Resistance to visceral obesity is associated with increased locomotion in mice expressing an endothelial cell-specific fibroblast growth factor 1 transgene.

Overdevelopment of visceral adipose is positively correlated with the etiology of obesity-associated pathologies including cardiovascular disease and insulin resistance. However, identification of genetic, molecular, and physiological factors regulating adipose development and function in response to nutritional stress is incomplete. Fibroblast Growth Factor 1 (FGF1) is a cytokine expressed and released by both adipocytes and endothelial cells under hypoxia, thermal, and oxidative stress. Expression of Fibroblast Growth Factor 1 (FGF1) in adipose is required for normal depot development and remodeling. Loss of FGF1 leads to deleterious changes in adipose morphology, metabolism, and insulin resistance. Conversely, diabetic and obese mice injected with recombinant FGF1 display improvements in insulin sensitivity and a reduction in adiposity. We report in this novel, in vivo study that transgenic mice expressing an endothelial-specific FGF1 transgene (FGF1-Tek) are resistant to high-fat diet-induced abdominal adipose accretion and are more glucose-tolerant than wild-type control animals. Metabolic chamber analyses indicate that suppression of the development of visceral adiposity and insulin resistance was not associated with alterations in appetite or resting metabolic rate in the FGF1-Tek strain. Instead, FGF1-Tek mice display increased locomotor activity that likely promotes the utilization of dietary fatty acids before they can accumulate in adipose and liver. This study provides insight into the impact that genetic differences dictating the production of FGF1 has on the risk for developing obesity-related metabolic disease in response to nutritional stress.

Comparison of balancing scores using the ANCOVA approach for estimating average treatment effect: a simulation study.

In this article, we conducted a simulation study to evaluate the performance of five balancing scores using the Analysis of Covariance (ANCOVA) approach, for adjusting bias in estimating average treatment effects (ATE) in observational studies. The five balancing scores which we used as the covariate(s) in the ANCOVA model were (1) propensity score (P), (2) prognostic score (G), (3) propensity score estimated by prognostic score (PG), (4) prognostic score estimated by propensity score (GP), and (5) both propensity and prognostic scores (P&G). The results of the five balancing scores using the ANCOVA approach were compared to the results of the classic regression approach, which included all observed covariates as the predictors. Simulation results showed that balancing scores P, GP, and (P&G) had the smallest bias and mean squared error (MSE) when the outcome variable and the observed covariates were linearly associated, and PG had the smallest or close to the smallest bias and MSE when the associations were nonlinear, nonadditive and nonlinear & nonadditive.

Characterizing the demographics of chronic pain patients in the state of Maine using the Maine all payer claims database.

BACKGROUND: Chronic pain is currently a significant health problem in the United States. A comprehensive strategy is needed to increase prevention of chronic pain and to improve care for chronic pain patients. However, development of a successful strategy relies, in part, on a better understanding of the demographics and socioeconomics of patients living with chronic pain conditions. The current study was designed to understand the burden of chronic pain in the state of Maine by identifying the prevalence of chronic pain and its relationship with selected demographic and socioeconomic factors in Maine. METHODS: The Maine All Payer Claims Database (MEAPCD) (2006-2011) was used in the secondary data analysis to assess the demographic characteristics (such as age, sex, insurance type, and county of residence) of chronic pain patients in Maine. Chronic pain patients were identified based on the presence of pre-identified chronic pain-associated ICD-9 code(s) and opioid prescription information. Potential associations between the prevalence of chronic pain and a number of socioeconomic factors were determined by comparisons to Maine Census data. RESULTS: More women in the state were identified as having chronic pain across all counties and all age groups (> 10 years old). Surprisingly, the majority of chronic pain patients were identified based on the diagnostic code criteria and not the opioid prescription criteria. A greater utilization of public health insurance was seen within the chronic pain patients. At the county level, although neither education level nor income were associated with the prevalence of chronic pain, these factors significantly correlated with the usage of public health insurance. CONCLUSIONS: Further detailed characterization of the chronic pain patient population in the state of Maine, using multiple data sources, can help design population-targeted strategies to prevent and manage chronic pain.

Murine immunodeficiency virus-induced peripheral neuropathy and the associated cytokine responses.

Distal symmetrical polyneuropathy is the most common form of HIV infection-associated peripheral neuropathy and is often associated with pain. C57BL/6 (B6) mice infected with LP-BM5, a murine retroviral isolate, develop a severe immunodeficiency syndrome similar to that in humans infected with HIV-1, hence the term murine AIDS. We investigated the induction of peripheral neuropathy after LP-BM5 infection in B6 mice. Infected B6 mice, like HIV-infected humans, exhibited behavioral (increased sensitivity to mechanical and heat stimuli) and pathological (transient loss of intraepidermal nerve fibers) signs of peripheral neuropathy. The levels of viral gag RNA were significantly increased in all tissues tested, including spleen, paw skin, lumbar dorsal root ganglia, and lumbar spinal cord, postinfection (p.i.). Correlated with the development of peripheral neuropathy, the tissue levels of several cytokines, including IFN-γ, IL-1ß, IL-6, and IL-12, were significantly elevated p.i. These increases had cytokine-specific and tissue-specific profiles and kinetics. Further, treatment with the antiretroviral agent zidovudine either significantly reduced or completely reversed the aforementioned behavioral, pathologic, and cytokine changes p.i. These data suggest that LP-BM5 infection is a potential mouse model of HIV-associated distal symmetrical polyneuropathy that can be used for investigating the roles of various cytokines in infection-induced neuropathic pain. Further investigation of this model could give a better understanding of, and lead to more effective treatments for, HIV infection-associated painful peripheral neuropathy.