Effect of Silicon Carbide and Tungsten Carbide on Concrete Composite

Flexural strength of concrete is an important property, especially for pavements. Concrete with higher flexural strength has fewer cracking and durability issues. Researchers use different materials, including fibers, polymers, and admixtures, to increase the flexural strength of concrete. Silicon carbide and tungsten carbide are some of the hardest materials on earth. In this research, the mechanical properties of carbide concrete composites were investigated. The silicon carbide and tungsten carbide at different percentages (1%, 2%, 3%, and 4%) by weight of cement along with hybrid silicon carbide and tungsten carbide (2% and 4%) were used to produce eleven mixes of concrete composites. The mechanical tests, including a compressive strength test and flexural strength test, along with the rapid chloride permeability test (RCPT), were conducted. It was concluded that mechanical properties were enhanced by increasing the percentages of both individual and hybrid carbides. The compressive strength was increased by 17% using 4% tungsten carbide, while flexural strength was increased by 39% at 4% tungsten carbide. The significant effect of carbides on flexural strength was also corroborated by ANOVA analysis. The improvement in flexural strength makes both carbides desirable for use in concrete pavement. Additionally, the permeability, the leading cause of durability issues, was reduced considerably by using tungsten carbide. It was concluded that both carbides provide promising results by enhancing the mechanical properties of concrete and are compatible with concrete to produce composites.     

Distribution of gene mutations associated with familial normosmic idiopathic hypogonadotropic hypogonadism

Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.     

Indications and outcomes of enucleation versus formal pancreatectomy for pancreatic neuroendocrine tumors

BackgroundPancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP.MethodsPatients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP.ResultsAmong 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5 cm, IQR:1.0–1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n = 109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p = 0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23–71) versus PD/DP (37 months, 95% CI: 33–47, p = 0.480).ConclusionComparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN.     

Study of promoter hypomethylation profiles of RAS oncogenes in hepatocellular carcinoma derived from hepatitis C virus genotype 3a in Pakistani population

Epigenetic modifications such as DNA methylation contribute to progression of hepatitis C virus (HCV) infection to life‐threatening hepatocellular carcinoma (HCC) by promoting the silencing of tumor suppressor genes through DNA hypermethylation and by causing genomic instability through global hypomethylation. However few studies have addressed the promoter region hypomethylation status of the oncogenes involved in HCV derived HCC. In this study, we analyzed the promoter region methylation pattern of RAS oncogenes (HRAS, KRAS, and NRAS) using methylation‐specific PCR for 50 chronic HCV patients infected with genotype 3a (27 HCC patients and 23 control non‐HCC patients). Methylation‐specific polymerase chain reaction analysis revealed that the NRAS oncogene promoter (P = .0025) was significantly hypomethylated in HCC patients compared to the non‐HCC patients suggesting its contribution to the progression of HCV towards HCC. To identify the agent for alteration in the RAS oncogene expression, 7 HCV genes were expressed in the Huh‐7 cell line followed by measurement of the NRAS expression level in Huh‐7 by a quantitative real‐time polymerase chain reaction. An increase in the messenger RNA level of the NRAS gene was detected when Huh‐7 were transfected with Core, NS5a, and NS2 genes. Our findings suggest the involvement of NRAS oncogene in the pathogenesis of HCV3a derived HCC in Pakistani population and also identifies the HCV genes responsible for its enhanced expression. Our study raises the hypothesis that a single HCV gene may increase the chances of malignancy. Therefore, our study may have identified a useful epigenetic biomarker of HCC progression in HCV patients and may help to develop novel diagnostic tools.     

Comparing the risk of hypothyroidism in HCV patients treated with different DAA drugs combinations (sofosbuvir + interferon + ribavirin and sofosbuvir + daclatasvir + ribavirin)

The recent development of direct-acting antiviral (DAA) drugs has revolutionized the area of hepatitis C virus (HCV) therapeutics but the efficacy and clinical outcome of interferon (IFN)-free therapy have not been extensively studied yet. We observed a dramatic increase in hypothyroidism among patients treated with sofosbuvir, IFN, and ribavirin. This is the first prospective study of the thyroid dysfunction in DAA drugs treated patients. This study compared the risk of hypothyroidism in two different groups of HCV patients treated with different DAA drugs regimens that were sofosbuvir + pegylated-IFN-α + ribavirin and sofosbuvir + daclatasvir + ribavirin. Our findings highlight the periodic screening of serum thyroid-stimulating hormone and T4 levels in HCV infected patients during the treatment and posttreatment.     

Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

Pleomorphic hyalinizing angiectatic tumor of renal hilum

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a recently described rare entity. The tumor histogenesis is proposed to be of primitive undifferentiated mesenchyme. The tumor has a predilection for the subcutaneous soft tissue especially of lower extremity, although other locations have been well documented. We report a case of PHAT arising in the hilum of the kidney, clinically mimicking an infiltrating malignant neoplasm of renal pelvis. The tumor was discovered during workup for unrelated gastrointestinal tract symptoms. Because of the location of the lesion, excision of mass and radical nephrectomy were performed. The tumor had strong immunohistochemical expression of vimentin, CD34, CD99, and vascular endothelial growth factor (VEGF). No additional lesions were documented during 3 years of follow-up. This is consistent with the current thinking that PHAT is a benign neoplasm with increased incidence of recurrence. We document the unique retroperitoneal location of this rare tumor and suggest that PHAT should be considered among the list of unusual lesions at this site.