Assessment of Translational and Interdisciplinary Clinical Research at an Oklahoma Health Sciences Center.

PURPOSE: In response to National Institutes of Health initiatives to improve translation of basic science discoveries we surveyed faculty to assess patterns of and barriers to translational research in Oklahoma. METHODS: An online survey was administered to University of Oklahoma Health Sciences Center, College of Medicine faculty, which included demographic and research questions. Results: Responses were received from 126 faculty members (24%). Two-thirds spent ≥ 20%time on research; among these, 90% conduct clinical and translational research. Identifying funding; recruiting research staff and participants; preparing reports and agreements; and protecting research time were commonly perceived as at least moderate barriers to conducting research. While respondents largely collaborated within their discipline, clinical investigators were more likely than basic science investigators to engage in interdisciplinary research. CONCLUSION: While engagement in translational research is common, specific barriers impact the research process. This could be improved through an expanded interdisciplinary collaboration and research support structure.

No association of genetic variants in BDNF with major depression: a meta- and gene-based analysis.

Major depressive disorder (MDD) is a complex psychiatric condition with strong genetic predisposition. The association of MDD with genetic polymorphisms, such as Val66Met (rs6265), in the brain derived neurotrophic factor (BDNF), have been reported in many studies and the results were conflicting. In this study, we performed a systematic literature search and conducted random-effects meta-analysis to evaluate genetic variants in BDNF with MDD. A gene-based analysis was also conducted to investigate the cumulative effects of genetic polymorphisms in BDNF. A total of 28 studies from 26 published articles were included in our analysis. Meta-analysis yielded an estimated odds ratio (OR) of 0.96 (95% CI: 0.89-1.05; P = 0.402) for Val66Met (rs6265), 0.83 (95% CI: 0.67-1.04; P = 0.103) for 11757C/G, 1.16 (95% CI: 0.74-1.82; P = 0.527) for 270T/C, 1.03 (95% CI: 0.18-5.75; P = 0.974) for 712A/G and 0.98 (95% CI: 0.85-1.14; P = 0.831) for rs988748. The gene-based analysis indicated that BDNF is not associated with MDD (P > 0.21). Our updated meta- and novel gene-based analyses provide no evidence of the association of BDNF with major depression.

No association of genetic polymorphisms in CYP1B1 with primary open-angle glaucoma: a meta- and gene-based analysis.

PURPOSE: To examine the effects of genetic polymorphisms in cytochrome P450, subfamily 1, polypeptide 1 (C1P1B1) on primary open-angle glaucoma (POAG). METHODS: A systematic literature search was performed, and random-effects meta-analyses were used to evaluate genetic polymorphisms in CYP1B1 with POAG. A gene-based analysis was conducted to investigate the cumulative effects of genetic polymorphisms in CYP1B1. RESULTS: A total of six studies from published papers were included in our analysis. Random-effects meta-analyses failed to detect any significant association of POAG with genetic polymorphisms in CYP1B1, including rs180040, rs1056836, rs10012, rs1056827, rs1056837, and rs2567206. The gene-based analysis indicated that the cumulative effect of genetic polymorphisms in CYP1B1 is not associated with POAG (p>0.50). CONCLUSIONS: We did not find any evidence of strong association of POAG with CYP1B1 genetic polymorphisms and their cumulative effect.

Orientation of the round window membrane: A normative study of inner ear anatomical orientation using 2D projections of 3D volumes.

INTRODUCTION: Orientation of the Round Window Membrane (RWM) is an important metric to establish if utilized as a potential access for targeted delivery of magnetically guided nanomedicines to the inner ear. Orientation with respect to an internal reference frame (such as the planes defined by the semicircular-canals [SCC]) may provide an internally consistent basis if the basis is orthogonal and consistent (from patient to patient). MATERIALS AND METHODS: Utilizing a micro computed tomography (CT), 20 temporal bones are scanned for anatomical information. The scanned data sets are loaded into an imaging program to provide volumetric reconstruction and segmentation. Volumetric models of the anatomical relationships between the inner ear SCC and the RWM are utilized to get normative projection angle information and are statistically analyzed. RESULTS: Micro-CT shows low to moderate reliability for reproducibility, intraobserver, and interobserver measurements; in addition, it provides mean values (±SD) for the various measured angles. The combined mean angular values for surface orientation of the RWM, with respect to the SCC basis (quasi-orthogonal spherical coordinate system), was 57.0° ± 20.9°as measured from the line defining the posterior SCC plane in the direction of the line defining the superior SCC plane. An angle of 65.2° ± 19.1° was measured for an angle away from the line defining the horizontal SCC plane.

Association of genetic variants in and promoter hypermethylation of CDH1 with gastric cancer: a meta-analysis.

Gastric cancer (GC) is a common cause of cancer-related death. The etiology and pathogenesis of GC remain unclear, with genetic and epigenetic factors playing an important role. Previous studies investigated the association of GC with many genetic variants in and promoter hypermethylation of E-cadherin gene (CDH1), with conflicting results reported.To clarify this inconsistency, we conducted updated meta-analyses to assess the association of genetic variants in and the promoter hypermethylation of CDH1 with GC, including C-160A (rs16260) and other less-studied genetic variants,Data sources were PubMed, Cochrane Library, Google Scholar, Web of Knowledge, and HuGE, a navigator for human genome epidemiology.Study eligibility criteria and participant details are as follows: studies were conducted on human subjects; outcomes of interest include GC; report of genotype data of individual genetic variants in (or methylation status of) CDH1 in participants with and without GC (or providing odds ratios [OR] and their variances).Study appraisal and synthesis methods included the use of OR as a measure of the association, calculated from random effects models in meta-analyses. We used I for the assessment of between-study heterogeneity, and publication bias was assessed using funnel plot and Egger test.A total of 33 studies from 30 published articles met the eligibility criteria and were included in our analyses. We found no association between C-160A and GC (OR = 0.88; 95% confidence interval [CI], 0.71-1.08; P = 0.215), assuming an additive model (reference allele C). C-160A was associated with cardia (OR = 0.21; 95% CI, 0.11-0.41; P = 2.60 × 10), intestinal (OR = 0.66; 95% CI, 0.49-0.90; P = 0.008), and diffuse GC (OR = 0.57; 95% CI, 0.40-0.82; P = 0.002). The association of C-160A with noncardia GC is of bottom line significance (OR = 0.65; 95% CI, 0.42-1.01; P = 0.054). Multiple other less-studied genetic variants in CDH1 also exhibited association with GC. Gene-based analysis indicated a significant cumulative association of genetic variants in CDH1 with GC (all Ps <10). Sensitivity analysis excluding studies not meeting Hardy-Weinberg equilibrium (HWE) yielded similar results. Analysis by ethnic groups revealed significant association of C-160A with cardia GC in both Asian and whites, significant association with noncardia GC only in Asians, and no significant association with intestinal GC in both ethnic groups. There was significant association of C160-A with diffuse GC in Asians (P = 0.011) but not in whites (P = 0.081). However, after excluding studies that violate HWE, this observed association is no longer significant (P = 0.126). We observed strong association of promoter hypermethylation of CDH1 with GC (OR = 12.23; 95% CI, 8.80-17.00; P = 1.42 × 10), suggesting that epigenetic regulation of CDH1 could play a critical role in the etiology of GC.Limitations of this study are as follows: we could not adjust for confounding factors; some meta-analyses were based on a small number of studies; sensitivity analysis was limited due to unavailability of data; we could not test publication bias for some meta-analyses due to small number of included studies.We found no significant association of the widely studied genetic variant C-160A, but identified some other genetic variants showing significant association with GC. Future studies with large sample sizes that control for confounding risk factors and/or intensively interrogate CpG sites in CDH1 are needed to validate the results found in this study and to explore additional epigenetic loci that affect GC risk.