Interferon regulatory factor 8 regulates pathways for antigen presentation in myeloid cells and during tuberculosis.

IRF8 (Interferon Regulatory Factor 8) plays an important role in defenses against intracellular pathogens, including several aspects of myeloid cells function. It is required for ontogeny and maturation of macrophages and dendritic cells, for activation of anti-microbial defenses, and for production of the Th1-polarizing cytokine interleukin-12 (IL-12) in response to interferon gamma (IFNγ) and protection against infection with Mycobacterium tuberculosis. The transcriptional programs and cellular pathways that are regulated by IRF8 in response to IFNγ and that are important for defenses against M. tuberculosis are poorly understood. These were investigated by transcript profiling and chromatin immunoprecipitation on microarrays (ChIP-chip). Studies in primary macrophages identified 368 genes that are regulated by IRF8 in response to IFNγ/CpG and that behave as stably segregating expression signatures (eQTLs) in F2 mice fixed for a wild-type or mutant allele at IRF8. A total of 319 IRF8 binding sites were identified on promoters genome-wide (ChIP-chip) in macrophages treated with IFNγ/CpG, defining a functional G/AGAAnTGAAA motif. An analysis of the genes bearing a functional IRF8 binding site, and showing regulation by IFNγ/CpG in macrophages and/or in M. tuberculosis-infected lungs, revealed a striking enrichment for the pathways of antigen processing and presentation, including multiple structural and enzymatic components of the Class I and Class II MHC (major histocompatibility complex) antigen presentation machinery. Also significantly enriched as IRF8 targets are the group of endomembrane- and phagosome-associated small GTPases of the IRG (immunity-related GTPases) and GBP (guanylate binding proteins) families. These results identify IRF8 as a key regulator of early response pathways in myeloid cells, including phagosome maturation, antigen processing, and antigen presentation by myeloid cells.

Fluctuations in vital signs and behavioural responses of brain surgery patients in the Intensive Care Unit: are they valid indicators of pain?

AIM: To examine the validity of behaviours and fluctuations in vital signs for pain assessment of postbrain surgery adults in the neurosurgical intensive care unit. BACKGROUND: Many patients in an intensive care unit may be unable to self-report their pain. In such cases, the use of observable indicators is recommended. Very little research has explored the validity of the use of behaviours and vital signs for pain assessment of neurocritically ill patients. DESIGN: Prospective repeated-measure within-subject observational design. METHODS: A total of 43 postbrain surgery patients were video recorded before, during and 15 minutes after a non-nociceptive (non-invasive blood pressure cuff inflation) and a nociceptive (turning) procedures. Their behaviours and vital signs were collected with a pre-tested behavioural checklist and a data collection computer connected to the bedside monitor. The patients' self-report of pain was obtained whenever possible. Data were collected between June-December in 2011. RESULTS: A larger number of pain-related behaviours were exhibited by participants during the nociceptive procedure compared with the non-nociceptive procedure supporting discriminant validation. Among vital signs, only respiratory rate differed significantly between the two procedures. Regarding criterion validation, only behaviours were positively correlated with self-reports of pain. CONCLUSION: Behaviours were found valid indicators of pain in neurocritically ill patients after elective brain surgery. Fluctuations in vital signs may suggest the presence of pain, but their validity for such use is not supported. They should only be used in combination with other validated pain assessment methods.

Exploring Novice Nurses' Experiences During the First Wave of the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic affected how nurses learn and prepare for their future careers. This study explored the experiences of college-prepared, novice nurses pursuing a baccalaureate degree during the first wave of the pandemic. METHOD: This qualitative descriptive study analyzed students' individual reflective assignments describing the effects of the COVID-19 pandemic on novice nurses' personal, professional, and educational lives. RESULTS: Three themes emerged: (1) emotions generated in the clinical workplace due to the lack of control and the unknown of working as novice nurses during a pandemic; (2) cognitive dissonance of the nursing role regarding novice nurses' moral distress and their growing empowerment within the scope of practice; and (3) a disconcerted image of nursing with contrasting views of nursing from the public's perspective and a disconnect between frontline workers and decision makers. CONCLUSION: Novel pedagogical strategies are needed to help novice nurses cope with stress, uncertainty, and role challenges to foster healthy learning in academic and working environments. [J Nurs Educ. 2023;62(8):461-466.].

Validation of the use of the Critical-Care Pain Observation Tool (CPOT) with brain surgery patients in the neurosurgical intensive care unit.

UNLABELLED: Many critically ill patients are unable to self-report their pain. In such situations, the use of valid behavioral pain scales is recommended. OBJECTIVE: To validate the use of the Critical-Care Pain Observation Tool (CPOT) with brain surgery adults in the neurosurgical intensive care unit. DESIGN: Repeated-measure within subject prospective design. SETTINGS: Forty-three elective brain surgery patients of a Canadian university hospital participated. METHOD: Participants were video recorded and scored with the CPOT before, during and after a non-nociceptive (non-invasive blood pressure using cuff inflation) and a nociceptive (turning) procedure for a total of six assessments. Self-reports of pain were also obtained. RESULTS: Discriminant validation was supported with higher mean CPOT scores during the nociceptive procedure compared with the non-nociceptive one. More participants reported higher pain intensity during turning compared with cuff inflation. Criterion validation was supported with a moderate positive correlation between self-reports of pain intensity and CPOT scores during turning. Interrater and intrarater reliability of CPOT scores through the viewing of participants' videos by two trained raters was supported with high Intraclass Correlation Coefficients. CONCLUSION: The CPOT appears to be valid for the detection of pain in elective brain surgery patients in the neurosurgical intensive care unit.