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Background Group prenatal care (GPC) models have been gaining popularity in recent years. Studies of high-risk groups have shown improved outcomes. Our objective was to review and summarize outcomes for women in GPC for women with specific high-risk conditions. Methods A systematic literature review of Ovid, PubMed, and Google Scholar was performed to identify studies reporting the effects of group prenatal care in high-risk populations. Studies were included if they reported on pregnancy outcome results for women using GPC. We also contacted providers known to be utilizing GPC for specific high-risk women. Descriptive results were compiled and summarized by high-risk population. Results We identified 37 reports for inclusion (8 randomized trials, 23 nonrandomized studies, 6 reports of group outcomes without controls). Preterm birth was found to be decreased among low-income and African American women. Attendance at prenatal visits was shown to increase among women in GPC in the following groups: Opioid Addiction, Adolescents, and Low-Income. Improved weight trajectories and compliance with the IOM’s weight recommendations were found in adolescents. Increased rates of breastfeeding were found in adolescents and African Americans. Increased satisfaction with care was found in adolescents and African Americans. Pregnancy knowledge was increased among adolescents, as was uptake of LARC. Improved psychological outcomes were found among adolescents and low-income women. Studies in women with diabetes demonstrated that fewer women required treatment with medication when exposed to GPC, and for those requiring treatment with insulin, GPC individuals required less than half the dose. Among women with tobacco use, those who had continued to smoke after finding out they were pregnant were 5 times more likely to quit later in pregnancy if they were engaged in GPC. Conclusions Several groups of high-risk pregnant women may have benefits from engaging in group prenatal care. Because there is a paucity of high-quality, well-controlled studies, more trials in high-risk women are needed to determine whether it improves outcomes and costs of pregnancy-related care.

Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable diseases with 10 million incident cases and 1·8 million deaths in 2015 alone based on the annual WHO report, due to inadequate health service resources in less-developed regions of the world, and exacerbated by the HIV/AIDS pandemic and emergence of multidrug-resistant strains of Mycobacterium tuberculosis. Recent findings from studies of tuberculosis infection and of patients with Mendelian predisposition to severe tuberculosis have started to reveal human loci influencing tuberculosis outcomes. In this Review, we assess the current understanding of the contribution of host genetics to disease susceptibility and to drug treatment. Despite remarkable progress in technology, only a few associated genetic variants have so far been identified, strongly indicating the need for larger global studies that investigate both common and under-represented rare variants to develop new approaches to combat the disease. Pharmacogenomic discoveries are also likely to lead to more efficient drug design and development, and ultimately safer and more effective therapies for tuberculosis.

This paper recounts the first successful cryo-cooling of protein crystals that demonstrated the reduction in X-ray damage to macromolecular crystals. The project was suggested by David C. Phillips in 1965 at the Royal Institution of Great Britain and continued in 1967 at the Weizmann Institute of Science, where the first cryo-cooling experiments were performed on lysozyme crystals, and was completed in 1969 at Purdue University on lactate dehydrogenase crystals. A 1970 publication in Acta Crystallographica described the cryo-procedures, the use of cryo-protectants to prevent ice formation, the importance of fast, isotropic cryo-cooling and the collection of analytical data showing more than a tenfold decrease in radiation damage in cryo-cooled lactate dehydrogenase crystals. This was the first demonstration of any method that reduced radiation damage in protein crystals, which provided crystallographers with suitable means to employ synchrotron X-ray sources for protein-crystal analysis. Today, fifty years later, more than 90% of the crystal structures deposited in the Protein Data Bank have been cryo-cooled.

Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 control individuals and with gestational hypertension in 11,027 cases and 412,788 control individuals across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are new (for example, MTHFR – CLCN6 , WNT3A , NPR3 , PGR and RGL3 ), including two loci ( PLCE1 and FURIN ) identified in the multitrait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external cohorts, independent of clinical risk factors, and reclassified eligibility for low-dose aspirin to prevent preeclampsia. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification. A multi-ancestry genetic meta-analysis identifies 12 new loci associated with preeclampsia and gestational hypertension and proposes the integration of polygenic scores and clinical factors for disease prediction

Preterm delivery is a common pregnancy complication that can result in significant neonatal morbidity and mortality. Limited tools exist to predict preterm birth, and none to predict neonatal morbidity, from early in pregnancy. The objective of this study was to determine if the progesterone metabolites 11-deoxycorticosterone (DOC) and 16-alpha hydroxyprogesterone (16α-OHP), when combined with patient demographic and obstetric history known during the pregnancy, are predictive of preterm delivery-associated neonatal morbidity, neonatal length of stay, and risk for spontaneous preterm delivery prior to 32 weeks' gestation. We conducted a cohort study of pregnant women with plasma samples collected as part of Building Blocks of Pregnancy Biobank at the Indiana University School of Medicine. The progesterone metabolites, DOC and 16α-OHP, were quantified by mass spectroscopy from the plasma of 58 pregnant women collected in the late first trimester/early second trimester. Steroid levels were combined with patient demographic and obstetric history data in multivariable logistic regression models. The primary outcome was composite neonatal morbidity as measured by the Hassan scale. Secondary outcomes included neonatal length of stay and spontaneous preterm delivery prior to 32 weeks' gestation. The final neonatal morbidity model, which incorporated antenatal corticosteroid exposure and fetal sex, was able to predict high morbidity (Hassan score ≥ 2) with an area under the ROC curve (AUROC) of 0.975 (95% CI 0.932, 1.00), while the model without corticosteroid and fetal sex predictors demonstrated an AUROC of 0.927 (95% CI 0.824, 1.00). The Hassan score was highly correlated with neonatal length of stay (p<0.001), allowing the neonatal morbidity model to also predict increased neonatal length of stay (53 [IQR 22, 76] days vs. 4.5 [2, 31] days, above and below the model cut point, respectively; p = 0.0017). Spontaneous preterm delivery prior to 32 weeks' gestation was also predicted with an AUROC of 0.94 (95% CI 0.869, 1.00). Plasma levels of DOC and 16α-OHP in early gestation can be combined with patient demographic and clinical data to predict significant neonatal morbidity, neonatal length of stay, and risk for very preterm delivery, though validation studies are needed to verify these findings. Early identification of pregnancies at risk for preterm delivery and neonatal morbidity allows for timely implementation of multidisciplinary care to improve perinatal outcomes.

Background 2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most extensively used herbicides in the United States. In 2012, 2,4-D was the most widely used herbicide in non-agricultural settings and the fifth most heavily applied pesticide in the US agricultural sector. The objective of this study was to examine trends in 2,4-D urinary biomarker concentrations to determine whether increases in 2,4-D application in agriculture are associated with increases in biomonitoring levels of urine 2,4-D. Methods Data from the National Health and Nutrition Examination Survey (NHANES) with available urine 2,4-D biomarker measurements from survey cycles between 2001 and 2014 were utilized. Urine 2,4-D values were dichotomized using the highest limit of detection (LOD) across all cycles (0.40 μg/L or 0.4 ppb). Agricultural use of 2,4-D was estimated by compiling publicly available federal and private pesticide application data. Logistic regression models adjusted for confounders were fitted to evaluate the association between agricultural use of 2,4-D and urine 2,4-D level above the dichotomization threshold. Results Of the 14,395 participants included in the study, 4681 (32.5%) had urine 2,4-D levels above the dichotomization threshold. The frequency of participants with high 2,4-D levels increased significantly ( p  < .0001), from a low of 17.1% in 2001–2002 to a high of 39.6% in 2011–2012. The adjusted odds of high urinary 2,4-D concentrations associated with 2,4-D agricultural use (per ten million pounds applied) was 2.268 (95% CI: 1.709, 3.009). Children ages 6–11 years ( n  = 2288) had 2.1 times higher odds of having high 2,4-D urinary concentrations compared to participants aged 20–59 years. Women of childbearing age (age 20–44 years) ( n  = 2172) had 1.85 times higher odds than men of the same age. Conclusions Agricultural use of 2,4-D has increased substantially from a low point in 2002 and it is predicted to increase further in the coming decade. Because increasing use is likely to increase population level exposures, the associations seen here between 2,4-D crop application and biomonitoring levels require focused biomonitoring and epidemiological evaluation to determine the extent to which rising use and exposures cause adverse health outcomes among vulnerable populations (particularly children and women of childbearing age) and highly exposed individuals (farmers, other herbicide applicators, and their families).

As a type of relatively new methodology, the transcriptome-wide association study (TWAS) has gained interest due to capacity for gene-level association testing. However, the development of TWAS has outpaced statistical evaluation of TWAS gene prioritization performance. Current TWAS methods vary in underlying biological assumptions about tissue specificity of transcriptional regulatory mechanisms. In a previous study from our group, this may have affected whether TWAS methods better identified associations in single tissues versus multiple tissues. We therefore designed simulation analyses to examine how the interplay between particular TWAS methods and tissue specificity of gene expression affects power and type I error rates for gene prioritization. We found that cross-tissue identification of expression quantitative trait loci (eQTLs) improved TWAS power. Single-tissue TWAS (i.e., PrediXcan) had robust power to identify genes expressed in single tissues, but, often found significant associations in the wrong tissues as well (therefore had high false positive rates). Cross-tissue TWAS (i.e., UTMOST) had overall equal or greater power and controlled type I error rates for genes expressed in multiple tissues. Based on these simulation results, we applied a tissue specificity-aware TWAS (TSA-TWAS) analytic framework to look for gene-based associations with pre-treatment laboratory values from AIDS Clinical Trial Group (ACTG) studies. We replicated several proof-of-concept transcriptionally regulated gene-trait associations, including UGT1A1 (encoding bilirubin uridine diphosphate glucuronosyltransferase enzyme) and total bilirubin levels (p = 3.59×10 −12 ), and CETP (cholesteryl ester transfer protein) with high-density lipoprotein cholesterol (p = 4.49×10 −12 ). We also identified several novel genes associated with metabolic and virologic traits, as well as pleiotropic genes that linked plasma viral load, absolute basophil count, and/or triglyceride levels. By highlighting the advantages of different TWAS methods, our simulation study promotes a tissue specificity-aware TWAS analytic framework that revealed novel aspects of HIV-related traits.

Background The objective of the Heartland Study is to address major knowledge gaps concerning the health effects of herbicides on maternal and infant health. To achieve this goal, a two-phased, prospective longitudinal cohort study is being conducted. Phase 1 is designed to evaluate associations between biomarkers of herbicide concentration and pregnancy/childbirth outcomes. Phase 2 is designed to evaluate potential associations between herbicide biomarkers and early childhood neurological development. Methods People (target enrollment of 2,000) who are seeking prenatal care, are ages 18 or older, and are ≤ 20 + 6 weeks gestation will be eligible for recruitment. The Heartland Study will utilize a combination of questionnaire data and biospecimen collections to meet the study objectives. One prenatal urine and buccal sample will be collected per trimester to assess the impact of herbicide concentration levels on pregnancy outcomes. Infant buccal specimens will be collected post-delivery. All questionnaires will be collected by trained study staff and clinic staff will remain blinded to all individual level research data. All data will be stored in a secure REDCap database. Hospitals in the agriculturally intensive states in the Midwestern region will be recruited as study sites. Currently participating clinical sites include Indiana University School of Medicine- affiliated Hospitals in Indianapolis, Indiana; Franciscan Health Center in Indianapolis, Indiana; Gundersen Lutheran Medical Center in La Crosse, Wisconsin, and University of Iowa in Iowa City, Iowa. An anticipated 30% of the total enrollment will be recruited from rural areas to evaluate herbicide concentrations among those pregnant people residing in the rural Midwest. Perinatal outcomes (e.g. birth outcomes, preterm birth, preeclampsia, etc.) will be extracted by trained study teams and analyzed for their relationship to herbicide concentration levels using appropriate multivariable models. Discussion Though decades of study have shown that environmental chemicals may have important impacts on the health of parents and infants, there is a paucity of prospective longitudinal data on reproductive impacts of herbicides. The recent, rapid increases in herbicide use across agricultural regions of the United States necessitate further research into the human health effects of these chemicals, particularly in pregnant people. The Heartland Study provides an invaluable opportunity to evaluate health impacts of herbicides during pregnancy and beyond. Trial registration The study is registered at clinicaltrials.gov, NCT05492708 with initial registration and release 05 August, 2022.

Background Induction of labor (IOL) is common with one in four labors being induced in the United States (US). IOL has been associated with lower birth satisfaction. Video education can address gaps in education and promote anticipatory guidance. Prior studies in obstetrics have focused on randomized designs in English-speaking patients, leaving opportunities to explore how these tools perform in a pragmatic fashion with diverse patient populations. Our objective was to evaluate the effects of a video education tool on patient satisfaction and knowledge of IOL experience in English and Spanish-speaking patients scheduled for IOL at a tertiary care hospital. Methods This was a single site pragmatic implementation of a quality improvement measure at an academic hospital. A bilingual survey was developed to evaluate the impact of an educational video on birth satisfaction and knowledge of IOL procedures. The video is freely available in English and Spanish. Baseline postpartum surveys were collected from June to July 2021. The video was subsequently recommended by providers when scheduling IOLs. Post-intervention surveys were collected from September to November 2021 after an implementation period. Groups were compared using t-tests for satisfaction scores and chi-square analyses for categorical variables. Results Thirty-two participants completed the baseline survey and 72 completed the post-implementation survey with response rates of 88.9% and 91.1%, respectively. There were no statistically significant changes between mean total satisfaction scores (26.9 vs 28.0 out of 40.0, p  = 0.290). 61 participants were English speaking (58%) and 43 Spanish (42%). Thirty (42%) patients reported watching the video. Correct identification of amniotomy use improved in the post-intervention group ( p  = 0.002). No changes were seen in anticipated duration of labor nor in whether patients would choose to be induced again. Conclusions Recommendation of video education before scheduled IOL was associated with little improvement in knowledge about IOL, but no significant improvement in patient satisfaction. While video education has improved these measures in randomized trials, our study demonstrated that real-world implementation and patient uptake may be initially difficult. This study may help providers emphasize direct education and counseling and promote optimal implementation of innovative educational media.

Opioid use disorder during pregnancy significantly increases the likelihood of adverse developmental outcomes in the offspring. Texture analysis serves as a quantitative technique that could be vital in identifying microstructural variations in placentas that have been exposed to opioids and other substances. This is a prospective, multisite cross-sectional study that recruited pregnant women that were greater than 16 weeks of gestation. We manually segmented placenta tissue from half-Fourier single-shot turbo spin-echo (HASTE) sequence MR images. We then assessed placental surface area and texture features using a radiomics pipeline. Using linear models, we assessed the association of substance use on placental surface area and texture features, accounting for demographic characteristics. There were 33 pregnant women with opioid use and 29 controls. Based on regression analysis, opioid exposure was associated with alterations in two texture features while tobacco exposure was associated with alterations in five texture features prior to multiple comparison correction. These were no longer significant after correcting for multiple comparisons. Additionally, tobacco exposure was significantly associated with greater placenta surface area.