Utilization of Mid-Thigh Magnetic Resonance Imaging to Predict Lean Body Mass and Knee Extensor Strength in Obese Adults

PurposeTo train and test a machine learning model to automatically measure mid-thigh muscle cross-sectional area (CSA) to provide rapid estimation of appendicular lean mass (ALM) and predict knee extensor torque of obese adults.MethodsObese adults [body mass index (BMI) = 30–40 kg/m2, age = 30–50 years] were enrolled for this study. Participants received full-body dual-energy X-ray absorptiometry (DXA), mid-thigh MRI, and completed knee extensor and flexor torque assessments via isokinetic dynamometer. Manual segmentation of mid-thigh CSA was completed for all MRI scans. A convolutional neural network (CNN) was created based on the manual segmentation to develop automated quantification of mid-thigh CSA. Relationships were established between the automated CNN values to the manual CSA segmentation, ALM via DXA, knee extensor, and flexor torque.ResultsA total of 47 obese patients were enrolled in this study. Agreement between the CNN-automated measures and manual segmentation of mid-thigh CSA was high (>0.90). Automated measures of mid-thigh CSA were strongly related to the leg lean mass (r = 0.86, p < 0.001) and ALM (r = 0.87, p < 0.001). Additionally, mid-thigh CSA was strongly related to knee extensor strength (r = 0.76, p < 0.001) and moderately related to knee flexor strength (r = 0.48, p = 0.002).ConclusionCNN-measured mid-thigh CSA was accurate compared to the manual segmented values from the mid-thigh. These values were strongly predictive of clinical measures of ALM and knee extensor torque. Mid-thigh MRI may be utilized to accurately estimate clinical measures of lean mass and function in obese adults

Increased Synthesis of Leukotrienes in the Mouse Model of Diabetic Retinopathy

Elevated glucose levels result in enhanced generation of proinflammatory leukotrienes by mouse bone marrow cells and by retinal glial and microvascular endothelial cells. Leukotrienes may contribute to chronic inflammation in diabetic retinopathy

Proinflammatory Responses Induced by CD40 in Retinal Endothelial and Müller Cells are Inhibited by Blocking CD40-Traf2,3 or CD40-Traf6 Signaling

Citation: Portillo J-AC, Schwartz I, Zarini S, et al. Proinflammatory responses induced by CD40 in retinal endothelial and Müller cells are inhibited by blocking CD40-TRAF2,3 or CD40-TRAF6 signaling. Invest Ophthalmol Vis Sci. 2014;55:8590-8597. DOI:10.1167/iovs.14-15340 PURPOSE. The cell surface receptor CD40 is required for the development of retinopathies induced by diabetes and ischemia/reperfusion. The purpose of this study was to identify signaling pathways by which CD40 triggers proinflammatory responses in retinal cells, since this may lead to pharmacologic targeting of these pathways as novel therapy against retinopathies. METHODS. Retinal endothelial and Müller cells were transduced with vectors that encode wildtype CD40 or CD40 with mutations in sites that recruit TNF receptor associated factors (TRAF): TRAF2,3 (DT2,3), TRAF6 (DT6), or TRAF2,3 plus TRAF6 (DT2,3,6). Cells also were incubated with CD40-TRAF2,3 or CD40-TRAF6 blocking peptides. We assessed intercellular adhesion molecule-1 (ICAM-1), CD40, monocyte chemoattractant protein-1 (MCP-1), VEGF, and prostaglandin E 2 (PGE 2 ) by fluorescence-activated cell sorting (FACS), ELISA, or mass spectrometry. Mice (B6 and CD40 À/À ) were made diabetic using streptozotocin. The MCP-1 mRNA was assessed by real-time PCR. RESULTS. The CD40-mediated ICAM-1 upregulation in endothelial and Müller cells was markedly inhibited by expression of CD40 DT2,3 or CD40 DT6. The CD40 was required for MCP-1 mRNA upregulation in the retina of diabetic mice. The CD40 stimulation of endothelial and Müller cells enhanced MCP-1 production that was markedly diminished by CD40 DT2,3 or CD40 DT6. Similar results were obtained in cells incubated with CD40-TRAF2,3 or CD40-TRAF6 blocking peptides. The CD40 ligation upregulated PGE 2 and VEGF production by Müller cells, that was inhibited by CD40 DT2,3 or CD40 DT6. All cellular responses tested were obliterated by expression of CD40 DT2,3,6. CONCLUSIONS. Blockade of a single CD40-TRAF pathway was sufficient to impair ICAM-1, MCP-1, PGE 2 , and VEGF upregulation in retinal endothelial and/or Müller cells. Blockade of CD40-TRAF signaling may control retinopathies