfsB (Gln44His, Phe84Ser, Arg107Cys, Gly192Ser, Arg207His) y RibE (Pro55His), así como la producción de proteínas truncadas NfsA (Gln67Stop y Gln147Stop) y NfsB (Glu54Stop), se asociaron a esta resistencia por la incapacidad que tendrían estas enzimas, alteradas estructuralmente, de generar los principios activos derivados del metabolismo de nitrofurantoína. En el caso de K. pneumoniae, de los 41 aislados clínicos estudiados, la resistencia a fosfomicina detectada en 24 de estos, se relacionó, fundamentalmente, con la presencia del gen fosAKP, responsable de la expresión de una enzima con actividad glutatión-S-transferasa que modifica e inactiva la molécula del antibiótico. Aunque 31 de los aislados de esta especie fueron resistentes a nitrofurantoína, tan solo en 12 de ellos se pudieron detectar modificaciones en las secuencias de las proteínas NfsA (Ala112Val y Gly125Trp) y NfsB (Ser37Asn, His47Asp y Pro190Arg) que pudiesen asociarse a resistencia, por lo que, nuestros hallazgos en esta especie bacteriana, no fueron suficientes para explicar todas las situaciones de resistencia encontradas. Finalmente, cabe señalar que la aparición y propagación de estos mecanismos de resistencia, especialmente la transferencia de resistencia a través de plásmidos, en aislados clínicos de estas especies bacterianas, podría comprometer la utilidad futura de fosfomicina y nitrofurantoína en el tratamiento de las ITUs.Tesis Univ. Granada

Caracterización integral de la cuenca hidrográfica del Río Baconao

La provincia Santiago tiene la cuenca hidrográfica del río Baconao, sobre ella se han puesto en práctica distintas actividades antrópicas, unidas a los impactos que producen los fenómenos extremos, generan múltiples problemas al medio ambiente. Esta investigación tiene como objetivo general una caracterización como herramienta fundamental, para la aplicación del sistema de gestión ambiental, profundizando en el comportamiento de las variables meteorológicas, en diferentes alturas, utilizando el método de cálculo de gradientes, zonificando zonas sísmicas del territorio, establecida en la NC 46:1999, áreas de penetración del mar e inundaciones. Se evalúa sus características físico-geográficas y socio administrativas, vinculando los distintos actores que tienen influencia en la alteración, mejoramiento y sostenibilidad del medio ambiente en la cuenca hidrográfica del río Baconao. Obteniéndose que las inundaciones fluviales en la cuenca Baconao son generalmente catalizadas por fuertes precipitaciones, produciéndose en la parte alta de la cuenca, la erosión constituye uno los principales peligros geológicos

A topoclimate model for Quaternary insular speciation

[Aim]: Understanding the drivers of speciation within islands is key to explain the high levels of invertebrate diversification and endemism often observed within islands. Here, we propose an insular topoclimate model for Quaternary diversification (ITQD), and test the general prediction that, within a radially eroded conical island, glacial climate conditions facilitate the divergence of populations within species across valleys. [Location]: Gran Canaria, Canary Islands. [Taxon]: The Laparocerus tessellatus beetle species complex (Coleoptera, Curculionidae). [Methods]: We characterize individual-level genomic relationships using single nucleotide polymorphisms produced by double-digest restriction site associated DNA sequencing (ddRAD-seq). A range of parameter values were explored in order to filter our data. We assess individual relatedness, species boundaries, demographic history and spatial patterns of connectivity. [Results]: The total number of ddRAD-seq loci per sample ranges from 4,576 to 512, with 11.12% and 4.84% of missing data respectively, depending on the filtering parameter combination. We consistently infer four genetically distinct ancestral populations and two presumed cases of admixture, one of which is largely restricted to high altitudes. Bayes factor delimitation support the hypothesis of four species, which is consistent with the four inferred ancestral gene pools. Landscape resistance analyses identified genomic relatedness among individuals in two out of the four inferred species to be best explained by annual precipitation during the last glacial maximum rather than geographic distance. [Main conclusions]: Our data reveal a complex speciation history involving population isolation and admixture, with broad support for the ITQD model here proposed. We suggest that further studies are needed to test the generality of our model, and enrich our understanding of the evolutionary process in island invertebrates. Our results demonstrate the power of ddRAD-seq data to provide a detailed understanding of the temporal and spatial dynamics of insular biodiversity.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) grants CGL2013‐42589‐P and CGL2017‐85718‐P, co‐financed by FEDER. V.G.O. is funded by a MINECO FPI contract and J.P. was funded by the MINECO through the Juan de la Cierva Program—Incorporation (IJCI‐2014‐19691) and Ramón y Cajal Program (RYC‐2016‐20506), and Marie Sklodowska‐Curie COFUND, Researchers' Night and Individual Fellowships Global (MSCA grant agreement no. 747238, “UNISLAND”).Peer Reviewe