Husamettin Gul

Background: Multifactor dimensionality reduction (MDR) is a nonparametric approach that can be used to detect relevant interactions between single-nucleotide polymorphisms (SNPs). The aim of this study was to build the best genomic model based on SNP associations and to identify candidate polymorphisms that are the underlying molecular basis of the bipolar disorders. Methods: This study was performed on Whole-Genome Association Study of Bipolar Disorder (dbGaP [database of Genotypes and Phenotypes] study accession number: phs000017.v3.p1) data. After preprocessing of the genotyping data, three classification-based data mining methods (ie, random forest, naïve Bayes, and k-nearest neighbor) were performed. Additionally, as a nonparametric, model-free approach, the MDR method was used to evaluate the SNP profiles. The validity of these methods was evaluated using true classification rate, recall (sensitivity), precision (positive predictive value), and F-measure. Results: Random forests, naïve Bayes, and k-nearest neighbors identified 16, 13, and ten candidate SNPs, respectively. Surprisingly, the top six SNPs were reported by all three methods. Random forests and k-nearest neighbors were more successful than naïve Bayes, with recall values >0.95. On the other hand, MDR generated a model with comparable predictive performance based on five SNPs. Although different SNP profiles were identified in MDR compared to the classification-based models, all models mapped SNPs to the DOCK10 gene. Conclusion: Three classification-based data mining approaches, random forests, naïve Bayes, and k-nearest neighbors, have prioritized similar SNP profiles as predictors of bipolar disorders, in contrast to MDR, which has found different SNPs through analysis of two-way and three-way interactions. The reduced number of associated SNPs discovered by MDR, without loss in the classification performance, would facilitate validation studies and decision support models, and would reduce the cost to develop predictive and diagnostic tests. Nevertheless, we need to emphasize that translation of genomic models to the clinical setting requires models with higher classification performance.

Hyperinsulinism, one of the most important causes of hypoglycaemia, can be congenital or acquired. Rarely, drug toxicity can be a reason for hyperinsulinism. In the context of Munchausen syndrome by proxy (MSP), toxicity usually occurs in children due to drug administration by a parent or caregiver. A 7-year-old girl was referred to our department due to a hyperglycaemic period and hypoglycaemic episodes. On admission, gliclazide was initiated due to her hyperglycaemia, which we attributed to maturity onset diabetes of the young. However, during follow-up, hypoglycaemic levels were detected. Despite cessation of gliclazide, hypoglycaemic seizures occurred. Even with the medications administered, hypoglycaemia could not be prevented. During follow-up, the mother's affect, characterized by anxiety and interest in her daughter's medical care, appeared discordant with the situation. Due to our suspicion of MSP, we discovered toxic levels of gliclazide in the blood and urine samples which had been sent to the toxicology laboratory to search for hypoglycaemic agents. The patient was isolated, and all medications were stopped. After isolation, her hypoglycaemia disappeared, and she became hyperglycaemic (250 mg/dl). Physicians should consider the possibility of MSP in hyperinsulinaemic patients with discordant laboratory results and clinical symptoms, even if the child's parents display great concern.

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon γ and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1β (TGF-1β) levels were significantly higher than the sham group (in all, p < 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p = 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1β levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Aim: To establish age- and sex-specific reference intervals for essential amino acids in a healthy Turkish pediatric population. Materials and methods: A total of 945 clinically healthy children (531 boys and 414 girls, ranging in age from birth to 14 years) were enrolled. Plasma and urine amino acids' concentrations were measured by high-performance liquid chromatography. Results: Concentrations of essential amino acids in plasma were higher in girls than in boys in the age groups of 0-1 months and 7-14 years; however, there was no difference in the other age groups. Concentrations of essential amino acids in urine were higher in girls than in boys in the age group of 0-1 months; however, there was no difference in the other age groups. Our results demonstrated the sex-related differences in concentrations of leucine, isoleucine, valine, phenylalanine, lysine, and histidine in plasma, which increased with age in boys but not in girls. The concentrations of leucine, tryptophan, methionine, and lysine in urine declined with age in girls but not in boys, which were sex-related differences, too. Conclusion: We defined essential amino acids' reference intervals in a Turkish pediatric population.

Background/aim: Despite the rise in type 2 diabetes prevalence worldwide, we do not have a method for early risk prediction. The predictive ability of genetic models has been found to be little or negligible so far. In this study, we aimed to develop a better early risk prediction method for type 2 diabetes. Materials and methods: We used phenotypic and genotypic data from the Nurses' Health Study and Health Professionals' Follow-up Study cohorts and analyzed them by using binary logistic regression. Results: Phenotypic variables yielded 70.7% overall correctness and an area under the curve (AUC) of 0.77. With regard to genotype, 798 single nucleotide polymorphisms with P-values of lower than 1.0E-3 yielded 90.0% correctness and an AUC of 0.965. This is the highest score in the literature, even including the scores obtained with phenotypic variables. The additive contributions of phenotype and genotype increased the overall correctness to 92.9% and the AUC to 0.980. Conclusion: Our results showed that genotype could be used to obtain a higher score, which could enable early risk prediction. These findings present new possibilities for genome-wide association study analysis in terms of discovering missing heritability. These results should be confirmed by follow-up studies.

Pulmonary fibrosis (PF) is a progressive fatal disorder. Bleomycin (BLM) is a widely used chemotherapeutic agent causing PF. Numerous agents have been investigated to prevent the progression of PF so far, but there is still a need to find more efficacious agents. Proanthocyanidin (PA) is a strong antioxidant, the main ingredient of grape seed extract. Since PA is ready for use in practice, we aimed to compare the preventive effect of PA in comparison with taurine (Tau) in BLM-induced PF. Forty Wistar male albino rats were used in the study and were divided into four groups: group 1, control; group 2, BLM-induced PF group; group 3, BLM-induced PF and treated with PA group; and group 4, BLM-induced PF and treated with Tau group. Treatments were begun 10 days before and continued 21 days after BLM injection. PA and Tau effectively inhibited inflammation, edema, severity of fibrosis, fibrosis extension, inflammatory cell accumulation, iNOS staining, and hydroxyproline level as well (p < 0.05). Total histological scores of the PA group were similar to the control group; Tau was significantly higher than the control group but lower than the BLM group (p < 0.05). We believe that PA could be a new treatment choice for PF, but further studies need to be conducted to verify the findings of the current study.