Diagnostic Accuracy of Acoustic Radiation Force Impulse (ARFI) in Diagnosis of Liver Fibrosis among Egyptian Patients with Chronic HCV Infection

BACKGROUND: Acoustic radiation force impulse (ARFI) evaluates liver stiffness non-invasively and was invented recently. This technique can easily and accurately assess the degree of liver fibrosis in clinical practice.AIM: The aim of this study was to detect the diagnostic performance of ARFI elastography in the staging of fibrosis in some Egyptian patients with chronic HCV infection. PATIENTS AND METHODS: One hundred ninety patients with chronic HCV infection; 142 men and 48 women were enrolled in the study. They underwent liver biopsy examination for liver fibrosis detection. All demographic; clinical and biochemical data were recoded. ARFI examination was done for all subjects to detect liver stiffness measurement in relation to liver fibrosis detected by pathological examination of liver biopsies. RESULTS: Medians of liver stiffness measurement by shear wave velocity showed a significant increase as a grade of liver fibrosis increases (p ≤ 0.0001, highly significant). Liver stiffness was directly correlated to age, AST; ALT; INR and liver steatosis (p values were: 0.009; 0.0001; 0.013; 0.006 and 0.04 respectively, significant). On the other hand, liver stiffness was inversely correlated to albumin; prothrombin concentration and platelets (p values were: 0.0001; 0.001, and 0.0001, respectively, significant). We found that shear wave velocity can predict F1; F2; F3 and F4 at cut-off values: 1.22; 1.32; 1.44 and 1.8 respectively.CONCLUSION: ARFI is a diagnostic noninvasive promising technique for liver fibrosis diagnosis among Egyptian patients with chronic HCV infection

Genome-Wide Association Study for Identification and Validation of Novel SNP Markers for \u3ci\u3eSr6\u3c/i\u3e Stem Rust Resistance Gene in Bread Wheat

Stem rust (caused by Puccinia graminis f. sp. tritici Erikss. & E. Henn.), is a major disease in wheat (Triticum aestivium L.). However, in recent years it occurs rarely in Nebraska due to weather and the effective selection and gene pyramiding of resistance genes. To understand the genetic basis of stem rust resistance in Nebraska winter wheat, we applied genome-wide association study (GWAS) on a set of 270 winter wheat genotypes (A-set). Genotyping was carried out using genotyping-by-sequencing and ~35,000 high-quality SNPs were identified. The tested genotypes were evaluated for their resistance to the common stem rust race in Nebraska (QFCSC) in two replications. Marker-trait association identified 32 SNP markers, which were significantly (Bonferroni corrected P \u3c 0.05) associated with the resistance on chromosome 2D. The chromosomal location of the significant SNPs (chromosome 2D) matched the location of Sr6 gene which was expected in these genotypes based on pedigree information. A highly significant linkage disequilibrium (LD, r2) was found between the significant SNPs and the specific SSR marker for the Sr6 gene (Xcfd43). This suggests the significant SNP markers are tagging Sr6 gene. Out of the 32 significant SNPs, eight SNPs were in six genes that are annotated as being linked to disease resistance in the IWGSC RefSeq v1.0. The 32 significant SNP markers were located in nine haplotype blocks. All the 32 significant SNPs were validated in a set of 60 different genotypes (V-set) using single marker analysis. SNP markers identified in this study can be used in marker-assisted selection, genomic selection, and to develop KASP (Kompetitive Allele Specific PCR) marker for the Sr6 gene

Relation between microRNAs and Apoptosis in Hepatocellular Carcinoma

AIM: To determine the relation between serum microRNAs and apoptotic markers as regards development of HCC to understand the underlying mechanism of HCV related hepatocarcinogenesis. PATIENTS AND METHODS: A total of 65 serum samples (25 samples from controls, 20 samples from hepatitis and 20 samples from HCC patients) were collected for miRNAs (mir 21, mir 199-a, and mir 155) detection. Human Programmed cell death protein-4 (PDCD-4) and Human Cytochrome-C (CYT-C) were determined. RESULTS: miRNAs 21 and 155 were over expressed in sera of patients with HCC compared to patients with chronic hepatitis (p < 0.0001). While serum means values of miR 199a was significantly decreased among HCC group patients when compared to patients with chronic hepatitis (p < 0.0001). The serum levels of PCDC4 and CYTC were increased in patients with HCC when compared to chronic hepatitis patients. They were also increased in patients with chronic hepatitis when compared to controls (p < 0.05, significant). There was direct correlations between apoptotic markers and oncomirs miRNAs 21 and 155 while apoptotic markers were inversely correlated with miRNA 199-a. CONCLUSION: Both microRNAs and apoptotic markers have roles in HCC pathogenesis. It seems that oncogenic microRNAs induce liver carcinogenesis in HCV patients irrespective of suppression of apoptosis.AIM: To determine the relation between serum microRNAs and apoptotic markers as regards development of HCC to understand the underlying mechanism of HCV related hepatocarcinogenesis. PATIENTS AND METHODS: A total of 65 serum samples (25 samples from controls, 20 samples from hepatitis and 20 samples from HCC patients) were collected for miRNAs (mir 21, mir 199-a, and mir 155) detection. Human Programmed cell death protein-4 (PDCD-4) and Human Cytochrome-C (CYT-C) were determined. RESULTS: miRNAs 21 and 155 were over expressed in sera of patients with HCC compared to patients with chronic hepatitis (p < 0.0001). While serum means values of miR 199a was significantly decreased among HCC group patients when compared to patients with chronic hepatitis (p < 0.0001). The serum levels of PCDC4 and CYTC were increased in patients with HCC when compared to chronic hepatitis patients. They were also increased in patients with chronic hepatitis when compared to controls (p < 0.05, significant). There was direct correlations between apoptotic markers and oncomirs miRNAs 21 and 155 while apoptotic markers were inversely correlated with miRNA 199-a. CONCLUSION: Both microRNAs and apoptotic markers have roles in HCC pathogenesis. It seems that oncogenic microRNAs induce liver carcinogenesis in HCV patients irrespective of suppression of apoptosis

Environmental, maternal, and reproductive risk factors for childhood acute lymphoblastic leukemia in Egypt : a case-control study

BACKGROUND\ud Acute lymphocytic leukemia (ALL) is the most common pediatric cancer. The exact cause is not known in most cases, but past epidemiological research has suggested a number of potential risk factors. This study evaluated associations between environmental and parental factors and the risk for ALL in Egyptian children to gain insight into risk factors in this developing country.\ud METHODS\ud We conducted a case-control design from May 2009 to February 2012. Cases were recruited from Children's Cancer Hospital, Egypt (CCHE). Healthy controls were randomly selected from the general population to frequency-match the cumulative group of cases by sex, age groups (<1; 1 - 5; >5 - 10; >10 years) and region of residence (Cairo metropolitan region, Nile Delta region (North), and Upper Egypt (South)). Mothers provided answers to an administered questionnaire about their environmental exposures and health history including those of the father. Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated using logistic regression with adjustment for covariates.\ud RESULTS\ud Two hundred ninety-nine ALL cases and 351 population-based controls frequency-matched for age group, gender and location were recruited. The risk of ALL was increased with the mother's use of medications for ovulation induction (ORadj = 2.5, 95 % CI =1.2 -5.1) and to a lesser extend with her age (ORadj = 1.8, 95 % CI = 1.1 - 2.8, for mothers ≥ 30 years old). Delivering the child by Cesarean section, was also associated with increased risk (ORadj = 2.01, 95 % CI =1.24-2.81).\ud CONCLUSIONS\ud In Egypt, the risk for childhood ALL appears to be associated with older maternal age, and certain maternal reproductive factors

Genetic architecture of common bunt resistance in winter wheat using genome-wide association study

Background: Common bunt (caused by Tilletia caries and T. foetida) has been considered as a major disease in wheat (Triticum aestivum) following rust (Puccinia spp.) in the Near East and is economically important in the Great Plains, USA. Despite the fact that it can be easily controlled using seed treatment with fungicides, fungicides often cannot or may not be used in organic and low-input fields. Planting common bunt resistant genotypes is an alternative. Results: To identify resistance genes for Nebraska common bunt race, the global set of differential lines were inoculated. Nine differential lines carrying nine different genes had 0% infected heads and seemed to be resistant to Nebraska race. To understand the genetic basis of the resistance in Nebraska winter wheat, a set of 330 genotypes were inoculated and evaluated under field conditions in two locations. Out of the 330 genotypes, 62 genotypes had different degrees of resistance. Moreover, plant height, chlorophyll content and days to heading were scored in both locations. Using genome-wide association study, 123 SNPs located on fourteen chromosomes were identified to be associated with the resistance. Different degrees of linkage disequilibrium was found among the significant SNPs and they explained 1.00 to 9.00% of the phenotypic variance, indicating the presence of many minor QTLs controlling the resistance. Conclusion: Based on the chromosomal location of some of the known genes, some SNPs may be associated with Bt1, Bt6, Bt11 and Bt12 resistance loci. The remaining significant SNPs may be novel alleles that were not reported previously. Common bunt resistance seems to be an independent trait as no correlation was found between a number of infected heads and chlorophyll content, days to heading or plant height

Nonchromosomal birth defects and risk of childhood acute leukemia : An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Genetic architecture of common bunt resistance in winter wheat using genome-wide association study

Background: Common bunt (caused by Tilletia caries and T. foetida) has been considered as a major disease in wheat (Triticum aestivum) following rust (Puccinia spp.) in the Near East and is economically important in the Great Plains, USA. Despite the fact that it can be easily controlled using seed treatment with fungicides, fungicides often cannot or may not be used in organic and low-input fields. Planting common bunt resistant genotypes is an alternative. Results: To identify resistance genes for Nebraska common bunt race, the global set of differential lines were inoculated. Nine differential lines carrying nine different genes had 0% infected heads and seemed to be resistant to Nebraska race. To understand the genetic basis of the resistance in Nebraska winter wheat, a set of 330 genotypes were inoculated and evaluated under field conditions in two locations. Out of the 330 genotypes, 62 genotypes had different degrees of resistance. Moreover, plant height, chlorophyll content and days to heading were scored in both locations. Using genome-wide association study, 123 SNPs located on fourteen chromosomes were identified to be associated with the resistance. Different degrees of linkage disequilibrium was found among the significant SNPs and they explained 1.00 to 9.00% of the phenotypic variance, indicating the presence of many minor QTLs controlling the resistance. Conclusion: Based on the chromosomal location of some of the known genes, some SNPs may be associated with Bt1, Bt6, Bt11 and Bt12 resistance loci. The remaining significant SNPs may be novel alleles that were not reported previously. Common bunt resistance seems to be an independent trait as no correlation was found between a number of infected heads and chlorophyll content, days to heading or plant height

Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the common lethal types of tumor all over the world. The lethality of HCC accounts for many reasons. One of them, the lack of reliable diagnostic markers at the early stage, in this context, serum miRNAs became promising diagnostic biomarkers. Herein, we aimed to identify the predictive value of two miRNAs (miR-122 and miR-224) in plasma of patients with HCC preceded by chronic HCV infection. Taqman miRNA assays specific for hsa-miR-122 and hsa-miR-224 were used to assess the expression levels of the chosen miRNAs in plasma samples collected from three groups; 40 patients with HCC related to HCV, 40 with CHC patients and 20 healthy volunteers. This study revealed that the mean plasma values of miRNA-122 were significantly lower among HCC group when compared to CHC and control groups (P 1.2 (RQ) and (AUC = 0.93, P < 0.001), while the accuracy of AFP to diagnose HCC was (AUC: 0.619; P = 0.06). In conclusion, the expression plasma of miR-122 and miR-224 could be used as noninvasive biomarkers for the early prediction of developing HCC at the early stage