Identification of functional tumor necrosis factor-alpha promoter variants associated with Helicobacter pylori infection in the Sudanese population: Computational approach.

BACKGROUND: Helicobacter pylori (H. pylori) is a ubiquitous bacterium that affects nearly half of the world's population with a high morbidity and mortality rate. Polymorphisms within the tumor necrosis factor-alpha (TNF-A) promoter region are considered a possible genetic basis for this disease. AIM: To functionally characterize the genetic variations in the TNF-A 5'-region (-584 to +107) of Sudanese patients infected with H. pylori using in silico tools. METHODS: An observational study was carried out in major public and private hospitals in Khartoum state. A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy. Genomic DNA was extracted. Genotyping of the TNF-A-1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to H. pylori infection in the Sudanese population. Furthermore, Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5'-region (-584 to +107) of TNF-A in H. pylori-infected patients. Bioinformatics analyses were used to predict whether these mutations would alter transcription factor binding sites or composite regulatory elements in this region. A comparative profiling analysis was conducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible conservation. Also, a multivariate logistic regression model was constructed to estimate odds ratios and their 95% confidence intervals for the association between TNF-A-1030, sociodemographic characteristics and H. pylori infection. Differences were statistically significant if P < 0.05. Statistical analyses were performed using Stata version 11 software. RESULTS: A total of seven single nucleotide polymorphisms were observed in the TNF-A 5'-region of Sudanese patients infected with H. pylori. Only one of them (T > A, -76) was located at the in silico-predicted promoter region (-146 to +10), and it was predicted to alter transcription factor binding sites and composite regulatory elements. A novel mutation (A > T, +27) was detected in the 5' untranslated region, and it could affect the post-transcriptional regulatory pathways. Genotyping of TNF-A-1030 showed a lack of significant association between -1030T and susceptibility to H. pylori and gastric cancer in the studied population (P = 0.1756) and (P = 0.8116), respectively. However, a significant association was detected between T/C genotype and H. pylori infection (39.34% vs 19.67%, odds ratio = 2.69, 95% confidence interval: 1.17-6.17, P = 0.020). Mammalian conservation was observed for the (-146 to +10) region in chimpanzee (99.4%), rhesus monkey (95.6%), cow (91.8%), domesticated dog (89.3%), mouse (84.3%), rat (82.4%) and opossum (78%). CONCLUSION: Computational analysis was a valuable method for understanding TNF-A gene expression patterns and guiding further in vitro and in vivo experimental validation.

Potential Role of Cardiopulmonary Exercise Testing as an Early Screening Tool for Patients With Suspected Pulmonary Hypertension Including Exercise-Induced Pulmonary Hypertension: Results From a Retrospective Analysis.

OBJECTIVE: The primary goal of our retrospective case-control study was to evaluate the ability of cardiopulmonary exercise testing to screen for underlying exercise-induced pulmonary hypertension (EIPH) in symptomatic patients who had a negative stress test and elevated right ventricular systolic pressure on echocardiogram. We also evaluated long-acting nitrates and ranolazine as medication challenges. SETTING: Performed at a single, tertiary-care medical center in the United States. PARTICIPANTS: Based on the inclusion and exclusion criteria, 81 patients were included in this study. The primary outcome of the study was to measure mean pulmonary arterial pressure at rest and exertion, as well as Wasserman curves. We also recorded patient demographics and risk factors, left ventricular ejection fraction, and mean oxygen consumption. Additionally, patients were monitored symptomatically after receiving long-acting nitrates and ranolazine. RESULTS: A total of 61 patients had resting pulmonary arterial hypertension, and 27 had EIPH. The EIPH group had a significantly higher mean age of 71.67 years. Wasserman curves calculated from the cardiopulmonary exercise testing data revealed 3 subgroups of EIPH patients: cardiac restriction, chronotropic incompetence, and combination of both patterns. The EIPH group showed significant improvement in symptoms after receiving long-acting nitrate therapy. CONCLUSIONS: Many patients with symptoms of angina, dyspnea, and/or fatigue on exertion with negative cardiac stress testing may have underlying pulmonary arterial hypertension, including EIPH. Therefore, these patients require adequate treatment and follow-up to prevent worsening of symptoms and pathology.

Accumulation of heavy metals in the fish, Oreochromis niloticus and Poecilia latipinna and their concentration in water and sediment of dam lake of Wadi Namar, Saudi Arabia.

The present study reports the accumulation of heavy metals like Cu, Hg, Cd, Pb and Cr in different tissues viz. liver, kidney, gills and muscles of Oreochromisniloticus and Poecilia latipinna from two sites in dam lake of Wadi Namar. Water and sediment samples were also collected from two sites for heavy metal analysis. Metal concentration in water and sediment samples of both the sites were observed in the following order: Cu>Cr>Pb>Cd>Hg; however, their concentration was found to be more at site 2 as compared to site 1. The order of metal accumulation in different tissues of O. niloticus and P. latipinna was in the following order: Cu>Cr>Pb>Cd>Hg at both the sites, while liver accumulated maximum amounts of metals followed by kidney, gills and muscles. The results showed the site 2 was more polluted by metals than Site 1 and O. niloticus accumulated greater amount of metals than P. latipinna.