The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia

Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid‐1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)‐induced lung injury in mice. For this, adult mice pre‐treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS‐challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre‐treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre‐treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI.     

Radiotherapy-specific interprofessional learning through simulation

IntroductionInterprofessional learning (IPL) is a vital aspect of training in radiation oncology professions, yet is rarely delivered to those professionals who work most closely together in clinical practice. Scenario-based learning using simulation facilities provides a unique opportunity to facilitate this learning and this project aimed to determine the impact and value of this initiative.MethodsSmall groups comprising post-graduate diploma pre-registration therapeutic radiographers, medical physics trainees and radiation oncology registrars were challenged with 4 plausible and challenging radiotherapy scenarios within an academic simulation centre. Pre- and post-event completion of the “Readiness for Interprofessional Learning Scale” measured impact and a Likert-style survey gathered feedback from participants.ResultsThe session increased participants' teamwork and collaboration skills as well as strengthening professional identities. Participants reported high levels of enjoyment related to collaborative working, communication and observing other professionals deploying their technical skills and specialist knowledge.ConclusionAlthough beneficial, simulated scenarios offering equal opportunities for engagement across the professions are challenging to plan and timetabling issues between the 3 groups present significant difficulties. The safe environment and unique opportunity for these groups to learn together was particularly well received and future oncology-specific simulated scenario sessions are planned with larger cohorts.Implications for practiceSimulated scenario training can be used to improve team working across the radiotherapy interprofessional team and may have wider use in other specialist interdisciplinary team development.     

Initial assessment of α-synuclein structure in platelets

Journal of Thrombosis and Thrombolysis - Over the last few years data from our group have indicated that α-synuclein is important in development of immune cells as well as potentially...     

Representation,Exemplification, and Risk: Resonance of Tobacco Graphic Health Warnings Across Diverse Populations

As countries implement Article 11 of the World Health Organization (WHO) Framework Convention on Tobacco Control, graphic warning labels that use images of people and their body parts to illustrate the consequences of smoking are being added to cigarette packs. According to exemplification theory, these case examples—exemplars—can shape perceptions about risk and may resonate differently among demographic subpopulations. Drawing on data from eight focus groups (N = 63) with smokers and nonsmokers from vulnerable populations, this qualitative study explores whether people considered exemplars in their reactions to and evaluations of U.S. graphic health warning labels initially proposed by the Food and Drug Administration. Participants made reference to prior and concurrent mass media messages and exemplars during the focus groups and used demographic cues in making sense of the images on the warning labels. Participants were particularly sensitive to age of the exemplars and how it might affect label effectiveness and beliefs about smoking. Race and socioeconomic status also were salient for some participants. We recommend that exemplars and exemplification be considered when selecting and evaluating graphic health warnings for tobacco labels and associated media campaigns.     

Sources of Variability in the Detection of Cerebral Emboli with Transcranial Doppler During Cardiac Surgery

OBJECTIVE: The application of intensity thresholds for embolus detection with transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion of high-intensity transient signals (HITS))whose intensities are below the threshold. The lack of consistent threshold criteria between clinical trials may explain part of the discrepancy in the reported HITS counts. We investigated the effect of choosing different thresholds on the sensitivity and specificity of detecting HITS during cardiopulmonary bypass (CPB). METHODS: Two observers independently analyzed TCD recordings from 8 patients under CPB. Doppler signals were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles according to preestablished criteria. The relative intensity of Doppler signals was measured by two different methods (TCD software vs manual). Receiver Operating Characteristic curves determined the optimal threshold for each of the two intensity methods. RESULTS: Reviewers achieved agreement in 96% of 2190 Doppler signals (kappa = 0.90). Relative intensities calculated with the TCD-software method were 3 dB (95% CI: 3.0-3.4) higher than the manual method. The optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with the software method and at 7 dB with the manual method (sensitivity: 96%; specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal increased the rejection of true HITS by 8% and 14%, respectively. CONCLUSIONS: Using intensity thresholds higher than the optimal for embolus detection decreases HITS counts. Choosing a threshold depends on the type of method used for measuring the signal intensity. Uniform threshold criteria and comparative studies between different Doppler devices are necessary for making clinical trials more comparable.     

Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Iron overload presenting as exacerbation of hepatic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation has not been previously described. We report 6 patients with established hepatic GVHD in whom iron overload (median serum ferritin, 7231 mug/dL; median transferrin saturation, 77%) resulting from a lifetime median of 20 units of packed red blood cell transfusions was manifested by worsening of liver function. Liver biopsies performed in 4 patients confirmed severe iron overload and also hepatic GVHD. Analysis for the C282Y and H63D hemochromatosis gene mutation was negative for the homozygous state in all 6 patients. Erythropoietin-assisted phlebotomy resulted in normalization of liver function at a median of 7 months and of serum ferritin at a median of 11 months. Immunosuppressive therapy was successfully tapered in all 4 patients who completed the phlebotomy program, and this supported the impression that iron overload, rather than GVHD, was the principal cause of liver dysfunction. At a median follow-up of 50 months (range, 18-76 months) from the transplantation and 25 months (range, 5-36 months) from ferritin normalization, all 4 patients require maintenance phlebotomy. We conclude that iron overload can mimic GVHD exacerbation, thus resulting in unnecessary continuation or intensification of immunosuppressive therapy for GVHD, and that maintenance phlebotomy is necessary after successful iron-reduction therapy.