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Foot-and-mouth disease (FMD) is a highly contagious disease that results in enormous economic loses worldwide. Although the protection provided by vaccination is limited during early infection, it is recognized as the best method to prevent FMD outbreaks. Furthermore, the mechanism of host early responses against foot-and-mouth disease virus (FMDV) infection remains unclear. In our study, a pig kidney cell line (PK-15) was used as a cell model to reveal the mechanism of early pig responses to FMDV infection. Four non-treated control and four FMDV-treated PK-15 cells were sequenced with RNA-seq technology, and the differentially expressed genes (DEGs) were analyzed. The results showed that 1212 DEGs were in the FMDV-infected PK-15 cells, including 914 up-regulated and 298 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the tumor necrosis factor (TNF), cytokine-cytokine receptor interaction, NOD-like receptor, toll-like receptor, NF-κB, and the chemokine signaling pathways. To verify the results of the DEGs, 30 immune-related DEGs (19 up-regulated and 11 down-regulated) were selected for Quantitative Reverse Transcriptase polymerase chain reaction (RT-qPCR) verification. The results showed that RT-qPCR-measured genes exhibited a similar pattern as the RNA-seq analyses. Based on bioinformatics analysis, during FMDV early infection, we found that a series of cytokines, such as interleukins (IL6), chemokines (CXCL2, CCL20 and CCL4), and transcription factors (ZFP36, FOS, NFKBIA, ZBTB3, ZNF503, ZNF283, dymeclin (DYM), and orthodenticle homeobox 1 (OTX1)) were involved in the battle between FMDV and the host. Combined with their features and functions, we propose inflammation as the main early mechanism by which the host responds to FMDV infection. These data provide an additional panel of candidate genes for deciphering the mechanisms of a host's early response against FMDV infection. Show less

We sought to determine the outcome of suicidal hanging and the impact of targeted temperature management (TTM) on hanging-induced cardiac arrest (CA) through an Eastern Association for the Surgery of Trauma (EAST) multicenter retrospective study. We analyzed hanging patient data and TTM variables from January 1992 to December 2015. Cerebral performance category score of 1 or 2 was considered good neurologic outcome, while cerebral performance category score of 3 or 4 was considered poor outcome. Classification and Regression Trees recursive partitioning was used to develop multivariate predictive models for survival and neurologic outcome. A total of 692 hanging patients from 17 centers were analyzed for this study. Their overall survival rate was 77%, and the CA survival rate was 28.6%. The CA patients had significantly higher severity of illness and worse outcome than the non-CA patients. Of the 175 CA patients who survived to hospital admission, 81 patients (46.3%) received post-CA TTM. The unadjusted survival of TTM CA patients (24.7% vs 39.4%, p < 0.05) and good neurologic outcome (19.8% vs 37.2%, p < 0.05) were worse than non-TTM CA patients. However, when subgroup analyses were performed between those with an admission Glasgow Coma Scale score of 3 to 8, the differences between TTM and non-TTM CA survival (23.8% vs 30.0%, p = 0.37) and good neurologic outcome (18.8% vs 28.7%, p = 0.14) were not significant. Targeted temperature management implementation and post-CA management varied between the participating centers. Classification and Regression Trees models identified variables predictive of favorable and poor outcome for hanging and TTM patients with excellent accuracy. Cardiac arrest hanging patients had worse outcome than non-CA patients. Targeted temperature management CA patients had worse unadjusted survival and neurologic outcome than non-TTM patients. These findings may be explained by their higher severity of illness, variable TTM implementation, and differences in post-CA management. Future prospective studies are necessary to ascertain the effect of TTM on hanging outcome and to validate our Classification and Regression Trees models. Therapeutic study, level IV; prognostic study, level III. Show less

To evaluate the 3D static articulation accuracy of 3 model scanner-CAD systems (Ceramill Map400 [AG], inEos X5 [SIR], Scanner S600 Arti [ZKN]) using a coordinate measuring machine (CMM). Trueness and precision for each system will be reported in Part I. The master model simulated a single crown opposing a 3-unit fixed dental prosthesis. Five mounted stone cast sets were prepared, and one set was randomly selected. Reference values were obtained by measuring interarch and interocclusal reference features with the CMM. The stone cast set was scanned 5 times consecutively and articulated virtually with each system (3 test groups, n = 5). STL files of the virtual models were measured with CMM software. dR For trueness values, mean interarch global distortions ranged from 13.1 to 40.3 μm for dR The overall interarch global distortion of all three model scanner-CAD systems was low and did not exceed 0.6%. Variations in scanner technology, virtual articulation algorithm, and use of physical articulators contributed to the differences in distortion observed among all three groups. Show less

Accurate maxillomandibular relationship transfer is important for CAD/CAM prostheses. This study compared the 3D-accuracy of virtual model static articulation in three laboratory scanner-CAD systems (Ceramill Map400 [AG], inEos X5 [SIR], Scanner S600 Arti [ZKN]) using two virtual articulation methods: mounted models (MO), interocclusal record (IR). The master model simulated a single crown opposing a 3-unit fixed partial denture. Reference values were obtained by measuring interarch and interocclusal reference features with a coordinate measuring machine (CMM). MO group stone casts were articulator-mounted with acrylic resin bite registrations while IR group casts were hand-articulated with poly(vinyl siloxane) bite registrations. Five test model sets were scanned and articulated virtually with each system (6 test groups, 15 data sets). STL files of the virtual models were measured with CMM software. dR Mean interarch 3D distortion ranged from -348.7 to 192.2 μm for dR Interarch and interocclusal distances increased in MO groups, while they decreased in IR groups. AG-IR had the greatest interarch distortion as well as interocclusal superior-inferior distortion. The other groups performed similarly to each other, and the overall interarch distortion did not exceed 0.7%. In these systems and articulation methods, interocclusal distortions may result in hyper- or infra-occluded prostheses. Show less

Prior studies have defined the accuracy of intraoral scanner (IOS) systems but the accuracy of the digital static interocclusal registration function of these systems has not been reported. This study compared the three-dimensional (3D) accuracy of the digital static interocclusal registration of 3 IOS systems using the buccal bite scan function. Three IOS systems compared were 3M Mean 3D distortion ranged from -471.9 to 31.7 μm for dR Interarch and global interocclusal distortions for the three IOS systems were significantly different. TRC performed overall the best and TDS was the worst. The interarch (dR Show less

The regulation of translation initiation factor 2 (eIF2) is important for erythroid survival and differentiation. Lack of iron, a critical component of heme and hemoglobin, activates Heme Regulated Inhibitor (HRI). This results in phosphorylation of eIF2 and reduced eIF2 availability, which inhibits protein synthesis. Translation of specific transcripts such as Atf4, however, is enhanced. Upstream open reading frames (uORFs) are key to this regulation. The aim of this study is to investigate how tunicamycin treatment, that induces eIF2 phosphorylation, affects mRNA translation in erythroblasts. Ribosome profiling combined with RNA sequencing was used to determine translation initiation sites and ribosome density on individual transcripts. Treatment of erythroblasts with Tunicamycin (Tm) increased phosphorylation of eIF2 2-fold. At a false discovery rate of 1%, ribosome density was increased for 147 transcripts, among which transcriptional regulators such as Atf4, Tis7/Ifrd1, Pnrc2, Gtf2h, Mbd3, JunB and Kmt2e. Translation of 337 transcripts decreased more than average, among which Dym and Csde1. Ribosome profiling following Harringtonine treatment uncovered novel translation initiation sites and uORFs. Surprisingly, translated uORFs did not predict the sensitivity of transcripts to altered ribosome recruitment in presence or absence of Tm. The regulation of transcription and translation factors in reponse to eIF2 phosphorylation may explain the large overall response to iron deficiency in erythroblasts. Show less

The purpose of this article is to describe a case of an accidental turbinectomy during nasal intubation for an elective oral and maxillofacial surgical case that was confirmed after extubation. While there are several reported cases, this still tends to be an overall rare complication in the field of anesthesia. This article highlights the complications encountered due to turbinectomy while also identifying causes, signs, and methods to prevent it. Show less

Substantial improvements in enzyme activity demand multiple mutations at spatially proximal positions in the active site. Such mutations, however, often exhibit unpredictable epistatic (non-additive) effects on activity. Here we describe FuncLib, an automated method for designing multipoint mutations at enzyme active sites using phylogenetic analysis and Rosetta design calculations. We applied FuncLib to two unrelated enzymes, a phosphotriesterase and an acetyl-CoA synthetase. All designs were active, and most showed activity profiles that significantly differed from the wild-type and from one another. Several dozen designs with only 3-6 active-site mutations exhibited 10- to 4,000-fold higher efficiencies with a range of alternative substrates, including hydrolysis of the toxic organophosphate nerve agents soman and cyclosarin and synthesis of butyryl-CoA. FuncLib is implemented as a web server (http://FuncLib.weizmann.ac.il); it circumvents iterative, high-throughput experimental screens and opens the way to designing highly efficient and diverse catalytic repertoires. Show less

Much of our knowledge on the function of proteins is deduced from their mature, folded states. However, it is unknown whether partially synthesized nascent protein segments can execute biological functions during translation and whether their premature folding states matter. A recent observation that a nascent chain performs a distinct function, co-translational targeting in vivo, has been made with the Escherichia coli signal recognition particle receptor FtsY, a major player in the conserved pathway of membrane protein biogenesis. FtsY functions as a membrane-associated entity, but very little is known about the mode of its targeting to the membrane. Here we investigated the underlying structural mechanism of the co-translational FtsY targeting to the membrane. Our results show that helices N Show less

Protein networks in all organisms comprise homologous interacting pairs. In these networks, some proteins are specific, interacting with one or a few binding partners, whereas others are multispecific and bind a range of targets. We describe an algorithm that starts from an interacting pair and designs dozens of new pairs with diverse backbone conformations at the binding site as well as new binding orientations and sequences. Applied to a high-affinity bacterial pair, the algorithm results in 18 new ones, with cognate affinities from pico- to micromolar. Three pairs exhibit 3-5 orders of magnitude switch in specificity relative to the wild type, whereas others are multispecific, collectively forming a protein-interaction network. Crystallographic analysis confirms design accuracy, including in new backbones and polar interactions. Preorganized polar interaction networks are responsible for high specificity, thus defining design principles that can be applied to program synthetic cellular interaction networks of desired affinity and specificity. Show less

Folding of proteins to their functional conformation is paramount to life. Though 75% of the proteome consists of multidomain proteins, our knowledge of folding has been based primarily on studies conducted on single-domain and fast-folding proteins. Nonetheless, the complexity of folding landscapes exhibited by multidomain proteins has received increased scrutiny in recent years. We study the three-domain protein adenylate kinase from E. coli (AK), which has been shown to fold through a series of pathways involving several intermediate states. We use a protein design method to manipulate the folding landscape of AK, and single-molecule FRET spectroscopy to study the effects on the folding process. Mutations introduced in the NMP binding (NMPbind) domain of the protein are found to have unexpected effects on the folding landscape. Thus, while stabilizing mutations in the core of the NMPbind domain retain the main folding pathways of wild-type AK, a destabilizing mutation at the interface between the NMPbind and the CORE domains causes a significant repartition of the flux between the folding pathways. Our results demonstrate the outstanding plasticity of the folding landscape of AK and reveal how specific mutations in the primary structure are translated into changes in folding dynamics. The combination of methodologies introduced in this work should prove useful for deepening our understanding of the folding process of multidomain proteins. Show less

The goal of an infection control program is to provide a safe working environment for dental health care personnel and their patients. Practitioners can achieve this by adopting measures that reduce health care-associated infections among patients and occupational exposures among dental health care personnel. It is crucial for all dental practitioners to be up to date on current Centers for Disease Control and Prevention guidelines, equipment, and techniques for proper infection control. Continuous evaluation of infection control practices is important. Patients and dental providers should be confident that oral health care can be delivered and received in a safe manner. Show less

Novel graphitic carbon nitride/CuO (g-C₃N₄/CuO) nanocomposite was synthesized through a facile precipitation method. Due to the strong ion-dipole interaction between copper ions and nitrogen atoms of g-C₃N₄, CuO nanorods (length 200-300 nm, diameter 5-10 nm) were directly grown on g-C₃N₄, forming a g-C₃N₄/CuO nanocomposite, which was confirmed via X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS). Finally, thermal decomposition of ammonium perchlorate (AP) in the absence and presence of the prepared g-C₃N₄/CuO nanocomposite was examined by differential thermal analysis (DTA), and thermal gravimetric analysis (TGA). The g-C₃N₄/CuO nanocomposite showed promising catalytic effects for the thermal decomposition of AP. Upon addition of 2 wt % nanocomposite with the best catalytic performance (g-C₃N₄/20 wt % CuO), the decomposition temperature of AP was decreased by up to 105.5 °C and only one decomposition step was found instead of the two steps commonly reported in other examples, demonstrating the synergistic catalytic activity of the as-synthesized nanocomposite. This study demonstrated a successful example regarding the direct growth of metal oxide on g-C₃N₄ by ion-dipole interaction between metallic ions, and the lone pair electrons on nitrogen atoms, which could provide a novel strategy for the preparation of g-C₃N₄-based nanocomposite. Show less

Proteins have evolved to balance efficient binding of desired partners with rejection of unwanted interactions. To investigate the evolution of protein-protein interactions, we selected a random library of pre-stabilized TEM1 β-lactamase against wild-type TEM1 using yeast surface display. Three mutations were sufficient to achieve micromolar affinity binding between the two. The X-ray structure emphasized that the main contribution of the selected mutations was to modify the protein fold, specifically removing the N'-terminal helix, which consequently allowed protein coupling via a β-sheet-mediated interaction resembling amyloid interaction mode. The only selected mutation located at the interaction interface (E58V) is reminiscent of the single mutation commonly causing sickle-cell anemia. Interestingly, the evolved mutations cannot be inserted into the wild-type protein due to reduced thermal stability of the resulting mutant protein. These results reveal a simple mechanism by which undesirable binding is purged by loss of thermal stability. Show less

Smith-McCort dysplasia (SMC OMIM 615222) and Dyggve-Melchior-Clausen dysplasia (DMC OMIM 223800) are allelic skeletal dysplasias caused by homozygous or compound heterozygous mutations in DYM (OMIM 607461). Both disorders share the same skeletal phenotypes characterized by spondylo-epi-metaphyseal dysplasia with distinctive lacy ilia. The difference rests on the presence or absence of intellectual disability, that is, intellectual disability in DMC and normal cognition in SMC. However, genetic heterogeneity was suspected in SMC. Recently, RAB33B (OMIM 605950) has been identified as the second gene for SMC. Nevertheless, only two affected families have been reported so far. Here we present three SMC patients with four novel pathogenic variants in RAB33B, including homozygosity for c.211C>T (p.R71*), homozygosity for c.365T>C (p.F122S), and compound heterozygosity for c.48delCGGGGCAG (p.G17Vfs*58) and c.490C>T (p.Q164*). We also summarize the clinical, radiological, and mutation profile of RAB33B after literature mining. This report ascertains the pathogenic relationship between RAB33B and SMC. © 2017 Wiley Periodicals, Inc. Show less

Osteomyelitis is an inflammation of bone marrow with a tendency for progression, involving the cortical plates and often periosteal tissues, with most cases occurring after trauma to bone or bone surgery or secondary to vascular insufficiency. Antimicrobial therapy and surgical débridement are the primary modalities of osteomyelitis treatment, although often it is associated with a prolonged course, requiring a large commitment between patient and clinician as well as sizable health care costs. Despite surgical and chemotherapeutic advancements, osteomyelitis remains difficult to treat, and no universally accepted protocol for treatment exists. Show less

Indwelling Foley catheter is a rare cause of urinary bladder perforation, a serious injury with high mortality that demands accurate and prompt diagnosis. While the gold standard for diagnosis of bladder injury is computed tomography (CT) cystography, few bladder ruptures associated with Foley catheter have been reported to be diagnosed in the emergency department (ED). An 83-year-old man with indwelling Foley catheter presented to the ED for hematuria and altered mental status. He was diagnosed to have intraperitoneal rupture of the urinary bladder in the ED using abdominal and pelvic CT without contrast, which demonstrated bladder wall discontinuity, intraperitoneal free fluid, and pneumoperitoneum. The patient was treated successfully with medical management and bladder drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To our knowledge, this is the first report of intraperitoneal urinary bladder perforation associated with Foley catheter diagnosed in the ED by CT without contrast. Pneumoperitoneum found in this case was a clue to the diagnosis and is a benign finding that does not necessitate urgent surgical intervention. The early and accurate diagnosis in this case allowed for effective management with good clinical outcome. The use of indwelling Foley catheter has a high prevalence, especially in long-term care facility residents, who are frequent visitors in the ED. Therefore, emergency physicians and radiologists should be familiar with the presentation and imaging findings of this potential injury associated with Foley catheters. Show less

We present a case of post-traumatic endophthalmitis with relatively good prognosis caused by Gordonia sputi, which, to our knowledge is the first case in the literature. A 24 year old man, who underwent an intraocular foreign body extraction half a month before presentation in the left eye, was referred to us complaining of blurred vision and slight pain for 5 days. His first presentation showed moderate intracameral and intravitreous purulent inflammation with a best corrected vision of counting fingers. After gram staining of the intravitreous samples revealed a gram-positive bacilli infection, a combination of amikacin and vancomycin was initially injected intravitreously. The left eye kept stable for three days but deteriorated on the 4th day. On the 5th day after presentation conventional culture characterized the bacterium as an Actinomyces sp. while 16S ribosomal RNA gene sequencing confirmed it as Gordonia sputi. Thereby a complete pars plana vitrectomy combined with lensectomy and silicone oil tamponade was performed. During the surgery an intraocular irrigation with penicillin G was adopted, followed by administration of intravenous penicillin G twice one day for a week. A relatively normal fundus with slight intracameral inflammation was observed a week after the operation, and the best corrected vision recovered to 0.15. One year later his vision remained 0.1. Gordonia sputi should be taken into consideration in patients with post-traumatic endophthalmitis especially due to foreign body penetration. Compared to conventional laboratories, molecular methods are recommended for an accurate diagnosis. A comprehensive strategy of antimicrobial agents and vitrectomy may render a satisfactory result. Show less

Situation awareness has been defined as the perception of the elements in the environment within volumes of time and space, the comprehension of their meaning, and the projection of their status in the near future. Intensivists often make time-sensitive critical decisions, and loss of situation awareness can lead to errors. It has been shown that simulation-based training is superior to lecture-based training for some critical scenarios. Because the methods of training to improve situation awareness have not been well studied in the medical field, we compared the impact of simulation vs. lecture training using the Situation Awareness Global Assessment Technique (SAGAT) score. To identify an effective method for teaching situation awareness. We randomly assigned 17 critical care fellows to simulation vs. lecture training. Training consisted of eight cases on airway management, including topics such as elevated intracranial pressure, difficult airway, arrhythmia, and shock. During the testing scenario, at random times between 4 and 6 minutes into the simulation, the scenario was frozen, and the screens were blanked. Respondents then completed the 28 questions on the SAGAT scale. Sample items were categorized as Perception, Projection, and Comprehension of the situation. Results were analyzed using SPSS Version 21. Eight fellows from the simulation group and nine from the lecture group underwent simulation testing. Sixty-four SAGAT scores were recorded for the simulation group and 48 scores were recorded for the lecture group. The mean simulation vs. lecture group SAGAT score was 64.3 ± 10.1 (SD) vs. 59.7 ± 10.8 (SD) (P = 0.02). There was also a difference in the median Perception ability between the simulation vs. lecture groups (61.1 vs. 55.5, P = 0.01). There was no difference in the median Projection and Comprehension scores between the two groups (50.0 vs. 50.0, P = 0.92, and 83.3 vs. 83.3, P = 0.27). We found a significant, albeit modest, difference between simulation training and lecture training on the total SAGAT score of situation awareness mainly because of the improvement in perception ability. Simulation may be a superior method of teaching situation awareness. Show less

Natural proteins must both fold into a stable conformation and exert their molecular function. To date, computational design has successfully produced stable and atomically accurate proteins by using so-called "ideal" folds rich in regular secondary structures and almost devoid of loops and destabilizing elements, such as cavities. Molecular function, such as binding and catalysis, however, often demands nonideal features, including large and irregular loops and buried polar interaction networks, which have remained challenging for fold design. Through five design/experiment cycles, we learned principles for designing stable and functional antibody variable fragments (Fvs). Specifically, we ( Show less

Protein complexes often represent an ensemble of different assemblies with distinct functions and regulation. This increased complexity is enabled by the variety of protein diversification mechanisms that exist at every step of the protein biosynthesis pathway, such as alternative splicing and post transcriptional and translational modifications. The resulting variation in subunits can generate compositionally distinct protein assemblies. These different forms of a single protein complex may comprise functional variances that enable response and adaptation to varying cellular conditions. Despite the biological importance of this layer of complexity, relatively little is known about the compositional heterogeneity of protein complexes, mostly due to technical barriers of studying such closely related species. Here, we show that native mass spectrometry (MS) offers a way to unravel this inherent heterogeneity of protein assemblies. Our approach relies on the advanced Orbitrap mass spectrometer capable of multistage MS analysis across all levels of protein organization. Specifically, we have implemented a two-step fragmentation process in the inject flatapole device, which was converted to a linear ion trap, and can now probe the intact protein complex assembly, through its constituent subunits, to the primary sequence of each protein. We demonstrate our approach on the yeast homotetrameric FBP1 complex, the rate-limiting enzyme in gluconeogenesis. We show that the complex responds differently to changes in growth conditions by tuning phosphorylation dynamics. Our methodology deciphers, on a single instrument and in a single measurement, the stoichiometry, kinetics, and exact position of modifications, contributing to the exposure of the multilevel diversity of protein complexes. Show less

The small GTPase Rab26 is involved in multiple processes, such as vesicle-mediated secretion and autophagy. However, the mechanisms and functions of Rab26 in the human pulmonary microvascular endothelial cells (HPMVECs) are not clear. In this study, we thoroughly investigated the role and novel mechanism of Rab26 in permeability and apoptosis of HPMVECs using a self-assembled Rab26 siRNA loaded DNA Y-motif nanoparticle (siRab26-DYM) and Rab26 adenovirus. We found that siRab26-DYM could be efficiently transfected into HPMVECs in a time- and dose-dependent manner. Importantly, the siRab26-DYM nanovector markedly aggravated the LPS-induced apoptosis and hyper-permeability of HPMVECs by promoting the nuclear translocation of Foxo1, and subsequent activation of Toll-like receptor 4 (TLR4) signal pathway. Overexpression of Rab26 by Rab26 adenoviruses partially inactivated LPS-induced TLR4 signaling pathway, suppressed the cell apoptosis and attenuated the hyperpermeability of HPMVECs. These results suggest that the permeability and apoptosis of HPMVECs can be modulated by manipulating Rab26 derived TLR4 signaling pathway, and that Rab26 can be potential therapeutic target for the treatment of vascular diseases related to endothelial barrier functions. Show less

Any dental office can face a variety of medical emergencies; therefore, the health care professional and the staff should always be prepared to deal with these emergencies in their office. Preparedness of the dental office staff and their prompt recognition of these emergencies will be the most important factor in dealing with the emergencies in any dental office. Health care professionals should follow the recommendations in this article to maintain a guideline for their staff and office and conduct regular emergency drills to examine the equipment and preparedness of their staff. Show less

Pharmacologic agents play an integral role in the overall management of temporomandibular joint disorder. The general dentist should be familiar with the different classes of drugs currently in use for dealing with this often complex medical/dental problem. Show less

This article highlights the commonly used medications used in dentistry and oral surgery. General dentists and specialists must be knowledgeable about the pharmacology of the drugs currently available along with their risks and benefits. Enteral sedation is a useful adjunct for the treatment of anxious adult and pediatric patients. When enteral sedation is used within the standards of care, the interests of the public and the dental profession are served through a cost-effective, effective service that can be widely available. Oral sedation enables dentists to provide dental care to millions of individuals who otherwise would have unmet dental needs. Show less

BACKGROUND Apoptosis plays an important role in the physiology of platelet function. We aimed to detect the effect of the platelet integrin αIIbβ3 inhibitor, tirofiban, on apoptotic events, including mitochondrial inner-membrane potential (ΔΨm), phosphatidylserine (PS) exposure on platelet surface, and the generation of reactive oxygen species (ROS), when washed platelets were stimulated with thrombin. MATERIAL AND METHODS The study included washed platelets from healthy humans, divided into 4 groups: vehicle, and tirofiban (0.05 μg/ml, 0.25 μg/ml, and 0.5 μg/ml). Platelets were pretreated with vehicle or tirofiban and incubated at 37°C with agitation for 6 h and 24 h. Before thrombin addition, the vehicle group divided into 2 equal groups. Except one vehicle group, the other 4 groups were all stimulated with thrombin (1 U/ml) for 30 min at 37°C. Using flow cytometry, we studied the DYm and PS exposure on platelet surfaces, and the generation of ROS in platelets. RESULTS We observed that at the time of 6 h and 24 h, thrombin-stimulated vehicle platelets induced significant depo-larization of ΔΨm, higher PS exposure, and increased ROS production compared with the vehicle group (P<0.01). However, the tirofiban group had significantly more recovery of DYm, PS exposure, and ROS production compared with the thrombin group (P<0.01). CONCLUSIONS The platelet integrin αIIbβ3 inhibitor, tirofiban, inhibits the depolarization of DYm, PS exposure on platelet surface, and ROS production when stimulated with thrombin. These results suggest that αIIbβ3 inhibitor inhibits the initiation of apoptosis in platelets, showing a potential clinical application of tirofiban as an apoptosis inhibitor. Show less

Clinical Question Does the addition of cyclobenzaprine or oxycodone with acetaminophen to naproxen result in improved functional outcomes at one week when compared to placebo in patients with acute low back pain? Article Chosen Friedman B, Dym A, Davitt, M, et al. Naproxen with cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating acute low back pain: a randomized clinical trial. JAMA 2015:20;314(15):1572-80. Study Objective The primary objective of this study was to compare functional outcomes at one week and three months after emergency department (ED) presentation for acute low back pain among patients prescribed naproxen plus one of the following: (1) oxycodone/acetaminophen; (2) cyclobenzaprine; or (3) placebo. Show less