Universidad de la República de Uruguay

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10 years and off antiseizure medicines for at least the last 5 years. "Resolved" is not necessarily identical to the conventional view of "remission or "cure." Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (2) for each of the groups A to D, escalation strategies for pharmacologic treatments are proposed; (3) the concept of deescalation of therapy is introduced in the treatment assessment scheme; (4) nonpharmacologic therapies are comprehensively presented; and (5) the importance of comorbid conditions in managing chronic obstructive pulmonary disease is reviewed.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

BACKGROUND: The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. METHODS: We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). FINDINGS: Worldwide, the age-standardised prevalence of daily smoking was 25·0% (95% uncertainty interval [UI] 24·2-25·7) for men and 5·4% (5·1-5·7) for women, representing 28·4% (25·8-31·1) and 34·4% (29·4-38·6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11·5% of global deaths (6·4 million [95% UI 5·7-7·0 million]) were attributable to smoking worldwide, of which 52·2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. INTERPRETATION: The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years. FUNDING: Bill & Melinda Gates Foundation and Bloomberg Philanthropies.

The application of anaerobic digestion technology is growing worldwide because of its economic and environmental benefits. As a consequence, a number of studies and research activities dealing with the determination of the biogas potential of solid organic substrates have been carrying out in the recent years. Therefore, it is of particular importance to define a protocol for the determination of the ultimate methane potential for a given solid substrates. In fact, this parameter determines, to a certain extent, both design and economic details of a biogas plant. Furthermore, the definition of common units to be used in anaerobic assays is increasingly requested from the scientific and engineering community. This paper presents some guidelines for biomethane potential assays prepared by the Task Group for the Anaerobic Biodegradation, Activity and Inhibition Assays of the Anaerobic Digestion Specialist Group of the International Water Association. This is the first step for the definition of a standard protocol.

Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.

We propose a linear-time line segment detector that gives accurate results, a controlled number of false detections, and requires no parameter tuning. This algorithm is tested and compared to state-of-the-art algorithms on a wide set of natural images.

Humans express a wide array of ideal mate preferences. Around the world, people desire romantic partners who are intelligent, healthy, kind, physically attractive, wealthy, and more. In order for these ideal preferences to guide the choice of actual romantic partners, human mating psychology must possess a means to integrate information across these many preference dimensions into summaries of the overall mate value of their potential mates. Here we explore the computational design of this mate preference integration process using a large sample of n = 14,487 people from 45 countries around the world. We combine this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets. Across cultures, people higher in mate value appear to experience greater power of choice on the mating market in that they set higher ideal standards, better fulfill their preferences in choice, and pair with higher mate value partners. Furthermore, we find that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.

The occurrence of protein tyrosine nitration under disease conditions is now firmly established and represents a shift from the signal transducing physiological actions of • NO to oxidative and potentially pathogenic pathways. Tyrosine nitration is mediated by reactive nitrogen species such as peroxynitrite anion (ONOO – ) and nitrogen dioxide ( • NO 2 ), formed as secondary products of • NO metabolism in the presence of oxidants including superoxide radicals ( \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{O}}_{2}^{{\bullet}-}\end{equation*}\end{document} ), hydrogen peroxide (H 2 O 2 ), and transition metal centers. The precise interplay between • NO and oxidants and the identification of the proximal intermediate(s) responsible for nitration in vivo have been under controversy. Despite the capacity of peroxynitrite to mediate tyrosine nitration in vitro , its role on nitration in vivo has been questioned, and alternative pathways, including the nitrite/H 2 O 2 /hemeperoxidase and transition metal-dependent mechanisms, have been proposed. A balanced analysis of existing evidence indicates that ( i ) different nitration pathways can contribute to tyrosine nitration in vivo , and ( ii ) most, if not all, nitration pathways involve free radical biochemistry with carbonate radicals ( \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{CO}}_{3}^{{\bullet}-}\end{equation*}\end{document} ) and/or oxo–metal complexes oxidizing tyrosine to tyrosyl radical followed by the diffusion-controlled reaction with • NO 2 to yield 3-nitrotyrosine. Although protein tyrosine nitration is a low-yield process in vivo , 3-nitrotyrosine has been revealed as a relevant biomarker of • NO-dependent oxidative stress; additionally, site-specific nitration focused on particular protein tyrosines may result in modification of function and promote a biological effect. Tissue distribution and quantitation of protein 3-nitrotyrosine, recognition of the predominant nitration pathways and individual identification of nitrated proteins in disease states open new avenues for the understanding and treatment of human pathologies.

Anthropogenic trade and development have broken down dispersal barriers, facilitating the spread of diseases that threaten Earth's biodiversity. We present a global, quantitative assessment of the amphibian chytridiomycosis panzootic, one of the most impactful examples of disease spread, and demonstrate its role in the decline of at least 501 amphibian species over the past half-century, including 90 presumed extinctions. The effects of chytridiomycosis have been greatest in large-bodied, range-restricted anurans in wet climates in the Americas and Australia. Declines peaked in the 1980s, and only 12% of declined species show signs of recovery, whereas 39% are experiencing ongoing decline. There is risk of further chytridiomycosis outbreaks in new areas. The chytridiomycosis panzootic represents the greatest recorded loss of biodiversity attributable to a disease.

In this study, we present the collation and analysis of the gridded land‐based dataset of indices of temperature and precipitation extremes: HadEX2. Indices were calculated based on station data using a consistent approach recommended by the World Meteorological Organization (WMO) Expert Team on Climate Change Detection and Indices, resulting in the production of 17 temperature and 12 precipitation indices derived from daily maximum and minimum temperature and precipitation observations. High‐quality in situ observations from over 7000 temperature and 11,000 precipitation meteorological stations across the globe were obtained to calculate the indices over the period of record available for each station. Monthly and annual indices were then interpolated onto a 3.75° × 2.5° longitude‐latitude grid over the period 1901–2010. Linear trends in the gridded fields were computed and tested for statistical significance. Overall there was very good agreement with the previous HadEX dataset during the overlapping data period. Results showed widespread significant changes in temperature extremes consistent with warming, especially for those indices derived from daily minimum temperature over the whole 110 years of record but with stronger trends in more recent decades. Seasonal results showed significant warming in all seasons but more so in the colder months. Precipitation indices also showed widespread and significant trends, but the changes were much more spatially heterogeneous compared with temperature changes. However, results indicated more areas with significant increasing trends in extreme precipitation amounts, intensity, and frequency than areas with decreasing trends.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991–2018. Across all study countries, we find that 37.0% (range 20.5–76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change. Current and future climate change is expected to impact human health, both indirectly and directly, through increasing temperatures. Climate change has already had an impact and is responsible for 37% of warm-season heat-related deaths between 1991 and 2018, with increases in mortality observed globally.

BACKGROUND: Kangaroo mother care (KMC), originally defined as skin-to-skin contact between a mother and her newborn, frequent and exclusive or nearly exclusive breastfeeding, and early discharge from hospital, has been proposed as an alternative to conventional neonatal care for low birthweight (LBW) infants. OBJECTIVES: To determine whether evidence is available to support the use of KMC in LBW infants as an alternative to conventional neonatal care before or after the initial period of stabilization with conventional care, and to assess beneficial and adverse effects. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches in CENTRAL (Cochrane Central Register of Controlled Trials; 2016, Issue 6), MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), LILACS (Latin American and Caribbean Health Science Information database), and POPLINE (Population Information Online) databases (all from inception to June 30, 2016), as well as the WHO (World Health Organization) Trial Registration Data Set (up to June 30, 2016). In addition, we searched the web page of the Kangaroo Foundation, conference and symposia proceedings on KMC, and Google Scholar. SELECTION CRITERIA: Randomized controlled trials comparing KMC versus conventional neonatal care, or early-onset KMC versus late-onset KMC, in LBW infants. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the methods of the Cochrane Neonatal Review Group. MAIN RESULTS: Twenty-one studies, including 3042 infants, fulfilled inclusion criteria. Nineteen studies evaluated KMC in LBW infants after stabilization, one evaluated KMC in LBW infants before stabilization, and one compared early-onset KMC with late-onset KMC in relatively stable LBW infants. Sixteen studies evaluated intermittent KMC, and five evaluated continuous KMC. KMC versus conventional neonatal care: At discharge or 40 to 41 weeks' postmenstrual age, KMC was associated with a statistically significant reduction in the risk of mortality (risk ratio [RR] 0.60, 95% confidence interval [CI] 0.39 to 0.92; eight trials, 1736 infants), nosocomial infection/sepsis (RR 0.35, 95% CI 0.22 to 0.54; five trials, 1239 infants), and hypothermia (RR 0.28, 95% CI 0.16 to 0.49; nine trials, 989 infants; moderate-quality evidence). At latest follow-up, KMC was associated with a significantly decreased risk of mortality (RR 0.67, 95% CI 0.48 to 0.95; 12 trials, 2293 infants; moderate-quality evidence) and severe infection/sepsis (RR 0.50, 95% CI 0.36 to 0.69; eight trials, 1463 infants; moderate-quality evidence). Moreover, KMC was found to increase weight gain (mean difference [MD] 4.1 g/d, 95% CI 2.3 to 5.9; 11 trials, 1198 infants; moderate-quality evidence), length gain (MD 0.21 cm/week, 95% CI 0.03 to 0.38; three trials, 377 infants) and head circumference gain (MD 0.14 cm/week, 95% CI 0.06 to 0.22; four trials, 495 infants) at latest follow-up, exclusive breastfeeding at discharge or 40 to 41 weeks' postmenstrual age (RR 1.16, 95% CI 1.07 to 1.25; six studies, 1453 mothers) and at one to three months' follow-up (RR 1.20, 95% CI 1.01 to 1.43; five studies, 600 mothers), any (exclusive or partial) breastfeeding at discharge or at 40 to 41 weeks' postmenstrual age (RR 1.20, 95% CI 1.07 to 1.34; 10 studies, 1696 mothers; moderate-quality evidence) and at one to three months' follow-up (RR 1.17, 95% CI 1.05 to 1.31; nine studies, 1394 mothers; low-quality evidence), and some measures of mother-infant attachment and home environment. No statistically significant differences were found between KMC infants and controls in Griffith quotients for psychomotor development at 12 months' corrected age (low-quality evidence). Sensitivity analysis suggested that inclusion of studies with high risk of bias did not affect the general direction of findings nor the size of the treatment effect for main outcomes. Early-onset KMC versus late-onset KMC in relatively stable infants: One trial compared early-onset continuous KMC (within 24 hours post birth) versus late-onset continuous KMC (after 24 hours post birth) in 73 relatively stable LBW infants. Investigators reported no significant differences between the two study groups in mortality, morbidity, severe infection, hypothermia, breastfeeding, and nutritional indicators. Early-onset KMC was associated with a statistically significant reduction in length of hospital stay (MD 0.9 days, 95% CI 0.6 to 1.2). AUTHORS' CONCLUSIONS: Evidence from this updated review supports the use of KMC in LBW infants as an alternative to conventional neonatal care, mainly in resource-limited settings. Further information is required concerning the effectiveness and safety of early-onset continuous KMC in unstabilized or relatively stabilized LBW infants, as well as long-term neurodevelopmental outcomes and costs of care.

Soil organic matter (SOM) anchors global terrestrial productivity and food and fiber supply. SOM retains water and soil nutrients and stores more global carbon than do plants and the atmosphere combined. SOM is also decomposed by microbes, returning CO 2 , a greenhouse gas, to the atmosphere. Unfortunately, soil carbon stocks have been widely lost or degraded through land use changes and unsustainable forest and agricultural practices. To understand its structure and function and to maintain and restore SOM, we need a better appreciation of soil organic carbon (SOC) saturation capacity and the retention of above- and belowground inputs in SOM. Our analysis suggests root inputs are approximately five times more likely than an equivalent mass of aboveground litter to be stabilized as SOM. Microbes, particularly fungi and bacteria, and soil faunal food webs strongly influence SOM decomposition at shallower depths, whereas mineral associations drive stabilization at depths greater than ∼30 cm. Global uncertainties in the amounts and locations of SOM include the extent of wetland, peatland, and permafrost systems and factors that constrain soil depths, such as shallow bedrock. In consideration of these uncertainties, we estimate global SOC stocks at depths of 2 and 3 m to be between 2,270 and 2,770 Pg, respectively, but could be as much as 700 Pg smaller. Sedimentary deposits deeper than 3 m likely contain >500 Pg of additional SOC. Soils hold the largest biogeochemically active terrestrial carbon pool on Earth and are critical for stabilizing atmospheric CO 2 concentrations. Nonetheless, global pressures on soils continue from changes in land management, including the need for increasing bioenergy and food production.

<b>Executive summary of the Global Strategy for Prevention, Diagnosis and Management of COPD 2023: the latest evidence-based strategy document from the Global Initiative for Chronic Obstructive Lung Disease (GOLD</b><b>)</b> https://bit.ly/3KCaTGe

Significance Aerobic life in humans imposes the hazard of excess oxidation in cell and tissue components that may compromise cell function and viability. The formation and accumulation of oxidized products in biomolecules such as proteins and lipids are observed in various pathologies and during the normal aging process. This review article aims to integrate some early and remarkable discoveries in the field, with more recent developments that helped to define a causative role of oxygen radicals, nitric oxide, and peroxynitrite in human physiology and pathology. These aspects of human redox biochemistry contribute to the understanding of the molecular basis of diseases and aging and open avenues for the development of preventive and therapeutic strategies in molecular medicine.