Publications by authors named "José Villar"

155 Publications

Fetal cranial growth trajectories are associated with growth and neurodevelopment at 2 years of age: INTERBIO-21st Fetal Study.

Nat Med 2021 Mar 18. Epub 2021 Mar 18.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.

Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections) and preventive interventions (for example, multiple-micronutrient supplementation) that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood. In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites worldwide, we studied the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks' gestation, against international standards, and growth and neurodevelopment up to 2 years of age. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-021-01280-2DOI Listing
March 2021

An Application of a Hybrid Intelligent System for Diagnosing Primary Headaches.

Int J Environ Res Public Health 2021 Feb 16;18(4). Epub 2021 Feb 16.

Faculty of Technical Sciences, University of Novi Sad, 21000 Novi Sad, Serbia.

(1) Background: Modern medicine generates a great deal of information that stored in medical databases. Simultaneously, extracting useful knowledge and making scientific decisions for diagnosis and treatment of diseases becomes increasingly necessary. Headache disorders are the most prevalent of all the neurological conditions. Headaches have not only medical but also great socioeconomic significance. The aim of this research is to develop an intelligent system for diagnosing primary headache disorders. (2) Methods: This research applied various mathematical, statistical and artificial intelligence techniques, among which the most important are: Calinski-Harabasz index, Analytical Hierarchy Process, and Weighted Fuzzy C-means Clustering Algorithm. These methods, techniques and methodologies are used to create a hybrid intelligent system for diagnosing primary headache disorders. The proposed intelligent diagnostic system is tested with original real-world data set with different metrics. (3) Results: First at all, nine of 20 attributes - features from International Headache Society (IHS) criteria are selected, and then only five most important attributes from IHS criteria are selected. The calculation result based on the Calinski-Harabasz index value (178) for the optimal number of clusters is three, and they present three classes of headaches: (i) migraine, (ii) tension-type headaches (TTHs), and (iii) other primary headaches (OPHs). The proposed hybrid intelligent system shows the following quality metrics: Accuracy 75%; Precision 67% for migraine, 74% for TTHs, 86% for OPHs, and Average Precision 77%; Recall 86% for migraine, 73% for TTHs, 67% for OPHs, Average Recall 75%; F score 75% for migraine, 74% for TTHs, 75% for OPHs, and Average F score 75%. (4) Conclusions: The hybrid intelligent system presents qualitative and respectable experimental results. The implementation of existing diagnostics systems and the development of new diagnostics systems in medicine is necessary in order to help physicians make quality diagnosis and decide the best treatments for the patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18041890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919804PMC
February 2021

Association Between Preterm-Birth Phenotypes and Differential Morbidity, Growth, and Neurodevelopment at Age 2 Years: Results From the INTERBIO-21st Newborn Study.

JAMA Pediatr 2021 Mar 1. Epub 2021 Mar 1.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2020.6087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922239PMC
March 2021

The γ-Benzylidene Digoxin Derivative BD-15 Increases the α3-Na, K-ATPase Activity in Rat Hippocampus and Prefrontal Cortex and no Change on Heart.

J Membr Biol 2021 Feb 18. Epub 2021 Feb 18.

Laboratório de Bioquímica Celular, Universidade Federal de São João Del Rei, Campus Centro-Oeste Dona Lindu, Av Sebastião Gonçalves Coelho, 400, Divinopolis, MG, Zip Code: 35501-296, Brazil.

Our study aimed to investigate the effects of the new cardiotonic steroid BD-15 (γ-benzylidene derivatives) in the behavioral parameters, oxidative stress and the Na, K-ATPase activity in the hippocampus, prefrontal cortex and heart from rats to verify the safety and possible utilization in brain disorders. For this study, groups of male Wistar rats were used after intraperitoneal injection of 20, 100 and 200 µg/Kg with BD-15. The groups were treated for three consecutive days and the control group received 0.9% saline. BD-15 did not alter behavior of rats treated with different doses. An increase in the specific α2,3-Na, K-ATPase activity was observed for all doses of BD-15 tested in the hippocampus. However, in the prefrontal cortex, only the dose of 100 µg/Kg increased the activity of all Na, K-ATPase isoforms. BD-15 did not cause alteration in the lipid peroxidation levels in the hippocampus, but in the prefrontal cortex, a decrease of lipid peroxidation (~ 25%) was observed. In the hippocampus, GSH levels increased with all doses tested, while in the prefrontal cortex no changes were found. Subsequently, when the effect of BD-15 on cardiac tissue was analyzed, no changes were observed in the tested parameters. BD-15 at a dosage of 100 µg/Kg proved to be promising because it is considered therapeutic for brain disorders, since it increases the activity of the α3-Na, K-ATPase in the hippocampus and prefrontal cortex, as well as decreasing the oxidative stress in these brain regions. In addition, this drug did not cause changes in the tissues of the heart and kidneys, preferentially demonstrating specificity for the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00232-021-00173-2DOI Listing
February 2021

International values for haemoglobin distributions in healthy pregnant women.

EClinicalMedicine 2020 Dec 2;29-30:100660. Epub 2020 Dec 2.

Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

Background: Anaemia in pregnancy is a global health problem with associated morbidity and mortality.

Methods: A secondary analysis of prospective, population-based study from 2009 to 2016 to generate maternal haemoglobin normative centiles in uncomplicated pregnancies in women receiving optimal antenatal care. Pregnant women were enrolled <14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21 Project which involved eight geographically diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, United Kingdom and United States. At each 5 ± 1 weekly visit until delivery, information was collected about the pregnancy, as well as the results of blood tests taken as part of routine antenatal care that complemented the study's requirements, including haemoglobin values.

Findings: A total of 3502 (81%) of 4321 women who delivered a live, singleton newborn with no visible congenital anomalies, contributed at least one haemoglobin value. Median haemoglobin concentrations ranged from 114.6 to 121.4 g/L, 94 to 103 g/L at the 3 centile, and from 135 to 141 g/L at the 97 centile. The lowest values were seen between 31 and 32 weeks' gestation, representing a mean drop of 6.8 g/L compared to 14 weeks' gestation. The percentage variation in maternal haemoglobin within-site was 47% of the total variance compared to 13% between sites.

Interpretation: We have generated International, gestational age-specific, smoothed centiles for maternal haemoglobin concentration compatible with better pregnancy outcomes, as well as adequate neonatal and early childhood morbidity, growth and development up to 2 years of age.

Funding: Bill & Melinda Gates Foundation Grant number 49038.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2020.100660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788439PMC
December 2020

The Food Bank of Madrid: A Linear Model for Optimal Nutrition.

Int J Environ Res Public Health 2020 Nov 3;17(21). Epub 2020 Nov 3.

INESC TEC-Institute for Systems and Computer Engineering, Technology and Science, 4200-465 Porto, Portugal.

This work proposes a mathematical linear programming model that addresses the food provisioning problem of the food bank of Madrid. It aims to determine the most appropriate weekly decisions to meet the macro-nutritional requirements of the beneficiaries of this social service, by minimizing the total cost considering third-party donations. The model has been applied to a realistic case study considering a sociological structure of beneficiaries categorized by age and gender and representing the first decile of incomes of the Spanish population. The demand of macronutrients is satisfied by means of nine different groups of food, used to provide some level of variability in the consumption patterns of the beneficiaries. The results provide insight on cost-cutting opportunities related to centralizing the decision-making process, indicating a 10% reduction both in provisioning costs and food quantities. This suggests that the proposed model might serve as a tool for designing new strategies for the provisioning or evaluation of economic and social support policies for the food bank of Madrid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17218097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663117PMC
November 2020

Impact of Individual Headache Types on the Work and Work Efficiency of Headache Sufferers.

Int J Environ Res Public Health 2020 09 22;17(18). Epub 2020 Sep 22.

Faculty of Technical Sciences, University of Novi Sad, 21000 Novi Sad, Serbia.

Headaches have not only medical but also great socioeconomic significance, therefore, it is necessary to evaluate the overall impact of headaches on a patient's life, including their work and work efficiency. The aim of this study was to determine the impact of individual headache types on work and work efficiency. : This research was designed as a cross-sectional study performed by administering a questionnaire among employees. The questionnaire consisted of general questions, questions about headache features, and questions about the impact of headaches on work. : Monthly absence from work was mostly represented by migraine sufferers (7.1%), significantly more than with sufferers with tension-type headaches (2.23%; = 0.019) and other headache types (2.15%; = 0.025). Migraine sufferers (30.2%) worked in spite of a headache for more than 25 h, which was more frequent than with sufferers from tension-type and other-type headaches (13.4%). On average, headache sufferers reported work efficiency ranging from 66% to 90%. With regard to individual headache types, this range was significantly more frequent in subjects with tension-type headaches, whereas 91-100% efficiency was significantly more frequent in subjects with other headache types. Lower efficiency, i.e., 0-40% and 41-65%, was significantly more frequent with migraine sufferers. : Headaches, especially migraines, significantly affect the work and work efficiency of headache sufferers by reducing their productivity. Loss is greater due to reduced efficiency than due to absenteeism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17186918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560060PMC
September 2020

Fetal growth velocity standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21 Project.

Am J Obstet Gynecol 2021 02 5;224(2):208.e1-208.e18. Epub 2020 Aug 5.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom; Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom.

Background: Human growth is susceptible to damage from insults, particularly during periods of rapid growth. Identifying those periods and the normative limits that are compatible with adequate growth and development are the first key steps toward preventing impaired growth.

Objective: This study aimed to construct international fetal growth velocity increment and conditional velocity standards from 14 to 40 weeks' gestation based on the same cohort that contributed to the INTERGROWTH-21 Fetal Growth Standards.

Study Design: This study was a prospective, longitudinal study of 4321 low-risk pregnancies from 8 geographically diverse populations in the INTERGROWTH-21 Project with rigorous standardization of all study procedures, equipment, and measurements that were performed by trained ultrasonographers. Gestational age was accurately determined clinically and confirmed by ultrasound measurement of crown-rump length at <14 weeks' gestation. Thereafter, the ultrasonographers, who were masked to the values, measured the fetal head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length in triplicate every 5 weeks (within 1 week either side) using identical ultrasound equipment at each site (4-7 scans per pregnancy). Velocity increments across a range of intervals between measures were modeled using fractional polynomial regression.

Results: Peak velocity was observed at a similar gestational age: 16 and 17 weeks' gestation for head circumference (12.2 mm/wk), and 16 weeks' gestation for abdominal circumference (11.8 mm/wk) and femur length (3.2 mm/wk). However, velocity growth slowed down rapidly for head circumference, biparietal diameter, occipitofrontal diameter, and femur length, with an almost linear reduction toward term that was more marked for femur length. Conversely, abdominal circumference velocity remained relatively steady throughout pregnancy. The change in velocity with gestational age was more evident for head circumference, biparietal diameter, occipitofrontal diameter, and femur length than for abdominal circumference when the change was expressed as a percentage of fetal size at 40 weeks' gestation. We have also shown how to obtain accurate conditional fetal velocity based on our previous methodological work.

Conclusion: The fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. Accordingly, we have produced international Fetal Growth Velocity Increment Standards to complement the INTERGROWTH-21 Fetal Growth Standards so as to monitor fetal well-being comprehensively worldwide. Fetal growth velocity curves may be valuable if one wants to study the pathophysiology of fetal growth. We provide an application that can be used easily in clinical practice to evaluate changes in fetal size as conditional velocity for a more refined assessment of fetal growth than is possible at present (https://lxiao5.shinyapps.io/fetal_growth/). The application is freely available with the other INTERGROWTH-21 tools at https://intergrowth21.tghn.org/standards-tools/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2020.07.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858163PMC
February 2021

Achieving accurate estimates of fetal gestational age and personalised predictions of fetal growth based on data from an international prospective cohort study: a population-based machine learning study.

Lancet Digit Health 2020 07 23;2(7):e368-e375. Epub 2020 Jun 23.

Department of Physics, University of Wisconsin, Milwaukee, WI, USA.

Background: Preterm birth is a major global health challenge, the leading cause of death in children under 5 years of age, and a key measure of a population's general health and nutritional status. Current clinical methods of estimating fetal gestational age are often inaccurate. For example, between 20 and 30 weeks of gestation, the width of the 95% prediction interval around the actual gestational age is estimated to be 18-36 days, even when the best ultrasound estimates are used. The aims of this study are to improve estimates of fetal gestational age and provide personalised predictions of future growth.

Methods: Using ultrasound-derived, fetal biometric data, we developed a machine learning approach to accurately estimate gestational age. The accuracy of the method is determined by reference to exactly known facts pertaining to each fetus-specifically, intervals between ultrasound visits-rather than the date of the mother's last menstrual period. The data stem from a sample of healthy, well-nourished participants in a large, multicentre, population-based study, the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). The generalisability of the algorithm is shown with data from a different and more heterogeneous population (INTERBIO-21st Fetal Study).

Findings: In the context of two large datasets, we estimated gestational age between 20 and 30 weeks of gestation with 95% confidence to within 3 days, using measurements made in a 10-week window spanning the second and third trimesters. Fetal gestational age can thus be estimated in the 20-30 weeks gestational age window with a prediction interval 3-5 times better than with any previous algorithm. This will enable improved management of individual pregnancies. 6-week forecasts of the growth trajectory for a given fetus are accurate to within 7 days. This will help identify at-risk fetuses more accurately than currently possible. At population level, the higher accuracy is expected to improve fetal growth charts and population health assessments.

Interpretation: Machine learning can circumvent long-standing limitations in determining fetal gestational age and future growth trajectory, without recourse to often inaccurately known information, such as the date of the mother's last menstrual period. Using this algorithm in clinical practice could facilitate the management of individual pregnancies and improve population-level health. Upon publication of this study, the algorithm for gestational age estimates will be provided for research purposes free of charge via a web portal.

Funding: Bill & Melinda Gates Foundation, Office of Science (US Department of Energy), US National Science Foundation, and National Institute for Health Research Oxford Biomedical Research Centre.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2589-7500(20)30131-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323599PMC
July 2020

INTERGROWTH-21st Project international INTER-NDA standards for child development at 2 years of age: an international prospective population-based study.

BMJ Open 2020 06 7;10(6):e035258. Epub 2020 Jun 7.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.

Objectives: To describe the construction of the international INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) standards for child development at 2 years by reporting the cognitive, language, motor and behaviour outcomes in optimally healthy and nourished children in the INTERGROWTH-21st Project.

Design: Population-based cohort study, the INTERGROWTH-21st Project.

Setting: Brazil, India, Italy, Kenya and the UK.

Participants: 1181 children prospectively recruited from early fetal life according to the prescriptive WHO approach, and confirmed to be at low risk of adverse perinatal and postnatal outcomes.

Primary Measures: Scaled INTER-NDA domain scores for cognition, language, fine and gross motor skills and behaviour; vision outcomes measured on the Cardiff tests; attentional problems and emotional reactivity measured on the respective subscales of the preschool Child Behaviour Checklist; and the age of acquisition of the WHO gross motor milestones.

Results: Scaled INTER-NDA domain scores are presented as centiles, which were constructed according to the prescriptive WHO approach and excluded children born preterm and those with significant postnatal/neurological morbidity. For all domains, except negative behaviour, higher scores reflect better outcomes and the threshold for normality was defined as ≥10th centile. For the INTER-NDA's cognitive, fine motor, gross motor, language and positive behaviour domains these are ≥38.5, ≥25.7, ≥51.7, ≥17.8 and ≥51.4, respectively. The threshold for normality for the INTER-NDA's negative behaviour domain is ≤50.0, that is, ≤90th centile. At 22-30 months of age, the cohort overlapped with the WHO motor milestone centiles, showed low postnatal morbidity (<10%), and vision outcomes, attentional problems and emotional reactivity scores within the respective normative ranges.

Conclusions: From this large, healthy and well-nourished, international cohort, we have constructed, using the WHO prescriptive methodology, international INTER-NDA standards for child development at 2 years of age. Standards, rather than references, are recommended for population-level screening and the identification of children at risk of adverse outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2019-035258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282399PMC
June 2020

Circular economy in plastic waste - Efficiency analysis of European countries.

Sci Total Environ 2020 Aug 1;730:139038. Epub 2020 May 1.

Centre for Power and Energy Systems, INESC TEC, Campus da FEUP, Rua Dr Roberto Frias, 4200-465 Porto, Portugal.

The way plastics are currently produced, used and disposed does not capture the economic benefits of a more 'circular' approach and is dramatically harming the environment. It is relevant to determine which European countries can be considered more or less efficient in the end-of-life of plastic products processes, what the sources of the inefficiencies are, and how those less efficient countries could improve their performance towards a more circular economy. Although some countries have developed a variety of quantitative indicators, there is scarcity of adequate metrics for performance measurements. This paper estimates the efficiency of 26 European countries in the context of Circular Economy, for the period 2006-2016, considering the generation of waste, recovery and recycling of plastic, with a methodology based on the Multidirectional Efficiency Analysis. Apart from identifying the most efficient countries in the studied period, results show that efficiency increases for most countries with time, and that many countries reach the full efficiency by the end of the study period, and especially by 2016. Input analysis shows that increasing capital seems to be a main driver towards efficiency, since the other inputs are used with a similar efficiency by most countries. Output analysis suggest that the difference among countries efficiency is not in their reduction of total waste or emissions, but rather in the improvement of their economic growth in a circular way, that is, improving GDP but also the recovering and recycling activities. These results could be useful to design policies towards a more efficient and circular use of plastics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.139038DOI Listing
August 2020

Hemicranial Cough-Induced Headache as a First Symptom of a Carotid-Cavernous Fistula-Case Report.

Medicina (Kaunas) 2020 Apr 23;56(4). Epub 2020 Apr 23.

Faculty of Technical Sciences, University of Novi Sad, TrgDositejaObradovića 6, 21000 Novi Sad, Serbia.

Spontaneous carotid-cavernous fistulas (CCFs) are rare, and they may be caused by an aneurysm rupture. A case of a man hospitalized for high-intensity hemicranial headache with sudden cough onset as part of an upper respiratory tract infection is presented. The pain was of a pulsating character, localized on the right, behind the eye, followed by nausea and vomiting. Neurological finding registered a wider rima oculi to the right and slight neck rigidity. Laboratory findings detected a mild leukocytosis with neutrophil predominance, while cytobiochemical findings of CSF and a computerized tomography (CT) scan of the endocranium were normal. Magnetic resonance imaging (MRI) angiography indicated the presence of a carotid cavernous fistula with a pseudoaneurysm to the right. Digital subtraction angiography (DSA) was performed to confirm the existence of the fistula. The planned artificial embolization was not performed because a complete occlusion of the fistula occurred during angiographic examination. Patient was discharged without subjective complaints and with normal neurological findings. Hemicranial cough-induced headache may be the first sign of carotid cavernous fistula, which was resolved by a spontaneous thrombosis in preparation for artificial embolization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/medicina56040194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230325PMC
April 2020

Late weaning and maternal closeness, associated with advanced motor and visual maturation, reinforce autonomy in healthy, 2-year-old children.

Sci Rep 2020 03 23;10(1):5251. Epub 2020 Mar 23.

Nuffield Department of Women's & Reproductive Health, University of Oxford and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.

We studied neurodevelopmental outcomes and behaviours in healthy 2-year old children (N = 1306) from Brazil, India, Italy, Kenya and the UK participating in the INTERGROWTH-21 Project. There was a positive independent relationship of duration of exclusive breastfeeding (EBF) and age at weaning with gross motor development, vision and autonomic physical activities, most evident if children were exclusively breastfed for ≥7 months or weaned at ≥7 months. There was no association with cognition, language or behaviour. Children exclusively breastfed from birth to <5 months or weaned at >6 months had, in a dose-effect pattern, adjusting for confounding factors, higher scores for "emotional reactivity". The positive effect of EBF and age at weaning on gross motor, running and climbing scores was strongest among children with the highest scores in maternal closeness proxy indicators. EBF, late weaning and maternal closeness, associated with advanced motor and vision maturation, independently influence autonomous behaviours in healthy children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-61917-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090084PMC
March 2020

The determinants for a circular economy in Europe.

Environ Sci Pollut Res Int 2020 Apr 30;27(11):12566-12578. Epub 2020 Jan 30.

GOVCOPP - Research Unit in Governance, Competitiveness and Public Policy, and DEGEIT - Department of Economics, Management, Industrial Engineering and Tourism, University of Aveiro, Aveiro, Portugal.

The circular economy contrasts with the traditional linear economy since it presents a sustainable way both to produce goods and services and to contribute to the development of economies. This paper aims to contribute to a better knowledge of the efficiency of resources productivity, a common indicator to compare how circular economies are, through the estimation of the main determinants for the circular economy in Europe. A systematic analysis and comparison of the performance of all the European Union countries was performed to get further insight into their root causes and to help designing future policies towards a more circular European Union economy. With this purpose, a set of determinant factors for a circular economy in Europe were analysed, under the period between 2000 and 2016. A cluster analysis was applied and complemented with three econometric estimation methods: panel unit root tests, panel cointegration tests and vector autoregression model. The main findings allowed to cluster European countries into three different groups according to the growth rate of their resources productivity and to explain them according to the selected exploratory factors. Special efforts were made to explain the highest productivity growth group, as a way to find relevant drivers towards sustainable productivity growths.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-07847-9DOI Listing
April 2020

Synthesis, antitrypanosomal and antimycobacterial activities of coumarinic N-acylhydrazonic derivatives.

Med Chem 2020 Jan 20. Epub 2020 Jan 20.

Instituto de Tecnologia em Fármacos - Farmanguinhos, Fundação Oswaldo Cruz, 21041-250 Rio de Janeiro, RJ. Brazil.

Background: Near to 5-7 million people are infected with T. cruzi in the world, and about 10,000 people per year die of problems associated to this disease.

Method: We reported herein the synthesis, antitrypanosomal and antimycobacterial activities of seventeen coumarinic N-acylhydrazonic derivatives.

Results: These compounds were synthesized using methodology with reactions global yields ranging from 46%-70%. T. cruzi in vitro effect were evaluated against trypomastigote and amastigote forms and M. tuberculosis activity were towards H37Rv sensitive strain and resistant strains.

Discussion: Against T. cruzi, the more active compounds revealed only moderate activity IC50/96h~20 µM for both trypomastigotes and amastigotes intracellular forms. (E)-2-oxo-N'-(3,4,5-trimethoxybenzylidene)-2H-chromene-3-carbohydrazide showed meaningful activity in INH resistant/RIP resistant strain.

Conclusion: These compound acting as multitarget could be good leads for the development of new trypanocidal and bactericidal agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1573406416666200121105215DOI Listing
January 2020

International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21 Project.

Am J Obstet Gynecol 2020 06 16;222(6):602.e1-602.e15. Epub 2020 Jan 16.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom; Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom. Electronic address:

Background: Reference values for umbilical artery Doppler indices are used clinically to assess fetal well-being. However, many studies that have produced reference charts have important methodologic limitations, and these result in significant heterogeneity of reported reference ranges.

Objectives: To produce international gestational age-specific centiles for umbilical artery Doppler indices based on longitudinal data and the same rigorous methodology used in the original Fetal Growth Longitudinal Study of the INTERGROWTH-21 Project.

Study Design: In Phase II of the INTERGROWTH-21 Project (the INTERBIO-21st Study), we prospectively continued enrolling pregnant women according to the same protocol from 3 of the original populations in Pelotas (Brazil), Nairobi (Kenya), and Oxford (United Kingdom) that had participated in the Fetal Growth Longitudinal Study. Women with a singleton pregnancy were recruited at <14 weeks' gestation, confirmed by ultrasound measurement of crown-rump length, and then underwent standardized ultrasound every 5±1 weeks until delivery. From 22 weeks of gestation umbilical artery indices (pulsatility index, resistance index, and systolic/diastolic ratio) were measured in a blinded fashion, using identical equipment and a rigorously standardized protocol. Newborn size at birth was assessed using the international INTERGROWTH-21 Standards, and infants had detailed assessment of growth, nutrition, morbidity, and motor development at 1 and 2 years of age. The appropriateness of pooling data from the 3 study sites was assessed using variance component analysis and standardized site differences. Umbilical artery indices were modeled as functions of the gestational age using an exponential, normal distribution with second-degree fractional polynomial smoothing; goodness of fit for the overall models was assessed.

Results: Of the women enrolled at the 3 sites, 1629 were eligible for this study; 431 (27%) met the entry criteria for the construction of normative centiles, similar to the proportion seen in the original fetal growth longitudinal study. They contributed a total of 1243 Doppler measures to the analysis; 74% had 3 measures or more. The healthy low-risk status of the population was confirmed by the low rates of preterm birth (4.9%) and preeclampsia (0.7%). There were no neonatal deaths and satisfactory growth, health, and motor development of the infants at 1 and 2 years of age were documented. Only a very small proportion (2.8%-6.5%) of the variance of Doppler indices was due to between-site differences; in addition, standardized site difference estimates were marginally outside this threshold in only 1 of 27 comparisons, and this supported the decision to pool data from the 3 study sites. All 3 Doppler indices decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age for each of the 3 indices are provided, as well as equations to allow calculation of any value as a centile and z scores. The mean pulsatility index according to gestational age = 1.02944 + 77.7456*(gestational age) - 0.000004455*gestational age.

Conclusion: We present here international gestational age-specific normative centiles for umbilical artery Doppler indices produced by studying healthy, low-risk pregnant women living in environments with minimal constraints on fetal growth. The centiles complement the existing INTERGROWTH-21 Standards for assessment of fetal well-being.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2020.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287403PMC
June 2020

21-Benzylidene digoxin decreases proliferation by inhibiting the EGFR/ERK signaling pathway and induces apoptosis in HeLa cells.

Steroids 2020 03 6;155:108551. Epub 2019 Dec 6.

Laboratório de Bioquímica Celular, Universidade Federal de São João del-Rei (UFSJ) Campus Centro-Oeste Dona Lindu, Divinópolis, MG, Brazil. Electronic address:

Cardiotonic steroids (CTS) are agents traditionally known for their capacity to bind to the Na,K-ATPase (NKA), affecting the ion transport and the contraction of the heart. Natural CTS have been shown to also have effects on cell signaling pathways. With the goal of developing a new CTS derivative, we synthesized a new digoxin derivative, 21-benzylidene digoxin (21-BD). Previously, we have shown that this compound binds to NKA and has cytotoxic actions on cancer, but not on normal cells. Here, we further studied the mechanisms of actions of 21-BD. Working with HeLa cells, we found that 21-BD decreases the basal, as well as the insulin stimulated proliferation. 21-BD reduces phosphorylation of the epidermal growth factor receptor (EGFR) and extracellular-regulated kinase (ERK), which are involved in pathways that stimulate cell proliferation. In addition, 21-BD promotes apoptosis, which is mediated by the translocation of Bax from the cytosol to mitochondria and the release of mitochondrial cytochrome c to the cytosol. 21-BD also activated caspases-8, -9 and -3, and induced the cleavage of poly (ADP-ribose) polymerase-1 (PARP-1). Altogether, these results show that the new compound that we have synthesized exerts cytotoxic actions on HeLa cells by inhibition of cell proliferation and the activation of both the extrinsic and intrinsic apoptotic pathways. These results support the relevance of the cardiotonic steroid scaffold as modulators of cell signaling pathways and potential agents for their use in cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2019.108551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028499PMC
March 2020

Synthesis and Biological Activity of Hydrazones and Derivatives: A Review.

Mini Rev Med Chem 2020 ;20(5):342-368

Medicinal Chemistry Group, Department of Chemistry, Military Institute of Engineering, Praca General Tiburcio 80, 22290-270, Rio de Janeiro, RJ, Brazil.

Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer's, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes. Our goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution to the development of potential new drugs for the treatment of various diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389557519666191014142448DOI Listing
November 2020

Pharmacologic potential of new nitro-compounds as antimicrobial agents against nosocomial pathogens: design, synthesis, and in vitro effectiveness.

Folia Microbiol (Praha) 2020 Apr 10;65(2):393-405. Epub 2019 Aug 10.

Laboratório de Microbiologia Médica, Universidade Federal de São João del-Rei (UFSJ), Campus Centro Oeste Dona Lindu/Universidade Federal de São João Del-Rei. Rua Sebastião Gonçalves Coelho, 400, Chanadour, Divinópolis, Minas Gerais, 35501-293, Brazil.

Nosocomial infections are an important cause of morbi-mortality worldwide. The increase in the rate of resistance to conventional drugs in these microorganisms has stimulated the search for new therapeutic options. The nitro moiety (NO) is an important pharmacophore of molecules with high anti-infective activity. We aimed to synthesize new nitro-derivates and to evaluate their antibacterial and anti-Candida potential in vitro. Five compounds [3-nitro-2-phenylchroman-4-ol (3); 3-nitro-2-phenyl-2H-chromene (4a); 3-nitro-2-(4-chlorophenyl)-2H-chromene (4b); 3-nitro-2-(4-fluorophenyl)-2H-chromene (4c), and 3-Nitro-2-(2,3-dichlorophenyl)-2H-chromene (4d)] were efficiently synthesized by Michael-aldol reaction of 2-hydroxybenzaldehyde with nitrostyrene, resulting in one β-nitro-alcohol (3) and four nitro-olefins (4a-4d). The antibacterial and anti-Candida potentials were evaluated by assaying minimal inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC). Mono-halogenated nitro-compounds (4b and 4c) showed anti-staphylococcal activity with MIC values of 15.6-62.5 μg/mL and MBC of 62.5 μg/mL. However, the activity against Gram-negative strains was showed to be considerably lower and our data suggests that this effect was associated with the outer membrane. Furthermore, nitro-compounds 4c and 4d presented activity against Candida spp. with MIC values ranging from 7.8-31.25 μg/mL and MFC of 15.6-500 μg/mL. In addition, these compounds were able to induce damage in fungal cells increasing the release of intracellular material, which was associated with actions on the cell wall independent of quantitative changes in chitin and β-glucan. Together, these findings show that nitro-compounds can be exploited as anti-staphylococcal and anti-Candida prototypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12223-019-00747-7DOI Listing
April 2020

Evaluation of neuroprotective activity of digoxin and semisynthetic derivatives against partial chemical ischemia.

J Cell Biochem 2019 10 16;120(10):17108-17122. Epub 2019 Jul 16.

Laboratório de Bioquímica Celular, Universidade Federal de São João del Rei, Divinópolis, Minas Gerais, Brazil.

Recently, cardiotonic steroids (CTS) have been shown to lead to the activation of Na,K-ATPase at low concentrations in brain, promoting neuroprotection against ischemia. We report here the results of the use of digoxin and its semisynthetic derivatives BD-14, BD-15, and BD-16 against partial chemical ischemic induction followed by reperfusion in murine neuroblastoma cells neuro-2a (N2a). For chemical ischemic induction, sodium azide (5 mM) was used for 5 hours, and then reperfusion was induced for 24 hours. Na,K-ATPase activity and protein levels were analyzed in membrane preparation of N2a cells pretreated with the compounds (150 nM), in the controls and in induced chemical ischemia. In the Na,K-ATPase activity and protein levels assays, the steroids digoxin and BD-15 demonstrated a capacity to modulate the activity of the enzyme directly, increasing its levels of expression and activity. Oxidative parameters, such as superoxide dismutase (SOD) activity, lipid peroxidation (thiobarbituric acid reactive substance), glutathione peroxidase (GPx), glutathione (GSH) levels, hydrogen peroxide content, and the amount of free radicals (reactive oxygen species) during induced chemical ischemia were also evaluated. Regarding the redox state, lipid peroxidation, hydrogen peroxide content, and GPx activity, we have observed an increase in the chemical ischemic group, and a reduction in the groups treated with CTS. SOD activity increased in all treated groups when compared to control and GSH levels decreased when treated with sodium azide and did not change with CTS treatments. Regarding the lipid profile, we saw a decrease in the content of phospholipids and cholesterol in the chemical ischemic group, and an increase in the groups treated with CTS. In conclusion, the compounds used in this study demonstrate promising results, since they appear to promote neuroprotection in cells exposed to chemical ischemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28971DOI Listing
October 2019

Deep clinical and biological phenotyping of the preterm birth and small for gestational age syndromes: The INTERBIO-21 Newborn Case-Control Study protocol.

Gates Open Res 2018 5;2:49. Epub 2019 Feb 5.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.

INTERBIO-21 is Phase II of the INTERGROWTH-21 Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. In the INTERBIO-21 Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/gatesopenres.12869.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545521PMC
February 2019

Neurodevelopmental milestones and associated behaviours are similar among healthy children across diverse geographical locations.

Nat Commun 2019 01 30;10(1):511. Epub 2019 Jan 30.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, OX3 9DU, UK.

It is unclear whether early child development is, like skeletal growth, similar across diverse regions with adequate health and nutrition. We prospectively assessed 1307 healthy, well-nourished 2-year-old children of educated mothers, enrolled in early pregnancy from urban areas without major socioeconomic or environmental constraints, in Brazil, India, Italy, Kenya and UK. We used a specially developed psychometric tool, WHO motor milestones and visual tests. Similarities across sites were measured using variance components analysis and standardised site differences (SSD). In 14 of the 16 domains, the percentage of total variance explained by between-site differences ranged from 1.3% (cognitive score) to 9.2% (behaviour score). Of the 80 SSD comparisons, only six were >±0.50 units of the pooled SD for the corresponding item. The sequence and timing of attainment of neurodevelopmental milestones and associated behaviours in early childhood are, therefore, likely innate and universal, as long as nutritional and health needs are met.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-07983-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353986PMC
January 2019

Social gradient of birthweight in England assessed using the INTERGROWTH-21 gestational age-specific standard.

Arch Dis Child Fetal Neonatal Ed 2019 Sep 21;104(5):F486-F492. Epub 2018 Nov 21.

Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

Objective: To determine the socioeconomic gradient of birthweights in England with reference to the prescriptive INTERGROWTH-21 Birthweight Standard.

Design: National cross-sectional study using data from Hospital Episode Statistics.

Setting: National Health Service in England.

Participants: All singleton babies, live born between 34 weeks' gestation and 42 weeks' gestation, between 1 April 2011 and 31 March 2012.

Main Outcome Measures: Birthweight distribution of babies with a birthweight of <10th centile or >90th centile, that is, small for gestational age (SGA) or large for gestational age (LGA) using Index of Multiple Deprivation quintiles as a proxy for socioeconomic status.

Results: Of 508 230 babies born alive between 1 April 2011 and 31 March 2012, 38 838 (7.6%) were SGA and 81 026 (15.9%) were LGA. Median birthweight was 3405 g, median z-score was 0.25 (SD 1.06). Birthweight z-score demonstrated a social gradient, from 0.26 (SD 1.1) in the most deprived areas to 0.53 (1.0) in the least deprived. Women in the most deprived areas were twice as likely to have SGA babies using the INTERGROWTH-21 chart (OR 1.94; 95% CI 1.87 to 2.01) compared with those in the least deprived areas. If all women had the same rate of SGA equivalent to those living in the least deprived areas, approximately 12 410 (30%) fewer babies would be born SGA in England each year.

Conclusions: This study gives a measure of the social gradient in singleton SGA and LGA babies across England using an international standard of newborn size at birth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2018-315295DOI Listing
September 2019

21‑Benzylidene digoxin, a novel digoxin hemi-synthetic derivative, presents an anti-inflammatory activity through inhibition of edema, tumour necrosis factor alpha production, inducible nitric oxide synthase expression and leucocyte migration.

Int Immunopharmacol 2018 Dec 10;65:174-181. Epub 2018 Oct 10.

Pharmacology of Pain and Inflammation Laboratory, Federal University of São João del-Rei, Divinópolis, Brazil. Electronic address:

Recent findings have demonstrated new therapeutic functions of cardiotonic steroids, a process that is termed drug repositioning. Despite the confirmed anti-inflammatory effects of cardiotonic steroids, their clinical use has been discouraged due to toxicity related to inhibition of the Na/K ATPase. A novel synthetic compound derived from digoxin, 21‑benzylidene digoxin (21‑BD), does not inhibit this enzyme. Herein, we evaluated the anti-inflammatory and antinociceptive effects and acute toxicity of 21‑BD. Murine (Swiss mice) models of paw oedema induced by carrageenan, acetic acid-induced abdominal writhing, and formalin and acute toxicity tests were used. Oral administration of 21‑BD (0.3 mg/kg) showed a significant and prolonged inhibition of paw oedema. Histological analysis demonstrated a reduction in inflammatory cells and expression of inducible nitric oxide synthase (iNOS) in footpads 6 h after administration of carrageenan. 21‑BD (0.3 mg/kg) also reduced the levels of tumour necrosis factor (TNF)-α 2 and 4 h after carrageenan. 21‑BD demonstrated antinociceptive activity, inhibiting abdominal writhes at all tested doses. However, in the formalin test, 21‑BD did not present antinociceptive activity. In the acute toxicity test, 21‑BD did not cause symptoms of toxicity or mortality. The present study demonstrated, for the first time, that 21‑BD is safe and exhibits a marked anti-inflammatory activity in acute local inflammation. This effect might be a consequence of its ability to inhibit the release of the PMN leucocyte-derived mediators, including TNF-α, and iNOS expression as well as its inhibitory effect on oedema and PMN leucocyte infiltration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2018.10.010DOI Listing
December 2018

Caesarean sections and the prevalence of preterm and early-term births in Brazil: secondary analyses of national birth registration.

BMJ Open 2018 08 5;8(8):e021538. Epub 2018 Aug 5.

Post Graduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil.

Objectives: To investigate whether the high rates of caesarean sections (CSs) in Brazil have impacted on the prevalence of preterm and early-term births.

Design: Individual-level, cross-sectional analyses of a national database.

Setting: All hospital births occurring in the country in 2015.

Participants: 2 903 716 hospital-delivered singletons in 3157 municipalities, representing >96% of the country's births.

Primary And Secondary Outcome Measures: CS rates and gestational age distribution (<37, 37-38, 39-41 and 42 or more weeks' gestation). Outcomes were analysed according to maternal education, measured in years of schooling and municipal CS rates. Analyses were also adjusted for maternal age, marital status and parity.

Results: Prevalence of CS was 55.5%, preterm prevalence (<37 weeks' gestation) was 10.1% and early-term births (37-38 weeks of gestation) represented 29.8% of all births, ranging from 24.9% among women with <4 years of schooling to 39.8% among those with >12 years of education. The adjusted prevalence ratios of preterm and early-term birth were, respectively, 1.215 (1.174-1.257) and 1.643 (1.616-1.671) higher in municipalities with≥80% CS compared with those <30%.

Conclusions: Brazil faces three inter-related epidemics: a CS epidemic; an epidemic of early-term births, associated with the high CS rates; and an epidemic of preterm birth, also associated with CS but mostly linked to poverty-related risk factors. The high rates of preterm and early-term births produce an excess of newborns at higher risk of short-term morbidity and mortality, as well as long-term developmental problems. Compared with high-income countries, there is an annual excess of 354 000 preterm and early-term births in Brazil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-021538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078248PMC
August 2018

Synthesis and Evaluation of the in vitro Antimicrobial Activity of Triazoles, Morpholines and Thiosemicarbazones.

Med Chem 2019 ;15(1):38-50

Laboratorio de Sintese Organica e Nanoestruturas, Universidade Federal de Sao Joao del-Rei, Campus Centro-Oeste Dona Lindu, Divinopolis, 35501-296, Brazil.

Background: Microbial infections is a global public health problem. The aim of this work was to synthesize and evaluate the antimicrobial activity of novel triazoles, morpholines and thiosemicarbazones.

Methods: Compounds were synthesized using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. The antimicrobial activity of these compounds against bacteria and yeast was evaluated by the broth microdilution method.

Results: The proposed route for synthesis gave high to moderate yields, moreover these compounds were successfully characterized by 1H NMR, 13C NMR and LC-MS. Antimicrobial testing indicated that the thiosemicarbazone and morphine derivatives had the best antimicrobial activity against the microorganisms tested with minimum inhibitory concentrations (MIC) between 0.29 and 5.30 µM. Thiosemicarbazone derivative (12) was able to inhibit the growth of C. tropicalis, with minimum fungicidal concentration (MFC) of 0.55 µM. In addition, this compound was active against E. coli, S. aureus and S. epidermidis, with MIC values ranging from 0.29 to 1.11 µM. Moreover, the morpholine derivative (15) had an MIC value of 0.83 µM against C. albicans and E. coli.

Conclusion: We have efficiently synthesized a series of eleven novel triazoles, thiosemicarbazones and morpholine derivatives using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. Thiosemicarbazone derivative (12) showed promising antifungal and antibacterial activity and these findings suggest that this compound can be used as scaffolds to design new antimicrobial drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1573406414666180730111954DOI Listing
February 2019

Growth of preterm infants at the time of global obesity.

Arch Dis Child 2019 08 21;104(8):725-727. Epub 2018 Jul 21.

Nuffield Department of Women's & Reproductive Health and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2018-315006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662948PMC
August 2019

INTERGROWTH-21st Gestational Dating and Fetal and Newborn Growth Standards in Peri-Urban Nairobi, Kenya: Quasi-Experimental Implementation Study Protocol.

JMIR Res Protoc 2018 Jun 22;7(6):e10293. Epub 2018 Jun 22.

Women and Health Initiative, Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States.

Background: The burden of preterm birth, fetal growth impairment, and associated neonatal deaths disproportionately falls on low- and middle-income countries where modern obstetric tools are not available to date pregnancies and monitor fetal growth accurately. The INTERGROWTH-21 gestational dating, fetal growth monitoring, and newborn size at birth standards make this possible.

Objective: To scale up the INTERGROWTH-21 standards, it is essential to assess the feasibility and acceptability of their implementation and their effect on clinical decision-making in a low-resource clinical setting.

Methods: This study protocol describes a pre-post, quasi-experimental implementation study of the standards at Jacaranda Health, a maternity hospital in peri-urban Nairobi, Kenya. All women with viable fetuses receiving antenatal and delivery services, their resulting newborns, and the clinicians caring for them from March 2016 to March 2018 are included. The study comprises a 12-month preimplementation phase, a 12-month implementation phase, and a 5-month post-implementation phase to be completed in August 2018. Quantitative clinical and qualitative data collected during the preimplementation and implementation phases will be assessed. A clinician survey was administered eight months into the implementation phase, month 20 of the study. Implementation outcomes include quantitative and qualitative analyses of feasibility, acceptability, adoption, appropriateness, fidelity, and penetration of the standards. Clinical outcomes include appropriateness of referral and effect of the standards on clinical care and decision-making. Descriptive analyses will be conducted, and comparisons will be made between pre- and postimplementation outcomes. Qualitative data will be analyzed using thematic coding and compared across time. The study was approved by the Amref Ethics and Scientific Review Committee (Kenya) and the Harvard University Institutional Review Board. Study results will be shared with stakeholders through conferences, seminars, publications, and knowledge management platforms.

Results: From October 2016 to February 2017, over 90% of all full-time Jacaranda clinicians (26/28) received at least one of the three aspects of the INTERGROWTH-21 training: gestational dating ultrasound, fetal growth monitoring ultrasound, and neonatal anthropometry standards. Following the training, implementation and evaluation of the standards in Jacaranda Health's clinical workflow will take place from March 2017 through March 5, 2018. Data analysis will be finalized, and results will be shared by August 2018.

Conclusions: The findings of this study will have major implications on the national and global scale up of the INTERGROWTH-21 standards and on the process of scaling up global standards in general, particularly in limited-resource settings.

Registered Report Identifier: RR1-10.2196/10293.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/10293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035346PMC
June 2018

Clarification of INTERGROWTH-21st newborn birthweight standards - Authors' reply.

Lancet 2018 05 17;391(10134):1996. Epub 2018 May 17.

Nuffield Department of Women's & Reproductive Health and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford OX2 6HG, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(18)31067-5DOI Listing
May 2018

New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations.

Chem Biol Drug Des 2018 09 13;92(3):1670-1682. Epub 2018 Jun 13.

Departamento de Sintese de Farmacos, Instituto de Tecnologia em Farmacos, Farmanguinhos - Fiocruz, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil.

Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cbdd.13333DOI Listing
September 2018