Poor Prognosis with In Vitro Fertilization in Indian Women Compared to Caucasian Women Despite Similar Embryo Quality

BACKGROUND: Disease prevalence and response to medical therapy may differ among patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF) treatment have been previously shown in Indian women compared to Caucasian women, and some evidence suggests that poor embryo quality may be a cause for the discrepancy. In our center, only patients with the highest quality cleavage stage embryos are considered eligible for extending embryo culture to the blastocyst stage. We compared live birth rates (LBR) between Indian and Caucasian women after blastocyst transfer to investigate whether differences in IVF outcomes between these ethnicities would persist in patients who transferred similar quality embryos. METHODOLOGY/PRINCIPAL FINDINGS: In this retrospective cohort analysis, we compared IVF outcome between 145 Caucasians and 80 Indians who had a blastocyst transfer between January 1, 2005 and June 31, 2007 in our university center. Indians were younger than Caucasians by 2.7 years (34.03 vs. 36.71, P = 0.03), were more likely to have an agonist down regulation protocol (68% vs. 43%, P<0.01), and were more likely to have polycystic ovarian syndrome (PCOS), although not significant, (24% vs. 14%, P = 0.06). Sixty eight percent of Indian patients had the highest quality embryos (4AB blastocyst or better) transferred compared to 71% of the Caucasians (P = 0.2). LBR was significantly lower in the Indians compared to the Caucasians (24% vs. 41%, P<0.01) with an odds ratio of 0.63, (95%CI 0.46-0.86). Controlling for age, stimulation protocol and PCOS showed persistently lower LBR with an adjusted odds ratio of 0.56, (95%CI 0.40-0.79) in the multivariate analysis. CONCLUSIONS/SIGNIFICANCE: Despite younger age and similar embryo quality, Indians had a significantly lower LBR than Caucasians. In this preliminary study, poor prognosis after IVF for Indian ethnicity persisted despite limiting analysis to patients with high quality embryos transferred. Further investigation into explanations for ethnic differences in reproduction is needed

Association of Cervical Effacement With the Rate of Cervical Change in Labor Among Nulliparous Women

OBJECTIVE: To assess the association of cervical effacement with the rate of intrapartum cervical change among nulliparous women. METHODS: We conducted a secondary analysis of a prospective trial of intrapartum fetal pulse oximetry. For women who had vaginal deliveries, interval-censored regression was used to estimate the time to dilate at 1-cm intervals. For each given centimeter of progressive cervical dilation, women were divided into those who had achieved 100% cervical effacement and those who had not. The analysis was performed separately for women in spontaneous labor and those who were given oxytocin. RESULTS: A total of 3,902 women were included in this analysis, 1,466 (38%) who underwent labor induction, 1,948 (50%) who underwent labor augmentation (combined for the analysis), and 488 (13%) who labored spontaneously. For women in spontaneous labor, the time to dilate 1 cm was shorter for those who were 100% effaced starting at 4 cm of cervical dilation (P=.01 to <.001). For women who received oxytocin, the time to dilate 1 cm was shorter for those who were 100% effaced throughout labor (P<.001). CONCLUSION: The rate of cervical dilation among nulliparous women is associated with not only the degree of cervical dilation, but also with cervical effacement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00098709

Citizen science reveals widespread negative effects of roads on amphibian distributions

Landscape structure is important for shaping the abundance and distribution of amphibians, but prior studies of landscape effects have been species or ecosystem-specific. Using a large-scale, citizen science-generated database, we examined the effects of habitat composition, road disturbance, and habitat split (i.e. the isolation of wetland from forest by intervening land use) on the distribution and richness of frogs and toads in the eastern and central United States. Undergraduates from nine biology and environmental science courses collated occupancy data and characterized landscape structure at 1617 sampling locations from the North American Amphibian Monitoring Program. Our analysis revealed that anuran species richness and individual species distributions were consistently constrained by both road density and traffic volume. In contrast, developed land around wetlands had small, or even positive effects on anuran species richness and distributions after controlling for road effects. Effects of upland habitat composition varied among species, and habitat split had only weak effects on species richness or individual species distributions. Mechanisms underlying road effects on amphibians involve direct mortality, behavioral barriers to movement, and reduction in the quality of roadside habitats. Our results suggest that the negative effects of roads on amphibians occur across broad geographic regions, affecting even common species, and they underscore the importance of developing effective strategies to mitigate the impacts of roads on amphibian populations

Regional and scale-specific effects of land use on amphibian diversity [poster]

Background/Question/Methods Habitat loss and degradation influence amphibian distributions and are important drivers of population declines. Our previous research demonstrated that road disturbance, development and wetland area consistently influence amphibian richness across regions of the U.S. Here, we examined the relative importance of these factors in different regions and at multiple spatial scales. Understanding the scales at which habitat disturbance may be affecting amphibian distributions is important for conservation planning. Specifically, we asked: 1) Over what spatial scales do distinct landscape features affect amphibian richness? and 2) Do road types (non-rural and rural) have similar effects on amphibian richness? This is the second year of a collaborative, nationwide project involving 11 U.S. colleges integrated within undergraduate biology curricula. We summarized North American Amphibian Monitoring Program data in 13 Eastern and Central U.S states and used geographic information systems to extract landscape data for 471 survey locations. We developed models to quantify the influence of landscape variables on amphibian species richness and site occupancy across five concentric buffers ranging from 300m to 10,000m. Results/Conclusions Across spatial scales, development, road density and agriculture were the best predictors of amphibian richness and site occupancy by individual species. Across regions, we found that scale did not exert a large influence on how landscape features influenced amphibian richness as effects were largely comparable across buffers. However, development and percent impervious surface had stronger influence on richness at smaller spatial scales. Richness was lower at survey locations with higher densities of non-rural and rural roads, and non-rural road density had a larger negative effect at smaller scales. Within regions, landscape features driving patterns of species richness varied. The scales at which these factors were associated with richness were highly variable within regions, suggesting the scale effects may be region specific. Our project demonstrates that networks of undergraduate students can collaborate to compile and analyze large ecological data sets, while engaging students in authentic and inquiry-based learning in landscape-scale ecology

Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants

Introduction: Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined. Methods and Results: We analyzed clinical manifestations of damaging biallelic ALPK3 variants in 19 pediatric patients, including nine previously published cases. Among these, 11 loss-of-function (LoF) variants, seven compound LoF and deleterious missense variants, and one homozygous deleterious missense variant were identified. Among 18 live-born patients, 8 exhibited neonatal dilated cardiomyopathy (44.4%; 95% CI: 21.5%-69.2%) that subsequently transitioned into ventricular hypertrophy. The majority of patients had extracardiac phenotypes, including contractures, scoliosis, cleft palate, and facial dysmorphisms. We observed no association between variant type or location, disease severity, and/or extracardiac manifestations. Myocardial histopathology showed focal cardiomyocyte hypertrophy, subendocardial fibroelastosis in patients under 4 years of age, and myofibrillar disarray in adults. Rare heterozygous ALPK3 variants were also assessed in adult-onset cardiomyopathy patients. Among 1548 Dutch patients referred for initial genetic analyses, we identified 39 individuals with rare heterozygous ALPK3 variants (2.5%; 95% CI: 1.8%-3.4%), including 26 missense and 10 LoF variants. Among 149 U.S. patients without pathogenic variants in 83 cardiomyopathy-related genes, we identified six missense and nine LoF ALPK3 variants (10.1%; 95% CI: 5.7%-16.1%). LoF ALPK3 variants were increased in comparison to matched controls (Dutch cohort, P = 1.6×10−5; U.S. cohort, P = 2.2×10−13). Conclusion: Biallelic damaging ALPK3 variants cause pediatric cardiomyopathy manifested by DCM transitioning to hypertrophy, often with poor contractile function. Additional extracardiac features occur in most patients, including musculoskeletal abnormalities and cleft palate. Heterozygous LoF ALPK3 variants are enriched in adults with cardiomyopathy and may contribute to their cardiomyopathy. Adults with ALPK3 LoF variants therefore warrant evaluations for cardiomyopathy

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children from Wild-type to Population Immunity: A Prospective Multicenter Cohort Study with Real-time Reporting

Background: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. Methods: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. Results: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. Conclusions: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Gestational hypertension and progression towards preeclampsia in Northern Ethiopia: prospective cohort study

Abstract Background Preeclampsia (PE) is one of the main causes of medical complication of pregnancy and is the main cause of perinatal mortality and morbidity. It is one of the top causes of maternal mortality in Ethiopia. Also known as transient hypertension, gestational hypertension (GH) is increased blood pressure during pregnancy without proteinuria, which is expected to return to normal by the 12th-week postpartum visit. PE is GH with proteinuria and /or other systemic manifestations. Evidence from high income countries show that GH significantly progresses towards PE. To our knowledge, this is the first study on the progression of GH towards PE in an African setting. The objective of this study is, therefore, to assess the incidence of GH, progression towards PE and factors associated with progression in Ethiopia. Methods This is a prospective cohort study conducted at Ayder Comprehensive Specialized Hospital (ACSH) and Mekelle General Hospital (MGH), the largest referral centers in Northern Ethiopia. Two hundred and forty women with GH were enrolled and followed up until delivery. Clinical and laboratory data at initial presentation and at follow-up were compared among women who progressed towards PE and who remained with the diagnosis of GH. Logistic regression analysis was employed to model the combined effects of the clinical and laboratory data as significant predictors of progression from GH to PE. Result The incidence of GH in this study was 6 % (4.9–8.5). The rate of progression was 17.1 % (13.4–23.8). Previous history of GH, anemia during pregnancy, previous second-trimester spontaneous abortion were significant predictors of progression. Conclusions There is a high rate of progression of GH towards PE. In a resource-limited setting where predictive and diagnostic tools are scarce, clinical profile of women should be taken into consideration for prediction and diagnosis of PE.http://deepblue.lib.umich.edu/bitstream/2027.42/173656/1/12884_2021_Article_3712.pd

Placental transcriptome analysis of hypertensive pregnancies identifies distinct gene expression profiles of preeclampsia superimposed on chronic hypertension

Abstract Background The pathogenesis of preeclampsia superimposed on chronic hypertension (SI) is poorly understood relative to preeclampsia (PreE) occurring in pregnant people without chronic hypertension. Placental transcriptomes in pregnancies complicated by PreE and SI have not been previously compared. Methods We identified pregnant people in the University of Michigan Biorepository for Understanding Maternal and Pediatric Health with hypertensive disorders affecting singleton, euploid gestations (N = 36) along with non-hypertensive control subjects (N = 12). Subjects were grouped as: (1) normotensive (N = 12), (2) chronic hypertensive (N = 13), (3) preterm PreE with severe features (N = 5), (4) term PreE with severe features (N = 11), (5) preterm SI (N = 3), or (6) term SI (N = 4). Bulk RNA sequencing of paraffin-embedded placental tissue was performed. The primary analysis assessed differential gene expression relative to normotensive and chronic hypertensive placentas, where Wald adjusted P values < 0.05 were considered significant. Unsupervised clustering analyses and correlation analyses were performed between conditions of interest, and a gene ontology was constructed. Results Comparing samples from pregnant people with hypertensive diseases to non-hypertensive controls, there were 2290 differentially expressed genes. The log2-fold changes in genes differentially expressed in chronic hypertension correlated better with term (R = 0.59) and preterm (R = 0.63) PreE with severe features than with term (R = 0.21) and preterm (R = 0.22) SI. A relatively poor correlation was observed between preterm SI and preterm PreE with severe features (0.20) as well as term SI and term PreE with severe features (0.31). The majority of significant genes were downregulated in term and preterm SI versus normotensive controls (92.1%, N = 128). Conversely, most term and preterm PreE with severe features genes were upregulated compared to the normotensive group (91.8%, N = 97). Many of the upregulated genes in PreE with the lowest adjusted P values are known markers of abnormal placentation (e.g., PAAPA, KISS1, CLIC3), while the downregulated genes with the greatest adjusted P values in SI have fewer known pregnancy-specific functions. Conclusions We identified unique placental transcriptional profiles in clinically relevant subgroups of individuals with hypertension in pregnancy. Preeclampsia superimposed on chronic hypertension was molecularly distinct from preeclampsia in individuals without chronic hypertension, and chronic hypertension without preeclampsia, suggesting that preeclampsia superimposed on hypertension may represent a distinct entity