Development and evaluation of a wearable peripheral vascular compensation sensor in a swine model of hemorrhage

Postpartum hemorrhage (PPH) is the leading and most preventable cause of maternal mortality, particularly in low-resource settings. PPH is currently diagnosed through visual estimation of blood loss or monitoring of vital signs. Visual assessment routinely underestimates blood loss beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The measured LSFI signal produced a linear response in phantom models and a strong correlation coefficient with blood loss averaged across subjects (\u3e0.9) in a large animal model, with superior performance to vital sign metrics

Pharmacological chaperones for the oxytocin receptor increase oxytocin responsiveness in myometrial cells

Oxytocin is a potent uterotonic agent administered to nearly all patients during childbirth in the United States. Inadequate oxytocin response can necessitate Cesarean delivery or lead to uterine atony and postpartum hemorrhage. Thus, it may be clinically useful to identify patients at risk for poor oxytocin response and develop strategies to sensitize the uterus to oxytocin. Previously, we showed that the V281M variant in the oxytocin receptor (OXTR) gene impairs OXTR trafficking to the cell surface, leading to a decreased oxytocin response in cells. Here, we sought to identify pharmacological chaperones that increased oxytocin response in cells expressing WT or V281M OXTR. We screened nine small-molecule agonists and antagonists of the oxytocin/vasopressin receptor family and identified two, SR49059 and L371,257, that restored both OXTR trafficking and oxytocin response in HEK293T cells transfected with V281M OXTR. In hTERT-immortalized human myometrial cells, which endogenously express WT OXTR, treatment with SR49059 and L371,257 increased the amount of OXTR on the cell surface by two- to fourfold. Furthermore, SR49059 and L371,257 increased the endogenous oxytocin response in hTERT-immortalized human myometrial cells by 35% and induced robust oxytocin responses in primary myometrial cells obtained from patients at the time of Cesarean section. If future studies demonstrate that these pharmacological chaperones or related compounds function similarly in vivo, we propose that they could potentially be used to enhance clinical response to oxytocin

Obesity, Second Stage Duration, and Labor Outcomes in Nulliparous Women

Objective: This study aimed to estimate second stage duration and its effects on labor outcomes in obese versus nonobese nulliparous women. Study design: This was a secondary analysis of a cohort of nulliparous women who presented for labor at term and reached complete cervical dilation. Adjusted relative risks (aRR) were used to estimate the association between obesity and second stage characteristics, composite neonatal morbidity, and composite maternal morbidity. Effect modification of prolonged second stage on the association between obesity and morbidity was assessed by including an interaction term in the regression model. Results: Compared with nonobese, obese women were more likely to have a prolonged second stage (aRR: 1.48, 95% CI: 1.18-1.85 for ≥3 hours; aRR: 1.65, 95% CI: 1.18-2.30 for ≥4 hours). Obesity was associated with a higher rate of second stage cesarean (aRR: 1.78, 95% CI: 1.34-2.34) and cesarean delivery for fetal distress (aRR: 2.67, 95% CI: 1.18-3.58). Obesity was also associated with increased rates of neonatal (aRR: 1.38, 95% CI: 1.05-1.80), but not maternal morbidity (aRR: 1.06, 95% CI: 0.90-1.25). Neonatal morbidity risk was not modified by prolonged second stage. Conclusion: Obesity is associated with increased risk of neonatal morbidity, which is not modified by prolonged second stage of labor

Naturally occurring genetic variants in the oxytocin receptor alter receptor signaling profiles

The hormone oxytocin is commonly administered during childbirth to initiate and strengthen uterine contractions and prevent postpartum hemorrhage. However, patients have wide variation in the oxytocin dose required for a clinical response. To begin to uncover the mechanisms underlying this variability, we screened the 11 most prevalent missense genetic variants in the oxytocin receptor

Mitochondrial Dysfunction and Apoptosis in Cumulus Cells of Type I Diabetic Mice

Impaired oocyte quality has been demonstrated in diabetic mice; however, the potential pathways by which maternal diabetes exerts its effects on the oocyte are poorly understood. Cumulus cells are in direct contact with the oocyte via gap junctions and provide essential nutrients to support oocyte development. In this study, we investigated the effects of maternal diabetes on the mitochondrial status in cumulus cells. We found an increased frequency of fragmented mitochondria, a decreased transmembrane potential and an aggregated distribution of mitochondria in cumulus cells from diabetic mice. Furthermore, while mitochondrial biogenesis in cumulus cells was induced by maternal diabetes, their metabolic function was disrupted as evidenced by lower ATP and citrate levels. Moreover, we present evidence suggesting that the mitochondrial impairments induced by maternal diabetes, at least in part, lead to cumulus cell apoptosis through the release of cytochrome c. Together the deleterious effects on cumulus cells may disrupt trophic and signaling interactions with the oocyte, contributing to oocyte incompetence and thus poor pregnancy outcomes in diabetic females

Early Pregnancy Loss: A Role For Glucose Utilization In The Endometrial Stroma

Recurrent pregnancy loss affects a large number of women, and the causes of this disorder remain largely unknown. One of the key steps in establishing a successful pregnancy is embryo implantation. While embryo abnormalities may certainly lead to pregnancy loss, it is equally important for the uterine endometrium to adequately progress to, what is termed, a receptive state. The endometrium is composed of several cell types, including the epithelial, stromal, endothelial and a number of resident immune cells. A hallmark of endometrial receptivity is the differentiation of the endometrial stromal cell (ESC) compartment into the decidua. During this process, termed decidualization, the ESCs undergo a number of morphological and functional changes, which results in their ability to support early embryo growth and development prior to full placental function. Decidual cells show evidence of drastic changes in glucose metabolism, which is evidenced by their high stores of glycogen granules. We, therefore, hypothesized that increased glucose uptake by ESCs is necessary for decidualization and that this excess glucose is differentially metabolized in the decidual cells versus undifferentiated stroma. We first explored the abundance of GLUT mRNAs in primary ESCs isolated from mice and humans. We found that GLUT1 mRNA is the most abundant among glucose transporter family members in the ESCs of both species studied, but several other transporters also show moderately high mRNA levels. We also determined that GLUT1 is required for proper decidualization of human ESCs since in vitro knockdown of this gene significantly lowered expression of the known decidualization markers, PRL and IGFBP1. Lastly, we also demonstrated that metabolism of glucose through the pentose phosphate pathway is a requirement for proliferation and decidualization of endometrial stroma. Inhibition of the pentose phosphate pathway led to a significant decrease in the decidual reaction both in vitro and in vivo. Taken together, the outcomes of this study highlight two distinct steps of glucose utilization, uptake via Glut1 and flux through the pentose phosphate pathway, which are both necessary for proper ESC decidualization. Abnormal glucose utilization by decidualizing ESCs may provide a mechanistic explanation for idiopathic recurrent pregnancy loss

Дослідження токсичності плівкоутворювальних композицій на основі хітозану

The object of research is chitosan-based film-forming compositions with the addition of decoctions from medicinal plants: Sweet flag, Senegalia catechu, Ledum, Bergenia crassifolia; Common yarrow, Eucalyptus globulus, Eleutherococcus senticosus, Hypericum perforatum; Chamaenerion angustifolium, Iceland moss, Calendula officinalis, Urtica; Peppermint, Potentilla alba, Common tansy, Plantago major; Artemisia absinthium, Motherwort, Sage, Common sunflower.Medicinal herbs have biological activity (toxicity), which accompanies the main therapeutic effect and depends on the dose. Toxicity is not observed in all medicinal herbs, but among them there are strong and even poisonous. Presented in the composition, medicinal herbs based on 2 % chitosan are not studied for toxicity, therefore, to establish the safety of their use as a packaging for fruit and vegetables, this must be done.The developed compositions are examined for:1) toxicity using bacteriological methods by sowing on 5 % blood agar;2) manifestation of hemolysis zones and growth of B.cereus culture by diffusion into agar (well method).During the research, positive results are obtained:1) all samples are not toxic;2) hemolysis zones are not identified;3) there is a suppression of the growth of B.cereus culture, which grew on the surface of blood agar (growth retardation zones of culture B.cereus 0–34 mm).Further expansion of the study will allow the use of chitosan-based film-forming compositions that have differentiated properties with respect to solubility, sorption, bactericidal and antioxidant effects as a factor in increasing the biological value of food in the absence of toxicity in fruit and vegetable products.Из рассмотренных композиций на основе хитозана и на основе анализа характеристики лекарственных отваров было выбрано 20 видов для дальнейшего составления композиции с хитозаном 2 %. Для установления их безопасносного использования в плодоовощной продукции все образцы исследованы на токсичность и зоны гемолиза. При проведении исследований получены положительные результаты – не было обнаружено токсичности и зоны гемолиза.Із розглянутих композицій на основі хітозану та на основі аналізу характеристики лікарських відварів було обрано 20 видів для подальшого складання композиції з хітозаном 2 %. Для встановлення їх безпечного використання в плодоовочевій продукції всі зразки досліджені на токсичність та зони гемолізу. При проведенні досліджень отримані позитивні результати – не було виявлено токсичності та зони гемолізу