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.
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 I2 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 × 10−6), 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 <10−5). 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 × 10−50), 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; sensi...
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.
Objective: Endovenous foam sclerotherapy (EFS) is widely performed in the U.S, but there is a paucity of studies evaluating clinical predictors of outcomes, including biomarkers, in patients with venous disorders. Methods:Patients undergoing EFS monotherapy for venous disorders were enrolled. Evaluation at baseline, 1 week, 12 weeks, and 26 weeks included clinical characteristics and biomarker analysis.Results: 100 patients with venous disease were treated. At one week follow-up, 44% underwent a second injection. At 3 months, 100% of patients had obliteration of at least 80% of their affected veins, and 96% reported improved venous stasis symptoms. Adverse events were minor and deep vein thrombosis was found 4 patients at 3 months. D-dimer levels were significantly higher at week one, but returned to baseline by week 12; fibrin monomer decreased and PPL increased at one week and 3 months relative to baseline. Conclusion:EFS monotherapy is effective in treating signs and symptoms of venous disease with few adverse effects. D-dimer levels are significantly associated with obliteration of venous segments suggesting an association between vein obliteration and activation of coagulation.
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