Maternal Vitamin D, Folate, and Polyunsaturated Fatty Acid Status and Bacterial Vaginosis during Pregnancy

Objective. To investigate associations among serum 25-hydroxy-vitamin D (25-OH-D), folate, omega-6/omega-3 fatty acid ratio and bacterial vaginosis (BV) during pregnancy. Methods. Biospecimens and data were derived from a random sample (N = 160) of women from the Nashville Birth Cohort. We compared mean plasma nutrient concentrations for women with and without BV during pregnancy (based on Nugent score ≥7) and assessed the odds of BV for those with 25-OH-D <12 ng/mL, folate <5 ug/L, and omega-6/omega-3 ratio >15. Results. The mean plasma 25-OH-D was significantly lower among women with BV during pregnancy (18.00±8.14 ng/mL versus 24.34±11.97 ng/mL, P = 0.044). The adjusted odds of BV were significantly increased among pregnant women with 25-OH-D <12 ng/mL (aOR 5.11, 95% CI: 1.19–21.97) and folate <5 ug/L (aOR 7.06, 95% CI: 1.07–54.05). Conclusion. Vitamin D and folate deficiencies were strongly associated with BV (Nugent score ≥7) during pregnancy

Разработка системы телемеханики куста № 3 Северо-Сильгинского газоконденсатного месторождения

ПРОЕКТ, СЕПАРАТОР ЦЕНТРОБЕЖНЫЙ ВИХРЕВОЙ, ТЕМПЕРАТУРА, ДАВЛЕНИЕ, ДАТЧИКИ, ИСПОЛНИТЕЛЬНЫЕ МЕХАНИЗМЫ, АВТОМАТИЗИРОВАННОЕ РАБОЧЕЕ МЕСТО, МНЕМОСХЕМА, SCADA - InTouch. Объектом исследования является газовый центробежный сепаратор СЦВ-7-159(1200) / 130. Цель работы – разработка системы телемеханики с использованием программируемого логического контроллера, на основе выбранной SCADA системы. В данном проекте была разработана система телемеханики в комплексе с системой контроля и управления технологическим процессом сепарации газа на базе промышленного контроллера Siemens S7-1200, с применением SCADA – системы InTouch.не

Myeloma coexisting with jejunal light chain amyloidosis

Amyloid Light chain (AL) amyloidosis is a rare disease, which is seen in approximately one-tenth of patients with multiple myeloma. We report a 52 years old male, who presented with complaints of anorexia and weight loss. He was diagnosed to have multiple myeloma-international staging score (ISS) Stage 3 and was started on VTD (Bortezomib, Thalidomide, and Dexamethasone) chemotherapy. Within 2 weeks of therapy, he had abdominal symptoms like abdominal pain, loose stools, vomiting and hematochezia. Imaging showed dilated proximal bowel loops with fluid filled contents and prominent vessels in rectum. Emergency surgical exploration revealed thickened proximal jejunum with blood clots in the lumen. Resection of proximal jejunum was done. Histopathological examination of resected specimen was suggestive of AL amyloidosis. Post-surgical resection of jejunum, patient had initial improvement followed by deterioration. He was discharged against medical advice as per relative’s request. Hence an index of clinical suspicion of amyloidosis must been present in all Multiple myeloma patients

Review on new approach methods to gain insight into the feto-maternal interface physiology

Non-human animals represent a large and important feature in the history of biomedical research. The validity of their use, in terms of reproducible outcomes and translational confidence to the human situation, as well as ethical concerns surrounding that use, have been and remain controversial topics. Over the last 10 years, the communities developing microphysiological systems (MPS) have produced new approach method (NAMs) such as organoids and organs-on-a-chip. These alternative methodologies have shown indications of greater reliability and translatability than animal use in some areas, represent more humane substitutions for animals in these settings, and – with continued scientific effort – may change the conduct of basic research, clinical studies, safety testing, and drug development. Here, we present an introduction to these more human-relevant methodologies and suggest how a suite of pregnancy associated feto-maternal interface system-oriented NAMs may be integrated as reliable partial-/full animal replacements for investigators, significantly aid animal-/environmental welfare, and improve healthcare outcomes

Spontaneous Prematurity, Innate Immune System, and Oxidative Stress at the Maternal-Fetal Interface: An Overview

Despite the multifactorial etiology of prematurity, intra-amniotic infection is present in 25–40% of preterm pregnancies. Bacteria in amniotic cavity synthesize phospholipases associated with the production of prostaglandins that leads to rupture of fetal membranes and uterine contractions. Bacterial pathogen-associated molecular patterns (PAMPs) activate pattern recognition receptors (PRRs) such as Toll-like (TLRs) and NOD-like receptors (NLRs), triggering pathways that culminate in the production of cytokines that further increase prostaglandin release. Importantly, endogenous molecules called damage-associated molecular patterns (DAMPs) released under stressful conditions can also activate PRRs. Risk factors for both preterm labor (PTL) and preterm premature rupture of membranes (PPROM), including infection-induced inflammation, may cause an increase of ROS release and depletion of antioxidant defenses. In spite of the similarity between the pathophysiology of PTL and PPROM, there are significant differences regarding molecular mediators, degree of tissue damage, and oxidative stress present in these two conditions. PPROM seems to be a consequence of notable tissue damage resulting from chronic oxidative stress, while PTL is associated with minimal tissue degradation resulting from acute exposure and greater antioxidant status. A better understanding of prematurity pathophysiology and the differences between PTL and PPROM can benefit therapeutic approaches to prevent these important inflammatory syndromes

Common polymorphisms in human lysyl oxidase genes are not associated with the adolescent idiopathic scoliosis phenotype

BACKGROUND: Although adolescent idiopathic scoliosis affects approximately 3% of adolescents, the genetic contributions have proven difficult to identify. Work in model organisms, including zebrafish, chickens, and mice, has implicated the lysyl oxidase family of enzymes in the development of scoliosis. We hypothesized that common polymorphisms in the five human lysyl oxidase genes (LOX, LOXL1, LOXL2, LOXL3, and LOXL4) may be associated with the phenotype of adolescent idiopathic scoliosis. METHODS: This was a case-control genetic association study. A total of 112 coding and tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 were genotyped in a discovery cohort of 138 cases and 411 controls. Genotypes were tested for association with adolescent idiopathic scoliosis by logistic regression with a two degree of freedom genotypic model and gender as a covariate. Fourteen SNPs with p < 0.1 in the discovery phase were genotyped in an independent replication cohort of 400 cases and 506 controls. RESULTS: No evidence for significant association was found between coding or tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 and the phenotype of adolescent idiopathic scoliosis. CONCLUSIONS: Despite suggestive evidence in model organisms, common variants and known coding SNPs in the five human lysyl oxidase genes do not confer increased genotypic risk for adolescent idiopathic scoliosis. The above methodology does not address rare variants or individually private mutations in these genes, and future research may focus on this area

Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy

Introduction: Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy. Current 2D or 3D cell models and animal models often fail to provide data that can effectively translate into clinical trials, leading to pregnant women being excluded from drug development considerations and clinical studies. To address this limitation, we explored the utility of in silico simulation modeling and microfluidic-based organ-on-a-chip platforms to assess potential interventional agents.Methods: We developed a multi-organ feto-maternal interface on-chip (FMi-PLA-OOC) utilizing microfluidic channels to maintain intercellular interactions among seven different cell types (fetal membrane-decidua-placenta). This platform enabled the investigation of drug pharmacokinetics in vitro. Pravastatin, a model drug known for its efficacy in reducing oxidative stress and inflammation during pregnancy and currently in clinical trials, was used to test its transfer rate across both feto-maternal interfaces. The data obtained from FMi-PLA-OOC were compared with existing data from in vivo animal models and ex vivo placenta perfusion models. Additionally, we employed mechanistically based simulation software (Gastroplus®) to predict pravastatin pharmacokinetics in pregnant subjects based on validated nonpregnant drug data.Results: Pravastatin transfer across the FMi-PLA-OOC and predicted pharmacokinetics in the in silico models were found to be similar, approximately 18%. In contrast, animal models showed supraphysiologic drug accumulation in the amniotic fluid, reaching approximately 33%.Discussion: The results from this study suggest that the FMi-PLA-OOC and in silico models can serve as alternative methods for studying drug pharmacokinetics during pregnancy, providing valuable insights into drug transport and metabolism across the placenta and fetal membranes. These advanced platforms offer promising opportunities for safe, reliable, and faster testing of therapeutic compounds, potentially reducing the number of pregnant women referred to as “therapeutic orphans” due to the lack of consideration in drug development and clinical trials. By bridging the gap between preclinical studies and clinical trials, these approaches hold great promise in improving maternal and neonatal health outcomes

Feto-maternal trafficking of exosomes in murine pregnancy models

Timing and initiation of labor are well-orchestrated by signals communicated between the fetal and maternal compartments; however, how these signals are communicated is not completely understood. Fetal exosomes, intercellular signaling vesicles, may play a key role in the process. The objective of this study was to evaluate exosome trafficking in vivo from fetal to maternal compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational day 16 and 17 with exosomes isolated from primary human amnion epithelial cells fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR). All our analyses were performed on samples collected on Day 18. After 24 h, mice were imaged using Bruker MS FX PRO In vivo Imager and tissues were collected. In vivo imaging of mouse showed fluorescence in the uterus, on the exosome-injected side whereas the uterine tissues from the uninjected side and saline and dye alone injected animals remained negative. Histological analysis of placenta showed exosome migration from the fetal to the maternal side of the placenta. Fluorescence released from exosomes was seen in maternal blood samples as well as in maternal uterus and kidneys. This study demonstrates that exosomal cargo can be carried through systemic route from the fetal to the maternal side of the uterine tissues during pregnancy, supporting the idea that fetal signals can be delivered via exosomes

Amnion epithelial cell derived exosomes induce inflammatory changes in uterine cells

Fetal endocrine signals are generally considered to contribute to the timing of birth and the initiation of labor. Fetal tissues under oxidative stress release inflammatory mediators that lead to sterile inflammation within the maternal-fetal interface. Importantly, these inflammatory mediators are packaged into exosomes, bioactive cell-derived extra cellular vesicles that function as vectors and transport them from the fetal side to the uterine tissues where they deposit their cargo into target cells enhancing uterine inflammatory load. This exosome-mediated signaling is a novel mechanism for fetal-maternal communication.This report tested the hypothesis that oxidative stress can induce fetal amnion cells to produce exosomes, which function as a paracrine intermediary between the fetus and mother and biochemically signal readiness for parturition.Primary amnion epithelial cells (AEC) were grown in normal cell culture (control) or exposed to oxidative stress conditions (induced by cigarette smoke extract). Exosomes were isolated from cell supernatant by sequential ultracentrifugation. Exosomes were quantified and characterized based on size, shape, and biochemical markers. Myometrial, decidual and placental cells (BeWo) were treated with 2x10, 2x10 and 2x10 control or oxidative stress derived AEC exosomes for 24 hours. Entry of AEC exosomes into cells was confirmed by confocal microscopy of fluorescent-labelled exosomes. The effect of AEC exosomes on target cell inflammatory status was determined by measuring production of IL-6, IL-8, IL-1β, TNF-α and PGE by ELISA and inflammatory gene transcription factor (NF-κβ) activation status by immunoblotting for phosphorylated RelA/p65. Localization of NANOG in term human myometrium and decidua obtained from women before labor and during labor was performed using immunohistochemistry. Data were analyzed by Wilcoxon-Mann-Whitney test to compare effects of exosomes from control and oxidative stress -treated AEC cells on inflammatory status of target cells.AECs released ∼125 nm, cup shaped exosomes with ∼ 899 and 1211 exosomes released per cell from control and oxidative stress induced cells respectively. AEC exosomes were detected in each target cell type after treatment using confocal microscopy. Treatment with AEC exosomes increased secretion of IL-6, IL-8 and PGE and activation of NF-κβ (each