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We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

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Haptoglobin is an abundant hemoglobin-binding protein present in the plasma. The function of haptoglobin is primarily to determine the fate of hemoglobin released from red blood cells after either intravascular or extravascular hemolysis. There are two common alleles at the Hp genetic locus denoted 1 and 2. There are functional differences between the Hp 1 and Hp 2 protein products in protecting against hemoglobin-driven oxidative stress that appear to have important clinical significance. In particular, individuals with the Hp 2-2 genotype and diabetes mellitus appear to be at significantly higher risk of microvascular and macrovascular complications. A pharmacogenomic strategy of administering high dose antioxidants specifically to Hp 2-2 DM individuals may be clinically effective.

Background. We recently have shown a high incidence of unexplained pulmonary hypertension (PHT) in end-stage renal disease (ESRD) patients on chronic haemodialysis (HD) therapy via arterio-venous (A-V) access. This study evaluated the possibility that PHT in these patients is triggered or aggravated by chronic HD via surgical A-V access, and the role of endothelin-1 (ET-1) and nitric oxide (NO) in this syndrome. Methods. Forty-two HD patients underwent clinical evaluation. Pulmonary artery pressure (PAP) was evaluated using Doppler echocardiography. Levels of ET-1 and NO metabolites in plasma were determined before and after the HD procedure and were compared between subgroups of patients with and without PHT. Results. Out of 42 HD patients studied, 20 patients (48%) had PHT (PAP ¼ 46±2; range 36-82 mmHg) while the rest had a normal PAP (29±1 mmHg) (P<0.0001). HD patients with PHT had higher cardiac output compared with those with normal PAP (6.0±1.2 vs 5.2±0.9 l/min, P<0.034). HD patients, with or without PHT, had elevated plasma ET-1 levels compared with controls (1.6±0.7 and 2.4±0.8 fmol/ml vs 1.0±0.2, P<0.05) that remained unchanged after the HD procedure. HD patients without PHT and control subjects showed similar basal plasma levels of NO 2 þ NO 3 (24.2±5.2 vs 19.7±3.1 mM, P>0.05) that was significantly higher compared with HD patients with PHT (14.3±2.3 mM, P<0.05). HD therapy caused a significant increase in plasma NO metabolites that was greater in patients without PHT (from 24.2±5.2 to 77.1±9.6 mM, P<0.0001, and from 14.3±2.3 to 39.9±11.4 mM, P<0.0074, respectively). Significant declines in PAP (from 49.8±2.8 to 38.6±2.2 mmHg, P<0.004) and cardiac output (CO) (from 7.6±0.6 to 6.1±0.3 l/min, P<0.03) were found in 11 HD patients with PHT that underwent successful transplantation. Similarly, temporary closure of the A-V access by a sphygmomanometer in eight patients with PHT resulted in a transient decrease in CO (from 6.4±0.6 to 5.3± 0.5 l/min, P ¼ 0.18) and systolic PAP (from 47.2±3.8 to 34.6±2.8 mmHg, P<0.028).Conclusions. This study demonstrates a high prevalence of PHT among patients with ESRD on chronic HD via a surgical A-V fistula. In view of the vasodilatory and antimitogenic properties of NO, it is possible that the attenuated basal and HD-induced NO production in patients with PHT contributes to the increased pulmonary vascular tone. Furthermore, the partial restoration of normal PAP and CO in HD patients that underwent either temporal A-V shunt closure or successful transplantation indicates that excessive pulmonary blood flow is involved in the pathogenesis of the disease.