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Introduction: Placental abruption (PA) is a major obstetric complication associated with worse maternal and neonatal outcomes. Though ultrasound findings may support the diagnosis of PA, the association of such findings to the severity of PA and maternal and neonatal outcomes is not yet clear. We aimed to assess the maternal and neonatal outcomes of PA cases with vs. without related sonographic findings., Methods: In this retrospective cohort study, all deliveries complicated by PA between 2009 and 2022 were included. Placental histopathology, obstetric, and neonatal outcomes were compared between cases of PA with vs. without supporting sonographic findings. A composite of severe neonatal morbidity was compared between the groups, including ≥1 of the following: seizures, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, periventricular leukomalacia, respiratory-distress syndrome, sepsis, anemia, blood transfusion or death., Results: Of the 420 cases with PA eligible for the study, 50 patients (12 %) were in the PA with sonographic features group and 370 (88 %) were in the PA without sonographic features group. The PA with sonographic features group was characterized by significantly higher rates of prematurity (p < 0.001), severe composite adverse neonatal outcome (p < 0.01), and a composite maternal vascular malperfusion lesions in placental histopathology (p = 0.001) In multivariable regression analyses, preterm birth was independently associated with the presence of sonographic features (aOR = 8.79, 95 % CI 2.41-31.93, p < 0.001)., Discussion: PA with supporting sonographic features is associated with higher rates of adverse obstetric and neonatal outcomes and placental lesions. These findings emphasize the importance of sonographic evaluation for every case of PA before deciding upon management., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: We aimed to assess neonatal and maternal outcomes in appropriate-for-gestational-weight (AGA) neonates of mothers with both gestational diabetes mellitus (GDM) and preeclampsia (PET)., Methods: Medical records of women diagnosed with GDM or PET were reviewed. Women with AGA neonates were divided into three groups- GDM, PET, and GDM + PET and maternal neonatal and placental outcomes were compared. The primary outcome was a composite of adverse neonatal outcomes, including intensive care unit admission (NICU), neurological morbidity, hypoglycemia, ventilation, respiratory distress syndrome (RDS), phototherapy, sepsis, blood transfusion, and neonatal death. Post-hoc analysis was performed to determine between-group significance., Results: Composite adverse neonatal outcomes are significantly lower in women with multiple morbidities compared to women with confined PET (p = 0.015), and a similar trend is observed when comparing neonatal outcomes between women with GDM to those with GDM + PET, yet these results are underpowered (18.9 % vs. 12.8 % respectively, p = 0.243). Placentas of women with GDM + PET were larger, with a lower rate of placentas below the 10th percentile as compared to placentas of women with isolated PET (p < 0.001), but with similar rates of MVM lesions., Discussion: While maternal and placental outcomes in patients of the GDM + PET group resemble the characteristics of the PET group, surprisingly, the neonatal outcomes in this group are significantly better compared to isolated morbidities. The paradoxical benefit attributed to the coexistence of GDM + PET may be explained by a balance of the opposing trends characterizing these morbidities-the reduced blood and nutrient supply characterizing PET vs. chronic overflow and abundance typical of GDM., Clinical Trial Registration: approval of local ethics committee WOMC-19-0152., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

With an on-going disproportional warming of the Arctic Ocean and the reduction of the sea ice cover, the risk of an accidental oil spill from ships or future oil exploration is increasing. It is hence important to know how crude oil weathers in this environment and what factors affect oil biodegradation in the Arctic. However, this topic is currently poorly studied. In the 1980s, the Baffin Island Oil Spill (BIOS) project carried out a series of simulated oil spills in the backshore zone of beaches located on Baffin Island in the Canadian High Arctic. In this study two BIOS sites were re-visited, offering the unique opportunity to study the long-term weathering of crude oil under Arctic conditions. Here we show that residual oil remains present at these sites even after almost four decades since the original oiling. Oil at both BIOS sites appears to have attenuated very slowly with estimated loss rates of 1.8-2.7% per year. The presence of residual oil continues to significantly affect sediment microbial communities at the sites as manifested by a significantly decreased diversity, differences in the abundance of microorganisms and an enrichment of putative oil-degrading bacteria in oiled sediments. Reconstructed genomes of putative oil degraders suggest that only a subset is specifically adapted for growth under psychrothermic conditions, further reducing the time for biodegradation during the already short Arctic summers. Altogether, this study shows that crude oil spilled in the Arctic can persist and significantly affect the Arctic ecosystem for a long time, in the order of several decades., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Fetal growth restriction (FGR) in dichorionic diamniotic (DCDA) twin gestations is a known complication associated with adverse neonatal outcomes. The international guidelines have no consensus on whether to use singleton or twin-specific growth charts. Thus, we aimed to compare growth charts in correlation with pregnancy outcomes and placental histopathology., Methods: The medical files of all DCDA twin deliveries between 2010 and 2020 were reviewed. Birthweight percentile for gestational age (GA) for each individual neonate was assigned using the updated local singleton and twin-specific growth chart. We then divided the study population into two groups, neonates that were FGR based on the local singleton charts (FGR-singleton group) versus FGR on both twin-specific and singleton charts (FGR-twin group). Placental lesions were classified as lesions related to maternal or fetal malperfusion lesions (MVM, FVM), vascular and villous changes, and inflammatory lesions., Results: Overall, 185 neonates met the inclusion criteria. The FGR-twin group (59/185) had a higher rate of PE, lower GA at delivery, lower birthweight, and a higher rate of neonatal composite adverse outcomes compared to the FGR-singleton group. Moreover, placental pathology of the FGR-twin group demonstrated a higher rate of MVM lesions (p = 0.035)., Discussion: In our cohort, neonates considered FGR based on twin-specific charts had worse neonatal outcomes with underlying placental insufficiency demonstrated by a higher rate of placental malperfusion vascular lesions. Our findings support using a twin-specific chart to diagnose FGR that is more clinically relevant., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Ltd.)

The Baffin Island Oil Spill (BIOS) Project is a long-term monitoring field study conducted in the early 1980s, seeking to examine the physical and chemical fate of crude oil released into a pristine Arctic setting. During the present study, sites of the BIOS Project were revisited in 2019 for the collection of oiled intertidal and backshore sediments. These samples were analyzed for several groups of petroleum hydrocarbons including saturates (n-alkanes, branched alkanes, and alkylcycloalkanes), hopane and sterane biomarkers, and alkylbenzenes. These hydrocarbon groups were present in concentrations ranging from 1.77-1210, 0.224-51.7, 0.0643-16.9, 0.00-11.7, and 0.0171-8.60 mg/kg within individual samples, respectively. When comparing current to limited results from past BIOS studies, a representative branched alkane (phytane), and medium-chain (nC18) and long-chain (nC30) n-alkanes demonstrate extensive weathering processes, exhibiting up to 90 %, 98 %, and 77 % loss since the penultimate BIOS revisitation in 2001, respectively., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Blake Hunnie, Gary Stern, Lars Schreiber, Charles Greer reports financial support was provided by Fisheries and Oceans Canada. Blake Hunnie, Gary Stern, Lars Schreiber, Charles Greer reports financial support was provided by Genome Canada. Blake Hunnie, Gary Stern, Lars Schreiber, Charles Greer reports financial support was provided by ArcticNet. Blake Hunnie, Gary Stern, Lars Schreiber, Charles Greer reports financial support was provided by Amundsen Science. Gary Stern reports financial support was provided by Natural Sciences and Engineering Research Council of Canada., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Introduction: Late fetal growth restriction (FGR) is associated with mild growth restriction and normal or mild abnormal doppler flows. The cerebroplacental ratio (CPR) has been demonstrated as more sensitive to hypoxia than its individual components in these fetuses. We hypothesized that abnormal CPR in late FGR is reflected in specific placental vascular malperfusion lesions., Methods: Retrospective cohort study of late FGR newborns between 2012 and 2022 in a tertiary hospital. Overall, 361 cases were included: 104 with pathological CPR (study group), and 257 with normal doppler flows (control group). The primary outcome was a composite of maternal vascular malperfusion lesions (MVM) and fetal vascular malperfusion lesions (FVM). Secondary outcomes were macroscopic placental characteristics and various obstetrical and neonatal outcomes., Results: The study group had lower birthweight compared with the normal CPR group (2063.5 ± 470.5 vs. 2351.6 ± 387.4 g. P < 0.0001), higher rates of composite adverse neonatal outcomes (34.2% vs. 22.5%, p < 0.0001), lower mean placental weight (318 ± 71.6 vs. 356.6 ± 76.5 g, p < 0.0001), as well as a higher prevalence of Vascular lesions of MVM (15.3% vs. 5.0%, p = 0.002), villous lesions of FVM (37.5% vs. 24.9%, p = 0.02), and composite FVM lesions (36.5% vs. 25.6%, p = 0.04). On multivariate regression analysis for MVM lesions and composite FVM lesions, abnormal CPR was found as an independent risk factor (aOR 2.17, 95% CI 1.63-4.19, and aOR 1.31, 95% CI 1.09-3.97, respectively)., Discussions: Abnormal CPR in late FGR is reflected in placental histopathologic vascular malperfusion lesions, and the incidence of these lesions is higher than in FGR placentas with normal CPR., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The Arctic is a unique environment characterized by extreme conditions, including daylight patterns, sea ice cover, and some of the lowest temperatures on Earth. Such characteristics in tandem present challenges when extrapolating information from oil spill research within warmer, more temperate regions. Consequently, oil spill studies must be conducted within the Arctic to yield accurate and reliable results. Sites of the Baffin Island Oil Spill (BIOS) project (Cape Hatt, Baffin Island, Canadian Arctic) were revisited nearly 40 years after the original oil application to provide long-term monitoring data for Arctic oil spill research. Surface and subsurface sediment samples were collected from the intertidal zone of the 1981 nearshore oil spill experiment (Bay 11), from 1980 supratidal control plots (Crude Oil Point) and 1982 supratidal treatment plots (Bay 106). Samples were analyzed for Polycyclic Aromatic Hydrocarbons (PAHs) and alkylated homologues via Gas Chromatography - Mass Spectrometry (GC-MS). Our results suggest that total mean concentrations of all measured PAHs range from 0.049 to 14 mg/kg, whereas total mean concentrations of the 16 US EPA priority PAHs range from 0.02 to 2.1 mg/kg. The relative proportions of individual PAHs were compared between sampling sites and with the original technical mixture. Where available, percent loss of individual PAHs was compared with data from samples collected at the BIOS site, in 2001. All three sites featured samples where concentrations of various priority PAHs exceeded the established Interim Marine Sediment Quality Guidelines. All supratidal samples contained potentially toxic levels of PAHs. Even after nearly four decades of weathering, the recalcitrant crude oil residues remain a potential hazard for the native organisms. Continued monitoring of this unique study site is crucial for establishing a timeline for oil degradation, and to observe a reduction in toxicity over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The biodegradability of residues derived from in-situ burning, an oil spill response strategy which involves burning an oil slick on the sea surface, has not yet been fully studied. With a growing risk of oil spills, the fate of the persistent burn residue containing potentially toxic substances must be better understood. Microcosms were used to study the microbial community response and potential biodegradability of in-situ burn residues generated from Ultra Low Sulphur (ULS) marine diesel. Microcosm studies were conducted using residues originating from the burning of unweathered and weathered diesel, with the addition of a fertilizer and a dispersant. Burn residues were incubated for 6 weeks at 7 °C in natural seawater with continual agitation in the dark. Samples were subsequently sacrificed for chemistry as well as 16S rRNA gene amplicon and shotgun metagenomic sequencing. Chemistry analyses revealed a reduction in hydrocarbon concentrations. Medium chain-length n-alkanes (nC 16 -nC 24 ) decreased by 8% in unweathered burn residue microcosms and up to 26% in weathered burn residue microcosms. A significant decrease in polycyclic aromatic hydrocarbon (PAH) concentrations was observed only for naphthalene, fluorene and their alkylated homologs, in the microcosms amended with residue produced from burning weathered diesel. Decreases of 2-24%, were identified depending on the compound. Microcosms amended with burn residues had distinct microbial communities marked by an increase in relative abundance of putative hydrocarbon degraders as well as an increase of known hydrocarbon-degradation genes. These novel results suggest that if in-situ burning is performed on ULS marine diesel, some of the indigenous bacteria would respond to the newly available carbon source and some of the residual compounds would be biodegraded. Future studies involving longer incubation periods could give a better understanding of the fate of burn residues by shedding light on the potential biodegradability of the more recalcitrant residual compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

In 1999, a tidal wetland located along the St. Lawrence River close to Ste. Croix de Lotbinière (Quebec, Eastern Canada) was the site of an experimental oil spill. Test plots were established and subjected to an experimental crude oil spill to evaluate natural attenuation, nutrient amendment and vegetation cropping as countermeasures. In 2020, this study re-visited the test plots to investigate residual oil and habitat recovery. Only concentrations of mid-chain length n-alkanes (C10-C36), but not of polycyclic aromatic hydrocarbons (PAHs), were significantly above detection limit, and were detected in both test plot and control sediments. Hydrocarbon, total organic carbon, nitrogen and phosphate contents did not differ significantly between test plot and control sediments. Microbial analyses did not detect significant differences in microbial load, microbial diversity or microbial community composition between test plot and control sediments. Key genes for the aerobic and anaerobic degradation of n-alkanes as well as for the aerobic degradation of PAHs were detected in all sediment samples. Associated gene abundances did not differ significantly between test plot and control sediments. This study shows that oil-exposed test plot sediments of the Ste. Croix wetland can be considered completely recovered after 21 years irrespective of the performed countermeasure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate (a) how many questions and negative emotions (cues/concerns) breast and/or gynecologic cancer patients and companions express during their case discussion in multidisciplinary tumor conferences (MTCs), (b) with which topics the emotions are linked, and (c) which patient- and context-related characteristics determine patients' communicative behavior., Methods: This observational study included audio/video recordings of MTCs with patient participation in three breast and gynecological cancer centers. Using the Verona Coding Definitions of Emotional Sequences, patients' and companions' questions and negative emotions expressed were analyzed. Multiple regression analyses were used to determine associations between communicative behavior and patient- and context-related characteristics., Results: We identified 607 questions and 230 cues/concerns expressed by patients/companions in 82 case discussions in MTCs. The number of questions was significantly associated with the hospital. In case discussions with patients who had need for psychological support and who were accompanied, more questions were asked by patients/companions., Conclusion: The results show that active patient participation does not depend only on patient characteristics, but also on the hospital setting., Practice Implications: If cancer centers want to enable patient participation in MTCs, they must define the role of the patient before. Subsequently, conditions must be created to enable this role expectation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Given the importance of completing multimodality therapy, the purpose of this qualitative study was to characterize physician perspectives on barriers and facilitators to delivering NT., Methods: A purposive sample of surgical, medical, and radiation oncologists participated in semi-structured interviews. Interviews were transcribed and coded by 3 independent researchers, iteratively identifying themes until saturation was achieved., Results: Participants (n = 27) were heterogeneous in specialty, years of experience, practice setting, gender, and geography. The most commonly cited advantage of NT was the ability to downstage patients. The most commonly cited barriers included lack of access and limited evidence. Patient preference for immediate surgery was frequently cited as a barrier, but most participants felt that patients eventually understood the treatment recommendation after informed discussion. Recommendations to enhance the delivery of NT included improved patient education, communication, and better evidence., Conclusion: In this qualitative study, indications for, barriers to, and opportunities to improve the delivery of NT for localized PDAC were identified. These results highlight the need for better evidence and protocol standardization for NT as well as methods of improving care coordination, communication, and education to improve patient-centered outcomes., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: An increased risk of an unfavorable obstetric outcome has been reported in relation with Müllerian anomalies (MA). We evaluated whether placental lesions are more frequent among patients with MA and correlates with adverse pregnancy outcomes., Methods: The medical records and placental histopathologyy of consecutive patients with MA between 2007 and 2020 were reviewed. A control group matched for maternal age and pregnancy complications was selected in a 1:1 ratio. Characteristics were then compared between the MA and control groups., Results: The study group included 110 patients with MA. Patients in the MA group gave birth at earlier gestational age as (35.8 ± 3.3 vs 39.1 ± 1.3 weeks, respectively, P < 0.001). Placental weight <10th percentile was significantly more frequent in the MA cohort compared with controls (31% vs. 6%, respectively, p < 0.001). Higher rates of vascular and villous lesions of maternal vascular malperfusion (MVM) were also detected in the MA group (P = 0.04, P = 0.01, respectively). On multivariable analysis the presence of MA was an independent predictor of composite placental MVM lesions (OR 3.9, 95% CI 2.2, 6, p = 0.04). Using multivariate logistic regression models, the presence of MA was also found to be an independent predictor of small for gestational age (SGA), (OR 4.2, 95% CI 2.7, 11.7, p = 0.01)., Discussion: MA are associated with placental MVM lesions and SGA independent of background confounders including gestational age - suggesting a placental involvement in the association between MA and adverse pregnancy outcomes. Prospective studies among larger cohorts are needed to corroborate our results., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Quantifying the detection rate of the widely used quantitative RT-PCR (RT-qPCR) test for severe acute respiratory syndrome coronavirus 2 and its dependence on patient demographic characteristics and disease progression is key in designing epidemiologic strategies. Analyzing 843,917 test results of 521,696 patients, a "positive period" was defined for each patient between diagnosis of coronavirus disease 2019 and the last positive test result. The fraction of positive test results within this period was then used to estimate detection rate. Regression analyses were used to determine associations of detection with time of sampling after diagnosis, patient demographic characteristics, and viral RNA copy number based on RT-qPCR cycle threshold values of the next positive test result. The overall detection rate in tests performed within 14 days after diagnosis was 83.1%. This rate was higher at days 0 to 5 after diagnosis (89.3%). Furthermore, detection rate was strongly associated with age and sex. Finally, the detection rate with the Allplex 2019-nCoV RT-qPCR kit was associated, at the single-patient level, with viral RNA copy number (P < 10 -9 ). These results show that the reliability of the test result is reduced in later days as well as for women and younger patients, in whom the viral loads are typically lower., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: We aimed to investigate obstetric and neonatal outcomes and placental histological findings in in vitro fertilization (IVF) pregnancies complicated by gestational diabetes mellitus (GDM) as compared to unassisted pregnancies., Methods: This was a retrospective cohort of deliveries at a single university affiliated center between 12/2008 and 01/2020. Included were singleton pregnancies complicated by GDM, for which placental histopathological examination was performed. Obstetric, neonatal and placental outcomes were compared between pregnancies following IVF and unassisted pregnancies. Placental lesions were categorized according to the "Amsterdam" criteria., Results: Included were 688 deliveries with a diagnosis of GDM with placental examination - 69 IVF pregnancies (IVF group) and 619 unassisted pregnancies (control group). The IVF group was characterized by a significantly higher maternal age and higher rate of nulliparous women - 60.8% vs. 32.9%, p < 0.001. There were no differences in GDM type between the study groups - about two thirds of cases were GDMA1 and on third GDMA2. A higher incidence of preeclampsia was noted in the IVF group - 17.3% vs. 9.3%, p = 0.03, with no difference in cesarean deliveries and birthweight. IVF deliveries were characterized by a significantly higher rate of adverse neonatal outcomes - 18.8% vs. 8.8%, p = 0.008, although this did not attain significance after adjustment to gestational age. No differences were noted in placental histology between the groups., Discussion: GDM in IVF is associated with a significantly higher rate of adverse neonatal outcomes, as compared with non-assisted pregnancies complicated by GDM. Placental histology does not shed light on these clinical associations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Sea ice loss is opening shipping routes in Canada's Northwest Passage, increasing the risk of an oil spill. Harnessing the capabilities of endemic microorganisms to degrade oil may be an effective remediation strategy for contaminated shorelines; however, limited data exists along Canada's Northwest Passage. In this study, hydrocarbon biodegradation potential of microbial communities from eight high Arctic beaches was assessed. Across high Arctic beaches, community composition was distinct, potential hydrocarbon-degrading genera were detected and microbial communities were able to degrade hydrocarbons (hexadecane, naphthalene, and alkanes) at low temperature (4 °C). Hexadecane and naphthalene biodegradation were stimulated by nutrients, but nutrients had little effect on Ultra Low Sulfur Fuel Oil biodegradation. Oiled microcosms showed a significant enrichment of Pseudomonas and Rhodococcus. Nutrient-amended microcosms showed increased abundances of key hydrocarbon biodegradation genes (alkB and CYP153). Ultimately, this work provides insight into hydrocarbon biodegradation on Arctic shorelines and oil-spill remediation in Canada's Northwest Passage., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: We aimed to investigate the effect of maternal passive smoking (MPS) during pregnancy-on placental pathology and pregnancy outcomes., Methods: A prospective case-control study. We recruited low-risk laboring women at 37+0-41 + 0 weeks between 9/2019-7/2020. MPS was defined as exposure to in-house spouse tobacco smoking of >20 cigarettes/day in the absence of maternal active-smoking. In attempt to "purify" the effect of MPS on placental pathology-we excluded cases with preeclampsia, diabetes, suspected fetal growth restriction (FGR), preterm labor, and illicit drug use. Maternal characteristics, pregnancy outcomes, and placental pathology were compared between the MPS group and a control group matched for gestational age, maternal age, and delivery date. Placental lesions were classified according to the "Amsterdam" criteria. The study was powered to detect a 33% difference in placental malperfusion lesions. Multivariable regression was performed to identify independent associations with placental malperfusion lesions., Results: In labor, the MPS group (n = 115) had higher rates of meconium stained amniotic fluid (MSAF, p < 0.001) and non-reassuring fetal heart-rate (NRFHR,p = 0.006), compared to controls (n = 115). Neonates in the MPS group had higher rates of undiagnosed FGR (p = 0.01) and NICU admissions (p = 0.004). The MPS group had higher rates of placental-hypoplasia (p = 0.02) and fetal vascular malperfusion (FVM) lesions (p = 0.04). In regression analysis MPS was associated with FVM lesions independent of background confounders (aOR = 1.24 95% CI 1.10-2.65)., Discussion: In otherwise low-risk pregnancies, MPS was associated with higher rates of MSAF, NRFHR, undiagnosed FGR, and NICU admissions, probably mediated via placental FVM. These worrisome findings mandate patient counseling and further investigation in larger population-based studies., Competing Interests: Declaration of competing interest There is not any financial relationship with any organization or any conflict of interest to report., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Antenatal corticosteroids (ACS) are frequently used to reduce neonatal morbidity in preterm births (PTBs). A 'rescue' dose of ACS can be administer, if the risk of PTB remains. Some reports indicated that repeated doses of ACS might impact placental histology and possibly its function. We aimed to study whether repeated doses of ACS effect placental histopathology and pregnancy outcome., Methods: The medical files and placental reports of all PTB, at 24-33 6 / 7 weeks, between Nov 2008-Dec 2019, were reviewed. The study population was divided into three groups; no-ACS (PTBs without ACS treatment), one-ACS (PTBs after a full or partial ACS course), and rescue-ACS (PTBs after a 'rescue' course of ACS). Placental lesions were classified according to "Amsterdam" criteria into maternal and fetal vascular malperfusion lesions, maternal and fetal inflammatory responses and chronic villitis. Placental lesions and pregnancy outcome were compared between the study groups., Results: The no-ACS group (n = 58) was characterized by increased rates of PTB<28 weeks (p = 0.003), perinatal death (p < 0.001) and composite neonatal infectious morbidity (p = 0.022), as compared to the one-ACS group (n = 331) and the rescue-ACS group (n = 53). Placental MIR lesions were more common among the rescue-ACS group, compared to the one- and no-ACS groups (p = 0.022). Other placental lesions did not differ between the groups. On multivariate logistic regression analysis, MIR lesions were independently associated with rescue-ACS treatment (aOR 3.00, 95% CI 1.10-8/17, p = 0.031)., Discussion: Rescue course of ACS is associated with increased rate of placental maternal inflammatory response. These findings probably result from maternal stress stimuli without an adverse impact on early neonatal outcome., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: We aimed to investigate the effect of placental histologic chorioamnionitis (HC) on neonatal outcomes in pregnancies complicated by fetal growth restriction (FGR)., Methods: - The computerized medical files of all pregnancies diagnosed with FGR (birthweight <10th percentile) at 24-42 weeks of gestation between 2008 and 2019 were reviewed. Maternal and neonatal outcomes were compared between FGR with and without evidence of placental HC. Placental lesions were classified according to "Amsterdam" criteria. Composite adverse neonatal outcome-included any of the following complications: neurological morbidity, neonatal respiratory assistance, RDS, NEC, sepsis, blood transfusion, phototherapy, hypoglycemia, or neonatal death. Composite severe adverse neonatal outcome included any of the following complications - neurological morbidity, blood transfusion, NEC, sepsis, RDS, neonatal death., Results: - Compared to FGR without HC (n = 446), FGR with HC (n = 57) was characterized by more advanced gestational age at delivery 39.2 (38.3-39.9) vs. 38.2 (36.9-39.2), weeks respectively, p < 0.001), higher rate of nulliparity (73.7% vs. 45.1%, p < 0.001), less vascular lesions of MVM (1.8% vs.11.2%, p = 0.02), higher rate of Apgar scores at 5 min <7 (10.5% vs. 2%, p = 0.004), increased neonatal death (7.0% vs. 0.9%, p = 0.007), higher rates of both composite adverse neonatal outcome (31.1% vs. 17.3% p = 0.02), and composite severe adverse neonatal outcome (16.3% vs. 8.2% p = 0.04). By multivariate regression analysis HC was found to be independently associated with composite adverse neonatal outcome (aOR = 1.21, 95% CI 1.08-2.38) and with severe composite adverse neonatal outcome (aOR = 1.39, 95% CI 1.16-3.76)., Conclusions: Pregnancies complicated by FGR with concomitant HC were associated with higher rates of adverse neonatal outcomes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: We aimed to compare obstetric and neonatal outcomes of deliveries complicated by meconium stained amniotic fluid (MSAF), according to placental histology of continuous vs. acute meconium associated changes., Methods: This was a retrospective cohort study of singleton deliveries complicated by MSAF at a single university-affiliated medical center during 2008-2018. Obstetric and neonatal outcomes were compared between cases with placental acute vs. continuous meconium exposure associated changes (columnar epithelial changes and meconium-laden macrophages, respectively). Regression analysis was used to identify independent associations with adverse neonatal outcomes., Results: The medical records of 294 deliveries at our institution were reviewed, along with medical records of the neonates and the histopathological reports of their placentas. Ninety-two cases were classified as an acute placental reaction to meconium (acute exposure group) and 200 as continuous placental exposure (continuous exposure group). Patient demographics did not differ between groups. Placentas from the continuous exposure to meconium were associated with a higher rate of placental weight <10th percentile (p = 0.03) while the acute exposure group was associated with a shorter time between rupture of membranes and delivery (p = 0.02). and higher rates of non-reassuring fetal heart rate in labor (p = 0.003), and of adverse neonatal outcome (p = 0.02). In multivariable analysis adverse neonatal outcome was associated with acute histologic exposure to meconium independent of background confounders (aOR = 1.51, 95% CI 1.12-3.67)., Conclusions: Acute histological changes of MSAF were independently associated with adverse neonatal outcomes as compared to continuous histologic MSAF., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, including any financial, personal or professional interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Research Question: What are the clinical characteristics of pregnancies complicated by fetal growth restriction (FGR) and preeclampsia in patients who have undergone IVF, and what is the correlation between these complications and histopathological placental findings in such pregnancies., Design: A retrospective cohort of patients who had delivered their babies at our institution who had been diagnosed with preeclampsia, whose babies had been diagnosed with FGR, or both. Deliveries in which the placenta was sent for histopathological examination were included. Computerized files and pathological reports were reviewed, and maternal, obstetric, neonatal outcomes and placental histopathological reports were compared between pregnancies conceived by IVF and controls. Placental lesions were classified according to the Amsterdam criteria., Results: Between December 2008 and December 2018, the placentas of 1114 singleton babies who had received a diagnosis of FGR, whose mothers had received a diagnosis of preeclampisa, or both, were examined. A total of 105 patients conceived with IVF and 1009 were conceived spontaneously. The IVF group was older, of lower parity and had a higher rate of diabetes and chronic hypertension. Deliveries occurred at an earlier gestational age, although birth weight was not significantly different between the groups. The rate of neonatal adverse composite outcome among IVF deliveries was significantly lower (59.0% versus 76.7%; P < 0.001). On placental examination, placental weight, maternal and fetal vascular malperfusion lesions were similar between the groups, whereas villitis of unknown etiology was significantly more common among the IVF group (16.2% versus 8.3%; P = 0.007)., Conclusion: Neonatal outcome is relatively favourable in IVF patients with placental-related diseases. Placental chronic villitis is more common in IVF patients, pointing to an additive immunological cause., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: Two possible causative pathways have been suggested to participate in the development of placental abruption (PA), an acute inflammatory pathway and placental vascular derived, a chronic pathway. We aimed to study the impact of the inflammatory pathway on maternal and neonatal outcome., Methods: The computerized medical files and placental reports of all pregnancies diagnosed with PA, between 11/2008-1/2019, at 24-42 weeks, were reviewed. Placental lesions were classified according to "Amsterdam" criteria into maternal and fetal vascular malperfusion lesions, acute inflammatory responses and chronic villitis. Composite neonatal morbidity included ≥1 of the following: seizures, intra-ventricular hemorrhage (IVH), hypoxic-ischemic encephalopathy, periventricular leukomalacia (PVL), blood transfusion, necrotizing enterocolitis (NEC), neonatal sepsis, respiratory distress syndrome, or neonatal death. Maternal and neonatal outcome were compared between PA with and without histologic chorioamnionitis (HC)., Results: As compared to the PA without HC group (n = 267), the PA with HC group (n = 77) was characterized by lower gestational age (GA) at delivery (32.9 ± 5.5 vs. 35.6 ± 4.1 weeks, p < 0.001), higher rates of oligohydramnios (p < 0.001), bloody amniotic fluid at labor (p < 0.001), maternal postpartum fever (p < 0.001), longer maternal hospitalization (<0.001), and increased composite adverse neonatal morbidity (41.6% vs. 22.8%, p = 0.002). By multivariate analysis, GA and HC were found to be independently associated with adverse neonatal outcome, aOR 0.63 95% CI 0.43-0.78, p < 0.001, and aOR1.12, 95% CI 1.02-3.87, p = 0.04, respectively., Discussion: The involvement of the inflammatory causative pathway in the development of placental abruption, is associated with increased maternal and neonatal morbidity., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective structured clinical examinations assess learners "showing how" to perform complex clinical tasks. Devised as summative evaluations, these examinations with immediate feedback are useful formative evaluations to improve learner performance. This review describes how objective structured clinical examinations have been used in rheumatology education. Steps for creating an objective structured clinical examination are discussed. Validity and reproducibility are important considerations, especially for high-stakes summative objective structured clinical examinations. Consideration of the potential benefits in clinical education and their hazards are reviewed. When well-designed, formative objective structured clinical examinations have high educational value for learners and medical educators., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Isolated term oligohydramnios (ITO) is an obstetrical complication of which the etiology, management, and clinical importance are controversial. In attempt to deepen our understanding, we aimed to study placental pathology and pregnancy outcomes in pregnancies complicated by ITO., Materials and Methods: - Maternal demographics, neonatal outcomes, and placental histopathology reports of all pregnancies complicated by ITO at 37 0/7 to 41 0/7 weeks were reviewed. Excluded were cases complicated by hypertensive disorders, intrauterine fetal growth restriction, placental abruption, and deliveries of undiagnosed small for gestational age neonates. Results were compared between the ITO group and a control group matched for gestational age and mode of delivery. Placental lesions were classified according to the current "Amsterdam" criteria. Composite adverse neonatal outcome was defined as one or more of the following early complications: neonatal intensive care unit admission, sepsis, blood transfusion, phototherapy, respiratory morbidity, cerebral morbidity, necrotizing enterocolitis, or death., Results: The study group included 108 patients with ITO that were compared to matched controls. Placentas from the ITO group were characterized by higher rates of placental weights <10th centile (p < 0.001), abnormal cord insertion (p < 0.001), and maternal vascular malperfusion (MVM) lesions (p < 0.001). Neonates from the ITO group had lower birth weights (p < 0.002), and worse composite adverse neonatal outcome (p = 0.028) compared to controls., Conclusion: - The current study demonstrates higher rates of placental MVM lesions, and worse neonatal outcome in pregnancies complicated by ITO. These novel findings suggest that ITO should be seen as part of the "placental insufficiency" spectrum., Competing Interests: Declaration of competing interest I declare there is not any financial relationship with any organization or any conflict of interest to report., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: In attempt to deepen our understanding of the etiopathogenesis of preeclampsia we aimed to study the placental component and pregnancy outcomes in two consecutive pregnancies complicated by preeclampsia in the same patient., Study Design: Pregnancy and placental reports of all pregnancies complicated by preeclampsia between 2008 and 2018 were reviewed. Included were only cases with recurrent preeclampsia in two consecutive pregnancies Neonatal outcomes and placental histopathology were compared between the first preeclampsia delivery (first preeclampsia group) and the subsequent preeclampsia delivery (subsequent preeclampsia group), thus each subject served as her own control in two consecutive pregnancies. Placental lesions were classified according to the current "Amsterdam" criteria. Adverse neonatal outcome was defined as ≥1 early neonatal complication., Results: Included in the study a total of 83 cases with recurrent preeclampsia. The first preeclampsia group delivered at an earlier gestational age (35.7 ± 3.7 vs. 36.8 ± 3.1 weeks, p = 0.03) and had higher rates of severe features (44.6% vs. 25.3%, p = 0.03), placental weight <10th percentile (44.5% vs. 26.5%, p = 0.02), maternal vascular malperfusion (MVM) lesions (84.3% vs. 62.6%, p = 0.002), SGA (44.5% vs. 33.7%, p = 0.03), and adverse neonatal outcome (55.4% vs. 34.9%,p = 0.01), compared to the subsequent preeclampsia group. Using multivariate logistic regression analysis, severe features (aOR = 1.36, 95%CI = 1.12-2.36), MVM lesions (aOR = 1.12, 95%CI = 1.04-1.87) and adverse neonatal outcome (aOR = 1.26 95%CI = 1.14-2.23) were found to be independently associated with the first preeclampsia group., Conclusion: The first event of preeclampsia is characterized by an earlier, more severe presentation, as well as a higher rate of MVM lesions, SGA, and adverse neonatal outcome, compared to preeclampsia in a subsequent pregnancy., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

The design, simulation, assembly and testing of a novel dedicated antisymmetric transmit/receive (Tx/Rx) coil array to demonstrate the feasibility of cardiac magnetic resonance imaging (cMRI) in pigs at 7 T was described. The novel antisymmetric array is composed of eight elements based on mirrored and reversed loop orientations to generate varying B 1 field harmonics for RF shimming. The central four loop elements formed together a pair of antisymmetric L-shaped channels to allow good decoupling between all neighboring elements of the entire array. The antisymmetric array was compared to a standard symmetric rectilinear loop array with an identical housing dimension. Both arrays were driven in the parallel transmit (pTx) mode forming an 8-channel transmit and 16-channel receive (8Tx/16Rx) coil array, where the same posterior array was combined with both anterior arrays. The hardware and imaging performance of the dedicated cardiac arrays were validated and compared by means of electromagnetic (EM) simulations, bench-top measurements, phantom, and ex-vivo MRI experiments with 46 kg female pig. Combined signal-to-noise ratio (SNR), geometry factor (g-factor), noise correlation maps, and high resolution ex-vivo cardiac images were acquired with an in-plane resolution of 0.3 mm × 0.3 mm using both arrays. The novel antisymmetric array enhanced the SNR within the heart by about two times and demonstrated good decoupling and improved control of the B + field harmonics for RF shimming. The central four loop elements formed together a pair of antisymmetric L-shaped channels to allow good decoupling between all neighboring elements of the entire array. The antisymmetric array was compared to a standard symmetric rectilinear loop array with an identical housing dimension. Both arrays were driven in the parallel transmit (pTx) mode forming an 8-channel transmit and 16-channel receive (8Tx/16Rx) coil array, where the same posterior array was combined with both anterior arrays. The hardware and imaging performance of the dedicated cardiac arrays were validated and compared by means of electromagnetic (EM) simulations, bench-top measurements, phantom, and ex-vivo MRI experiments with 46 kg female pig. Combined signal-to-noise ratio (SNR), geometry factor (g-factor), noise correlation maps, and high resolution ex-vivo cardiac images were acquired with an in-plane resolution of 0.3 mm × 0.3 mm using both arrays. The novel antisymmetric array enhanced the SNR within the heart by about two times and demonstrated good decoupling and improved control of the B 1 + field distributions for RF shimming compared to the standard coil array. Parallel imaging with acceleration factor (R) up to 4 was possible using the novel antisymmetric coil array while maintaining the mean g-factor within the heart region of 1.13., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: In attempt to shed new light on the etiopathogenesis of fetal growth restriction (FGR) we aimed to compare pregnancy outcomes and placental histopathology in cases of first vs. subsequent FGR occurrence., Study Design: Pregnancy and placental reports of FGR pregnancies (defined by birth weight <10th percentile), born between 2008 and 2018 were reviewed. Included only cases with recurrent FGR, in two consecutive pregnancies, thus each subject served as her own control in two FGRs consecutive pregnancies. Neonatal outcome and placental histopathology were compared between the first FGR delivery (first FGR group) and the subsequent FGR delivery (subsequent FGR group). Composite adverse neonatal outcome was defined as one or more early neonatal complications., Results: Included in the study a total of 96 cases with recurrence of FGR pregnancies. Placentas from the first FGR group were characterized by higher rate of maternal vascular malperfusion (MVM) lesions as compared with the subsequent FGR group (71.8% versus 55.2%, respectively, p = 0 .02). Adverse neonatal outcome was more prevalent in the first FGR group as compared to the recurrent FGR group (41.6% versus 25%, respectively, p = 0.02). After controlling for confounders, using multivariate regression analysis, placental MVM lesions (aOR = 1.36, 95% CI = 1.12-1.45) and composite adverse neonatal outcome (aOR = 1.18 95% CI = 1.09-1.55) were found to be independently associated with the first FGR group., Conclusion: First event of FGR is associated with a higher rate of placental MVM lesions and adverse neonatal outcome as compared to FGR in subsequent pregnancies., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: We aimed to compare pregnancy outcome and placental histopathology in women with preeclampsia (PE) with and without severe features., Methods: The medical records and placental pathology reports of all pregnancies complicated by PE during 2008-2016, were reviewed. Results were compared between those with and without severe features (severe PE vs. mild PE groups), according to current ACOG guidelines. Placental lesions were classified to maternal/fetal vascular supply lesions, and maternal/fetal inflammatory responses. Small for gestational age (SGA) was defined as neonatal birth-weight ≤10th%. Composite adverse neonatal outcome was defined as one or more of the following: sepsis, transfusion, phototherapy, respiratory morbidity, cerebral morbidity, NEC, or death., Results: The severe PE group (n = 284) was characterized by lower gestational age at delivery (p < 0.001), and higher rates of antenatal corticosteroid use (p = 0.003), and cesarean deliveries (p < 0.001) as compared to the mild PE group (n = 151). More placentas <10th% and more composite maternal vascular malperfusion (MVM) lesions were observed in the severe PE group as compared to the mild PE group (p < 0.001 for both). In multivariate analysis, composite placental MVM lesions were independently associated with severe PE (aOR = 1.75, 95%CI 1.4-4.9). Higher rates of SGA (p = 0.016), and composite adverse neonatal outcome (p = 0.002) characterized the severe PE group. In multivariate analysis, adverse neonatal outcome was independently associated with gestational age (aOR = 0.54, 95%CI 0.49-0.68), SGA (aOR = 1.75, 95%CI = 1.15-3.59), severe PE (aOR = 1.8, 95%CI = 1.13-3.54) and placental MVM lesions (aOR = 2.13, 95%CI = 1.05-4.39)., Conclusion: More pronounced placental pathology and higher rate of adverse neonatal outcome characterize preeclampsia with severe features as compared with the milder form of the disease., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: We aimed to compare placental histopathological lesions and neonatal outcome in singleton vs. twin pregnancies complicated by gestational diabetes mellitus (GDM)., Methods: Maternal characteristics, neonatal outcomes, and placental histopathology reports of pregnancies complicated by GDM, between 1/2008-10/2016, were reviewed. Results were compared between singletons (singleton group) and dichorionic-diamniotic twins (twin group). Placental lesions were classified as placental weight abnormalities, maternal and fetal vascular malperfusion lesions (MVM, FVM), inflammatory lesions, and lesions associated with chronic villitis. LGA was defined as birth-weight ≥90th percentile. Composite adverse neonatal outcome was defined as one or more early neonatal complications., Results: Compared with the twin group (n = 57), the singleton group (n = 228) was characterized by higher gestational-age (38.6 ± 0.9 vs. 35.1 ± 1.8 weeks, p < 0.001) and a higher rate of insulin treatment (32.9% vs. 17.5%, p = 0.023). Placentas from the singleton group were characterized by higher rates of MVM lesions (54.4% vs. 30.7%, p < 0.001), villitis of unknown etiology (VUE, 5.7% vs. 0.9%, p = 0.040), villous immaturity (10.1% vs. 0.9%, p = 0.001), and placental weight <10th percentile (16.7% vs. 8.8%, respectively, p = 0.049). Using multivariable regression analysis, MVM (aOR = 2.2, 95% CI = 1.6-4.1), VUE (aOR = 1.2, 95% CI = 1.1-2.1), villous immaturity (aOR = 2.3, 95% CI 1.8-7.6), and placental weight <10th percentile (aOR = 1.1, 95% CI = 1.02-1.6), were the only lesions associated with singleton pregnancies. Composite adverse neonatal outcome was more common in the twin group (54.3% vs. 14.0%, p < 0.001) and it was associated only with lower GA (aOR = 3.7, 95% CI 2.1-7.3)., Conclusion: Higher rate of placental weight <10th percentile, MVM lesions, villous immaturity, and VUE characterize GDM singleton pregnancy as compared to twins GDM gestation, suggesting different placental alterations in the diabetic environment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We examined the impact of chronic hypertension (HTN), gestational HTN, and preeclampsia on placental maternal and fetal vascular circulation. Of the 1047 women who gave birth and underwent a placental histopathologic examination between 2007 and 2013 at Wolfson Medical Center, 140 women were included in the present study: 34 women with preeclampsia, 25 women with chronic HTN, 28 women with gestational HTN, and 53 women without hypertensive disorder, matched by age, gravidity, parity, and mode of delivery.Placental lesions related to maternal vascular malperfusion (MVM) differed significantly across groups (P < .0001) and were highest in subjects with chronic HTN and preeclampsia (72% and 65%, respectively) and lowest in women without hypertensive disorder (26%). Placental fetal vascular malperfusion rate did not differ significantly between groups (P = .767). In the logistic regression analysis, chronic HTN emerged as a significant predictor of placental MVM and increased the risk of this outcome more than sixfold (odds ratio 6.614, 95% confidence interval 2.047-21.37, P = .002). Preeclampsia emerged as a significant predictor of MVM and more than tripled the risk of this outcome (odds ratio 3.468, 95% confidence interval 1.083-11.103, P = .036). Gestational HTN was not significantly associated with increased MVM rate. We demonstrated that chronic HTN and preeclampsia were associated with an increased rate of vascular placental maternal malperfusion and emerged as significant independent predictors of this outcome., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to compare obstetric outcome and placental-histopathology in pregnancies complicated by preeclampsia with severe features with and without HELLP syndrome., Methods: Labor, maternal characteristics, neonatal outcome and placental histopathology of pregnancies complicated with severe preeclampsia during 2008-2015 were reviewed. Results were compared between those without signs of HELLP syndrome (severe preeclampsia group) and those with concomitant HELLP syndrome (HELLP group). Placental lesions were classified to maternal vascular lesions consistent with malperfusion, fetal vascular lesions consistent with fetal thrombo-occlusive disease, and inflammatory lesions. Small-for-gestational-age (SGA) was defined as birth-weight ≤10th% and ≤5th%. Composite adverse neonatal outcome was defined as one or more early neonatal complications., Results: Compared to the severe preeclampsia group (n = 223), the HELLP group (n = 64) was characterized by earlier gestational-age, 34.1 ± 2.7 vs. 35.3 ± 3.4 weeks, p = 0.010, higher rates of multiple pregnancies (p = 0.024), and thrombophilia (p = 0.028). Placentas in the HELLP group had higher rates of vascular and villous lesions consistent with maternal malperfusion (p = 0.023, p = 0.037 respectively). By multivariate logistic regression analysis models, vascular and villous lesions of maternal malperfusion were independently associated with HELLP syndrome (aOR 1.9, aOR 1.8, respectively). SGA was also more common in the HELLP group, both below the 10th percentile (p = 0.044) and the 5th percentile (p = 0.016). Composite adverse neonatal outcome did not differ between the groups., Conclusion: Severe preeclampsia and HELLP syndrome have similar placental histopathologic findings. However, HELLP syndrome is associated with higher rates of placental maternal vascular supply lesions and SGA suggesting that the two clinical presentations share a common etiopathogenesis, with higher placental dysfunction in HELLP syndrome., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The mechanisms involved in bleeding in cases of placenta previa (PP) and the effect on pregnancy outcome is unclear., Objectives: We aimed to compare pregnancy outcome and placental histopathology in pregnancies complicated with symptomatic (bleeding) vs. non-symptomatic PP, and to study the effects of the co-existence of histopathological retro-placental hemorrhage (RPH) in cases of symptomatic PP on neonatal and maternal outcomes., Study Design: Labor and maternal characteristics, neonatal outcome and placental histopathology lesions of pregnancies with PP, delivered between 24 and 42weeks, during 2009-2015, were reviewed. Results were compared between PP who had elective cesarean delivery (CD) (previa group) and PP with bleeding necessitating emergent CD (symptomatic previa group). Placental lesions were classified to lesions consistent with maternal malperfusion or fetal thrombo-occlusive disease (vascular and villous changes), and inflammatory lesions., Results: Compared to the previa group (n=63), the symptomatic previa group (n=74) was characterized by older patients (p<0.001), higher rate of smokers (p=0.005), thrombophilia (p=0.038), and preterm deliveries (p<0.001). Placentas within the symptomatic previa group were smaller, with higher rates of weight<10th% (p=0.02), RPH (p<0.001) and villous changes related to maternal malperfusion (p=0.023). As compared to symptomatic PP without RPH, co-existence of RPH was associated with higher rate of adverse neonatal outcome (p<0.001) and maternal blood transfusion (p=0.02). On multivariate regression analysis, composite adverse neonatal outcome was found to be dependent on coexisting RPH (OR=2.8, 95%CI 1.2-11.7, p=0.03), and low gestational age (OR=3.1, 95%CI 1.6-4.9, p=0.02)., Conclusions: Symptomatic placenta previa is associated with increased placental malperfusion lesions suggesting an association of maternal malperfusion with abnormal placental separation. The coexisting finding of RPH with symptomatic placenta previa can be seen as a marker for more extensive/severe placental separation, hence the association with maternal transfusion requirements and poorer fetal outcome., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Suberin is a biopolyester found in specialized plant tissues, both internal and external, with key frontier physiological functions. The information gathered so far from its monomer and oligomer composition, and in situ studies made by solid state techniques, haven't solved the enigma of how the suberin polyester is assembled as a macromolecule. To investigate how monomers are linked in suberin, we analyzed oligomer fragments solubilized by the partial depolymerization of suberin from potato (Solanum tuberosum) tuber periderms. The structure of the suberin oligomers, namely which monomers they included, and the type and frequency of the inter-monomer ester linkages, was assessed by ESI-MS/MS and high resolution NMR analysis. The analyzed potato periderms included the one from wild type (cv. Desirée) and from plants where suberin-biosynthesis genes were downregulated in chain elongation (StKCS6), ω-hydroxylation (CYP86A33) and feruloylation (FHT). Two building blocks were identified as possible key structures in the macromolecular development of the potato periderm suberin: glycerol - α,ω-diacid - glycerol, as the core of a continuous suberin aliphatic polyester; and glycerol - ω-hydroxyacid - ferulic acid, anchoring this polyaliphatic matrix at its periphery to the vicinal polyaromatics, through linking to ferulic acid. The silencing of the StKCS6 gene led to non-significant alterations in suberin structure, showing the relatively minor role of the very-long chain (>C28) fatty acids in potato suberin composition. The silencing of CYP86A33 gene impaired significantly suberin production and disrupted the biosynthesis of acylglycerol structures, proving the relevance of the latter and thus of the glycerol - α,ω-diacid - glycerol unit for the typical suberin lamellar organization. The silencing of the FHT gene led to a lower frequency of ferulate linkages in suberin polyester but to more polyphenolic guaiacyl units as seen by FTIR analyses in the intact polymer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The presence of nerve fibres in the functional layer of the endometrium has been strongly associated with endometriosis. Presence of nerve fibres in the endometrium of women undergoing IVF has not been previously assessed. This prospective pilot study assessed the presence of nerve fibres in endometrium of women undergoing IVF due to various causes and examined the correlation between the presence of nerve fibres and IVF success. A total of 32 IVF patients underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fibres were identified by immunohistochemical staining. Correlations between the presence and density of nerve fibres and aetiology of infertility and IVF success were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%) women with a satisfactory biopsy. Presence of nerve fibres was not correlated with cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%) patients, without correlation to presence of nerve fibres in the endometrium. Nerve fibres were identified in a substantial percentage of women undergoing IVF, possibly reflecting underdiagnosis of endometriosis in this population. The presence of nerve fibres does not appear to interfere with implantation. The significance of nerve fibres in the endometrium of IVF patients warrants further research. The presence of nerve fibres in the functional layer of the endometrium has been strongly associated with endometriosis. The presence of nerve fibres in the endometrium of women undergoing IVF has not been previously assessed. Our aim was to assess the presence of nerve fibres in endometrium of women with various causes of infertility undergoing IVF and to examine the association between the presence of nerve fibres in the endometrium and IVF success. In a prospective study, 32 IVF patients underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fibres were identified by immunohistochemical staining. Associations between the presence and density of nerve fibres and the aetiology of infertility and IVF success were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%) women with a satisfactory biopsy. No association was found between the presence of nerve fibres and the cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%) patients, without association with the presence of nerve fibres in the endometrium. Nerve fibres can be identified in a substantial percentage of women undergoing IVF, possibly reflecting underdiagnosis of endometriosis in this population. Their presence does not interfere with embryo implantation. The significance of nerve fibres in the endometrium of IVF patients warrants further research., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Our objective was to investigate the placental component in early- and late-onset fetal growth restriction (FGR) compared to placentas from neonates appropriate for gestational age (AGA)., Study Design: Placentas from normotensive women who gave birth at 24-42 weeks to neonates with a birth-weight below the 10th percentile (FGR group), or to healthy AGA neonates (AGA group), were analyzed. Placental lesions were classified to lesions related to maternal underperfusion, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions. Findings were compared between patients who delivered ≤ 34 weeks (early-onset FGR) or >34 weeks (late-onset FGR) and controls with AGA neonates., Results: The early-onset FGR group (n = 24) had a higher rate of placental vascular lesions related to maternal underperfusion than the late-FGR group (n = 334) (41.7% vs. 8.7%, P < 0.001) and more villous lesions related to maternal underperfusion than the preterm AGA group (n = 68) (70.8% vs. 5.9%, P < 0.001). The late-onset FGR group had more placental villous lesions related to maternal underperfusion (57% vs. 19% P < 0.001) and more lesions consistent with fetal thrombo-occlusive disease (26.3% vs. 8.5%, P < 0.001) than the term AGA group (n = 153)., Conclusion: Early- and late-onset FGR have different placental pathology compared with AGA controls, suggesting that a combination of fetal and maternal vascular compromise is more dominant in the late-onset FGR, rather than more severe maternal vascular compromise in early-onset FGR., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Cannabis is the most widely used illicit substance and has been associated with cognitive impairment. It is unclear whether such impairment can occur in the absence of potential confounding influences of co-morbid axis-I disorders and use of other illicit substances., Method: Young adult volunteers (18-29 years) were recruited from the general community on the basis of having no axis-I disorders or history of illicit substance use other than cannabis use. Subjects were then grouped according to presence or absence of cannabis use (>1 time/week over past 12 months). Cognition was compared between groups using selected paradigms from the CANTAB., Results: Cannabis users (N=16) and controls (N=214) did not differ significantly on salient demographic characteristics. Compared to controls, cannabis users showed significant impairments on quality of decision-making (Cambridge Gamble task), and executive planning (One Touch Stockings of Cambridge task). Response inhibition, spatial working memory, and sustained attention were intact., Conclusions: This study identified cognitive deficits in cannabis users even in the absence of axis-I disorders and a history of using other illicit drugs. Future work should use longitudinal designs to track whether these deficits predate cannabis use or are due to its consumption., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the association between different placental lesions and non-reassuring fetal heart rate (NRFHR) pattern and fetal acidosis in labor., Study Design: Placentas from 213 women who underwent cesarean section because of NRFHR with or without fetal acidosis (pH < 7.2) were classified by histopathologic findings: consistent with maternal circulation abnormalities i.e., namely, marginal or retroplacental hemorrhage (M0), maternal underperfusion, vascular (M1) or villous changes (M2), and those consistent with fetal thrombo-occlusive disease due to vascular (F1) or villous (F2) changes. Lesions were also analyzed by maternal (MIR) or fetal (FIR) origin of inflammatory responses., Results: Cord blood pH was normal in 169 neonates (7.29 ± 0.04; control group) and <7.2 in 44 (7.10 ± 0.07; study group). The study group had higher rates of histologic chorioamnionitis; MIR was detected in 34.1% compared to17.8% of controls (p = 0.018), and FIR, in 18.2% compared to 6.5% (p = 0.016). Neonates in the study group had lower Apgar scores and longer hospitalization., Conclusions: Placental MIR and FIR are associated with cord blood acidosis in neonates delivered by cesarean section for NRFHR tracings in labor., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The effects of air pollutants such as aldehydes, ozone, nitrogen dioxide and benzene on fatty acid ω-hydroxylase activity in Vicia sativa microsomes have been investigated. Four days old etiolated V. sativa seedlings were exposed to different concentrations of selected pollutants for varying exposure times. Growing etiolated V. sativa seedlings in air containing the gaseous benzaldehyde (150 nM) led to an 8-fold enhancement of lauric acid ω-hydroxylase activity in microsomes of treated plants compared to controls grown in pure air (96 ± 10 versus 12 ± 2 pmol/min/mg protein, respectively). The induction increased with increasing gas phase concentrations (10-1300 nM) and the maximum of activity was measured after 48 h of exposure. Northern blot analysis revealed that this induction occurred via transcriptional activation of the gene coding for CYP94A1. The absence of CYP94A2 and CYP94A3 transcription activation together with the missing effect on epoxide hydrolases activities indicate the specificity of CYP94A1 induction by benzaldehyde. Exposure to nitrogen dioxide, ozone and formaldehyde also stimulated lauric acid ω-hydroxylases activity while exposure to benzene did not show any effect., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Pregnancy-induced hypertension/preeclampsia (PIH) and fetal growth restriction (FGR) share a common placental origin. The pathologic classification that divides placental lesions to maternal or fetal origin was compared between these disorders., Study Design: Placentas from pregnancies that were complicated by PIH, normotensive FGR, or by both (combined) were analyzed, and lesions were classified as those consistent with maternal under-perfusion and with fetal thromboocclusive disease., Results: Maternal vascular lesions were more common in the PIH group and combined group (61% and 59%, respectively), compared with the FGR group (16.2%; P < .001), and villous lesions were more common in the combined group, compared with the FGR and PIH groups (79.5%, 53.5%, and 46.9%, respectively; P = .004). Fetal villous changes were observed in 16.2% in the FGR group, compared with 3.1% in the PIH group (P = .03), and chronic villitis was 15.2% in the FGR group vs 1.6% in the PIH group (P = .004)., Conclusion: Placental lesions correspond with different clinical presentations., (Copyright 2010 Mosby, Inc. All rights reserved.)

A technique for continuous production of solutions containing hyperpolarized (129)Xe is explored for MRI applications. The method is based on hollow fiber membranes which inhibit the formation of foams and bubbles. A systematic analysis of various carrier agents for hyperpolarized (129)Xe has been carried out, which are applicable as contrast agents for in vivo MRI. The image quality of different hyperpolarized Xe solutions is compared and MRI results obtained in a clinical as well as in a nonclinical MRI setting are provided. Moreover, we demonstrate the application of (129)Xe contrast agents produced with our dissolution method for lung MRI by imaging hyperpolarized (129)Xe that has been both dissolved in and outgassed from a carrier liquid in a lung phantom, illustrating its potential for the measurement of lung perfusion and ventilation.

Objective: We studied ovarian cancers for the expression of membrane markers of hematopoietic origin., Study Design: We used flow cytometry to systematically characterize the expression of more than 30 hematologic antigens on ovarian carcinoma cell lines and to assess their stability under estrogen exposure. The expression of the antigens was validated by a bioinformatics survey and immunohistochemical staining of ovarian cancer specimens., Results: Several antigens were expressed by the majority of the cells, such as CD15, CD71, and CD138, whereas others were found on small and distinct cellular subpopulations. The expression patterns of the different markers were unaffected by estrogen exposure, indicating their stability., Conclusion: The antigens described in our work may serve as potential targets for new and existing targeted drugs.

Tumorogenic transformation is a multifaceted cellular process involving combinatorial protein-protein interactions that modulate different cellular functions. Here, we report apparent involvement in two independent tumorogenic processes by distinct partner protein interactions of the stress-induced acetylcholinesterase AChE-R and N-AChE-R variants. Human testicular tumors showed elevated levels of N-terminally extended N-AChE-R compared with healthy tissue, indicating alternate promoter usage in the transformed cells. Two-hybrid screens demonstrate that the C-terminus common to both N-AChE-R and AChE-R interacts either with the glycolytic enzyme enolase or with the scaffold protein RACK1. In vitro, the AChE-R C-terminal peptide ARP elevated enolase's activity by 12%, suggesting physiological relevance for this interaction. Correspondingly, CHO cells expressing either human AChE-R or N-AChE-R but not AChE-S showed a 25% increase in cellular ATP levels, indicating metabolic significance for this upregulation of enolase activity. ATP levels could be reduced by AChE-targeted siRNA in CHO cells expressing AChE-R but not AChE-S, attributing this elevation to the AChE-R C-terminus. Additionally, transfected CHO cells expressing AChE-R but not N-AChE-R showed resistance to up to 60 microM of the common chemotherapeutic agent, cis-platinum, indicating AChE-R involvement in another molecular pathway. cis-Platinum elevates the expression of the apoptosis-regulator p53-like protein, p73, which is inactivated by interaction with the scaffold protein RACK1. In co-transfected cells, AChE-R competed with endogenous RACK1 for p73 interaction. Moreover, AChE-R-transfected CHO cells presented higher levels than control cells of the pro-apoptotic TAp73 as well as the anti-apoptotic dominant negative DeltaNp73 protein, leading to an overall decrease in the proportion of pro-apoptotic p73. Together, these findings are compatible with the hypothesis that in cancer cells, both AChE-R and N-AChE-R elevate cellular ATP levels and that AChE-R modifies p73 gene expression by facilitating two independent cellular pathways, thus conferring both a selective metabolic advantage and a genotoxic resistance.

The composition of wax and cutin from developing sweet cherry (Prunus avium) fruit was studied by GC-MS between 22 and 85 days after full bloom (DAFB). In this and our previous study, fruit mass and surface area increased in a sigmoidal pattern with time, but mass of the cuticular membrane (CM) per unit fruit surface area decreased. On a whole fruit basis, mass of CM increased up to 36 DAFB and remained constant thereafter. At maturity, triterpenes, alkanes and alcohols accounted for 75.6%, 19.1% and 1.2% of total wax, respectively. The most abundant constituents were the triterpenes ursolic (60.0%) and oleanolic acid (7.5%), the alkanes nonacosane (13.0%) and heptacosane (3.0%), and the secondary alcohol nonacosan-10-ol (1.1%). In developing fruit triterpenes per unit area decreased, but alkanes and alcohols remained essentially constant. The cutin fraction of mature fruit consisted of mostly C16 (69.5%) and, to a lower extent, C18 monomers (19.4%) comprising alkanoic, omega-hydroxyacids, alpha,omega-dicarboxylic and midchain hydroxylated acids. The most abundant constituents were 9(10),16-dihydroxy-hexadecanoic acid (53.6%) and 9,10,18-trihydroxy-octadecanoic acid (7.8%). Amounts of C16 and C18 monomers per unit area decreased in developing fruit, but remained approximately constant on a whole fruit basis. Within both classes of monomers, opposing changes occurred. Amounts of hexadecandioic, 16-hydroxy-hexadecanoic, 9(10)-hydroxy-hexadecane-1,16-dioic and 9,10-epoxy-octadecane-1,18-dioic acids increased, but 9,10,18-trihydroxy-octadecanoic and 9,10,18-trihydroxy-octadecenoic acids decreased. There were no qualitative and minor quantitative differences in wax and cutin composition between cultivars at maturity. Our data indicate that deposition of some constituents of wax and cutin ceased during early fruit development.

Objective: The objective of this study was to assess the expression of Her-2/neu in nonepithelial ovarian malignancies., Study Design: Formalin-fixed paraffin-embedded archival tissue blocks of 20 unselected nonepithelial ovarian malignancies (12 granulosa cell tumors and 8 germ cell tumors) diagnosed between 1993 and 2005 were immunohistochemically stained for Her-2/neu., Results: Immunohistochemical staining for Her-2/neu was not present in any of these nonepithelial malignancies examined., Conclusion: Our limited sample size does not allow a generalized conclusion concerning the lack of Her-2/neu expression in nonepithelial ovarian malignancies, but it adds information with regard to the expression of this oncogene in these rare neoplasms and seems to indicate that it is not a frequent occurrence.

Cutinized and suberized cell walls form physiological important plant-environment interfaces as they act as barriers limiting water and nutrient loss and protect from radiation and invasion by pathogens. Due to the lack of protocols for the isolation and analysis of cutin and suberin in Arabidopsis, the model plant for molecular biology, mutants and transgenic plants with a defined altered cutin or suberin composition are unavailable, causing that structure and function of these apoplastic barriers are still poorly understood. Transmission electron microscopy (TEM) revealed that Arabidopsis leaf cuticle thickness ranges from only 22 nm in leaf blades to 45 nm on petioles, causing the difficulty in cuticular membrane isolation. We report the use of polysaccharide hydrolases to isolate Arabidopsis cuticular membranes, suitable for depolymerization and subsequent compositional analysis. Although cutin characteristic omega-hydroxy acids (7%) and mid-chain hydroxylated fatty acids (8%) were detected, the discovery of alpha,omega-diacids (40%) and 2-hydroxy acids (14%) as major depolymerization products reveals a so far novel monomer composition in Arabidopsis cutin, but with chemical analogy to root suberin. Histochemical and TEM analysis revealed that suberin depositions were localized to the cell walls in the endodermis of primary roots and the periderm of mature roots of Arabidopsis. Enzyme digested and solvent extracted root cell walls when subjected to suberin depolymerization conditions released omega-hydroxy acids (43%) and alpha,omega-diacids (24%) as major components together with carboxylic acids (9%), alcohols (6%) and 2-hydroxyacids (0.1%). This similarity to suberin of other species indicates that Arabidopsis roots can serve as a model for suberized tissue in general.

Chemical analysis of 4-day-old corn (Zea mays L.) root cell walls revealed that the lipophilic biopolymer suberin forms an important constituent of rhizodermal and hypodermal cell walls. Identified aliphatic monomers had chain lengths ranging from C16 to C26 and they belonged to 5 substance classes (omega-hydroxycarboxylic acids, 1,omega-dicarboxylic acids, 2-hydroxycarboxylic acids, carboxylic acids and alcohols) by which suberin is characterized. Biochemical experiments proved the occurrence of elongase activities in corn roots. Highest enzymatic activities were found in corn root microsomes, and major products synthesized by root elongases were elongated fatty acids with chain lengths ranging from C20 to C24. Preferred substrates of root elongases were acyl-CoAs of the chain length C18 and C20, whereas monounsaturated acyl-CoAs (C16:1 and C18:1) and acyl-CoAs of lower (C12-C16) and higher chain lengths (C22-C24) were rarely elongated. Elongase activities significantly decreased over the length (40 cm) of 10-day-old corn roots going from the young tip to the older base of the root. Thus, results presented here show the presence and activity of elongases in roots of plants.

Cutins from the leaves and fruits of seven plant species were depolymerized by NaOCH(3)-methanolysis. The monomers that were released mostly included C16 and C18 omega-hydroxyacids with mid-chain oxygenated substitutions, namely epoxy and hydroxyl groups. Glycerol was also solubilized as a monomer in quantities that ranged from 1 to 14% of the methanolysates. Partial depolymerization of three cutins by CaO-methanolysis released the same monomers as had been obtained in the previous reaction, as well as small quantities of 1- and 2-monoacylglyceryl esters of omega-hydroxyacids. Molar proportions of glycerol permit the esterification of a significant part of the aliphatic omega-hydroxyacids, thereby possibly playing a major role in the polyester structure of cutin. Glycerol had not previously been known to form part of the cutin polymer.