Schizophrenia is a common, clinically heterogeneous disorder associated with lifelong morbidity and early mortality. Several genetic variants associated with schizophrenia have been identified, but the majority of the heritability remains unknown. In this study, we report on a case-control sample of Ashkenazi Jews (AJ), a founder population that may provide additional insights into genetic etiology of schizophrenia. We performed a genome-wide association analysis (GWAS) of 592 cases and 505 controls of AJ ancestry ascertained in the US. Subsequently, we performed a meta-analysis with an Israeli AJ sample of 913 cases and 1640 controls, followed by a meta-analysis and polygenic risk scoring using summary results from Psychiatric GWAS Consortium 2 schizophrenia study. The U.S. AJ sample showed strong evidence of polygenic inheritance (pseudo-R(2) ∼9.7%) and a SNP-heritability estimate of 0.39 (P = 0.00046). We found no genome-wide significant associations in the U.S. sample or in the combined US/Israeli AJ meta-analysis of 1505 cases and 2145 controls. The strongest AJ specific associations (P-values in 10(-6) -10(-7) range) were in the 22q 11.2 deletion region and included the genes TBX1, GLN1, and COMT. Supportive evidence (meta P < 1 × 10(-4) ) was also found for several previously identified genome-wide significant findings, including the HLA region, CNTN4, IMMP2L, and GRIN2A. The meta-analysis of the U.S. sample with the PGC2 results provided initial genome-wide significant evidence for six new loci. Among the novel potential susceptibility genes is PEPD, a gene involved in proline metabolism, which is associated with a Mendelian disorder characterized by developmental delay and cognitive deficits.

Background:Whether methylation of the microRNA (mir)-124-3 CpG island is of relevance for the clinical course of a solid cancer and whether it shows association with clinicopathology or survival of patients with renal cell cancer (RCC) is not known as yet.Methods:In a cross-sectional study, relative methylation of mir-124-3 was measured in 111 RCC samples and 77 paired normal appearing tissues using quantitative methyl-specific PCR. Results were statistically compared with tumour histology, clinicopathological parameters and disease recurrence.Results:We found tumour-specific hypermethylation of mir-124-3 in samples of RCCs with clear cell histology (ccRCC) compared with paired normal appearing tissues (P<0.0001). Methylation was significantly increased in tumours with state of advanced disease (P<0.0001). Higher relative methylation was associated with worse recurrence-free survival in both univariate (hazard ratio=9.37; P=0.0005) as well as bivariate Cox regression analyses considering age, sex, diameter of tumours and state of advanced disease, metastasis and lymph node metastases as covariates (hazard ratios=5.9–18.2; P-values of 0.0003–0.008).Conclusion:We identified mir-124-3 CpG islands (CGI) methylation as a relevant epigenetic mark for ccRCC thus underlining the need for functional studies of potentially affected signalling pathways in kidney tumour models. Methylation of mir-124-3 is suggested as an independent prognosticator for ccRCC.

Purpose To evaluate transrectal (TR) and transperineal (TP) approaches for MRI/ultrasound (MRI/US) fusion-guided biopsy to detect prostate cancer (PCa). Materials and Methods 154 men underwent multiparametric MRI and MRI/US fusion-guided biopsy between July 2012 and October 2016. 79/154 patients were biopsied with a TR approach and 75/154 with a TP approach. MRI was retrospectively analyzed according to PI-RADS version 2. PI-RADS scores were compared with histopathological results. Descriptive statistics, accuracy, and negative and positive predictive values were calculated. Histopathological results of first, second, and third MRI targeted biopsy cores were compared to evaluate the impact of one verus multiple targeted cores. Results Detection rates of PCa were 39% for TR biopsy and 75% for TP biopsy. Sensitivity/specificity for tumor detection with PI-RADS ≥ 4 were 81/69% for TR biopsy and 86/84% for TP biopsy. In 31% for TR biopsy and 19% for TP biopsy, PCa was found in the second or third MRI targeted biopsy core only. Conclusion MRI/US fusion-guided biopsy may be conducted with the TR as well as the TP approach with high accuracy, giving more flexibility for diagnosis and the option for focal treatment of PCa.

In patients with cervical spine fractures or dislocations crossing the course of the vertebral artery, VAI are relatively frequent and may be associated with significant morbidity and mortality. VAI were identified by DSA in 27.5%. Despite anticoagulation therapy, 5.8% became clinically symptomatic and 2.9% died due to cerebrovascular ischemia.

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