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The tightly linked A and E blood alloantigen systems are 2 of 13 blood systems identified in chickens. Reported herein are studies showing that the genes encoding A and E alloantigens map within or near to the chicken regulator of complement activation (RCA) gene cluster, a region syntenic with the human RCA. Genome-wide association studies, sequence analysis, and sequence-derived single-nucleotide polymorphism information for known A and/or E system alleles show that the most likely candidate gene for the A blood system is C4BPM gene (complement component 4 binding protein, membrane). Cosegregation of single-nucleotide polymorphism–defined C4BPM haplotypes and blood system A alleles defined by alloantisera provide a link between chicken blood system A and C4BPM. The best match for the E blood system is the avian equivalent of FCAMR (Fc fragment of IgA and IgM receptor). C4BPM is located within the chicken RCA on chicken microchromosome 26 and is separated from FCAMR by 89 kbp. The genetic variation observed at C4BPM and FCAMR could affect the chicken complement system and differentially guide immune responses to infectious diseases.

To expand and optimize the behavioral health workforce, it is necessary to improve primary care providers' (PCPs) overall knowledge and clinical skills in primary care-based psychiatry. Studies on the effects of postgraduate psychiatric education programs for PCPs on psychiatric knowledge are limited.A total of 251 PCPs completed a 1-year fellowship. Data from program development and evaluation were analyzed for 4 fellowship years (2016-2019). Fellows were surveyed at baseline, midpoint, and postfellowship about mental health stigma, perceived competency, attitudes about psychiatry, satisfaction with current psychiatric knowledge, confidence and comfort to treat psychiatric illnesses, and program satisfaction. Psychiatric knowledge was evaluated at baseline, midpoint, and postfellowship.Large effects were noted on perceived competency/self-efficacy and confidence in the treatment of common psychiatric disorders encountered in primary care settings. Positive effects were observed on attitudes of mental health stigma, and even more robust effects were found with improvement in psychiatry clinical knowledge. Knowledge improved by 12% at postfellowship (P.0001). Correlations of the degree of change in attitude with improved psychiatric literacy demonstrated significant relationships with reduction of stigma total score (r = -0.2133, P = .0043), increased willingness (r = 0.1941, P = .0096), and increased positive attitudes (r = 0.1894, P = .0111).Innovative initiatives to improve and expand psychiatric knowledge and clinical skills among those who provide the most behavioral health care (PCPs) can have marked impacts on attitudes toward mental health care delivery, stigma, and competency/self-efficacy. Future studies are necessary to consider the impact of this program on clinical practice pattern outcomes on a larger scale.

A current shift in intergroup relations research aims to delve deeper into whether, and how, individual differences predict social attitudes. Recent research goes beyond the measurement of typical personality traits and focuses also on the subclinical area of malicious traits. The present studies aimed at exploring the role of one such trait, psychopathy, as a predictor of negative social attitudes. The role of empathy was examined as a key underlying process explaining the relationship between primary and secondary psychopathy and social attitudes. Study 1 (N = 171) and Study 2 (N = 332) demonstrated that when entered as simultaneous predictors of negative attitudes toward immigrants (Study 1) and racism (Study 2), only primary psychopathy emerged as a significant predictor. Study 1 further demonstrated that lower levels of empathy mediated the psychopathy—attitudes path. Study 2 decomposed empathy into cognitive and affective, and tested the explanatory role of social dominance orientation (SDO) and right-wing authoritarianism (RWA). Primary psychopathy predicted lower cognitive and affective empathy, which sequentially predicted racism via SDO (in the case of cognitive empathy) and RWA (in the case of affective empathy). The results are discussed in the context of an integration between the personality and intergroup relations literature.

Objective: Asynchronous telepsychiatry (ATP) is an integrative model of behavioral health service delivery that is applicable in a variety of settings and populations, particularly consultation in primary care. This article outlines the development of a training model for ATP clinician skills. Methods: Clinical and procedural training for ATP clinicians (n = 5) was provided by master's-level, clinical mental health providers developed by three experienced telepsychiatrists (P.Y. D.H., and J.S) and supervised by a tele-psychiatrist (PY, GX, DL) through seminar, case supervision, and case discussions. A training manual and one-on-one sessions were employed for initial training. Unstructured expert discussion and feedback sessions were conducted in the training phase of the study in year 1 and annually thereafter over the remaining 4 years of the study. The notes gathered during those sessions were synthesized into themes to gain a summary of the study telepsychiatrist training recommendations for ATP interviewers. Results: Expert feedback and discussion revealed three overarching themes of recommended skill sets for ATP interviewers: (1) comprehensive skills in brief psychiatric interviewing, (2) adequate knowledge base of behavioral health conditions and therapeutic techniques, and (3) clinical documentation, integrated care/consultation practices, and e-competency skill sets. The model of training and skill requirements from expert feedback sessions included these three skill sets. Technology training recommendations were also identified and included: (1) awareness of privacy/confidentiality for electronic data gathering, storage, management, and sharing; (2) technology troubleshooting; and (3) video filming/retrieval. Conclusions: We describe and provide a suggested training model for the use of ATP integrated behavioral health. The training needs for ATP clinicians were assessed on a limited convenience sample of experts and clinicians, and more rigorous studies of training for ATP and other technology-focused, behavioral health services are needed. Clinical Trials number: NCT03538860.

Introduction Rapid aeromedical evacuation (AE) is standard of care in current conflicts. However, not much is known about possible effects of hypobaric conditions. We investigated possible effects of hypobaria on organ damage in a swine model of acute lung injury. Methods Lung injury was induced in anesthetized swine via intravenous oleic acid infusion. After a stabilization phase, animals were subjected to a 4 hour simulated AE at 8000 feet (HYPO). Control animals were kept at normobaria. After euthanasia and necropsy, organ damage was assessed by combined scores for hemorrhage, inflammation, edema, necrosis, and microatelectasis. Results Hemodynamic, neurological, or hematologic measurements were similar prior to transport. Hemodynamic instability became apparent during the last 2 hours of transport in the HYPO group. Histological injury scores in the HYPO group were higher for all organs (lung, kidney, liver, pancreas, and adrenal glands) except the brain, with the largest difference in the lungs (P Conclusions Swine with mild acute lung injury subjected to a 4 hour simulated AE showed more injury to most organs and, in particular, to the lungs compared with ground transport. This may exacerbate otherwise subclinical pathology and, eventually, manifest as abnormalities in gas exchange or possibly end-organ function.

OBJECTIVE: To compare clinical recommendations given by psychiatrists and the adherence to these recommendations by primary care physicians (PCP) following consultations conducted by asynchronous telepsychiatry (ATP) and synchronous telepsychiatry (STP). MATERIALS AND METHODS: ATP and STP consultations were compared using intermediate data from a randomized clinical trial with adult participant enrollment between April 2014 and December 2017. In both study arms, PCPs received written recommendations from the psychiatrist after each encounter. Independent clinicians reviewed PCP documentation to measure adherence to those recommendations in the 6 months following the baseline consultation. RESULTS: Medical records were reviewed for 645 psychiatrists’ consult recommendations; 344 from 61 ATP consultations and 301 from 62 STP consultations. Of those recommendations, 191 (56%) and 173 (58%) were rated fully adherent by two independent raters for ATP and STP, respectively. In a multilevel ordinal logistic regression model adjusted for recommendation type and recommended implementation timing, there was no statistically significant difference in adherence to recommendations for ATP compared with STP (adjusted odds ratio = 0.91, 95% confidence interval = 0.51–1.62). The profiles of recommendation type were comparable between ATP and STP. CONCLUSIONS: This is the first PCP adherence study comparing two forms of telemedicine. Although we did not find evidence of a difference between ATP and STP; this study supports the feasibility and acceptability of ATP and STP for the provision of collaborative psychiatric care. Clinical Trial Identifier NCT02084979.

Objective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees’ truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE’s implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE’s suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question.Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart.Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 μA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve’s center were, on average, half those of leads located near the periphery (54.92 μA vs. 110.71 μA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads’ thresholds decreased or remained stable over the 3-week span. The remaining two leads’ thresholds increased by 70–74%, possibly due to scarring or device failure.Significance: This work represents an important first step in establishing the MSE’s viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms.

Involving research users in setting priorities for musculoskeletal research is essential to raise awareness of the unmet needs for MSK research, to ensure research outcomes are patient-centred and relevant, have a high likelihood of resulting in patient benefit, reduce research waste and increase research value and impact. In 2018, Versus Arthritis convened an MSK Disorders Research Advisory Group (RAG) which included people with arthritis, health care professionals and researchers in MSK, in order to identify and prioritise research areas with a long-term aim of improving quality and impact of MSK research. On further review, there were few previous prioritisation approaches in this area looking across discovery science to more clinical research, at important research questions which might be common to a range of disorders or approaches incorporating input at all stages of the process by a range of stakeholders including people with arthritis. The group identified that more work to define research priorities in these areas was justified and designed a research priority setting process for MSK disorders. This manuscript documents the methodology that was developed by the group for this process.MethodsFollowing a review, the Child Health and Nutrition Research Initiative (CHNRI) method for research prioritisation was selected as best aligning with the needs of this process. The group agreed on adaptations to the CHNRI approach, context, purpose and remit of the exercise and identified through consensus four priority research Domains: Mechanisms of disease; Diagnosis (including early diagnosis) and measuring the impact of these disorders; Living well with MSK disorders and Successful Translation. From all published CHNRI scoring criteria for generated research avenues or themes of research, the group identified six which were most relevant to this process. To ensure accessibility of the survey and scoring, these were refined to three: Equity (considered cross cutting, not scored but considered throughout the process), Importance (Will research in this area have potential to lead to important new knowledge) and Impact (Might research in this area make a difference). Importance and Impact were to be scored on a scale of 1-10 for each research avenue with equal weighting of these two criteria in the subsequent generation of a total score.Data collectionFollowing ethical approval, an electronic first survey asking for important research uncertainties in the four research domains and any other areas will be distributed to all stakeholders (people with arthritis, researchers in all stages of MSK disorders research, healthcare professionals, industry e.g. pharmaceutical and medical technology companies, research funders, healthcare providers, government policy makers and charities). The next step is to consolidate all the gathered research uncertainties from the first survey into finalised research domains and avenues. Uncertainties will be summarised using deductive thematic analysis and organised into possible themes which will then be considered and refined by each of four appointed subgroups within the RAG. Following group and lay review and refinement of the wording including tests of readability, the second survey including this full list of research avenues will be submitted for ethical approval. The second survey will be completed by the same range of stakeholders as the first survey, both those who previously completed and new respondents. Respondents will be invited to rate each research avenue using the two scoring criteria, with the avenues presented in a random sequence to avoid bias.Analysis PlanAll available data will be analysed, from all respondents completing the survey in full and all partial respondents. For each research avenue, a mean criterion score will be calculated for each of the two criteria from all available survey responses (considering the number of respondents in each case), and then the two mean criterion scores will be summed to create a total score. Response rates and missing data for scoring of avenues will be reported. The primary prioritisation output of this exercise will be to produce a single ranked list of these total scores of research avenues, from highest to lowest. The most highly ranked avenues will be highlighted, for example the top five to top ten overall and from each research domain, with the exact number and nature of this depending on the distribution of the data. Respondent characteristics will be summarised including self-identified stakeholder group, age group, gender and ethnic background, to describe the diversity and representation within the survey respondents as far as possible.Dissemination planFindings will be communicated in a number of formats, both written and spoken, to ensure accessibility to all stakeholders, and will also be used by the charity in internal strategy development. Dissemination will include the submission of a manuscript to a peer-reviewed journal.

Posterior tarsal tunnel syndrome (PTTS) is an entrapment neuropathy due to compression of the tibial nerve or one of its terminal branches within the tarsal tunnel in the medial ankle. The tarsal tunnel is formed by the flexor retinaculum, while the floor is composed of the distal tibia, talus, and calcaneal bones. The tarsal tunnel contains a number of significant structures, including the tendons of 3 muscles as well as the posterior tibial artery, vein, and nerve. Focal compressive neuropathy of PTTS can originate from anything that physically restricts the volume of the tarsal tunnel. The variety of etiologies includes distinct movements of the foot, trauma, vascular disorders, soft tissue inflammation, diabetes mellitus, compression lesions, bony lesions, masses, lower extremity edema, and postoperative injury. Generally, compression of the posterior tibial nerve results in clinical findings consisting of numbness, burning, and painful paresthesia in the heel, medial ankle, and plantar surface of the foot. Diagnosis of PTTS can be made with the presence of a positive Tinel sign in combination with the physical symptoms of pain and numbness along the plantar and medial surfaces of the foot. Initially, patients are treated conservatively unless there are signs of muscle atrophy or motor nerve involvement. Conservative treatment includes activity modification, heat, cryotherapy, non-steroidal anti-inflammatory drugs, corticosteroid injections, opioids, GABA analog medications, tricyclic antidepressants, vitamin B-complex supplements, physical therapy, and custom orthotics. If PTTS is recalcitrant to conservative treatment, standard open surgical decompression of the flexor retinaculum is indicated. In recent years, a number of alternative minimally invasive treatment options have been investigated, but these studies have small sample sizes or were conducted on cadaveric models.

Exposure to blast overpressure may result in cerebrovascular impairment, including cerebral vasospasm. The mechanisms contributing to this vascular response are unclear. The aim of this study was to evaluate the relationship between blast and functional alterations of the cerebral microcirculation and to investigate potential underlying changes in vascular microstructure. Cerebrovascular responses were assessed in sham- and blast-exposed male rats at multiple time points from 2 h through 28 days after a single 130-kPa (18.9-psi) exposure. Pial microcirculation was assessed through a cranial window created in the parietal bone of anesthetized rats. Pial arteriolar reactivity was evaluated in vivo using hypercapnia, barium chloride, and serotonin. We found that exposure to blast leads to impairment of arteriolar reactivity >24 h after blast exposure, suggesting delayed injury mechanisms that are not simply attributed to direct mechanical deformation. Observed vascular impairment included a reduction in hypercapnia-induced vasodilation, increase in barium-induced constriction, and reversal of the serotonin effect from constriction to dilation. A reduction in vascular smooth muscle contractile proteins consistent with vascular wall proliferation was observed, as well as delayed reduction in nitric oxide synthase and increase in endothelin-1 B receptors, mainly in astrocytes. Collectively, the data show that exposure to blast results in delayed and prolonged alterations in cerebrovascular reactivity that are associated with changes in the microarchitecture of the vessel wall and astrocytes. These changes may contribute to long-term pathologies involving dysfunction of the neurovascular unit, including cerebral vasospasm.

BACKGROUND The aim of this study was to determine if transfusion with RBCs is associated with a rise in mean pulmonary artery pressure (MPAP) and whether such a rise is influenced by the duration of RBC storage. STUDY DESIGN AND METHODS A retrospective chart review of intensive care unit patients with pulmonary artery catheters was conducted at two military medical centers. RESULTS RBC transfusion is associated with a sustained (≥4 hours) statistically significant 2- to 3-mm Hg rise in MPAP relative to both pretransfusion levels (p < 0.05) and compared to asanguinous fluid infusions (p < 0.05). The magnitude of the rise (all infusions, RBCs, and asanguinous) correlates positively with in-hospital mortality (p < 0.01) and hospital length of stay (p < 0.01). The duration of RBC storage was not statistically correlated with the magnitude of rise in the population studied. Mean infusion volume was greater for RBC (vs. asanguinous) infusions, but volume adjustment of MPAP values did not alter the pattern or statistical significance of the results. CONCLUSIONS Analysis of retrospectively collected data suggests that transfusion of RBC-containing fluids results in a sustained elevation of MPAP. In the patient population studied, the duration of RBC storage did not correlate with the magnitude of MPAP rise. Future prospective studies of transfusion effects should consider including assessment of MPAP and subpopulation analyses.

Most psychiatric care is delivered in primary care settings, where depression is the most common presenting psychiatric symptom. Given the high prevalence of depression worldwide and the well-established consequences of untreated depression, the ability of primary care clinicians to effectively diagnose and treat it is critically important. This article offers up-to-date guidance for the diagnosis and treatment of major depressive disorder, including practical considerations for delivering optimal and efficient care for these patients.

Pre-hospital treatment of traumatic brain injury (TBI) with co-existing polytrauma is complicated by requirements for intravenous fluid volume vs. hypotensive resuscitation. A low volume, small particle-size-oxygen-carrier perfluorocarbon emulsion NVX-428 (dodecafluoropentane emulsion, 2% w/v) could improve brain tissue with minimal additional fluid volume. This study examined whether the oxygen-carrier NVX-428 shows safety and efficacy for pre-hospital treatment of TBI. Anesthetized swine underwent fluid percussion injury TBI and received 1 mL/kg IV NVX-428 (TBI-NVX) at 15 min (T15) or normal saline (no-treatment) (TBI-NON). Similarly, uninjured swine received NVX-428 (SHAM-NVX) or normal saline (SHAM-NON). Animals were monitored and measurements were taken for physiological and neurological parameters before euthanasia at the six-hour mark (T360). Histopathological analysis was performed on paraffin embedded tissues. Physiological, biochemical and blood gas parameters were not different, with the exception of a significant but transient increase in mean pulmonary artery pressure observed in the TBI-experimental group immediately after drug administration. There were no initial differences in brain oxygenation at baseline, but over time oxygen decreased ~50% in both TBI groups. Histological brain injury scores were similar between TBI-NVX and TBI-NON, although a number of subcategories (spongiosis-ischemic/dead neurons-hemorrhage-edema) in TBI-NVX had a tendency for lower scores. The cerebellum showed significantly lower spongiosis and ischemic/dead neuron injury scores and a lower number of Fluoro-Jade-B-positive cerebellar-Purkinje-cells after NVX-428 treatment compared to controls. NVX-428 may assist in mitigating secondary cellular brain damage.

BACKGROUND Asynchronous telepsychiatry (ATP; delayed-time) consultations are a novel form of psychiatric consultation in primary care settings. Longitudinal studies comparing clinical outcomes for ATP with synchronous telepsychiatry (STP) are lacking. OBJECTIVE This study aims to determine the effectiveness of ATP in improving clinical outcomes in English- and Spanish-speaking primary care patients compared with STP, the telepsychiatry usual care method. METHODS Overall, 36 primary care physicians from 3 primary care clinics referred a heterogeneous sample of 401 treatment-seeking adult patients with nonurgent psychiatric disorders. A total of 184 (94 ATP and 90 STP) English- and Spanish-speaking participants (36/184, 19.6% Hispanic) were enrolled and randomized, and 160 (80 ATP and 80 STP) of them completed baseline evaluations. Patients were treated by their primary care physicians using a collaborative care model in consultation with the University of California Davis Health telepsychiatrists, who consulted with patients every 6 months for up to 2 years using ATP or STP. Primary outcomes (the clinician-rated Clinical Global Impressions [CGI] scale and the Global Assessment of Functioning [GAF]) and secondary outcomes (patients’ self-reported physical and mental health and depression) outcomes were assessed every 6 months. RESULTS For clinician-rated primary outcomes, ATP did not promote greater improvement than STP at 6-month follow-up (ATP vs STP, adjusted difference in follow-up at 6 months vs baseline differences for CGI: 0.2, 95% CI −0.2 to 0.6; P=.28; and GAF: −0.6, 95% CI −3.1 to 1.9; P=.66) or 12-month follow-up (ATP vs STP, adjusted difference in follow-up at 12 months vs baseline differences for CGI: 0.4, 95% CI −0.04 to 0.8; P=.07; and GAF: −0.5, 95% CI −3.3 to 2.2; P=.70), but patients in both arms had statistically and clinically significant improvements in both outcomes. There were no significant differences in improvement from baseline between ATP and STP on any patient self-reported ratings at any follow-up (all P values were between .17 and .96). Dropout rates were higher than predicted but similar between the 2 arms. Of those with baseline visits, 46.8% (75/160) did not have a follow-up at 1 year, and 72.7% (107/147) did not have a follow-up at 2 years. No serious adverse events were associated with the intervention. CONCLUSIONS This is the first longitudinal study to demonstrate that ATP can improve clinical outcomes in English- and Spanish-speaking primary care patients. Although we did not find evidence that ATP is superior to STP in improving clinical outcomes, it is potentially a key part of stepped mental health interventions available in primary care. ATP presents a possible solution to the workforce shortage of psychiatrists and a strategy for improving existing systems of care. CLINICALTRIAL ClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979.

Current clinical research into mild traumatic brain injury (mTBI) has focused on white matter changes as identified by advanced MRI based imaging techniques. However, perivascular tau accumulation in the brains of individuals diagnosed with mTBI suggests that the vasculature plays a key role in the pathology. This study used a rat model to examine whether the endothelial glycocalyx, a layer of the vasculature responsible for sensing luminal shear forces, is damaged by exposure to repeated low intensity blast, and whether this layer is associated with observed behavioral deficits. The blast exposure used consisted of 12, 40 kPa blast exposures conducted with a minimum of 24 h between blasts. We found that repeated blast exposure reduced glycocalyx length and density in various brain regions indicating damage. This blast exposure paradigm was associated with a mild performance decrement in the Morris water maze (MWM) which assesses learning and memory. Administration of hyaluronidase, an enzyme that binds to and degrades hyaluronan (a major structural component of the glycocalyx) prior to blast exposure reduced the observed behavioral deficits and induced a thickening of the glycocalyx layer. Taken together these findings demonstrate that the endothelial glycocalyx degradation following repeated blast is associated with behavioral decrements which can be prevented by treatment with hyaluronidase.

Objective: Integrated behavioral healthcare models typically involve a range of consultation options for mental healthcare. Asynchronous telepsychiatry (ATP) consults may be an additional potential choice, so we are conducting a 5-year clinical trial comparing ATP with synchronous telepsychiatry (STP) consultations. Methods: Patients referred by primary care providers are randomly assigned to one of the two treatment groups, ATP or STP. Clinical outcome, satisfaction, and economic data are being collected from patients for 2 years at 6-month intervals. Results: Baseline characteristics for the first 158 patients and case examples of ATP are presented. Conclusion: Implementing ATP in existing integrated behavioral healthcare models could make mental healthcare more efficient.

BackgroundAsynchronous telepsychiatry (ATP; delayed-time) consultations are a novel form of psychiatric consultation in primary care settings. Longitudinal studies comparing clinical outcomes for ATP with synchronous telepsychiatry (STP) are lacking.ObjectiveThis study aims to determine the effectiveness of ATP in improving clinical outcomes in English- and Spanish-speaking primary care patients compared with STP, the telepsychiatry usual care method.MethodsOverall, 36 primary care physicians from 3 primary care clinics referred a heterogeneous sample of 401 treatment-seeking adult patients with nonurgent psychiatric disorders. A total of 184 (94 ATP and 90 STP) English- and Spanish-speaking participants (36/184, 19.6% Hispanic) were enrolled and randomized, and 160 (80 ATP and 80 STP) of them completed baseline evaluations. Patients were treated by their primary care physicians using a collaborative care model in consultation with the University of California Davis Health telepsychiatrists, who consulted with patients every 6 months for up to 2 years using ATP or STP. Primary outcomes (the clinician-rated Clinical Global Impressions [CGI] scale and the Global Assessment of Functioning [GAF]) and secondary outcomes (patients’ self-reported physical and mental health and depression) outcomes were assessed every 6 months.ResultsFor clinician-rated primary outcomes, ATP did not promote greater improvement than STP at 6-month follow-up (ATP vs STP, adjusted difference in follow-up at 6 months vs baseline differences for CGI: 0.2, 95% CI −0.2 to 0.6; P=.28; and GAF: −0.6, 95% CI −3.1 to 1.9; P=.66) or 12-month follow-up (ATP vs STP, adjusted difference in follow-up at 12 months vs baseline differences for CGI: 0.4, 95% CI −0.04 to 0.8; P=.07; and GAF: −0.5, 95% CI −3.3 to 2.2; P=.70), but patients in both arms had statistically and clinically significant improvements in both outcomes. There were no significant differences in improvement from baseline between ATP and STP on any patient self-reported ratings at any follow-up (all P values were between .17 and .96). Dropout rates were higher than predicted but similar between the 2 arms. Of those with baseline visits, 46.8% (75/160) did not have a follow-up at 1 year, and 72.7% (107/147) did not have a follow-up at 2 years. No serious adverse events were associated with the intervention.ConclusionsThis is the first longitudinal study to demonstrate that ATP can improve clinical outcomes in English- and Spanish-speaking primary care patients. Although we did not find evidence that ATP is superior to STP in improving clinical outcomes, it is potentially a key part of stepped mental health interventions available in primary care. ATP presents a possible solution to the workforce shortage of psychiatrists and a strategy for improving existing systems of care.Trial RegistrationClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979.

Blast-related traumatic brain injury (TBI) has been a common cause of injury in the recent conflicts in Iraq and Afghanistan. Blast waves can damage blood vessels, neurons, and glial cells within the brain. Acutely, depending on the blast energy, blast wave duration, and number of exposures, blast waves disrupt the blood-brain barrier, triggering microglial activation and neuroinflammation. Recently, there has been much interest in the role that ongoing neuroinflammation may play in the chronic effects of TBI. Here, we investigated whether chronic neuroinflammation is present in a rat model of repetitive low-energy blast exposure. Six weeks after three 74.5-kPa blast exposures, and in the absence of hemorrhage, no significant alteration in the level of microglia activation was found. At 6 weeks after blast exposure, plasma levels of fractalkine, interleukin-1β, lipopolysaccharide-inducible CXC chemokine, macrophage inflammatory protein 1α, and vascular endothelial growth factor were decreased. However, no differences in cytokine levels were detected between blast-exposed and control rats at 40 weeks. In brain, isolated changes were seen in levels of selected cytokines at 6 weeks following blast exposure, but none of these changes was found in both hemispheres or at 40 weeks after blast exposure. Notably, one animal with a focal hemorrhagic tear showed chronic microglial activation around the lesion 16 weeks post-blast exposure. These findings suggest that focal hemorrhage can trigger chronic focal neuroinflammation following blast-induced TBI, but that in the absence of hemorrhage, chronic neuroinflammation is not a general feature of low-level blast injury.

Hemorrhaged animals have benefited from resuscitation with the hemoglobin-based oxygen carrier (HBOC-201). Co-infusion of nitric oxide (NO) via separate intravascular lines is effective in attenuating HBOC-induced elevation of blood pressure. We tested whether nitroglycerin (NTG) and HBOC-201 can be packaged together as a single drug for resuscitation. Since NTG binds easily to plastics such as polyvinylchloride, we assessed the stability of this combination in oxygen barrier double-layer ethylene-vinyl alcohol/polyolefin bags over a 30-day period. Outcome measures indicative of the stability of HBOC/NTG were reported as changes in levels of hemoglobin (Hb), methemoglobin (MetHb), NTG, and nitrite over time. Individual tightly sealed small aliquots of HBOC/NTG were prepared under nitrogen and analyzed in a timely fashion from 0 to 30 days using hematology instruments, HPLC, FPLC, and chemiluminescence. The level of NTG in the HBOC/NTG mixture was reduced significantly over time whereas it was stable in control mixtures of NTG/saline. The level of total Hb in the HBOC/NTG and HBOC/saline mixtures remained stable over time. MetHb formed and increased to 6% up to day 1 and then slowly decreased in the HBOC/NTG mixture whereas it remained unchanged in the HBOC/saline mixture. Nitrite was produced in the HBOC/NTG group upon mixing, was increased at day 1, and then became undetectable. The reaction between HBOC-201 and NTG occurring upon mixing and developing over time in polyolefin bags makes the long-term storage of this mixed combination inappropriate.

Traumatic brain injury resulting from exposure to blast overpressure (BOP) is associated with neuropathology including impairment of the blood-brain barrier (BBB). This study examined the effects of repeated exposure to primary BOP and post-blast treatment with an antioxidant, N-acetylcysteine amide (NACA) on the integrity of BBB. Anesthetized rats were exposed to three 110 kPa BOPs separated by 0.5 h. BBB integrity was examined in vivo via a cranial window allowing imaging of pial microcirculation by intravital microscopy. Tetramethylrhodamine isothiocyanate Dextran (TRITC-Dextran, mw = 40 kDa or 150 kDa) was injected intravenously 2.5 h after the first BOP exposure and the leakage of TRITC-Dextran from pial microvessels into the brain parenchyma was assessed. The animals were randomized into 6 groups (n = 5/group): four groups received 40 kDa TRITC-Dextran (BOP-40, sham-40, BOP-40 NACA, and sham-40 NACA), and two groups received 150 kDa TRITC-Dextran (BOP-150 and sham-150). NACA treated groups were administered NACA 2 h after the first BOP exposure. The rate of TRITC-Dextran leakage was significantly higher in BOP-40 than in sham-40 group. NACA treatment significantly reduced TRITC-Dextran leakage in BOP-40 NACA group and sham-40 NACA group presented the least amount of leakage. The rate of leakage in BOP-150 and sham-150 groups was comparable to sham-40 NACA and thus these groups were not assessed for the effects of NACA. Collectively, these data suggest that BBB integrity is compromised following BOP exposure and that NACA treatment at a single dose may significantly protect against blast-induced BBB breakdown.

Background Over the last 5 years, attendances at major emergency departments (ED) have increased by 3000 patients per day. Primary care streaming has the potential to mitigate this increased demand. However, while one UK study in a tertiary paediatric ED found that a co-located General Practitioner (GP) significantly reduced waiting times and admissions, a Cochrane review has concluded there is a lack of evidence to support the effectiveness of primary care services in ED. Aim To evaluate the impact of primary care streaming on the paediatric ED service for patients presenting with non-urgent medical problems. Method This service evaluation was conducted from January – December 2018 in a tertiary paediatric ED. At triage, patients who met specified criteria were assigned to the ‘primary care’ category. The evaluation compared patients seen by a co-located GP during term time, between 1800–2300 on weekdays and 1100–2000 on weekends, with patients seen by ED staff presenting at other times, or when the GP service was full/unstaffed. Data was collected from ED and GP electronic systems and analysed using Excel. The main outcome measures were patient numbers, length of stay (LOS), admission rates, unplanned ED re-attendances, number of investigations and prescriptions. Results Interim results show that, from January – June 2018, 3646 primary care patients attended the ED. 38.2% attended during primary care streaming hours, of which, 30% saw a GP. The difference in median LOS was 45 min (ED 108.25 vs. GP 63.5). The GP investigated 5.4% (ED 7.6% vs GP 7.2%) and prescribed for 1.7% (ED 34.9% vs GP 34.3%) fewer patients than ED staff. Admission rates were similar in both groups (ED 3.15% vs GP 3.5%). There was a 31.7% reduction in the re-attendance rate for patients seen by the GP (ED 9.7% vs GP 7.1%). Conclusion For patients with non-urgent medical problems, primary care streaming significantly reduces length of ED stay without an increased admission rate. Additionally, is a trend towards a reduced re-attendance rate suggesting that the primary care streaming model implemented is safe and effective.

Telehealth facilitates integrated, patient-centred care. Synchronous video, telepsychiatry (TP), or telebehavioural health provide outcomes as good as in-person care. It also improves access to care, leverages expertise at a distance, and is effective for education and consultation to primary care. Other technologies on an e-behavioural health spectrum are also useful, like telephone, e-mail, text, and e-consults. This paper briefly organizes these technologies into low, mid and high intensity telehealth models and reviews the evidence base for interventions to primary care, and, specifically, for TP and integrated care (IC). Technology, mobile health, and IC competencies facilitate quality care. TP is a high intensity model and it is the best-studied option. Studies of IC are preliminary, but those with collaborative and consultative care show effectiveness. Low- and mid-intensity technology options like telephone, e-mail, text, and e-consults, may provide better access for patients and more timely provider communication and education. They are also probably more cost-effective and versatile for health system workflow. Research is needed upon all technology models related to IC for adult and paediatric primary care populations. Effective healthcare delivery matches the patients' needs with the model, emphasizes clinician competencies, standardizes interventions, and evaluates outcomes.

Background:Behcet’s disease is a systemic autoimmune vasculitis that typically involves mucocutaneous surfaces, the eyes and the skin with varying manifestations. Skin ulceration often secondary to pathergy is a common feature.Objectives:To raise awareness of breast ulceration as a clinical manifestation in Behcet’s disease.Methods:We report a case of complex Bechet’s disease associated with severe refractory breast ulceration successfully treated with cyclophosphamide.Results:A 27 year old female patient presented to the rheumatology department with a non-healing lesion on her face secondary to a cat scratch. She reported previous episodes of ulceration usually as a result of minor trauma such as IV cannulation, as well as a two year history of severe oral and genital ulceration. She had also been diagnosed with ‘colitis’ requiring iliocaecal resection two years prior to presentation. Previous treatments for her bowel included azathioprine, infliximab, adalimumab and vedolizumab. Over the next three years she developed recurrent eye involvement in the form of scleritis with ongoing oral and genital ulceration. Further treatment under our care included ustekinumab, entanercept, benepali, certolizumab and tacrolimus with background prednisolone. She then developed a small area of broken skin on her left breast which continued to extend and ulcerate despite treatment with IV steroids. Tissue biopsy showed deep focal vasculitis with intravascular thrombi. Anticoagulation was commenced and she was treated with tocilizumab IV for 3 months with no clinical improvement. Involvement extended to include 80 percent of the breast surface and the nipple self-amputated. Due to the severity and extent of the ulceration which was extremely painful and distressing, she was given 3 months of IV cyclophosphamide at a dose of 15mg/kg every 2-3 weeks. The ulceration showed rapid clinical improvement (see Figure 1).Figure 1.Breast ulceration before and after 3 months of cyclophosphamide treatmentConclusion:Involvement of the breast in systemic vasculitides (such as GPA or PAN) has been reported, although usually manifesting as a palpable mass with diagnosis on biopsy 1. Similar presentations in Behcet’s disease have been recognised 2, although much less commonly. Our case demonstrates that severe breast ulceration can be a clinical manifestation of this condition and can be refractory to usual therapies.References:[1]Ren J, Liu J, Su J, Zhang J, Zhao J. Systemic vasculitis involving the breast: a case report and literature review. Rheumatol Int. 2019 Aug;39(8):1447-1455[2]Soleto MJ, Marcos L. Behçet’s disease involving the breast. Eur Radiol. 2002 Dec;12 Suppl 3:S98-S100. doi: 10.1007/s00330-002-1420-4.Disclosure of Interests:None declared

Perfluorocarbons (PFCs) can transport 50 times more oxygen than human plasma. Their properties may be advantageous in preservation of tissue viability in oxygen-deprived states, such as in acute lung injury. We hypothesized that an intravenous dose of the PFC emulsion Oxycyte® would improve tissue oxygenation and thereby mitigate the effects of acute lung injury. Intravenous oleic acid (OA) was used to induce lung injury in anesthetized and instrumented Yorkshire swine assigned to three experimental groups: (1) PFC post-OA received Oxycyte® (5 ml/kg) 45 min after oleic acid-induced lung injury (OALI); (2) PFC pre-OA received Oxycyte® 45 min before OALI; and (3) Controls which received equivalent dose of normal saline. Animals were observed for 3 h after OALI began, and then euthanized. The median survival times for PFC post-OA, PFC pre-OA, and control were 240, 87.5, and 240 min, respectively (p = 0.001). Mean arterial pressure and mean pulmonary arterial pressure were both higher in the PFC post-OA (p

Objectives Perforation of the chest (open pneumothorax) with and without lung injury can cause air accumulation in the chest, positive intrapleural pressure and lead to tension pneumothorax if untreated. The performance of chest seals to prevent tension physiology depends partially on their ability to adhere to the skin and seal the chest wound. Novel non-occlusive vented chest seals were assessed for their adhesiveness on skin of live swine under normal and extreme environmental conditions to simulate austere battlefield conditions. Methods Chest seals were applied on the back of the swine on skin that was soiled by various environmental contaminants to represent battlefield situations. A peeling (horizontal rim peeling) and detachment and breaching (vertical pulling) techniques were used to quantify the adhesive performance of vented chest seals. Among eight initially selected vented seals, five (Bolin, Russell, Fast breathe, Hyfin and SAM) were further down-selected based on their superior adherence scores at ambient temperatures. The adherence of these seals was then assessed after approximately 17h storage at extreme cold (−19.5°C) and hot (71.5°C) temperatures. Results Adherence scores for peeling (above 90%) and detachment scores (less than 25%) were comparable for four vented chest seals when tested at ambient temperature, except for the Bolin seal which had higher breaching. Under extreme storage temperatures, adherence peeling scores were comparable to those at ambient temperatures for four chest seals. Scores were significantly lower for the Bolin seal at extreme temperatures. This seal also had the highest detachment and breaching scores. In contrast, the Russell, Fast breathe, Hyfin and SAM seals showed similar ability to stay air tight without breaching after hot storage. Conclusion No significant difference was found in skin adherence of the five vented chest seals at ambient temperature and the four seals (Russell, Fast breathe, Hyfin and SAM) maintained superior adherence even after exposure to extreme temperatures compared to the Bolin. To select the most effective product from the 5 selected vented chest seals, further functional evaluation of the valve of these chest seals on a chest wound with the potential for tension in the pneumothorax or hemopneumothorax is warranted.

Background There is inadequate information on the physiologic effects of aeromedical evacuation on wounded war fighters with traumatic brain injury (TBI). At altitudes of 8,000 ft, the inspired oxygen is lower than standard sea level values. In troops experiencing TBI, this reduced oxygen may worsen or cause secondary brain injury. We tested the hypothesis that the effects of prolonged aeromedical evacuation on critical neurophysiologic parameters (i.e., brain oxygenation [PbtO2]) of swine with a fluid percussion injury/TBI would be detrimental compared with ground (normobaric) transport. Methods Yorkshire swine underwent fluid percussion injury/TBI with pretransport stabilization before being randomized to a 4-hour aeromedical transport at simulated flight altitude of 8,000 ft (HYPO, n = 8) or normobaric ground transport (NORMO, n = 8). Physiologic measurements (i.e., PbtO2, cerebral perfusion pressure, intracranial pressure, regional cerebral blood flow, mean arterial blood pressure, and oxygen transport variables) were analyzed. Results Survival was equivalent between groups. Measurements were similar in both groups at all phases up to and including onset of flight. During the flight, PbtO2, cerebral perfusion pressure, and mean arterial blood pressure were significantly lower in the HYPO than in the NORMO group. At the end of flight, regional cerebral blood flow was lower in the HYPO than in the NORMO group. Other parameters such as intracranial pressure, cardiac output, and mean pulmonary artery pressure were not significantly different between the two groups. Conclusion A 4-hour aeromedical evacuation at a simulated flight altitude of 8,000 ft caused a notable reduction in neurophysiologic parameters compared with normobaric conditions in this TBI swine model. Results suggest that hypobaric conditions exacerbate cerebral hypoxia and may worsen TBI in casualties already in critical condition.

Background Hypoxia is a critical secondary injury mechanism in traumatic brain injury (TBI), and early intervention to alleviate post-TBI hypoxia may be beneficial. NVX-108, a dodecafluoropentane perfluorocarbon, was screened for its ability to increase brain tissue oxygen tension (PbtO 2 ) when administered soon after TBI. Methods Ketamine-acepromazine anesthetized rats ventilated with 40% oxygen underwent moderate controlled cortical impact (CCI)-TBI at time 0 (T0). Rats received either no treatment (NON, n =8) or 0.5 ml/kg intravenous (IV) NVX-108 (NVX, n =9) at T15 (15 min after TBI) and T75. Results Baseline cortical PbtO 2 was 28±3 mm Hg and CCI-TBI resulted in a 46±6% reduction in PbtO 2 at T15 ( P P =0.013) were found when comparing either absolute or percentage change of PbtO 2 to post-injury (mixed-model ANOVA) suggesting that administration of NVX-108 increased PbtO 2 above injury levels while it remained depressed in the NON group. Specifically in the NVX group, PbtO 2 increased to a peak 143% of T15 ( P =0.02) 60 min after completion of NVX-108 injection (T135). Systemic blood pressure was not different between the groups. Conclusion NVX-108 caused an increase in PbtO 2 following CCI-TBI in rats and should be evaluated further as a possible immediate treatment for TBI.

The chicken Major Histocompatibility Complex (MHC) is very strongly associated with disease resistance and thus is a very important region of the chicken genome. Historically, MHC (B locus) has been identified by the use of serology with haplotype specific alloantisera. These antisera can be difficult to produce and frequently cross-react with multiple haplotypes and hence their application is generally limited to inbred and MHC-defined lines. As a consequence, very little information about MHC variability in heritage chicken breeds is available. DNA-based methods are now available for examining MHC variability in these previously uncharacterized populations. A high density SNP panel consisting of 101 SNP that span a 230,000 bp region of the chicken MHC was used to examine MHC variability in 17 heritage populations of chickens from five universities from Canada and the United States. The breeds included 6 heritage broiler lines, 3 Barred Plymouth Rock, 2 New Hampshire and one each of Rhode Island Red, Light Sussex, White Leghorn, Dark Brown Leghorn, and 2 synthetic lines. These heritage breeds contained from one to 11 haplotypes per line. A total of 52 unique MHC haplotypes were found with only 10 of them identical to serologically defined haplotypes. Furthermore, nine MHC recombinants with their respective parental haplotypes were identified. This survey confirms the value of these non-commercially utilized lines in maintaining genetic diversity. The identification of multiple MHC haplotypes and novel MHC recombinants indicates that diversity is being generated and maintained within these heritage populations.

Intracranial pressure (ICP) measurements are essential in evaluation and treatment of neurological disorders such as subarachnoid and intracerebral hemorrhage, ischemic stroke, hydrocephalus, meningitis/encephalitis, and traumatic brain injury (TBI). The techniques of ICP monitoring have evolved from invasive to non-invasive—with both limitations and advantages. Some limitations of the invasive methods include short-term monitoring, risk of infection, restricted mobility of the subject, etc. The invasiveness of a method limits the frequency of ICP evaluation in neurological conditions like hydrocephalus, thus hampering the long-term care of patients with compromised ICP. Thus, there has been substantial interest in developing noninvasive techniques for assessment of ICP. Several approaches were reported, although none seem to provide a complete solution due to inaccuracy. ICP measurements are fundamental for immediate care of TBI patients in the acute stages of severe TBI injury. In severe TBI, elevated ICP is associated with mortality or poor clinical outcome. ICP monitoring in conjunction with other neurological monitoring can aid in understanding the pathophysiology of brain damage. This review article presents: (a) the significance of ICP monitoring; (b) ICP monitoring methods (invasive and non-invasive); and (c) the role of ICP monitoring in the management of brain damage, especially TBI.

Newcastle disease is considered the number one disease constraint to poultry production in low and middle-income countries, however poultry that is raised in resource-poor areas often experience multiple environmental challenges. Heat stress has a negative impact on production, and immune response to pathogens can be negatively modulated by heat stress. Candidate genes and regions chosen for this study were based on previously reported associations with response to immune stimulants, pathogens, or heat, including: TLR3, TLR7, MX, MHC-B (major histocompatibility complex, gene complex), IFI27L2, SLC5A1, HSPB1, HSPA2, HSPA8, IFRD1, IL18R1, IL1R1, AP2A2, and TOLLIP. Chickens of a commercial egg-laying line were infected with a lentogenic strain of NDV (Newcastle disease virus), half the birds were maintained at thermoneutral temperature and the other half were exposed to high ambient temperature before the NDV challenge and throughout the remainder of the study. Phenotypic responses to heat, to NDV, or to heat + NDV were measured. Selected SNPs (single nucleotide polymorphisms) within 14 target genes or regions were genotyped, and genotype effects on phenotypic responses to NDV or heat + NDV were tested in each individual treatment group and the combined groups. Seventeen significant haplotype effects, among seven genes and seven phenotypes, were detected for response to NDV or heat or NDV + heat. These findings identify specific genetic variants that are associated with response to heat and/or NDV which may be useful in the genetic improvement of chickens to perform favorably when faced with pathogens and heat stress.

There has been a rapid increase in the incidence of chronic kidney disease and those requiring renal replacement therapy. Managing these patients requires a multidisciplinary team approach. Clinical nurse specialists (CNS's) play a vital role in ensuring the highest quality care is delivered in a cost-effective manner. There is an acute shortage of CNS' in the Middle East and other developing countries. Development of the CNS's role necessitates comprehensive training programs in conjunction with multi-stakeholder acceptance. This article hereby addresses the various steps in developing such a role as facilitating nurses to work to their full professional and academic potential ensures best practice.

Background Aeromedical evacuation to definitive care is standard in current military conflicts. However, there is minimal knowledge on the effects of hypobaria (HYPO) on either the flight crew or patients. The effects of HYPO were investigated using healthy swine. Methods Anesthetized Yorkshire swine underwent a simulated 4 h "transport" to an altitude of 2,441 m (8,000 feet.; HYPO, N = 6) or at normobaric conditions (NORMO, N = 6). Physiologic and biochemical data were collected. Organ damage was assessed for hemorrhage, inflammation, edema, necrosis, and for lungs only, microatelectasis. Results All parameters were similar prior to and after "transport" with no significant effects of HYPO on hemodynamic, neurologic, or oxygen transport parameters, nor on blood gas, chemistry, or complete blood count data. However, the overall Lung Injury Score was significantly worse in the HYPO than the NORMO group (10.78 ± 1.22 vs. 2.31 ± 0.71, respectively) with more edema/fibrin/hemorrhage in the subpleural, interlobular and alveolar space, more congestion in alveolar septa, and evidence of microatelectasis (vs. no microatelectasis in the NORMO group). There was also increased severity of pulmonary neutrophilic (1.69 ± 0.20 vs. 0.19 ± 0.13) and histiocytic inflammation (1.83 ± 0.23 vs. 0.47 ± 0.17) for HYPO versus NORMO, respectively. On the other hand, there was increased renal inflammation in NORMO compared with HYPO (1.00 ± 0.13 vs. 0.33 ± 0.17, respectively). There were no histopathological differences in brain (whole or individual regions), liver, pancreas, or adrenals. Conclusion Hypobaria, itself, may have an adverse effect on the respiratory system, even in healthy individuals, and this may be superimposed on combat casualties where there may be preexisting lung injury. The additional effects of anesthesia and controlled ventilation on these results are unknown, and further studies are indicated using awake models to better characterize the mechanisms for this pathology and the factors that influence its severity.

Introduction A stressful environment may contribute to poor outcomes after TBI. The current study evaluates the impact of acute stress in a polytrauma rat model. Methods Rats were stressed by a 45-minute immobilization period before instrumentation under ketamine (t1). Polytrauma was produced by blast overpressure and controlled hemorrhage (t2). Rats were euthanized immediately after a 3 h simulated Medevac-transport time (t3) or after 72 h post-trauma (t4). Corticosterone, ACTH, and ACTH receptor gene expression were measured at these time points. Physiological parameters were monitored throughout the study. Results HR was higher in stressed compared to unstressed animals at t1. Corticosterone and ACTH levels were similar for all conditions at t1 and t2; ACTH and corticosterone became elevated in all groups at t3 and at t4, respectively. The ACTH receptor gene expression trended towards higher values at t4 for the stressed animals whether being injured or not. Survival after injury was 83% in both unstressed and stressed animals. Conclusion Overall, corticosterone was not significantly affected following acute stress in ketamine-anesthetized rats. Early mortality was primarily due to polytrauma and change in the animal’s biochemical parameters appeared at t4 post trauma. The findings indicate that ketamine-anesthesia and/or surgery may have overshadowed the effect of the initial stress.

A striking observation among veterans returning from the recent conflicts in Iraq and Afghanistan has been the co-occurrence of blast-related mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI might coexist due to additive effects of independent psychological and physical traumas experienced in a war zone. Alternatively blast injury might induce PTSD-related traits or damage brain structures that mediate responses to psychological stressors, increasing the likelihood that PTSD will develop following a subsequent psychological stressor. Rats exposed to repetitive low-level blasts consisting of three 74.5 kPa exposures delivered once daily for three consecutive days develop a variety of anxiety and PTSD-related behavioral traits that are present for at least 9 months after blast exposure. A single predator scent challenge delivered 8 months after the last blast exposure induces additional anxiety-related changes that are still present 45 days later. Because the blast injuries occur under general anesthesia, it appears that blast exposure in the absence of a psychological stressor can induce chronic PTSD-related traits. The reaction to a predator scent challenge delivered many months after blast exposure suggests that blast exposure in addition sensitizes the brain to react abnormally to subsequent psychological stressors. The development of PTSD-related behavioral traits in the absence of a psychological stressor suggests the existence of blast-induced “PTSD”. Findings that PTSD-related behavioral traits can be reversed by BCI-838, a group II metabotropic glutamate receptor antagonist offers insight into pathogenesis and possible treatment options for blast-related brain injury. This article is part of the Special Issue entitled “Novel Treatments for Traumatic Brain Injury”.

Objective Serotonin syndrome (SS) is an adverse drug reaction occurring among patients receiving serotonergic agents (SAs), and although SAs are commonly prescribed, the epidemiology and economic burden of SS with concomitant SA use have not been comprehensively examined. The objective of this study was to investigate the prevalence, incidence, and economic burden of SS with SA use. Methods A retrospective cohort study was conducted using Veterans Health Administration (VHA) records (identification period: October 1, 2008-September 30, 2012) and commercially insured patient records (Intercontinental Marketing Services PharMetrics Plus; identification period: January 1, 2010-December 31, 2013). Cohorts were based on drug classification and exposure: single monoamine oxidase inhibitor (MAOI), MAOIs in combination with SAs, single non-MAOI SA, and multiple non-MAOI SAs (2, 3, 4, ≥ 5). Participants were aged ≥ 18 years with continuous health plan enrollment for 12 months prior to the first SA claim. Outcomes were SS events (ICD-9-CM: 333.99), annual incidence and prevalence, related health care utilization and costs, and SS incidence relative risk. Results Over 15 million patients were identified and categorized by SA prescription type. SS incidence in both populations decreased: 0.19%-0.07% (VHA) and 0.17%-0.09% (commercially insured). Overall SS prevalence decreased during the study period. Compared to single non-MAOI SA patients, SS incidence relative risk was highest among patients prescribed ≥ 5 non-MAOI SAs. Inpatient stays accounted for 4.35% (VHA) and 0.88% (commercially insured) of all SS events. Of SS-related inpatient stays, median costs were $8,765 (VHA) and $10,792 (commercially insured). Conclusions SS incidence and prevalence and SS-related hospitalization risk among patients prescribed SAs were low in both populations. This study provides additional information regarding SS risk associated with SA use.