voluntary-breath-hold-technique-for-reducing-heart-dose-left-breast

Voluntary Breath-hold Technique for Reducing Heart Dose in Left Breast Radiotherapy

Breath-holding techniques reduce the amount of radiation received by cardiac structures during tangential-field left breast radiotherapy. With these ...

Royal Marsden NHS Foundation Trust

In addition to cross-cultural and environmental stressors, aid workers and missionaries are frequently exposed to trauma. We explored the frequency of traumatic events, their mental health impact, and factors associated with posttraumatic stress in two groups of missionaries, one representing a predominantly stable setting (Europe) and the other an unstable setting (West Africa). The 256 participants completed self-report measures assessing lifetime traumatic events, current posttraumatic stress, depressive and anxiety symptoms, resilience, and functioning. The rate of traumatic events was significantly higher in the unstable setting. More-frequent traumatic events were associated with higher posttraumatic stress. Factors associated with the severity of posttraumatic stress were depression, functional impairment, subjective severity and number of traumatic events, and the level of resilience.

Traumatic events and posttraumatic stress in cross-cultural mission assignments.

Listeria monocytogenes (LM) is a gram-positive bacterium that is a common contaminant of processed meats and dairy products. In humans, ingestion of LM can result in intracellular infection of the spleen and liver, which can ultimately lead to septicemia, meningitis, and spontaneous abortion. Interleukin (IL)-23 is a cytokine that regulates innate and adaptive immune responses by inducing the production of IL-17A, IL-17F, and IL-22. We have recently demonstrated that the IL-23/IL-17 axis is required for optimal recruitment of neutrophils to the liver, but not the spleen, during LM infection. Furthermore, these cytokines are required for the clearance of LM during systemic infection. In other infectious models, IL-22 induces the secretion of anti-microbial peptides and protects tissues from damage by preventing apoptosis. However, the role of IL-22 has not been thoroughly investigated during LM infection. In the present study, we show that LM induces the production of IL-22 in vivo. Interestingly, IL-23 is required for the production of IL-22 during primary, but not secondary, LM infection. Our findings suggest that IL-22 is not required for clearance of LM during primary or secondary infection, using both systemic and mucosal models of infection. IL-22 is also not required for the protection of LM infected spleens and livers from organ damage. Collectively, these data indicate that IL-22 produced during LM infection must play a role other than clearance of LM or protection of tissues from pathogen- or immune-mediated damage.

IL-22 production is regulated by IL-23 during Listeria monocytogenes infection but is not required for bacterial clearance or tissue protection.

Previous studies have suggested that neutrophils are required for resistance during infection with multiple pathogenic microorganisms. However, the depleting antibody used in those studies binds to both Ly6G and Ly6C (anti-Gr-1; clone RB6-8C5). This antibody has been shown to deplete not only neutrophils but also monocytes and a subset of CD8(+) T cells. Recently, an antibody against Ly6G, which specifically depletes neutrophils, was characterized. In the present study, neutrophils are depleted using the antibody against Ly6G during infection with the intracellular bacterium Listeria monocytogenes (LM). Our data show that neutrophil-depleted mice are much less susceptible to infection than mice depleted with anti-Gr-1. Although neutrophils are required for clearance of LM, their importance is more pronounced in the liver and during a high-dose bacterial challenge. Furthermore, we demonstrate that the protection mediated by neutrophils is due to the production of TNF-α, but not IFN-γ. Additionally, neutrophils are not required for the recruitment of monocytes or the generation of adaptive T-cell responses during LM infection. This study highlights the importance of neutrophils during LM infection, and indicate that depletion of neutrophils is less detrimental to the host than depletion of all Gr-1-expressing cell populations.

Specific depletion reveals a novel role for neutrophil-mediated protection in the liver during Listeria monocytogenes infection.

Reactive oxygen species and reactive nitrogen species play important roles during immune responses to bacterial pathogens. Extracellular superoxide dismutase (ecSOD) regulates extracellular concentrations of reactive oxygen species and reactive nitrogen species and contributes to tissue protection during inflammatory insults. The participation of ecSOD in immune responses seems therefore intuitive, yet is poorly understood. In the current study, we used mice with varying levels of ecSOD activity to investigate the involvement of this enzyme in immune responses against Listeria monocytogenes. Surprisingly, our data demonstrate that despite enhanced neutrophil recruitment to the liver, ecSOD activity negatively affected host survival and bacterial clearance. Increased ecSOD activity was accompanied by decreased colocalization of neutrophils with bacteria, as well as increased neutrophil apoptosis, which reduced overall and neutrophil-specific TNF-α production. Liver leukocytes from mice lacking ecSOD produced equivalent NO· compared with liver leukocytes from mice expressing ecSOD. However, during infection, there were higher levels of peroxynitrite (NO(3)·(-)) in livers from mice lacking ecSOD compared with livers from mice expressing ecSOD. Neutrophil depletion studies revealed that high levels of ecSOD activity resulted in neutrophils with limited protective capacity, whereas neutrophils from mice lacking ecSOD provided superior protection compared with neutrophils from wild-type mice. Taken together, our data demonstrate that ecSOD activity reduces innate immune responses during bacterial infection and provides a potential target for therapeutic intervention.

Extracellular superoxide dismutase inhibits innate immune responses and clearance of an intracellular bacterial infection.

To determine whether voluntary deep-inspiratory breath-hold (v_DIBH) and deep-inspiratory breath-hold with the active breathing coordinator™ (ABC_DIBH) in patients undergoing left breast radiotherapy are comparable in terms of normal-tissue sparing, positional reproducibility and feasibility of delivery.

Karen Carr

Department of Radiotherapy

Royal Marsden NHS Foundation Trust

Voluntary Breath-hold Technique for Reducing Heart Dose in Left Breast Radiotherapy

Karen Carr

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Royal Marsden NHS Foundation Trust

Voluntary Breath-hold Technique for Reducing Heart Dose in Left Breast Radiotherapy

Department of Radiotherapy