Interferon- γ receptor-1 gene promoter polymorphisms and susceptibility for brucellosis in Makkah region

Background: Genetic polymorphisms that affect the production levels of certain cytokines and/or their receptors may determine the risk, severity or protection in some infectious diseases like brucellosis.Objectives: The aim of this study was to investigate the association of certain known Interferon-γ Receptor-1 (IFN-γ R1) gene promoter polymorphisms and the susceptibility to infection with Brucellosis in Saudi population.Methods: A cases-control association study was conducted in 69 individuals with human brucellosis and 94 healthy individuals. Genotyping of IFN-γ R1 – 56 C>T and IFN-γ R1 – 611 A>G polymorphism in both patients and healthy controls was done by PCR- restriction enzyme length polymorphisms (PCR-RFLP) and PCR- confronting two primer pairs (PCR-CTPP) methods and were assessed for potential associations with susceptibility for human brucellosis and their mode of penetrance.Results: Interestingly, we have designed a PCR-CTPP system to be used for genotyping of    IFN-γ R1 – 611 A > G polymorphism. The PCR-CTPP is an accurate method for genotyping of SNPs. Moreover, it is time-saving, inexpensive and easy to perform.Conclusion: Both tested polymorphisms, IFN-γ R1 – 56 C>T and IFN-γ R1 -611 A>G polymorphism had no role in genetic susceptibility to human brucellosis in the study population. The PCR-CTPP can be used for genotyping IFN-γ R1 – 611 A > G polymorphism and other types of mutation.Keywords: Brucellosis; susceptibility; IFN-γ R1 gene promoter polymorphisms

Interferon- \u3b3 receptor-1 gene promoter polymorphisms and susceptibility for brucellosis in Makkah region

Background: Genetic polymorphisms that affect the production levels of certain cytokines and/or their receptors may determine the risk, severity or protection in some infectious diseases like brucellosis. Objectives: The aim of this study was to investigate the association of certain known Interferon-\u3b3 Receptor-1 (IFN-\u3b3 R1) gene promoter polymorphisms and the susceptibility to infection with Brucellosis in Saudi population. Methods: A cases-control association study was conducted in 69 individuals with human brucellosis and 94 healthy individuals. Genotyping of IFN-\u3b3 R1 \u2013 56 C>T and IFN-\u3b3 R1 \u2013 611 A>G polymorphism in both patients and healthy controls was done by PCR- restriction enzyme length polymorphisms (PCR-RFLP) and PCR- confronting two primer pairs (PCR-CTPP) methods and were assessed for potential associations with susceptibility for human brucellosis and their mode of penetrance. Results: Interestingly, we have designed a PCR-CTPP system to be used for genotyping of IFN-\u3b3 R1 \u2013 611 A > G polymorphism. The PCR-CTPP is an accurate method for genotyping of SNPs. Moreover, it is time-saving, inexpensive and easy to perform. Conclusion: Both tested polymorphisms, IFN-\u3b3 R1 \u2013 56 C>T and IFN-\u3b3 R1 -611 A>G polymorphism had no role in genetic susceptibility to human brucellosis in the study population. The PCR-CTPP can be used for genotyping IFN-\u3b3 R1 \u2013 611 A > G polymorphism and other types of mutation

Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with Schistosomes

Abnormal fibrosis occurs during chronic hepatic inflammations and is the principal cause of death in hepatitis C virus and schistosome infections. Hepatic fibrosis (HF) may develop either slowly or rapidly in schistosome-infected subjects. This depends, in part, on a major genetic control exerted by genes of chromosome 6q23. A gene (connective tissue growth factor [CTGF]) is located in that region that encodes a strongly fibrogenic molecule. We show that the single nucleotide polymorphism (SNP) rs9402373 that lies close to CTGF is associated with severe HF (P = 2 × 10−6; odds ratio [OR] = 2.01; confidence interval of OR [CI] = 1.51–2.7) in two Chinese samples, in Sudanese, and in Brazilians infected with either Schistosoma japonicum or S. mansoni. Furthermore, SNP rs12526196, also located close to CTGF, is independently associated with severe fibrosis (P = 6 × 10−4; OR = 1.94; CI = 1.32–2.82) in the Chinese and Sudanese subjects. Both variants affect nuclear factor binding and may alter gene transcription or transcript stability. The identified variants may be valuable markers for the prediction of disease progression, and identify a critical step in the development of HF that could be a target for chemotherapy

High prevalence of urinary schistosomiasis in two communities in South Darfur: implication for interventions

<p>Abstract</p> <p>Background</p> <p>There are few data on the prevalence of schistosomiasis in Darfur. We conducted this study in response to reports of 15 laboratory confirmed cases of schistosomiasis and visible haematuria among children from two communities in South Darfur. The aim of the study was to estimate the prevalence of schistosomiasis in the area and to decide on modalities of intervention.</p> <p>Methods</p> <p>A cross-sectional survey involving 811 children and adults from schools and health facilities was conducted in two communities of South Darfur in March 2010. Urine samples were collected and examined for ova of <it>Schistosoma haematobium </it>using a sedimentation technique. A semi-structured format was used to collect socio-demographic characteristics of the participants.</p> <p>Results</p> <p>Eight hundred eleven (811) urine samples were collected, 415 from Alsafia and 396 from Abuselala. Of the collected samples in 56.0% (95% Confidence Interval (CI); 52.6-59.4) <it>Schistosoma </it>eggs were found. The prevalence was high in both Abuselala 73.3% (95% CI; 68.9-77.6) and Alsafia 39.5% (95% CI; 34.8-44.2). More males (61.7%, 95%CI; 56.5-64.9) were infected than females (52.1%, 95%CI; 48.2-56.0). Children in the age group 10-14 has the highest (73.0%, 95%CI; 68.7-77.2) infection rate. School age children (6-15 years) are more likely to be infected than those >15 years (Adjusted Odds Ratio (AOR) = 2.70, 95% CI; 1.80-4.06). Individuals in Abuselala are more likely to be infected than those who live in Alsafia (AOR = 4.3, 95% CI; 3.2-5.9).</p> <p>Conclusion</p> <p>The findings of this study indicate that <it>S. hematobium </it>is endemic in Alsafia and Abuselala South Darfur in Sudan with a high prevalence of infection among older children. This signifies the importance of urgent intervention through Mass Drug Administration (MDA) to halt the infection cycle and tailored health messages to targeted groups. Based on the findings MDA was conducted in the villages.</p

REGRESSION OF LIVER FIBROSIS IN SCHISTOSOMA MANSONI INFECTED SUDANESE SUBJECTS AFTER PRAZIQUANTEL TREATMENT

Objectives: 1-To evaluate the effect of Praziquantel (PZQ) therapy on the regression of liver fibrosis in an endemic population. 2-To determine the factors controlling the regression of hepatic fibrosis (e.g. gender, age and grade of fibrosis). &nbsp; Material and methods: An association study of a cohort of one hundred seventy seven Sudanese patients infected with Schistosoma mansoni (82 males 46%, 95 females 54%) was conducted to evaluate the factors controlling the regression of liver fibrosis 39 months after treatment with PZQ using ultrasound evaluation. SPSS (Statistical Package for Social Science) software was used for statistical analysis. Chi- Square was used to compare the two phenotypes (regression and progression) in the study subjects. Results: PPF was regressed in 63 patients (36%) from higher grades of fibrosis to lower ones. While in 24 patients (13 %) the disease progressed to higher grades. In addition, the grade of PPF did not change in 90 patients (51%).&nbsp; The mean values of portal vein diameter (PVD), splenic vein diameter (SVD), and index liver size (ILS) in subjects in whom PPF regressed after treatment were significantly lower than in subjects in whom the disease was progressed (P &lt; .0001, P = .031, and P = .003 respectively).The progression of hepatic fibrosis in males (n = 15, 18 %) was greater than that of females (n = 9, 9 %). Patients who showed regression of PPF or progression of the disease tend to cluster in certain families

Short-Term Forecasting for Energy Consumption through Stacking Heterogeneous Ensemble Learning Model

In the real-life, time-series data comprise a complicated pattern, hence it may be challenging to increase prediction accuracy rates by using machine learning and conventional statistical methods as single learners. This research outlines and investigates the Stacking Multi-Learning Ensemble (SMLE) model for time series prediction problem over various horizons with a focus on the forecasts accuracy, directions hit-rate, and the average growth rate of total oil demand. This investigation presents a flexible ensemble framework in light of blend heterogeneous models for demonstrating and forecasting nonlinear time series. The proposed SMLE model combines support vector regression (SVR), backpropagation neural network (BPNN), and linear regression (LR) learners, the ensemble architecture consists of four phases: generation, pruning, integration, and ensemble prediction task. We have conducted an empirical study to evaluate and compare the performance of SMLE using Global Oil Consumption (GOC). Thus, the assessment of the proposed model was conducted at single and multistep horizon prediction using unique benchmark techniques. The final results reveal that the proposed SMLE model outperforms all the other benchmark methods listed in this study at various levels such as error rate, similarity, and directional accuracy by 0.74%, 0.020%, and 91.24%, respectively. Therefore, this study demonstrates that the ensemble model is an extremely encouraging methodology for complex time series forecasting

Identification of a novel G245R polymorphism in the IL-2 receptor beta membrane proximal domain associated with human visceral leishmaniasis

International audienceBinding of the interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) triggers a series of intracellular events culminating in lymphocyte proliferation and differentiation. We report here the identification of a novel G245R polymorphism in the membrane proximal domain of the IL-2 receptor beta chain (IL-2Rbeta). Present at a frequency of 7.2%, the IL-2-Rbeta G245R was identified in a population of Eastern Sudan exposed to a severe outbreak of visceral leishmaniasis (VL), a disease associated with a marked depression of T-cell antigen-specific responses. The location of the G245R polymorphism next to the box1/box2 proximal cytokine receptor homology segment and suggestive genetic association with the development of disease (P=0.043), suggest that it may affect Janus kinase (JAK) association and impair growth signal transduction. However, additional genetic association with a synonymous single nucleotide polymorphism (IL2RB+8777T) suggests that other variations of IL2RB or nearby genes participate in the highly significant linkage with VL at 22q12 previously reported for this population

Frequency and Distribution of Fok1rs 2228570 of Vitamin D Receptor Gene among Healthy Sudanese Population

Background: Vitamin D plays a role in critical cellular processes such as apoptosis, cell development, and division. The Fok1 polymorphism in the VRD gene is T/C resulting in larger vitamin D receptor protein with lesser expression activity. Fok1 polymorphism is thought to be linked to many diseases including diabetes mellitus, cancers, and rheumatoid arthritis. The snipe also provides effective and sensitive diagnostic and predictive tools and affected by differences in ethnicity and individuals' life style. This study reports on the frequency and distribution of Fok1 SNP among healthy Sudanese transplantation donors. Method: This cross sectional study was conduct in National Cancer Institute University of Gezira, Sudan. One hundred and forty six healthy Sudanese transplantation donors were enrolled in this study. Two ml of venous blood was collected from each participant and stored at -20 till DNA extraction. Qaigen kit was used for DNA extraction. VDR Fok1 was genotyped by CTPP-PCR with proper primers designing and PCR condition. Data was collected by structured questionnaire and analyzed by SNP Stats online tool and medical calculator. Results: According to study results theFok1 polymorphism distributed among Sudanese with percentage of 49.9% (TT + CT), frequency of SNP variants was 69.8% regarding C allele and 30.2% for T allele, while the three genotypes was 10.2% for TT, 39.7% for TC and 50.1% for CC genotype. Conclusion: The frequency of Fok1 VDR SNP was high among healthy Sudanese transplantation donors, this necessitate the conduction of wide area survey among other healthy Sudanese population. This intern will help in investigating the nature of the relation of this SNP with other different diseases. Keywords: Vitamin D, Fok1rs. 2225870, VDR SNP, Sudanes

Exome sequencing identifies two variants of the alkylglycerol monooxygenase gene as a cause of relapses in visceral leishmaniasis in children, in Sudan

Visceral leishmaniasis (kala-azar, KA) is the most severe form of leishmaniasis, characterized by fever, weight loss, hepatosplenomegaly, and lymphadenopathy. During an outbreak of KA in Babar El Fugara (Sudan), 5.7% of cured patients displayed relapses, with familial clustering in half the cases. We performed whole-exome sequencing on 10 relapsing individuals and 11 controls from 5 nuclear families. Rare homozygous and compound-heterozygous nonsense (c.1213C > T, rs139309795, p.Arg405*) and missense (c.701A > G, rs143439626, p.Lys234Arg) mutations of the alkylglycerol monooxygenase (AGMO) gene were associated with KA relapse in 3 families. Sequencing in additional family members confirmed the segregation of these mutations with relapse and revealed an autosomal dominant mode of transmission. These mutations were detected heterozygous in 2 subjects among 100 unrelated individuals with KA who never relapsed after cure, suggesting incomplete penetrance of AGMO deficiency. AGMO is expressed in hematopoietic cells, and is strongly expressed in the liver. AGMO modulates PAF production by mouse macrophages, suggesting that it may act through the PAF/PAF receptor pathway previously shown to have anti-Leishmania activity. This is the first demonstration that relapses after a first episode of KA are due to differences in human genetic susceptibility and not to modifications of parasite pathogenicity