Demet Tekin

Bio: Demet Tekin is an academic researcher from Ankara University. The author has contributed to research in topics: Hypoxia (medical) & Intermittent hypoxia. The author has an hindex of 13, co-authored 23 publications receiving 633 citations. Previous affiliations of Demet Tekin include John P. Hussman Institute for Human Genomics & Virginia Commonwealth University.

Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents

Abstract: Hearing loss is the most common sensory deficit in humans with causative variants in over 140 genes. With few exceptions, however, the population-specific distribution for many of the identified variants/genes is unclear. Until recently, the extensive genetic and clinical heterogeneity of deafness precluded comprehensive genetic analysis. Here, using a custom capture panel (MiamiOtoGenes), we undertook a targeted sequencing of 180 genes in a multi-ethnic cohort of 342 GJB2 mutation-negative deaf probands from South Africa, Nigeria, Tunisia, Turkey, Iran, India, Guatemala, and the United States (South Florida). We detected causative DNA variants in 25 % of multiplex and 7 % of simplex families. The detection rate varied between 0 and 57 % based on ethnicity, with Guatemala and Iran at the lower and higher end of the spectrum, respectively. We detected causative variants within 27 genes without predominant recurring pathogenic variants. The most commonly implicated genes include MYO15A, SLC26A4, USH2A, MYO7A, MYO6, and TRIOBP. Overall, our study highlights the importance of family history and generation of databases for multiple ethnically discrete populations to improve our ability to detect and accurately interpret genetic variants for pathogenicity.

Identifying Consensus Disease Pathways in Parkinson's Disease Using an Integrative Systems Biology Approach

Abstract: Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p<0.01) from a joint analysis of three existing PD GWAS were identified and each assigned to a gene. For gene expression, rather than the traditional comparison of one anatomical region between sets of patients and controls, we identified differentially expressed genes between adjacent Braak regions in each individual and adjusted using average control expression profiles. Over-represented pathways were calculated using a hyper-geometric statistical comparison. An integrated, systems meta-analysis of the over-represented pathways combined the expression and GWAS results using a Fisher's combined probability test. Four of the top seven pathways from each approach were identical. The top three pathways in the meta-analysis, with their corrected p-values, were axonal guidance (p = 2.8E-07), focal adhesion (p = 7.7E-06) and calcium signaling (p = 2.9E-05). These results support that a systems biology (pathway) approach will provide additional insight into the genetic etiology of PD and that these pathways have both biological and statistical support to be important in PD.

Evidence that NOS2 acts as a trigger and mediator of late preconditioning induced by acute systemic hypoxia.

Abstract: Chronic systemic hypoxia (SH) enhances myocardial ischemic tolerance in mammals. We studied the delayed cardioprotection caused by acute SH and associated signaling mechanism. Conscious adult male ...

Influence of knee osteoarthritis on exercise capacity and quality of life in obese adults.

Abstract: Objective: The objective was to determine whether knee osteoarthritis (OA) reduces exercise ambulatory capacity and impairs quality of life (QOL) in obese individuals. Research Methods and Procedures: There were 56 subjects, with and without knee OA, who were obese. The subjects were evaluated with anthropometric measurements, a body composition assessment, maximal cardiopulmonary exercise test, 6-minute walk test (6-MWT), perceived exertion (RPE), self-reported disability [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)], and the Medical Outcomes Study Short Form 36 (SF-36). Results: VO2peak was significantly higher in the controls when compared with the patients (mean ± standard deviation, 1.584 ± 0.23 L/kg per min vs. 0.986 ± 0.20 L/kg per min; p < 0.001). Obese subjects without knee OA walked a significantly longer distance in the 6-MWT than obese patients with knee OA (p < 0.001). We also observed significant negative correlation between Vo2max and RPE, WOMAC pain and physical limitation, and bodily pain and general health domains of short-form 36. Discussion: Knee OA reduces exercise and ambulatory capacity and impairs QOL in obese individuals. RPE, WOMAC pain, and SF-36 items might provide information about exercise capacity in the obese subjects with knee OA. Our study confirms that exercise capacity and QOL might be improved by energetic and intensive treatment of pain resulting from knee OA.

Possible effects of antioxidant status on increased platelet aggregation in childhood iron-deficiency anemia.

Abstract: Background: Alterations in platelet function and antioxidant status in children with iron-deficiency anemia (IDA) have been reported previously The present study was performed to better understand possible interactions between these two systems Methods: Erythrocyte superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activity and platelet function were evaluated in 15 children (aged 11/2–15 years) with IDA The antioxidant enzyme activity was determined spectrophotometrically Platelet aggregation and secretion studies were performed using impedance and bioluminescence methods, respectively Ten age-matched healthy children were included as a control group Results: There were no differences in SOD and CAT activities between patients and controls However, GSH-Px activity was significantly lower in the iron-deficient children Platelet aggregation responses to collagen and ADP were also significantly higher in iron-deficient children than in controls Conclusions: Decreased antioxidant defense in IDA may cause increased oxidant stress, which, in turn, may result in a tendency towards platelet aggregation

The Medical Risks of Obesity

Abstract: Obesity is associated with a number of medical conditions that lead to increased morbidity and increased mortality. Both the National Institutes of Health and the World Health Organization define obesity as a body mass index (BMI) > or = 30 kg/m2 and overweight as a BMI 25-30. The most common conditions associated with obesity are insulin resistance, diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, gallstones and cholecystitis, sleep apnea and other respiratory dysfunction, and the increased incidence of certain cancers. These are discussed below.

Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

Abstract: Objective: To formulate clinical practice guidelines for the pharmacological management of obesity. Participants: An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. This guideline was co-sponsored by the European Society of Endocrinology and The Obesity Society. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the European Society of Endocrinology, and The Obesity Society reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize some of the supporting evidence. Conclusions: Weight loss is a pathway to health improvement for patients with obesity-associated risk factors and comorbidit...

The late phase of preconditioning.

Abstract: —Unlike the early phase of preconditioning (PC), which lasts 2 to 3 hours and protects against infarction but not against stunning, the late phase of PC lasts 3 to 4 days and protects against both infarction and stunning, suggesting that it may have greater clinical relevance. It is now clear that late PC is a polygenic phenomenon that requires the simultaneous activation of multiple stress-responsive genes. Chemical signals released by a sublethal ischemic stress (such as NO, reactive oxygen species, and adenosine) trigger a complex cascade of signaling events that includes the activation of protein kinase C, Src protein tyrosine kinases, and nuclear factor κB and culminates in increased synthesis of inducible NO synthase, cyclooxygenase-2, aldose reductase, Mn superoxide dismutase, and probably other cardioprotective proteins. An analogous sequence of events can be triggered by a variety of stimuli, such as heat stress, exercise, and cytokines. Thus, late PC appears to be a universal response of the heart to stress in general. Importantly, the cardioprotective effects of late PC can be reproduced pharmacologically with clinically relevant agents (eg, NO donors, adenosine receptor agonists, endotoxin derivatives, or opioid receptor agonists), suggesting that this phenomenon might be exploited for therapeutic purposes. The purpose of this review is to summarize current information regarding the pathophysiology and mechanism of late PC.