Overexpression of Connexin 40 in the Vascular Endothelial Cells of Placenta with Acute Chorioamnionitis.

BACKGROUND: Connexins (Cx) 43 and 40 play a role in leukocytes recruitment in acute inflammation. They are expressed in the endothelial cells. They are also found in the placenta and involved in the placenta development. Acute chorioamnionitis is associated with an increased risk of adverse perinatal outcomes. The aim of this study was to determine the expressions of Cx43 and Cx40 in the placenta of mothers with acute chorioamnionitis, and to correlate their association with the severity of chorioamnionitis and adverse perinatal outcomes. METHODS: This study comprised a total of 81 cases, consisting of 39 placenta samples of mothers with acute chorioamnionitis and 42 non-acute chorioamnionitis controls. Cx43 and Cx40 immunohistochemistry were performed on all cases and their expressions were evaluated on cytotrophoblasts, syncytiotrophoblasts, chorionic villi endothelial cells, stem villi endothelial cells, maternal endothelial cells and decidua of the placenta. RESULTS: Primigravida has a significantly higher risk of developing acute chorioamnionitis (p < 0.001). Neonates of mothers with a higher stage of fetal inflammatory response was significantly associated with lung complications (p = 0.041) compared to neonates of mothers with a lower stage. The expression of Cx40 was significantly higher in fetal and maternal vascular endothelial cells in acute chorioamnionitis (p < 0.001 and p = 0.037, respectively) compared to controls. Notably, Cx43 was not expressed in most of the types of cells in the placenta, except for decidua. Both Cx43 and Cx40 expressions did not have correlation with the severity of acute chorioamnionitis and adverse perinatal outcomes. CONCLUSION: Cx40 was overexpressed in the fetal and maternal vascular endothelial cells in the placenta of mothers with acute chorioamnionitis, and it may have a role in the development of inflammation in placenta.

Non-hypertensive gestational diabetes mellitus: Placental histomorphology and its association with perinatal outcomes.

INTRODUCTION: Gestational diabetes mellitus (GDM) exerts a great impact on the placenta and reflects changes on placentas both morphological and functionally. The aims of this study are to evaluate the prevalence of placental histopathological lesions in pregnancies complicated by GDM compared to gestational age-matched controls, and their association with maternal and fetal complications. METHODS: Fifty-four singleton GDM-complicated pregnancies were recruited and compared to 33 consecutive normal pregnancies. Two pathologists, blinded to all clinical data, reviewed and evaluated all histological samples of the placentas in accordance with Amsterdam criteria. Relevant demographic, clinical data and primary birth outcomes were recorded. RESULTS: A myriad of histomorphological abnormalities, including chronic inflammation (n = 9/54, p = 0.031), histological chorioamnionitis (n = 23/54, p < 0.001), umbilical/chorionic vasculitis (n = 9/54, p = 0.031), changes related to maternal vascular malperfusion (n = 22/54, p = 0.003), chorangiosis (n = 10/54, p = 0.046) and villous dysmaturity (n = 9/54, p = 0.012) were observed more frequently in the GDM placentas compared to the controls. Additionally, GDM significantly increased the risk of fetal complications, including macrosomia/fetal growth restriction (n = 13/54, p = 0.004). DISCUSSION: Histoarchitectural abnormalities were observed more frequently in placentas of GDM pregnancies compared to the controls. Our findings support the hypothesis that diabetic-induced damage in the placental function may be associated with the increased in fetal growth disorders in GDM-complicated pregnancies.

Cat Scratch Disease-A Benign Disease with Thymic Hyperplasia Mimicking Lymphoma.

Cat scratch disease (CSD) is a benign condition caused by the inoculation of Bartonella henselae. The imaging findings are non-specific, and it is difficult to diagnose the disease via imaging. However, imaging studies help exclude other differential diagnoses in diagnostic dilemmas. We encountered a case of a 17-year-old adolescent who presented with painful neck swelling. CT showed multiple bilateral cervical lymphadenopathies with triangular soft tissue mass at the anterior mediastinum likely to be thymic hyperplasia, which is unusual in CSD and was mistaken for a lymphoproliferative disorder. Tissue diagnosis with a thorough clinical history yielded the diagnosis of cat scratch disease, and follow-up imaging showed resolution of the cervical lymphadenopathy and thymic hyperplasia.

Diagnostic Utility of TSSC3 and RB1 Immunohistochemistry in Hydatidiform Mole.

The general notion of complete hydatidiform moles is that most of them consist entirely of paternal DNA; hence, they do not express p57, a paternally imprinted gene. This forms the basis for the diagnosis of hydatidiform moles. There are about 38 paternally imprinted genes. The aim of this study is to determine whether other paternally imprinted genes could also assist in the diagnostic approach of hydatidiform moles. This study comprised of 29 complete moles, 15 partial moles and 17 non-molar abortuses. Immunohistochemical study using the antibodies of paternal-imprinted (RB1, TSSC3 and DOG1) and maternal-imprinted (DNMT1 and GATA3) genes were performed. The antibodies' immunoreactivity was evaluated on various placental cell types, namely cytotrophoblasts, syncytiotrophoblasts, villous stromal cells, extravillous intermediate trophoblasts and decidual cells. TSSC3 and RB1 expression were observed in all cases of partial moles and non-molar abortuses. In contrast, their expression in complete moles was identified in 31% (TSSC3) and 10.3% (RB1), respectively (p < 0.0001). DOG1 was consistently negative in all cell types in all cases. The expressions of maternally imprinted genes were seen in all cases, except for one case of complete mole where GATA3 was negative. Both TSSC3 and RB1 could serve as a useful adjunct to p57 for the discrimination of complete moles from partial moles and non-molar abortuses, especially in laboratories that lack comprehensive molecular service and in cases where p57 staining is equivocal.

Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.

Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.

SARS-CoV-2 Transplacental Transmission: A Rare Occurrence? An Overview of the Protective Role of the Placenta.

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global public health crisis, causing substantial concern especially to the pregnant population. Pregnant women infected with SARS-CoV-2 are at greater risk of devastating pregnancy complications such as premature delivery and stillbirth. Irrespective of the emerging reported cases of neonatal COVID-19, reassuringly, confirmatory evidence of vertical transmission is still lacking. The protective role of the placenta in limiting in utero spread of virus to the developing fetus is intriguing. The short- and long-term impact of maternal COVID-19 infection in the newborn remains an unresolved question. In this review, we explore the recent evidence of SARS-CoV-2 vertical transmission, cell-entry pathways, placental responses towards SARS-CoV-2 infection, and its potential effects on the offspring. We further discuss how the placenta serves as a defensive front against SARS-CoV-2 by exerting various cellular and molecular defense pathways. A better understanding of the placental barrier, immune defense, and modulation strategies involved in restricting transplacental transmission may provide valuable insights for future development of antiviral and immunomodulatory therapies to improve pregnancy outcomes.

Maternal and fetal outcomes of pregnant women with bacterial vaginosis.

Background: Bacterial vaginosis (BV) is a common infection in women of reproductive age group because of vaginal dysbiosis. The impact of BV during pregnancy is still not well defined. The objective of this study is to assess the maternal-fetal outcome in women with BV. Materials and Methods: A prospective cohort study over one-year duration was conducted from December, 2014 until December, 2015, involving 237 women who presented with abnormal vaginal discharge, preterm labour or preterm prelabour rupture of membrane between 22- and 34-weeks period of gestation. Vaginal swabs were sent for culture and sensitivity, BV® Blue testing and PCR for Gardnerella vaginalis (GV). Results: BV was diagnosed in 24/237 (10.1%) cases. The median gestational age was 31.6 weeks. GV was isolated from 16 out of 24 (66.7%) in the BV positive group. There was a significantly higher preterm birth rate, below 34 weeks (22.7% vs. 6.2%, p = 0.019) in women with BV. There was no statistically significant difference in maternal outcome such as clinical chorioamnionitis or endometritis. However, placental pathology revealed more than half (55.6%) of women with BV had histologic chorioamnionitis. Neonatal morbidity was significantly higher with exposure to BV, with a lower median birth weight, higher rate of neonatal intensive care unit admission (41.7% vs. 19.0%, p = 0.010), increased intubation for respiratory support (29.2% vs. 7.6%, p = 0.004) and respiratory distress syndrome (33.3% vs. 9.0%, p = 0.002). Conclusion: More research is needed to formulate guidelines for prevention, early detection and treatment of BV during pregnancy to reduce intrauterine inflammation and the associated adverse fetal outcomes.

Protocol paper: kainic acid excitotoxicity-induced spinal cord injury paraplegia in Sprague-Dawley rats.

BACKGROUND: Excitotoxicity-induced in vivo injury models are vital to reflect the pathophysiological features of acute spinal cord injury (SCI) in humans. The duration and concentration of chemical treatment controls the extent of neuronal cell damage. The extent of injury is explained in relation to locomotor and behavioural activity. Several SCI in vivo methods have been reported and studied extensively, particularly contusion, compression, and transection models. These models depict similar pathophysiology to that in humans but are extremely expensive (contusion) and require expertise (compression). Chemical excitotoxicity-induced SCI models are simple and easy while producing similar clinical manifestations. The kainic acid (KA) excitotoxicity model is a convenient, low-cost, and highly reproducible animal model of SCI in the laboratory. The basic impactor approximately cost between 10,000 and 20,000 USD, while the kainic acid only cost between 300 and 500 USD, which is quite cheap as compared to traditional SCI method. METHODS: In this study, 0.05 mM KA was administered at dose of 10 µL/100 g body weight, at a rate of 10 µL/min, to induce spinal injury by intra-spinal injection between the T12 and T13 thoracic vertebrae. In this protocol, detailed description of a dorsal laminectomy was explained to expose the spinal cord, following intra-spinal kainic acid administration at desired location. The dose, rate and technique to administer kainic acid were explained extensively to reflect a successful paraplegia and spinal cord injury in rats. The postoperative care and complication post injury of paraplegic laboratory animals were also explained, and necessary requirements to overcome these complications were also described to help researcher. RESULTS: This injury model produced impaired hind limb locomotor function with mild seizure. Hence this protocol will help researchers to induce spinal cord injury in laboratories at extremely low cost and also will help to determine the necessary supplies, methods for producing SCI in rats and treatments designed to mitigate post-injury impairment. CONCLUSIONS: Kainic acid intra-spinal injection at the concentration of 0.05 mM, and rate 10 µL/min, is an effective method create spinal injury in rats, however more potent concentrations of kainic acid need to be studied in order to create severe spinal injuries.

High EZH2 Protein Expression Is a Poor Prognostic Predictor in IDH1 R132H-Negative Gliomas.

Accumulating data indicates that enhancer of zeste homology 2 (EZH2) and isocitrate dehydrogenase 1 (IDH1) are implicated in promoting tumourigenesis in a myriad of malignancies including gliomas. We aimed to determine the immunoexpression of EZH2 in gliomas and its correlation with clinicopathological variables. The prognostic value of the combined immunoexpression of EZH2 and IDH1 was further explored in a retrospective analysis involving 56 patients with histologically confirmed gliomas in Universiti Kebangsaan Malaysia Medical Centre from 2010 to 2016. The patients were then followed up for a period of five years. EZH2 and IDH1 R132H immunoexpressions were performed and analysed on respective tissue blocks. Five-year progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan−Meier analysis. Univariate and multivariate Cox proportional hazard regression models were performed to evaluate the value of EZH2 as an independent factor for the prediction of PFS and OS. High EZH2 immunoexpression was demonstrated in 27 (48.2%) gliomas. High EZH2 expression was significantly correlated with older age (p = 0.003), higher tumour grade (p < 0.001), negative IDH1 R132H immunoexpression (p = 0.039), a poor 5-year PFS (mean = 9.7 months, p < 0.001) and 5-year OS (mean = 28.2 months, p = 0.007). In IDH1 R132H-negative gliomas, there was a trend toward shorter 5-year PFS (mean = 8.0 months, p = 0.001) and 5-year OS (mean = 28.7 months, p = 0.06) in gliomas demonstrating high EZH2 expression compared with those with low EZH2 expression. High EZH2 immunoexpression is an unfavourable independent prognostic predictor of poor survival in gliomas. EZH2 analysis might therefore be of clinical value for risk stratification, especially in patients with IDH1 R132H-negative gliomas.

In Vitro Growth Inhibition, Caspase-Dependent Apoptosis, and S and G2/M Phase Arrest in Breast Cancer Cells Induced by Fluorine-Incorporated Gold I Compound, Ph3PAu[SC(OMe)=NC6H4F-3].

Gold-based anticancer compounds have been attracting increasing research interest due to their ability to kill cancer cells resistant to platinum-based compounds. Gold I- and gold III-based complexes have shown satisfactory anticancer activities. In this study, two new fluorine-incorporated gold (I) compounds such as Ph3PAu[SC(OMe)=NC6H4F-3] and DPPFeAu2[(SC(OMe)=NC6H4F-3)]2 were evaluated for their in vitro activities against human breast cancer cell lines, primary breast cancer cells, and breast cancer stem cells (parental breast cancer stem cells, BCSC-P, and breast cancer stem cells, BCSC). Assays for growth inhibition and cytotoxicity, including real-time cell analysis, were carried out to screen effective antibreast cancer compounds. In addition, further in vitro assays such as apoptosis, caspase 3/7 activity, and cell cycle analysis were performed to observe the action and mechanism of killing breast cancer cells by the selected gold I compound, Ph3PAu[SC(OMe)=NC6H4F-3]. The gold (I) compound, Ph3PAu[SC(OMe)=NC6H4F-3], showed low toxicity to H9c2 normal cells and significant growth inhibition in MDA-MB-231 and MCF-7 cells, primary breast cancer cells, and breast cancer stem cells (BCSC-P and BCSC). The IC50 doses of the gold (I) compound Ph3PAu[SC(OMe)=NC6H4F-3] against the breast cancer cell lines MDA-MB-231 and MCF-7 were approximately 6-fold lower than that of cisplatin (cis-diamineplatinum (II) dichloride, CDDP). Moreover, the compound Ph3PAu[SC(OMe)=NC6H4F-3] induced caspase 3/7-dependent apoptosis and cell cycle arrest at S and G2/M phases. Ph3PAu[SC(OMe)=NC6H4F-3], a gold (I) compound incorporated with fluorine, is a potential candidate for the treatment of breast cancer.

PD-L1 Expression in Endometrial Cancer and Its Association with Clinicopathological Features: A Systematic Review and Meta-Analysis.

Endometrial cancer (EC) is one of the most common malignancies of the female genital tract and its current treatment mainly relies on surgical removal of the tumour bulk, followed by adjuvant radiotherapy with or without chemotherapy/hormonal therapy. However, the outcomes of these approaches are often unsatisfactory and are associated with severe toxicity and a higher recurrence rate of the disease. Thus, more clinical research exploring novel medical intervention is needed. Involvement of the immune pathway in cancer has become important and the finding of a high positive expression of programmed cell death-ligand 1 (PD-L1) in EC may offer a better targeted therapeutic approach. Numerous studies on the PD-L1 role in EC have been conducted, but the results remained inconclusive. Hence, this systematic review was conducted to provide an update and robust analysis in order to determine the pooled prevalence of PD-L1 expression in EC and evaluate its association with clinicopathological features in different focuses of tumour cells (TC) and immune cells (IC). A comprehensive literature search was conducted using the PubMed, Web of Science, and Scopus databases. Twelve articles between 2016 and 2021 with 3023 EC cases met the inclusion criteria. The effect of PD-L1 expression on the outcome parameters was estimated by the odds ratios (ORs) with 95% confidence intervals (CIs) for each study. The pooled prevalence of PD-L1 was 34.26% and 51.39% in the tumour cell and immune cell, respectively, among women with EC. The PD-L1 expression was significantly associated with Stage III/IV disease (in both TC and IC) and correlated to the presence of lympho-vascular invasion in IC. However, the PD-L1 expression in TC was not associated with the age groups, histology types, myometrial invasion, and lympho-vascular invasion. In IC, PD-L1 expression was not associated with age group, histology type, and myometrial invasion. The meta-analysis survival outcomes of PD-L1 high expression had a significant association with worse OS in IC but not in TC.

SARS-CoV-2 Infection in Pregnancy: Placental Histomorphological Patterns, Disease Severity and Perinatal Outcomes.

The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnancy outcomes. A retrospective cohort study on 47 pregnant women with confirmed SARS-CoV-2 infection, matched with non-infected controls, was conducted. Relevant clinicopathological data and primary birth outcomes were recorded. Histomorphology and SARS-CoV-2 immunohistochemistry analyses of placental tissues were performed. Only 1 of 47 cases showed SARS-CoV-2 immunoreactivity in the syncytiotrophoblasts. Histologically, decidual vasculopathy (n = 22/47, p = 0.004), maternal vascular thrombosis (n = 9/47, p = 0.015) and chronic histiocytic intervillositis (n = 10/47, p = 0.027) were significantly higher in the COVID-19-infected placentas when compared to the control group. Maternal vascular thrombosis was a significant feature in the active COVID-19 group. A significant lower gestational age (p < 0.001)) at delivery and a higher caesarean section rate (p = 0.007) were observed in the active SARS-CoV-2-infected cases, resulting in a significant lower fetal-placental weight ratio (p = 0.022) and poorer Apgar score (p < 0.001). Notably, active (p = 0.027), symptomatic (p = 0.039), severe-critical (p = 0.002) maternal COVID-19 infection and placental inflammation (p = 0.011) were associated with an increased risk of preterm delivery. Altered placental villous maturation and severe-critical maternal COVID-19 infection were associated with an elevated risk of poor Apgar scores at birth (p = 0.018) and maternal mortality (p = 0.023), respectively.

Placental Cyclophilin A Expression in Pregnancies Complicated with Hypertension.

Introduction: Cyclophilin A was reported to be increased in the serum of mothers with preeclampsia, and is implicated in its pathogenesis. This study aimed to determine the expression of cyclophilin A in the placenta of mothers with and without hypertension, and to correlate its expression with maternal complications and adverse perinatal outcomes. Materials and Methods: This study consisted of a total of 70 cases (35 cases of mothers with hypertension, and 35 normotensive mothers as a control). Cyclophilin A immunohistochemistry was performed on a paraffin-embedded tissue section of placenta submitted at full thickness in order to evaluate the expression in fetal endothelial cells, cytotrophoblasts, syncytiotrophoblasts, maternal endothelial cells and decidual cells. The cyclophilin A expression was scored as weak, moderate or strong intensity. Results: The hypertensive group was more likely to have preterm deliveries (p < 0.0001), caesarean sections (p < 0.0001), and infants admitted to the intensive care unit (p < 0.001). Fifty-one percent of the fetal endothelial cells and cytotrophoblasts expressed cyclophilin A in the hypertensive group, compared to only 28.6% in the normotensive group. However, the difference was not statistically significant (p = 0.086). Conclusion: We found no significant difference in placental cyclophilin A expression between hypertensive and normotensive mothers. There was also no difference in expression in mothers with and without maternal complications and adverse perinatal outcomes.

Selective Immunoreactivity for WT1 Carboxy-Terminus Distinguishes Desmoplastic Small Round Cell Tumor From its Histologic Mimics.

Desmoplastic small round cell tumor (DSRCT) is an aggressive pediatric round cell sarcoma containing a characteristic EWSR1-WT1 gene fusion. In the absence of genetic data, distinguishing DSRCT from other small round cell tumors of childhood can be problematic due to overlapping histologic and immunohistochemical features. We studied the utility of immunohistochemistry with antibodies targeting both the amino-terminal and carboxy-terminal regions of the Wilms tumor-1 (WT1) protein in differentiating these groups of tumors. The study cohort included 33 cases of genetically confirmed pediatric round cell tumors (10 DSRCTs, 12 Wilms tumors, 10 Ewing sarcomas, and 1 CIC-rearranged sarcoma). Immunoreactivities and immunolocalization of both the WT1 amino-terminus and carboxy-terminus were scored and documented. All DSRCTs displayed selective reactivity for only the WT1 carboxy-terminus (10/10), while dual immunoreactivity for both the WT1 carboxy-terminus (12/12) and amino-terminus antibodies (12/12) were characteristic of Wilms tumors. CIC-rearranged sarcoma showed variable WT1 nuclear immunopositivity (1/1, 1/1) and Ewing sarcomas were consistently WT1-negative for both the WT1 amino-terminus (0/10) and carboxy-terminus (0/10). Dual WT1 amino-terminus and carboxy-terminus immunohistochemistry remains a helpful diagnostic tool in discriminating intraabdominal small round cell tumors, which serves as an adjunct to the genetic information in preventing misdiagnosis.

Papillary Thyroid Carcinoma with Spindle Cell Metaplasia: A Rare Encounter.

A myriad of histological variants of papillary thyroid carcinoma (PTC) have been described, some of which can be diagnostically challenging due to their rarity and overlapping histomorphology with other entities. One of the scarce and poorly characterised variants is PTC with spindle cell metaplasia, of which fewer than 20 cases have been reported in the literature hitherto. Our patient was a 51-year-old woman with a four-month history of painless, gradually enlarging neck swelling. Physical examination revealed a solitary left thyroid nodule. Thyroid ultrasonography demonstrated a hypoechoic nodule with irregular borders and speckles of microcalcification at the periphery. Total thyroidectomy with central and lateral lymph node dissection was performed. Grossly, there was a poorly circumscribed mass occupying the entire left thyroid lobe measuring 30 mm in the largest dimension. Histopathological examination revealed features of a classical PTC. Incidentally, a well-circumscribed 9 mm nodule was identified within the tumour mass. The nodule comprised of spindle cells arranged in loose fascicles, displaying uniform bland looking nuclei. No mitosis, necrosis or nuclear atypia was observed. Immunohistochemically, the spindle cells were immunopositive to TTF-1 and thyroglobulin, indicating thyroid follicular cell lineage. p53 and BRAF V600E mutant protein immunoexpression were focally noted. They were negative for calcitonin, S100, and desmin. Loss of E-cadherin and CK19 were also demonstrated. A diagnosis of PTC with spindle cell metaplasia was rendered. The nature of spindle cell in PTC needs to be meticulously defined. Careful histomorphology examination and judicious use of immunohistochemistry stains are helpful in arriving at an accurate diagnosis.

Loss of CXC-Chemokine Receptor 1 Expression in Chorioamnionitis Is Associated with Adverse Perinatal Outcomes.

Background: Chorioamnionitis complicates about 1−5% of deliveries at term and causes about one-third of stillbirths. CXC-chemokine receptor 1 (CXCR1) binds IL-8 with high affinity and regulates neutrophil recruitment. We aimed to determine the immunoexpression of CXCR1 in placentas with chorioamnionitis, and its association with adverse perinatal outcomes. Methods: A total of 101 cases of chorioamnionitis and 32 cases of non-chorioamnionitis were recruited over a period of 2 years. CXCR1 immunohistochemistry was performed, and its immunoexpression in placentas was evaluated. The adverse perinatal outcomes included intrauterine death, poor APGAR score, early neonatal death, and respiratory complications. Results: Seventeen cases (17/101, 16.8%) with chorioamnionitis presented as preterm deliveries. Lung complications were more common in mothers who were >35 years (p = 0.003) and with a higher stage in the foetal inflammatory response (p = 0.03). Notably, 24 cases (23.8%) of histological chorioamnionitis were not detected clinically. Interestingly, the loss of CXCR1 immunoexpression in the umbilical cord endothelial cells (UCECs) was significantly associated with foetal death (p = 0.009). Conclusion: The loss of CXCR1 expression in UCECs was significantly associated with an increased risk of adverse perinatal outcomes and could be used as a biomarker to predict adverse perinatal outcomes in chorioamnionitis. Further study is warranted to study the pathophysiology involved in the failure of CXCR1 expression in these cells.

Rectal Polyposis in Mucosal Prolapse Syndrome.

Mucosal prolapse syndrome is also known as solitary rectal ulcer syndrome. It may either presents as an ulcer or polyp, which could mimic other pathological lesions such as juvenile polyp, hyperplastic polyp, adenomatous polyp, polyp related inflammatory bowel disease and adenocarcinoma. It can pose as a diagnostic challenge to both the surgeons and pathologists due to the overlapping gross and histological features. The characteristic histological features of mucosal prolapse syndrome are fibromuscular obliteration of lamina propria and splayed hypertrophic muscularis mucosae. It can occur in a wide range of ages, including children and teenagers. Rectal bleeding is one of the common presenting symptoms. Here, we described two cases of mucosal prolapse syndrome presented as rectal polyposis and provide a discussion on its histological differential diagnosis.

Surface-engineered liposomes for dual-drug delivery targeting strategy against methicillin-resistant Staphylococcus aureus (MRSA).

This study focused on the encapsulation of vancomycin (VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and N-hydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine. This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV-vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane-DAPT-VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells, in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.

Gardnerella vaginalis infection in pregnancy: Effects on placental development and neonatal outcomes.

INTRODUCTION: Gardnerella vaginalis (GV)-associated bacterial vaginosis is recognised for its detrimental effects on pregnancy resulting in poor obstetric and neonatal outcomes. There is limited knowledge of the effects on placental histomorphology following GV infection in pregnancy. We investigated the effects of GV infection on the placenta, particularly with regards to the syncytiotrophoblasts and vascular development, and related these to neonatal outcomes. METHODS: A prospective cohort study involving GV-positive pregnant women presented with abnormal vaginal discharge, with gestational age-matched healthy pregnant women controls. Placental sampling was performed upon delivery and examined histologically. Vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) mRNA and protein expression were analysed by real-time PCR and immunohistochemistry respectively. The standard measures in neonatal outcomes were recorded. RESULTS: Placentas from GV-positive mothers were found to have significant histological evidence of maternal and/or fetal inflammatory response compared with the controls (17/28: 60.7% vs 2/20: 10%) (p = 0.0011). There was an increase in the percentage of syncytial nuclear aggregates (SNAs) per villus (47.4 ± 11.09%) in placentas from GV-positive mothers (p < 0.0001). VEGF-A was significantly increased in specifically, the villous endothelial cells of placentas with GV infection, but no difference in the immunoexpression of HIF-1α in these cells between groups. However, these were not associated with adverse neonatal outcomes. DISCUSSION: Increased placental VEGF-A expression associated with increased SNAs in pregnant women with GV infection of the genital tract may be an intrauterine response towards placental vascular remodeling, that may also serve as a protective role in moderating birth outcomes.

Intestinal Obstruction Secondary to Malformation in a Child with Mayer-Rokitansky-Küster-Hauser Syndrome.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by underdevelopment of the uterus and vagina. CASE: A 4-year-old girl was declared dead on arrival to the hospital with a history of chronic constipation since birth. Postmortem examination showed Müllerian remnants attached to abnormal fibrous tissue. The fibrous tissue extended from the descending colon to the rectum and connected to a urinary bladder duplication cyst. The fibrous tissue formed into a constricted band around the rectum. The cause of death was Streptococcus pyogenes sepsis with intestinal obstruction secondary to the rectal fibrotic band and urinary bladder duplication cyst. SUMMARY AND CONCLUSION: MRKH syndrome is a rare congenital disorder, and the malformations rarely cause death. We describe the features of abnormal fibrous tissue and urinary bladder duplication cyst in a patient with MRKH syndrome.