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Essentials Many mediators increase tissue factor (TF) expression in a wide variety of cell types. The only known example of TF downregulation is by pericytes during wound healing angiogenesis. Downregulation of TF mRNA and protein in cultured pericytes is Protein Kinase C (PKC) dependent. Pericyte TF regulation is unique, since PKC mediates increased TF in all other cell types tested. SUMMARY: Background Embryonic and tumor-associated angiogenesis are linked to elevated expression of the procoagulant transmembrane receptor tissue factor (TF). In contrast, we have reported that high baseline TF expression by perivascular cells (pericytes) is dramatically reduced during angiogenesis at sites of wound healing. This is the only setting in which active TF downregulation has been reported, thus revealing a novel mechanism of TF regulation. Objectives To define the mechanisms underlying the unique pattern of TF expression in pericytes. Methods TF expression in primary cultures of human pericytes is not altered by angiogenic cytokines or growth factors, but is actively downregulated by phorbol 12-myristate 13-acetate (PMA). We characterized TF transcription, protein stability and trafficking in response to PMA. Results Exposure to PMA reduced TF mRNA synthesis and shortened the half-life of TF protein from 11 h to 4.5 h. Addition of PMA rapidly triggered endocytosis of cell surface TF, followed by degradation in lysosomes. Cell surface TF coagulant activity was maintained until internal stores were depleted. Reduction of TF transcription, TF endocytosis and enhanced degradation of TF protein were all blocked by broad-spectrum inhibitors of protein kinase C (PKC). This was a surprising finding, because PKC activation increases TF expression in other cell types that have been tested. Conclusions The unique PKC-dependent pathway of TF downregulation in pericytes suggests that TF downregulation may play a functional role in angiogenesis. Distinct pathways regulating pathological and physiological TF expression could be utilized to modulate TF expression for therapeutic purposes., (© 2019 International Society on Thrombosis and Haemostasis.)

Background: Behavior in response to distressful events during outpatient pediatric surgery can contribute to postoperative maladaptive behaviors, such as temper tantrums, nightmares, bed-wetting, and attention seeking. Currently available perioperative behavioral assessment tools have limited utility in guiding interventions to ameliorate maladaptive behaviors because they cannot be used in real time, are only intended to be used during 1 phase of the experience (e.g., perioperative), or provide only a static assessment of the child (e.g., level of anxiety). A simple, reliable, real-time tool is needed to appropriately identify children and parents whose behaviors in response to distressful events at any point in the perioperative continuum could benefit from timely behavioral intervention. Our specific aims were to (1) refine the Perioperative Adult Child Behavioral Interaction Scale (PACBIS) to improve its reliability in identifying perioperative behaviors and (2) validate the refined PACBIS against several established instruments., Methods: The PACBIS was used to assess the perioperative behaviors of 89 children aged 3 to 12 years presenting for adenotonsillectomy and their parents. Assessments using the PACBIS were made during perioperative events likely to prove distressing to children and/or parents (perioperative measurement of blood pressure, induction of anesthesia, and removal of the IV catheter before discharge). Static measurements of perioperative anxiety and behavioral compliance during anesthetic induction were made using the modified Yale Preoperative Anxiety Scale and the Induction Compliance Checklist (ICC). Each event was videotaped for later scoring using the Child-Adult Medical Procedure Interaction Scale-Short Form (CAMPIS-SF) and Observational Scale of Behavioral Distress (OSBD). Interrater reliability using linear weighted kappa (kappa(w)) and multiple validations using Spearman correlation coefficients were analyzed., Results: The PACBIS demonstrated good to excellent interrater reliability, with kappa(w) ranging from 0.62 to 0.94. The Child Coping and Child Distress subscores of the PACBIS demonstrated strong concurrent correlations with the modified Yale Preoperative Anxiety Scale, ICC, CAMPIS-SF, and OSBD. The Parent Positive subscore of the PACBIS correlated strongly with the CAMPIS-SF and OSBD, whereas the Parent Negative subscore showed significant correlation with the ICC. The PACBIS has strong construct and predictive validities., Conclusions: The PACBIS is a simple, easy to use, real-time instrument to evaluate perioperative behaviors of both children and parents. It has good to excellent interrater reliability and strong concurrent validity against currently accepted scales. The PACBIS offers a means to identify maladaptive child or parental behaviors in real time, making it possible to intervene to modify such behaviors in a timely fashion.