Citations

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[18F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([11C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m−2·min−1) to 3-h saline infusion. Lean controls ( n = 10) were compared with glycemically controlled volunteers with T2DM ( n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption ( P = 0.04) and perfusion ( P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids ( P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions ( P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups ( P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM ( P = 0.003). Myocardial work efficiency was lower in T2DM ( P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization ( P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM.

Abstract Picornaviruses have emerged as promising cancer therapies due to their ability to drive cytotoxic cellular immune responses and for promoting oncolysis. These properties include preferential replication in tumor cells, the induction of strong innate and adaptive immune responses, and the ease with which their genomes can be manipulated. We have developed Theiler's murine encephalomyelitis virus (TMEV) as an immunotherapy vector that promotes strong adaptive immune responses to tumor antigens embedded within its genome. To further explore its usefulness as cancer therapy, we investigated whether direct intratumoral delivery of TMEV could promote tumor regression. We generated several picornavirus hybrids using substrains of TMEV that have unique immunopathologic characteristics, despite their extensive sequence homology. These hybrids exhibit a unique propensity to infect and replicate in melanoma. We have identified GD7-KS1, a virus that is particularly effective at replicating and infecting B16 melanoma in vitro and provides benefit as an oncolytic therapy in vivo after intratumoral injection. In addition, this virus promotes the mobilization and accumulation of CD8+ T cells within treated tumors. Altogether, these findings demonstrate that picornavirus substrains can be used to rationally design virus hybrids that promote antitumor responses and add to the known strategies identified by us and others to further enhance the therapeutic potential of vectors used to treat cancer. Mol Cancer Ther; 15(3); 523–30. ©2016 AACR.

Background Hyper‐ and hypokalemia are clinically silent, common in patients with renal or cardiac disease, and are life threatening. A noninvasive, unobtrusive, blood‐free method for tracking potassium would be an important clinical advance. Methods and Results Two groups of hemodialysis patients (development group, n=26; validation group, n=19) underwent high‐resolution digital ECG recordings and had 2 to 3 blood tests during dialysis. Using advanced signal processing, we developed a personalized regression model for each patient to noninvasively calculate potassium values during the second and third dialysis sessions using only the processed single‐channel ECG . In addition, by analyzing the entire development group's first‐visit data, we created a global model for all patients that was validated against subsequent sessions in the development group and in a separate validation group. This global model sought to predict potassium, based on the T wave characteristics, with no blood tests required. For the personalized model, we successfully calculated potassium values with an absolute error of 0.36±0.34 mmol/L (or 10% of the measured blood potassium). For the global model, potassium prediction was also accurate, with an absolute error of 0.44±0.47 mmol/L for the training group (or 11% of the measured blood potassium) and 0.5±0.42 for the validation set (or 12% of the measured blood potassium). Conclusions The signal‐processed ECG derived from a single lead can be used to calculate potassium values with clinically meaningful resolution using a strategy that requires no blood tests. This enables a cost‐effective, noninvasive, unobtrusive strategy for potassium assessment that can be used during remote monitoring.

Abstract Peterson, BJ, Fitzgerald, JS, Dietz, CC, Ziegler, KS, Baker, SE, and Snyder, EM. Off-ice anaerobic power does not predict on-ice repeated shift performance in hockey. J Strength Cond Res 30(9): 2375–2381, 2016—Anaerobic power is a significant predictor of acceleration and top speed in team sport athletes. Historically, these findings have been applied to ice hockey although recent research has brought their validity for this sport into question. As ice hockey emphasizes the ability to repeatedly produce power, single bout anaerobic power tests should be examined to determine their ability to predict on-ice performance. We tested whether conventional off-ice anaerobic power tests could predict on-ice acceleration, top speed, and repeated shift performance. Forty-five hockey players, aged 18–24 years, completed anthropometric, off-ice, and on-ice tests. Anthropometric and off-ice testing included height, weight, body composition, vertical jump, and Wingate tests. On-ice testing consisted of acceleration, top speed, and repeated shift fatigue tests. Vertical jump (VJ) ( r = −0.42; r = −0.58), Wingate relative peak power (WRPP) ( r = −0.32; r = −0.43), and relative mean power (WRMP) ( r = −0.34; r = −0.48) were significantly correlated ( p ≤ 0.05) to on-ice acceleration and top speed, respectively. Conversely, none of the off-ice tests correlated with on-ice repeated shift performance, as measured by first gate, second gate, or total course fatigue; VJ ( r = 0.06; r = 0.13; r = 0.09), WRPP ( r = 0.06; r = 0.14; r = 0.10), or WRMP ( r = −0.10; r = −0.01; r = −0.01). Although conventional off-ice anaerobic power tests predict single bout on-ice acceleration and top speed, they neither predict the repeated shift ability of the player, nor are good markers for performance in ice hockey.

PurposeTo investigate the feasibility of utilizing brain stiffness as a potential biomarker for behavioral variant frontotemporal dementia (bvFTD) patients. Magnetic resonance elastography (MRE) is a noninvasive technique for evaluating the mechanical properties of brain tissue in vivo. MRE has demonstrated decreased brain stiffness in patients with Alzheimer's disease.Materials and MethodsWe examined five male subjects with bvFTD and nine cognitively normal age‐matched male controls (NC) with brain 3T MRE. Stiffness was calculated in nine regions of interest (ROIs): whole brain (entire cerebrum excluding cerebellum), frontal lobes, occipital lobes, parietal lobes, temporal lobes, deep gray matter / white matter (GM/WM; insula, deep gray nuclei and white matter tracts), cerebellum, sensorimotor cortex (pre‐ and postcentral gyri), and a composite region labeled FT (frontal and temporal lobes excluding the pre‐ and postcentral gyri).ResultsSignificantly lower stiffness values were observed in the whole brain (P = 0.007), frontal lobe (P = 0.001), and temporal lobes (P = 0.005) of bvFTD patients compared to NC. No significant stiffness differences were observed in any other ROIs of bvFTD patients compared to NC (P > 0.05). These results demonstrate that statistically significant brain softening occurs in the frontal and temporal lobes of bvFTD patients, which corresponds to the expected pathophysiology of bvFTD.ConclusionFuture studies evaluating the feasibility of brain MRE for early disease detection and monitoring disease progression could shed new insights into understanding the mechanisms involved in bvFTD. J. Magn. Reson. Imaging 2016;43:474–478.

Purpose Noninvasive stiffness imaging techniques (elastography) can image myocardial tissue biomechanics in vivo. For cardiac MR elastography (MRE) techniques, the optimal vibration frequency for in vivo experiments is unknown. Furthermore, the accuracy of cardiac MRE has never been evaluated in a geometrically accurate phantom. Therefore, the purpose of this study was to determine the necessary driving frequency to obtain accurate three‐dimensional (3D) cardiac MRE stiffness estimates in a geometrically accurate diastolic cardiac phantom and to determine the optimal vibration frequency that can be introduced in healthy volunteers. Methods The 3D cardiac MRE was performed on eight healthy volunteers using 80 Hz, 100 Hz, 140 Hz, 180 Hz, and 220 Hz vibration frequencies. These frequencies were tested in a geometrically accurate diastolic heart phantom and compared with dynamic mechanical analysis (DMA). Results The 3D Cardiac MRE was shown to be feasible in volunteers at frequencies as high as 180 Hz. MRE and DMA agreed within 5% at frequencies greater than 180 Hz in the cardiac phantom. However, octahedral shear strain signal to noise ratios and myocardial coverage was shown to be highest at a frequency of 140 Hz across all subjects. Conclusion This study motivates future evaluation of high‐frequency 3D MRE in patient populations. Magn Reson Med 77:351–360, 2017. © 2016 Wiley Periodicals, Inc.

Background: Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach. Purpose: To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions. Study Design: Controlled laboratory study. Methods: Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 weeks. Coefficients of multiple correlation were calculated to assess the reliability of kinematic and kinetic measures during the landing phase of the movement. Results: Between-centers reliability for kinematic waveforms in the frontal and sagittal planes was good, but moderate in the transverse plane. Between-centers reliability for kinetic waveforms was good in the sagittal, frontal, and transverse planes. Conclusion: Based on these findings, the single-leg cross drop task has moderate to good reliability of kinematic and kinetic measures across institutions after implementation of a standardized testing protocol. Clinical Relevance: Multicenter collaborations can increase study numbers and generalize results, which is beneficial for studies of relatively rare phenomena, such as ACL injury. An important step is to determine the reliability of risk assessments across institutions before a multicenter collaboration can be initiated.