Introduction: A better understanding of the determinants of placental growth is needed. Our primary aim was to explore associations between maternal ethnic origin and cardio-metabolic factors during pregnancy, and placental weight, surface area, shape and thickness. Methods: A multi -ethnic population -based cohort study of 474 pregnant women examined at mean 15 and 28 weeks' gestation. Placentas were inspected after birth by a placental pathologist. Outcome measures were trimmed placental weight and three uncorrelated placental components; surface area, shape (oval vs round) and thickness, created through a principal components analysis. Multivariate linear regression models were used to explore the associations with maternal factors. Results: Compared with ethnic European women, mothers with South- and East Asian ethnicity had placentas with lower weight (-51 g (95% CI: 75, -27) and -55 g (-95, -14) respectively), primarily due to a smaller surface area. The association between South Asian ethnicity and placental surface area was still significant after adjusting for maternal characteristics and cardio-metabolic factors. Fat mass index in early pregnancy was associated with higher placental weight and thickness. Placental surface area was positively associated with midgestational increases in fat mass, fasting glucose and triglycerides and with the 2-h glucose value at the 28 week oral glucose tolerance test, and inversely with a mid -gestational increase in HDL-cholesterol. Discussion: Mid -gestational changes in fat mass, glucose, triglycerides and cholesterol were associated with, but only partly explained ethnic differences in placental surface area, while maternal fat mass in early pregnancy was associated with placental thickness.

Abstract Background The fibrinolytic system plays an important role in coronary artery atherothrombosis, and especially circulating plasminogen-activator inhibitor (PAI) type 1 (PAI-1) associates with increased mortality, infarct size and heart failure in patients with myocardial infarction (MI). In a cross-sectional study, we aimed to study whether genes encoding tissue plasminogen activator (tPA), urinary-type plasminogen activator (uPA), PAI-1 and PAI-2 are expressed in coronary thrombi from acute ST-elevation MI (STEMI) patients. Any relations to myocardial injury measured by peak troponin T, time from symptom onset to Percutaneous Coronary Intervention (PCI), and to different cell types present in the thrombi were also explored. Methods Intracoronary thrombi were aspirated from 33 STEMI patients treated with primary PCI. The thrombi were snap-frozen for gene expression analyses, relatively quantified by RT PCR. Peripheral blood samples were drawn. Correlations were performed by Spearmans rho. Results The genes were present in 74–94% of the thrombi. Median peak troponin T was 3434 μ/L and median ischemic time 152 min. There were no significant correlations between the measured genes and troponin T, or ischemic time. Genes encoding tPA, u-PA, PAI-1 and PAI-2 all correlated significantly to the presence of monocytes/macrophages (CD68) in the thrombi (p = 0.028, p < 0.001, p = 0.003, p < 0.001). PAI-1 and PAI-2 also correlated to endothelial cells (CD31) (p = 0.002, p = 0.016). uPA associated with neutrophil granulocytes (CD 66b) (p = 0.019). Conclusion Genes encoding tPA, uPA, PAI-1 and PAI-2 were highly expressed in human coronary thrombi from STEMI patients, indicating fibrinolytic regulators playing active roles in the thrombi, although not related to myocardial injury. All markers related to the presence of monocytes/macrophages, indicating connection to local inflammatory cells. Trial registration The study is registered at clinicaltrials.gov with identification number NCT02746822 .

Background Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are considered important both in atherosclerosis and remodeling after acute myocardial infarction (AMI). We aimed to study genetic expression and presence of MMP-2, MMP-9, TIMP-1, TIMP-2 and the extracellular MMP-inducer (EMMPRIN) in coronary thrombi. Circulating levels and genetic expression in circulating leukocytes were also assessed, and relations to degree of myocardial injury measured by troponin T and time from symptom to PCI were explored. Expression of cell markers were also analyzed, indicating relations to cell types. Methods Intracoronary thrombi were aspirated from 33 patients with ST-elevation myocardial infarction (STEMI). Blood samples with Pax-gene tubes were drawn at end of PCI and the next day. RNA was isolated from thrombi and leukocytes, and genes were relatively quantified by RT-PCR. Each thrombus was preserved for histology and immunohistochemistry analyzes. Results Genes coding for the five markers were present in 84–100% of thrombi and immunohistochemically stained in 96–100%. Expression of TIMP-1 in thrombi and in leukocytes correlated significantly to peak troponin T (r = 0.393 P = 0.026, r = 0.469 P = 0.006, respectively). No significant correlations between genes expressed in thrombi and time from symptom to PCI were observed. TIMP-1 was connected mainly to monocytes/macrophages in the thrombi. Conclusion MMP-2, MMP-9, TIMP-1, TIMP-2 and EMMPRIN were highly expressed in human coronary thrombi. The correlation between troponin T and the expression of TIMP-1 both in thrombi and in leukocytes at time of PCI indicates that TIMP-1 plays a role in myocardial damage early post-MI.

BACKGROUND:Visualization of the lesions in the lower genital tract is the mainstay for diagnosis of the four lesions found in female genital schistosomiasis (FGS), but colposcopes are generally not available in low-resource settings.OBJECTIVE:We sought to review handheld devices that could potentially be used for FGS diagnosis.SEARCH STRATEGY:We searched Medline and Embase 2015-2019 for handheld devices used in cervical cancer screening and FGS diagnosis.SELECTION CRITERIA:We excluded studies that did not compare the device to standard-of-care colposcopes or histopathology.MAIN RESULTS AND CONCLUSION:In 11 studies, four handheld colposcopes, two smartphones, and one compact digital camera were evaluated. Two handheld colposcopes were found to be potentially adequate for FGS diagnosis, namely Gynocular and Mobile ODT. The smartphones and digital camera did not have sufficient magnification to diagnose grainy sandy patches, one of the FGS lesion types. Customized software should be made to support the diagnosis of both FGS and cervical neoplasia. Real-time postgraduate training and quality control should be considered in future studies of handheld colposcopes. For patients from schistosomiasis endemic areas, we recommend that handheld devices are used for FGS. Studies are needed to determine which of the two devices is most adequate for FGS diagnosis in schistosomiasis endemic areas.

Background. The Nod-Like-Receptor-Protein-3 (NLRP3) inflammasome and the Interleukin-6 (IL-6) pathways are central mechanisms of the inflammatory response in myocardial reperfusion injury. Expanding our knowledge about the inflammasome signaling axis is important to improve treatment options. In a cross-sectional study, we aimed to study presence, localization, and genetic expression of inflammasome- and IL-6- signaling-related proteins in coronary thrombi and circulating leukocytes from ST-elevation myocardial infarction (STEMI) patients, with relation to myocardial injury and time from symptoms to PCI. Methods. Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were drawn. mRNA of Toll-Like-Receptor-4 (TLR4), NLRP3, caspase 1, Interleukin-1β (IL1-β), Interleukin-18 (IL-18), IL-6, IL-6-receptor (IL-6R), and glycoprotein 130 (gp130) were isolated from thrombi and circulating leukocytes and relatively quantified by RT-PCR. A part of each thrombus was embedded in paraffin for histology and immunohistochemistry analyses. Results. Genes encoding the 8 markers were present in 76-100% of thrombi. Expression of TLR4 in thrombi significantly correlated to troponin T (r=0.455, p=0.013), as did NLRP3 (r=0.468, p=0.024). Troponin T correlated with expression in circulating leukocytes of TLR4 (r=0.438, p=0.011), NLRP3 (r=0.420, p=0.0149), and IL-1β (r=0.394, p=0.023). IL-6R expression in thrombi correlated significantly to troponin T (r=0.434, p=0.019), whereas gp130 was inversely correlated (r=−0.398, p=0.050). IL-6 in circulating leukocytes correlated inversely to troponin T (r=−0.421, p=0.015). There were no significant correlations between genes expressed in thrombi and time from symptom to PCI. Conclusions. The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI, in association with myocardial damage measured by troponin T. This supports the strategy of medically targeting this pathway in treating myocardial infarction and contributes to sort out optimal timing and targets for anti-inflammatory treatment. The study is registered at clinicaltrials.gov with identification number NCT02746822.

Introduction: Maternal alloimmunization against human platelet antigen (HPA)-1a has been implied to mediate both reduced birth weight and chronic placental inflammation. Fetal growth restriction is associated with different types of chronic inflammation in the placenta, mainly chronic histiocytic intervillositis and chronic villitis. The aim of this prospective study was to do a systematic examination of placentas from HPA-1a alloimmunized pregnancies, with focus on the histopathological and immunohistochemical diagnosis of variants of chronic inflammation. Material and methods: In a Polish-Norwegian study, 48 placentas were examined. The histopathology of placentas from 27 HPA-1a immunized women was compared with 21 placentas from non-immunized HPA-1a negative women (controls). In the group of alloimmunized women, ten received antenatal intravenous immunoglobulin G (IVIg). Tissue sections from formalin fixed paraffin embedded placental tissue were stained with hematoxylin and eosin and microscopically examined with focus on various types of chronic placental inflammations. Results: Chronic histiocytic intervillositis was observed in 40.7% of placentas from HPA-1a alloimmunized pregnancies, compared to none in the control group (p = 0.001). Chronic villitis of unknown etiology was more frequently found in the alloimmunized group, however this difference was not statistically significant. Maternal administration of IVIg did not seem to protect against chronic inflammatory lesions. Discussion: Placentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis.

This case report discusses a patient with nephrotic syndrome, pulmonary hypertension, and repeated episodes of infections. He had a history of intravenous drug abuse. Kidney biopsy revealed the rare finding of numerous foam cells, mainly in glomeruli. The solvent used for the drugs is thought to be responsible for the foam cells. In line with previous reports, we suspect that the pulmonary hypertension is consistent with foam cells in pulmonary capillaries or fat embolism syndrome due to the intravenous administered drugs. Our case demonstrates that the use of intravenous drugs can lead to widely varying symptoms. Globally, the prevalence of substance abuse is increasing. Knowledge about their damaging effects is crucial in both clinical practice and anatomic pathology.

This case report discusses a patient with nephrotic syndrome, pulmonary hypertension, and repeated episodes of infections. He had a history of intravenous drug abuse. Kidney biopsy revealed the rare finding of numerous foam cells, mainly in glomeruli. The solvent used for the drugs is thought to be responsible for the foam cells. In line with previous reports, we suspect that the pulmonary hypertension is consistent with foam cells in pulmonary capillaries or fat embolism syndrome due to the intravenous administered drugs. Our case demonstrates that the use of intravenous drugs can lead to widely varying symptoms. Globally, the prevalence of substance abuse is increasing. Knowledge about their damaging effects is crucial in both clinical practice and anatomic pathology.

ABSTRACT Purpose To investigate the feasibility of using Optisol-GS as a convenient, xenogeneic-free alternative for storage of cultured human limbal epithelial cells (HLECS) for use in treatment of limbal stem cell deficiency (LSCD). In the present study, we compared storage of cultured HLEC using the conventional hypothermic Optisol-GS storage method at 4°C versus storage at 23°C (room temperature). Materials and Methods HLECs were cultured for three weeks on amniotic membrane (AM), transferred to polypropylene containers and stored in Optisol-GS for 4 days at 23°C and 4°C. A calcein-acetoxymethyl ester/ethidium homodimer-1 assay was used to assess viability. Morphology and phenotype were analyzed by light microscopy and immunohistochemistry, respectively. Results Expression of stem cell and proliferation markers p63, ∆Np63α, ABCG2, K19, K3, Cx43, Ki67, and PCNA was maintained at pre-storage control levels during storage at 23°C. ABCG2 and PCNA expression were both significantly altered during storage at 4°C. HLEC cell sheet viability also significantly declined following storage at 4°C. HLEC sheets stored at 4°C demonstrated extensive detachment of basal cells from the AM in sharp contrast to storage at 23°C, where attachment to the AM was maintained throughout the storage period. Conclusions The present study demonstrates the feasibility of short-term storage of cultured HLECs in Optisol-GS, which offers a convenient standardized xenogeneic-free storage method. Storage temperature highly affected the results. Maintenance of cell viability, morphology and undifferentiated proliferative phenotype of cultured HLEC sheets favored storage at 23°C.

Objectives: Acute atherosis (AA) is a uteroplacental spiral artery lesion, identified by intramural lipid-laden foam cells, with highest rates in preeclampsia (PE). We compared AA detection rates in preeclampsia (PE) across three different decidual spiral artery collection methods in same patients. We tested whether the rate and topographical distribution of AA associates with clinical parameters. Study design: Three decidual tissue types were harvested from each of 107 preeclamptic women delivered by cesarean section. Routine sampled basal surface placenta (decidua basalis, DB) and fetal membrane roll (decidua parietalis, DP) biopsies were compared with decidual vacuum suction biopsies (DB), regarding spiral artery rate and AA presence. Spiral arteries and AA were identified using predefined, immunohistochemically based criteria on serial sections. Main outcome measures and results: Detection of spiral arteries (87%) and AA (35%) was highest in DB samples collected by vacuum suction compared to the two other methods. Pregnancies with AA detected in vacuum suctioned DB had lower gestational age at delivery, lower birth weight percentile and more often fetal growth restriction. Basal plate DB samples demonstrating AA associated with pregnancies affected by pathological fetal Dopplers, whereas AA detected in DP membrane rolls, did not. Conclusions: Placental bed vacuum suction provides more spiral arteries and higher AA rate, suggesting underestimation of AA in conventional pathology samples of basal plate DB biopsies and DP. The association of AA with PE-related clinical parameters varies according to tissue collection method. Longitudinal studies could elucidate whether AA also identifies women with future premature cardiovascular risk.

To describe oncological and functional outcomes in patients treated with reconstructive organ-sparing surgery (OSS) for squamous cell carcinoma of the penis. Plastic reconstructive OSS of the penis with a split thickness skin graft has been proposed as a treatment option for penile cancer, with the objective being preservation of physiological voiding and sexual function without comprising oncological control.Multicenter study reporting clinicopathological data of 57 patients with malignant lesions of the penis treated with OSS and plastic reconstructive surgery with split thickness skin graft from 2007 to 2019. Health related quality of life (HRQoL) was assessed with EuroQoL-5D-3L, urinary symptoms with the International Consultation on Incontinence Modular Questionnaire for Male Lower Urinary Tract Symptoms, and erectile function with the International Index of erectile function (IIEF)-5.Fifty-seven patients underwent OSS reconstructive surgery. Twenty underwent glans resurfacing, 23 partial penectomy, and 14 glansectomy. Median age was 55.1 years (interquartile range [IQR] 29-90), median follow-up 55.7 months (3-149). At the time of data analysis, 6 patients had died of Squamous Cell Carcinoma (SCC) (12.5%) and 10 (17.8%) had progressed. Kaplan-Meier estimates showed a 5-year survival rate of 87.5% and a 5-year progression-free survival of 83%. We assessed HRQoL and functional outcomes in 32 patients. EuroQol 5D-3L showed a mean health status of 82.5%, median Voiding score of the ICIQ-MLTUS was 4 (IQR 1-15), and median IIEF-5 19 (IQR 10.75-25).OSS of the penis remains a safe and viable option for the treatment of SCC, ensuring a favorable appearance of the penis, preserving urinary and sexual function, with good HRQoL and without comprising oncological safety in selected cases.

INTRODUCTION:Acute atherosis (AA) is a lesion affecting uteroplacental spiral arteries during pregnancy, most frequently in preeclampsia but occasionally in normal pregnancy. It is commonly observed in untransformed spiral arteries (intact smooth muscle cell layer, lacking intramural trophoblasts). The mechanism causing lesion development is unknown. AA shares some morphological similarities with atherosclerosis, in which endothelial activation occurs early. Here we histologically characterize decidua basalis spiral arteries with and without AA, focusing on endothelial status and activation.METHODS:Formalin-fixed and paraffin-embedded decidua basalis tissue sections from 32 patients (16 normotensive, 5 with AA, 16 preeclampsia, 7 with AA) were stained with H + E, PAS, MSB (Martius Scarlet Blue), desmin, CK7, CD68, CD31, vWF and ICAM-1. We logged remodeling status, presence of AA, endothelial morphology, endothelial CD31 intensity and activation (ICAM-1-positive cells).RESULTS:We observed fully or partially transformed spiral arteries in most decidua basalis samples, and no untransformed arteries. AA arteries were also observed, characterized by intramural CD68-positive vacuolated cells and fibrinoid necrosis. They lacked a smooth muscle cell layer and intramural trophoblasts. The fibrinoid necrosis in AA lesions stained red with MSB. AA arteries were associated with lower CD31 staining intensity of endothelial cells. More arteries had an abnormal or destroyed endothelium relative to arteries without AA. Endothelial activation was not observed in the majority of AA arteries.DISCUSSION:Our results indicate an altered endothelial phenotype as important in the development of AA, supporting previous observations. The histology of AA differs from that of atherosclerosis.

Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development.

Purpose: Cultured epidermal cell sheets (CECS) are used in the treatment of large area burns to the body and have potential to treat limbal stem cell deficiency (LSCD) as shown in animal studies. Despite widespread use, storage options for CECS are limited. Short-term storage allows flexibility in scheduling surgery, quality control and improved transportation to clinics worldwide. Recent evidence points to the phenotype of cultured epithelial cells as a critical predictor of post-operative success following transplantation of CECS in burns and in transplantation of cultured epithelial cells in patients with LSCD. This study, therefore assessed the effect of a range of temperatures, spanning 4-37 degrees C, on the phenotype of CECS stored over a 2-week period in a xenobiotic-free system.Materials and Methods: Progenitor cell (p63, Np63 and ABCG2) and differentiation (C/EBP and CK10) associated marker expression was assessed using immunocytochemistry. Immunohistochemistry staining of normal skin for the markers p63, ABCG2 and C/EBP was also carried out. Assessment of progenitor cell side population (SP) was performed using JC1 dye by flow cytometry.Results: P63 expression remained relatively constant throughout the temperature range but was significantly lower compared to control between 20 and 28 degrees C (p<0.05). High C/EBP together with low p63 suggested more differentiation beginning at 20 degrees C and above. Lower CK10 and C/EBP expression most similar to control was seen at 12 degrees C. The percentage of ABCG2 positive cells was most similar to control between 8 and 24 degrees C. Between 4 and 24 degrees C, the SP fluctuated, but was not significantly different compared to control. Results were supported by staining patterns indicating differentiation status associated with markers in normal skin sections.Conclusions: Lower storage temperatures, and in particular 12 degrees C, merit further investigation as optimal storage temperature for maintenance of undifferentiated phenotype in CECS.

Background: Globally, Africa has the highest prevalence of HIV, schistosomiasis and another neglected entity: cervical cancer. Genital schistosomiasis manifests in lesions that are hypothesized to link with HIV and cervical atypia. Methods & Materials: This study was conducted among 833 young women aged 16-23 years from rural high schools in KwaZulu-Natal. Risk factors for schistosomiasis and cervical atypia and the association of genital schistosomiasis and squamous atypia of the cervix were investigated using diagnostic cytology, urine microscopy, and questionnaire data. Results: Participants were sexually active from a young age and 523 (63.0%) had at least one child and 742 (89.1%) relied on rivers as their primary water source. The Schistosoma prevalence detected cytologically and via urine microscopy was 12 (1.4%) and 178 (21.4%) respectively. Squamous cell atypia was detected among 567 (68%). There was a significant association between the participants who were positive for any squamous cell atypia and those who had S. haematobium eggs in Pap smears (OR = 5.6, P = 0.005; 95% CI 1.6-21.0) and for S. haematobium eggs in urine OR = 2.9, 95% CI 1.72 - 4.99, P = 0.005). Conclusion: The specificity of cytology for Schistosoma detection was low using is seen previously, it is possible that an improved detection rate of genital schistosomiasis could be achieved using cervico-vaginal lavage Schistosoma DNA testing. While a significant association exists between urogenital schistosomiasis as detected by cytology and urine microscopy with squamous atypia in this young population, it must be noted that more than half of the young women have cervical atypia that could potentially regress. Cytology was useful in revealing the squamous atypia among this young population who is not routinely screened, a limitation is that it was not feasible to confirm results using histology or other complementary tests. The relationship between schistosomiasis and cervical cancer is complex, while there may be association, it was not possible to prove causality or eliminate all confounders. In communities at risk, health promotion, screening and health care targeting not only HIV and schistosomiasis, but also cervical cancer should be made available in order to reduce the prevalence of these preventable diseases.