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Rationale: Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation of circulating proteins. Objectives: To quantify and analyze the plasma proteome of patients with PAH using inherited genetic variation to inform on underlying molecular drivers. Methods: An aptamer-based assay was used to measure plasma proteins in 357 patients with idiopathic or heritable PAH, 103 healthy volunteers, and 23 relatives of patients with PAH. In discovery and replication subgroups, the plasma proteomes of PAH and healthy individuals were compared, and the relationship to transplantation-free survival in PAH was determined. To examine causal relationships to PAH, protein quantitative trait loci (pQTL) that influenced protein levels in the patient population were used as instruments for Mendelian randomization (MR) analysis. Measurements and Main Results: From 4,152 annotated plasma proteins, levels of 208 differed between patients with PAH and healthy subjects, and 49 predicted long-term survival. MR based on cis-pQTL located in proximity to the encoding gene for proteins that were prognostic and distinguished PAH from health estimated an adverse effect for higher levels of netrin-4 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.08) and a protective effect for higher levels of thrombospondin-2 (OR, 0.83; 95% CI, 0.74-0.94) on PAH. Both proteins tracked the development of PAH in previously healthy relatives and changes in thrombospondin-2 associated with pulmonary arterial pressure at disease onset. Conclusions: Integrated analysis of the plasma proteome and genome implicates two secreted matrix-binding proteins, netrin-4 and thrombospondin-2, in the pathobiology of PAH.

There is a close association between intestinal metaplasia (IM) and the development of gastric cancer as well as a relationship between Helicobacter pylori, IM, and gastric cancer. Our aim was to study the frequency and subtypes of IM in a Saudi population with dyspepsia, a population with a low prevalence of gastric cancer.Endoscopic antral biopsy specimens were histologically studied for the presence of IM and H. pylori in consecutive patients who underwent upper gastrointestinal endoscopy for evaluation of dyspepsia. Hematoxylin and eosin and Giemsa stain were used to study IM, inflammation, and H. pylori, whereas Alcian blue, pH 2.5/periodic acid-Schiff and high iron diamine/Alcian blue, pH 2.5, were used to study IM subtypes.Seven hundred and seventy-eight consecutive patients were recruited in this study, 415 men and 363 women, with a mean age of 43 +/- 17.6 years. Of the 778 patients, IM was identified in 118 (15.2%). The mean ages of patients with IM (48.8 +/- 18.7) and without IM (41.9 +/- 17.4) were statistically significant (P0.0001), whereas the patients' sex did not influence the presence of IM. Most had type-I IM (59.3%), whereas 26.3% and 14.4% had types II and III, respectively. The overall rate of infection with H. pylori was 75.4%. There was no difference in the frequency of IM in patients with or without H. pylori (15.5% versus 14.1%; P = 0.65). Of the 118 patients with IM, the 91 patients (77.1%) who also had H. pylori were older (55 +/- 23 years) than those without H. pylori (47 +/- 17 years, P = 0.05).This study has documented mainly that the prevalence of IM and IM subtype III is low in our population. Furthermore, we found no significant relationship between a high rate of H. pylori infection with either IM in general or with IM subtype III in particular, possibly accounting for a low incidence of gastric cancer in the Saudi population.

Screening for blood cholesterol levels has become an essential need in many countries. The aim of this study was to evaluate the performance of Reflotron analyzer in screening for blood cholesterol in terms of its precision and accuracy. We have compared the results obtained by the Reflotron with those obtained by a standard hospital laboratory procedure for the same samples. An optimal precision that met the 1992 LSP standards for precision was observed (CV = 2.27%). On the other hand, a suboptimal accuracy of Reflotron was detected, where more than 80% of the Reflotron values differed from the reference laboratory values by more than 5%. As a consequence, 21% of individuals were misclassified as normal due to the very low sensitivity in spite of the optimum specificity observed for the Reflotron. Using the receiver operating characteristic curve analysis, the optimum cut-off points giving the best validity values for the test were 170 mg/dl and 190 mg/dl (4.4 mmol/L and 4.9 mmol/L) for the border-line and true hypercholesterolemia, respectively. At these levels, sensitivity was 0.89 and 0.86, specificity 0.93 and 0.93, and positive predictive value was 0.91 and 0.82, respectively. Considering some limitations of the study, it is concluded that the Reflotron could be of more potential validity for the use in cholesterol measurement surveys when the recommended cut-off points are used.