Major depressive disorder (MDD) is a chronic mental illness that affects an estimated 5-26% of adults at some time in their lives. Treatment is often started as pharmacotherapy using a single drug such as a selective serotonin reuptake inhibitor. If a patient fails to respond adequately to the initial antidepressant, typically three pharmacotherapy options are available to the practitioner. The dose of the current therapy can be maximized, a change can be made to a different drug, or the current regimen can be augmented with another drug. Atypical antipsychotics have recently become a major focus for augmentation of traditional antidepressant therapy. This review summarizes the evidence for efficacy and safety of augmenting treatment-refractory or treatment-resistant depression with atypical antipsychotics. The National Library of Medicine's MEDLINE database was searched for all English-language articles published from January 1966-December 2011 describing the use of atypical antipsychotics in treatment-resistant depression. The literature retrieved was limited to case series, open-label trials, and randomized controlled trials (RCT). Studies of bipolar depression, psychotic depression, or studies conducted in children and adolescents were excluded. Thirty-five studies using atypical antipsychotics for augmentation treatment of depression were included in this analysis. Trials were identified for aripiprazole (six open-label; three RCT), clozapine (one case series), olanzapine (three open-label, including two case series; four RCT), quetiapine (four open-label; five RCT), risperidone (two open-label; five RCT), and ziprasidone (two open-label). The atypical antipsychotics may be effective as adjunctive therapy in MDD; however, their adverse effect profile may be unfavorable to some patients. Trying at least one alternative treatment strategy after an initial antidepressant is indicated before augmentation is implemented with these agents. If atypical antipsychotics are used, safety and efficacy should be frequently reassessed and dosage should be individualized.

The amounts of muscle and fat in a person's body, known as body composition, are correlated with cancer risks, cancer survival, and cardiovascular risk. The current gold standard for measuring body composition requires time-consuming manual segmentation of CT images by an expert reader. In this work, we describe a two-step process to fully automate the analysis of CT body composition using a DenseNet to select the CT slice and U-Net to perform segmentation. We train and test our methods on independent cohorts. Our results show Dice scores (0.95-0.98) and correlation coefficients (R=0.99) that are favorable compared to human readers. These results suggest that fully automated body composition analysis is feasible, which could enable both clinical use and large-scale population studies. Equal contribution

Glioblastoma multiforme (GBM) is the most common and severe form of brain cancer. The median survival time of patients is approximately 12 months due to poor responses to surgery and chemoradiation. In order to understand the mechanisms involved in radioresistance, we conducted a genetic screen using an shRNA library to identify genes whose inhibition would sensitize cells to radiation. The results were cross-referenced with the Oncomine and Rembrandt databases to focus on genes that are highly expressed in GBM tumors and associated with poor patient outcomes. Spermidine/spermine-N1-acetyltransferase 1 (SAT1), an enzyme involved in polyamine catabolism, was identified as a gene that promotes resistance to ionizing radiation (IR), is overexpressed in brain tumors, and correlates with poor outcomes. Knockdown of SAT1 using shRNA and siRNA approaches in multiple cell and neurosphere lines resulted in sensitization of GBM cells to radiation in colony formation assays and tumors, and decreased tumorigenesis in vivo. Radiosensitization occurred specifically in G2/M and S phases, suggesting a role for SAT1 in homologous recombination (HR) that was confirmed in a DR-GFP reporter system. Mechanistically, we found that SAT1 promotes acetylation of histone H3, suggesting a new role of SAT1 in chromatin remodeling and regulation of gene expression. In particular, SAT1 depletion led to a dramatic reduction in BRCA1 expression, explaining decreased HR capacity. Our findings suggest that the biological significance of elevated SAT1 expression in GBM lies in its contribution to cell radioresistance and that SAT1 may potentially be a therapeutic target to sensitize GBM to cancer therapies.