Defining and estimating effects in cluster randomized trials: A methods comparison.

Across research disciplines, cluster randomized trials (CRTs) are commonly implemented to evaluate interventions delivered to groups of participants, such as communities and clinics. Despite advances in the design and analysis of CRTs, several challenges remain. First, there are many possible ways to specify the causal effect of interest (eg, at the individual-level or at the cluster-level). Second, the theoretical and practical performance of common methods for CRT analysis remain poorly understood. Here, we present a general framework to formally define an array of causal effects in terms of summary measures of counterfactual outcomes. Next, we provide a comprehensive overview of CRT estimators, including the t-test, generalized estimating equations (GEE), augmented-GEE, and targeted maximum likelihood estimation (TMLE). Using finite sample simulations, we illustrate the practical performance of these estimators for different causal effects and when, as commonly occurs, there are limited numbers of clusters of different sizes. Finally, our application to data from the Preterm Birth Initiative (PTBi) study demonstrates the real-world impact of varying cluster sizes and targeting effects at the cluster-level or at the individual-level. Specifically, the relative effect of the PTBi intervention was 0.81 at the cluster-level, corresponding to a 19% reduction in outcome incidence, and was 0.66 at the individual-level, corresponding to a 34% reduction in outcome risk. Given its flexibility to estimate a variety of user-specified effects and ability to adaptively adjust for covariates for precision gains while maintaining Type-I error control, we conclude TMLE is a promising tool for CRT analysis.

Adapting the preterm birth phenotyping framework to a low-resource, rural setting and applying it to births from Migori County in western Kenya.

BACKGROUND: Preterm birth is the leading cause of neonatal and under-five mortality worldwide. It is a complex syndrome characterized by numerous etiologic pathways shaped by both maternal and fetal factors. To better understand preterm birth trends, the Global Alliance to Prevent Prematurity and Stillbirth published the preterm birth phenotyping framework in 2012 followed by an application of the model to a global dataset in 2015 by Barros, et al. Our objective was to adapt the preterm birth phenotyping framework to retrospective data from a low-resource, rural setting and then apply the adapted framework to a cohort of women from Migori, Kenya. METHODS: This was a single centre, observational, retrospective chart review of eligible births from November 2015 - March 2017 at Migori County Referral Hospital. Adaptations were made to accommodate limited diagnostic capabilities and data accuracy concerns. Prevalence of the phenotyping conditions were calculated as well as odds of adverse outcomes. RESULTS: Three hundred eighty-seven eligible births were included in our study. The largest phenotype group was none (no phenotype could be identified; 41.1%), followed by extrauterine infection (25.1%), and antepartum stillbirth (16.7%). Extrauterine infections included HIV (75.3%), urinary tract infections (24.7%), malaria (4.1%), syphilis (3.1%), and general infection (3.1%). Severe maternal condition was ranked fourth (15.6%) and included anaemia (69.5%), chronic respiratory distress (22.0%), chronic hypertension prior to pregnancy (5.1%), diabetes (3.4%), epilepsy (3.4%), and sickle cell disease (1.7%). Fetal anaemia cases were the most likely to transfer to the newborn unit (OR 5.1, 95% CI 0.8, 30.9) and fetal anomaly cases were the most likely to result in a pre-discharge mortality (OR 3.9, 95% CI 0.8, 19.2). CONCLUSIONS: Using routine data sources allowed for a retrospective analysis of an existing dataset, requiring less time and fewer resources than a prospective study and demonstrating a feasible approach to preterm phenotyping for use in low-resource settings to inform local prevention strategies.

Preterm birth is a complex syndrome, yet it is the leading cause of death in children worldwide. To help unravel the clinical complexities, preterm birth phenotyping is a framework that considers multiple diagnoses in the mother, helping to evaluate trends in causes of preterm birth in a given region. In our study, we adapted this international phenotyping framework to accommodate a rural, low-resource setting where obstetrical and neonatal technologies were limited, but preterm birth rates were high. We evaluated data from the patient records of a large hospital in Migori, Kenya, in the southwestern region of the country. By lowering the threshold of diagnostic criteria, we were able to apply this framework to our dataset and see that maternal infection and maternal chronic illness appear to be a significant driving forces of preterm birth. Given high rates of HIV and malaria in the region, this is not a surprising finding, but one that can inform antenatal care practices, mainly the need to test and treat for common infections (HIV, malaria, as well as urinary and reproductive tract infections), and to increase the frequency of antenatal care interactions per the World Health Organization recommendations.

Implementing the WHO Safe Childbirth Checklist modified for preterm birth: lessons learned and experiences from Kenya and Uganda.

BACKGROUND: The WHO Safe Childbirth Checklist (SCC) contains 29 evidence-based practices (EBPs) across four pause points spanning admission to discharge. It has been shown to increase EBP uptake and has been tailored to specific contexts. However, little research has been conducted in East Africa on use of the SCC to improve intrapartum care, particularly for preterm birth despite its burden. We describe checklist adaptation, user acceptability, implementation and lessons learned. METHODS: The East Africa Preterm Birth Initiative (PTBi EA) modified the SCC for use in 23 facilities in Western Kenya and Eastern Uganda as part of a cluster randomized controlled trial evaluating a package of facility-based interventions to improve preterm birth outcomes. The modified SCC (mSCC) for prematurity included: addition of a triage pause point before admission; focus on gestational age assessment, identification and management of preterm labour; and alignment with national guidelines. Following introduction, implementation lasted 24 and 34 months in Uganda and Kenya respectively and was supported through complementary mentoring and data strengthening at all sites. PRONTO® simulation training and quality improvement (QI) activities further supported mSCC use at intervention facilities only. A mixed methods approach, including checklist monitoring, provider surveys and in-depth interviews, was used in this analysis. RESULTS: A total of 19,443 and 2229 checklists were assessed in Kenya and Uganda, respectively. In both countries, triage and admission pause points had the highest rates of completion. Kenya's completion was greater than 70% for all pause points; Uganda ranged from 39 to 75%. Intervention facilities exposed to PRONTO and QI had higher completion rates than control sites. Provider perceptions cited clinical utility of the checklist, particularly when integrated into patient charts. However, some felt it repeated information in other documentation tools. Completion was hindered by workload and staffing issues. CONCLUSION: This study highlights the feasibility and importance of adaptation, iterative modification and complementary activities to reinforce SCC use. There are important opportunities to improve its clinical utility by the addition of prompts specific to the needs of different contexts. The trial assessing the PTBi EA intervention package was registered at ClinicalTrials.gov NCT03112018 Registered December 2016, retrospectively registered.

Sealing of cavitated occlusal carious lesions in the dentine of deciduous molars: a two-year randomised controlled clinical trial.

OBJECTIVES: This two-arm, parallel-group, tooth-randomised, controlled noninferiority clinical trial aimed to compare survival rates between the sealing and restoring of cavitated occlusal carious lesions in dentine [International Caries Detection and Assessment System (ICDAS) 5] of deciduous molars using resin-modified glass-ionomer cement (RMGIC) and to assess caries progression radiographically. MATERIALS AND METHODS: A total of 68 molars with ICDAS 5 occlusal lesions were randomly allocated into two groups, a sealing group (n = 31), in which RMGIC was placed directly over the carious lesion, and a restoration group (n = 37), in which a restoration with the same material was placed after selective caries removal. During the baseline and follow-up visits, dental caries was registered and caries activity was assessed according to a visuotactile criterion. At baseline, patient caries status (dmf-t) and cavity depth and extent (mesiodistal and buccolingual) were measured before RMGIC placement. An independent and blinded examiner evaluated the treated teeth using the USPHS criteria after one and two years. Standardised interproximal radiographs were taken for caries progression assessments. RESULTS: During the follow-up period, no lesion progression was observed radiographically. After one year (n = 60; 27 sealed and 33 restored) and two years (n = 48; 23 sealed and 25 restored) of follow-up, the treatment success rates were 78.8% and 76.0% in the restoration group and 59.3% and 47.8% in the sealing group, respectively. Multivariate Cox regression showed that lesions smaller than 2 mm in the mesiodistal extent were less prone to fail after one year (p = 0.03). However, survival curves (log-rank test) were statistically significantly different only after two years (p < 0.001). CONCLUSIONS: Sealing ICDAS 5 occlusal lesions of deciduous molars using RMGIC achieved lower survival rates than restorations. Both sealing and restoration effectively arrested caries progression for two years. Clinical relevance Sealing dentine carious lesions can be effective for treating lesions involving the inner and outer half of the dentine. Ultraconservative treatments can arrest carious lesions presenting obvious cavitation in primary molars. TRIAL REGISTRATION: ReBEC Register no. RBR-225n35.

Evolution of lbx spinal cord expression and function.

Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals. Amniotes have two Lbx genes, but only Lbx1 is expressed in spinal cord. In contrast, teleosts have three lbx genes and we show here that zebrafish lbx1a, lbx1b, and lbx2 are expressed by distinct spinal cell types, and that lbx1a is expressed in dI4, dI5, and dI6 interneurons, as in amniotes. Our data examining lbx expression in Scyliorhinus canicula and Xenopus tropicalis suggest that the spinal interneuron expression of zebrafish lbx1a is ancestral, whereas lbx1b has acquired a new expression pattern in spinal cord progenitor cells. lbx2 spinal expression was probably acquired in the ray-finned lineage, as this gene is not expressed in the spinal cords of either amniotes or S. canicula. We also show that the spinal function of zebrafish lbx1a is conserved with mouse Lbx1. In zebrafish lbx1a mutants, there is a reduction in the number of inhibitory spinal interneurons and an increase in the number of excitatory spinal interneurons, similar to mouse Lbx1 mutants. Interestingly, the number of inhibitory spinal interneurons is also reduced in lbx1b mutants, although in this case the number of excitatory interneurons is not increased. lbx1a;lbx1b double mutants have a similar spinal interneuron phenotype to lbx1a single mutants. Taken together these data suggest that lbx1b and lbx1a may be required in succession for correct specification of dI4 and dI6 spinal interneurons, although only lbx1a is required for suppression of excitatory fates in these cells.

The network structure of core depressive symptom-domains in major depressive disorder following antidepressant treatment: a randomized clinical trial.

BACKGROUND: Network analysis (NA) conceptualizes psychiatric disorders as complex dynamic systems of mutually interacting symptoms. Major depressive disorder (MDD) is a heterogeneous clinical condition, and very few studies to date have assessed putative changes in its psychopathological network structure in response to antidepressant (AD) treatment. METHODS: In this randomized trial with adult depressed outpatients (n = 151), we estimated Gaussian graphical models among nine core MDD symptom-domains before and after 8 weeks of treatment with either escitalopram or desvenlafaxine. Networks were examined with the measures of cross-sectional and longitudinal structure and connectivity, centrality and predictability as well as stability and accuracy. RESULTS: At baseline, the most connected MDD symptom-domains were fatigue-cognitive disturbance, whereas at week 8 they were depressed mood-suicidality. Overall, the most central MDD symptom-domains at baseline and week 8 were, respectively, fatigue and depressed mood; in contrast, the most peripheral symptom-domain across both timepoints was appetite/weight disturbance. Furthermore, the psychopathological network at week 8 was significantly more interconnected than at baseline, and they were also structurally dissimilar. CONCLUSION: Our findings highlight the utility of focusing on the dynamic interaction between depressive symptoms to better understand how the treatment with ADs unfolds over time. In addition, depressed mood, fatigue, and cognitive/psychomotor disturbance seem to be central MDD symptoms that may be viable targets for novel, focused therapeutic interventions.

An exploration of patient-provider dynamics and childbirth experiences in rural and urban Peru: a qualitative study.

BACKGROUND: Between 2006 and 2013, Peru implemented national programs which drastically decreased rates of maternal and neonatal mortality. However, since 2013, maternal and neonatal mortality in Peru have increased. Additionally, discrimination, abuse, and violence against women persists globally and impacts birthing experiences and mental health. This qualitative study sought to better understand the attitudes and beliefs regarding childbirth among women and providers in Southern Peru. This study also explores how these beliefs influence utilization of skilled care, patient-provider dynamics, and childbirth experiences and identifies factors that impact providers' provision of care. METHODS: Thirty semi-structured interviews were conducted with 15 participants from rural Colca Canyon and 15 participants from urban Arequipa between April and May 2018. In each region, 10 women who had experienced recent births and five providers were interviewed. Provider participants predominantly identified as female and were mostly midwives. All interviews were conducted, transcribed, and coded in Spanish. A framework analysis was followed, and data were charted into two separate thematic frameworks using contextual and evaluative categories of conceptualization of childbirth. RESULTS: All recent births discussed were facility-based births. Four domains emerged: women's current birth experiences, provision of childbirth care, beliefs about childbirth among women and providers, and future health-seeking behavior. Findings suggest that women's feelings of helplessness and frustration were exacerbated by their unmet desire for respectful maternity care and patient advocacy or companionship. Providers attributed strain to perceived patient characteristics and insufficient support, including resources and staff. CONCLUSIONS: Our findings suggest current childbirth experiences placed strain on the patient-provider dynamic and influenced women's attitudes and beliefs about future experiences. Currently, the technical quality of safe childbirth is the main driver of skilled birth attendance and facility-based births for women regardless of negative experiences. However, lack of respectful maternity care has been shown to have major long-term implications for women and subsequently, their children. This is one of the first studies to describe the nuances of patient-provider relationships and women's childbirth experiences in rural and urban Peru.

Causes of preterm and low birth weight neonatal mortality in a rural community in Kenya: evidence from verbal and social autopsy.

BACKGROUND: Under-five mortality in Kenya has declined over the past two decades. However, the reduction in the neonatal mortality rate has remained stagnant. In a country with weak civil registration and vital statistics systems, there is an evident gap in documentation of mortality and its causes among low birth weight (LBW) and preterm neonates. We aimed to establish causes of neonatal LBW and preterm mortality in Migori County, among participants of the PTBI-K (Preterm Birth Initiative-Kenya) study. METHODS: Verbal and social autopsy (VASA) interviews were conducted with caregivers of deceased LBW and preterm neonates delivered within selected 17 health facilities in Migori County, Kenya. The probable cause of death was assigned using the WHO International Classification of Diseases (ICD-10). RESULTS: Between January 2017 to December 2018, 3175 babies were born preterm or LBW, and 164 (5.1%) died in the first 28 days of life. VASA was conducted among 88 (53.7%) of the neonatal deaths. Almost half (38, 43.2%) of the deaths occurred within the first 24 h of life. Birth asphyxia (45.5%), neonatal sepsis (26.1%), respiratory distress syndrome (12.5%) and hypothermia (11.0%) were the leading causes of death. In the early neonatal period, majority (54.3%) of the neonates succumbed to asphyxia while in the late neonatal period majority (66.7%) succumbed to sepsis. Delay in seeking medical care was reported for 4 (5.8%) of the neonatal deaths. CONCLUSION: Deaths among LBW and preterm neonates occur early in life due to preventable causes. This calls for enhanced implementation of existing facility-based intrapartum and immediate postpartum care interventions, targeting asphyxia, sepsis, respiratory distress syndrome and hypothermia.

Proteomic profile of the acquired enamel pellicle of professional wine tasters with erosive tooth wear.

The aim of this study was to compare the acquired enamel pellicle protein profile of professional wine tasters with mild and moderate erosive tooth wear. Twelve professional wine tasters participated (3 from a low tooth wear group; 9 from a high tooth wear group). Acquired enamel pellicle samples were collected and processed for proteomic analysis (nLC-ESI-MS/MS). The acquired enamel pellicle proteomic profile was different between the groups. The proteins found exclusively in the low tooth wear group were histatins 1 and 3 and mucins 7 and 21. When comparing the wear groups, proteins with higher levels in the low tooth wear group included neutrophil defensins (1 and 3), lysozyme C, lysozyme, myeloperoxidase, and squalene monooxygenase. In conclusion, the findings indicate that the proteins found at higher levels in the low tooth wear group and proteins exclusively found in the low tooth wear group might be protective and, therefore, could be good candidates for further studies regarding their potential to be added to dental products to protect professional wine tasters from extrinsic erosive tooth wear.

Predictors of postpartum family planning in Rwanda: the influence of male involvement and healthcare experience.

BACKGROUND: Strengthened efforts in postpartum family planning (PPFP) is a key priority to accelerate progress in reproductive, maternal, newborn, and child health outcomes. This secondary data analysis explores factors associated with PPFP uptake in Rwanda. The purpose of this study was to explore variables that may influence PPFP use for postpartum women in Rwanda including health facility type, respectful maternity care, locus of control, and mental health status. METHODS: This secondary analysis of data from a cluster randomized control trial used information abstracted from questionnaires administered to women (≥ 15 years of age) at two time points-one during pregnancy (baseline) and one after delivery of the baby (follow-up). The dependent variable, PPFP uptake, was evaluated against the independent variables: respectful care, locus of control, and mental health status. These data were abstracted from linked questionnaires completed from January 2017 to February 2019. The sample size provided 97% power to detect a change at a 95% significance level with a sample size of 640 at a 15% effect size. Chi-square testing was applied for the bivariate analyses. A logistic regression model using the generalized linear model function was performed; odds ratio and adjusted (by age group and education group) odds ratio with 95% confidence interval were reported. RESULTS: Of the 646 respondents, although 92% reported not wanting another pregnancy within the next year, 72% used PPFP. Antenatal care wait time (p = < 0.01; Adj OR (Adj 95% CI) 21-40 min: 2.35 (1.46,3.79); 41-60 min: 1.50 (0.84,2.69); 61-450 min: 5.42 (2.86,10.75) and reporting joint healthcare decision-making between the woman and her partner (male) (p = 0.04; Adj OR (Adj 95% CI) husband/partner: 0.59 (0.35,0.97); mother and partner jointly: 1.06 (0.66,1.72) were associated with PPFP uptake. CONCLUSIONS: These results illustrate that partner (male) involvement and improved quality of maternal health services may improve PPFP utilization in Rwanda.

The use of photobiomodulation therapy or LED and mineral trioxide aggregate improves the repair of complete tibial fractures treated with wire osteosynthesis in rodents.

The repair of large bone defects is lengthy and complex. Both biomaterials and phototherapy have been used to improve bone repair. We aimed to describe histologically the repair of tibial fractures treated by wiring (W), irradiated or not, with laser (λ780 nm, 70 mW, CW, spot area of 0.5 cm2, 20.4 J/cm2 (4 × 5.1 J/cm2, Twin Flex Evolution®, MM Optics, Sao Carlos, SP, Brazil) per session, 300 s, 142.8 J/cm2 per treatment) or LED (λ850 ± 10 nm, 150 mW, spot area of 0.5 cm2, 20.4 J/cm2 per session, 64 s, 142.8 J/cm2 per treatment, Fisioled®, MM Optics, Sao Carlos, Sao Paulo, Brazil) and associated or not to the use of mineral trioxide aggregate (MTA, Angelus®, Londrina, PR, Brazil). Inflammation was discrete on groups W and W + LEDPT and absent on the others. Phototherapy protocols started immediately before suturing and repeated at every other day for 15 days. Collagen deposition intense on groups W + LEDPT, W + BIO-MTA + LaserPT and W + BIO-MTA + LEDPT and discrete or moderate on the other groups. Reabsorption was discrete on groups W and W + LEDPT and absent on the other groups. Neoformation varied greatly between groups. Most groups were partial and moderately filed with new-formed bone (W, W + LaserPT, W + LEDPT, W + BIO-MTA + LEDPT). On groups W + BIO-MTA and W + BIO-MTA + LaserPT bone, neoformation was intense and complete. Our results are indicative that the association of MTA and PBMT (λ = 780 nm) improves the repair of complete tibial fracture treated with wire osteosynthesis in a rodent model more efficiently than LED (λ = 850 ± 10 nm).

Association of differential symptoms of stress to hair cortisol and cortisone concentrations among pregnant women in Kenya.

Objectives: The purpose of this study was to characterize the stress experienced by pregnant women in Kenya and assess the relationship between perceived stress and stress-related biomarkers of cortisol and cortisone.Background: Kenyan women are exposed to multiple stressors that may result in chronic stress. However, antenatal stress has not been examined and characterized in Kenya; nor has the relationship between pregnant women's self-reported stress and stress biomarkers been established.Methods: One hundred and fifty women were recruited between 22 and 28 weeks gestation. Participants completed the Perceived Stress Scale (PSS) and a sociodemographic questionnaire. Hair samples were obtained for analysis of cortisol and cortisone. Factor analysis was used to extract unique clusters of stress symptoms from items in the PSS. Regression models were computed to examine relationships of stress to cortisone and cortisol, controlling for obstetric risk.Results: Mean age of the women was 25 years (SD = 5, ±16-41). Their degree of perceived stress and cortisol/cortisone concentrations both indicated moderate levels of stress. There was no association between general perceived stress and either hair cortisol or cortisone. However, factor analysis of the PSS identified three clusters of stress symptoms and one cluster - a woman's negative frame of mind regarding life and inefficacy in handling its problems - was associated with higher levels of cortisone (ß= -.231, p = 0.011).Conclusions: Specific stress symptoms may have unique relationships to specific biomarkers and be more useful in assessment than general perceived stress. Assays of both hair cortisol and cortisone might enable a more comprehensive assessment of glucocorticoid activity and better prediction of health risks from stress.Lay summaryUnderstanding stress among rural pregnant Kenyan women may help in addressing risks during pregnancy that lead to adverse birth outcomes. Findings suggest that a woman's tendency to think negatively about life and to doubt her ability to handle life's problems are symptoms of stress that may contribute to higher levels of stress hormones. Assessing women's specific symptoms of stress and different stress hormones during pregnancy may more effectively identify women who need intervention to reduce their health risk.

Maternal genitourinary infections and poor nutritional status increase risk of preterm birth in Gasabo District, Rwanda: a prospective, longitudinal, cohort study.

BACKGROUND: Preterm birth (PTB) is a leading cause of early childhood mortality and morbidity, including long-term physical and mental impairment. The risk factors for PTB are complex and include maternal nutritional status and infections. This study aimed to identify potentially modifiable risk factors for targeted interventions to reduce the occurrence of PTB in Rwanda. METHODS: We conducted a prospective, longitudinal cohort study of healthy pregnant women aged 18 to 49 years. Women at 9-15 gestational weeks were recruited from 10 health centers in Gasabo District, Kigali Province between September and October 2017. Pregnancy age was estimated using ultrasonography and date of last menstruation. Anthropometric and laboratory measurements were performed using standard procedures for both mothers and newborns. Surveys were administered to assess demographic and health histories. Categorical and continuous variables were depicted as proportions and means, respectively. Variables with p <  0.25 in bivariate analyses were included in multivariable logistic regression models to determine independent predictors of PTB. The results were reported as odds ratios (ORs) and 95% confidence intervals (CI), with statistical significance set at p <  0.05. RESULTS: Among 367 participants who delivered at a mean of 38.0 ± 2.2 gestational weeks, the overall PTB rate was 10.1%. After adjusting for potential confounders, we identified the following independent risk factors for PTB: anemia (hemoglobin < 11 g/dl) (OR: 4.27; 95%CI: 1.85-9.85), urinary tract infection (UTI) (OR:9.82; 95%CI: 3.88-24.83), chlamydia infection (OR: 2.79; 95%CI: 1.17-6.63), inadequate minimum dietary diversity for women (MDD-W) score (OR:3.94; CI: 1.57-9.91) and low mid-upper arm circumference (MUAC) < 23 cm (OR: 3.12, 95%CI; 1.31-7.43). indicators of nutritional inadequacy (low MDD-W and MUAC) predicted risk for low birth weight (LBW) but only UTI was associated with LBW in contrast with PTB. CONCLUSION: Targeted interventions are needed to improve the nutritional status of pregnant women, such as maternal education on dietary diversity and prevention of anemia pre-pregnancy. Additionally, prevention and treatment of maternal infections, especially sexually transmitted infections and UTIs should be reinforced during standard antenatal care screening which currently only includes HIV and syphilis testing.

Association between micronutrients and maternal leukocyte telomere length in early pregnancy in Rwanda.

BACKGROUND: Exposure to environmental stressors can lead to shorter leukocyte telomere length and increase the risk of chronic diseases. Preservation of leukocyte telomere length by reducing oxidative stress exposure and reinforcing immunity may be a mechanism by which nutritional factors delay or prevent chronic disease development. METHODS: Healthy pregnant women (aged 18-45 years) at 9-15 weeks of gestation living in Gasabo District, Kigali, Rwanda, were recruited from 10 health centers for a prospective, longitudinal study from September to October 2017 to determine possible associations between nutrition health, infectious disease and leukocyte telomere length. Anthropometric and laboratory measurements were performed using standard procedures; sociodemographic parameters and health histories were assessed via surveys, and leukocyte telomere length was assessed using quantitative PCR expressed as the ratio of a telomeric product to a single-copy gene product (T/S). RESULTS: Mean gestational age of participants (n = 297) at enrollment was 13.04 ± 3.50 weeks, age was 28.16 ± 6.10 years and leukocyte telomere length was 1.16 ± 0.22 (T/S). Younger age; no schooling vs. primary schooling; and lower levels of ferritin, soluble transferrin receptors and retinol-binding protein were independent predictors of longer telomere length in multivariable models. CONCLUSIONS: Leukocyte telomere length is an indicator of biological aging in pregnant Rwandan women. Maternal micronutrient status, specifically lower ferritin, soluble transferrin receptor levels, and retinol-binding protein levels were associated with longer maternal telomere length in contrast with some studies from North America and Europe. There were no associations between inflammation and infectious disease status and maternal leukocyte telomere length. Further studies are needed to enhance our understanding of the interplay between maternal nutritional status and infectious disease in relation to leukocyte telomere length in developing countries.

FUSE certification enhances performance on a virtual computer based simulator for dispersive electrode placement.

BACKGROUND: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) has developed the fundamental use of surgical energy (FUSE) didactic curriculum in order to further understanding of the safe use of surgical energy. The virtual electrosurgical skill trainer (VEST) is being developed as a complementary simulation-based curriculum, with several modules already existing. Subsequently, a new VEST module has been developed about dispersive electrode placement. The purpose of this study is to assess knowledge about dispersive electrode placement in surgeons and surgical trainees in addition to describing a new VEST module. METHODS: Forty-six subjects (n = 46) were recruited for participation at the 2016 SAGES conference Learning Center. Subjects were asked to complete demographic surveys, a five-question pre-test, and a five-question post-test after completing the VEST dispersive electrode module. Subjects were then asked to rate different aspects of the module using a five-point Likert scale questionnaire. RESULTS: Mean pre-simulator and post-simulator assessment scores were 1.5 and 3.4, respectively, with Wilcoxon signed rank analysis showing a significant difference in the means (p < 0.05). Subjects were grouped by the presence (n = 12) or absence (n = 31) of prior FUSE experience and by training level. Mann-Whitney U testing showed no significant difference in pre-simulator assessment scores between attending surgeons and trainees (p > 0.05). In those with and without FUSE exposure, a significant difference (p < 0.05) was seen in pre-simulator assessment scores, and no significant difference in Likert scale assessment scores was seen. CONCLUSIONS: This study demonstrated a new VEST educational module. Consistently high Likert assessment scores showed that users felt that the VEST module helped their understanding of dispersive electrode placement. Additionally, the study reflected a potential knowledge deficit in the safe use of dispersive electrodes in the surgical community, also demonstrating that even some exposure to the FUSE curriculum developed by SAGES provides increased awareness about dispersive electrode use.

Laser/LED phototherapy on the repair of tibial fracture treated with wire osteosynthesis evaluated by Raman spectroscopy.

The aim of the present study was to assess, by means of Raman spectroscopy, the repair of complete surgical tibial fractures fixed with wire osteosynthesis (WO) treated or not with infrared laser (λ780 nm) or infrared light emitting diode (LED) (λ850 ± 10 nm) lights, 142.8 J/cm2 per treatment, associated or not to the use of mineral trioxide aggregate (MTA) cement. Surgical tibial fractures were created on 18 rabbits, and all fractures were fixed with WO and some groups were grafted with MTA. Irradiated groups received lights at every other day during 15 days, and all animals were sacrificed after 30 days, being the tibia removed. The results showed that only irradiation with either laser or LED influenced the peaks of phosphate hydroxyapatite (~ 960 cm-1). Collagen (~ 1450 cm-1) and carbonated hydroxyapatite (~ 1070 cm-1) peaks were influenced by both the use of MTA and the irradiation with either laser or LED. It is concluded that the use of either laser or LED phototherapy associated to MTA cement was efficacious on improving the repair of complete tibial fractures treated with wire osteosynthesis by increasing the synthesis of collagen matrix and creating a scaffold of calcium carbonate (carbonated hydroxyapatite-like) and the subsequent deposition of phosphate hydroxyapatite.

Effect of chitosan addition on the properties of films prepared with corn and cassava starches.

Starch and chitosan are biodegradable polymers from renewable sources that can be used to overcome the serious environmental problem caused by improper disposal of synthetic plastic materials, non-biodegradable, derived from petroleum sources. The starch-chitosan based films manufactured allow improving the better characteristics of each one, adding their good characteristics and compensating for some limitations. In this work, it was studied: two sources of starch (corn and cassava), two different modes of chitosan addition (chitosan blended in the starch filmogenic solution and chitosan as coating), and the effect of glutaraldehyde as crosslinking agent. All films were prepared by casting using glycerol as a plasticizer and were characterized by their physicochemical (water vapor permeability, water contact angle, and FTIR), mechanical, and antimicrobial properties. The properties analyzed were influenced by all variables tested. Moreover, the principal component analysis was also conducted in order to relate and describe the variables analyzed. The antimicrobial activity of the corn starch-based films containing chitosan was confirmed, and these films have potential for development of active packaging.

Toward Improving Early Diagnosis of Congenital Chagas Disease in an Endemic Setting.

BACKGROUND: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect >50% of infected neonates, and 9-month follow-up is low. METHODS: Women who presented for delivery at 2 urban hospitals in Santa Cruz Department, Bolivia, were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR), and immunoglobulin (Ig)M trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month and by IgG serology at 6 and 9 months. RESULTS: Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot, and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1%, and 16.7%/100%, respectively. When birth and 1-month results were combined, cumulative sensitivities reached 84.2%, 73.7%, and 34.2%, respectively. Low birthweight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. CONCLUSIONS: The proportion of T. cruzi-infected infants with clinical signs has fallen since the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings.

A central region of Gli2 regulates its localization to the primary cilium and transcriptional activity.

Signaling through vertebrate Hedgehog (Hh) proteins depends on the primary cilium. In response to Hh signals, the transcriptional activator of the pathway, Gli2, accumulates at the ciliary tip, raising the possibility that ciliary localization is important for Gli2 activation. To test this hypothesis, we used the Floxin system to create knock-in Gli2 alleles in embryonic stem cells (ESCs) to allow methodical testing of which domains and residues are essential for the ciliary localization of Gli2. The Gli2 zinc fingers, transcriptional activation domain, repressor domain, phosphorylation cluster and a Sufu binding motif were each dispensable for ciliary localization. Mutating residues that are required for Gli2 sumoylation and nuclear trafficking also did not abrogate ciliary localization. By contrast, several other domains restricted Gli2 nuclear localization, and a central region, distinct from previously characterized domains, was required for ciliary localization. In addition to an inability to localize to cilia, Gli2 lacking this central domain was unable to activate target genes. Thus, our systematic analysis in ESCs reveals that distinct regions of Gli2 regulate its nuclear and ciliary localization. The identification of a domain essential for both ciliary localization and transcriptional activity suggests that ciliary localization of Gli2 is required for its activation.