MUSCLE METABOLISM AFTER TOTAL KNEE ARTHROPLASTY WITH AND WITHOUT TOURNIQUET

Total knee arthroplasty (TKA) is the most common and cost effective surgery used to mitigate painful end-stage knee osteoarthritis. Projections suggest that by 2030 over 3.5 million older adults will undergo primary TKA annually in the U.S. It is estimated that a tourniquet is used by 95% of orthopedic surgeons during TKA to create a bloodless field and to ensure proper bone implant cementing. Prior studies by our lab suggest that tourniquet use may be detrimental, potentially leading to ischemia-reperfusion injury and cell swelling acutely following surgery; however, these studies focused on the vastus lateralis muscle. To our knowledge, less is known about how tourniquet use during TKA may impact the tibialis anterior (TA) muscle, which in older adults provides greater postural control support relative to younger individuals. PURPOSE: Determine if tourniquet use during TKA alters pH and oxidative capacity in the tibialis anterior (TA) 2 weeks after surgery. METHODS: Non-invasive in-vivo 31-phosphorous magnetic resonance spectroscopy was used to assess muscle metabolism in both the operative and non-operative TA 2 weeks ±4 days after surgery in two groups: those who had tourniquet (T) during surgery and those who did not (NT). RESULTS: Average resting pH in the NT group operative leg (n=2) was 7.025 and non-operative leg was 7.02. Average resting pH in the T group operative leg (n=3) was 7.01 and non-operative leg was 7.027. Oxidative capacity in the NT group operative leg (n=1) was .0177 and non-operative leg (n=1) was .0303. Oxidative capacity in the T group operative leg (n=2) was .0406 while the non-operative leg (n=1) was .0238. CONCLUSIONS: Our preliminary results suggest that tourniquet use during TKA alters muscle metabolism in the TA, which may be significant because older adults rely on the TA for balance control and ambulation more than younger individuals. Alterations in TA metabolism following TKA surgery using tourniquet may impact recovery of strength and function in this population of older adults. Further analysis is required in order to determine if TKA with tourniquet alters metabolism 2 weeks post-surgery. Supported by NIH grant: R01AG04640

Photochemistry of UV-Excited Trifluoroacetylacetone and Hexafluoroacetylacetone I: Infrared Spectra of Fluorinated Methylfuranones Formed by HF Photoelimination

The photochemistry of gas-phase 1,1,1-trifluoroacetylacetone (TFAA) excited with ultraviolet (UV) light involves a significant photoelimination channel that produces hydrogen fluoride and a fluorinated methylfuranone, 2,2-difluoro-5-methyl-3­(2<i>H</i>)-furanone (2FMF). This pathway is remarkable because it is a gas-phase unimolecular reaction that forms a five-membered ring product. This report is the first of such a TFAA photoelimination channel, which is similar to one observed with 1,1,1,5,5,5-hexafluoroacetylacetone (HFAA), resulting in 2,2-difluoro-5-trifluoromethyl-3­(2<i>H</i>)-furanone. We present infrared spectral observations of 2FMF produced by pulsed, UV-laser excitation of TFAA, along with analogous results from HFAA, supported by density functional theory (DFT) computational studies. DFT results for the infrared spectrum of 5-methyl-3­(2<i>H</i>)-furanone, the expected comparable acetylacetone photoelimination product, help suggest that UV excitation of acetylacetone fails to follow a similar type of photoelimination. We use a weighted RMS approach as a figure of merit for comparing calculated infrared frequencies with experimental data. Results from the three acetylacetones reveal how the presence of fluorine atoms in acetylacetone influences the gas-phase molecular photochemistry

A comparison of statistical and machine learning methods for creating national daily maps of ambient PM2.5 concentration

A typical challenge in air pollution epidemiology is to perform detailed exposure assessment for individuals for which health data are available. To address this problem, in the last few years, substantial research efforts have been placed in developing statistical methods or machine learning techniques to generate estimates of air pollution at fine spatial and temporal scales (daily, usually) with complete coverage. However, it is not clear how much the predicted exposures yielded by the various methods differ, and which method generates more reliable estimates. In this paper, we aim to address this gap by evaluating a variety of exposure modeling approaches, comparing their predictive performance. Using PM2.5 in year 2011 over the continental U.S. as a case study, we generate national maps of ambient PM2.5 concentration using: (i) ordinary least squares and inverse distance weighting; (ii) kriging; (iii) statistical downscaling models, that is, spatial statistical models that use the information contained in air quality model outputs; (iv) land use regression, that is, linear regression modeling approaches that leverage the information in Geographical Information System (GIS) covariates; and (v) machine learning methods, such as neural networks, random forests and support vector regression. We examine the various methods' predictive performance via cross-validation using Root Mean Squared Error, Mean Absolute Deviation, Pearson correlation, and Mean Spatial Pearson Correlation. Additionally, we evaluated whether factors such as, season, urbanicty, and levels of PM2.5 concentration (low, medium or high) affected the performance of the different methods. Overall, statistical methods that explicitly modeled the spatial correlation, e.g. universal kriging and the downscaler model, outperform all the other exposure assessment approaches regardless of season, urbanicity and PM2.5 concentration level. We posit that the better predictive performance of spatial statistical models over machine learning methods is due to the fact that they explicitly account for spatial dependence, thus borrowing information from neighboring observations. In light of our findings, we suggest that future exposure assessment methods for regional PM2.5 incorporate information from neighboring sites when deriving predictions at unsampled locations or attempt to account for spatial dependence

MUSCLE CELL REGENERATIVE POTENTIAL FOLLOWING AMINO ACID SUPPLEMENTATION IN TOTAL KNEE ARTHROPLASTY PATIENTS

N. Bigot1, E. Owen2, T. Kirkpartick2, A. Poluso2, M. Bremer2, L. Strycker3, K. Smolkowski3, B. Lantz4, S. Shah4, C. Mohler4, B. Jewett4, J. Muyskens1, H. Dreyer1 1University of Oregon; 2Slocum Research and Education Foundation; 3Oregon Research Institute;4Slocum Center for Orthopedics and Sports Center, Eugene, OR PURPOSE: More than 600,000 Americans receive total knee arthroplasty (TKA) annually. Our goal is to improve functional outcomes following TKA by mitigating the extensive muscle loss that occurs during the first two weeks post surgery. Previously, we showed that essential amino acid supplementation (EAAs) improves function and reduces muscle atrophy as measured by MRI. This study aimed to determine muscle cell-level changes related to regenerative potential in TKA patients receiving EAAs compared to Placebo. METHODS Using a double-blind Placebo-controlled randomized clinical trial, 39 older adults (age 50-80 y) having TKA were randomized to ingest either 20 g of EAA (n = 19) or Placebo (n = 20) 2x/d between meals for 1 wk before, and 6 wk after TKA. Bilateral muscle biopsies (vastus lateralis (VL)) were obtained prior to surgery and at 1 or 2 weeks post TKA. Histological analysis determined cross-sectional area (CSA) of VL cells (anti-laminin), number of myonuclei per muscle cell (DAPI), fiber type composition (anti-MHC1), and satellite cell number (anti-Pax7). In addition, we assayed for shifts in inflammatory (M1) vs regenerative (M2) macrophage populations. RESULTS: Our preliminary results reveal satellite cell numbers are elevated in the EAA group vs Placebo for Type I cells (0.127±.02 vs, 0.073±.01, respectively, p=.054) and Type II cells (0.084±.02 vs. 0.039±.01, p=.64) after just 7 days of twice-daily EAA prior to surgery. After surgery in the EAA group, satellite cell numbers were reduced relative to baseline for both Type I (-37%) and II (-27%) fibers (p\u3c0.05). No changes in the satellite cell populations were measured in either leg for the Placebo group. Muscle CSA was reduced (-12%) in the Placebo group in the operative leg (p =.017). The treatment group did not display the corresponding decrease in CSA (p =.098). M1 macrophage populations were reduced in the operative leg of the treatment group at 1-week post surgery (p =.017). No changes in macrophage populations were measured for the Placebo group. CONCLUSIONS: Our data suggest that amino acid supplementation may attenuate muscle atrophy through preservation of satellite cells and a reduction in inflammatory macrophage numbers. NIA:R01AG04640