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.

Giant paratesticular dedifferentiated liposarcoma with intraabdominal extension: a case report.

Giant paratesticular liposarcoma is a rare presentation of paratesticular tumor. We present a case of the largest paratesticular liposarcoma described to date with a weight of 4,100 g and measuring 460 × 210 × 130 mm. It was initially mistaken as an inguinoscrotal hernia until a contrast-enhanced computed tomography (CECT) scan of the abdomen and pelvis revealed a huge left paratesticular tumor extending from the scrotum to the mid-abdomen. The challenge was to achieve a tumor-free margin orchidectomy due to the poor fat plane of the tumor to the external iliac artery, psoas muscle, descending colon, and anterior abdominal wall. The surgery was started with laparoscopic dissection for the intraabdominal part of tumor from the vital structure, then followed by inguinal radical orchidectomy and inguinal mesh repair. Postoperative histopathological report revealed a paratesticular dedifferentiated liposarcoma with rhabdomyosarcomatous differentiation with clear margin. The patient had good recovery post operation.

Abnormal Pap smear among pregnant women - Feasibility of opportunistic cervical screening.

Objective: The uptake of cervical cancer screening is poor, especially in developing countries. Thus, pregnancy represents a good opportunity to have the test done. The aim of this study is to determine the prevalence of abnormal Pap smear among pregnant women during their antenatal check-ups. Study design: A prospective study involving five hundred and ninety-six women was recruited over a 1-year duration from 15th January 2018 until 14th January 2019 in a tertiary referral center, in Malaysia. Pap smears were performed on all consented pregnant women using liquid-based cytology and the results were obtained to evaluate the prevalence of abnormal Pap smear during pregnancy. Maternal risk factors associated with abnormal Pap smear were identified and the outcomes of abnormal Pap smear were followed up. Results: A total of 670 participants were approached and 596 participants agreed to participate, giving a response rate of 89.0 %. Therefore, 587 participants were available for analysis. There were nine unsatisfactory smears (1.5 %). The prevalence of premalignant lesions reported on p % ap smear was 0.8 %. Three respondents had atypical squamous cells of undetermined significance (ASCUS) (0.5 %) and two respondents had low-grade squamous intraepithelial lesions (LSIL) (0.3 %). Almost one-third (30.3 %) of respondents had an infection and 24 (4.1 %) smears were reported as reactive changes associated with inflammation. Respondents between the age of 20-30 years old had a significant association with an abnormal pre-cancerous smear (p = 0.000) as well as nulliparity (p = 0.0.40). There was no significant association between height, weight, BMI, sexual partner, age of first intercourse, smoking habit, history of sexually transmitted disease and history of abnormal Pap smear. Conclusion: The prevalence of abnormal pre-cancerous smears during pregnancy is low. However, it is desirable to perform cervical screening as it provides an opportunity to no screening at all.

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.

Changing Laboratory Practice for Early Detection of a Fetal Inflammatory Response: A Contemporary Approach.

Neonates born with the fetal inflammatory response (FIR) are at risk of complications such as early-onset neonatal sepsis, meningitis, and pneumonia. Providing an early histopathological diagnosis of FIR is important to guide management but can be a challenge in busy laboratories. This is a retrospective cross-sectional study over a four-month duration recruiting all placental cases with histological chorioamnionitis in our institution. The diagnostic performance of the umbilical cord (UC) section in identifying FIR, relative to the corresponding subsequent placental sections, was assessed. Clinical predictors of umbilical cord FIR were also investigated. A total of 390 UC sections were analyzed, of which 206 (52.8%) were found positive for FIR: 111 cases (53.9%) stage 1, 87 (42.2%) stage 2, and 8 (3.9%) stage 3. Our data revealed a good diagnostic sensitivity, specificity, positive predictive value, and accuracy of 76.2% (95%CI: 68.6-82.7%), 82.4% (95%CI: 65.5-93.2%), 95.0% (95%CI: 90.2-97.6%), and 77.3% (95%CI: 70.6-83.1%) respectively, in cases when clinical chorioamnionitis, fever and/or prolonged rupture of membrane (PROM) were suspected, with the area under the curve of 0.793. A maternal inflammatory response (MIR) was correlated with FIR (p < 0.001). Multivariate logistic regression analysis indicated that the higher the gestational age, clinical suspicion of chorioamnionitis, fever, and/or PROM, and the higher the stage of MIR significantly increased the odds of FIR (p < 0.001). UC section diagnosis of FIR is reasonably accurate in cases with clinical chorioamnionitis, fever, and/or PROM. Changing current laboratory practice to rapid processing of UC ahead of the rest of the other placental sections can be recommended in busy pathology departments.

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.

Case report: Triple whammy: Synchronous radiotherapy induced glioblastoma multiforme and papillary thyroid cancer following nasopharyngeal carcinoma.

Secondary malignancies following radiotherapy are well documented, with an estimated incidence of 5%. These may manifest as carcinomas, gliomas, or sarcomas within the previous radiation field. Glioblastoma multiforme following radiotherapy for nasopharyngeal carcinoma is an uncommon occurrence and carries a poor prognosis, whereas papillary thyroid carcinoma following radiotherapy is well documented, though the exact incidence is not well documented. The occurrence of synchronous radiotherapy-induced malignancy over both sites has not been described in the literature before. We describe a middle-aged gentleman diagnosed with glioblastoma multiforme and papillary thyroid carcinoma 6 years after radiotherapy for nasopharyngeal carcinoma. Though our case is the first reported case of a synchronous tumour of its nature, it is likely that such cases are under-reported. Long-term vigilance for loco-regional radiotherapy-induced secondary malignancies is a must, and the presence of a second distinct secondary malignancy must be entertained.

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.

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.

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.