Role of Macrophage Migration Inhibitory Factor in Obesity, Insulin Resistance, Type 2 Diabetes, and Associated Hepatic Co-Morbidities: A Comprehensive Review of Human and Rodent Studies

<p>Obesity is associated with a chronic low-grade inflammatory state that drives the -development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate in the adipose tissue, which becomes inflamed and insulin resistant when it is no longer able to expand in response to excess caloric and nutrient intake. The production of inflammatory mediators by dysfunctional adipose tissue is thought to drive the development of more complex forms of disease such as type 2 diabetes and NAFLD. An important factor that may contribute to metabolic inflammation is the cytokine macrophage migration inhibitory factor (MIF). Increasing evidence suggests that MIF is released by adipose tissue in obesity and that it is also involved in metabolic and inflammatory processes that underlie the development of obesity-related pathologies. This review provides a comprehensive summary of our current knowledge on the role of MIF in obesity, its production by adipose tissue, and its involvement in the development of insulin resistance, type 2 diabetes, and NAFLD. We discuss the main findings from recent clinical studies in obese subjects and weight-loss intervention studies as well as results from clinical studies in patients with insulin resistance and type 2 diabetes. Furthermore, we summarize findings from experimental disease models studying the contribution of MIF in obesity and insulin resistance, type 2 diabetes, and hepatic lipid accumulation and fibrosis. Although many of the findings support a pro-inflammatory role of MIF in disease development, recent reports also provide indications that MIF may exert protective effects under certain conditions.</p

An experimental technique for performing 3-D LDA measurements inside whirling annular seals

During the last several years, the Fluid Mechanics Division of the Turbomachinery Laboratory at Texas A&M University has developed a rather unique facility with the experimental capability for measuring the flow field inside journal bearings, labyrinth seals, and annular seals. The facility consists of a specially designed 3-D LDA system which is capable of measuring the instantaneous velocity vector within 0.2 mm of a wall while the laser beams are aligned almost perpendicular to the wall. This capability was required to measure the flow field inside journal bearings, labyrinth seals, and annular seals. A detailed description of this facility along with some representative results obtained for a whirling annular seal are presented

Measurements of the Diffuse Ultraviolet Background and the Terrestrial Airglow with the Space Telescope Imaging Spectrograph

Far-UV observations in and near the Hubble Deep Fields demonstrate that the Space Telescope Imaging Spectrograph (STIS) can potentially obtain unique and precise measurements of the diffuse far-ultraviolet background. Although STIS is not the ideal instrument for such measurements, high-resolution images allow Galactic and extragalactic objects to be masked to very faint magnitudes, thus ensuring a measurement of the truly diffuse UV signal. The programs we have analyzed were not designed for this scientific purpose, but would be sufficient to obtain a very sensitive measurement if it were not for a weak but larger-than-expected signal from airglow in the STIS 1450-1900 A bandpass. Our analysis shows that STIS far-UV crystal quartz observations taken near the limb during orbital day can detect a faint airglow signal, most likely from NI\1493, that is comparable to the dark rate and inseparable from the far-UV background. Discarding all but the night data from these datasets gives a diffuse far-ultraviolet background measurement of 501 +/- 103 ph/cm2/sec/ster/A, along a line of sight with very low Galactic neutral hydrogen column (N_HI = 1.5E20 cm-2) and extinction (E(B-V)=0.01 mag). This result is in good agreement with earlier measurements of the far-UV background, and should not include any significant contribution from airglow. We present our findings as a warning to other groups who may use the STIS far-UV camera to observe faint extended targets, and to demonstrate how this measurement may be properly obtained with STIS.Comment: 7 pages, Latex. 4 figures. Uses corrected version of emulateapj.sty and apjfonts.sty (included). Accepted for publication in A

Court Strategy

This session focuses on the following issues: (1) access to the courts, (2) secrecy of court documents and settlements, (3) court bias, and (4) public education and tools. The panelists present possible solutions for the issues discussed

Simple and objective prediction of survival in patients with lung cancer: staging the host systemic inflammatory response

Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer

Changing trends in residents-as-teachers across graduate medical education

BACKGROUND: Teaching residents how to teach is a critical part of residents' training in graduate medical education (GME). The purpose of this study was to assess the change in resident-as-teacher (RaT) instruction in GME over the past 15 years in the US. METHODS: We used a quantitative and qualitative survey of all program directors (PDs) across specialties. We compared our findings with a previous work from 2000-2001 that studied the same matter. Finally, we qualitatively analyzed PDs' responses regarding the reasons for implementing and not implementing RaT instruction. RESULTS: Two hundred and twenty-one PDs completed the survey, which yields a response rate of 12.6%. Over 80% of PDs implement RaT, an increase of 26.34% compared to 2000-2001. RaT instruction uses multiple methods with didactic lectures reported as the most common, followed by role playing in simulated environments, then observing and giving feedback. Residents giving feedback, clinical supervision, and bedside teaching were the top three targeted skills. Through our qualitative analysis we identified five main reasons for implementing RaT: teaching is part of the residents' role; learners desire formal RaT training; regulatory bodies require RaT training; RaT improves residents' education; and RaT prepares residents for their current and future roles. CONCLUSION: The use of RaT instruction has increased significantly in GME. More and more PDs are realizing its importance in the residents' formative training experience. Future studies should examine the effectiveness of each method for RaT instruction

Mannose binding lectin is required for alphavirus-induced arthritis/myositis

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3(-/-) mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis.This work was supported by NIH/NIAMS R01 AR 047190 awarded to MTH

Estimating the impact of city-wide Aedes aegypti population control: An observational study in Iquitos, Peru.

During the last 50 years, the geographic range of the mosquito Aedes aegypti has increased dramatically, in parallel with a sharp increase in the disease burden from the viruses it transmits, including Zika, chikungunya, and dengue. There is a growing consensus that vector control is essential to prevent Aedes-borne diseases, even as effective vaccines become available. What remains unclear is how effective vector control is across broad operational scales because the data and the analytical tools necessary to isolate the effect of vector-oriented interventions have not been available. We developed a statistical framework to model Ae. aegypti abundance over space and time and applied it to explore the impact of citywide vector control conducted by the Ministry of Health (MoH) in Iquitos, Peru, over a 12-year period. Citywide interventions involved multiple rounds of intradomicile insecticide space spray over large portions of urban Iquitos (up to 40% of all residences) in response to dengue outbreaks. Our model captured significant levels of spatial, temporal, and spatio-temporal variation in Ae. aegypti abundance within and between years and across the city. We estimated the shape of the relationship between the coverage of neighborhood-level vector control and reductions in female Ae. aegypti abundance; i.e., the dose-response curve. The dose-response curve, with its associated uncertainties, can be used to gauge the necessary spraying effort required to achieve a desired effect and is a critical tool currently absent from vector control programs. We found that with complete neighborhood coverage MoH intra-domicile space spray would decrease Ae. aegypti abundance on average by 67% in the treated neighborhood. Our framework can be directly translated to other interventions in other locations with geolocated mosquito abundance data. Results from our analysis can be used to inform future vector-control applications in Ae. aegypti endemic areas globally