Serum microRNA-486-5p expression in obese Egyptian children and its possible association with fatty liver.

AIMS: Several microRNAs (miRNAs) are involved in regulating the process of adipogenesis. White adipose tissue is a major source for these miRNAs. We aimed to evaluate the expression of miR-486-5p in children with obesity and its possible association with nonalcoholic fatty liver disease (NAFLD). METHOD: This case-control study included 100 obese and overweight children and 100 normal-weight children of matched age and sex. All children were subjected to anthropometric measurements and evaluation of miR-486-5p expression levels using the SYBR green-based real-time RT-PCR technique. RESULTS: Obese children showed significantly up-regulated miR-486-5p gene expression (p value < 0.001) when compared to control group. MiR-486-5p gene expression showed significant positive correlation with weight (r = 0.924), BMI (r = 0.497), waist circumference (r = 0.387), fat mass (r = 0.361), LDL(r = 0.351), TG (r = 0.867), TC (r = 0.875) and presence of fatty liver (r = 0.760). The best cutoff value of miR-486-5p gene expression in the prediction of obesity was 0.44 with AUC 0.736 that has a sensitivity 60% and specificity 90%, CONCLUSION: The serum level of the miR-486-5p gene is up-regulated in obese and overweight children and might be an independent predictor for obesity and fatty liver susceptibility.

Serum Levels of Eosinophil-derived Neurotoxin in Patients with Chronic Urticaria.

BACKGROUND: Despite the many theories that have been published over the years, the exact pathology of chronic urticaria (CU) is still largely unknown. Eosinophils have been implicated in many cutaneous disorders-serving as major effector cells, inducing tissue damage and dysfunction by releasing granule proteins, including eosinophil cationic protein (ECP), inflammatory lipid mediators, mitochondrial DNA, and eosinophil-derived neurotoxin (EDN), which is relatively neutral with some cytotoxic properties. OBJECTIVE: We sought to evaluate serum levels of EDN in patients with CU and to correlate their levels with the severity of their disease. PARTICIPANTS: Fifty patients with CU and 30 matching healthy individuals, serving as controls, were recruited from the outpatient clinic of the Dermatology, Venereology, and Andrology Department of Benha University Hospitals. METHODS: 5ml of venous blood were drawn from all participants in a fasted state, stored in sterile tubes, and used to measure the serum level of EDN following the manufacturer's instructions. RESULTS: The serum level of EDN was statistically significantly different in both groups, and the serum level of EDN significantly correlated with the severity of CU. CONCLUSION: The significantly higher EDN level in patients with CU suggests its role in the pathogenesis of the disease, and its significant positive correlation with the severity of the disease suggests promising therapeutic solutions.

Assessment of Endocan Serum Level in Patients with Behçet Disease: Relation to Disease Activity and Carotid Intima Media Thickness.

Behçet disease (BD) is a form of vasculopathy that can influence blood vessels of variable diameters. Endocan is a biomarker of endothelial activation and it is secreted from endothelial cells as a soluble proteoglycan. The aim of the work was to assess endocan serum level in patients with BD and to examine its relationship with disease activity parameters and carotid intima media thickness (IMT). The study encompassed 42 patients with BD (25 males and 17 females) diagnosed according to the International Study Group Criteria of BD and 42 age and sex matched apparently healthy volunteers as controls. Human Endothelial cell-specific Molecule-1 (Endocan) was assessed using ELISA. Carotid mean IMT was calculated by Color Doppler ultrasonography. Thickness measurement more than 1 mm was considered abnormal:BD patients had significantly increased endocan serum levels (median, 249.5; IQR, 174 - 445 ng/l) compared to healthy controls (median, 190.5; IQR, 128 - 235 ng/l, P=0.002), endocan serum level was increased in BD patients with active disease (median, 434; IQR, 246 - 617.5 ng/l) compared to those with inactive disease (median, 195.5; IQR, 145 - 235 ng/l, P < 0.001) and healthy controls (P < 0.001). Endocan serum levels showed significant positive correlations with erythrocyte sedimentation rate (P=0.04), C-reactive protein (P < 0.001), BD Current Activity form (P < 0.001) and carotid IMT (P=0.008). In conclusion, Endocan can be used to monitor disease activity and endothelial dysfunction in BD.

Kidney injury molecule-1/creatinine as a urinary biomarker of acute kidney injury in critically ill neonates.

INTRODUCTION: Acute kidney injury (AKI) is a complex disorder, means acute deterioration of renal function generally occurring over hours to days. Serum creatinine (SCr) is a suboptimal biomarker in neonates as the creatinine concentration reflects the maternal level for up to 72 h after birth, to improve the ability for early prediction of AKI and improve clinical outcomes, there has been a significant amount of research to identify novel biomarkers of damage to allow for the earlier identification of neonates with AKI. OBJECTIVE: This study aimed to study the effectiveness of urinary kidney injury molecule-1/creatinine (uKIM-1/cr) in the diagnosis of AKI in critically ill neonates. STUDY DESIGN: The patients' group included 50 critically ill full-term septic neonates (39 of them developed AKI according to guidelines of AKI diagnosis), and control group including 50 healthy neonates. Full history taking, clinical assessment and laboratory testing of the renal functions (urea & creatinine), eGFR, uKIM-1 by ELISA technique and uKIM-1/cr ratio on admission, and on day 3 of admission. RESULTS: Urea, serum creatinine increased, whereas, eGFR decreased significantly in the second sample when compared to the first sample of the AKI group. uKIM-1 and uKIM-1/cr were high in the first sample, uKIM-1 concentration and uKIM-1/creatinine were higher in second sample (2.2 ± 0.6 ng/ml & 7.1 ± 2.1 ng/mg) when compared to first sample (0.6 ± 0.1 ng/ml & 2.6 ± 0.9 ng/mg) in critically ill neonates with AKI. Serum creatinine, uKIM-1 and uKIM-1/cr ratio were significantly associated with higher KDIGO stages. Applying the ROC curve at the first sample for discrimination between critically ill neonatal patients with and without AKI, uKIM-1/cr AUC was significantly higher when compared to AUCs of creatinine, eGFR, uKIM-1. Regression analysis revealed that high uKIM-1 & uKIM-1/cr are independent predictors for AKI within critically ill neonates. So, uKIM-1 & uKIM-1/cr are early biomarkers as their level increased before creatinine increases. CONCLUSIONS: uKIM-1 and uKIM-1/cr are good early indicators for AKI in neonates suffering from a critical illness.

Association between seminal granulysin and malondialdehyde in infertile men with varicocele and the potential effect of varicocelectomy.

This study assessed the seminal plasma granulysin and malondialdehyde (MDA) levels in patients suffering from varicocele-associated infertility prior to and after varicocelectomy. This study was conducted on 34 infertile men with varicocele (group A) and same patients after varicocelectomy (group B) and 32 fertile normozoospermic males (group C). A detailed history taking, clinical examination, scrotal doppler ultrasound for varicocele diagnosis and grading, semen analysis and estimation of seminal granulysin and MDA before and after varicocelectomy were done to all participants. The mean (SD) granulysin and MDA levels in patients with varicocele were higher than in controls with highly significant differences. Post-operatively, there was a significant reduction in mean (SD) granulysin and in MDA level. Basal seminal granulysin positively correlated with basal seminal MDA, abnormal forms and negatively correlated with basal sperm count, concentration, and progressive motility. The receiver operating characteristic curve of seminal granulysin and MDA levels were conducted for discrimination between infertility cases with varicocele and control groups. Excellent AUCs were found for both markers (AUC = 0.971, 0.991 respectively). We concluded that high levels of granulysin and MDA in the semen of infertile males with varicocele negatively impact their spermatogenesis. Varicocelectomy leads to the improvement of semen parameters and significantly decreases seminal plasma granulysin and MDA levels. Hence, seminal granulysin and MDA could be used as a prognostic test in infertile patients with varicocele.

Plasma cystatin C versus renal resistive index as early predictors of acute kidney injury in critically ill neonates.

INTRODUCTION: Acute kidney injury (AKI) independently predicts morbidity and mortality of critically ill neonates. Serum cystatin C is a promising early biomarker for AKI. Evaluating the renal resistive index (RRI) by Doppler ultrasound demonstrates abnormal intrarenal vascular impendence. OBJECTIVE: The objective of this study was to compare the ability of plasma cystatin C and the RRI to predict AKI early in critically ill neonates. STUDY DESIGN: Sixty critically ill neonates in neonatal intensive care units were assigned to three groups: group 1 (cases) of thirty participants fulfilling the AKI diagnostic criteria of neonatal Kidney Disease Improving Global Outcome, group 2 of thirty participants not fulfilling the criteria, as well as the 3rd group of thirty age- and sex-matching healthy participants. RESULTS: Group 1 demonstrated a significantly high mean cystatin C level during the 1st day of incubation compared with the other two groups [group 1 (3.18 ± 1.25), group 2 (1.68 ± 0.66), and group 3 (0.80 ± 0.26)]. Serum creatinine and RRI were insignificantly different among all groups. At a cutoff value of 2.68 (mg/l), cystatin C level had significantly higher area under the curve (AUC) (0.804) than both serum creatinine (0.453) and RRI (0.551) and had 53.3% sensitivity and 100% specificity in the early prediction of neonates with AKI. The RRI had a lower non-significant AUC (0.551) at a cutoff value of 0.53 and had 100% sensitivity and 40% specificity, while serum creatinine had a low non-significant AUC (0.453) at a cutoff value of 0.49 (mg/dl) and had 33.3% sensitivity and 86.7% specificity. Applying regression analysis to predict AKI in critically ill neonates as early as possible, higher plasma cystatin C and lower estimated glomerular filtration rate cystatin were the only independent risk factors within critically ill neonates. CONCLUSIONS: The level of plasma cystatin C increased 48 h before both RRI and serum creatinine did in critically ill neonates who developed AKI, so it is more reliable in predicting AKI in critically ill neonates than serum creatinine and RRI.

Diagnostic value of serum cytokeratin-18 in children with chronic liver disease.

AIM: This study aimed to assess the diagnostic value of serum cytokeratin-18 (CK-18) in children with chronic liver diseases (CLD) and correlate its serum level with liver histology and other liver biomarkers. METHODS: This study included two groups, the first group included children with CLD and the second group included healthy matched age and gender subjects as a control group, complete history and clinical examination, and serum CK-18 was measured using the sandwich enzyme-linked immunosorbent assay technique. RESULTS: Serum concentrations of CK-18 were significantly elevated in CLD patients with mean ± standard deviation (1070.63 ± 699.2 ng/mL) compared to healthy controls mean ± standard deviation (203.95 ± 83.57 ng/mL). CK-18 levels were associated with a change in hepatocyte and portal tract (P = 0.005) as it was elevated with cirrhosis and fibrosis stage (P = 0.02) as it was elevated with moderate and severe fibrosis than mild fibrosis, also it showed a gradual increase in accordance with child Pugh score. There was a positive correlation between CK-18 levels and Total IgG, paediatric end-stage liver disease score and model for end-stage liver disease scores, the best cutoff point of CK-18 was 624 ng/mL, with sensitivity 93.06%, specificity 62.5% and diagnostic accuracy 90.0% for detection of fibrosis. CONCLUSION: CK-18 could be used as a non-invasive diagnostic marker in children with CLD.

Association between interleukin-10 genetic variant (-1082G>A) with detection and severity of respiratory distress syndrome in preterm neonates.

BACKGROUND: Abnormal cytokine production derived from specific polymorphisms can have effect on development of respiratory distress syndrome (RDS). Therefore, the present study aimed to determine whether polymorphisms of IL10 in preterm newborn are associated with RDS. METHODS: A total of one hundred and one venous blood samples were collected from preterm neonates, and they were classified as 51 with no RDS and 50 with RDS. Grading of RDS, history of surfactant administration or ventilator was assessed in the diseased group. Genetic variant of IL10-1082G/A (rs1800896) was genotyped by PCR-RFLP. RESULTS: The RDS group showed a higher prevalence of IL10-1082 AA and lower prevalence of IL10-1082 GG (p < .001). We found that the incidence of the allele G in the IL10-1082 polymorphism was lower in the RDS group (24%) than the non-RDS group (51%) (p < .001). Allele model (A vs. G): OR = 0.304, 95% CI: 0.166-0.554, p ≤ .001; Dominant model (AA vs. AG + GG): OR = 0 0.470, 95% CI: 0.282-0.783, p = .04. More severe grades of RDS, need for surfactant and mechanical ventilation, were significantly associated with AA genotype when compared to AG + GG genotypes. IL10 (AG + GG) genotypes were considered as an independent predictor for lower risk of RDS within preterm neonates. CONCLUSION: IL10-1082 A/A genotype associated with increased susceptibility to RDS. Also, A allele has been associated with increase severity of RDS in preterm neonates. Regression analysis revealed that IL10 AG + GG genotypes were considered as independent predictors for lower risk development of RDS within preterm neonates.

Diagnostic value of soluble programmed cell death protein-1 in type-1 autoimmune hepatitis in Egyptian children.

Programmed cell death protein-1 (PDCD1) is considered a key factor in immune regulation and is expressed mainly on activated T cells. The current study aimed to assess the clinical value of soluble PDCD1/PD1 as a marker for diagnosing type-1 autoimmune hepatitis in children. Sixty children with chronic hepatitis as patients' groups further divided into autoimmune hepatitis group and other chronic liver disease group and 20 healthy children as a control group were enrolled in this study. All children have been studied for clinical profile, biochemical, histological features and serum level of soluble programmed cell death protein-1 by ELISA. There was a significant increase regarding soluble PDCD1/PD1 in the autoimmune hepatitis group than the chronic liver disease group, with the lowest level in the control group. Soluble PDCD1/PD1 level increased with higher fibrosis stage and higher Child Pugh score, also higher in relapsed patients than patients with complete remission in AIH groups. There was a positive correlation between soluble PDCD1/PD1 and PT, IgG, fibrosis stage, HAI, ALT, AST, simplified and revised score system, PELD and MELD among the AIH group. The best cutoff value of PDCD1/PD1 in the prediction of autoimmune hepatitis was 1.73 ng/ml with AUC:0.895 that has a sensitivity of 80%, specificity of 78%. sPDCD1/PD1 level represents a possible promising biomarker of AIH patients who will represent an incomplete response for regular treatment. This finding can be considered as the first step to prove the pivotal role of soluble PDCD1/PD1 in the diagnosis of AIH.

Association between vitamin D receptor (FokI) genetic variant rs2228570 and iron profile in hemodialysis patients.

Iron deficiency is a common etiology of anemia that causes suboptimal response to erythropoietin therapy in hemodialysis (HD) patients. This study investigated the association between vitamin D receptor (VDR) genetic variant (FokI) rs2228570 with iron indices (serum iron, transferrin, transferrin saturation, and ferritin). Sixty adequately hemodialyzed patients subdivided into two groups; 31 patients with transferrin saturation (TSAT) < 20% and 29 with TSAT > 20% who received I.V sodium ferric gluconate, calcium, and vitamin D. Sixty normal healthy were selected as the control group.. VDR genetic variant (SNP rs2228570) was genotyped in all subjects using PCR/RFLP. HD patients showed a higher frequency of rs2228570 FF genotype (38.3%) than controls (31.7%). The frequency of ff genotype and f allele in patients (8.4 and 35% respectively) were significantly lower than controls (25 and 46.7% respectively). Allele model (f vs. F): OR 0.721, 95% CI 0.521-0.998, P = 0.049. While (ff vs. FF): OR 0.452, 95% CI 0.223-0.917, P = 0.028. The distribution of Ff + ff genotypes in HD cases with TSAT > 20% was higher than in HD cases with TSAT < 20%, Dominant model (Ff +ff vs FF): OR 2.753, 95% CI 1.902-3.409, P = 0.048. f allele showed lower frequency in low TSAT group than high TSAT group (27.4 vs. 43.1%) with significant P value (P = 0.042) with allele model (f vs. F): OR 2.012, 95% CI 1.923-4.226, P = 0.042. Fok-1 ff, Ff + ff genotypes were significantly associated with TSAT > 20% with a protective effect against low TSAT in HD patients.

Clinical Value of Serum Interleukin-33 Biomarker in Infants With Neonatal Cholestasis.

OBJECTIVES: The present study aimed to estimate the value of serum interleukin-33 (IL-33) levels in infants with cholestasis, correlate serum IL-33 levels with the clinicopathological profile of infants with cholestasis, and compare its level with that of healthy infants who served as control. METHODS: Sixty infants with cholestasis were enrolled in the present study and divided into biliary atresia (BA) group and non-BA group, in addition to 30 healthy infants as a control group. All infants were analyzed for their clinical and biochemical features, histopathological profile, and serum level of IL-33 by enzyme-linked immune sorbent assay. RESULTS: Serum level of IL-33 in BA group (median 48.0, interquartile range: 28.9-106.2) was significantly higher than that of the non-BA group (median 17.3, interquartile range: 13.7-18.8 pg/mL) and both were higher than that of the control group. There was a positive correlation between serum IL-33 and aspartate aminotransferase, alanine aminotransferase, bilirubin (total and direct) levels, and fibrosis stage among the BA group. Serum IL-33 at a cut-off value of 20.8 pg/mL can detect BA with a specificity of 95% and a sensitivity of 96.7%. CONCLUSION: The significantly higher production of IL-33 in patients with BA compared to non-BA suggests a potential role of IL-33 for initiation and progression of the disease process, also, IL-33 may have a diagnostic role in infants with BA.

Study of C677T variant of methylene tetrahydrofolate reductase gene in autistic spectrum disorder Egyptian children.

BACKGROUND: Autism spectrum disorders (ASD) is a heterogeneous neurodevelopmental disease, various articles reported that dysfunctional folate-methionine pathway enzymes might assume a paramount part in the pathophysiology of autism. Methylene tetrahydrofolate reductase (MTHFR) is a basic catalyst for this pathway, also MTHFR gene C677T variant accounted as a risk factor of autism. OBJECTIVE: The present study aimed to investigate the association of MTHFR gene rs1801133(C677T) variant among Egyptian autistic children. METHODS: The study included 78 autistic children, and 80 matched healthy control children. Full clinical and radiological examinations were conducted. MTHFR genetic variant, rs1801133(C677T) was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods followed by direct sequencing technique. RESULTS: MTHFR (C677T) allele frequency was found to be higher significantly in ASD cases compared with nonautistic children. Also, we had a higher distribution of combined CT + TT genotypes among autistic patients with consanguinity and family history of psychological disease. In Gastrointestinal tract (GIT) and sleep disorders showed a higher distribution of hetero CT genotype as well as combined CT + TT genotypes. CONCLUSION: This study demonstrated a role of MTHFR gene (C667T) variant with the increased risk for ASD.

Association of NKX2-5, GATA4, and TBX5 polymorphisms with congenital heart disease in Egyptian children.

BACKGROUND: Several genes encoding transcription factors are known to be the primary cause of congenital heart disease. NKX2-5 and GATA4 were the first congenital heart disease-causing genes identified by linkage analysis. This study designed to study the association of five single-nucleotide variants of NKX2-5, GATA4, and TBX5 genes with sporadic nonsyndromic cases of a congenital cardiac septal defect in Egyptian children. METHODS: Venous blood samples from 150 congenital heart disease children (including a ventricular septal defect, atrial septal defect, tetralogy of Fallot, and patent ductus arteriosus) and 90 apparently healthy of matched age and sex were studied by polymerase chain reaction followed by direct sequencing in order to study two single-nucleotide variants of NKX2-5 (rs2277923, rs28936670), two single-nucleotide variants of GATA4 (rs368418329, rs56166237) and one single-nucleotide variant TBX5 (rs6489957). The distribution of genotype and allele frequency in the congenital heart diseases (CHD) group and control group were analyzed. RESULTS: We found different genotype frequencies of the two variants of NKX2-5, as CT genotype of rs2277923 was present in 58% and 36% in cases and control respectively, and TT genotype present in 6% of the cases. Also regarding missense variant rs28936670, heterozygous AG presented in 82% of the cases. Also, we observed a five prime UTR variant rs368418329, GT (42% of the cases) and GG (46% of the cases) genotypes showed the most frequent presentation in cases. While regarding a synonymous variant rs56166237, GT and GG were the most presented in cases (41.4%, 56% respectively) in contrast to control group (20%, 1.7% respectively). Also, a synonymous variant in TBX5, the distribution of genotype frequency was significantly different between the CHD group and control group. CT genotype of TBX5 -rs6489957 was found in 12 ASD, 24 VSD, six PDA, three aortic coarctation and nine fallot that represent 42% of the cases. CONCLUSIONS: Significantly higher frequency of different allelle of five variants was observed in cases when compared to the control group, with significant risky effect for the development of septal defect. In addition to two polymorphisms of NKX2-5 (rs2277923, rs28936670) variant in the cardiac septal defect, two variants in GATA4 (rs368418329, rs56166237) and one variant in TBX5 (rs6489957) seem to have a role in the pathogenesis of congenital heart disease.

Evaluation of TG-HDL Ratio Instead of HOMA Ratio as Insulin Resistance Marker in Overweight and Children with Obesity.

BACKGROUND: Homeostasis model assessment for insulin resistance (HOMA-IR) is widely used as a marker of insulin resistance in adults and has also been validated in children and adolescents. Triglyceride (TG) and HDL-C on the other hand is a routine test and inexpensive compared to insulin. Previous studies reported conflicting findings on the usefulness of the triglyceride to HDL-C ratio (TG:HDL-C ratio) as predictor or marker of IR. The aim of this work was to investigate the usefulness of Triglyceride to HDL-C ratio (TG/HDL-C) as an Insulin Resistance (IR) marker in overweight and children with obesity. METHODS: This study was a comparative cross sectional study which was conducted on ninety overweight and children with obesity attending National Nutrition Institute "Pediatric obesity clinic. They were classified into 2 groups as follows: group (1) included overweight and children with obesity with insulin resistance, group (2) included overweight and children with obesity with non-insulin resistance. All the subjects were subjected to history, clinical examination and laboratory investigations including total lipid profile, fasting glucose, insulin and TG:HDL-C ratio instead of HOMA ratio. RESULTS: Prevalence of IR among the studied sample was 42 (46.7%). Mean value of TG/ HDL-C ratio was greater among the insulin resistance group than non insulin resistance group (p value= < 0.001)value). TG/HDL ratio ≥1.36 had 85.7% sensitivity, 66.7% specificity. There was statistically significant positive correlation between TG/HDL ratio and HOMA-IR. CONCLUSION: TG:HDL ratio ≥1.36 is a significant early and sensitive predictor of insulin resistance in children instead of HOMA-IR.

Evaluation of loss of heterozygosity of chromosome 22q11.21 region in patients with congenital heart diseases.

The 22q11.21 region is prone to low-copy repeats events that lead to congenital anomaly disorders. We tested genomic DNA of 20 families with non-syndromic CHD patients using a set of three known consecutive high polymorphic short tandem repeat (STR) markers along the 22q11.21 region; D22S941, D22S944 and D22S264 loci. We found loss of heterozygosity (LOH) in D22S941 locus in 2 out of 20 families (10%) with 2 offspring affected by ASD combined with PS and TOF respectively. No LOH found in D22S944 and D22S264 loci either in affected cases or control group and no LOH found in D22S941 in the control group. Also we observed that D22S944 locus prone to be less allele diversity than D22S941 and D22S264 loci.

Serum human endothelial cell-specific molecule-1 (endocan) and vascular endothelial growth factor in cirrhotic HCV patients with hepatocellular carcinoma as predictors of mortality.

OBJECTIVES: The aim of this study was to assess serum levels of endocan & VEGF in patients with hepatitis C virus-related HCC and their diagnostic and predictive value of mortality. METHODS: A total of 195 patients with CHC were subdivided into the following two groups: 105 HCV cirrhotic patients with HCC and 90 HCV cirrhotic patients without HCC. Sixty apparently healthy subjects served as the control group. The serum VEGF and endocan were assessed by ELISA. RESULTS: The mean serum endocan level was 4257.6± 847.6 pg/mL in HCC patients, compared to 2099.2± 459.6 pg/mL in liver cirrhosis patients without HCC. VEGF levels in the HCC group were non-significantly higher than those of the non-HCC group, and control group. Endocan at cut-off value 2967 pg/ml had higher sensitivity and higher specificity in diagnosis of HCC than AFP and VEGF. The median follow up period was 9 months, survival curve analysis was done in HCC group and showed that probability of survival among HCC group with higher levels of VEGF and endocan were significantly lower than that patients with low levels. In HCC patients, elevated serum endocan levels were significantly associated with poor hepatic functions and a greater number and size of tumours. Multivariate analysis showed that serum endocan levels (≥4000 pg/ml), as well as elevated serum fetoprotein (>100 ng/dl), were independent prognostic biomarkers for mortality. CONCLUSION: Endocan may be a useful diagnostic marker for HCC and a good predictor of mortality, especially when combined with AFP and VEGF.

IRS-1 genetic polymorphism (r.2963G>A) in type 2 diabetes mellitus patients associated with insulin resistance.

BACKGROUND: Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling. Several polymorphisms in the IRS genes have been identified, but only the Gly to Arg 972 substitution of IRS-1 seems to have a pathogenic role in the development of type 2 diabetes mellitus (T2DM). Many polymorphisms described in IRS-1 gene, especially Gly972Arg substitution, are shown to be associated with insulin resistance (IR) in T2DM. SUBJECTS AND METHODS: This prospective case-control study was performed during the period from November 2014 to May 2015. All patients were selected from the Department of Internal Medicine and were screened for eligibility for this study. Subjects were divided into two groups: first group consisted of 100 T2DM patients; second group consisted of 120 nondiabetic controls. First group was further divided into two subgroups: 66 IR patients and 34 insulin-sensitive (IS) patients (homeostatic model assessment [HOMA] was performed). Restriction fragment length polymorphism (RFLP) was performed using specific primers for scanning single-nucleotide polymorphisms (SNPs) such as Gly972Arg (rs1801278 SNP). RESULTS: Taking GG genotype and G allele as references, GA, GA+AA genotypes and A allele showed significantly higher frequency in the T2DM group when compared to the control group, with higher risk to develop T2DM in healthy controls. Taking GG as a reference, rs1801278GA+AA genotype and A allele showed significantly higher proportion in IR when compared to IS, with higher risk to develop IR in T2DM patients. Logistic regression analysis showed that higher FBG, fasting plasma insulin (FPI), HOMA-IR, GA+AA genotypes were associated with higher risk to develop IR in univariable analysis. CONCLUSION: IRS-1 genetic factor may be a significant genetic determinant for IR in T2DM patients during severe/acute-phase hyperglycemia.

Independent of DAZL-T54A variant and AZF microdeletion in a sample of Egyptian patients with idiopathic non-obstructed azoospermia.

BACKGROUND: The microdeletion events that occur in the Y chromosome-azoospermia factor (AZF) region may lead to dyszoospermia. Also, the deleted azoospermia (DAZ) gene on AZFc and autosomal deleted azoospermia like gene (DAZL) are suggested to represent impairment, so it is interesting to determine the independency pattern of the AZF region and DAZL gene in azoospermic patients. AIM: To study the molecular characterization of AZFc and DAZL in 64 idiopathic non-obstructed azoospermia patients and 30 sexually reproductive men. METHODS: SYBR Green I (Q-PCR) and AZF-STS analysis was used for DAZ gene, and SNV-PCR and confirmative Sanger sequencing for DAZL gene. RESULTS: The present study observed that 15.6% had AZFc microdeletion, out of which 10% had DAZ1/2 deletion, and no T54A variant in the DAZL gene was found. CONCLUSION: In the current work, the novelty is that spermatogenic impairment phenotype, present with AZFc microdeletions, is independent of the T54A variant in the DAZL gene, and AZFc microdeletions could be a causative agent in spermatogenic impairment.

Association between Q192R polymorphism in the PON1 gene and statin responses in cardiac patients.

INTRODUCTION: Paraoxonases are a group of different forms enzymes that consist of three non-similar isoforms, PON1, PON2 and PON3, which are located near to each other on the long arm of chromosome7. This study aims to investigate the association of a Q192R polymorphism of PON1 gene and statin response in patients with ischemic heart disease with dyslipidemia. METHODS: The studied population included three hundred patients with coronary artery disease with dyslipidemia who were prescribed statins. Total lipid profile was measured in these patients both before and after approximately 6 months of treatment. Q192R polymorphism of PON1 gene was assessed by real-time PCR. RESULTS: There were no significant differences in baseline lipid levels according to different genotypes in all studied casesof Q192R (rs662) polymorphism. HDL-C goals were attained less often in patients with RR homozygosity than in Q allele carriers. Analysis by univariate logistic regression confirmed that QQ/QR carriers had an increased chance of attaining HDL-C goals. CONCLUSION: This study shows that the Q192R polymorphism of PON1gene has important role in interindividual variety in accomplishment of HDL-C goals in response to statins.

Mean platelet volume and serum uric acid in neonatal sepsis: A case-control study.

BACKGROUND: Mean platelet volume (MPV) is a measure of platelet volume. It reveals the presence of inflammatory burden and disease activity in many diseases. Serum uric acid (SUA) is one of the most important antioxidants in human biological fluids and is responsible for neutralizing > 50% of the free radicals in the human blood. For this reason, it was thought that the antioxidant effects of SUA could increase the life expectancy and/or reduce the incidence of malignancy. OBJECTIVES: To determine the role of mean platelet volume (MPV) and serum uric acid (SUA) level in the diagnosis of neonatal sepsis (NS). METHODS: This case-control study was done on 80 newborns divided into 3 groups: group A (n = 22): clinical NS, group B (n = 18): Proven NS and Group C (n = 40): apparently healthy control. All patients in the study were subjected to adequate assessment of history, full clinical examination, complete blood count including MPV, C - reactive protein (CRP), blood culture in CRP positive cases, and SUA level at the time of diagnosis of sepsis. RESULTS: Septic neonates showed statistically higher values of MPV and statistically lower levels of SUA than the control group. The diagnostic cut-off values of MPV and SUA for NS were 10.2 fL, and 3.70 mg/dL, respectively. CONCLUSIONS: MPV could be assessed in the early diagnosis of neonatal sepsis while SUA level has lower sensitivity in neonatal sepsis.