Association between preterm-birth phenotypes and differential morbidity, growth, and neurodevelopment at age 2 years: Results from the INTERBIO-21st newborn study

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

An RNAi in silico approach to find an optimal shRNA cocktail against HIV-1

<p>Abstract</p> <p>Background</p> <p>HIV-1 can be inhibited by RNA interference <it>in vitro </it>through the expression of short hairpin RNAs (shRNAs) that target conserved genome sequences. <it>In silico </it>shRNA design for HIV has lacked a detailed study of virus variability constituting a possible breaking point in a clinical setting. We designed shRNAs against HIV-1 considering the variability observed in naïve and drug-resistant isolates available at public databases.</p> <p>Methods</p> <p>A Bioperl-based algorithm was developed to automatically scan multiple sequence alignments of HIV, while evaluating the possibility of identifying dominant and subdominant viral variants that could be used as efficient silencing molecules. Student t-test and Bonferroni Dunn correction test were used to assess statistical significance of our findings.</p> <p>Results</p> <p>Our <it>in silico </it>approach identified the most common viral variants within highly conserved genome regions, with a calculated free energy of ≥ -6.6 kcal/mol. This is crucial for strand loading to RISC complex and for a predicted silencing efficiency score, which could be used in combination for achieving over 90% silencing. Resistant and naïve isolate variability revealed that the most frequent shRNA per region targets a maximum of 85% of viral sequences. Adding more divergent sequences maintained this percentage. Specific sequence features that have been found to be related with higher silencing efficiency were hardly accomplished in conserved regions, even when lower entropy values correlated with better scores. We identified a conserved region among most HIV-1 genomes, which meets as many sequence features for efficient silencing.</p> <p>Conclusions</p> <p>HIV-1 variability is an obstacle to achieving absolute silencing using shRNAs designed against a consensus sequence, mainly because there are many functional viral variants. Our shRNA cocktail could be truly effective at silencing dominant and subdominant naïve viral variants. Additionally, resistant isolates might be targeted under specific antiretroviral selective pressure, but in both cases these should be tested exhaustively prior to clinical use.</p

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

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

Cuentos del Olivar

En este apasionante viaje tenemos las puertas abiertas para todo aquel que se quiera sumar, ya sea trabajando en pos de la difusión de la cultura ligada al olivo o disfrutando de lecturas como las que se recogen en este libro, que seguro les depara un sabroso disfrute y les descubre una cultura del olivar que tiene a sus espaldas varios milenios de historia. Les deseo que paladeen cada uno de estos relatos, que conforman un excelente aperitivo literario.Área de Historia del Art

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Childbearing during adolescence and offspring mortality: findings from three population-based cohorts in southern Brazil

Abstract Background The role of young maternal age as a determinant of adverse child health outcomes is controversial, with existing studies providing conflicting results. This work assessed the association between adolescent childbearing and early offspring mortality in three birth cohort studies from the city of Pelotas in Southern Brazil. Methods All hospital births from 1982 (6,011), 1993 (5,304), and 2004 (4,287) were identified and these infants were followed up. Deaths were monitored through vital registration, visits to hospitals and cemeteries. The analyses were restricted to women younger than 30 years who delivered singletons (72%, 70% and 67% of the original cohorts, respectively). Maternal age was categorized into three groups ( Results There were no interactions between maternal age and cohort year. After adjustment for confounding, pooled ORs for mothers aged 12-19 years were 0.6 (95% CI = 0.4; 1.0) for fetal death, 0.9 (0.6; 1.3) for perinatal death, 1.0 (0.7; 1.6) for early neonatal death, 1.6 (0.7; 3.4) for late neonatal death, 1.8 (1.1; 2.9) for postneonatal death, and 1.6 (1.2; 2.1) for infant death, when compared to mothers aged 20-29 years. Further adjustment for mediating variables led to the disappearance of the excess of postneonatal mortality. The number of mothers younger than 16 years was not sufficient for most analyses. Conclusion The slightly increased odds of postneonatal mortality among children of adolescent mothers suggest that social and environmental factors may be more important than maternal biologic immaturity.</p

Estimating family planning coverage from contraceptive prevalence using national household surveys

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