Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia.

Motivational deficits play a central role in disability due to negative symptoms of schizophrenia (SZ), but limited pathophysiological understanding impedes critically needed therapeutic development. We applied an fMRI Effort Discounting Task (EDT) that quantifies motivation using a neuroeconomic decision-making approach, capturing the degree to which effort requirements produce reductions in the subjective value (SV) of monetary reward. An analyzed sample of 21 individuals with SZ and 23 group-matched controls performed the EDT during fMRI. We hypothesized that ventral striatum (VS) as well as extended brain motivation circuitry would encode SV, integrating reward and effort costs. We also hypothesized that VS hypoactivation during EDT decisions would demonstrate a dimensional relationship with clinical amotivation severity, reflecting greater suppression by effort costs. As hypothesized, VS as well as a broader cortico-limbic network were activated during the EDT and this activation correlated positively with SV. In SZ, activation to task decisions was reduced selectively in VS. Greater VS reductions correlated with more severe clinical amotivation in SZ and across all participants. However, these diagnosis and amotivation effects could not be explained by the response to parametric variation in reward, effort, or model-based SV. Our findings demonstrate that VS hypofunction in schizophrenia is manifested during effort-based decisions and reflects dimensional motivation impairment. Dysfunction of VS impacting effort-based decision-making can provide a target for biomarker development to guide novel efforts to assess and treat disabling amotivation.

A cost comparison of unicompartmental and total knee arthroplasty.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty (TKA) in appropriately selected patients. There is a paucity of data comparing hospital resource utilization and costs for UKA versus TKA. METHODS: We retrospectively reviewed 128 patients who underwent UKA or TKA for osteoarthritis by a single surgeon in the 2011 Fiscal Year. Sixty-four patients in each group were matched based on sex, age, race, body mass index, Charlson Comorbidity Index, and insurance type. Clinical data were obtained from medical records while costs were obtained from hospital billing. Bivariate analyses were used to compare outcomes. RESULTS: Both anesthesia and operative time (minutes) were significantly shorter for patients undergoing UKA (125.7 vs. 156.4; p<0.001, and 81.4 vs. 112.2; p<0.001). UKA patients required fewer transfusions (0% vs. 11.0%; p=0.007) and had a shorter hospital stay (2.2 vs. 3.8days; p<0.001). 96% of UKAs were discharged home compared with 75% of TKAs (p<0.001). Hospital direct costs were lower for UKA ($7893 vs. $11,156; p<0.001) as were total costs (hospital direct costs plus overhead; $11,397 vs. $16,243; p<0.001). Supply costs and implant costs were similarly lower for UKA ($701 vs. $781; p<0.001, and $3448 vs. $5006; p<0.001). CONCLUSION: Our data suggest that UKA provides a cost-effective alternative to TKA in appropriately selected patients. As the number of patients with end-stage arthritis of the knee requiring surgical care continues to rise, the costs of caring for these patients must be considered. LEVEL OF EVIDENCE: Level III, case control study.

The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins.

Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers.