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Introduction: The placental syncytiotrophoblast is the primary barrier between the mother and the fetus. To cross the placenta, nutrients and wastes must be transported across the apical microvillous and basal plasma membranes. While the syncytiotrophoblast basal plasma membrane is typically represented as relatively smooth, it has been shown to have invaginations that may increase its surface area. This study aimed to quantify how folding of the syncytiotrophoblast basal membrane contributes to its surface area and to visualise three-dimensional structures of the basal membrane and cytotrophoblast cell structures.Methods: Transmission electron microscope images of human term placenta were analysed using stereological approaches to quantify how folding of the syncytiotrophoblast basal plasma membrane affected surface area. Serial block-face scanning electron microscopy was used to visualise the three-dimensional structure of the syncytiotrophoblast basal membrane and cytotrophoblast cells.Results: Syncytiotrophoblast basal membrane covered 69.1% of the basal lamina, with cytotrophoblast cells covering the remaining 30.9%. In basal lamina adjacent to syncytiotrophoblast, 34% was adjacent to smooth basal membrane and 66% to folded basal membrane. Syncytiotrophoblast basal membrane folds increased the surface area adjacent to basal lamina by 305%. Including regions overlying the cytotrophoblast cells, basal membrane folds increased syncytiotrophoblast basal membrane surface area by 4.4-fold relative to the basal lamina in terminal villi. Terminal and intermediate villi were similar in terms of trophoblast coverage of the basal lamina and basal membrane folding. The three-dimensional structures of the syncytiotrophoblast basal plasma membrane and cytotrophoblast cells were generated from serial block-face scanning electron microscopy image stacks.Discussion: These findings indicate that the surface area of the syncytiotrophoblast basal plasma membrane is far larger than had been appreciated. We suggest that these folds increase the surface area available for transport to and from the fetus. Changes in the extent of basal membrane folding could affect nutrient transfer capacity and underlie pathological fetal growth, including fetal growth restriction and macrosomia. [ABSTRACT FROM AUTHOR]

Introduction: Pericytes are a common feature in the placental microvasculature but their roles are not well understood. Pericytes may provide physical or endocrine support for endothelium and in some tissues mediate vasoconstriction.Methods: This study uses serial block-face scanning electron microscopy (SBFSEM) to generate three-dimensional (3D) reconstructions of placental pericytes of the terminal villi and transmission electron microscopy (TEM) to study pericyte endothelial cell interactions. The proportion of endothelial cell junctions covered by pericytes was determined.Results: The detailed 3D models of placental pericytes show pericyte structure at a new level of detail. Placental pericytes have many fingers extending from the cell body which can span multiple capillary branches. The proportion of endothelial cell-cell junctions covered by pericytes was significantly higher than pericyte coverage of capillary endothelium as a whole (endothelium: 14%, junctions: 43%, p < 0.0001). However, the proportion of endothelial cell-cell junctions covered by pericytes in regions adjacent to trophoblast was reduced compared to regions >3 μm away from trophoblast (27% vs 62% respectively, p < 0.001). No junctional complexes were observed connecting pericytes and endothelial cells but there were regions of cell membrane with features suggestive of intercellular adhesions.Discussion: These data suggest that the localisation of pericytes on the villous capillary is not random but organised in relation to both endothelial junctions and the location of adjacent trophoblast. This further suggests that pericyte coverage may favour capillary permeability in regions that are most important for exchange, but limit capillary permeability in other regions. [ABSTRACT FROM AUTHOR]

Organophosphates and carbamates have been among the most commonly used insecticides, with both agricultural and residential uses. Previous studies have suggested associations of non-Hodgkin lymphoma (NHL) with some of these chemicals; however, many studies have been limited in their ability to evaluate associations with lymphoma subtypes. We evaluated the use of eleven organophosphate and two carbamate insecticides in association with NHL in the North American Pooled Project, which includes data from case-control studies in the United States and Canada (1690 cases/5131 controls). We used unconditional logistic regression adjusting for potential confounders, including use of other pesticides, to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between these chemicals and NHL overall, and NHL subtypes, i.e., follicular (FL), diffuse large B-cell (DLBCL), small lymphocytic lymphoma (SLL) and others. Ever use of malathion was associated with increased risk of NHL overall (OR = 1.43; 95% CI: 1.14–1.81) compared with never users. Categories using tertiles of duration (<4 yrs., 4–12 yrs., and >12 yrs) also showed a significant exposure-response for increasing years of use of malathion and risk of NHL (OR <4vsUnex = 1.33 (0.88, 2.03), OR 4-12vsUnex = 1.42 (1.02, 1.96), OR >12vsUnex = 1.55 (1.05, 2.28, p-trend < 0.01)). In addition, malathion use was statistically significantly associated with FL (OR = 1.58; 95% CI: 1.11–2.27) and DLBCL (OR = 1.61; 95% CI: 1.16–2.22) while there were no apparent associations with SLL or other subtypes, the p-value for heterogeneity across subtypes, however, was not significant. These results support previous studies suggesting an association between insecticide use and NHL overall, and provide new information on associations with NHL subtypes. • Increasing duration of exposure to organophosphate (OP) and carbamate insecticides significantly increases the risk of NHL • Increasing years of use of malathion, an OP insecticide, increased the risk of NHL overall • Malathion use was also significantly associated with the follicular and diffuse large b-cell subtypes of lymphoma [ABSTRACT FROM AUTHOR]

Passive air samplers (PAS) were evaluated for measuring indoor concentrations of phthalates, novel brominated flame retardants (N-BFRs), polybrominated diphenyl ethers (PBDEs), and organophosphate esters (OPEs). Sampling rates were obtained from a 50-day calibration study for two newly introduced PAS, polydimethylsiloxane (PDMS) or silicone rubber PAS (one with and one without a coating of styrene divinyl benzene co-polymer, XAD) and the commonly used polyurethane foam (PUF) PAS. Average sampling rates normalized to PAS surface area were 1.5 ± 1.1 m 3 day −1  dm −2 for both unsheltered PDMS and XAD-PDMS, and 0.90 m 3  ± 0.6 day −1 dm −2 for partially sheltered PUF. These values were derived based on the compound-specific sampling rates measured here and in the literature for the PAS tested, to reasonably account for site-specific variability of sampling rates. PDMS and PUF were co-deployed for three weeks in 51 homes located in Ottawa and Toronto, Canada. Duplicate PUF and PDMS samplers gave concentrations within 10% of each other. PDMS and PUF-derived air concentrations were not statistically different for gas-phase compounds. PUF had a higher detection of particle-phase compounds such as some OPEs. Phthalate and OPE air concentrations were ∼100 times higher than those of N-BFRs and PBDEs. Concentrations were not systematically related to PM 10 , temperature or relative humidity. We conclude that both PAS provide replicable estimates of indoor concentrations of these targeted semi-volatile organic compounds (SVOCs) over a three-week deployment period. However, PUF is advantageous for collecting a wider range of compounds including those in the particle phase. [ABSTRACT FROM AUTHOR]

As placental processes occur within the bounds of a three-dimensional (3D) anatomical structure, the quantification of placental structures across different scales is necessary for a proper understanding of placental function and disease (Lewis and Pearson-Farr, Placenta. 2020;102:55-60). Three-dimensional imaging techniques have recently identified and quantified novel structures in human placental villi. In equidae, fetal growth relies on feto-maternal exchanges taking place in placental villi facing the entire uterine endometrium. Villi length increases throughout pregnancy, but branching and internal blood flow have been poorly explored so far. Here, we present a workflow for correlative multiscale 3D imaging combining X-ray Computed Microtomography (microCT) and Serial Block Face Scanning Electron Microscopy (SBF-SEM) applied to villi from sections (∼3 × 3 mm) of the chorioallantois taken from term placentas in horses (n=2),zebras (n=2), donkeys (n=3), and mules (n=5). Although this work is still ongoing and biological conclusions are pending, this workflow, resulting in 3D villi reconstructions, enabled the quantification of the 3D villus structure across multiple orders of magnitude for metrics such as surface area, volume, and branching angle. Not only were the reconstructions able to identify novel nanoscale structures in equine villi, such as stromal macrovesicles previously only observed in human placental villi, but they also allowed the computational modelling of physiological processes such as blood flow and diffusion through realistic tissue geometries. Taken together, the structural data generated from this correlative workflow will help us to better resolve equine placental organization, contribute towards a holistic understanding of equine placental function in health and disease, and identify potential differences between different equid species. [ABSTRACT FROM AUTHOR]

Background: Little is known about compliance with universal precautions (CUP) or occupational exposures to blood and body fluids among Emergency Medical Services (EMS) providers. The objective of this study was to obtain estimates of CUP and knowledge of universal precautions (KUP), occupational exposures, and needle and lancet sticks in the prehospital environment. Methods: A convenience sample of workers (n=311, 51% response) from 17 agencies in Virginia that provided emergency ground transportation (volunteer, commercial, government rescue squads, and fire departments) completed a questionnaire on certification and training, KUP, CUP, exposures and needlesticks, risk perceptions, and demographic variables. Results: Nearly all EMS providers reported exposures and were concerned about risk of HIV and hepatitis. Providers reported inconsistent CUP when treating patients or using needles, including failure to wear gloves (17%) and to appropriately dispose of contaminated materials (79%), including needles (87%), at all times. Certification type (advanced and basic) was related to both KUP and CUP. Of those respondents reporting current sharps use, 40% recapped needles. A lancet stick was reported by 1.4% (n=5), and 4.5% reported a needlestick (n=14). Conclusion: EMS providers working in the prehospital environment experience significant exposures but are not consistently using universal precautions. [Copyright &y& Elsevier]

Organophosphate esters (OPEs) are high-production volume chemicals. Use of OPEs has largely increased since the phase-out/ban of polybrominated diphenyl ethers (PBDEs). The ubiquitous occurrence of OPEs, in higher concentrations in abiotic matrices than brominated flame retardants (BFRs), is a concern because several of the OPEs have been linked to adverse health effects. In this study, urinary metabolites of OPEs were measured in a subset of a population-based sample of women of child bearing age recruited in Ontario, and associations between serum lipid levels and urinary concentrations of OPE metabolites were evaluated. Urine samples (n = 120) were extracted using automated solid phase extraction and analysed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Diphenyl phosphate (DPHP), bis(2-chloropropyl) phosphate (BCIPP) and bis(1,3-dichloro-2 propyl) phosphate (BDCIPP) were detected with frequencies of 100%, 76% and 75% at median concentrations of 13.8 ng/mL, 0.5 ng/mL and 1.8 ng/mL, respectively. Bis(2-chloroethyl) hydrogen phosphate (BCEP) and di-cresyl phosphate (DCP; mixture of 3 isomers) were detected in 52% and 42% of the samples, respectively. Detected at lower frequencies were 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP, 29%), bis-2(butoxyethyl) phosphate (BBOEP, 11%), and desbutyl-tris-(2-butoxy-ethyl) phosphate (desbutyl TBOEP, 9%). Using multiple regression model, a negative statistically significant correlation was observed between BCEP and cholesterol (p = 0.04), as well as BCEP and total lipid (p = 0.04). Whereas BCIPP was positively and significantly correlated with cholesterol (p = 0.003) and LDL (p = 0.001). Additional work to further explore these relationships and to evaluate more recently identified OPE metabolites is warranted. Image 1 • Urinary metabolites of OPEs were measured in Canadian women. • Chlorinated phosphate esters, and diphenyl phosphate were commonly detected. • BCEP was negatively and significantly correlated with cholesterol and total lipid. • BCIPP was positively and significantly correlated with cholesterol and LDL. [ABSTRACT FROM AUTHOR]

Antibodies to the phospholipase A2 receptor 1 (PLA2R1) have been reported in 70% of cases of idiopathic membranous nephropathy (IMN). The genetic susceptibility of IMN has been accounted for by HLA DQA1 and PLA2R1 genes. Here we retrospectively quantified PLA2R antibodies by ELISA, and genotyped DQ alleles and PLA2R1 single-nucleotide polymorphisms for association with clinical criteria for disease activity at the time of first sample and with outcome over a median total follow-up of 90 months. In 90 prevalent patients with biopsy-proven IMN, anti-PLA2R antibodies were present in 75% of patients with IMN with active disease and were significantly higher than in patients in partial or complete remission at the time of antibody measurement. There was a differential IgG subclass response (4>2>3>1) at an early stage, i.e., within 6 months of biopsy. Levels of PLA2R antibodies were significantly linked to DQA1*05:01 and DQB1*02:01. Survival analysis of patients with IMN showed that PLA2R antibodies are significantly linked with outcome. Thus, high levels of PLA2R antibodies are linked with active disease and a higher risk of declining renal function during follow-up. Future therapeutic trials in IMN should monitor anti-PLA2R, as patients with a high antibody burden may benefit from earlier therapeutic intervention. [ABSTRACT FROM AUTHOR]