BackgroundDespite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear.Methodology/Principal FindingsIn this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration.ConclusionWe conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.
Background
Risk-adjusted analyses are critical in evaluating trauma outcomes. The National Trauma Data Bank (NTDB) is a statistically robust registry that allows such analyses; however, analytical techniques are not yet standardized. In this study, we examine peer-reviewed manuscripts published using NTDB data, with particular attention to characteristics strongly associated with trauma outcomes. Our objective is to determine if there are substantial variations in the methodology and quality of risk-adjusted analyses and thus, whether the development of best practices for risk-adjusted analyses is warranted.
Study Design
A database of all studies utilizing NTDB data published through December 2010 was created by searching Pubmed and Embase. Studies with multivariate risk-adjusted analyses were examined for their central question, main outcome measures, analytical techniques, the co-variates in adjusted analyses, and handling of missing data.
Results
Of 286 NTDB publications, 122 performed a multivariable adjusted analysis. These studies focused on Clinical Outcomes (51), Public Health Policy or Injury Prevention (30), Quality (16), Disparities (15), Trauma Center Designation (6) or Scoring Systems (4). Mortality was the main outcome in 98 of these studies. There were considerable differences in the co-variates used for case adjustment. The three most frequently controlled for co-variates were age (95%), Injury Severity Score (85%) and gender (78%). Up to 43% of studies did not control for the five basic covariates necessary to conduct a risk-adjusted analysis of trauma mortality. Less than 10% of studies used clustering to adjust for facility differences or imputation to handle missing data.
Conclusions
There is significant variability in how risk-adjusted analyses using data from the NTDB are performed. Best practices are needed to further improve the quality of research from the NTDB.
Background: Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear.
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