Serum MicroRNA-146b Expression for Malignancy Prediction in Euthyroid Patients with Indeterminate Thyroid Nodules.

Thyroid nodules are frequently found, but the vast majority of them are benign. The difficulty in managing thyroid nodules is correctly diagnosing the minority of those who have malignancy. Thyroid fine-needle aspiration cytology (FNAC) with indeterminate cytology continues to raise doubts about the presence of thyroid cancer, leading to an unnecessary thyroidectomy. Circulating miRNAs may be useful as diagnostic and prognostic markers for a variety of cancers, including thyroid cancer. The goal of the present study was to determine the predictive value of serum miRNA-146b expression level for thyroid cancer by estimating its level in a group of euthyroid patients with thyroid nodules with indeterminate FNAC results. This cross-sectional study included 45 euthyroid patients with indeterminate thyroid nodules who visited the Endocrine Outpatient Clinic and Endocrine Surgical Ward at Ain Shams University Hospitals. For all patient thyroid profiles, ultrasound of the thyroid gland and FNAC of the thyroid nodule were performed. In addition, preoperative assessment of serum microRNA-146b expression by real-time PCR was achieved and the results correlated with post-operative thyroid histopathology. There was no difference in serum miRNA-146b expression between patients with benign thyroid nodules versus patients with malignant nodules (p= 0.789). The risk of malignancy increased with the increase in size of the dominant thyroid nodules, as larger nodules had a higher risk of malignancy (p= 0.027). In conclusion, in euthyroid patients with indeterminate thyroid nodules, serum miRNA-146b is a poor predictor of thyroid malignancy, however, the larger the nodule size, the higher the risk of cancer.

Association of Interleukin-33 with Recurrent Pregnancy Loss in Egyptian Women

Background: A successful pregnancy requires a distinct and complex immunological state. Cytokines appear to be critical for the establishment of a tolerogenic environment towards the semi-allogenic foetus during the foeto-maternal interphase, and a shift from a Th1- to a Th2-cytokine profile may be crucial. An imbalance of cytokines can be a significant factor in recurrent pregnancy loss (RPL). Interleukin-33 (IL-33) is a member of the IL- 1 cytokine family, involved in both the innate and adaptive immune responses coordinating immune cell function for a broad range of physiological and pathological processes, including the regulation of pregnancy outcome. Objectives: The aim of this study was to investigate a possible association between IL-33 and RPL in Egyptian women. Methods: The study was conducted on 66 Egyptian females recruited from Ain Shams University Specialized Hospital and 66 matched healthy non-pregnant females of typical childbearing age without a history of RPL. Serum IL-33 was measured in all subjects using a sandwich ELISA technique. Results: Serum IL-33 levels were significantly higher in patients with RPL than in the healthy control group. In addition, in the patient group, there was a positive correlation between serum IL-33 level and both age and number of miscarriages and a negative correlation between serum IL-33 level and the number of deliveries. Conclusion: In Egyptian women, serum levels of IL-33 are associated with RPL, thus IL-33 level could be a predictive biomarker for RPL in early pregnancy.

T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) as markers of early T cell and B cell immune recovery after haematopoietic stem cell transplantation (HSCT).

Hematopoietic stem cell transplantation (HSCT) is a key therapeutic strategy for a number of hematological malignancies and non-malignant disorders of the hematopoietic system. One of the most important events post SCT is the immune system reconstitution-a process characterized by a considerable dynamic and is critical in promoting overall survival of transplant patients, restoring immune protection from opportunistic infections, and mediating an alloreactive graft-versus-tumor effect against residual malignant disease. T cell receptor excision circles (TRECs) and Kappa deleting recombination excision circles (KRECs) are byproducts of T cells and B cells receptor recombination processes, respectively and can be used in monitoring denovo synthesis of T cells and B cells post SCT. The aim of this study was to determine the role of combined TRECs and KRECs quantitation in follow up of allogenic HSCT patients through testing samples at 1, 3 and 6 months post-transplant as well as their role in predicting outcomes of transplantation. The study was conducted on 32 patients receiving allogenic HSCT from an HLA identical sibling. Combined quantification of TRECs and KRECs in the genomic DNA of peripheral blood mononuclear cells was performed using quantitative real-time PCR using a standard curve. TRECs and KRECs levels were inversely related to age and significantly lower in patients transplanted for malignant diseases than benign diseases (p <0.05). TREC levels could predict relapse as an outcome and graft versus host disease (GvHD) at 6 months posttransplant. In conclusion, age and nature of disease determined TRECs and KRECs levels posttransplant. In addition, monitoring immune reconstitution using combined TRECs/KRECs quantitiation by real time PCR may be informative and could help predict outcomes of transplantation in allogenic HSCT.

DNMT3A and TET2; Potential Estimates of Generic DNA Methylation in Children and Adolescents with Obesity; Relation to Metabolic Dysregulation.

INTRODUCTION: The role of DNA methylation in metabolic dysregulation is emerging. However, the functional role of methylation in obesity and metabolic dysregulation is poorly understood. AIM: The aim of this study was to compare DNA methyltransferase-3A (DNMT3A) and ten-eleven translocase-2 (TET2) levels in children and adolescents with obesity to normal-weighed children and adolescents and to correlate them to various metabolic parameters. METHODS: Fifty children and adolescents with obesity were compared to 50 matched normal-weighed children and adolescents. Participants underwent assessment for anthropometric measurements, Tanner staging, acanthosis nigricans, and mean blood pressure percentile on three different occasions. TET2, DNMT3A, fasting lipids, and insulin were measured with calculation of the homeostatic model assessment insulin resistance (HOMA-IR). RESULTS: The median BMI SDS of the studied children and adolescents with obesity was 3.40, their mean TET2 was 178.40 ng/mL, and their mean DNMT3A was 2.18 ng/mL. TET2 is significantly lower (p = 0.009), while DNMT3A is significantly higher (p < 0.001) in children and adolescents with obesity than controls. Children and adolescents with obesity and insulin resistance have significantly lower TET2 (p = 0.012) and significantly higher DNMT3A (p = 0.013) than those without insulin resistance. Diastolic blood pressure percentile and HOMA-IR are positively correlated to DNMT3A (p < 0.001) and negatively correlated to TET-2 (p < 0.001). Multivariate logistic regression analysis revealed that TET2 and DNMT3A are independently associated with diastolic blood pressure percentile (p = 0.03 and p = 0.014, respectively) and HOMA-IR (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Children and adolescents with obesity have significantly higher DNMT3A and significantly lower TET2 than controls. This is more evident in those having insulin resistance than those without. DNMT3A and TET2 are independently associated with systemic hypertension and insulin resistance in children with obesity.

PD1 expression on bone marrow T-cells in newly diagnosed Egyptian AML patients: Correlation with hematological parameters, aberrant antigens expression, and response to induction therapy.

Background: Programed cell death protein 1 (PD-1) is a key mediator for the development of T cell exhaustion that develops in response to persistent antigen stimulation. Aim: In this study, we measured PD1 expression on CD3 positive bone marrow T-lymphocytes in newly diagnosis AML patients and its relation to clinical/ prognostic outcomes in addition to response to induction therapy (day 28). Methods: This study was conducted on 59 newly diagnosed AML patients and 20 healthy controls. Complete blood counts, flow cytometry using acute leukemia panel in addition to PD1 monoclonal antibodies were performed on bone marrow lymphocytes (CD3+), whereas cytogenetic/molecular studies were used to determine risk group. The patients' remission status following induction therapy was determined. Results: PD1 was brightly expressed in 91.5% of the cases than control sample with highly significant difference (P = .001). A cutoff of 3.5 for mean fluorescence intensity was used to divide patients into two groups (higher vs normal PD1 expression). A significant difference between the two groups regarding platelet count and aberrant CD7 expression (P = .007 and .023, respectively) was found. Those normally expressed PD1 respond better to induction therapy. Conclusion: PD1 expression on BM T-cells had a predictive value and providing an immunotherapeutic target for AML.

Corynebacterium urealyticum: a comprehensive review of an understated organism.

Corynebacterium urealyticum is a Gram positive, slow-growing, lipophilic, multi-drug resistant, urease positive micro-organism with diphtheroid morphology. It has been reported as an opportunistic nosocomial pathogen and as the cause of a variety of diseases including but not limited to cystitis, pyelonephritis, and bacteremia among others. This review serves to describe C. urealyticum with respect to its history, identification, laboratory investigation, relationship to disease and treatment in order to allow increased familiarity with this organism in clinical disease.