Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders

Role of 11C-acetate and 18F FDG dual tracer PET-CT scan for detection of hepatocellular carcinoma

PURPOSE: Up to 45% of Hepatocellular Carcinoma (HCC) show atypical contrast enhancement (CE) pattern on CT/MR, thereby requiring histologic confirmation. The aim of this study is to evaluate the additional value of Dual Tracer (DT) PET with 11C Acetate (Ac) and 18F FDG for detection and characterization of HCC. MATERIAL & METHOD: Consecutive patients who had histological confirmation of HCC and underwent CT/MR and DT in our centres from 2014-16 were identified. CE and PET uptake patterns were reviewed. Typical CE pattern on CT/MR was arterial hyper-enhancement followed by portovenous/delayed phase washout. All other CE patterns were considered atypical. On PET, a lesion was deemed positive by visual inspection of lesion above background liver uptake on Ac and/or FDG. Results were compared with tumor size and grade on histology. Tumour size were separated into 5 cm groups as each has different treatment option. Grading was based on Edmondson and Steiner system. Pearson’s Chi-Square tests were applied to compare the sensitivities and ANOVA-test for subgroup analysis. RESULTS: Thirty-two HCC lesions from 24 patients were identified (mean size SD 34 27 mm). The sensitivity of CT/MR by CE pattern was 53%, FDG alone 56%, Ac alone 94%, DT 97% and combined CT/MR with DT 100% (p5cm respectively. Histological grade available in 30 lesions were well differentiated HCC (n=7), moderately-differentiated HCC (n=22) and poorly differentiated HCC (n=1). Atypical enhancement pattern was more common in well-differentiated compared to moderately-differentiated lesions (71% vs 45%). No trend was observed for tracer avidities in different grades of HCC. CONCLUSION: DT combined with CT/MR increases the sensitivity of HCC detection compared to CT/MR alone, providing 100% sensitivity and hence, being most helpful in equivocal liver lesions with atypical contrast enhancement. CLINICAL RELEVANCE: The use of DT obviates tissue sampling for diagnosing HCC in patients with liver lesions with atypical CT/MR contrast enhancement

Management of spontaneous perforation of esophageal cancer with covered self expanding metallic stents

Optimal management of esophageal perforation is controversial, especially in the presence of malignancy. Esophagectomy has traditionally been employed for patients with malignant perforations. However, in patients with advanced disease, other less invasive treatment options may be of benefit. We present two cases of spontaneous perforation of advanced esophageal cancer successfully managed by insertion of covered self-expanding metallic stents and a review of the literature. © 2005 ISDE.link_to_subscribed_fulltex