Identification of allergens from Aspergillus fumigatus-Potential association with lung damage in asthma.

Background: Component-resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1- or 2-dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained.

Methods: We used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus.

Principal component analysis of a swine injury model identifies multiple phenotypes in trauma.

Background: Trauma is the third leading cause of death in the United States and the primary cause of death for people between the ages of 1 year and 44 years. In addition to tissue damage, trauma may also activate an inflammatory state known as trauma-induced coagulopathy (TIC) that is associated with clotting malfunctions, acidemia, and end-organ dysfunction. Prior work has also demonstrated benefit to acknowledging the type and severity of endothelial injury, coagulation derangements, and systemic inflammation in the management of trauma patients.

FFP maintains normal coagulation while Kcentra induces a hypercoagulable state in a porcine model of pulmonary contusion and hemorrhagic shock.

Background: Moderate injury can lead to a coagulopathy. Fresh frozen plasma (FFP) corrects coagulopathy by means of a balanced array of clotting factors. We sought to compare the late effects of FFP and a prothrombin complex concentrate (PCC) on the coagulopathy of trauma using a porcine model of pulmonary contusion (PC) and hemorrhagic shock (HS) designed to evaluate the organ protective effects of these treatments.

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease.

Allergy to airway-colonising, thermotolerant, filamentous fungi represents a distinct eosinophilic endotype of often severe lung disease. This endotype, which particularly affects adult asthma, but also complicates other airway diseases and sometimes occurs de novo, has a heterogeneous presentation ranging from severe eosinophilic asthma to lobar collapse. Its hallmark is lung damage, characterised by fixed airflow obstruction (FAO), bronchiectasis and lung fibrosis.

Fungal bronchitis is a distinct clinical entity which is responsive to antifungal therapy.

Chronic productive cough in the context of exacerbations of airway disease can be associated with positive sputum cultures for fungi, in particular and spp., suggesting fungal bronchitis, a condition not widely recognised, as a possible cause for the exacerbation. Our objective was to determine the response to antifungal therapy in patients with suspected fungal bronchitis.

Tranexamic acid administration in the field does not affect admission thromboelastography after traumatic brain injury.

Background: No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI.

Early Tranexamic Acid Administration After Traumatic Brain Injury Is Associated With Reduced Syndecan-1 and Angiopoietin-2 in Patients With Traumatic Intracranial Hemorrhage.

Objective: To evaluate the effect of early tranexamic acid (TXA) administration on circulating markers of endotheliopathy.

Setting: Twenty trauma centers in the United States and Canada.

Participants: Patients with moderate-to-severe traumatic brain injury (TBI) (MS-TBI) and intracranial hemorrhage who were not in shock (systolic blood pressure ≥90 mm Hg).

The airway fungal microbiome in asthma.

Background: Fungal involvement in asthma is associated with severe disease. The full spectrum of fungal species in asthma is not well described and is derived largely from insensitive culture techniques.

Objectives: To use high-throughput sequencing to describe the airway mycobiota in asthmatics with and without fungal sensitization and healthy controls; to compare samples representing different airway compartments; to determine whether the mycobiota was influenced by the fungal composition of outdoor air; and to compare findings with clinically relevant outcomes.

Use of bilobed partial resuscitative endovascular balloon occlusion of the aorta is logistically superior in prolonged management of a highly lethal aortic injury.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable technique for management of noncompressible torso hemorrhage. The major limitation of the current unilobed fully occlusive REBOA catheters is below-the-balloon ischemia-reperfusion complications. We hypothesized that partial aortic occlusion with a novel bilobed partial (p)REBOA-PRO would result in the need for less intraaortic balloon adjustments to maintain a distal goal perfusion pressure as compared with currently available unilobed ER-REBOA.

γ' fibrinogen levels are associated with blood clot strength in traumatic brain injury patients.

Background: γ' fibrinogen is an alternatively-spliced fibrinogen variant that displays different coagulation parameters in vitro than the major form of fibrinogen. Purified γ' fibrinogen has slower clotting kinetics than unfractionated fibrinogen, but forms clots that are stronger and resistant to fibrinolysis. However, these properties have only been investigated in human populations in a limited number of studies.

Fibrinolytic Activation in Patients with Progressive Intracranial Hemorrhage after Traumatic Brain Injury.

Progression of intracranial hemorrhage (PICH) is a significant cause of secondary brain injury in patients with traumatic brain injury (TBI). Previous studies have implicated a variety of mediators that contribute to PICH. We hypothesized that patients with PICH would display either a hypocoagulable state, hyperfibrinolysis, or both.

The effects of cryopreserved red blood cell transfusion on tissue oxygenation in obese trauma patients.

Background: Low tissue oxygenation (StO2) is associated with poor outcomes in obese trauma patients. A novel treatment could be the transfusion of cryopreserved packed red blood cells (CPRBCs), which the in vitro biochemical profile favors red blood cell (RBC) function. We hypothesized that CPRBC transfusion improves StO2 in obese trauma patients.

Behavioral Characteristics of Adult Zebrafish () after MS222 Anesthesia for Fin Excision.

The health of laboratory animals is an ethical responsibility of researchers and a critical determinant of experimental outcome. Therefore, all husbandry procedures should be evaluated for their effects on mortality, behavior, and physiology to maximize animal welfare and minimize experimental variability. For adult zebrafish, the excision of a small portion of the caudal fin (that is, 'fin clipping') under MS222 anesthesia is a common procedure to obtain tissue for genotyping.

Allergic Fungal Airway Disease.

Fungi are ubiquitous and form their own kingdom. Up to 80 genera of fungi have been linked to type I allergic disease, and yet, commercial reagents to test for sensitization are available for relatively few species. In terms of asthma, it is important to distinguish between species unable to grow at body temperature and those that can (thermotolerant) and thereby have the potential to colonize the respiratory tract.

Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma and Surgical Patients: A Randomized Clinical Trial.

Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE.

Transfusion of cryopreserved packed red blood cells is safe and effective after trauma: a prospective randomized trial.

Objectives: To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients.

Background: Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing.

Effect of ascorbic acid concentrations on hemodynamics and inflammation following lyophilized plasma transfusion.

Background: Compared with lyophilized plasma (LP) buffered with other acids, LP with ascorbic acid (AA) attenuates systemic inflammation and DNA damage in a combat relevant polytrauma swine model. We hypothesize that increasing concentrations of AA in transfused LP will be safe, will be hemodynamically well tolerated, and will attenuate systemic inflammation following polytraumatic injury and hemorrhage in swine.

Methods: This prospective, randomized, blinded study involved 52 female swine.

Reconstitution fluid type does not affect pulmonary inflammation or DNA damage following infusion of lyophilized plasma.

Background: Dysfunctional inflammation following traumatic hemorrhage can lead to multiple-organ failure and death. In our polytrauma swine model, lyophilized plasma (LP) reconstituted with sterile water and ascorbic acid suppressed systemic inflammation and attenuated DNA damage. However, it remains unknown whether the inflammatory response is affected by the type of fluid used to reconstitute LP.

Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.

Background: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates.

Contribution of a membrane estrogen receptor to the estrogenic regulation of body temperature and energy homeostasis.

The hypothalamus is a key region of the central nervous system involved in the control of homeostasis, including energy and core body temperature (Tc). 17β-Estradiol (E2) regulates Tc, in part, via actions in the basal hypothalamus and preoptic area. E2 primarily controls hypothalamic functions via the nuclear steroid receptors, estrogen receptor α/β.

17Beta-estradiol regulation of T-type calcium channels in gonadotropin-releasing hormone neurons.

T-type calcium channels are responsible for generating low-threshold spikes that facilitate burst firing and neurotransmitter release in neurons. Gonadotropin-releasing hormone (GnRH) neurons exhibit burst firing, but the underlying conductances are not known. Previously, we found that 17beta-estradiol (E2) increases T-type channel expression and excitability of hypothalamic arcuate nucleus neurons.

GPR30 contributes to estrogen-induced thymic atrophy.

The mechanisms by which prolonged estrogen exposures, such as estrogen therapy and pregnancy, reduce thymus weight, cellularity, and CD4 and CD8 phenotype expression, have not been well defined. In this study, the roles played by the membrane estrogen receptor, G protein-coupled receptor 30 (GPR30), and the intracellular estrogen receptors, estrogen receptor alpha (ERalpha) and beta (ERbeta), in 17beta-estradiol (E2)-induced thymic atrophy were distinguished by construction and the side-by-side comparison of GPR30-deficient mice with ERalpha and ERbeta gene-deficient mice. Our study shows that whereas ERalpha mediated exclusively the early developmental blockage of thymocytes, GPR30 was indispensable for thymocyte apoptosis that preferentially occurs in T cell receptor beta chain(-/low) double-positive thymocytes.