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Abstract Introduction The objective of this study was to investigate regional organ perfusion acutely following uncontrolled hemorrhage in an animal model that simulates a penetrating vascular injury and accounts for prehospital times in urban trauma. We set forth to determine if hypotensive resuscitation (permissive hypotension) would result in equivalent organ perfusion compared to normotensive resuscitation. Methods Twenty four (n=24) male rats randomized to 4 groups: Sham, No Fluid (NF), Permissive Hypotension (PH) (60% of baseline mean arterial pressure - MAP), Normotensive Resuscitation (NBP). Uncontrolled hemorrhage caused by a standardised injury to the abdominal aorta; MAP was monitored continuously and lactated Ringer’s was infused. Fluorimeter readings of regional blood flow of the brain, heart, lung, kidney, liver, and bowel were obtained at baseline and 85 minutes after hemorrhage, as well as, cardiac output, lactic acid, and laboratory tests; intra-abdominal blood loss was assessed. Analysis of variance was used for comparison. Results Intra-abdominal blood loss was higher in NBP group, as well as, lower hematocrit and hemoglobin levels. No statistical differences in perfusion of any organ between PH and NBP groups. No statistical difference in cardiac output between PH and NBP groups, as well as, in lactic acid levels between PH and NBP. NF group had significantly higher lactic acidosis and had significantly lower organ perfusion. Conclusions Hypotensive resuscitation causes less intra-abdominal bleeding than normotensive resuscitation and concurrently maintains equivalent organ perfusion. No fluid resuscitation reduces intra-abdominal bleeding but also significantly reduces organ perfusion.

Abstract Background The study of the endotoxin tolerance phenomenon in light of the recently defined roles of mast cells and toll-like receptors as essential components of the innate immune response and as orchestrators of acquired immunity may reveal potentially useful mechanisms of immunomodulation of infectious and allergic inflammatory responses, such as sepsis or asthma. Here we evaluated the phenomenon of direct tolerance of endotoxins, as well as the induction of cross-tolerance and synergism by stimulation with toll-like receptor-2 (TLR2) and FcεR1 agonists, in murine mast cells prestimulated with lipopolysaccharide (LPS). Additionally, we evaluated some stimulatory and inhibitory signaling molecules potentially involved in these phenomena. Methods MC/9 cells and primary bone marrow-derived mast cells obtained from C57BL/6 and TLR4-/- knock-out mice were sensitized to DNP-HSA (antigen) by incubation with DNP-IgE and were prestimulated with LPS for 18 hr prior to stimulation. Cultures were stimulated with LPS or Pam3Cys-Ser-(Lys)4 3HCl (P3C), a TLR2 agonist, individually or in combination with antigen. The production of IL-6 and TNFα, the phosphorylation of NFκB and p38 MAPK, and the expression of TLR4 and SOCS-1 and -3 were analyzed. Results We found that production of TNFα and IL-6 in murine mast cells that have been pretreated with LPS and challenged with TLR4 (LPS) or -2 (P3C) agonists was reduced, phenomena described as endotoxin tolerance (LPS) and cross-tolerance (P3C), respectively. The expression of TLR4 was not affected by LPS pretreatment. Our results show that the FcεR1 agonist DNP-HSA (antigen) interacts synergistically with LPS or P3C to markedly enhance production of cytokines (TNFα and IL-6). This synergistic effect with LPS and P3C was also attenuated by LPS pretreatment and was mediated by TLR4. These results may be attributed to the reduction in phosphorylation of the mitogen-activated protein kinase (MAPK), p38, and the transcription factor NFκB, as well as to an increase in the expression of the suppressors of cytokine signaling (SOCS)-1 and -3 proteins in LPS-pretreated mast cells. Conclusions These findings can be explored with respect to the modulation of inflammatory responses associated with infectious and allergic processes in future studies.

We present two fast parallel implementations of the Frankhn- Vogt multiple observer siting algorithm, using either OpenMP or CUDA. In this problem, the objective is to site observers on a raster terrain such that the joint area visible by them is maximized. On a portion of terrain with 16,385×16,385 cells, assuming that observers can see out to a radius-of-interest of 100 cells, finding the approximate 15,000 observers that have the greatest coverage takes only 17s in CUDA. That is a factor of 70 speedup from the sequential version. The OpenMF version exhibits a factor of 17 speedup on a 16 core system. Applications for the multiple observer siting problem include radio transmission towers, environmental monitoring sites, and path planning for surveillance drones. The algorithm has four steps: finding the visibility indices of all points, selecting a candidate subset of potential top observers, finding each one's viewshed, and greedily constructing the final solution [ABSTRACT FROM AUTHOR]

This paper presents PinMesh, a very fast algorithm with implementation to preprocess a polyhedral mesh, also known as a multi-material mesh, in order to perform 3D point location queries. PinMesh combines several innovative components to efficiently handle the largest available meshes. Because of a 2-level uniform grid, the expected preprocessing time is linear in the input size, and the code parallelizes well on a shared memory machine. Querying time is almost independent of the dataset size. PinMesh uses exact arithmetic with rational numbers to prevent roundoff errors, and symbolic perturbation with Simulation of Simplicity (SoS) to handle geometric degeneracies or special cases. PinMesh is intended to be a subroutine in more complex algorithms. It can preprocess a dataset and perform 1 million queries up to 27 times faster than RCT (Relative Closest Triangle), the current fastest algorithm. Preprocessing a sample dataset with 50 million triangles took only 14 elapsed seconds on a 16-core Xeon processor. The mean query time was 0.6μs. [ABSTRACT FROM AUTHOR]

Background: The molecules that provide access to activated T cells in the CNS, including chemokines, have been considered to be a crucial step in the pathogenesis of multiple sclerosis (MS). Aims: In this study, we investigated serial serum chemokine levels in patients with relapsing-remitting MS over 1 year and the association of these chemokine levels with treatment regimens, lesions on MRI and patients' characteristics. Methods: Serum CXCL9, CXCLIO, CCL2, CCL4 and CCL5 levels were evaluated using ELISA every 2 months for a year in 28 healthy controls and 28 MS patients during their treatment with interferon (IFN)-ß. Patients under-went MRI and were evaluated using the Expanded Disability Status Scale (EDSS) at the first and final evaluations. Results: CXCL1 0 serum levels were higher in MS patients compared with controls, were positively correlated with T2 lesions on MRI and were slightly increased during relapses. Treatment with IFNß-1a or IFNß-lb was associated with increased CXCL1O levels when evaluated more than 36 hours after subcutaneous injection. The CXCL9 levels were higher after MS relapse. There was significant variability in CCL4 and CCL5 levels in the serial evaluations, associated with gender and treatment. CCL2 levels were higher in treated MS patients than healthy controls, particularly among those patients with a stable form of the disease. Conclusion: Serum is a feasible resource for searching for an immunological marker in MS. Peripheral chemokine levels correlated in different ways with IFNß therapy and with disease and patient characteristics. Clinical trial registration number: 1SRCTN45526724. [ABSTRACT FROM AUTHOR]

Heart failure due to Chagas cardiomyopathy (HFCC) differs from failure with other etiologies because of the occurrence of intense inflammatory infiltrate and right ventricle compromise. This article investigates correlations of B-type natriuretic peptide (BNP) levels with parameters of severity in HFCC. Twenty-eight patients and 8 normal controls underwent heart catheterization and clinical and laboratory analyses. BNP levels were higher in patients with HFCC (P <.0001) and correlated with New York Heart Association (NYHA) class; right atrial pressure; wedge pressure; cardiac output; levels of serum sodium, hemoglobin, urea, and tumor necrosis factor-α; and ejection fraction. Interferon-γ and transforming growth factor-β did not correlate with BNP level. The authors conclude that BNP levels are elevated in patients experiencing HFCC, irrespective of NYHA class, and that the occurrence of HFCC correlates with severity of disease. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Chagas disease is a prevalent cause of heart failure in Latin America, and its prognosis is worse than other etiologies. The Heart Failure Survival Score has been used to assess prognosis in patients with heart failure; however, this score has not yet been studied in patients with Chagas cardiopathy., Methods: The Heart Failure Survival Score was calculated in 55 patients with severe left ventricular systolic dysfunction due to Chagas disease. Correlations were assessed between the Heart Failure Survival Score and variables obtained from, cardiopulmonary exercise tests, quality-of-life measures, and 6-minute walking tests., Results: Patients were distributed among New York Heart Association classes II-IV; 89% were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 62% were taking beta-blockers, 86% were taking diuretics, and 74% were taking aldosterone receptor blockers. The mean Heart Failure Survival Score was 8.75 (0.80). The score correlated well with cardiopulmonary test variables such as peak oxygen uptake (0.662; P<.01), oxygen uptake at the anaerobic threshold (0.644; P<.01), ventilation carbon dioxide efficiency slope (-0.417; P<.01), oxygen pulse (0.375; P<.01), oxygen uptake efficiency slope (0.626; P<.01), 6-minute walking test (0.370; P<.01), left ventricle ejection fraction (0.650; P=.01), and left atrium diameter (-0.377; P<.01). There was also a borderline significant correlation between the Heart Failure Survival Score and quality of life (-0.283; P<.05)., Conclusions: In heart failure patients with Chagas disease, the Heart Failure Survival Score correlated well with the main prognostic functional test variables., (Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

In the most severe cases of human envenoming by Tityus serrulatus, pulmonary oedema is a frequent finding and can be the cause of death. We have previously demonstrated a role for neuropeptides acting on tachykinin NK(1) receptors in the development of lung oedema following i.v. injection of T. serrulatus venom (TsV) in experimental animals. The present work was designed to investigate whether capsaicin-sensitive primary afferent neurons were a potential source of NK(1)-acting neuropeptides. To this end, sensory nerves were depleted of neuropeptides by neonatal treatment of rats with capsaicin. The effectiveness of this strategy at depleting sensory nerves was demonstrated by the inhibition of the neuropeptide-dependent response to intraplantar injection of formalin. Pulmonary oedema, as assessed by the levels of extravasation of Evans blue dye in the bronchoalveolar lavage and in the left lung, was markedly inhibited in capsaicin-treated animals. In contrast, capsaicin treatment failed to alter the increase in arterial blood pressure or the lethality following i.v. injection of TsV. Our results demonstrate an important role for capsaicin-sensitive sensory nerves in the cascade of events leading to lung injury following the i.v. administration of TsV.