Placenta microRNA profile of patient with Obstetric Antiphospholipid Syndrome.

The onset of obstetric antiphospholipid syndrome (APS) occurs when antiphospholipid antibodies act upon the placenta. During pregnancy, APS exhibits traits such as vascular thrombosis, inflammation, and hindered trophoblast implantation. The involvement of microRNA expression has been proposed as a genetic factor contributing to the syndrome's development. MicroRNAs play a role in regulating gene expression in various cellular processes, including the formation of placental tissue. Therefore, additional research is needed to explore the control of placental miRNA in APS. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesised signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation while Retinoblastoma gene (RET), Dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) genes were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade.

Distinct microRNA expression pattern in breast cancer cells following anti-neoplastic treatment: A systematic review and functional analysis of microRNA target genes.

Breast cancer remains a significant cause of mortality in females worldwide, despite advances in technology and treatment. MicroRNA expression in breast cancer is studied both as potential biomarkers and for therapeutic purposes. Accumulated evidence revealed microRNA profile of various types of cancer cells following antineoplastic treatment. The progression of research in this area provides better understanding on the anti-cancer mechanism of various natural compounds and drugs specifically on the microRNA regulation. Hence, we aim to systematically review differentially expressed microRNA in MCF-7, a commonly studied breast cancer cell line, after treatment with anti-neoplastic agents. Relevant keywords were used to screen for research articles that reported on the differentially expressed microRNAs in experimental models of MCF-7 before and after anti-neoplastic treatment. Target genes of microRNAs were identified from MiRTarbase and further in silico functional analysis of the target genes were performed using DAVID bioinformatic resources. Two upregulated microRNAs (mir-200c and let-7d) and 3 downregulated microRNAs (mir-27a, mir-27b and mir-203) were identified by highest number of studies. Three microRNAs (let-7a, mir-23a and mir-7) showed inconsistent direction of expression. Genes functional analysis revealed the regulatory effect of microRNA on genes related to angiogenesis, hypoxia, P53, FoxO and PI3K-AKT signalling. Clusters of genes associated to the pathway of angiogenesis, cancers, cell proliferation and apoptosis were noted through protein-protein interaction analysis. MicroRNAs, especially the mir-200c, let-7d, mir-27a, mir-27b and mir-203 from this review could be further validated experimentally to serve as molecular target or biomarkers for anti-neoplastic therapy.

Chronic histiocytic intervillositis in consecutive miscarriages: A potential pitfall in routine examination of conceptus.

INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare placental lesion strongly associated with recurrent miscarriages and fetal losses. It requires histopathological diagnosis and can only be made after delivery of the products of conception (POC). We describe a case of CHI in a 41-yearold lady with a 16-year history of thirteen recurrent consecutive first trimester miscarriages. CASE REPORT: The patient is a 41-year-old lady who suffered first trimester miscarriages in all her thirteen pregnancies. The relevant clinical investigations revealed neither significant nor helpful findings in determining the cause of recurrent miscarriages. Histological findings in each except one of the submitted conceptual tissue showed similar features of histiocytic aggregates primarily within the intervillous spaces, a characteristic description of CHI. One of the samples showed degenerative changes. DISCUSSION: Practicing pathologists are not familiar with the histological features of CHI and this may be a potential pitfall in routine examination of POCs. Recognising this entity allows for accurate diagnosis and hence better management. The aetiology remains unclear, although an immunopathological basis are being explored.

Gene expression in obstetric antiphospholipid syndrome: a systematic review.

BACKGROUND: Antiphospholipid syndrome (APS) is a multisystem disease that may present as venous or arterial thrombosis and/or pregnancy complications with the presence of antiphospholipid antibodies. Until today, heterogeneity of pathogenic mechanism fits well with various clinical manifestations. Moreover, previous studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in Obstetric APS. METHODOLOGY: Electronic search was performed until 31st March 2015 through PubMed and Embase databases; where the following Medical Subject Heading (MeSH) terms were used and they had been specified as the primary focus of the articles; gene, antiphospholipid, obstetric, and pregnancy in the title or abstract. From 502 studies retrieved from the search, only original publications that had performed gene expression analyses of human placental tissue that reported on differentially expressed gene in pregnancies with Obstetric APS were included. Two reviewers independently scrutinized the titles and the abstracts before examining the eligibility of studies that met the inclusion criteria. For each study; diagnostic criteria for APS, method for analysis, and the gene signature were extracted independently by two reviewers. The genes listed were further analysed with the DAVID and the KEGG pathways. RESULTS: Three eligible gene expression studies involving obstetric APS, comprising the datasets on gene expression, were identified. All three studies showed a reduction in transcript expression on PRL, STAT5, TF, DAF, ABCA1, and HBEGF in Obstetric APS. The high enrichment score for functionality in DAVID had been positive regulation of cell proliferation. Meanwhile, pertaining to the KEGG pathway, two pathways were associated with some of the listed genes, which were ErBb signalling pathway and JAK-STAT signalling pathway. CONCLUSION: Ultimately, studies on a genetic level have the potential to provide new insights into the regulation and to widen the basis for identification of changes in the mechanism of Obstetric APS.

MicroRNA expression in antiphospholipid syndrome: a systematic review and microRNA target genes analysis.

INTRODUCTION: Antiphospholipid antibodies (aPL) are autoantibodies that attack phospholipid through anti-beta 2-glycoprotein 1. The actions of aPL are associated with events leading to thrombosis and morbidity in pregnancy. Antiphospholipid syndrome (APS) is diagnosed when a patient is persistently positive for aPL and also has recognised clinical manifestations such as recurrent pregnancy losses, arterial or venous thrombosis and in a catastrophic case, can result in death. Unfortunately, the pathogenesis of APS is still not well established. Recently, microRNA expressed in many types of diseased tissues were claimed to be involved in the pathological progression of diseases and has become a useful biomarker to indicate diseases, including APS. OBJECTIVE: This systematic review aims to search for research papers that are focussing on microRNA expression profiles in APS. METHOD: Three search engines (Ebcohost, ProQuest and Ovid) were used to identify papers related to expression of specific microRNA in antiphospholipid syndrome. RESULTS AND DISCUSSION: A total of 357 papers were found and screened, out of which only one study fulfilled the requirement. In this particular study blood samples from APS patients were tested. The microRNAs found to be related to APS were miR-19b and miR-20a. No data was found on specific microRNA being expressed in obstetric antiphospholipid syndrome. Analysis on the microRNA target genes revealed that most genes targeted by miR-19b and miR-20a involve in TGF-Beta Signalling and VEGF, hypoxia and angiogenesis pathways. CONCLUSION: In view of the limited data on the expressions of microRNA in APS we recommend further research into this field. Characterization of microRNA profile in blood as well as in placenta tissue of patients with APS could be useful in identifying microRNAs involved in obstetric APS.

Tracheal agenesis: a rare cause of unsuccessful tracheal intubation during resuscitation.

Tracheal agenesis is a rare congenital airway anomaly that usually results in a fatal outcome. The diagnosis is usually made through post-mortem examination. In the current literature, there has been no reported long-term survival although a few reports claimed prolongation of life of several hours to days. This condition is commonly associated with premature birth, polyhydramnios and a male predominance. In 90% of the cases, it is associated with multiple cardiovascular, gastrointestinal and genitourinary tract anomalies which are incompatible with life. We report a case of a premature newborn with severe respiratory distress, absent cry and cyanosis soon after birth. Attempts at endotracheal intubation failed as it was no possible to negotiate the tube beyond the vocal cords. Needle cricothyrotomy and attempted tracheostomy also failed to secure the airway. The diagnosis was confirmed at post-mortem examination.

MTHFR C677T polymorphism as a risk factor of neural tube defects in Malay: a case control study.

Major congenital malformations occur in about 3% of newborn. Several studies have suggested that homozygosity for the C677T methylenetetrahydrofolate reductase (MTHFR) variant is a potential risk factor for neural tube defects (NTDs). It has been hypothesized that the maternal folic acid supplementation prevents NTDs by partially correcting reduced MTHFR activity associated with the variant form of the enzyme. This association has not been found in some ethnic groups. In this study, we attempted to assess the association between NTDs and MTHFR C677T in Malaysian Malay population. Results show that MTHFR 677TT genotype was absent in both patient and control groups.

Metastatic penile cancer presenting as hypercalcemia and pathological fracture of the humerus: a rare event.

Distant haematogenous metastasis in penile cancer is rare. A patient who had total penectomy and bilateral inguinal lymphadenectomy for penile cancer but later presented with hypercalcemia of malignancy and pathological fracture of the humerus is reported.

The role of serum insulin-like growth factor I (IGF-I) in neonatal outcome.

AIMS: To determine the role of serum insulin-like growth factor I (IGF-I) in predicting the occurrence of septal hypertrophic cardiomyopathy in infants of mothers with diabetes. METHODS/MATERIALS: In this prospective study, 100 pregnant women (50 with diabetes and 50 controls), matched for age and race, were studied. One intrapartum blood sample was taken at 28 weeks of gestation from both groups of mothers and another sample at delivery. All samples were analysed for maternal IGF-I by an enzyme linked immunosorbent assay method. A chest radiograph and an electrocardiogram were performed on the babies of the mothers with diabetes within the first 24 hours of life. An echocardiogram was performed in the first 3 days of life to look for septal hypertrophy and to measure the myocardial thickness. RESULTS: In the six cases of neonatal septal hypertrophic cardiomyopathy, all the mothers had greatly raised IGF-I concentrations of more than 400 ng/ml at the time of delivery compared with a mean (SD) of 302 (25) ng/ml in control mothers. CONCLUSIONS: In the present study a crude analysis revealed that increased IGF-I concentrations correlate with neonatal septal hypertrophic cardiomyopathy.

Diffuse neonatal haemangiomatosis: a rare cause of haemorrhagic shock and refractory coagulopathy in the newborn.

A term newborn infant developed hypovolaemic shock shortly after birth. She was pale with gross hepatomegaly. She required multiple boluses of intravenous fluids, blood products as well as inotropic support. Blood investigations showed persistent thrombocytopenia, anaemia and disseminated intravascular coagulopathy (DIC). She also developed heart failure. She finally succumbed on the eleventh day of life. Autopsy revealed haemangiomatosis involving the liver, lungs, gastrointestinal tract, kidneys and adrenals.

Spermatic cord metastasis from a medulloblastoma.

A 4-year-old boy presented with metastases in the spermatic cord and ribs 2 years after treatment for a primary medulloblastoma (MB). The testis was free of tumor. A MB presenting with a metastasis to the spermatic cord has not been reported to date. The role of a ventriculo-peritoneal shunt in promoting such spread should be considered in planning management.

Management and short-term outcome of persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis).

BACKGROUND/AIM OF STUDY: Persistent hyperinsulinaemic hypoglycaemia is a rare metabolic disorder of glucose regulation. It is however the most common cause of persistent hypoglycaemia in the neonatal period. Various drugs have been used with generally poor results, but diazoxide and a long-acting somatostatin analogue, octreotide, have been found to be rather successful. When medical therapy fails, early pancreatectomy is recommended to maintain euglycaemia. Since pancreatectomy seems to carry the long-term risk of diabetes mellitus, some authors recommend long-term medical therapy as an alternative to surgery. The outcome of treatment seems to correlate with neurological status prior to surgery. Even in early recognised and treated patients, publications suggest that a subtle neurological deficit may be present despite apparently normal intelligence. In view of the varying recommendations on treatment and the variations in outcome, we reviewed our experience over a period of three years (1992-1995) to determine whether we could formulate a rational approach to the management. METHODS: From our records, we identified 8 children who fullfilled the criteria for the diagnosis of persistent hyperinsulinaemic hypoglycaemia of infancy and retrospectively reviewed their documents. We also included 2 more who presented to us during the study period. RESULTS: Two out of the 10 were born premature and four were considered large for gestational age, mean birth weight was 3679 gms (range 2580-4400 gms). All except three were symptomatic by day two of life. All except one were given hydrocortisone prior to transfer to our care at a mean age of 22 days (range 8-52 days). Our regime included a trial of diazoxide and octreotide. Near total pancreatectomy was performed in nine patients, seven following a short trial of octreotide. Our two most recent cases were given a longer trial of medical therapy of 9 and 6 months respectively prior to pancreatectomy. Our two early cases in the series had recurrence of hypoglycaemia within a week post-pancreatectomy. One still needed insulin therapy 5 months post-surgery. Seven were available for outcome assessment; while longitudinal growth is normal in all, three were developmentally delayed. CONCLUSION: Based on our experience with short and prolonged course of somatostation analogue, we conclude that early pancreatectomy should be performed on those with inadequate maintenance of euglycaemia while prolonged course of medical therapy is feasible only in selected cases.

The usefulness of limited placental sampling in stillbirths.

144 placentas were sampled from all cases of stillbirth weighing 500 g and above seen over a period of thirteen months in the UKM Unit of the Maternity Hospital, Kuala Lumpur. Sampling was limited to 1-3 blocks per placenta for histological study. Placental abnormalities were found in 121 (85%) placentas, 78 of which had definite lesions known to contribute to foetal death while the remainder showed lesions suggestive of an underlying disease. This study supports the usefulness of limited sampling of the placenta in the face of unavailability of complete placental examination and autopsy for assessment of the cause of stillbirth.

Incidence of acute atherosis in complete molar pregnancy.

A clinicohistological study of acute atherosis in molar pregnancy was undertaken. Maternal decidual vessels in currettage samples of 38 histologically confirmed complete hydatidiform moles were examined histologically for acute atherosis, recognised as fibrinoid necrosis of the smooth muscle wall with a perivascular mononuclear cell infiltrate, with or without lipophages. Acute atherosis was detected in eight of 38 cases, an incidence of 18.4%. All the patients were normotensive. The significance of acute atherosis in molar pregnancy remains to be clarified.

Fine needle aspiration cytology of the breast: an analysis of 1,094 aspirates.

Our experience with 1,094 consecutive fine needle aspirations (FNAs) of the breast in 918 cases is presented. Correlation between the FNA cytology and subsequent histology of the lesions was available in 211 cases. FNA had a sensitivity rate of 87.3%, a specificity rate of 99.3% and a positive predictive value of 98.2%. A false negative diagnosis rate of 5.1% occurred. The overall diagnostic accuracy rate was 95.7%.

Large bowel cancer in a young adult presenting as an acute intussusception--a case report.

A 14 year old Malay boy with an adenocarcinoma of the transverse colon is reported. A lesion was discovered early when he presented with an uncommon complication in the form of a bowel intussusception. Emergency segmental colonic resection was performed, followed later by an extended left hemicolectomy following histological confirmation of the disease. Benign adenomatous polyp is believed to be the predisposing condition. Both rarities, colorectal cancer in young adults and adult intussusception, are discussed.