Secondly, understanding the cellular basis of aberrant synchroni

Secondly, understanding the cellular basis of aberrant synchronized discharges of neurons during epileptic seizures also yields insights into the mechanisms of normal synchronization in the

brain. Finally, the necessity to perform invasive electrode (depth and subdural) recordings in patients with epilepsy results in unique opportunities to study human cognitive processes at extremely high time resolution by recording Inhibitors,research,lifescience,medical field or even single unit potentials during cognitive tasks. This technique can be combined with different functional imaging techniques, which ideally complement invasive recordings from the human brain by providing excellent spatial resolution. Research into the basic mechanisms of epilepsy The study of idiopathic genetic epilepsies : how do single gene mutations cause epilepsy? Genetic factors are the major determinants in at least

40% of all epilepsies; these are designated Inhibitors,research,lifescience,medical as “idiopathic epilepsies.” Only about 2% of these idiopathic epilepsies are inherited as monogenic disorders, in which one gene conveys the major heritable impact, while environment and lifestyle Inhibitors,research,lifescience,medical play a limited role. Genetic studies have allowed identification of the first disease genes that define monogenic idiopathic epilepsies.1,2 In these cases, genetic studies have identified causal gene variants, many of them neuronal ion channels, receptors, or associated proteins. Subsequently, the function of these variants was examined carefully in expression Inhibitors,research,lifescience,medical systems, and selleck kinase inhibitor specific functional changes were found. These analyses, while compelling in implicating specific genes in idiopathic epilepsies, are not the last word in understanding how a gene mutation leads to a behavioral and clinical phenotype. We are beginning to obtain such an understanding in some instances from transgenic mouse models that carry disease-associated gene Inhibitors,research,lifescience,medical variants.3 The advantage of such models is that they harbor human disease-associated

gene variants, and can be examined at various points during the development second of epilepsy with in vitro and molecular techniques. The limitation of such models is that the mechanisms of epileptogenesis may not be the same in mice and humans, and that disease-associated human gene variants are expressed on a background of mouse genes that may interact in unexpected ways with the human ortholog. Nevertheless, such studies are increasingly part of an integrated strategy to understand the mechanisms of monogenic epilepsies involving both human genetics and physiological, and molecular studies in transgenic mouse models. The study of focal epilepsy What are the mechanisms of seizures? By far most types of epilepsies, however, are not monogenic.

Despite this change, the molecule bears sufficient similarity to

Despite this change, the molecule bears sufficient similarity to glucose to be taken up by living cells in proportion to their metabolic demands. The radiation emitted by the tracer after it has been absorbed by the cells can therefore be used to construct

a map depicting the glucose demands of the different tissues. FDG-PET scans have a characteristic appearance that can facilitate the diagnosis of AD (Silverman et al. 2001; Drzezga et al. 2005). In addition, PET scans have clinical utility for discerning between AD and dementia caused by frontotemporal lobar degeneration (FTLD) (Foster et al. 2007). Several research this website studies Inhibitors,research,lifescience,medical have evaluated the utility of PET scans for diagnosing AD (Minoshima et al. 1995; Silverman et al. 2001) or for predicting the progression of MCI or AD (Chetelat et al. 2003; Drzezga et al. 2005; Landau et al. 2010, 2011; Walhovd et al., 2010). PET scans for studies such as these are often subjected to complex Inhibitors,research,lifescience,medical post-processing, such as segmentation into volumes of interest, or surface projection. The current work focuses on automatic Inhibitors,research,lifescience,medical detection of AD or elevated MCI conversion risk, making use of elementary information retrieval (IR) techniques. IR is a broad field that is concerned chiefly with the rapid selection of relevant documents from vast databases. The documents in question are traditionally text, and this has shaped many IR techniques. The simplest approach is to formulate a query as a list

of key Inhibitors,research,lifescience,medical words and to retrieve only documents that contain all of the key words. This approach does not perform well in practice, however. Another approach that is almost as simple is to arrange word

counts from numerous documents in a matrix and then to treat the rows and columns of the matrix as vectors. This permits comparison of documents and queries using simple mathematical measurements on vectors, such as Euclidean distance (a generalization of the Pythagorean theorem) and cosine similarity (a measure of the angle between two vectors that is maximal when the vectors are parallel). Inhibitors,research,lifescience,medical More typically, the term-document matrix is subjected to Rutecarpine further mathematical processing for extracting the most salient features of the data, such as singular value decomposition or latent semantic analysis (Widdows 2004). This vector-space model of information has proven to be very useful, and the possibility of extending it to retrieval of images and music is an area of active research (Casey et al. 2008; Datta et al. 2008). The diagnosis of AD (or identification of patients who meet other clinical criteria) may be approached from an IR perspective. In this case, we wish to search a database of brain images and retrieve those images that belong to patients with AD or elderly controls. Somewhat more compelling (and more difficult) is the retrieval of scans from patients with memory impairment who are destined to develop AD. The immediate problem that arises is the formulation of the query.

Unlike BMPM, they also have mural lymphoid aggregates and smooth

Unlike BMPM, they also have mural lymphoid aggregates and smooth muscle unlike (1),(11). Malignant lesions to consider are malignant AS-703026 concentration mesothelioma and serous tumors that involve the peritoneum. BMPM usually

presents with vague lower abdominal pain, mass, or both, but is also commonly diagnosed incidentally upon laparotomy for other surgeries (1). The patient may also present with obstructive symptoms such as nausea, bloating, Inhibitors,research,lifescience,medical or vomiting. Despite its relatively benign process some patients may present with an acute abdomen (11). CT scans may be diagnostically beneficial but, as in this case, can also indicate a more acute need for surgery as actually necessary. Pre-operative fine needle core biopsies have been reported to be of some benefit in the differential diagnosis of BMPM (11),(16). Cytologic features of peritoneal

washings in cases of BMPM have shown the washings to be hypercellular with a population Inhibitors,research,lifescience,medical of mesothelial and squamous metaplastic cells (6). Ultimately, the diagnosis is usually made by the pathologist after surgical resection has been performed. Due to its rarity, BMPM treatment options remain an area of controversy and there is no streamlined treatment plan. Currently aggressive surgical resection is the mainstay of treatment with palliative Inhibitors,research,lifescience,medical debulking and reoperation for recurrence (15),(11),(5). With up to 50 percent recurrence rates and its malignant potential, debulking surgery does not appear to be the most acceptable treatment Inhibitors,research,lifescience,medical option for these patients. Patients may suffer from poorly controlled chronic abdominal and pelvic pain (15). Uncertain results have been reported with patients receiving adjuvant chemotherapy and/or radiation therapy (5). Other approaches such as sclerosive therapy with tetracycline, continuous hyperthermic peritoneal perfusion

with cisplatin, and antiestrogenic drugs have been suggested (11). The optimal treatment may be cytoreductive surgery with peritonectomy combined with perioperative intraperitoneal chemotherapy to eliminate all gross and microscopic Inhibitors,research,lifescience,medical disease (5). The goal of this treatment regimen is to reduce the likelihood of all progression or recurrence. Although the prognosis for BMPM is very good, aggressive approaches to this disease should be considered. Patients have a high likelihood of recurrence and repeat surgeries are common. The intention of this report is to increase the awareness of this disease entity and to consider it whenever the patient’s presentation does not match that of the working diagnosis. This patient presented without peritoneal signs despite a CT scan that suggested a more severe pathology. Before jumping into an exploratory laparotomy based on imaging findings, surgeons should trust our physical exam and pursue a more definitive diagnosis. With a definitive diagnosis we can approach the surgical issue in the most appropriate manner.

The same holds true for MSH2 and its binding partner MSH6 Table

The same holds true for MSH2 and its binding partner MSH6. Table 3 Immunohistochemical staining patterns and interpretation for MMR proteins Figure 20 A MSI tumor showing loss of MLH1 (A) and PMS2 (D) protein expression, and normal expression of MSH2 (B) and MSH6 (C). Note the presence of positive staining in benign colonic crypts and inflammatory cells, which serve as good internal controls for the … The sensitivity of PCR-based MSI test using the Bethesda panel ranges from 55% to 84% for Inhibitors,research,lifescience,medical the detection of mutations in different MMR gene.

The sensitivity is increased if three or more mononucleotide repeat markers are used. The specificity of MSI test is 90%. Immunohistochemistry has been accepted as a reliable substitute for MSI with a concordance rate of >90%. It also

provides additional information over PCR-based MSI test in Inhibitors,research,lifescience,medical that it allows gene-specific DNA sequence analysis based on the staining pattern. However, immunohistochemistry may miss rare MSI cases that are caused by germline mutations by other genes and does not discriminate germline mutation from epigenetic alteration when loss of MLH1 protein expression is detected. Thus, the most recent recommendation is to perform both PCR-based MSI test and immunohistochemistry in order to minimize the chance of Erlotinib manufacturer missing the diagnosis of Lynch syndrome (117). It is also recently advocated to test Inhibitors,research,lifescience,medical all Inhibitors,research,lifescience,medical newly diagnosed colorectal cancers regardless of patient’s age and family history because ~25% of the patients with Lynch syndrome do not meet Amsterdam Criteria II or Bethesda guidelines (117). In that setting, only one test, either immunohistochemistry or MSI analysis,

may be performed because the cost of the tests will become Inhibitors,research,lifescience,medical an issue. KRAS testing Mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog) gene lead to expression of a constitutively activated KRAS protein, which are detected in ~40% of colorectal cancers (2,118). As a critical downstream molecule in the epidermal growth factor receptor (EGFR) signaling pathway, mutant KRAS renders tumors resistant to EGFR-targeted therapies (2,119-121). As a result, the American Society for Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) have recommended mutation analysis of the KRAS gene for Metalloexopeptidase candidate patients who will receive anti-EGFR therapies (122,123). Greater than 95% of KRAS mutations occur in codons 12 and 13 in exon 2 (118,124,125), and thus PCR-based methodologies designed to detect KRAS mutations are primarily for these mutations. Mutations can also occur in other loci such as codons 61 and 146 (126), but they are generally not screened because of rarity. Clinically available real-time PCR-based methods include allele-specific amplification assay and post-PCR melting curve analysis.

Furthermore, anti-VEGR2 monoclonal antibodies reduce endothelial

Furthermore, anti-VEGR2 monoclonal antibodies reduce endothelial progenitor cells in murine models and inhibit tumor growth (82). Additionally, resistance to tumor vascular disrupting agents is mediated by endothelial progenitors and can be overcome by VEGFR and PDGFR inhibition (83). Increased levels of circulating VEGFR2+ BMDC progenitors are associated with worse overall survival compared to low levels in patients with advanced

cancer (84). Accordingly, suppression of endothelial cell progenitors may be one of the underlying mechanisms of anti-VEGF therapies. A number of distinct immune cells are also recruited to the tumor Inhibitors,research,lifescience,medical microenvironment by secreted cytokines (including G-CSF, PlGF, stromal derived factor 1α) and release proangiogenic factors which influence resistance to Inhibitors,research,lifescience,medical anti-VEGF therapies (77,85,86). For example, tumor infiltration by CD11b+Gr1+ myeloid cells is associated with anti-VEGF resistance; recruitment of these cells confers resistance by release of the proangiogenic factor Bv8 (87,88). Tie2 expressing monocytes or macrophages are physically associated with tumor vessels as well in a number of malignancies, Inhibitors,research,lifescience,medical and promote angiogenesis

via paracrine release of factors including VEGFA (89,90). Ang2 secreted by tumor cells alters the genetic phenotype of Tie2+ monocytes/macrophages and increases expression of multiple proangiogenic genes (91). Indeed, inhibition of Ang2 signaling is effective at decreasing tumor growth and angiogenesis by impeding upregulation Inhibitors,research,lifescience,medical of Tie2 and association of Tie2+ cells with blood vessels (92). Future strategies aimed at mediating the inflammatory cytokines driving recruitment of various BMDCs and blunting proangiogenic signals are a promising avenue of research. Biomarkers Given the prominent use of anti-angiogenic agents in colorectal cancer and other malignancies today, predictive biomarkers are urgently needed in order to maximize clinical Inhibitors,research,lifescience,medical benefit, decreased unnecessary drug toxicity, and improve costs of cancer care. Biomarkers to predict benefit and guide use of therapies targeting angiogenesis can be measured

at baseline (pretreatment) or by relative change during treatment. While baseline measurement why may reflect preexisting, intrinsic mechanisms of resistance, angiome changes during treatment may offer insight into acquired or upregulated pathways of angiogenesis. Thus far, biomarkers for both have remained elusive for a check details multitude of reasons (93). Aside from the complexity of tumor angiogenesis, a major consideration is that robust blood and tissue based biomarker programs were not often embedded into large randomized trials, where such work is best done. In addition, many targets are of low abundance and are highly processed, and reagents for many targets are often limited. Plasma VEGFA levels in a variety of malignancies, including colorectal cancer, have well-established prognostic value.

228 As a slow-acting neurotransmitter, or neuromodulator, DA’s sy

228 As a slow-acting neurotransmitter, or neuromodulator, DA’s synaptic effects unfold over hundreds of milliseconds and may last a minute or more. In contrast, glutamate and GABA, when acting through ionotropic receptors, produce

their corresponding depolarizing and hyperpolarizing postsynaptic effects within a millisecond of binding to their individual receptors, and these effects last only from about a millisecond to a few tens of milliseconds, respectively. DA receptors belong to the A family of seven-transmembrane Inhibitors,research,lifescience,medical receptors and are grouped into two subclasses, d1 and d2, based on their Wee1 inhibitor coupling to G-proteins that either increase (d1-like) or decrease (d2-like) cytoplasmic cyclic adenosine monophosphate (cAMP).229 The d2 subclass includes the d1 and d5 receptors, and the d2 subclass comprises d2, d3, and d4 receptors.229 DA’s synaptic actions are mediated through intracellular signaling Inhibitors,research,lifescience,medical pathways that regulate the phosphorylation of DARPP32 (DA and cAMP-regulated phosphoprotein, molecular weight = 32 kda), which in turn controls the sensitivity of Inhibitors,research,lifescience,medical glutamate and GABA receptors.230 By controlling the particular sites and level of DARPP-32 phosphorylation, DA exerts an indirect but powerful influence over the efficacy of converging synaptic actions of the fast-acting neurotransmitters glutamate

and GABA.231 This control is imposed through DARPP-32′s regulation of the phosphorylation of synaptic receptors for these and other neurotransmitters. Activation of Inhibitors,research,lifescience,medical d1-like receptors leads to increased phosphorylation – and hence increased sensitivity – of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid) and NMDA glutamate receptors as well as GABAA receptors.231 Activation of d2-like receptors leads to the opposite effect: decreased phosphorylation and sensitivity of AMPA, NMDA, and GABAA receptors to their Inhibitors,research,lifescience,medical respective agonists. DARPP-32

is heavily concentrated within the spines of MSNs.232,233 While nigrostriatal DA neurons send topographical projections to restricted foci within the striatum, the striatonigral input, they receive in turn is convergent, arising from much broader segments of the striatum than the circumscribed territories Phosphatidylinositol diacylglycerol-lyase they themselves innervate.234 For example, ventrolateral SNc DA neurons that project selectively to the sensorimotor territory within the putamen receive striatonigral input not only from putamen but from associative (caudate nucleus) and limbic striatum as well.234 This multimodal striatal input may account for the remarkable fact that the activity of midbrain DA neurons appears to encode a secondary reinforcement signal distilled in real time from complex contingencies implicit in a subject’s ongoing behavior.

In the authors’ opinion, the response may be related to hypothal

In the authors’ opinion, the response may be related to hypothalamicpituitary axis activation secondary to stress, resulting in a functional impact on the end organ. Similar effects on the gastrointestinal system, in accordance with those previously reported, suggested that this response may be initiated centrally. Although this study did not review pain or urgency, it made an advancing step in understanding the pathophysiology of these complex disorders. Risk Factors of De Novo OAB and Stress Incontinence After Urethral Diverticulectomy The most recognized complications after surgical

removal of urethral Inhibitors,research,lifescience,medical diverticulum are diverticula recurrence, urethrovaginal fistula, and de novo urinary incontinence. The incidence of de novo urinary incontinence is reported in the literature to occur in 1.7% to 20.3% of patients, but only a few research papers debate whether it is required to perform a preventive surgery in those patients at risk. In this study, Dr. Young-Ho Kim7 and colleagues from the Department of Urology, SCH Inhibitors,research,lifescience,medical University Bucheon Hospital (Bucheon, South Korea) assessed risk factors related to de novo stress urinary incontinence (SUI) and OAB by retrospective review of past history, and findings of pelvic magnetic resonance (MR) imaging of patients with urethral Inhibitors,research,lifescience,medical diverticulum. The method consisted of reviewing the 28 patients who underwent surgical removal

of urethral diverticulum between 2002 and 2007 regarding medical history, physical examination, pelvic MR imaging, Inhibitors,research,lifescience,medical changes of voiding 5-HT Receptor inhibitor symptoms (by Bristol female lower urinary tract symptoms), and occurrence of SUI. The authors also analyzed risk factors of OAB and SUI including age, body mass index (BMI), number of deliveries, size and location of diverticulum, and history of pelvic surgery. Mean

age of patients was 38 (range, 20 to 59 years). OAB was present before surgery in 4 patients and occurred afterward in another 5 patients (20.8%). De novo SUI occurred in 4 of 28 patients (14.3%) after surgical procedure- one of them having both SUI and OAB. Age, BMI, number of deliveries, and history of pelvic surgery did not statistically relate to occurrence Inhibitors,research,lifescience,medical of SUI or OAB. The authors found a relationship between diverticulum size and position and de novo SUI or OAB. SUI occurred in 3 and OAB in 5 out of the 7 patients with diverticulum > 3 cm. Among 11 patients with diverticulum located in proximal urethra, SUI occurred in 4 patients and OAB in 5 patients. In patients with urethral diverticulum > 3 cm Thalidomide in diameter and located in proximal urethra on pelvic MR imaging, incidence of SUI and OAB was significantly higher. The authors reported that 3 out of 28 patients had a large defect of urethra after removal of urethral diverticulum or weakened periurethral fascia by repeated inflammation and simultaneously underwent Martius labial fat pad interposition. None of them complained about any symptom of SUI or OAB after surgery.

Decreased glial number has been one of the most consistent findin

Decreased glial number has been one of the most consistent findings of postmortem studies.24,25 This includes decreased numbers of astrocytes and oligodendrocytes in PFC. Preclinical studies also demonstrate that stress decreases glial fibrillary

acidic protein (GFAP)-labeled astrocytes as well as the proliferation of oligodendrocytes.24 Conversely, chronic antidepressant administration increases the proliferation of oligodendrocytes in the PFC.24 Glial cells play an important role in providing metabolic support for neurons, and loss of glia could contribute to the atrophy and Inhibitors,research,lifescience,medical loss of neurons caused by stress and depression. This is an interesting, yet understudied, area of research that has important implications for elucidating the pathophysiology of stress and depression. Stress decreases brain-derived neurotrophic factor expression One of the mechanisms that has Inhibitors,research,lifescience,medical been studied for the atrophy and loss of neurons caused by stress and depression is disruption of neurotrophic/growth factor

support, most notably brain-derived neurotrophic factor (BDNF) (Figure 2). Neurotrophic factors were first identified and characterized for their role Inhibitors,research,lifescience,medical during development, including guidance, maturation, and survival of neurons, but it is now well-established that these factors continue to play an important role in the adult brain, including activity-dependent synaptic plasticity as well as survival.26 BDNF, a member of the nerve growth factor family, is one of the most highly expressed neurotrophic factors in the brain, and can be regulated at the level of gene expression as well as activity-stimulated release at synapses. Stress significantly impacts the expression of BDNF, decreasing Inhibitors,research,lifescience,medical levels of messenger RNA (mRNA) and protein in the hippocampus and PFC.3,4 A possible role

Inhibitors,research,lifescience,medical for BDNF in depression is supported by studies demonstrating that levels of this factor are decreased in postmortem cerebral cortex of depressed subjects.3 Surprisingly, blood levels of BDNF are also decreased in depressed aminophylline subjects.27 Studies of BDNF heterozygous deletion mutant mice have not revealed an outright depressive phenotype as might be expected, although BDNF deletion increases vulnerability to depressive behavior in rodents, selleck chemical measured in models of despair, anxiety, and anhedonia.28 The finding that the BDNF deletion mutants do not display depressive behavior could be due to region-specific effects of BDNF (ie, BDNF is prodepressant in the mesolimbic dopamine system, but antidepressant in the PFC and hippocampus).29 This possibility is supported by recent studies demonstrating that hippocampus-specific knockdown of BDNF produces depressive behavior.30 Figure 2. Stress and depression decrease, while rapid-acting antidepressants (eg, ketamine) increase, synaptic connections.

This dimension of care requires the necessary competence to provi

This dimension of care requires the necessary competence to provide the actual care in a professional way. By sorting patients competently, triage functions as a necessary part of good-quality emergency care. From a care ethics perspective, competent triage not only comprises the medical competence of sorting patients according to criteria of clinical urgency, but also includes attention to proper communication and respect for Inhibitors,research,lifescience,medical the patient’s privacy, thus avoiding psychological harm. Good care requires feedback and verification that the patient’s needs are actually being met. This brings us to the final dimension of care, namely that of ‘care receiving’ and the corresponding attitude of responsiveness, which refers

to the response of the patient to the given care. The dimension of care receiving is mostly lacking in the practice of triage and at times leads to conflict. Nevertheless,

checking to see how the given care is being received is very important since the decisions made by the triage officer can have potential negative impact on patient’s condition (e.g. patient’s safety may Inhibitors,research,lifescience,medical be endangered or their condition may deteriorate) and on their experiences (distress, fear, anger). The result is not merely inconvenience but rather a degradation of the entire care process. As such, and in combination with the attitude of attentiveness, the triage officer needs to Inhibitors,research,lifescience,medical seek the responsiveness of the patient, which helps to address ethically JNK IN8 relevant issues like respect for autonomy and the issue of informed consent, Inhibitors,research,lifescience,medical lack of communication, lack of privacy and psychological harm. Framework of Interpersonal Relationships Care practices always take place within a framework of interpersonal relationships, where the caregiver(s) and the care receiver are reciprocally involved in a dynamic interaction of giving and receiving care [41]. Reciprocity consists of verifying Inhibitors,research,lifescience,medical that the given care meets the patient’s needs, thus avoiding the risk of paternalistic or inadequate care. In his theoretical study, Gastmans points at the fact that the characteristics of relatedness

and reciprocity should also be understood against the background of a very particular social context [41,77]. Applied to ED triage, we can point at the way in which the reception of people is being organized and at the way in which people in need are being approached in their first contact with the ED staff. The way in which people are being received STK38 and taken care of when entering the ED, their contact with the triage officer, are important parts of the particular care process, because they are the first encounters between patients, their relatives, caregivers and the hospital, and often the starting point of an overall care process. Institutional Framework In general, care ethics is mainly considered as an ethics of individual relationships [39]. However, care practices should always be considered against a broader horizon of social practices as a whole.

CG linked

the ethical analysis of emergency triage with

CG linked

the ethical analysis of emergency triage with care ethics and also revised the manuscript. YD guided to design the ethical analysis, contributed on the distributive justice and revised the manuscript at this website several stages of preparation. All authors read and approved the final manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: Acknowledgements The authors are grateful to Prof. Peter Campion (University of Hull, United Kingdom) Inhibitors,research,lifescience,medical for reviewing the paper from a medical perspective and offering assistance in language matters.
During recent decades, emergency medicine research has continued to expand in scope and increasingly focuses not only on immediate patient outcomes but also on patient outcomes well beyond emergency department (ED) departure. Inception cohort studies examining long term outcomes among patients experiencing acute illness or trauma Inhibitors,research,lifescience,medical benefit from enrolling patients in the ED because it is the site of their initial care. In addition, for many patients the ED serves Inhibitors,research,lifescience,medical as their only source of care [1,2]. For these reasons, an increasing number of large scale multidisciplinary research projects have utilized ED-based inception cohorts to evaluate long term outcomes after screening, risk stratification, or

interventions performed in the ED [3-8]. This report describes the methods of Project CRASH, an example of a type of ED-based inception cohort study which we anticipate will become increasingly common in the future. Project CRASH uses an ED-based inception cohort to enroll patients soon after injury, and examines genetic factors associated with long

term patient outcomes. A prior study examined genetic variations in alcohol metabolism as a risk factor for trauma Inhibitors,research,lifescience,medical center admission [9], but to our knowledge no studies have used ED-based inception cohorts to examine genetic characteristics associated with long term patient outcomes in the hope of advancing understanding of Inhibitors,research,lifescience,medical disease pathophysiology. The goal of Project CRASH is to gain new insights into the pathophysiology of persistent pain and psychological sequelae after motor vehicle collision (MVC). Approximately 6 million people present to United States EDs each year for care after MVC. More than 90% of these individuals do not have serious physical injury and are discharged MRIP to home after ED evaluation [10]. However, persistent post-MVC pain (most commonly neck pain) is experienced by 10-20% of individuals after “minor” MVC [11,12] with significant associated economic cost [13]. The mechanisms by which patients develop acute and chronic pain after minor MVC remain poorly understood [14]. Interestingly, increasing evidence suggests that stress systems, such as the sympathetic nervous system and adrenomedullary hormonal system, may modulate neurosensory processing after trauma exposure, contributing to the development of chronic pain [15].