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Carey Holleran,Jeffrey Konrad,Barbara Norton,Tamara Burlis,Steven Ambler 한국보건의료인국가시험원 2023 보건의료교육평가 Vol.20 No.-
Purpose The purpose of this project was to implement a process for learner-driven, formative, prospective, ad-hoc, entrustment assessment in Doctor of Physical Therapy clinical education. Our goals were to develop an innovative entrustment assessment tool, and then explore whether the tool detected (1) differences between learners at different stages of development and (2) differences within learners across the course of a clinical education experience. We also investigated whether there was a relationship between the number of assessments and change in performance. Methods A prospective, observational, cohort of clinical instructors (CIs) was recruited to perform learner-driven, formative, ad-hoc, prospective, entrustment assessments. Two entrustable professional activities (EPAs) were used: (1) gather a history and perform an examination and (2) implement and modify the plan of care, as needed. CIs provided a rating on the entrustment scale and provided narrative support for their rating. Results Forty-nine learners participated across 4 clinical experiences (CEs), resulting in 453 EPA learner-driven assessments. For both EPAs, statistically significant changes were detected both between learners at different stages of development and within learners across the course of a CE. Improvement within each CE was significantly related to the number of feedback opportunities. Conclusion The results of this pilot study provide preliminary support for the use of learner-driven, formative, ad-hoc assessments of competence based on EPAs with a novel entrustment scale. The number of formative assessments requested correlated with change on the EPA scale, suggesting that formative feedback may augment performance improvement.
Michael Mackey,Laurena Holleran,Gary Donohoe,Declan P. McKernan 대한신경정신의학회 2022 PSYCHIATRY INVESTIGATION Vol.19 No.12
Objective Immune system dysregulation is hypothesised to be central to the aetiopathogenesis of schizophrenia; however, the role of sterile inflammation remains unclear. Damage associated molecular patterns are key initiators of sterile inflammation and are detectable in peripheral blood. Methods A defined systematic search of the Web of Science, PubMed, and Scopus was performed to identify adult case-control studies published between January 1990 and June 2022. Three studies consisting of 242 cases and 83 controls met inclusion for the systematic review and meta-analysis of HMGB1 while twenty-eight studies consisting of 1,544 cases and 1,248 healthy controls were included for S100B. Results A significant standardised mean difference in peripheral S100B and HMGB1 concentrations was detected between cases and controls. S100B subgroup analysis determined the largest significant effect size for unmedicated individuals diagnosed with schizophrenia. Conclusion This study provides evidence that peripheral S100B and HMGB1 concentrations are elevated in individuals diagnosed with schizophrenia when compared with healthy controls. These results should be interpreted with caution as significant heterogeneity was present during meta-analysis of S100B in the entire sample and in sub-group analysis. The persistence of significant heterogeneity throughout subgroup analysis indicates that the current diagnostic groupings may be a barrier to understanding human behaviours and emotions.
Kim, Young-Il,Park, Kyungho,Kim, Jong Youl,Seo, Ho Seong,Shin, Kyong-Oh,Lee, Yong-Moon,Holleran, Walter M.,Elias, Peter M.,Uchida, Yoshikazu American Society for Microbiology 2014 Molecular and cellular biology Vol.34 No.24
<P>Antimicrobial peptides (AMP) are ubiquitous innate immune elements in epithelial tissues. We recently discovered that a signaling lipid, the ceramide metabolite sphingosine-1-phosphate (S1P), regulates production of a major AMP, cathelicidin antimicrobial peptide (CAMP), in response to a subtoxic level of endoplasmic reticulum (ER) stress that can be induced by external perturbants in keratinocytes. We hypothesized that an ER stress-initiated signal could also regulate production of another major class of AMPs: i.e., the human beta-defensins 2 (hBD2) and 3 (hBD3). Keratinocytes stimulated with a pharmacological ER stressor, thapsigargin (Tg), increased hBD2/hBD3 as well as CAMP mRNA expression. While inhibition of sphingosine-1-phosphate production did not alter hBD expression following ER stress, blockade of ceramide-1-phosphate (C1P) suppressed Tg-induced hBD2/hBD3 but not CAMP expression. Exogenous C1P also increased hBD2/hBD3 production, indicating that C1P stimulates hBD expression. We showed further that C1P-induced hBD2/hBD3 expression is regulated by a novel pathway in which C1P stimulates downstream hBD via a cPLA2a→15d-PGJ<SUB>2</SUB>→PPARα/PPARβ/δ→Src kinase→STAT1/STAT3 transcriptional mechanism. Finally, conditioned medium from C1P-stimulated keratinocytes showed antimicrobial activity against <I>Staphylococcus aureus</I>. In summary, our present and recent studies discovered two new regulatory mechanisms of key epidermal AMP, hBD2/hBD3 and CAMP. The C1P and S1P pathways both signal to enhance innate immunity in response to ER stress.</P>
Park, K.,Kim, Y.I.,Shin, K.O.,Seo, H.S.,Kim, J.Y.,Mann, T.,Oda, Y.,Lee, Y.M.,Holleran, W.M.,Elias, P.M.,Uchida, Y. Butterworths ; Elsevier Science Ltd 2014 The Journal of nutritional biochemistry Vol.25 No.7
We recently discovered that a signaling lipid, sphingosine-1-phosphate (S1P), generated by sphingosine kinase 1, regulates a major epidermal antimicrobial peptide's [cathelicidin antimicrobial peptide (CAMP)] expression via an NF-κB→C/EBPα-dependent pathway, independent of vitamin D receptor (VDR) in epithelial cells. Activation of estrogen receptors (ERs) by either estrogens or phytoestrogens also is known to stimulate S1P production, but it is unknown whether ER activation increases CAMP production. We investigated whether a phytoestrogen, genistein, simulates CAMP expression in keratinocytes, a model of epithelial cells, by either a S1P-dependent mechanism(s) or the alternate VDR-regulated pathway. Exogenous genistein, as well as an ER-β ligand, WAY-200070, increased CAMP mRNA and protein expression in cultured human keratinocytes, while ER-β antagonist, ICI182780, attenuated the expected genistein- and WAY-200070-induced increase in CAMP mRNA/protein expression. Genistein treatment increased acidic and alkaline ceramidase expression and cellular S1P levels in parallel with increased S1P lyase inhibition, accounting for increased CAMP production. In contrast, siRNA against VDR did not alter genistein-mediated up-regulation of CAMP. Taken together, genistein induces CAMP production via an ER-β→S1P→NF-κB→C/EBPα- rather than a VDR-dependent mechanism, illuminating a new role for estrogens in the regulation of epithelial innate immunity and pointing to potential additional benefits of dietary genistein in enhancing cutaneous antimicrobial defense.
Park, Kyungho,Ikushiro, Hiroko,Seo, Ho Seong,Shin, Kyong-Oh,Kim, Young il,Kim, Jong Youl,Lee, Yong-Moon,Yano, Takato,Holleran, Walter M.,Elias, Peter,Uchida, Yoshikazu National Academy of Sciences 2016 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.113 No.10
<P>We recently identified a previously unidentified sphingosine-1-phosphate (S1P) signaling mechanism that stimulates production of a key innate immune element, cathelicidin antimicrobial peptide (CAMP), in mammalian cells exposed to external perturbations, such as UVB irradiation and other oxidative stressors that provoke subapoptotic levels of endoplasmic reticulum (ER) stress, independent of the well-known vitamin D receptor-dependent mechanism. ER stress increases cellular ceramide and one of its distal metabolites, S1P, which activates NF-kappa B followed by C/EBP alpha activation, leading to CAMP production, but in a S1P receptor-independent fashion. We now show that S1P activates NF-kappa B through formation of a previously unidentified signaling complex, consisting of S1P, TRAF2, and RIP1 that further associates with three stress-responsive proteins; i.e., heat shock proteins (GRP94 and HSP90 alpha) and IRE1 alpha. S1P specifically interacts with the N-terminal domain of heat shock proteins. Because this ER stress-initiated mechanism is operative in both epithelial cells and macrophages, it appears to be a universal, highly conserved response, broadly protective against diverse external perturbations that lead to increased ER stress. Finally, these studies further illuminate how ER stress and S1P orchestrate critical stress-specific signals that regulate production of one protective response by stimulating production of the key innate immune element, CAMP.</P>