Genetic Associations with Gestational Duration and Spontaneous Preterm Birth

BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0x10(-8)) or an association with suggestive significance (P<1.0x10(-6)) in the discovery set. RESULTS In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONS In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.Peer reviewe

Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy

A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs). Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome.Vincent J. Lynch, Mauris C. Nnamani, Aurélie Kapusta, Kathryn Brayer, Silvia L. Plaza, Erik C. Mazur, Deena Emera, Shehzad Z. Sheikh, Frank Grützner, Stefan Bauersachs, Alexander Graf, Steven L. Young, Jason D. Lieb, Francesco J. DeMayo, Cédric Feschotte, Günter P. Wagne

Ectopic pregnancy at a tertiary hospital in North Eastern Nigeria: a 2 year review of the clinical presentations and management

Background: Ectopic pregnancy is a life threatening gynaecological condition associated with adverse reproductive health consequences. It commonly implants in the fallopian tube and most patients in the developing world present &nbsp;late when it has ruptured leading to maternal morbidity and mortality if intervention is delayed. Method: This was a descriptive cross-sectional retrospective study of patients with ectopic pregnancy managed at Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, North east Nigeria between 1st January, 2013 and 31st December, 2014. Data on the age, parity, clinical symptoms and signs and the types of surgical treatment offered was extracted and computed using excel spreadsheet and statistical analysis was done using SPSS (version 23) and results presented as frequency tables, percentages, and mean (± SD). Results: There were 1,577 gynaecological admissions during the period of study and 98 of them (6.2%) were ectopic pregnancies. The total number of deliveries during the same period was 6,738, putting the incidence of ectopic pregnancy to be 1.45% of all deliveries. Majority of the affected patients (39.2%) were between 25- 29 years with a mean and SD of 26.5 ± 4.9 years. Majority of the patients who had ectopic pregnancy 26 (35.1%) were nulliparous women. Of these patients, 97.3% presented with symptoms of abdominal pain, amenorrhoea (83.8%) and vaginal bleeding (68.9%). 97.3% of them had salpingectomy of the affected side. Conclusion: Ectopic pregnancy is a common life-threatening emergency in early pregnancy. Efforts made to improve early diagnosis prior to tubal rupture, would help reduce the associated maternal morbidity and eliminate mortality from this condition

Effects of Vitamin E Supplementation in Male Rats with Crude Oil-Induced Reproductive Toxicity

Crude oil intoxication is a major threat among people and animals living around the crude oil producing regions of the world, hence the search for ameliorating agents. Forty-four male Wistar rats assigned into three groups were used to investigate the effects of vitamin E supplementation on crude oil-induced reprotoxicity (reproductive toxicity) in male rats. Group A represented the unexposed control, whereas groups B and C were exposed orally to 0.15 and 0.3 ml of crude oil respectively every other day for 56 days. Both the low dose and high dose oral administration of crude oil caused a significant reduction in the serum testosterone level (STL) and cauda epididymal sperm reserve (CESR) of the exposed rats when compared to the control. Crude oil withdrawal and vitamin E supplementation significantly improved the cauda epididymal sperm reserve (CESR) in all the subgroups. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities of the control and low dose group were significantly lower than those of the high dose group. The high dose crude oil administration significantly decreased the mean serum total protein (STP) and sodium ions (Na+) concentration. The mean serum total cholesterol (STC) value of the low dose group was significantly higher than those of the control and high dose group. However, crude oil withdrawal and vitamin E supplementation did not significantly alter the mean serum total protein (STP) and mean serum total cholesterol (STC) values in all the subgroups. Vitamin E supplementation following low dose crude oil withdrawal enhanced the mean serum Chloride ions (Cl-)concentration. The present findings revealed that Nigerian Qua Iboe Brent crude oil induced serious reprotoxic effects in male rats which vitamin E administration within 28 days did not completely reverse

Effects of physical exercises on inflammatory biomarkers and cardiopulmonary function in patients living with HIV: a systematic review with meta-analysis

Abstract Background Pro-inflammatory cytokines expressed in human immune deficiency virus (HIV) infection, may induce oxidative stress likely to compromise the patency of the airways or damage the lung tissues/cardiac function. However, physical (aerobic and/or resistance) exercise-induced release of heat shock protein, immune function alteration or reduced tissue hypoxia, have been highlighted as possible mechanisms by which increasing physical activity may reduce plasma pro-inflammatory cytokines in uninfected individuals and should be appraised in the literature for evidence of similar benefits in people living with HIV (PLWH). Therefore, we evaluated the effects of physical exercises on 1) inflammatory biomarkers and 2) cardiopulmonary function (VO2 Max) in PLWH. Method A systematic review was conducted using the Cochrane Collaboration protocol. Searching databases, up to January 2018. Only randomized control trials investigating the effects of either aerobic or resistance or a combination of both exercise types with a control/other intervention(s) for a period of at least 4 weeks among adults living with HIV, were included. Two independent reviewers determined the eligibility of the studies. Data were extracted and risk of bias (ROB) was assessed with the Cochrane Collaboration ROB tool. Meta-analyses were conducted with random effect models using the Review Manager (RevMan) computer software. Result Twenty-three studies met inclusion criteria (n = 1073 participants at study completion) comprising male and female with age range 18–65 years. Three meta-analyses across three sub-groups comparisons were performed. The result showed no significant change in biomarkers of inflammation (IL-6 and IL-1β) unlike a significant (Z = 3.80, p < 0.0001) improvement in VO2 Max. Overall, the GRADE evidence for this review was of moderate quality. Conclusion There was evidence that engaging in either aerobic or resistance exercise, or a combination of both exercises, two to five times per week can lead to a significant improvement in cardiopulmonary function but not biomarkers of inflammation (IL-6 and IL-1β). However, this should not be interpreted as “No evidence of effect” because the individual trial studies did not attain sufficient power to detect treatment effects. The moderate grade evidence for this review suggests that further research may likely have an important impact on our confidence in the estimate of effects and may change the estimate

The mammalian decidual cell evolved from a cellular stress response.

Among animal species, cell types vary greatly in terms of number and kind. The number of cell types found within an organism differs considerably between species, and cell type diversity is a significant contributor to differences in organismal structure and function. These observations suggest that cell type origination is a significant source of evolutionary novelty. The molecular mechanisms that result in the evolution of novel cell types, however, are poorly understood. Here, we show that a novel cell type of eutherians mammals, the decidual stromal cell (DSC), evolved by rewiring an ancestral cellular stress response. We isolated the precursor cell type of DSCs, endometrial stromal fibroblasts (ESFs), from the opossum Monodelphis domestica. We show that, in opossum ESFs, the majority of decidual core regulatory genes respond to decidualizing signals but do not regulate decidual effector genes. Rather, in opossum ESFs, decidual transcription factors function in apoptotic and oxidative stress response. We propose that rewiring of cellular stress responses was an important mechanism for the evolution of the eutherian decidual cell type

Instrumental Neutron Activation Analysis (INAA) As-sessment of REE of Soil from Mining Site Umuahia, Abia State, South East, Nigeria

In this work, the main goal was to examine the REE concentration and distribution pattern in soil from Umuahia, Abia State, Southeast, Nigeria, in a clay mining site compared with a non-contaminated site approximately 3 km away. The REE were determined by Instrumental Neutron Activation Analysis (INAA) at IPEN, Brazil. The main mineralogy of the samples was determined by XRD. The following REE were determined: Ce, Eu, La, Lu, Nd, Sm, Tb and Yb. Soil samples from the mining area present quartz and kaolinite as their main constituents, with REE concentrations comparable with that of the Upper Continental Crust and the North American Shale Composite. The calculated Geoaccumulation index (IGeo) indicate that REE have natural origin and ∑LREEN/∑HREEN ratio show an enrichment of the light over heavy REE, in samples of the clay mining area

A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1

Transcription factors (TFs) play multiple roles in development. Given this multifunctionality, it has been assumed that TFs are evolutionarily highly constrained. Here, we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires interaction with FOXO1, and that the physical interaction between these proteins evolved before their functional cooperativity. Here, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex

Patient Perceptions on Barriers and Facilitators to Accessing Low-acuity Surgery During COVID-19 Pandemic.

BackgroundThe onset of the COVID-19 pandemic led to the postponement of low-acuity surgical procedures in an effort to conserve resources and ensure patient safety. This study aimed to characterize patient-reported concerns about undergoing surgical procedures during the pandemic.MethodsWe administered a cross-sectional survey to patients who had their general and plastic surgical procedures postponed at the onset of the pandemic, asking about barriers to accessing surgical care. Questions addressed dependent care, transportation, employment and insurance status, as well as perceptions of and concerns about COVID-19. Mixed methods and inductive thematic analyses were conducted.ResultsOne hundred thirty-five patients were interviewed. We identified the following patient concerns: contracting COVID-19 in the hospital (46%), being alone during hospitalization (40%), facing financial stressors (29%), organizing transportation (28%), experiencing changes to health insurance coverage (25%), and arranging care for dependents (18%). Nonwhite participants were 5 and 2.5 times more likely to have concerns about childcare and transportation, respectively. Perceptions of decreased hospital safety and the consequences of possible COVID-19 infection led to delay in rescheduling. Education about safety measures and communication about scheduling partially mitigated concerns about COVID-19. However, uncertainty about timeline for rescheduling and resolution of the pandemic contributed to ongoing concerns.ConclusionsProviding effective surgical care during this unprecedented time requires both awareness of societal shifts impacting surgical patients and system-level change to address new barriers to care. Eliciting patients' perspectives, adapting processes to address potential barriers, and effectively educating patients about institutional measures to minimize in-hospital transmission of COVID-19 should be integrated into surgical care