Evidence for somatic gene conversion and deletion in bipolar disorder,Crohn's disease,coronary artery disease,hypertension, rheumatoid arthritis,type-1 diabetes,and type-2 diabetes

Background  

During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale.     

Wernicke's Encephalopathy Presenting as Acute Psychosis after Gastric Bypass

Background and Objectives: Patients frequently present to the Emergency Department (ED) with psychiatric complaints. The differential diagnosis for acute psychosis is extensive, and determining a possible etiology requires a thorough history and physical. Small details can help the physician in differentiating organic disease from non-organic disease. Many times patients are thought to be “crazy” without a thorough history and physical being done. Case Report: In this case, the diagnosis hinged on the history of having gastric bypass surgery. A thorough physical examination was performed, and the patient had neurologic findings suggestive of severe thiamine deficiency. The patient's thiamine level was low. The patient was started on i.v. thiamine and slowly began to recover. Conclusion: Cerebral beriberi, more commonly known as Wernicke's encephalopathy, is a difficult diagnosis to make in the ED. A thorough neurologic examination is difficult to perform in the ED environment, but it is necessary when trying to determine the etiology of the patient's altered mental status. The number of patients with Wernicke's encephalopathy may increase with bariatric surgery becoming more common. This disease can present with a wide variety of findings, and the classic triad is not very common. With this in mind, the physician should have a low threshold for administering thiamine intravenously.     

Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms

Variable clinical responses, tumor heterogeneity, and drug resistance reduce long-term survival outcomes for metastatic melanoma patients. To guide and accelerate drug development, we characterized tumor responses for five melanoma patient derived xenograft models treated with Vemurafenib. Three BRAF^V600E models showed acquired drug resistance, one BRAF^V600E model had a complete and durable response, and a BRAF^V600V model was expectedly unresponsive. In progressing tumors, a variety of resistance mechanisms to BRAF inhibition were uncovered, including mutant BRAF alternative splicing, NRAS mutation, COT (MAP3K8) overexpression, and increased mutant BRAF gene amplification and copy number. The resistance mechanisms among the patient derived xenograft models were similar to the resistance pathways identified in clinical specimens from patients progressing on BRAF inhibitor therapy. In addition, there was both inter- and intra-patient heterogeneity in resistance mechanisms, accompanied by heterogeneous pERK expression immunostaining profiles. MEK monotherapy of Vemurafenib-resistant tumors caused toxicity and acquired drug resistance. However, tumors were eradicated when Vemurafenib was combined the MEK inhibitor. The diversity of drug responses among the xenograft models; the distinct mechanisms of resistance; and the ability to overcome resistance by the addition of a MEK inhibitor provide a scheduling rationale for clinical trials of next-generation drug combinations.