Collaborative Mining of Whole Genome Sequences for Intelligent HIV-1 Sub-Strain(s) Discovery.

BACKGROUND: Effective global antiretroviral vaccines and therapeutic strategies depend on the diversity, evolution, and epidemiology of their various strains as well as their transmission and pathogenesis. Most viral disease-causing particles are clustered into a taxonomy of subtypes to suggest pointers toward nucleotide-specific vaccines or therapeutic applications of clinical significance sufficient for sequence-specific diagnosis and homologous viral studies. These are very useful to formulate predictors to induce cross-resistance to some retroviral control drugs being used across study areas. OBJECTIVE: This research proposed a collaborative framework of hybridized (Machine Learning and Natural Language Processing) techniques to discover hidden genome patterns and feature predictors for HIV-1 genome sequences mining. METHODS: 630 human HIV-1 genome sequences above 8500 bps were excavated from the National Center for Biotechnology Information (NCBI) database (https://www.ncbi.nlm.nih.gov) for 21 countries across different continents, except for Antarctica. These sequences were transformed and learned using a self-organizing map (SOM). To discriminate emerging/new sub-strain(s), the HIV-1 reference genome was included as part of the input isolates/samples during the training. After training the SOM, component planes defining pattern clusters of the input datasets were generated for cognitive knowledge mining and subsequent labeling of the datasets. Additional genome features, including dinucleotide transmission recurrences, codon recurrences, and mutation recurrences, were finally extracted from the raw genomes to construct output classification targets for supervised learning. RESULTS: SOM training explains the inherent pattern diversity of HIV-1 genomes as well as interand intra-country transmissions in which mobility might play an active role, as corroborated by the literature. Nine sub-strains were discovered after disassembling the SOM correlation hunting matrix space attributed to disparate clusters. Cognitive knowledge mining separated similar pattern clusters bounded by a certain degree of correlation range, as discovered by the SOM. Kruskal-Wallis ranksum test and Wilcoxon rank-sum test showed statistically significant variations in dinucleotide, codon, and mutation patterns. CONCLUSION: Results of the discovered sub-strains and response clusters visualizations corroborate the existing literature, with significant haplotype variations. The proposed framework would assist in the development of decision support systems for easy contact tracing, infectious disease surveillance, and studying the progressive evolution of the reference HIV-1 genome.

Serum Testosterone, 17ß-Estradiol and PSA Levels in Subjects with Prostate Disorders.

Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death as a result of cancer in men in the US and other parts of the world. There are conflicting reports on the serum levels of testosterone and 17ß-estradiol (E2) in benign prostatic hyperplasia (BPH) and prostate cancer. This study was designed to evaluate the serum concentrations of these hormones in patients with these disorders. Serum levels of prostate specific antigen (PSA), total testosterone and estradiol were determined in 228 subjects comprising of 116 subjects with BPH, 62 subjects with prostate cancer (CaP) and 50 age-matched apparently healthy controls, using ELISA methods. PSA levels were significantly elevated (p < 0.05) in BPH subjects than controls, while there was no significant difference (p > 0.05) in testosterone and estradiol levels of these subjects. PSA and estradiol levels were significantly higher (p < 0.05) in CaP subjects than in controls, while there was no observed significant difference (p > 0.05) in testosterone levels. CaP subjects had significantly raised PSA, testosterone, and estradiol levels than BPH subjects. The mean molar ratio of testosterone: E2 was lowest among CaP patients (134:1) and highest among controls (166:1). Significant positive correlation between PSA and 17ß-estradiol was observed in prostate disorders (BPH and CaP patients: r = 0.347; p = 0.000). Significant negative correlations between testosterone and PSA were also observed among BPH patients (r = -0.221, p = 0.049) and control subjects (r = -0.490, p = 0.000). No significant correlation existed between testosterone and PSA in CaP patients (r = 0.051, p = 0.693). Correlations between age and estradiol in both BPH and CaP were not significant (p > 0.05). This study has shown that, there was a significant increase in serum estradiol in CaP subjects, while the testosterone levels in both BPH and CaP subjects were not different from those of controls.

Urate synthesis and oxidative stress in phenytoin hepatotoxicity: the role of antioxidant vitamins.

Phenytoin is known to induce microsomal enzymes including xanthine oxidase which catalyzes uric acid synthesis with superoxides as byproducts, thus contributing to the oxidative stress of phenytoin hepatotoxicity. To investigate the role of antioxidant vitamins in ameliorating phenytoin induced hepatic changes through possible actions on xanthine oxidase activities as measured by urate concentration. Growing albino rats of Wistar strain were randomly divided into 8 groups of 7 rats each. Group 2, 3, 4, 5, 6, 7 and 8 were treated with phenytoin alone, phenytoin + folic acid, phenytoin + vitamin E, phenytoin + vitamin E + vitamin C, phenytoin + vitamin C, phenytoin + folic acid + vitamin E and phenytoin + vitamin E + vitamin C + folic acid respectively while animals in group 1 were given normal saline to serve as control. Serum concentrations of uric acid, albumin, total protein and the activities of aspartate and alanine aminotransferases (AST and ALT) and catalase were measured spectrophotometrically using appropriate commercial reagent kits. Result showed that administration of phenytoin alone caused significant (p < 0.05) increase in serum levels of globulin, uric acid, AST and ALT activities while the levels of albumin and catalase were reduced significantly (p < 0.05). Supplementation of phenytoin treatment with vitamins resulted in various degrees of protection. However, the elevated level of uric acid in serum was not significantly (p < 0.05) affected by any of the vitamins used and there was no significant correlation between the activities of aminotransferases and uric acid concentration in the vitamin treated animals as was observed between aminotransferases and catalase. The findings in this study suggest that antioxidant vitamins were able to ameliorate phenytoin hepatotoxic effects by improving oxidant radicals removal in the animals but would not inhibit further generation of the superoxides by xanthine oxidase activity and that xanthine oxidase may contribute significantly to the oxidative stress of phenytoin therapy.

Plasma fibronectin concentration in obese/overweight pregnant women: a possible risk factor for preeclampsia.

Plasma fibronectin (FN) levels in obese/overweight and non-obese pregnant women were evaluated as a possible risk factor for preeclampsia. A total of one hundred and sixty three pregnant women attending antenatal clinic at University of Calabar Teaching Hospital participated in the study and sixty non-pregnant women served as control. About 77 (47.24%) of the pregnant women were followed up for any subsequent development of preeclampsia during the pregnancy. Fibronectin levels in plasma were measured by ELISA assay and serum total protein, urea and creatinine were determined spectrophotometrically. The mean plasma FN concentration of non-obese pregnant women in first trimester was lower than those of the non-pregnant women by 24%, but however, increased to the non-pregnant level in second and third trimesters. Obese/overweight pregnant women had significantly (P < 0.05) higher values than non-obese pregnant women in second and third trimesters. FN in obese/overweight pregnant women correlated positively with mean arterial blood pressure (MAP: r = 0.414, P = 0.04). About 28.57% of the pregnant women with FN above cut off point of 330 µg/ml at 18-24 weeks of gestation developed preeclampsia. This value increased to 40.0% when only the obese/overweight women were considered. On analysis of both fibronectin >330 µg/ml and MAP > 90, the predictive value increased to 66.7%. We therefore conclude that elevated FN may be regarded as a risk factor of preeclampsia especially among the obese women.

The Hepatoprotective Effect of Vitamin A against Gasoline Vapor Toxicity in Rats.

BACKGROUND: Changes in the activities of plasma alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP) are used to assess the functional state of the liver. Significant increase in the activities of these enzymes commonly indicates the hepatotoxicity of chemical agent(s) in the body. Exposure of male and female rats to 17.8 cm3h-1m-3 of Premium Motor Spirit (PMS) blend unleaded gasoline (UG) vapors for 6 hr/day, 5 days/week for 20 weeks have been observed to cause hepatotoxicity. In this study, the potential hepatoprotective effect of vitamin A (retinol) against gasoline vapours-induced toxicity was investigated in male and female rats. METHODS: Retinol (400 IU/kg/day) was orally administered to the test rats concomitant with the gasoline vapor exposure in the last two weeks of the experiment. RESULTS: The results obtained from this study showed that exposure to gasoline vapors caused significant increase (P < 0.05) in the activities of serum ALT, AST, ALP, GGT and bilirubin in both male and female rats. The treatment of the male and female test rats with vitamin A produced a significant decrease (P < 0.05) in the activities of these parameters, compared with the test rats without treatment; but insignificant increase(P ≥ 0.05), compared with the control. CONCLUSIONS: The result of this study demonstrates the beneficial effects of retinol, at prophylactic dosage, against gasoline vapours hepatotoxicity in male and female rats, thereby suggesting that retinol may be used to prevent hepatotoxicity in individuals frequently exposed to gasoline vapours.

Effect of folic acid and vitamin B(12) administration on phenytoin induced toxicity in rats.

Folic acid and vitamin B(12) are very important vitamins needed for normal cellular metabolic activities. The effects of folic acid and vitamin B(12) on liver integrity of growing Wistar albino rats following therapeutic dose of phenytoin administration were investigated. The activities of serum AST, ALT, ALP were investigated. Serum total protein level and lipid profile were also measured as indices of biochemical changes. The ingestion of phenytoin alone in rats significantly reduced serum protein while AST, ALT activities incresed as compared to the control (P<0.05). Supplementation of phenytoin with oral administration of 70microgram/kg body wt of folic acid resulted in a significant reversal in serum total protein and suppression in serum AST and ALT activities. Vitamin B(12) supplementation did not afford any significant protection against the effect of phenytoin ingestion but rather phenytoin toxicity was exacerbated in this study. However, the combined effects of vitamin B(12) and folic acid ameliorated the effects of phenytoin on serum enzymes of experimental rats. The effect of combination of phenytoin with folic acid or folic acid and vitamin B(12) is an interesting finding. Supplementation of phenytoin with folic acid or combination of these vitamins may be recommended for the purpose of ameliorating the adverse biochemical changes which are associated with phenytoin therapy. Further work is ongoing to help elucidate the effects of phenytoin and these vitamins on oxidative stress inducing mechanism.