CD36 participates in macrophage internalization of a variety of particles, and has been implicated in inflammatory responses to many of these ligands. To what extent CD36 cooperates with other receptors in mediating these processes remains unclear. Because CD36 has been shown to cooperate with TLR2, we investigated the roles and interactions of CD36 and TLRs in inflammation and phagocytosis. Using Ab-induced endocytosis of CD36 and phagocytosis of erythrocytes displaying Abs to CD36, we show that selective engagement and internalization of this receptor did not lead to proinflammatory cytokine production by primary human and murine macrophages. In addition, CD36-mediated phagocytosis of Plasmodium falciparum malaria-parasitized erythrocytes (PEs), which contain parasite components that activate TLRs, also failed to induce cytokine secretion from primary macrophages. Furthermore, we demonstrate that CD36-mediated internalization did not require TLR2 or the TLR-signaling molecule IRAK4. However, macrophage pretreatment with TLR agonists markedly stimulated particle uptake via CD36. Similarly, PE uptake was unaffected by TLR deficiency, but in wild-type cells was increased by pretreatment with purified P. falciparum glycosylphosphatidylinositols, which activate TLR2. Our findings indicate that CD36 must cooperate with other receptors such as TLRs to participate in cytokine responses. Although purified P. falciparum components activate TLRs, CD36-mediated internalization of intact PEs is not inflammatory. Further, CD36 mediates internalization of particles, including PEs, independently of TLR signaling, but can functionally cooperate with TLRs to enhance internalization.
Background Moral distress was first described by Jameton in 1984, and has been defined as distress experienced by an individual when they are unable to carry out what they believe to be the right course of action because of real or perceived constraints on that action. This complex phenomenon has been studied extensively among healthcare providers, and intensive care professionals in particular report high levels of moral distress. This distress has been associated with provider burnout and associated consequences such as job attrition, with potential impacts on patient and family care. There is a paucity of literature exploring how middle and late career healthcare providers experience and cope with moral distress. Objectives We explore the experience of moral distress and the strategies and resources invoked to mitigate that distress in mid- and late-career healthcare providers practicing in paediatric intensive care, in order to identify ways in which the work environment can build a culture of moral resilience. Research design An exploratory, qualitative quality improvement project utilizing focus group and semi-structured interviews with pediatric intensive care front-line providers. Participants Mid-and-later career (10 + years in practice) pediatric intensive care front line providers in a tertiary pediatric hospital. Research context This work focuses on paediatric intensive care providers in a single critical care unit, in order to explore the site-specific perspectives of health care providers in that context with respect to moral distress coping strategies. Ethical considerations The study was approved by the Quality Management Office at the institution; consent was obtained from participants, and no identifying data was included in this project. Findings Participants endorsed perspective-building and described strategies for positive adaptation including; active, reflective and structured supports. Participants articulated interest in enhanced and accessible formal supports. Discussion Findings in this study resonate with the current literature in healthcare provider moral distress, and exposed ways in which the work environment could support a culture of moral resilience. Avenues are described for the management and mitigation of moral distress in this setting. Conclusion This exploratory work lays the groundwork for interventions that facilitate personal growth and meaning in the midst of moral crises in critical care practice.
BackgroundRapid diagnosis and appropriate antimicrobial therapy are of major importance to decrease morbidity and mortality in patients with blood stream infections (BSI). Blood culture, the current gold standard for detecting bacteria in blood, requires at least 24–48 hours and has limited sensitivity if obtained during antibiotic treatment of the patient. The aim of this prospective multicenter study was to clinically evaluate the application of a commercial universal 16S/18S rDNA PCR, SepsiTest™ (PCR-ST), directly on whole blood.MethodsIn total 236 samples from 166 patients with suspected sepsis were included in the study. PCR-ST results were compared to blood culture, the current gold standard for detecting BSI. Because blood cultures can give false-negative results, we performed an additional analysis to interpret the likelihood of bloodstream infection by using an evaluation based on clinical diagnosis, other diagnostic tests and laboratory parameters.ResultsClinical interpretation of results defined the detected organism to be contaminants in 22 of 43 positive blood cultures (51.2 %) and 21 of 47 positive PCR-ST results (44.7 %). Excluding these contaminants resulted in an overall sensitivity and specificity of the PCR-ST of 66.7 and 94.4 % respectively. Of the 36 clinically relevant samples, 11 BSI were detected with both techniques, 15 BSI were detected with PCR-ST only and 10 with blood culture only. Therefore, in this study, SepsiTest™ detected an additional 71 % BSI compared to blood culture alone.ConclusionsMore clinically relevant BSI were diagnosed by molecular detection, which might influence patient treatment. An improved SepsiTest™ assay suited for routine use can have additional value to blood culture in diagnosing bacteremia in septic patients.
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