Transgenic overexpression of CTRP3 prevents alcohol-induced hepatic triglyceride accumulation.

This study tested the ability of a novel adipose tissue derived cytokine, C1q TNF-related protein-3 (CTRP3), to prevent alcohol-induced hepatic lipid accumulation, or alcoholic fatty liver disease (ALD). Previous work has demonstrated that CTRP3 is effective at preventing high-fat diet-induced fatty liver; however, the potential of CTRP3 to inhibit ALD has not been explored. To test the potential protective effects of CTRP3, transgenic mice overexpressing CTRP3 (Tg) or wild-type littermates (WT) were subjected to one of two different models of ALD. In the first model, known as the NIAAA model, mice were fed control or alcohol-containing liquid diets (5% vol/vol) for 10 days followed by a single gavage of ethanol (5 g/kg). In the second model, the chronic model, mice were fed control or alcohol-containing diets for 6 wk with no gavage. This study found that CTRP3 reduced triglyceride accumulation in the chronic model of alcohol consumption by ~50%, whereas no reduction was observed in the NIAAA model. Further analysis of isolated primary hepatocytes from WT and Tg mice demonstrated that CTRP3 increased oxygen consumption in the presence of fatty acids, indicating that CTRP3 increases hepatic fatty acid utilization. In conclusion, this study indicates that CTRP3 attenuates hepatic triglyceride accumulation in response to long-term chronic, but not short-term, alcohol consumption.

Randomized Controlled Trial to Improve Self-Efficacy in People With Multiple Sclerosis: The Community Reintegration for Socially Isolated Patients (CRISP) Program.

OBJECTIVE: We examined the efficacy of a 12-wk educational socialization program, Community Reintegration for Socially Isolated Patients (CRISP), in improving self-efficacy for people with multiple sclerosis (MS). We also examined whether participants in the experimental group with increased self-efficacy experienced reduced loneliness and depression. METHOD: This randomized controlled group design included 91 participants with MS (experimental group, n = 51; control group, n = 40). Participants were between ages 20 and 68 yr, and the majority experienced a relapsing-remitting MS course (86%) and mild to moderate disability. Participants completed baseline and posttreatment assessments, including questionnaires assessing self-efficacy, loneliness, and depression. RESULTS: Experimental group participants significantly improved in self-efficacy compared with control group participants. Experimental group participants who demonstrated improved self-efficacy reported reduced perceptions of loneliness but not depressive symptoms. CONCLUSION: CRISP is a promising intervention to improve self-efficacy for people with MS. However, results need to be treated with caution given the study's limitations.

Callosal Interhemispheric Communication in Mild Traumatic Brain Injury: A Mediation Analysis on WM Microstructure Effects.

BACKGROUND AND PURPOSE: Because the corpus callosum connects the left and right hemispheres and a variety of WM bundles across the brain in complex ways, damage to the neighboring WM microstructure may specifically disrupt interhemispheric communication through the corpus callosum following mild traumatic brain injury. Here we use a mediation framework to investigate how callosal interhemispheric communication is affected by WM microstructure in mild traumatic brain injury. MATERIALS AND METHODS: Multishell diffusion MR imaging was performed on 23 patients with mild traumatic brain injury within 1 month of injury and 17 healthy controls, deriving 11 diffusion metrics, including DTI, diffusional kurtosis imaging, and compartment-specific standard model parameters. Interhemispheric processing speed was assessed using the interhemispheric speed of processing task (IHSPT) by measuring the latency between word presentation to the 2 hemivisual fields and oral word articulation. Mediation analysis was performed to assess the indirect effect of neighboring WM microstructures on the relationship between the corpus callosum and IHSPT performance. In addition, we conducted a univariate correlation analysis to investigate the direct association between callosal microstructures and IHSPT performance as well as a multivariate regression analysis to jointly evaluate both callosal and neighboring WM microstructures in association with IHSPT scores for each group. RESULTS: Several significant mediators in the relationships between callosal microstructure and IHSPT performance were found in healthy controls. However, patients with mild traumatic brain injury appeared to lose such normal associations when microstructural changes occurred compared with healthy controls. CONCLUSIONS: This study investigates the effects of neighboring WM microstructure on callosal interhemispheric communication in healthy controls and patients with mild traumatic brain injury, highlighting that neighboring noncallosal WM microstructures are involved in callosal interhemispheric communication and information transfer. Further longitudinal studies may provide insight into the temporal dynamics of interhemispheric recovery following mild traumatic brain injury.

Trend for decreasing Multiple Sclerosis Severity Scores (MSSS) with increasing calendar year of enrollment into the New York State Multiple Sclerosis Consortium.

BACKGROUND: Although the natural history of multiple sclerosis has been charted extensively, it is still not known whether the trajectory of disability accumulation has changed in the era of disease-modifying therapies (DMTs). OBJECTIVE: The objective of this study was to examine trends in Multiple Sclerosis Severity Score (MSSS) with regard to calendar year of enrollment into the New York State MS Consortium (NYSMSC). METHODS: Distributions of MSSS were calculated for each year of enrollment, from 1996 to 2007. Quantile regression was used in a multivariable analysis to model for conditional distribution of MSSS quantiles as functions of potential confounders. RESULTS: The cohort consisted of 6238 patients. Mean age at enrollment was 38 years (SD=10) and mean disease duration was 10.1 years (SD=7.3); 57% were on DMTs. The quantile regression model of trends in MSSS between 1996 and 2007 controlled for age, sex, ethnicity, diagnostic delay, and disease duration and demonstrated a robust trend toward lower MSSS with increasing year of enrollment. The model-predicted median MSSS at enrollment in 1996 was 5.04 (95% CI, 4.86-5.21), and in 2007 was 3.78 (95%CI, 3.36-4.20; p<0.001). The downward trend in MSSS during the enrollment period was confirmed by analysis of Expanded Disability Status Scale (EDSS) distributions, adjusted for disease duration, in successive years of enrollment. CONCLUSIONS: The recent enrollees into the NYSMSC had lower MSSSs compared to the earlier enrollees. The apparent slowing in disability accumulation is likely due to a complex combination of factors: advent of DMTs and improvements in MS care, as well as selection, migration, and recall biases.

Sound Lateralization Test Distinguishes Unimpaired MS Patients from Healthy Controls.

There is an urgent need to develop a practical and reliable clinical measure of disease progression in early and mild MS. We hypothesized that a test of sound lateralization, which is exquisitely sensitive to transmission delays in auditory brainstem, could be more useful for detecting processing speed deficits in mildly impaired MS subjects than standard cognitive tasks. Objective. To develop a practical test of sound lateralization for the clinic and to compare performance of MS subjects with variable disability and healthy subjects on Sound Lateralization Test (SLT) and two speed-of-processing tasks. Design. 42 healthy controls and 90 subjects with clinically definite MS, divided into no, mild, and moderate disability strata, were administered the Symbol Digit Modalities Test (SDMT), and 3-second Paced Auditory Serial Addition Test (PASAT). Results. All of the tests showed an overall difference in performance between controls and the three MS groups, but only the SLT measured a significant difference between controls and the no disability group. Conclusion. SLT is rapidly applied, technically simple, and superior to standard processing speed tests for discriminating between healthy controls and nondisabled MS subjects. SLT should be investigated as an outcome measure in early-phase trials and for monitoring early disease progression in the clinic.