The WHO atlas for female-genital schistosomiasis: Co-design of a practicable diagnostic guide, digital support and training.

Up to 56 million young and adult women of African origin suffer from Female Genital Schistosomiasis (FGS). The transmission of schistosomiasis happens through contact with schistosomiasis infested fresh water in rivers and lakes. The transmission vector is the snail that releases immature worms capable of penetrating the human skin. The worm then matures and mates in the blood vessels and deposits its eggs in tissues, causing urogenital disease. There is currently no gold standard for FGS diagnosis. Reliable diagnostics are challenging due to the lack of appropriate instruments and clinical skills. The World Health Organisation (WHO) recommends "screen-and-treat" cervical cancer management, by means of visual inspection of characteristic lesions on the cervix and point-of-care treatment as per the findings. FGS may be mistaken for cervical cancer or sexually transmitted diseases. Misdiagnosis may lead to the wrong treatment, increased risk of exposure to other infectious diseases (human immunodeficiency virus and human papilloma virus), infertility and stigmatisation. The necessary clinical knowledge is only available to a few experts in the world. For an appropriate diagnosis, this knowledge needs to be transferred to health professionals who have minimal or non-existing laboratory support. Co-design workshops were held with stakeholders (WHO representative, national health authority, FGS experts and researchers, gynaecologists, nurses, medical doctors, public health experts, technical experts, and members of the public) to make prototypes for the WHO Pocket Atlas for FGS, a mobile diagnostic support tool and an e-learning tool for health professionals. The dissemination targeted health facilities, including remote areas across the 51 anglophone, francophone and lusophone African countries. Outcomes were endorsed by the WHO and comprise a practical diagnostic guide for FGS in low-resource environments.

Placental weight, surface area, shape and thickness - Relations with maternal ethnicity and cardio-metabolic factors during pregnancy.

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 mid-gestational 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.

Injuries associated with mechanical chest compressions and active decompressions after out-of-hospital cardiac arrest: A subgroup analysis of non-survivors from a randomized study.

Background: Both skeletal and visceral injuries are reported after cardiopulmonary resuscitation (CPR). This subgroup analysis of a randomized clinical study describes/compares autopsy documented injury patterns caused by two mechanical, piston-based chest compression devices: standard LUCAS® 2 (control) and LUCAS® 2 with active decompression (AD, intervention) in non-survivors with out-of-hospital cardiac arrest (CA). Method: We compared injuries documented by autopsies (medical/forensic) after control and intervention CPR based on written relatives consent to use patients' data. The pathologists were blinded for the device used. The cause of CA and injuries reported were based on a prespecified study autopsy template. We used Pearson's chi-squared test and logistic regression analysis with an alpha level of 0.05. Results: 221 patients were included in the main study (April 2015-April 2017) and 207 did not survive. Of these, 114 (55%, 64 control and 50 intervention) underwent medical (N = 73) or forensic (N = 41) autopsy. The cause of CA was cardiac 53%, respiratory 17%, overdose/intoxication 14%, ruptured aorta 10%, neurological 1%, and other 5%. There were no differences between control and intervention in the incidence of rib fractures (67% vs 72%; p-value = 0.58), or sternal fractures (44% vs 48%; p-value = 0.65), respectively. The most frequent non-skeletal complication was bleeding (26% of all patients) and intrathoracic was the most common location. Ten of the 114 patients had internal organ injuries, where lungs were most affected. Conclusion: In non-survivors of OHCA patients, the most frequent cause of cardiac arrest was cardiogenic. Skeletal and non-skeletal fractures/injuries were found in both control and intervention groups. Bleeding was the most common non-skeletal complication. Internal organ injuries were rare.

Gene expression of fibrinolytic markers in coronary thrombi.

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 .

TIMP-1 expression in coronary thrombi associate with myocardial injury in ST-elevation myocardial infarction patients.

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.

Platelet alloimmunization is associated with low grade chronic histiocytic intervillositis - A new link to a rare placental lesion?

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.

The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI.

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-1ß (IL1-ß), 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-1ß (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.

A systematic review of handheld tools in lieu of colposcopy for cervical neoplasia and female genital schistosomiasis.

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.

Optisol-GS Storage of Cultured Human Limbal Epithelial Cells at Ambient Temperature Is Superior to Hypothermic Storage.

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.

Nephrotic syndrome and pulmonary hypertension as complications of intravenous drug abuse.

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.

Uteroplacental acute atherosis in preeclamptic pregnancies: Rates and clinical outcomes differ by tissue collection methods.

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.

Acute atherosis of decidua basalis; characterization of spiral arteries, endothelial status and activation.

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.

Cultured Human Retinal Pigment Epithelial (hRPE) Sheets: A Search for Suitable Storage Conditions.

The advancement of human retinal pigment epithelial cell (hRPE) replacement therapy is partly dependent on optimization of cell culture, cell preservation, and storage medium. This study was undertaken to search for a suitable storage temperature and storage medium for hRPE. hRPE monolayer sheets were cultured under standard conditions at 37°C and then randomized for storage at six temperatures (4, 16, 20, 24, 28, and 37°C) for 7 days. After revealing a suitable storage temperature, hRPE sheets were subsequently stored with and without the silk protein sericin added to the storage medium. Live/dead assay, light microscopy, pH, and phenotypic expression of various proteins were used to assess cell cultures stored at different temperatures. After 7 days of storage, hRPE morphology was best preserved at 4°C. Addition of sericin to the storage medium maintained the characteristic morphology of the preserved cells, and improved pigmentation and levels of pigmentation-related proteins in the cultured hRPE sheets following a 7-day storage period at 4°C.

Unexplained chronic liver disease in Ethiopia: a cross-sectional study.

BACKGROUND: 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. METHODS: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. RESULTS: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25-40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. CONCLUSION: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation.

Indications for Cesarean Sections in Rural Nepal.

OBJECTIVE: Globally, cesarean section (CS) rate is close to 26 %. Nepal has a reported CS rate of 5 %, with huge differences in rural (3.5 %) and urban (15 %) areas. The aim of the study was to determine the rate and indications for CS in a remote hospital in a rural area of Nepal. METHODS: A one-year cross-sectional prospective study from August 2014 to August 2015 was performed at Okhaldhunga Community Hospital (OCH). Semi-structured interviews of all women undergoing CS (91) were done, partly with the assistance of a local translator. A maternal waiting home is connected to the hospital. RESULTS: Out of the 864 births in the hospital, 91 CS were performed giving a CS rate of 9.5 %. The most frequent indications were: prolonged labor in 24 CS (26.4 %), abnormal fetal lie in 23 CS (25.3 %) and fetal distress in 18 CS (19.8 %). Three-quarters of CS were performed as an emergency. Almost half of the women stayed in the maternal waiting home prior to birth. CONCLUSION: The CS rate at OCH was relatively low, within WHO's recommendation, with types of indication similar to other countries. There were no signs of CS overuse. Maternal request was not the sole indication in any CS.

Cervical cytology as a diagnostic tool for female genital schistosomiasis: Correlation to cervical atypia and Schistosoma polymerase chain reaction.

BACKGROUND: Female genital schistosomiasis (FGS) is a tissue reaction to lodged ova of Schistosoma haematobium in the genital mucosa. Lesions can make the mucosa friable and prone to bleeding and discharge. Women with FGS may have an increased risk of HIV acquisition, and FGS may act as a cofactor in the development of cervical cancer. OBJECTIVES: To explore cytology as a method for diagnosing FGS and to discuss the diagnostic challenges in low-resource rural areas. The correlation between FGS and squamous cell atypia (SCA) is also explored and discussed. Cytology results are compared to Schistosoma polymerase chain reaction (PCR) in vaginal lavage and urine and in urine microscopy. MATERIALS AND METHODS: In a clinical study, 394 women aged between 16 and 23 years from rural high schools in KwaZulu-Natal, South Africa, underwent structured interviews and the following laboratory tests: Cytology Papanicolaou (Pap) smears for S. haematobium ova and cervical SCA, real-time PCR for Schistosoma-specific DNA in vaginal lavage and urine samples, and urine microscopy for the presence of S. haematobium ova. RESULTS: In Pap smears, S. haematobium ova were detected in 8/394 (2.0%). SCA was found in 107/394 (27.1%), seven of these had high-grade squamous intraepithelial lesion (HSIL). Schistosoma specific DNA was detected in 38/394 (9.6%) of vaginal lavages and in 91/394 (23.0%) of urines. Ova were found microscopically in 78/394 (19.7%) of urines. CONCLUSION: Schistosoma PCR on lavage was a better way to diagnose FGS compared to cytology. There was a significant association between S. haematobium ova in Pap smears and the other diagnostic methods. In low-resource Schistosoma-endemic areas, it is important that cytology screeners are aware of diagnostic challenges in the identification of schistosomiasis in addition to the cytological diagnosis of SCA. Importantly, in this study, three of eight urines were negative but showed Schistosoma ova in their Pap smear, and one of them was also negative for Schistosoma DNA in urine. In this study, SCA was not significantly associated with schistosomiasis. HSIL detected in this young population might need future consideration.

Hampered Lung Maturation in Methimazole-Induced Hypothyroidism in Fetal Chicken: Morphological and Molecular Correlates to Human Fetal Development.

BACKGROUND: Molecular understanding of lung development is crucial for developing therapies and diagnostic tools. Animal models with altered thyroid hormone signaling provide mechanistic insight into thyroid-dependent neonatal lung disease. Repression of Klf2 (Krüppel-like factor 2), a suggested T3 target gene, is associated with disrupted lung development in mice. Klf2 is proposed to be specifically involved in type I pneumocyte differentiation. OBJECTIVES: To explore mechanisms of thyroid-dependent lung disease, we studied developing chicken fetuses with experimentally induced hypothyroidism. METHODS: Morphology and the expression of a panel of molecules linked to Klf2 were assessed using histology, immunohistochemistry, Western blot and qPCR. RESULTS: Methimazole injections at E14 hampered lung maturation. The effects of methimazole were evident in several tissue compartments, and impacted on both pneumocyte and vascular differentiation, suggesting cellular and molecular pleiotropy. CONCLUSIONS: Concomitant expression changes in a panel of selected microRNAs regulated by Klf2 suggest importance in lung development. These microRNAs may thus represent potential clinical targets and diagnostic and prognostic tools in thyroid-dependent lung disease.

Effect of Storage Temperature on the Phenotype of Cultured Epidermal Cells Stored in Xenobiotic-Free Medium.

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 °C, on the phenotype of CECS stored over a 2-week period in a xenobiotic-free system. MATERIALS AND METHODS: Progenitor cell (p63, ΔNp63α and ABCG2) and differentiation (C/EBPδ and CK10) associated marker expression was assessed using immunocytochemistry. Immunohistochemistry staining of normal skin for the markers p63, ABCG2 and C/EBPδ 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 °C (p < 0.05). High C/EBPδ together with low p63 suggested more differentiation beginning at 20 °C and above. Lower CK10 and C/EBPδ expression most similar to control was seen at 12 °C. The percentage of ABCG2 positive cells was most similar to control between 8 and 24 °C. Between 4 and 24 °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 °C, merit further investigation as optimal storage temperature for maintenance of undifferentiated phenotype in CECS.

Acute atherosis in vacuum suction biopsies of decidua basalis: An evidence based research definition.

BACKGROUND: Acute atherosis (AA) of the uteroplacental spiral arteries has been characterised by subendothelial lipid-laden foam cells, perivascular leukocyte infiltrates (PVI) and fibrinoid necrosis. Because precise diagnostic criteria are not available for comparative research studies we developed and tested new simplified criteria based on 237 cases. METHODS: Decidual basalis samples were collected by vacuum suction at elective cesarean deliveries. Spiral arteries were evaluated in serial decidual tissue sections from women with normal pregnancy, preeclampsia, and diabetes. Features of AA were sought in parallel sections stained with H&E and immunostained for CD68, cytokeratin CK7 and desmin, and costained with Periodic Acid Schiff (PAS). RESULTS: Foam cell lesions were defined as two or more adjacent, intramural, vacuolated CD68 positive cells, PVI as a focal perivascular lymphocyte accumulation, more dense than in the surrounding decidua. Increased fibrinoid (PAS positive) was identified if present in ≥75% of the arterial wall circumference. PVI and increased fibrinoid were significantly associated with preeclampsia but not specifically associated with the presence of foam cell lesions. Hence we diagnosed decidua basalis AA lesions solely by the presence of foam cell lesions, occurring in preeclampsia (37%), diabetes (10%) and healthy normotensive women (11%). The simplified criterion was reproducible by different investigators. Decidua basalis AA occurred most commonly and extensively in preeclampsia, but did not distinguish between preterm and term disease. DISCUSSION: Our evidence based criterion for decidua basalis AA diagnosis in vacuum suction biopsies may not apply to myometrial or decidua parietalis arteries. In decidual basalis samples it should facilitate comparisons between research studies, to improve pathophysiological understanding of AA and preeclampsia.