Desert particulate matter from Afghanistan increases airway obstruction in human distal lungs exposed to type 2 cytokine IL-13

IntroductionDeployment related asthma-like symptoms including distal airway obstruction have been described in U.S. military personnel who served in Iraq and Afghanistan. The mechanisms responsible for the development of distal airway obstruction in deployers exposed to desert particulate matter (PM) is not well understood. We sought to determine if respiratory exposure to PM from Afghanistan (PMa) increases human distal airway hyperresponsiveness (AHR) with or without exposures to IL-13, a type 2 cytokine. We further tested whether mitochondrial dysfunction, such as ATP signaling and oxidative stress, may contribute to PMa- mediated AHR.MethodsPrecision-cut lung slices from donors without a history of lung disease, tobacco smoking, or vaping were pre-treated with IL-13 for 24 h. This was followed by exposure to PMa or PM from California (PMc, control for PMa) for up to 72 h. The role of hydrogen peroxide and ATP in AHR was assessed using the antioxidant enzyme catalase or an ATP receptor P2Y13 antagonist MRS2211. AHR in response to methacholine challenges as well as cytokine IL-8 production were measured.ResultsPMa alone, but not PMc alone, trended to increase AHR. Importantly, the combination of PMa and IL-13 significantly amplified AHR compared to control or PMc+IL-13. PMa alone and in combination with IL-13 increased IL-8 as compared to the control. PMa increased H2O2 and ATP. MRS211 and catalase reduced AHR in PCLS exposed to both PMa and IL-13.DiscussionOur data suggests that PMa in a type 2 inflammation-high lung increased AHR in part through oxidative stress and ATP signaling

Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome

INTRODUCTION: Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. METHODS: A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. RESULTS: In medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001). CONCLUSION: In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of sepsis in this population

Regenerative Medicine and the Developing World

This is the first study to systematically identify and prioritize which applications of regenerative medicine are the most promising for improving health in developing countries

Corporate identity at the stakeholder group level

There is a paucity of literature regarding the construction and operation of corporate identity at the stakeholder group level. This article examines corporate identity from the perspective of an individual stakeholder group, namely, front-line employees. A stakeholder group that is central to the development of an organization’s corporate identity as it spans an organization’s boundaries, frequently interacts with both internal and external stakeholders, and influences a firm’s financial performance by building customer loyalty and satisfaction. The article reviews the corporate identity, branding, services and social identity literatures to address how corporate identity manifests within the front-line employee stakeholder group, identifying what components comprise front-line employee corporate identity and assessing what contribution front-line employees make to constructing a strong and enduring corporate identity for an organization. In reviewing the literature the article develops propositions that, in conjunction with a conceptual model, constitute the generation of theory that is recommended for empirical testing