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Background: Maternal nutrition interventions are efficacious in improving birth outcomes. It is important to demonstrate that if delivered in field conditions they produce improvements in health and nutrition.Objective: Analyses of scaling-up of five program implemented in several countries. These include micronutrient supplementation, food fortification, food supplements, nutrition education and counseling, and conditional cash transfers (as a platform for delivering interventions). Evidence on impact and cost-effectiveness is assessed, especially on achieving high, equitable, and sustained coverage, and reasons for success or failureMethods: Systematic review of articles on large-scale programs in several databases. Two separate reviewers carried out independent searches. A separate review of the gray literature was carried out including websites of the most important organizations leading with these programs. With Google Scholar a detailed review of the 100 most frequently cited references on each of the five above topics was conducted.Results: Food fortification programs: iron and folic acid fortification were less successful than salt iodization initiatives, as the latter attracted more advocacy. Micronutrient supplementation programs: Nicaragua and Nepal achieved good coverage. Key elements of success are antenatal care coverage, ensuring availability of tablets, and improving compliance. Integrated nutrition programs in India, Bangladesh, and Madagascar with food supplementation and/or behavioral change interventions report improved coverage and behaviors, but achievements are below targets. The Mexican conditional cash transfer program provides a good example of use of this platform to deliver maternal nutritional interventions.Conclusions: Programs differ in complexity, and key elements for success vary with the type of program and the context in which they operate. Special attention must be given to equity, as even with improved overall coverage and impact inequalities may even be increased. Finally, much greater investments are needed in independent monitoring and evaluation. [ABSTRACT FROM AUTHOR]

The use of technological environments with virtual reality (VR) techniques for the practice of arthrocentesis offers an effective and safe way to learn and improve the necessary skills to carry out a medical procedure and patient care. This article presents an interactive simulator using immersive VR, in which the participant experiences practicing clinical management and decision-making in the face of a person presenting with monoarthritis in a medical consultation. The objective with this development is for the user to acquire the competence to perform, correctly and safely, a knee arthrocentesis and to differentiate the types of synovial fluids that can be found in a joint. In turn, it provides clinical guidance and assists with the user's medical decision-making. Therefore, the aim is to improve the quality of care and patient safety when practicing this technique previously through clinical simulation., Competing Interests: Conflict of interests The authors have no conflict of interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Studies using real-world data (RWD) can complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This review presents the experience resulting from the European Medicines Agency (EMA) pilot to generate RWE to support evaluations by EU regulators and down-stream decision makers from September 2021 to February 2023. A total of 61 research topics were identified for RWE generation during this period, covering a wide range of research questions, primarily generating evidence on medicines safety (22, 36%), followed by questions on the design and feasibility of clinical trials (11, 18%), drug utilization (10, 16%), clinical management (10, 16%), and disease epidemiology. A significant number of questions were related to the pediatric population and/or rare diseases. A total of 27 regulatory-led RWD studies have been conducted. Most studies were descriptive and aimed at estimating incidence and prevalence rates of clinical outcomes including adverse events or to evaluate medicines utilization. The review highlights key learnings to guide further efforts to enable the use and establish the value of real-world evidence (RWE) for regulatory decisions. For instance, there is a need to access additional fit-for-purpose and representative data, and to explore further means to provide timely evidence that meets regulatory timelines. The need for early interactions and close collaboration with study requesters, e.g., from the Agency's scientific Committees, to better understand the research question is equally important. Finally, the review provides our perspective on the way forward to maximize the potential of regulatory-led RWE generation., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Gastritis cystica profunda (GCP) is a rare entity characterized by foveolar hyperplasia and cystic dilation of the gastric mucosa and submucosal glands. Its etiopathogenesis remains unknown. It has been associated with chronic inflammatory conditions, such as gastric surgery or bile reflux. The diagnosis is histological, although endoscopic ultrasound (EUS) may be useful for initial suspicion. We present a series of cases from our center, where six cases of GCP were collected between 2012 and 2022, with no history of gastric surgery. The most common locations were the antrum (50%), fundus (33%), and body (17%). Endoscopic findings included polyps ranging from 7 to 50 mm. The treatment was en bloc mucosectomy for lesions ≤20 mm and piecemeal mucosectomy for lesions >20 mm. Recurrence was observed in four patients (67%). Histologically, displaced gastric glands were found in the submucosa with cystic dilation, without dysplastic changes.

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary This is a case of a laterally spreading lesion referred for surgical resection and found to be an adenoma-like adenocarcinoma. This uncommon histologic subtype of adenocarcinoma is associated with a more favorable prognosis. In assessing the risk of deep invasion in laterally spreading lesions, it is important to rely on multiple lesion characteristics rather than surface pattern alone. Despite a surface pit pattern (NICE II) suggestive of a premalignant lesion, the authors made the appropriate decision of referring for surgical resection. As the authors demonstrate here, careful attention to factors other than surface pattern can help guide appropriate management. Morphologic factors increasing the risk of invasion include a depressed component, the bulkiness of the lesion, and a “chicken-skin” or dimpled appearance of the mucosa at the periphery of the lesion. That having been said, the mentioned factors are suggestive but not conclusive for estimating depth of invasion. For example, a chicken-skin appearance is seen in bulky benign lesions, and heterogenous granular laterally spreading tumors may have depressed noninvasive components as well. The current case highlights the importance of taking into consideration all morphologic characteristic related to depth of invasion before endoscopic resection is embarked on. Fares Ayoub, MD, Assistant Professor of Medicine, Baylor College of Medicine, Houston, Texas, USA Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function 1 . We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women 2 , selected using World Health Organization recommendations for growth standards 3 . Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age 4,5 . The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline 6-8 . The atlas corresponds structurally to published magnetic resonance images 9 , but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment., (© 2023. The Author(s).)

In this paper, sediments from the Santiago River were characterized to look for an alternative source of inoculum for biogas production. A proteomic analysis of methane-processing archaea present in these sediments was carried out. The Euryarchaeota superkingdom of archaea is responsible for methane production and methane assimilation in the environment. The Santiago River is a major river in México with great pollution and exceeded recovery capacity. Its sediments could contain nutrients and the anaerobic conditions for optimal growth of Euryarchaeota consortia. Batch bioreactor experiments were performed, and a proteomic analysis was conducted with current database information. The maximum biogas production was 266 NmL·L -1 ·g VS -1 , with 33.34% of methane, and for proteomics, 3206 proteins were detected from 303 species of 69 genera. Most of them are metabolically versatile members of the genera Methanosarcina and Methanosarcinales , both with 934 and 260 proteins, respectively. These results showed a diverse euryarcheotic species with high potential to methane production. Although related proteins were found and could be feeding this metabolism through the methanol and acetyl-CoA pathways, the quality obtained from the biogas suggests that this metabolism is not the main one in carbon use, possibly the sum of several conditions including growth conditions and the pollution present in these sediments.

Importance: The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures., Objective: To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years., Design, Setting, and Participants: The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020., Exposures/interventions: Preterm-birth phenotypes., Main Outcomes and Measures: Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool., Results: A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype., Conclusions and Relevance: Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.

Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections) 1 and preventive interventions (for example, multiple-micronutrient supplementation) 2 that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood 3 . In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites worldwide 4 , we studied the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks' gestation, against international standards 5,6 , and growth and neurodevelopment up to 2 years of age 7,8 . We identified five trajectories associated with specific neurodevelopmental, behavioral, visual and growth outcomes, independent of fetal abdominal growth, postnatal morbidity and anthropometric measures at birth and age 2. The trajectories, which changed within a 20-25-week gestational age window, were associated with brain development at 2 years of age according to a mirror (positive/negative) pattern, mostly focused on maturation of cognitive, language and visual skills. Further research should explore the potential for preventive interventions in pregnancy to improve infant neurodevelopmental outcomes before the critical window of opportunity that precedes the divergence of growth at 20-25 weeks' gestation.

Wastewater treatment (WWT) is a priority around the world; conventional treatments are not widely used in rural areas owing to the high operating and maintenance costs. In Mexico, for instance, only 40% of wastewater is treated. One sustainable option for WWT is through the use of constructed wetlands (CWs) technology, which may remove pollutants using cells filled with porous material and vegetation that works as a natural filter. Knowing the optimal material and density of plants used per square meter in CWs would allow improving their WWT effect. In this study, the effect of material media (plastic/mineral) and plant density on the removal of organic/inorganic pollutants was evaluated. Low (three plants), medium (six plants) and high (nine plants) densities were compared in a surface area of 0.3 m 2 of ornamental plants ( Alpinia purpurata , Canna hybrids and Hedychium coronarium ) used in polycultures at the mesocosm level of household wetlands, planted on the two different substrates. Regarding the removal of contaminants, no significant differences were found between substrates ( p ≥ 0.05), indicating the use of plastic residues (reusable) is an economical option compared to typical mineral materials. However, differences ( p = 0.001) in removal of pollutants were found between different plant densities. For both substrates, the high density planted CWs were able to remove COD in a range of 86-90%, PO 4 -P 22-33%, NH 4 -N in 84-90%, NO 3 -N 25-28% and NO 2 -N 38-42%. At medium density, removals of 79-81%, 26-32, 80-82%, 24-26%, and 39-41%, were observed, whereas in CWs with low density, the detected removals were 65-68%, 20-26%, 79-80%, 24-26% and 31-40%, respectively. These results revealed that higher COD and ammonia were removed at high plant density than at medium or low densities. Other pollutants were removed similarly in all plant densities (22-42%), indicating the necessity of hybrid CWs to increase the elimination of PO 4 -P, NO 3 -N and NO 2 -N. Moreover, high density favored 10 to 20% more the removal of pollutants than other plant densities. In addition, in cells with high density of plants and smaller planting distance, the development of new plant shoots was limited. Thus, it is suggested that the appropriate distance for this type of polyculture plants should be from 40 to 50 cm in expansion to real-scale systems in order to take advantage of the harvesting of species in these and allow species of greater foliage, favoring its growth and new shoots with the appropriate distance to compensate, in the short time, the removal of nutrients.

In this study we evaluated the effect of the reduction in the endoplasmic reticulum calcium concentration ([Ca 2+ ] ER ), changes in the cytoplasmic calcium concentration ([Ca 2+ ] i ), alteration of the mitochondrial membrane potential, and the ER stress in the activation of caspase-3 in neonatal cerebellar granule cells (CGN). The cells were loaded with Fura-2 to detect changes in the [Ca 2+ ] i and with Mag-fluo-4 to measure variations in the [Ca 2+ ] ER or with TMRE to follow modifications in the mitochondrial membrane potential in response to five different inducers of CGN cell death. These inducers were staurosporine, thapsigargin, tunicamycin, nifedipine and plasma membrane repolarization by switching culture medium from 25 mM KCl (K25) to 5 mM KCl (K5). Additionally, different markers of ER stress were determined and all these parameters were correlated with the activation of caspase-3. The different inducers of cell death in CGN resulted in three different levels of activation of caspase-3. The highest caspase-3 activity occurred in response to K5. At the same time, staurosporine, nifedipine, and tunicamycin elicited an intermediate activation of caspase-3. Importantly, thapsigargin did not activate caspase-3 at any time. Both K5 and nifedipine rapidly decreased the [Ca 2+ ] i , but only K5 immediately reduced the [Ca 2+ ] ER and the mitochondrial membrane potential. Staurosporine and tunicamycin increased the [Ca 2+ ] i and they decreased both the [Ca 2+ ] ER and mitochondrial membrane potential, but at a much lower rate than K5. Thapsigargin strongly increased the [Ca 2+ ] i , but it took 10 min to observe any decrease in the mitochondrial membrane potential. Three cell death inducers -K5, staurosporine, and thapsigargin- elicited ER stress, but they took 30 min to have any effect. Thapsigargin, as expected, displayed the highest efficacy activating PERK. Moreover, a specific PERK inhibitor did not have any impact on cell death triggered by these cell death inducers. Our data suggest that voltage-gated Ca 2+ channels, that are not dihydropyridine-sensitive, load the ER with Ca 2+ and this Ca 2+ flux plays a critical role in keeping the mitochondrial membrane potential polarized. A rapid decrease in the [Ca 2+ ] ER resulted in rapid mitochondrial membrane depolarization and strong activation of caspase-3 without the intervention of the ER stress in CGN., (Copyright © 2020 Benítez-Rangel, Olguín-Albuerne, López-Méndez, Domínguez-Macouzet, Guerrero-Hernández and Morán.)

Introduction: Self-rated health is strongly associated with morbidity and mortality. It is largely influenced by individual factors but also by individuals' social surroundings and environment., Objective: To investigate individual, household, and locality factors associated with self-rated ealth in Colombian adults., Materials and Methods: We conducted a cross-sectional multilevel study using data from national databases on 19 urban localities and 37,352 individuals nested within 15,788 households using a population-based survey. Given the natural hierarchical structure of the data, the estimates of self-rated health related to individual, household, and locality characteristics were obtained by fitting a three-level logistic regression., Results: The adjusted multilevel logistic models showed that at individual level, higher odds of poor self-rated health were found among older adults, persons from low socio-economic status, those living without a partner, with no regular physical activity, and reporting morbidities. At the household level, poor self-rated health was associated with households of low socioeconomic status located near noise sources and factories and in polluted and insecure areas. At the locality level, only poverty was associated with poor self-rated health after adjusting for individual and household variables., Conclusions: These results highlight the need for a more integrated framework when designing and implementing strategies and programs that aim to improve health conditions in urban populations in Latin America.

Background: With the adoption of the Sustainable Development Goals (SDGs), there is a renewed commitment of tackling the varied challenges of undernutrition, particularly stunting (SDG 2.2). Health equity is also a priority in the SDG agenda and there is an urgent need for disaggregated analyses to identify disadvantaged subgroups. We compared time trends in socioeconomic inequalities obtained through stratification by wealth quintiles and deciles for stunting prevalence., Methods: We used 37 representative Demographic and Health Surveys and Multiple Indicator Cluster surveys from nine Latin American and Caribbean (LAC) countries conducted between 1996 and 2016. Stunting in children under-5 years was assessed according to the 2006 WHO Child Growth Standards and stratified by wealth quintiles and deciles. Within-country socioeconomic inequalities were measured through concentration index (CIX) and slope index of inequality (SII). We used variance-weighted least squares regression to estimate annual changes., Results: Eight out of nine countries showed a statistical evidence of reduction in stunting prevalence over time. Differences between extreme deciles were larger than between quintiles in most of countries and at every point in time. However, when using summary measures of inequality, there were no differences in the estimates of SII with the use of deciles and quintiles. In absolute terms, there was a reduction in socioeconomic inequalities in Peru, Honduras, Dominican Republic, Belize, Suriname and Colombia. In relative terms, there was an increase in socioeconomic inequalities in Peru, Bolivia, Haiti, Honduras and Guatemala., Conclusions: LAC countries have made substantial progress in terms of reducing stunting,. Nevertheless, renewed actions are needed to improve equity. Particularly in those countries were absolute and relative inequalities did not change over time such Bolivia and Guatemala. Finer breakdowns in wealth distribution are expected to elucidate more differences between subgroups; however, this approach is relevant to cast light on those subgroups that are still lagging behind within populations and inform equity-oriented health programs and practices.

The Golgi apparatus (GA) is a bona fide Ca 2+ store; however, there is a lack of GA-specific Ca 2+ mobilizing agents. Here, we report that emetine specifically releases Ca 2+ from GA in HeLa and HL-1 atrial myocytes. Additionally, it has become evident that the trans-Golgi is a labile Ca 2+ store that requires a continuous source of Ca 2+ from either the external milieu or from the ER, to enable it to produce a detectable transient increase in cytosolic Ca 2+ . Our data indicates that the emetine-sensitive Ca 2+ mobilizing mechanism is different from the two classical Ca 2+ release mechanisms, i.e. IP 3 and ryanodine receptors. This newly discovered ability of emetine to release Ca 2+ from the GA may explain why chronic consumption of ipecac syrup has muscle side effects.

In stably-transfected human neuroblastoma SH-SY5Y cells, we have compared the effect of activating two isoforms of 445 and 365 amino acids of the human histamine H 3 receptor (hH 3 R 445 and hH 3 R 365 ) on [ 35 S]-GTPγS binding, forskolin-induced cAMP formation, depolarization-induced increase in the intracellular concentration of Ca 2+ ions ([Ca 2+ ]i) and depolarization-evoked [ 3  H]-dopamine release. Maximal specific binding (B max ) of [ 3  H]-N-methyl-histamine to cell membranes was 953 ± 204 and 555 ± 140 fmol/mg protein for SH-SY5Y-hH 3 R 445 and SH-SY5Y-hH 3 R 365 cells, respectively, with similar dissociation constants (K d , 0.86 nM and 0.81 nM). The mRNA of the hH 3 R 365 isoform was 40.9 ± 7.9% of the hH 3 R 445 isoform. No differences in receptor affinity were found for the H 3 R ligands histamine, immepip, (R)(-)-α-methylhistamine (RAMH), A-331440, clobenpropit and ciproxifan. Both the stimulation of [ 35 S]-GTPγS binding and the inhibition of forskolin-stimulated cAMP accumulation by the agonist RAMH were significantly larger in SH-SY5Y-hH 3 R 445 cells ([ 35 S]-GTPγS binding, 158.1 ± 7.5% versus 136.5 ± 3.6% for SH-SY5Y-hH 3 R 365 cells; cAMP accumulation, -74.0 ± 4.9% versus -43.5 ± 5.3%), with no significant effect on agonist potency. In contrast, there were no differences in the efficacy and potency of RAMH to inhibit [ 3  H]-dopamine release evoked by 100 mM K + (-18.9 ± 3.0% and -20.5 ± 3.3%, for SH-SY5Y-hH 3 R 445 and SH-SY5Y-hH 3 R 365 cells), or the inhibition of depolarization-induced increase in [Ca 2+ ]i (S2/S1 ratios: parental cells 0.967 ± 0.069, SH-SY5Y-hH 3 R 445 cells 0.639 ± 0.049, SH-SY5Y-hH 3 R 365 cells 0.737 ± 0.045). These results indicate that in SH-SY5Y cells, hH 3 R 445 and hH 3 R 365 isoforms regulate in a differential manner the signaling pathways triggered by receptor activation.

The aim of this study was to assess the presence of suicidal ideation and depressive symptoms among adolescents in Chiapas, Mexico based on predictor variables. A cross-sectional study adopting an ex post facto design was conducted with a non-probability sample of 4,759 students of both sexes with an average age of 18.4 years and using the following tools: the Center for Epidemiologic Studies Depression Scale, Roberts' Suicidal Ideation Scale, the Impulsiveness Scale (IS), and the Rosenberg Self-Esteem Scale. The mean score obtained by the suicidal ideation scale was 0.2, which is lower than that reported by other studies, while the mean score for depressive symptoms was similar to those in the literature. The prevalence of suicidal ideation was 7.8%, which is lower than reported in national and international studies. Multivariable logistic regression showed that impulsiveness (OR = 1.907) and depressive symptoms (OR = 9.006) lead to a twofold and ninefold increase in the likelihood of suicidal ideation, respectively. The findings also showed a strong association between suicidal ideation and depressive symptoms, showing that the latter is a predictor of suicidal ideation among adolescents.

Objective: To evaluate the association between growth trajectories from birth to adolescence and cardiovascular risk marker levels at age 18 years in a population-based cohort. In order to disentangle the effect of weight gain from that of height gain, growth was analysed using conditional weight relative to linear growth (CWh) and conditional length/height (CH)., Design: Prospective study., Setting: 1993 Pelotas birth cohort, Southern Brazil., Participants: Individuals who have been followed up from birth to adolescence (at birth, 1, 4, 11, 15 and 18 years)., Primary Outcome Measures: C-reactive protein (CRP), total cholesterol (TC), LDL cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TGL), systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI) and waist circumference (WC)., Results: In both sexes, greater CWh at 1 year was positively associated with BMI and WC, whereas greater CWh at most age periods in childhood and adolescence predicted higher CRP, TC, LDL-C, TGL, SBP, DBP, BMI and WC levels, as well as lower HDL-C level. Higher CH during infancy and childhood was positively related with SBP in boys and girls, and with BMI and WC only in boys., Conclusion: Our study shows that rapid weight gain from 1 year onwards is positively associated with several markers of cardiovascular risk at 18 years. Overall, our results for the first year of life add evidence to the 'first 1000 days initiative' suggesting that prevention of excessive weight gain in childhood might be important in reducing subsequent cardiovascular risk., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The last decade has seen a breakthrough in the treatment of erectile dysfunction (ED) with the advent of phosphodiesterase-5 inhibitors. There are few population-based observational studies on the prevalence of use of these drugs. We conducted a cross-sectional population-based study in the city of Pelotas (Brazil). Our sample comprised 1,082 men aged 20 years or older who answered a confidential and self-administered questionnaire. Prevalence of EDD use was 5% (IC95% = 4%;7%). ED and advanced age were strongly associated with a higher prevalence of EDD use. ED prevalence in men who used EDD was 68%, which was much higher than the one found in the entire sample (27%). The use of EDD was more frequently reported among separated men, respondents with higher level of education and those without ED. A high proportion of respondents (68%) did not seek medical advice on the use of EDD. Sildenafil was the most commonly used drug (38%) but non-regulated and non-evidence-based drugs were also frequently used (14%). Prevalence of EDD use is higher among individuals with ED, opposing to the notion of recreational use of EDD.

Background: Wealth quintiles derived from household asset indices are routinely used for measuring socioeconomic inequalities in the health of women and children in low and middle-income countries. We explore whether the use of wealth deciles rather than quintiles may be advantageous., Methods: We selected 46 countries with available national surveys carried out between 2003 and 2013 and with a sample size of at least 3000 children. The outcomes were prevalence of under-five stunting and delivery by a skilled birth attendant (SBA). Differences and ratios between extreme groups for deciles (D1 and D10) and quintiles (Q1 and Q5) were calculated, as well as two summary measures: the slope index of inequality (SII) and concentration index (CIX)., Results: In virtually all countries, stunting prevalence was highest among the poor, and there were larger differences between D1 and D10 than between Q1 and Q5. SBA coverage showed pro-rich patterns in all countries; in four countries the gap was greater than 80 pct points. With one exception, differences between extreme deciles were larger than between quintiles. Similar patterns emerged when using ratios instead of differences. The two summary measures provide very similar results for quintiles and deciles. Patterns of top or bottom inequality varied with national coverage levels., Conclusion: Researchers and policymakers should consider breakdowns by wealth deciles, when sample sizes allow. Use of deciles may contribute to advocacy efforts, monitoring inequalities over time, and targeting health interventions. Summary indices of inequalities were unaffected by the use of quintiles or deciles in their calculation.

We investigated the mechanism of action on the photosynthesis light reactions of three major secondary metabolites produced by the endophytic fungus Xylaria feejeensis strain SM3e-1b, isolated from Sapium macrocarpum; and four novel derivatives of coriloxine, a major compound produced by X. feejeensis. The natural phytotoxins include one epoxycyclohexenone derivative, coriloxine (1), and two quinone derivatives (2-3). The semisynthetic derivatives of coriloxine are two cyclohexenone (4-6) and two quinone compounds (5-7). Cyclohexenone (4), (4R,5S,6R)-6-chloro-4,5-dihydroxy-3-methoxy-5-methylcyclohex-2-enone, inhibited ATP synthesis in freshly lysed spinach chloroplasts from water to MV; it also partly inhibited the basal and uncoupled photosynthetic electron transport, and significantly enhanced the phosphorylating electron transport and Mg 2+ -ATPase activity, thus demonstrating its action as an uncoupler agent. On the other hand, quinone (7), 2-((4-butylphenyl)amino)-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione, inhibited ATP synthesis, and non-cyclic electron transport from water to MV in basal, phosphorylating and uncoupled conditions in a concentration-dependent manner. Hence, (7) behaves as a Hill reaction inhibitor at the PSII electron transport on the water splitting enzyme (OEC), and on the acceptor side between P 680 and Q A . This mechanism of action was confirmed by chlorophyll a fluorescence measurements. These results indicate that coriloxine derivatives 4 and 7 could work as prototype structures for the development of new herbicides. Contrastingly, natural products 1-3, and derivatives 5 and 6 did not show a significant inhibitory effect on ATP synthesis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The histamine H 3 receptor (H 3 R) is abundantly expressed in the Central Nervous System where it regulates several functions pre and postsynaptically. H 3 Rs couple to Gα i/o proteins and trigger or modulate several intracellular signaling pathways, including the cAMP/PKA pathway and the opening of N- and P/Q-type voltage-gated Ca 2+ channels. In transfected cells, activation of the human H 3 R of 445 amino acids (hH 3 R 445 ) results in phospholipase C (PLC) stimulation and release of Ca 2+ from intracellular stores. In this work we have studied whether H 3 R activation induces Ca 2+ mobilization from intracellular stores in native systems, either isolated nerve terminals (synaptosomes) or neurons in primary culture. In rat striatal synaptosomes H 3 R activation induced inositol 1,4,5-trisphosphate (IP 3 ) formation but failed to increase the intracellular calcium concentration ([Ca 2+ ] i ). In striatal primary cultures H 3 R activation resulted in IP 3 formation and increased the [Ca 2+ ] i in 18 out of 70 cells that responded with an elevation in the [Ca 2+ ] i to membrane depolarization with KCl (100 mM) as evaluated by microfluorometry. Confocal microscopy studies corroborated the increase in [Ca 2+ ]i induced by H 3 R activation in a fraction of those cells that were responsive to membrane depolarization. These results indicate that H 3 R activation stimulates the PLC/IP 3 /Ca 2+ pathway but only in a subpopulation of striatal neurons., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The Brazilian SUS (Unified Health System) was created in 1988 within the new constitution, based on the premises of being universal, comprehensive, and equitable. The SUS offers free health care, independent of contribution or affiliation. Since then, great efforts and increasing investments have been made for the system to achieve its goals. We assessed how coverage and equity in selected reproductive and maternal interventions progressed in Brazil from 1986 to 2013., Methods: We reanalysed data from four national health surveys carried out in Brazil in 1986, 1996, 2006 and 2013. We estimated coverage for six interventions [use of modern contraceptives; antenatal care (ANC) 1+ visits by any provider; ANC 4+ visits by any provider; first ANC visit during the first trimester of pregnancy; institutional delivery; and Caesarean sections] using standard international definitions, and stratified results by wealth quintile, urban or rural residence and country regions. We also calculated two inequality indicators: the slope index of inequality (SII) and the concentration index (CIX)., Results: All indicators showed steady increases in coverage over time. ANC 1+ and 4+ and institutional delivery reached coverage above 90 % in 2013. Prevalence of use of modern contraceptives was 83 % in 2013, indicating nearly universal satisfaction of need for contraception. On a less positive note, the proportion of C-sections has also grown continuously, reaching 55 % in 2013. There were marked reductions in wealth inequalities for all preventive interventions. Inequalities were significantly reduced for all indicators except for the C-section rate (p = 0.06), particularly in absolute terms (SII)., Conclusions: Despite the difficulties faced in the implementation of SUS, coverage of essential interventions increased and equity has improved dramatically, due in most cases to marked increase in coverage among the poorest 40 %. An increase in unnecessary Caesarean sections was also observed during the period. Further evaluation on the quality of healthcare provided is needed.

There is an urgent need to develop novel antimicrobial substances. Antimicrobial peptides (AMPs) are considered as promising candidates for future therapeutic use. Because of the re-emergence of the Flavivirus infection, and particularly the yellow fever virus (YFV), we have compared the antiviral activities from skin secretions of seven different frog species against YFV (strain 17D). Secretions from Sphaenorhynchus lacteus, Cryptobatrachus boulongeri and Leptodactylus fuscus displayed the more powerful activities. S. lacteus was found to inhibit viral lysis of Vero E6 cells even at the highest viral concentration evaluated of 10 LD 50 . We also report the identification of a novel frenatin-related peptide from S. lacteus and found that this peptide-on its own-can lead to 35% protection against YVF, while displaying no cytotoxicity against somatic cells even at fivefold higher concentrations. These results are attractive and support the need for continued exploration of new sources of AMPs from frog skin secretions such as those described here in the development of new compounds for the treatment of infectious diseases in general and specific viral infections in particular.

Objective: To investigate disparities in full immunization coverage across and within 86 low- and middle-income countries., Methods: In May 2015, using data from the most recent Demographic and Health Surveys and Multiple Indicator Cluster Surveys, we investigated inequalities in full immunization coverage - i.e. one dose of bacille Calmette-Guérin vaccine, one dose of measles vaccine, three doses of vaccine against diphtheria, pertussis and tetanus and three doses of polio vaccine - in 86 low- or middle-income countries. We then investigated temporal trends in the level and inequality of such coverage in eight of the countries., Findings: In each of the World Health Organization's regions, it appeared that about 56-69% of eligible children in the low- and middle-income countries had received full immunization. However, within each region, the mean recorded level of such coverage varied greatly. In the African Region, for example, it varied from 11.4% in Chad to 90.3% in Rwanda. We detected pro-rich inequality in such coverage in 45 of the 83 countries for which the relevant data were available and pro-urban inequality in 35 of the 86 study countries. Among the countries in which we investigated coverage trends, Madagascar and Mozambique appeared to have made the greatest progress in improving levels of full immunization coverage over the last two decades, particularly among the poorest quintiles of their populations., Conclusion: Most low- and middle-income countries are affected by pro-rich and pro-urban inequalities in full immunization coverage that are not apparent when only national mean values of such coverage are reported.

This study focuses on trends and inequalities in health risk behaviors among adolescents. A cross-sectional study compared two birth cohorts in the city of Pelotas, Rio Grande do Sul State, Brazil. The sample included 1,281 adolescents from the 1982 cohort and 4,106 from the 1993 cohort, followed in 2001 and 2011, respectively. The study recorded alcohol intake, illegal drug use, smoking, sexual initiation < 16 years, lack of condom use, and multiple sex partners. Total prevalence rates were calculated for each cohort, stratified by gender and per capita income, besides absolute and relative measures of inequality. There was a decrease from 2001 to 2011 in prevalence rates for trying alcohol, illegal drug use, smoking, and lack of condom use, and an increase in the number of sex partners. The gap between boys and girls increased for non-use of condoms and decreased for the other behaviors. The gap between income groups decreased for sexual initiation before 16 years of age and increased for episodes of intoxication. Socioeconomic inequalities persist, despite the downward trend in prevalence of risk behaviors.

Background: Peru has made great improvements in reducing stunting and child mortality in the past decade, and has reached the Millennium Development Goals 1 and 4. The remaining challenges or missed opportunities for child survival needs to be identified and quantified, in order to guide the next steps to further improve child survival in Peru., Methods: We used the Lives Saved Tool (LiST) to project the mortality impact of proven interventions reaching every women and child in need, and the mortality impact of eliminating inequalities in coverage distribution between wealth quintiles and urban-rural residence., Results: Our analyses quantified the remaining missed opportunities in Peru, where prioritizing scale-up of facility-based case management for all small and sick babies will be most effective in mortality reduction, compared to other evidenced-based interventions that prevent maternal and child deaths. Eliminating coverage disparities between the poorest quintiles and the richest will reduce under-five and neonatal mortality by 22.0 and 40.6 %, while eliminating coverage disparities between those living in rural and urban areas will reduce under-five and neonatal mortality by 29.3 and 45.2 %. This projected neonatal mortality reduction achieved by eliminating coverage disparities is almost comparable to that already achieved by Peru over the past decade., Conclusions: Although Peru has made great strides in improving child survival, further improvement in child health, especially in newborn health can be achieved if there is universal and equitable coverage of proven, quality health facility-based interventions. The magnitude of reduction in mortality will be similar to what has been achieved in the past decade. Strengthening health system to identify, understand, and direct resources to the poor and rural areas will ensure that Peru achieve the Sustainable Development Goals by 2030.

Aim: Glycated haemoglobin (HbA1c), a marker of glucose control in individuals with diabetes mellitus, is also related with the incidence of cardiometabolic risk in populations free of disease. The aim of this study was to describe the distribution of HbA1c levels according to early-life and contemporary factors in adolescents and adults without diabetes mellitus., Methods: HbA1c was measured in adults aged 30 years and adolescents aged 18 years who are participants in the 1982 and 1993 Pelotas Birth Cohorts, respectively. Bivariate and multivariate analyses were performed to describe the HbA1c mean values according to early-life and contemporary characteristics collected prospectively since birth., Results: The distribution of the HbA1c was approximately normal in both cohorts, with a mean (SD) 5.10% (0.43) in the 1982 cohort, and 4.89% (0.50) in the 1993 cohort. HbA1c mean levels were significantly higher in individuals self-reported as black/brown skin color compared to those self-reported as white in both cohorts. Parental history of diabetes was associated with higher HbA1c mean in adults, while stunting at one year old presented an inverse relation with the outcome in adolescents. No other early and contemporary factors were associated with HbA1c levels in adults or adolescents., Conclusions: We found a consistent relationship between HbA1c and skin color in both cohorts. Further research is needed to understand the role of genomic ancestry on levels of HbA1c concentrations which may inform policies and preventive actions for diabetes mellitus and cardiometabolic risk., Competing Interests: The authors have declared that no competing interests exist.

Background: Peru has impressively reduced its neonatal mortality rate (NMR). We aimed, for the period 2000-2013, to: (a) describe national and district NMR variations over time; (b) assess NMR trends by wealth quintile and place of residence; (c) describe evolution of mortality causes; (d) assess completeness of registered mortality; (e) assess coverage and equity of NMR-related interventions; and (f) explore underlying driving factors., Methods: We compared national NMR time trends from different sources. To describe NMR trends by wealth quintiles, place of residence and districts, we pooled data on births and deaths by calendar year for neonates born to women interviewed in multiple surveys. We disaggregated coverage of NMR-related interventions by wealth quintiles and place of residence. To identify success factors, we ran regression analyses and combined desk reviews with qualitative interviews and group discussions., Results: NMR fell by 51 % from 2000 to 2013, second only to Brazil in Latin America. Reduction was higher in rural and poorest segments (52 and 58 %). District NMR change varied by source. Regarding cause-specific NMRs, prematurity decreased from 7.0 to 3.2 per 1,000 live births, intra-partum related events from 2.9 to 1.2, congenital abnormalities from 2.4 to 1.8, sepsis from 1.9 to 0.8, pneumonia from 0.9 to 0.4, and other conditions from 1.2 to 0.7. Under-registration of neonatal deaths decreased recently, more in districts with higher development index and lower rural population. Coverage of family planning, antenatal care and skilled birth attendance increased more in rural areas and in the poorest quintile. Regressions did not show consistent associations between mortality and predictors. During the study period social determinants improved substantially, and dramatic out-of-health-sector and health-sector changes occurred. Rural areas and the poorest quintile experienced greater NMR reduction. This progress was driven, within a context of economic growth and poverty reduction, by a combination of strong societal advocacy and political will, which translated into pro-poor implementation of evidence-based interventions with a rights-based approach., Conclusions: Although progress in Peru for reducing NMR has been remarkable, future challenges include closing remaining gaps for urban and rural populations and improving newborn health with qualified staff and intermediate- and intensive-level health facilities.

Background and Objectives: Hygiene during childbirth is essential to the health of mothers and newborns, irrespective of where birth takes place. This paper investigates the status of water and sanitation in both the home and facility childbirth environments, and for whom and where this is a more significant problem., Methods: We used three datasets: a global dataset, with information on the home environment from 58 countries, and two datasets for each of four countries in Eastern Africa: a healthcare facility dataset, and a dataset that incorporated information on facilities and the home environment to create a comprehensive description of birth environments in those countries. We constructed indices of improved water, and improved water and sanitation combined (WATSAN), for the home and healthcare facilities. The Joint Monitoring Program was used to construct indices for household; we tailored them to the facility context-household and facility indices include different components. We described what proportion of women delivered in an environment with improved WATSAN. For those women who delivered at home, we calculated what proportion had improved WATSAN by socio-economic status, education and rural-urban status., Results: Among women delivering at home (58 countries), coverage of improved WATSAN by region varied from 9% to 53%. Fewer than 15% of women who delivered at home in Sub-Saharan Africa, had access to water and sanitation infrastructure (range 0.1% to 37%). This was worse among the poorest, the less educated and those living in rural areas. In Eastern Africa, where we looked at both the home and facility childbirth environment, a third of women delivered in an environment with improved water in Uganda and Rwanda; whereas, 18% of women in Kenya and 7% in Tanzania delivered with improved water and sanitation. Across the four countries, less than half of the facility deliveries had improved water, or improved water and sanitation in the childbirth environment., Conclusions: Access to water and sanitation during childbirth is poor across low and middle-income countries. Even when women travel to health facilities for childbirth, they are not guaranteed access to basic WATSAN infrastructure. These indicators should be measured routinely in order to inform improvements.

Objective:: To assess time trends in maternal mortality in Brazil and its five geographical regions from 2001 to 2012, as well as to describe its main causes., Methods:: This is a time series analysis, from data obtained in the Mortality Information System (SIM) and in the Live Births Information System (SINASC). Maternal mortality ratio (MMR) and causes of maternal death were described according to the categories of the Tenth Revision of the International Classification of Diseases, in the years 2001, 2006, and 2011. To estimate time trends, linear regression was used., Results:: The highest MMR in Brazil was observed in 2009 (77.31 per 100,000 live births). A significant decreasing trend was observed in the Northeast and South regions and a significant increasing trend was found in the Midwest. There was an increase in deaths from other obstetric conditions and a decrease in deaths from edema, proteinuria and hypertensive disorders., Conclusion:: Although there was a decreasing trend in the MMR in the Northeast and South regions, the high ratio observed in Brazil reveals the need to improve health care in prenatal, childbirth, and puerperium periods.

Bioactivity-directed fractionation of the combined culture medium and mycelium extract of the endophytic fungus Xylaria feejeensis strain SM3e-1b, isolated from Sapium macrocarpum, led to the isolation of three known natural products: (4S,5S,6S)-4-hydroxy-3-methoxy-5-methyl-5,6-epoxycyclohex-2-enone or coriloxine, 1; 2-hydroxy-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione, 2; and 2,6-dihydroxy-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione or fumiquinone B, 3. This is the first report of compound 3 being isolated from this species. Additionally, four new derivatives of coriloxine were prepared: (4R,5S,6R)-6-chloro-4,5-dihydroxy-3-methoxy-5-methylcyclohex-2-enone, 4; 6-hydroxy-5-methyl-3-(methylamino)cyclohexa-2,5- diene-1,4-dione, 5; (4R,5R,6R)-4,5-dihydroxy-3-methoxy-5-methyl-6-(phenylamino)cyclohex-2-enone, 6; and 2-((4-butylphenyl)amino)-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione, 7. X-ray analysis allowed us to unambiguously determine the structures and absolute configuration of semisynthetic derivatives 4, 5, and 6. The phytotoxic activity of the three isolated natural products and the coriloxine derivatives is reported. Germination of the seed, root growth, and oxygen uptake of the seedlings of Trifolium pratense, Medicago sativa, Panicum miliaceum, and Amaranthus hypochondriacus were significantly inhibited by all of the tested compounds. In general, they were more effective inhibiting root elongation than suppressing the germination and seedling oxygen uptake processes as shown by their IC50 values.

Background: Peru is an upper-middle-income country with wide social and regional disparities. In recent years, sustained multisectoral antipoverty programmes involving governments, political parties, and civil society have included explicit health and nutrition goals and spending increased sharply. We did a country case study with the aim of documenting Peru's progress in reproductive, maternal, neonatal, and child health from 2000-13, and explored the potential determinants., Methods: We examined the outcomes of health interventions coverage, under-5 mortality, neonatal mortality, and prevalence of under-5 stunting. We obtained data from interviews with key informants, a literature review of published and unpublished data, national censuses, and governmental reports. We obtained information on social determinants of health, including economic growth, poverty, unmet basic needs, urbanisation, women's education, water supply, fertility rates, and child nutrition from the annual national households surveys and the Peruvian Demographic and Health Surveys. We obtained national mortality data from the Interagency Group for Child Mortality Estimation, and calculated subnational rates from 11 surveys. Analyses were stratified by region, wealth quintiles, and urban or rural residence. We calculated coverage indicators for the years 2000-13, and we used the Lives Saved Tool (LiST) to estimate the effect of changes in intervention coverage and in nutritional status on mortality., Findings: From 2000 to 2013, under-5 mortality fell by 58% from 39·8 deaths per 1000 livebirths to 16·7. LiST, which was used to predict the decline in mortality arising from changes in fertility rates, water and sanitation, undernutrition, and coverage of indicators of reproductive, maternal, neonatal, and child health predicted that the under-5 mortality rate would fall from 39·8 to 28·4 per 1000 livebirths, accounting for 49·2% of the reported reduction. Neonatal mortality fell by 51% from 16·2 deaths per 1000 livebirths to 8·0. Stunting prevalence remained stable at around 30% until 2007, decreasing to 17·5% by 2013, and the composite coverage index for essential health interventions increased from 75·1% to 82·6%, with faster increases among the poor, in rural areas, and in the Andean region. Socioeconomic, urban-rural, and regional inequalities in coverage, mortality, and stunting were substantially reduced. The proportion of the population living below the poverty line reduced from 47·8% to 23·9%, women with fewer than 4 years of schooling reduced from 11·5% to 6·9%, urbanisation increased from 68·1% to 75·6%, and the total fertility rate decreased from 3·0 children per woman to 2·4. We interviewed 175 key informants and they raised the following issues: economic growth, improvement of social determinants, civil society empowerment and advocacy, out-of-health and within-health-sector changes, and sustained implementation of evidence-based, pro-poor reproductive, maternal, neonatal, and child health interventions., Interpretation: Peru has made substantial progress in reducing neonatal and under-5 mortality, and child stunting. This country is a good example of how a combination of political will, economic growth, broad societal participation, strategies focused on poor people, and increased spending in health and related sectors can achieve significant progress in reproductive, maternal, neonatal, and child health. The remaining challenges include continuing to address inequalities in wealth distribution, poverty, and access to basic services, especially in the Amazon and Andean rural areas., Funding: Bill & Melinda Gates Foundation., (Copyright © 2016 Huicho et al. Open Access article distributed under the terms of CC BY 4.0. Published by Elsevier Ltd.. All rights reserved.)

Background: Antenatal care (ANC) is critical for improving maternal and newborn health. WHO recommends that pregnant women complete at least four ANC visits. Countdown and other global monitoring efforts track the proportions of women who receive one or more visits by a skilled provider (ANC1+) and four or more visits by any provider (ANC4+). This study investigates patterns of drop-off in use between ANC1+ and ANC4+, and explores inequalities in women's use of ANC services. It also identifies determinants of utilization and describes countries' ANC-related policies, and programs., Methods: We performed secondary analyses using Demographic Health Survey (DHS) data from seven Countdown countries: Bangladesh, Cambodia, Cameroon, Nepal, Peru, Senegal and Uganda. The descriptive analysis illustrates country variations in the frequency of visits by provider type, content, and by household wealth, women's education and type of residence. We conducted a multivariable analysis using a conceptual framework to identify determinants of ANC utilization. We collected contextual information from countries through a standard questionnaire completed by country-based informants., Results: Each country had a unique pattern of ANC utilization in terms of coverage, inequality and the extent to which predictors affected the frequency of visits. Nevertheless, common patterns arise. Women having four or more visits usually saw a skilled provider at least once, and received more evidence-based content interventions than women reporting fewer than four visits. A considerable proportion of women reporting four or more visits did not report receiving the essential interventions. Large disparities exist in ANC use by household wealth, women's education and residence area; and are wider for a larger number of visits. The multivariable analyses of two models in each country showed that determinants had different effects on the dependent variable in each model. Overall, strong predictors of ANC initiation and having a higher frequency (4+) of visits were woman's education and household wealth. Gestational age at first visit, birth rank and preceding birth interval were generally negatively associated with initiating visits and with having four or more visits. Information on country policies and programs were somewhat informative in understanding the utilization patterns across the countries, although timing of adoption and actual implementation make direct linkages impossible to verify., Conclusion: Secondary analyses provided a more detailed picture of ANC utilization patterns in the seven countries. While coverage levels differ by country and sub-groups, all countries can benefit from specific in-country assessments to properly identify the underserved women and the reasons behind low coverage and missed interventions. Overall, emphasis needs to be put on assessing the quality of care offered and identifying women's perception to the care as well as the barriers hindering utilization. Country policies and programs need to be reviewed, evaluated and/or implemented properly to ensure that women receive the recommended number of ANC visits with appropriate content, especially, poor and less educated women residing in rural areas.

Background: An estimated 23 million infants are still not being benefitted from routine immunization services. We assessed how many children failed to be fully immunized even though they or their mothers were in contact with health services to receive other interventions., Design: Fourteen countries with Demographic and Health Surveys and Multiple Indicator Cluster Surveys carried out after 2000 and with coverage for DPT (Diphtheria-tetanus-pertussis) vaccine below 70% were selected. We defined full immunization coverage (FIC) as having received one dose of BCG (bacille Calmette-Guérin), one dose of measles, three doses of polio, and three doses of DPT vaccines. We tabulated FIC against: antenatal care (ANC), skilled birth attendance (SBA), postnatal care for the mother (PNC), vitamin A supplementation (VitA) for the child, and sleeping under an insecticide-treated bed-net (ITN). Missed opportunities were defined as the percentage of children who failed to be fully immunized among those receiving one or more other interventions., Results: Children who received other health interventions were also more likely to be fully immunized. In nearly all countries, FIC was lowest among children born to mothers who failed to attend ANC, and highest when the mother had four or more ANC visits Côte d'Ivoire presented the largest difference in FIC: 54 percentage points (pp) between having four or more ANC visits and lack of ANC. SBA was also related with higher FIC. For instance, the coverage in children without SBA was 36 pp lower than for those with SBA in Nigeria. The largest absolute difference on FIC in relation to PNC was observed for Ethiopia: 31 pp between those without and with PNC. FIC was also positively related with having received VitA. The largest absolute difference was observed in DR Congo: 41 pp. The differences in FIC among whether or not children slept under ITN were much smaller than for other interventions. Haiti presented the largest absolute difference: 16 pp., Conclusions: Our results show the need to develop and implement strategies to vaccinate all children who contact health services in order to receive other interventions.

Background: Contraception is one of the most important health interventions currently available and yet, many women and couples still do not have reliable access to modern contraceptives. The best indicator for monitoring family planning is the proportion of women using contraception among those who need it. This indicator is frequently called demand for family planning satisfied and we argue that it should be called family planning coverage (FPC). This indicator is complex to calculate and requires a considerable number of questions to be included in a household survey., Objectives: We propose a model that can predict FPC from a much simpler indicator - contraceptive use prevalence - for situations where it cannot be derived directly., Design: Using 197 Multiple Indicator Cluster Surveys and Demographic and Health Surveys from 82 countries, we explored least-squares regression models that could be used to predict FPC. Non-linearity was expected in this situation and we used a fractional polynomial approach to find the best fitting model. We also explored the effect of calendar time and of wealth on the models explored., Results: Given the high correlation between the variables involved in FPC, we managed to derive a relatively simple model that depends only on contraceptive use prevalence but explains 95% of the variability of the outcome, with high precision for the estimated regression line. We also show that the relationship between the two variables has not changed with time. A concordance analysis showed agreement between observed and fitted results within a range of ±9 percentage points., Conclusions: We show that it is possible to obtain fairly good estimates of FPC using only contraceptive prevalence as a predictor, a strategy that is useful in situations where it is not possible to estimate FPC directly.

Objective: Much is known about national trends in child undernutrition, but there is little information on how socio-economic inequalities are evolving over time. We aimed to assess socio-economic inequalities in stunting prevalence over time., Design: We selected nationally representative surveys carried out since the mid-1990s for which information was available on asset indices and on child anthropometry. We identified twenty-five countries that had at least two surveys over an interval of 10 years or more, totalling eighty-seven surveys. Stunting prevalence was calculated according to wealth quintiles. Absolute and relative inequalities were calculated and time trends were obtained by regression. Setting Nationally representative household surveys from twenty-five low- and middle-income countries., Subjects: Children <5 years of age., Results: National prevalence declined significantly in twenty-two of the twenty-five countries. In eighteen out of twenty-five countries, relative reductions were higher among the rich than among the poor. Overall, there was no indication that inequalities improved. Striking examples are Nepal, with a 17·0 percentage points decline in stunting per decade, but where inequalities increased sharply; and Brazil, where stunting fell by 6·7 percentage points and inequalities were all but eliminated., Conclusions: Global progress in reducing stunting has not been accompanied by improved equity, but countries varied markedly in how successful they were in reducing prevalence among the poorest children. It is important to document how some countries were able to reduce inequalities, so that these lessons can be used to foster global progress, particularly in light of the increased importance of within-country inequalities in the post-2015 agenda.

This study aimed to assess the prevalence of access to continuous prescription drugs for a group of chronic diseases and to investigate the existence of socioeconomic inequalities in access. The data are from the Brazilian National Demographic and Health Survey on Women and Children (2006), with a sample of 15,575 women 15 to 49 years of age. Among these women, 7,717 were diagnosed with a chronic disease that required acquiring medicine and were considered eligible for the study. The dependent variable was defined as the diagnosis of a chronic disease and the need to obtain medication for treatment. Multivariate analysis used Poisson regression. Higher access was associated with residence in a rural area, having one or two chronic diseases, and higher socioeconomic status. Prevalence of access to medication was high, but the analysis revealed socioeconomic inequality in access to medicines in favor of the wealthy, while identifying the most vulnerable groups as the poorest and those with more chronic diseases.

Objective: To expand the "Countdown to 2015" analyses of health inequalities beyond the 75 countries being monitored worldwide to include all countries in Latin America and the Caribbean (LAC) that have adequate data available., Methods: Demographic and Health Surveys and Multiple Indicator Cluster Surveys were used to monitor progress in health intervention coverage and inequalities in 13 LAC countries, five of which are included in the Countdown (Bolivia, Brazil, Guatemala, Haiti, and Peru) and eight that are not (Belize, Colombia, Costa Rica, Dominican Republic, Guyana, Honduras, Nicaragua, and Suriname). The outcomes included neonatal and under-5 year mortality rates, child stunting prevalence, and the composite coverage index-a weighted average of eight indicators of coverage in reproductive, maternal, newborn, and child health. The slope index of inequality and concentration index were used to assess absolute and relative inequalities., Results: The composite coverage index showed monotonic patterns over wealth quintiles, with lowest levels in the poorest quintile. Under-5 and neonatal mortality as well as stunting prevalence were highest among the poor. In most countries, intervention coverage increased, while under-5 mortality and stunting prevalence fell most rapidly among the poor, so that inequalities were reduced over time. However, Bolivia, Guatemala, Haiti, Nicaragua, and Peru still show marked inequalities. Brazil has practically eliminated inequalities in stunting., Conclusions: LAC countries presented substantial progress in terms of reducing inequalities in reproductive, maternal, newborn, and child health interventions, child mortality, and nutrition. However, the poorest 20% of the population in most countries is still lagging behind, and renewed actions are needed to improve equity.

Background: We examined the associations of maternal age with low birthweight (LBW) and preterm birth in four cohorts from a middle- and a high-income country, where the patterning of maternal age by socio-economic position (SEP) is likely to differ., Methods: Population-based birth cohort studies were carried out in the city of Pelotas, Brazil in 1982, 1993, and 2004, and in Avon, UK in 1991 [Avon Longitudinal Study of Parents and Children (ALSPAC)]. Adjustment for multiple indicators of SEP were applied., Results: Low SEP was associated with younger age at childbearing in all cohorts, but the magnitudes of these associations were stronger in ALSPAC. Inverse associations of SEP with LBW and preterm birth were observed in all cohorts. U-shaped associations were observed between maternal age and odds of LBW in all cohorts. After adjustment for SEP, increased odds of LBW for young mothers (<20 years) attenuated to the null but remained or increased for older mothers (≥ 35 years). Very young (<16 years) maternal age was also associated with both outcomes even after full SEP adjustment. SEP adjusted odds ratio of having a LBW infant in women <16 years and ≥ 35 years, compared with 25-29 years, were 1.48 [95% confidence interval (CI) 1.00, 2.20] and 1.66 [95% CI 1.36, 2.02], respectively. The corresponding results for preterm birth were 1.80 [95% CI 1.23, 2.64)] and 1.38 [95% CI 1.15, 1.67], respectively., Conclusion: Confounding by SEP explains much of the excess risk of LBW and preterm among babies born to teenage mothers as a whole, but not for mothers aged <16 or ≥ 35 years. Given that the proportion of women becoming pregnant at <16 years is smaller than for those ≥ 35 years, the population burden is greater for older age., (© 2014 The Authors. Paediatric and Perinatal Epidemiology Published by John Wiley & Sons Ltd.)

Liver cirrhosis in Mexico is one of the most important causes of death in persons between the ages of 25 and 50 years. One of the reasons for therapeutic failure is the lack of knowledge about the molecular mechanisms that cause liver disorder and make it irreversible. One of its prevalent anatomical characteristics is an excessive deposition of fibrous tissue that takes different forms depending on etiology and disease stage. Liver biopsy, traditionally regarded as the gold standard of fibrosis staging, has been brought into question over the past decade, resulting in the proposal for developing non-invasive technologies based on different, but complementary, approaches: a biological one that takes the serum levels of products arising from the fibrosis into account, and a more physical one that evaluates scarring of the liver by methods such as ultrasound and magnetic resonance elastography; some of the methods were originally studied and validated in patients with hepatitis C. There is great interest in determining non-invasive markers for the diagnosis of liver fibrosis, since at present there is no panel or parameter efficient and reliable enough for diagnostic use. In this paper, we describe the biomarkers that are currently being used for studying liver fibrosis in humans, their advantages and disadvantages, as well as the implementation of new-generation technologies and the evaluation of their possible use in the diagnosis of fibrosis., (Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

We performed a systematic literature review on the associations between birth size and abdominal adiposity in adults, while also investigating the role of the adjustment for adult body mass index (BMI). MEDLINE, Scopus, Web of Science, LILACS and SciELO databases were searched for articles published up to February 2013. Only prospective studies were included. After screening 2,570 titles, we selected 31 publications for the narrative synthesis, of which 13 were considered to be of high methodological quality. Six main indicators of birth size were identified, and birth weight (BW) was the most extensively studied. Most studies relied on anthropometric measurements as proxies for abdominal fatness or as indicators of body fat distribution. Few studies assessed abdominal adiposity through imaging methods, generally with small sample sizes. Eleven articles could be included in the meta-analyses. BW was found to be positively associated with waist circumference in adulthood, but the association disappeared after adjustment for adult BMI. In contrast, there was no association between BW and waist-to-hip ratio, whereas a strong negative association became evident after controlling for adult BMI. In conclusion, BW seems to be associated with larger adult size in general, including both waist and hip circumferences. The marked change in coefficients after adjustment for adult BMI suggests that post-natal growth strongly affects relative central adiposity, whereas BW per se does not play a role. Given the potential impact of post-natal growth, further research is needed to identify different growth trajectories that lead to abdominal adiposity, as well as studies on interactions of foetal and post-natal growth patterns., (© 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.)