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Monte Carlo codes are naturally suited to act as computational kernels for ray tracing visualization applications because of the similarities between the ray tracing algorithm and the Monte Carlo neutral particle tracking algorithm. This paper presents a simplified ray tracing algorithm suitable for engineering applications, as well as optimizations to make the algorithm more amenable to computation on a GPU. This algorithm was implemented in a GPU-based ray tracing code called MantaRay. This code has been used as a backend kernel in MCVIZ, a real-time, interactive 3D visualization tool for MC21 models. MCVIZ+MantaRay allows for interactive rendering of extremely large models at 1024x768 resolution at framerates of 15 fps and greater.

In radiation transport calculations, the effects of material temperature on neutron/nucleus interactions must be taken into account through Doppler broadening adjustments to the microscopic cross section data. Historically, Monte Carlo transport simulations have accounted for this temperature dependence by interpolating among precalculated Doppler broadened cross sections at a variety of temperatures. More recently, there has been much interest in on-the-fly Doppler broadening methods, where reference data is broadened on-demand during particle transport to any temperature. Unfortunately, Doppler broadening operations are expensive on traditional central processing unit (CPU) architectures, making on-the-fly Doppler broadening unaffordable without approximations or complex data preprocessing. This work considers the use of graphics processing unit (GPU)s, which excel at parallel data processing, for on-the-fly Doppler broadening in continuous-energy Monte Carlo simulations. Two methods are considered for the broadening operations – a GPU implementation of the standard SIGMA1 algorithm and a novel vectorized algorithm that leverages the convolution properties of the broadening operation in an attempt to expose additional parallelism. Numerical results demonstrate that similar cross section lookup throughput is obtained for on-the-fly broadening on a GPU as cross section lookup throughput with precomputed data on a CPU, implying that offloading Doppler broadening operations to a GPU may enable on-the-fly temperature treatment of cross sections without a noticeable reduction in cross section processing performance in Monte Carlo transport codes.

Magnesium and its alloys are attractive materials for use in automotive and aerospace applications because of their low density and good mechanical properties. However, difficulty in forming magnesium and the limited number of available commercial alloys limit their use. The present work reviews the efforts to improve the attractiveness of magnesium through non-traditional processing, and presents the results of producing AZ31 magnesium alloy via powder metallurgy P/M. P/M can be used to alleviate the formability problem through near-net-shape processing, and also allows unique chemical compositions that can lead to the development of new alloys with novel properties.

Abstract Background Alcohol use disorders (AUDs) lead to alterations in central nervous system (CNS) architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs) produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Results Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs) of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP) assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1) was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5) showed a highly significant correlation with AUD-induced decreases in the volume of the left parietal supramarginal gyrus and neuropsychological measures. Conclusions These results demonstrate that alcohol-induced changes in genes related to proliferation, apoptosis, and DNA-repair are observable in the peripheral blood and may serve as a useful biomarker for CNS structural damage and functional performance deficits in human AUD subjects.

Abstract Background Acute changes in environmental parameters (e.g., O2, pH, UV, osmolarity, nutrients, etc.) evoke a common transcriptomic response in yeast referred to as the "environmental stress response" (ESR) or "common environmental response" (CER). Why such a diverse array of insults should elicit a common transcriptional response remains enigmatic. Previous functional analyses of the networks involved have found that, in addition to up-regulating those for mitigating the specific stressor, the majority appear to be involved in balancing energetic supply and demand and modulating progression through the cell cycle. Here we compared functional and regulatory aspects of the stress responses elicited by the acute inhibition of respiration with antimycin A and oxygen deprivation under catabolite non-repressed (galactose) conditions. Results Gene network analyses of the transcriptomic responses revealed both treatments result in the transient (10 – 60 min) down-regulation of MBF- and SBF-regulated networks involved in the G1/S transition of the cell cycle as well as Fhl1 and PAC/RRPE-associated networks involved in energetically costly programs of ribosomal biogenesis and protein synthesis. Simultaneously, Msn2/4 networks involved in hexose import/dissimilation, reserve energy regulation, and autophagy were transiently up-regulated. Interestingly, when cells were treated with antimycin A well before experiencing anaerobiosis these networks subsequently failed to respond to oxygen deprivation. These results suggest the transient stress response is elicited by the acute inhibition of respiration and, we postulate, changes in cellular energetics and/or the instantaneous growth rate, not oxygen deprivation per se. After a considerable delay (≥ 1 generation) under anoxia, predictable changes in heme-regulated gene networks (e.g., Hap1, Hap2/3/4/5, Mot3, Rox1 and Upc2) were observed both in the presence and absence of antimycin A. Conclusion This study not only differentiates between the gene networks that respond to respiratory inhibition and those that respond to oxygen deprivation but suggests the function of the ESR or CER is to balance energetic supply/demand and coordinate growth with the cell cycle, whether in response to perturbations that disrupt catabolic pathways or those that require rapidly up-regulating energetically costly programs for combating specific stressors.

Approximately 3.3 billion people live with the threat of Plasmodium vivax malaria. Infection can result in liver-localized hypnozoites, which when reactivated cause relapsing malaria. This work demonstrates that an enzyme-cleavable polymeric prodrug of tafenoquine addresses key requirements for a mass administration, eradication campaign: excellent subcutaneous bioavailability, complete parasite control after a single dose, improved therapeutic window compared to the parent oral drug, and low cost of goods sold (COGS) at less than $1.50 per dose. Liver targeting and subcutaneous dosing resulted in improved liver:plasma exposure profiles, with increased efficacy and reduced glucose 6-phosphate dehydrogenase-dependent hemotoxicity in validated preclinical models. A COGS and manufacturability analysis demonstrated global scalability, affordability, and the ability to redesign this fully synthetic polymeric prodrug specifically to increase global equity and access. Together, this polymer prodrug platform is a candidate for evaluation in human patients and shows potential for P. vivax eradication campaigns.

Background: The creatinine height index (CHI) is an estimate of lean body mass. We hypothesize that a modified CHI estimate using serum creatinine (sCr) levels in patients with normal renal function when performed soon after injury would reflect preinjury protein nutrition status., Methods: The urine CHI (uCHI) was calculated using the 24-h urine sample. The serum-derived estimated CHI (sCHI) was calculated using the sCr on admission. Correlation between abdominal computed tomography images at specific lumbar vertebral levels and total body fat and muscle content was used for comparison as an independent measurement of nutrition status unlikely to be substantially altered by trauma., Results: A total of 45 patients were enrolled, all with a significant injury burden (median injury severity score [ISS] = 25; interquartile range, 17-35). The calculated sCHI on admission was 71.0% (SD = 26.9%) and likely underestimates the CHI when compared with uCHI (mean = 112.5%, SD = 32.6%). Stratifying by degree of stress demonstrated that in a group of 23 moderately and severely stressed patients, uCHI (mean = 112.7%, SD = 5.7%) and sCHI (mean = 60.8%, SD = 1.9%) were significantly different and without correlation (r = -0.26, P = 0.91). In patients without stress, there was a significant negative correlation between sCHI and psoas muscle area (r = -0.869, P = 0.03), and in patients with severe stress there was a significant positive correlation between uCHI and psoas muscle area (r = 0.733, P = 0.016)., Conclusion: The CHI calculated from the initial sCr is not an appropriate estimate of uCHI in critically ill trauma patients and is not a valid measure of psoas muscle mass in this setting., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Identifying risk factors for traumatic lower extremity reconstruction outcomes has been limited by sample size. We evaluated patient and procedural characteristics associated with reconstruction outcomes using data from almost four million patients., Methods: The National Trauma Data Bank (2015-2018) was queried for lower extremity reconstructions. Univariable and multivariable analyses determined associations with inpatient outcomes., Results: There were 4675 patients with lower extremity reconstructions: local flaps (77%), free flaps (19.2%), or both (3.8%). Flaps were most commonly local fasciocutaneous (55.1%). Major injuries in reconstructed extremities were fractures (56.2%), vascular injuries (11.8%), and mangled limbs (2.9%). Ipsilateral procedures prereconstruction included vascular interventions (6%), amputations (5.6%), and fasciotomies (4.3%). Postoperative surgical site infection and amputation occurred in 2% and 2.6%, respectively. Among survivors (99%), mean total length of stay (LOS) was 23.2 ± 21.1 days and 46.8% were discharged to rehab. On multivariable analysis, vascular interventions prereconstruction were associated with increased infection [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.05-3.79, P = 0.04], amputation (OR 4.38, 95% CI 2.56-7.47, P < 0.001), prolonged LOS (OR 1.59, 95% CI 1.14-2.22, P = 0.01), and discharge to rehab (OR 1.49, 95% CI 1.07-2.07, P = 0.02). Free flaps were associated with prolonged LOS (OR 2.08, 95% CI 1.74-2.49, P < 0.001)., Conclusions: Prereconstruction vascular interventions were associated with higher incidences of adverse outcomes. Free flaps correlated with longer LOS, but otherwise similar outcomes. Investigating reasons for increased complication and healthcare utilization likelihood among these subgroups is warranted., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction: Approximately 27.5% of adults 65 and older fall each year, over 3 million are treated in an emergency department, and 32 000 die. The American College of Surgeons and its Committee on Trauma (ACSCOT) have urged trauma centers (TCs) to screen for fall risk, but information on the role of TC in this opportunity for prevention is largely unknown., Methods: A 29-item survey was developed by an ACSCOT Injury Prevention and Control Committee, Older Adult Falls workgroup, and emailed to 1000 trauma directors of the National Trauma Data Bank using Qualtrics. US TCs were surveyed regarding fall prevention, screening, intervention, and hospital discharge practices. Data collected and analyzed included respondent's role, location, population density, state designation or American College of Surgeons (ACS) level, if teaching facility, and patient population., Results: Of the 266 (27%) respondents, 71% of TCs include fall prevention as part of their mission, but only 16% of TCs use fall risk screening tools. There was no significant difference between geographic location or ACS level. The number of prevention resources (F = 31.58, P < .0001) followed by the presence of a formal screening tool (F = 21.47, P < .0001) best predicted the presence of a fall prevention program., Conclusion: Older adult falls remain a major injury risk and injury prevention opportunity. The majority of TCs surveyed include prevention of older adult falls as part of their mission, but few incorporate the components of a fall prevention program. Development of best practices and requiring TCs to screen and offer interventions may prevent falls.

Background: The management of complicated ventral hernias (CVH), namely ventral hernias in actively or recently infected/contaminated operative fields, and open abdomens in which the native fascia cannot be primarily reapproximated, pose a surgical challenge. Fetal Bovine and Porcine Acellular Dermal Matrix (BADM and PADM) biologic meshes are being increasingly used in these scenarios. A comparison, however, of clinically relevant outcomes between the two is lacking. With this investigation, we aim to review and compare clinically relevant outcomes in patients that underwent abdominal wall herniorrhaphy with either BADM or PADM at a tertiary urban academic institution over a 5-year period., Methods: Patients who had a BADM or PADM implanted during CVH over a 5-year period at a tertiary urban academic hospital were identified. Baseline clinical and hernia characteristics, as well as postoperative outcomes were compared after a retrospective chart review. Phone interviews were also conducted to assess for recurrence, followed by in-person visits as indicated. Cox Proportional Hazard regression was fitted to identify risk factors for recurrence., Results: Of the 140 patients who underwent biologic mesh implantation for CVH, 109 were for ventral hernia repair and 31 for open abdomen bridging. Mean age was 52.7 ± 14.2 and males constituted 57.9% of our sample, while 25.1% had undergone > 5 prior abdominal operations. Thirty percent were active smokers, and another 30% required emergency surgery. Only immunosuppression was a risk factor for recurrence [HR 13.3 (1.04-169.2), p = 0.047] on Cox Proportional Hazard regression, while mesh selection had no effect., Conclusions: Both BADM and PADM meshes perform well in CVH, with satisfactory recurrence rates, only slightly higher compared to traditional synthetic mesh repairs., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Establishing a permanent human presence on the Moon or Mars requires a secure supply of oxygen for life support and refueling. The electrolysis of water has attracted significant attention in this regard as water-ice may exist on both the Moon and Mars. However, to date there has been no study examining how the lower gravitational fields on the Moon and Mars might affect gas-evolving electrolysis when compared to terrestrial conditions. Herein we provide experimental data on the effects of gravitational fields on water electrolysis from 0.166 g (lunar gravity) to 8 g (eight times the Earth's gravity) and show that electrolytic oxygen production is reduced by around 11% under lunar gravity with our system compared to operation at 1 g. Moreover, our results indicate that electrolytic data collected using less resource-intensive ground-based experiments at elevated gravity (>1 g) may be extrapolated to gravitational levels below 1 g., (© 2022. The Author(s).)

While "stay-at-home" orders for COVID-19 were in effect, many American cities witnessed a rise in community and interpersonal violence. Our own institution, the largest regional trauma facility and Boston's safety net hospital, saw a paradoxical rise in penetrating violent trauma admissions despite decreases in other hospital admissions, leading to our most violent summer in five years. It has been established that minoritized and marginalized communities have faced the harshest impacts of the pandemic. Our findings suggest that the conditions created by the COVID-19 pandemic have amplified the inequities that exist in communities of color that place them at risk for exposure to violence. The pandemic has served to potentiate the impacts of violence already plaguing the communities and patients we serve., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially life-saving intervention. However, recent reports of associations with limb loss and mortality have called its safety into question. We aimed to evaluate patient and hospital characteristics associated with major amputation and in-hospital mortality among patients undergoing REBOA for trauma., Methods: The National Trauma Data Bank (2015-2017) was queried for patients presenting to trauma centers and treated with REBOA. We included REBOA performed on hospital day 1 in patients who survived 6 or more hours from presentation. Univariable and multivariable analyses evaluated associations with major amputation and in-hospital mortality., Results: A total of 316 patients underwent REBOA and survived in the acute period after presentation. Overall, mean age was 45 ± 20 years and the majority were male (73%) and White (56%). Most patients presented to level I trauma centers (72%) after blunt injuries (79%) with an average Injury Severity Score (ISS) of 31 ± 15, indicating major trauma. In 15 patients (5%), there were 18 major amputations-7 above knee and 11 below knee. A subgroup of 11 amputations were either traumatic amputations (73%) or mangled limbs requiring amputation within 24 hours (27%). Of the remaining amputations, 71% were associated with ipsilateral vascular or orthopedic lower extremity injuries of serious to severe Abbreviated Injury Scale severity. Comparing patients with amputations with those without amputations, there were no significant differences in patient demographics, comorbidities, or hospital characteristics. During hospitalization, patients requiring amputation more frequently received open peripheral vascular interventions (40% vs 10%; P = .002), underwent similar numbers of endovascular interventions (6.7% vs 4.7%; P = .5), and more often developed compartment syndrome (13% vs 2%; P = .04). Overall, there were 110 deaths (35%). The major amputation prevalence was similar between patients who died vs those who survived (3.6% vs 5.3%; P = .5). In multivariable analysis, prehospital cardiac arrest (odds ratio [OR], 8.47; 95% confidence interval [CI], 1.47-48.66; P = .02), penetrating vs blunt trauma (OR, 5.5; 95% CI, 1.05-28.82; P = .04), decreased Glasgow Coma Scale score (OR, 1.18; 95% CI, 1.05-1.32; P = .01), older age (OR, 1.06; 95% CI, 1.03-1.10; P < .001), and increased Injury Severity Score (OR, 1.05; 95% CI, 1.0-1.1; P = .03) were associated with higher mortality., Conclusions: The majority of major amputations in patients undergoing REBOA were secondary to the initial traumatic mechanism. Injury type and severity, as well as initial hemodynamic derangements, are associated with mortality after REBOA. Despite concerns about prohibitive limb complications of REBOA, baseline injuries seem to be the primary cause of limb loss, but further prospective analysis is needed., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Primaquine and tafenoquine are the two 8-aminoquinoline (8-AQ) antimalarial drugs approved for malarial radical cure - the elimination of liver stage hypnozoites after infection with Plasmodium vivax. A single oral dose of tafenoquine leads to high efficacy against intra-hepatocyte hypnozoites after efficient first pass liver uptake and metabolism. Unfortunately, both drugs cause hemolytic anemia in G6PD-deficient humans. This toxicity prevents their mass administration without G6PD testing given the approximately 400 million G6PD deficient people across malarial endemic regions of the world. We hypothesized that liver-targeted delivery of 8-AQ prodrugs could maximize liver exposure and minimize erythrocyte exposure to increase their therapeutic window. Primaquine and tafenoquine were first synthesized as prodrug vinyl monomers with self-immolative hydrolytic linkers or cathepsin-cleavable valine-citrulline peptide linkers. RAFT polymerization was exploited to copolymerize these prodrug monomers with hepatocyte-targeting GalNAc monomers. Pharmacokinetic studies of released drugs after intravenous administration showed that the liver-to-plasma AUC ratios could be significantly improved, compared to parent drug administered orally. Single doses of the liver-targeted, enzyme-cleavable tafenoquine polymer were found to be as efficacious as an equivalent dose of the oral parent drug in the P. berghei causal prophylaxis model. They also elicited significantly milder hemotoxicity in the humanized NOD/SCID mouse model engrafted with red blood cells from G6PD deficient donors. The clinical application is envisioned as a single subcutaneous administration, and the lead tafenoquine polymer also showed excellent bioavailability and liver-to-blood ratios exceeding the IV administered polymer. The liver-targeted tafenoquine polymers warrant further development as a single-dose therapeutic via the subcutaneous route with the potential for broader patient administration without a requirement for G6PD diagnosis., (Copyright © 2020. Published by Elsevier B.V.)

Background: . Hospitalized self-inflicted firearm injuries have not been extensively studied, particularly regarding clinical diagnoses at the index admission. The objective of this study was to discover the diagnostic phenotypes (DPs) or clusters of hospitalized self-inflicted firearm injuries., Methods: . Using Nationwide Inpatient Sample data in the US from 1993 to 2014, we used International Classification of Diseases, Ninth Revision codes to identify self-inflicted firearm injuries among those ≥18 years of age. The 25 most frequent diagnostic codes were used to compute a dissimilarity matrix and the optimal number of clusters. We used hierarchical clustering to identify the main DPs., Results: . The overall cohort included 14072 hospitalizations, with self-inflicted firearm injuries occurring mainly in those between 16 to 45 years of age, black, with co-occurring tobacco and alcohol use, and mental illness. Out of the three identified DPs, DP1 was the largest (n=10,110), and included most common diagnoses similar to overall cohort, including major depressive disorders (27.7%), hypertension (16.8%), acute post hemorrhagic anemia (16.7%), tobacco (15.7%) and alcohol use (12.6%). DP2 (n=3,725) was not characterized by any of the top 25 ICD-9 diagnoses codes, and included children and peripartum women. DP3, the smallest phenotype (n=237), had high prevalence of depression similar to DP1, and defined by fewer fatal injuries of chest and abdomen., Limitations: . Claims data., Conclusions: . There were three distinct diagnostic phenotypes in hospitalizations due to self-inflicted firearm injuries. Further research is needed to determine how DPs can be used to tailor clinical care and prevention efforts., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Develop a model for quality improvement in tracheostomy care and decrease tracheostomy-related complications., Methods: This study was a prospective quality improvement project at an academic tertiary care hospital. A multidisciplinary team was assembled to create institutional guidelines for clinical care during the pre-operative, intra-operative, and post-operative periods. Baseline data was compiled by retrospective chart review of 160 patients, and prospective tracking of select points over 8 months in 73 patients allowed for analysis of complications and clinical parameters., Results: Implementation of a quality improvement team was successful in creating guidelines, setting baseline parameters, and tracking data with run charts. Comparison of pre- and post-guideline data showed a trend toward decreased rate of major complications from 4.38% to 2.74% (p = 0.096). Variables including time to tracheotomy for prolonged intubation, surgical technique, day of first tracheostomy tube change, and specialty performing surgery did not show increased risk of complications. There were increased tracheostomy-related complications in cold months (p = 0.04)., Conclusions: An interdisciplinary quality improvement team can improve tracheostomy care by identifying system factors, standardizing care among specialties, and providing continuous monitoring of select data points., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: While damage control resuscitation is known to confer a survival advantage in severely injured patients, high-ratio blood component therapy should be initiated only in carefully selected trauma patients, due to the morbidity associated with blood product use. With this project, we aim to identify the effect of platelet transfusion in non-massively transfused bluntly injured patients., Methods: The Glue Grant database was retrospectively queried and severely injured blunt trauma patients who underwent non-massive transfusion were identified. Patients were divided into quartiles depending on platelet volume they were transfused in the first 48 h. Outcomes of interest included mortality; ventilator, Intensive Care Unit (ICU) and hospital length of stay (LOS); infectious and non-infectious complications. Multivariable regression models were fitted for these outcomes, controlling for age, pre-existing comorbidities, injury severity, acute physiologic derangement, neurologic injury burden, and other fluid and blood product resuscitation., Results: There was no difference in mortality, LOS, or the incidence of multi-organ failure and infectious complications. However, patients receiving ≥ 250 mL of platelets were more likely to develop acute respiratory distress syndrome (ARDS) compared to those who received < 250 mL [odds ratio 1.91 (95% CI 1.10-3.33, p = 0.022)]., Conclusions: Pre-emptive platelet transfusion should be avoided in non-massively transfused blunt injury victims in the absence of true or functional thrombocytopenia, as it increases risk for ARDS with no survival benefit.

Massive transfusion protocols (MTP) vary at different institutions. We implemented an algorithm in the transfusion service to support our Level I trauma center in 2007 and periodically monitor MTP utilization as part of ongoing quality management. At the last review in 2013, median plasma: RBC ratio was 1:1.8. We undertook a retrospective 3-year review of MTP activations stratifying by trauma versus non-trauma indications, and blood component utilization of the massive transfusion (MT) cases, adding a review of tranexamic acid (TXA) administration to the audit. The median transfused plasma: RBC ratio was 1:1.9 in trauma MT, and 1:1.6 in the non-trauma MT cases. Non-trauma MT patients at our institution were significantly older and more coagulopathic at MTP initiation compared to trauma MT patients, received fewer RBC units (15.5 versus 20.2), and had higher mortality. TXA adherence increased over the 3-year period to 60% of all trauma MTP activations in 2017., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Prescription drug marketing to physicians often includes clinical trial data. Prior research has shown that physicians may not have the necessary knowledge to understand all clinical trial results and they can be influenced by how these results are reported. This study focused on physicians' reactions to and evaluations of clinical trial data presented in professional prescription drug promotion., Methods: We conducted 60-minute interviews with practicing physicians across the United States (50 primary care physicians and 22 endocrinologists). Physicians viewed prescription drug promotional materials that contained clinical trial data and answered follow-up questions., Results: Physicians demonstrated low to moderate knowledge about clinical trial-related terms found in promotional prescription drug materials., Discussion: Results from this qualitative analysis underscore a need to determine how clinical trial data in prescription drug promotional materials affect physicians' attitudes and decision making., Competing Interests: Conflict of interest: none declared., (© Copyright 2018 by the American Board of Family Medicine.)

Background: In the United States, there is a perceived divide regarding the benefits and risks of firearm ownership. The American College of Surgeons Committee on Trauma Injury Prevention and Control Committee designed a survey to evaluate Committee on Trauma (COT) member attitudes about firearm ownership, freedom, responsibility, physician-patient freedom and policy, with the objective of using survey results to inform firearm injury prevention policy development., Methods: A 32-question survey was sent to 254 current U.S. COT members by email using Qualtrics. SPSS was used for χ exact tests and nonparametric tests, with statistical significance being less than 0.05., Results: Our response rate was 93%, 43% of COT members have firearm(s) in their home, 88% believe that the American College of Surgeons should give the highest or a high priority to reducing firearm-related injuries, 86% believe health care professionals should be allowed to counsel patients on firearms safety, 94% support federal funding for firearms injury prevention research. The COT participants were asked to provide their opinion on the American College of Surgeons initiating advocacy efforts and there was 90% or greater agreement on 7 of 15 and 80% or greater on 10 of 15 initiatives., Conclusion: The COT surgeons agree on: (1) the importance of formally addressing firearm injury prevention, (2) allowing federal funds to support research on firearms injury prevention, (3) retaining the ability of health care professionals to counsel patients on firearms-related injury prevention, and (4) the majority of policy initiatives targeted to reduce interpersonal violence and firearm injury. It is incumbent on trauma and injury prevention organizations to leverage these consensus-based results to initiate prevention, advocacy, and other efforts to decrease firearms injury and death., Level of Evidence: Prognostic/epidemiologic study, level I; therapeutic care, level II.

Background: Histone deacetylase inhibitors (HDACI) are members of a family of epigenetic modifying agents with broad anti-inflammatory properties. These anti-inflammatory properties may have important therapeutic implications in acute respiratory distress syndrome (ARDS). However, administration of HDACI may create an immunosuppressive environment conducive to bacterial growth. Accordingly, the aim of the current study is to investigate the effect of HDACI valproic acid (VPA) on host inflammatory response and bacterial burden in a murine model of Escherichia coli pneumonia-induced ARDS., Methods: ARDS was induced in male C57BL6 mice (n = 24) by endotracheal instillation of 3 × 10 E. coli. VPA (250 mg/kg) was administered 30 minutes after E. coli instillation in the intervention group. Blood samples were collected at 3 and 6 hours, and animals were sacrificed at 6 hours. Bronchoalveolar lavage (BAL) was performed, and tissue specimens were harvested. Cytokine levels were measured in blood and BAL, and so was transalveolar protein transit. Cell counts and colony forming units were quantified in BAL fluid., Results: VPA reduced neutrophil influx into the lungs and local tissue destruction through decreased myeloperoxidase activity. It also ameliorated the pulmonary and systemic inflammatory response. This led to greater bacterial proliferation in the pulmonary parenchyma., Conclusion: Administration of VPA in a clinically relevant bacterial model of murine ARDS mitigates the host inflammatory response, essentially preventing ARDS, but creates an immunosuppressive environment that favors bacterial overgrowth.

Importance: Trauma patients admitted to the hospital are at increased risk of bleeding and thrombosis. The use of inferior vena cava (IVC) filters in this population has been increasing, despite a lack of high-quality evidence to demonstrate their efficacy., Objective: To determine if IVC filter insertion in trauma patients affects overall mortality., Design, Setting, and Participants: This retrospective cohort study used stratified 3:1 propensity matching to select a control population similar to patients who underwent IVC filter insertion at Boston Medical Center (a level I trauma center at Boston University School of Medicine) between August 1, 2003, and December 31, 2012. Among patients with an IVC filter and matched controls, age, sex, race/ethnicity, and Injury Severity Score were entered into a multivariable logistic regression model to calculate a propensity score. Matching was stratified by the date of injury., Main Outcomes and Measures: Multivariable logistic regression was used to compare hospital mortality across both groups, adjusting for age, sex, race/ethnicity, Injury Severity Score, and brain injury severity using the head and neck Abbreviated Injury Score. To determine any significant difference in mortality, patient characteristics and mortality data from the National Death Index were analyzed in all patients and in those who survived 24, 48, and 72 hours after injury, as well as at hospital discharge., Results: Among 451 trauma patients with an IVC filter and 1343 matched controls without an IVC filter, the mean (SD) age was 47.4 (21.5) years. The median Injury Severity Score overall was 24 (range, 1-75). Based on a mean follow-up of 3.8 years (range, 0-9.4 years), there was no significant difference in overall mortality or cause of mortality in patients with vs without an IVC filter who survived more than 24 hours from the time of injury, independent of the presence or absence of deep vein thrombosis or pulmonary embolism at the time of IVC filter placement. Additional analyses at shorter intervals of 6 months and 1 year after discharge also showed no significant difference between the 2 groups of patients. Eight percent (38 of 451) of the IVC filters were removed at Boston Medical Center during the follow-up period., Conclusions and Relevance: The research herein demonstrates no significant difference in survival in trauma patients with vs without placement of an IVC filter, whether in the presence or absence of venous thrombosis. The use of IVC filters in this population should be reexamined because filter removal rates are low and there is increased risk of morbidity in patients with filters that remain in place.

The objective of this study was to determine the incidence and interobserver agreement of individual CT findings as well as the bowel injury prediction score (BIPS) in surgically proven bowel injury after blunt abdominal trauma. This HIPAA-compliant retrospective study was IRB approved and consent was waived. All patients 14 years or older who sustained surgically proven bowel injury after blunt abdominal trauma between 1/1/2004 and 6/30/2015 were included. Admission trauma MDCT scans were independently interpreted by two abdominal fellowship-trained radiologists who recorded the following CT findings: intraperitoneal fluid, mesenteric hematoma/fat stranding, bowel wall thickening/hematoma, active intravenous contrast extravasation, free intraperitoneal air, bowel wall discontinuity, and focal bowel hypoenhancement. Subsequently, the electronic medical records of the included patients, admission abdominal physical exam results, admission white blood cell count, and findings at exploratory laparotomy of the included patients were recorded. Thirty-three patients met the inclusion criteria. The incidence and interobserver agreement of the CT findings were as follows: intraperitoneal fluid 93.9 %, kappa = 0.784 (good); mesenteric hematoma/fat stranding 84.8 %, kappa = 0.718 (good); bowel wall thickening/hematoma 42.4 %, kappa = 0.491 (moderate); active IV contrast extravasation 36.3 %, kappa = 1.00 (perfect); free intraperitoneal air 21.2 %, kappa = 0.904 (very good), bowel wall discontinuity 6.1 %, kappa = 1.00 (perfect); and focal bowel hypoenhancement 6.1 %, kappa = 0.468 (moderate). An absence of the specified CT findings was encountered in 9.1 % with surgically proven bowel injuries (kappa = 1.00, perfect). In our study, 9/16 patients or 56.3 % had a bowel injury prediction score (BIPS) of 2 or more as defined by McNutt et al. (J Trauma Acute Care Surg 78(1):105-111, 2014). The presence of intraperitoneal fluid and mesenteric hematoma/fat stranding are the most common CT findings in bowel injuries proven at laparotomy. A small percentage of patients have no abnormal CT findings. This grading system did not prove to be useful in our study likely due to our inherently small patient population; however, the use of BIPS deserves further investigation as it may help in identifying blunt bowel and mesenteric injury patients with often subtle or nonspecific CT findings.

Introduction: Among people aged ≥65 years, falling is the leading cause of emergency department visits. Emergency medical services (EMS) are often called to help older adults who have fallen, with some requiring hospital transport. Chief aims were to determine where falls occurred and the circumstances under which patients were transported by EMS, and to identify future fall prevention opportunities., Methods: In 2012, a total of 42 states contributed ambulatory data to the National EMS Information System, which were analyzed in 2014 and 2015. Using EMS records from 911 call events, logistic regression examined patient and environmental factors associated with older adult transport., Results: Among people aged ≥65 years, falls accounted for 17% of all EMS calls. More than one in five (21%) of these emergency 911 calls did not result in a transport. Most falls occurred at home (60.2%) and residential institutions such as nursing homes (21.7%). Logistic regression showed AORs for transport were greatest among people aged ≥85 years (AOR=1.14, 95% CI=1.13, 1.16) and women (AOR=1.30, 95% CI=1.29, 1.32); for falls at residential institutions or nursing homes (AOR=3.52, 95% CI=3.46, 3.58) and in rural environments (AOR=1.15, 95% CI=1.13, 1.17); and where the EMS impression was a stroke (AOR=2.96, 95% CI=2.11, 4.10), followed by hypothermia (AOR=2.36, 95% CI=1.33, 4.43)., Conclusions: This study provides unique insight into fall circumstances and EMS transport activity. EMS personnel are in a prime position to provide interventions that can prevent future falls, or referrals to community-based fall prevention programs and services., (Published by Elsevier Inc.)

There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity., (Copyright © 2016 Leggett et al.)

Background: The Joint Commission requires hospitals to develop systems in which a team of clinicians can rapidly recognize and respond to changes in a patient's condition. The rapid response team (RRT) concept has been widely adopted as the solution to this mandate. The role of house staff in RRTs and the impact on resident education has been controversial. At Christiana Care Health System, eligible residents in their second through final years lead the RRTs., Objective: To evaluate the use of a team-based, interdisciplinary RRT training program for educating and training first-year residents in an effort to improve global RRT performance before residents start their second year., Methods: This pilot study was administered in 3 phases. Phase 1 provided residents with classroom-based didactic sessions using case-based RRT scenarios. Multiple choice examinations were administered, as well as a confidence survey based on a Likert scale before and after phase 1 of the program. Phase 2 involved experiential training in which residents engaged as mentored participants in actual RRT calls. A qualitative survey was used to measure perceived program effectiveness after phase 2. In phase 3, led by senior residents, simulated RRTs using medical mannequins were conducted. Participants were divided into 5 teams, in which each resident would rotate in the roles of leader, nurse, and respiratory therapist. This phase measured resident performance with regard to medical decision making, data gathering, and team behaviors during the simulated RRT scenarios. Performance was scored by an attending and a senior resident., Results: A total of 18 residents were eligible (N=18) for participation. The average multiple choice test score improved by 20% after didactic training. The average confidence survey score before training was 3.44 out of 5 (69%) and after training was 4.13 (83%), indicating a 14% improvement. High-quality team behaviors correlated with medical decision making (0.92) more closely than did high-quality data gathering (0.11). This difference narrowed during high-pressure scenarios (0.84 and 0.72, respectively)., Conclusion: Our data suggest that resident training using a team-based, interdisciplinary RRT training program may improve resident education, interdisciplinary team-based dynamics, and global RRT performance. In turn, data gathering and medical decision making may be enhanced, which may result in better patient outcomes during RRT scenarios.

Background: Fourteen percent (43.1 million) of the population in the United States was 65 years and older in 2012. This population is projected to reach 20% (88.5 million) by 2050. Older adults accounted for 17% of all traffic fatalities and 9% of all vehicle occupant injuries in 2012. We explored the effectiveness of three interventions to help older adults assess their current driving behaviors at a Level 1 trauma center., Methods: During 2010 to 2012, 1,216 inpatients 70 years and older admitted for surgical and medical services were screened for eligibility, and 120 were enrolled. Participants completed a driving assessment and preintervention questionnaires and were subsequently randomized to one of the following interventions: (1) brief negotiated interview plus an educational kit by the American Automobile Association about older driving plus an accompanying list of Web-based resources for older adult drivers; (2) American Automobile Association document and a list of Web-based resources; (3) online referral sheet of the list of Web-based resources only. A 3-month postintervention follow-up questionnaire was administered over the telephone to measure changes in (1) driving-related knowledge, attitudes, and beliefs as well as (2) driving-related behaviors and intended behaviors., Results: A total of 113 randomized patients were included in the analysis. The mean (SD) age was 76.8 (5.23) years; majority of patients were white (64%), followed by black African American (33%); and 51% were males and 49% were females. Multivariate analysis showed that older adults' driving knowledge, attitudes, and beliefs (p < 0.0001, R = 0.37) as well as behaviors and intentions (p < 0.0001, R = 0.27) toward driving were positively correlated, controlling for other predictors in the model. Intervention assignment did not affect changes in outcomes, although outcomes improved across experimental conditions., Conclusion: Our pilot study suggests that older adults are likely to make changes in their driving behavior on the basis of minimal hospital-based intervention.

Purpose: The development of eligibility criteria and use of tranexamic acid in conjunction with a massive transfusion protocol (MTP) are described., Summary: The trauma surgery and pharmacy departments collaborated to operationalize tranexamic acid administration in trauma patients for whom an MTP was activated. The MTP at Boston Medical Center, an urban, tertiary, academic medical center, is activated by the attending physician when the patient is expected to require at least 10 units of packed red blood cells in 24 hours. Tranexamic acid was considered in MTP trauma patients who arrived at the medical center within 8 hours of traumatic injury, were 15 years of age or older, and weighed at least 40 kg. Eligible patients were to receive a loading dose of tranexamic acid 1 g i.v. over 10 minutes followed by a maintenance dose of 1 g infused over 8 hours. To ensure that tranexamic acid use was limited to trauma patients, both its location of use and physician-ordering privileges were restricted by the pharmacy department. A 16-month assessment revealed that 16 patients received tranexamic acid, 13 (81%) of whom met all criteria for use. Tranexamic acid was used in 13 (38%) of 34 eligible MTP patients. Barriers to the use of tranexamic acid include a lack of familiarity with the medication among staff, drug availability, the complexity of administration, and the critical setting of MTP activation., Conclusion: Multidisciplinary collaboration and standardization of tranexamic acid use in conjunction with an MTP promoted use of the drug within a trauma population., (Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Objectives: To elucidate the mechanisms of spore resistance to and killing by the oxidizing microbicide peracetic acid (PAA)., Methods: Mutants of Bacillus subtilis lacking specific spore structures were used to identify resistance properties in spores and to understand the mechanism of action of PAA. We also assessed the effect of PAA treatment on a number of spore properties including heat tolerance, membrane integrity and germination., Results: The spore coat is essential for spore PAA resistance as spores with defective coats were greatly sensitized to PAA treatment. Small acid-soluble spore proteins apparently provide no protection against PAA. Defects in spore germination, specifically in germination via the GerB and GerK but not the GerA germination receptors, as well as leakage of internal components suggest that PAA is active at the spore inner membrane. It is therefore likely that the inner membrane is the major site of PAA's sporicidal activity., Conclusions: PAA treatment targets the spore membrane, with some of its activity directed specifically against the GerB and GerK germination receptors., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Although the association between trauma exposure and posttraumatic stress disorder (PTSD) symptoms is well established, how such trauma is incorporated into identity, or the centrality of the negative event, is also of considerable importance in understanding the development of psychological symptoms. Alternatively, positive event centrality may have positive effects on well-being in the face of trauma. Thus, the current study examined associations between positive and negative event centrality, and both adaptive and maladaptive outcomes, above and beyond the impact of traumatic experience. A sample of 214 college students completed a series of self-report questionnaires. As anticipated, negative event centrality predicted PTSD and other maladaptive measures of functioning, even after controlling for traumatic experience. High levels of positive event centrality predicted adaptive, as opposed to maladaptive, psychological functioning. Results also suggested that both positive and negative event centrality predicted posttraumatic growth, controlling for traumatic experience. These findings suggest that assessing centrality of trauma may also be valuable in the prediction of psychological symptoms. The implications of these findings and proposals for future work are discussed further., ((c) 2015 APA, all rights reserved).)

The formulation and delivery of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, poses substantial challenges owing to their large size and susceptibility to degradation. In this Review we highlight recent advances in formulation and delivery strategies--such as the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs--and discuss their advantages and limitations. We also highlight current and emerging delivery routes that provide an alternative to injection, including transdermal, oral and pulmonary delivery routes. In addition, the potential of targeted and intracellular protein delivery is discussed.

A loop-mediated isothermal amplification (LAMP) assay for open reading frame 1 (ORF1) of the glutamine synthetase gene of Neisseria gonorrhoeae was able to tolerate urea concentrations of ≤ 1.8 M, compared with a PCR assay that was functional at concentrations of <100 mM. The LAMP assay was as sensitive as the PCR assay while being faster and simpler to perform., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Penetrating neck injuries are commonly related to stab wounds and gunshot wounds in the United States. The injuries are classified by penetration site in terms of the three anatomical zones of the neck. Based on this zonal classification system, penetrating injuries to the head and neck have traditionally been evaluated by conventional angiography and/or surgical exploration. In recent years, multidetector-row computed tomography (CT) angiography has significantly improved detectability of vascular injuries and extravascular injuries in the setting of penetrating injuries. CT angiography is a fast and minimally invasive imaging modality to evaluate penetrating injuries of the head and neck for stable patients. The spectrum of penetrating neck injuries includes vascular injury (extravasation, pseudoaneurysm, dissection, occlusion, and arteriovenous fistula), aerodigestive injury (esophageal and tracheal injuries), salivary gland injury, neurologic injury (spinal canal and cerebral injuries), and osseous injury, all of which can be evaluated using CT angiography. Familiarity with the complications and imaging characteristics of penetrating injuries of the head and neck is essential for accurate diagnosis and optimal treatment.

Background: Prion contamination is a risk during device reprocessing, being difficult to remove and inactivate. Little is known of the combined effects of cleaning, disinfection and sterilization during a typical reprocessing cycle in clinical practice., Aim: To investigate the combination of cleaning, disinfection and/or sterilization on reducing the risk of surface prion contamination., Methods: In vivo test methods were used to study the impact of cleaning alone and cleaning combined with thermal disinfection and high- or low-temperature sterilization processes. A standardized test method, based on contamination of stainless steel wires with high titres of scrapie-infected brain homogenates, was used to determine infectivity reduction., Findings: Traditional chemical methods of surface decontamination against prions were confirmed to be effective, but extended steam sterilization was more variable. Steam sterilization alone reduced the risk of prion contamination under normal or extended exposure conditions, but did show significant variation. Thermal disinfection had no impact in these studies. Cleaning with certain defined formulations in combination with steam sterilization can be an effective prion decontamination process, in particular with alkaline formulations. Low-temperature, gaseous hydrogen peroxide sterilization was also confirmed to reduce infectivity in the presence and absence of cleaning., Conclusion: Prion decontamination is affected by the full reprocessing cycle used on contaminated surfaces. The correct use of defined cleaning, disinfection and sterilization methods as tested in this report in the scrapie infectivity assay can provide a standard precaution against prion contamination., (Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Purpose: Approximately 35% to 60% of all patients with head and neck cancer are malnourished at the time of their diagnosis because of tumor burden and obstruction of intake or the anorexia and cachexia associated with their cancer. The purpose of this article is to provide a contemporary review of the nutritional aspects of care for patients with head and neck cancer., Materials and Methods: A literature search was performed in Medline, Cochrane, and other available databases from 1990 through 2012 for the clinical effectiveness of nutritional support, treatment modalities, and methods of delivery in relation to patients with head and neck malignancies. Human studies published in English and having nutritional status and head and neck cancer as a predictor variable were included. Randomized controlled trials, meta-analyses, prospective clinical studies, and systemic reviews were selected based on their relevance to the abovementioned subtitles. The resultant articles were analyzed and summarized into the definition, impact, assessment, treatment, and modes of administration of nutrition on the outcome of patients with head and neck cancer., Results: Articles were reviewed that focused on the etiology and assessment of malnutrition and current nutritional treatments for cancer-induced anorexia and cachexia. Two hundred forty-eight articles were found: 2 clinical trials, 10 meta-analyses, 210 review studies, and 26 systematic reviews. Because of the lack of prospective data, a summative review of the conclusions of the studies is presented., Conclusion: Nutritional interventions should be initiated before cancer treatment begins and these interventions need to be ongoing after completion of treatment to ensure optimal outcomes for patients. A nutritional assessment must be part of all comprehensive treatment plans for patients with head and neck cancer. Alternative medical interventions, such as immune-enhancing nutrients or anticytokine pharmaceutical agents, also may be effective as adjuvant therapies, but more research is needed to quantify their clinical effect., (Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. All rights reserved.)

Nucleic acid therapeutics are attracting renewed interest due to recent clinical advances and product approvals. Most leading programs use chemical conjugates, or viral vectors in the case of gene therapy, while several use no delivery system at all. Polymer systems, which have been at the periphery of this renaissance, often involve greater molecular complexity than competing approaches, which must be justified by their advantages. Advanced analytical methods, along with biological tools for characterizing biotransformation and intracellular trafficking, are increasingly being applied to nucleic acid delivery systems including those based on polymers. These frontiers of investigation create the opportunity for an era where highly defined polymer compositions are optimized based on mechanistic insights in a way that has not been previously possible, offering the prospect of greater differentiation from alternatives. This will require integrated collaboration between polymer scientists and those from other disciplines.

Purpose: Clinical development of cancer drugs has a low success rate. Prognostic and predictive biomarkers using minimally invasive approaches hold promise for increasing the probability of success by enabling disease characterization, patient selection and early detection of drug treatment effect. Enumeration and molecular characterization of circulating tumor cells (CTC) may address some of these needs, and thus were evaluated for utility in a Phase I solid tumor clinical study., Experimental Design: Blood samples for CTC analysis were obtained from 24 cancer patients in a multi-center all-comer Phase I study of MEDI-575, a novel anti-PDGFRα antibody. Samples were taken at screening and analyzed for enumeration of CTC using the CellSearch(®) platform and for molecular characterization using a novel quantitative RT-PCR assay., Results: Fifty-nine percent of the patients showed at least 1 CTC per 7.5 ml of blood at baseline. Progression-free survival (PFS) and overall survival (OS) of patients with 0 CTCs at baseline were longer than PFS and Os for patients with 1-3 and >3 CTCs (8.8 versus 1.4 and 1.3 months PFS, P = 0.02; 9.0 vs 7.4 and 3.5 months OS, P = 0.20, respectively). Patients with 0 CTC showed a greater percentage of stable disease than the other 2 groups with 1-3 and >3 CTCs (57% vs 29% and 0%). The multimarker qRT-PCR method detected CTC in 40% of the patients, and 80% of these patients were positive for pre-selected drug target genes., Conclusion: CTC enumeration of patients in an all-comer study is feasible and may allow for patient stratification for PFS and Os to evaluate the clinical response of investigational agents. Gene expression profiling of isolated CTC may provide a means for molecular characterization of selected tumor targets.

Hepatocyte nuclear factor (HNF)-4α is a key member of the transcription factor network regulating hepatocyte differentiation and function. Genetic and molecular evidence suggests that expression of HNF-4α is mainly regulated at the transcriptional level. Activation of HNF-4A gene involves the interaction of distinct sets of transcription factors and co-transcription factors within enhancer and promoter regions. Here we study the inhibitory effect of microRNAs (miRNAs) on the 3'-untranslated region (3'-UTR) of HNF-4A mRNA. The potential recognition elements of a set of miRNAs were identified utilizing bioinformatics analysis. The family members of miR-34 and miR-449, including miR-34a, miR-34c-5p and miR-449a, share the same target elements located at two distinct locations within the 3'-UTR of HNF-4A. The over-expression of miR-34a, miR-34c-5p or miR-449a in HepG2 cells led to a significant decrease in the activity of luciferase reporter carrying 3'-UTR of HNF-4A. The repressive effect on reporter activity was partially or fully eliminated when one or two of the binding site(s) for miR-34a/miR-34c-5p/miR-449a were deleted within the 3'-UTR. The protein level of HNF-4α was dramatically reduced by over-expression of miR-34a, miR-34c-5p and miR-449a, which correlates with a decrease in the binding activity of HNF-4α and transactivation of HNF-4α target genes. These results suggest that the recognition sites of miR-34a, miR-34c-5p and miR-449a within 3'-UTR of HNF-4A are functional. The mechanism of down-regulation of the binding activity and transactivation of HNF-4α by the miRNAs involves the decrease in HNF-4α protein level via miRNAs selectively targeting HNF-4A 3'-UTR, leading to the translational repression of HNF-4α expression., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The hepatic acute phase response(APR) is an organ-specific response to a diverse array of insults and is largely under transcriptional control. Liver-specific transcription factors, hepatic nuclear factors (HNFs)-1α and 4α play important roles in maintenance of liver phenotype and function and their binding activity changes early after injury. However, their roles in modulation of the liver's response over time are not defined., Materials and Methods: C57/BL6 mice were anesthetized and exposed to 95°C water for 10 s to create a 15% body surface area full-thickness burn. At specific time points, the mice were sacrificed. An ELISA for IL-6 was performed on serum and hepatic mRNA levels for fibrinogen-γ and serum amyloid A(SAA)-3 were obtained through polymerase chain reaction (PCR). Transcriptional factor binding activity was assessed with electrophoretic mobility shift assays., Results: Serum IL-6 levels peaked at 3 h and fibrinogen-γ and SAA mRNA levels increased more than 6-fold at 12 h before returning to control levels at 48 h. The binding activity of HNF-4α and HNF-1α rapidly declined after injury (1.5 h) but recovered to near control level at 24 and 6 h, respectively., Conclusions: Changes in HNF-4α and HNF-1α binding occurred before changes in acute phase protein mRNA levels and were preceded by the peak in IL-6 levels. The rapid suppression and reconstitution of liver-specific transcription factor binding after injury may represent a mechanism that allows the normal liver phenotype to change and an injury-response phenotype to prevail. This mechanism in the liver's adaptive response to injury suggests a central role for both HNF-4α and HNF-1α in transcriptional regulation of the hepatic APR., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Chest radiography is routinely used post-tracheostomy to evaluate for complications. Often, the chest X-ray findings do not change clinical management. The present study was conducted to evaluate the utility of post-tracheostomy X-rays., Method: This retrospective review of 255 patients was performed at a single-center, university, level I trauma center. All patients underwent tracheostomy and were evaluated for postprocedure complications., Results: Of the 255 patients, 95.7% had no change in postprocedure chest X-ray findings. New significant chest X-ray findings were found in 4.3% of patients, including subcutaneous emphysema, pneumothorax, and new significant consolidation. Only three of these patients required change in clinical management, and all changes were based on clinical presentation alone., Conclusions: Routine chest X-ray following tracheostomy fails to provide additional information beyond clinical examination. Therefore radiographic examination should be performed only after technically difficult procedures or if the patient experiences clinical deterioration. Significant cost savings and minimization of radiation exposure can be achieved when chest radiography after tracheostomy is performed exclusively for clinical indications.