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Modern, reliable, and valid outcome measures are essential to understanding the health needs of young children with burn injuries. Burn-specific and age-appropriate legacy assessment tools exist for this population but are hindered by the limitations of existing paper-based instruments. The purpose of this study was to develop item pools comprised of questions appropriate for children aged 1-5 with burn injuries. Item development was based on a framework provided by previous work to develop the Preschool Life Impact Burn Recovery Evaluation (LIBRE) Conceptual Model. The Preschool LIBRE Conceptual Model work established four sub-domains of functioning for children with burns aged 1-5. Item development involved a systematic literature review, a qualitative item review process with clinical experts, and parent cognitive interviews. Four item pools were established: (1) communication and language development; (2) physical functioning; (3) psychological functioning and (4) social functioning for preschool-aged children with burn injuries. We selected and refined candidate items, recall periods, survey instructions, and response option choices through clinical and parental feedback during the qualitative review and cognitive interview processes. Item pools are currently being field-tested as part of the process to calibrate and validate the Preschool 1-5 LIBRE Computer Adaptive Test (CAT) Profile., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Background and Aims: Cholesterol metabolism is tightly regulated by transcriptional and post-transcriptional mechanisms. Accordingly, dysregulation of cholesterol metabolism is a major risk factor for the development of coronary artery disease and associated complications. In recent years, it has become apparent that next to the liver, the intestine plays a key role in systemic cholesterol metabolism by governing cholesterol absorption, secretion, and incorporation into lipoprotein particles. We have previously demonstrated that the Liver X receptor (LXR)-regulated E3 ubiquitin ligase inducible degrader of LDLR (IDOL) is a regulator of cholesterol uptake owing to its ability to promote the ubiquitylation of the low-density lipoprotein receptor (LDLR). However, whether the LXR-IDOL-LDLR axis regulates the LDLR in the intestine and whether this influences intestinal cholesterol homeostasis is not known., Methods: In this study, we evaluated the role of the LXR-IDOL-LDLR axis in enterocyte cell models and in primary enterocytes isolated from Idol (-/-) and wild type mice. Furthermore, we studied the regulation of intestinal LDLR in Idol (-/-) and in wild type mice treated with the LXR agonist GW3965. Finally, we assessed ezetimibe-induced trans-intestinal cholesterol efflux in Idol (-/-) mice., Results: We show that in a wide range of intestinal cell lines LXR activation decreases LDLR protein abundance, cell surface occupancy, and LDL uptake in an IDOL-dependent manner. Similarly, we find that pharmacological dosing of C57BL6/N mice with the LXR agonist GW3965 increases Idol expression across the intestine with a concomitant reduction in Ldlr protein. Conversely, primary enterocytes isolated from Idol (-/-) mice have elevated Ldlr. To test whether these changes contribute to trans-intestinal cholesterol efflux, we measured fecal cholesterol in mice following ezetimibe dosing, but found no differences between Idol (-/-) and control mice in this setting., Conclusions: In conclusion, our study establishes that the LXR-IDOL-LDLR axis is active in the intestine and is part of the molecular circuitry that maintains cholesterol homeostasis in enterocytes., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The purpose of this study was to determine the impact of healing touch (HT) on sleep, anxiety, anesthesia emergence and pain., Methods: HT, sham HT, control with an aide (CP) and control groups without the presence of an aide (CNP), underwent polysomnography (PSG) preoperatively. The Yale Preoperative Anxiety Scale (YPAS) score was obtained preoperatively before medications were given and in the preoperative surgery area. Sedation score, anesthesia emergence score and vital signs were recorded. Pain scores were determined by the Observation Pain Assessment Scale (OPAS) postoperatively and at time of discharge. Preoperative laboratory blood was drawn for C-reactive protein (CRP), glucose, cortisol and vitamin D25 levels as indicators of stress and anxiety, and a HT satisfaction survey was given., Results: Thirty-nine patients consented to participate and were randomly assigned to HT (9), HT sham (12), CP (7) and CNP (11) groups. Mean patient age was 13.0 years, and no significant group differences were found for age, sex, race or patient procedure, categorized as laser, burn reconstruction and plastic surgery reconstruction. Additionally, no significant group differences were detected for any of the PSG parameters, YPAS scores, OPAS scores, medications, anesthesia emergence score, bloodwork or satisfaction survey score. CRP, glucose and cortisol levels were higher in the CNP group, suggesting that pediatric patients undergoing elective surgeries may benefit from more pre-operative support, possibly by HT., Conclusions: Although no tracked parameters showed statistically significant findings, anecdotal HT benefits included enhanced relaxation and sounder sleep., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Low density lipoprotein (LDL) cholesterol is taken up into cells via clathrin-mediated endocytosis of the LDL receptor (LDLR). Following dissociation of the LDLR-LDL complex, LDL is directed to lysosomes whereas the LDLR recycles to the plasma membrane. Activation of the sterol-sensing nuclear receptors liver X receptors (LXRs) enhances degradation of the LDLR. This depends on the LXR target gene inducible degrader of the LDLR (IDOL), an E3-ubiquitin ligase that promotes ubiquitylation and lysosomal degradation of the LDLR. How ubiquitylation of the LDLR by IDOL controls its endocytic trafficking is currently unknown. Using genetic- and pharmacological-based approaches coupled to functional assessment of LDL uptake, we show that the LXR-IDOL axis targets a LDLR pool present in lipid rafts. IDOL-dependent internalization of the LDLR is independent of clathrin, caveolin, macroautophagy, and dynamin. Rather, it depends on the endocytic protein epsin. Consistent with LDLR ubiquitylation acting as a sorting signal, degradation of the receptor can be blocked by perturbing the endosomal sorting complex required for transport (ESCRT) or by USP8, a deubiquitylase implicated in sorting ubiquitylated cargo to multivesicular bodies. In summary, we provide evidence for the existence of an LXR-IDOL-mediated internalization pathway for the LDLR that is distinct from that used for lipoprotein uptake.

Nucleophilic addition of alkyl- and aryl zinc reagents to a C(4) functionalized isoxazolyl aldehyde proceeded effectively with high enantioselectivity (85-94% e.e.). The amino alcohol catalyst (S)-2-piperidinyl-1,1,2-triphenyl ethanol (10) afforded the (R)-product 2b, as established by x-ray crystallography.

The lithio-anion of isoxazole 2 was found to ring open propylene oxide in good yields with complete regioselectivity. Vinylic and benzylic epoxides were utilized as key examples of electrophiles and found to produce a mixture of regioisomeric adducts. Additionally, the use of chiral epoxides was explored, and absolute configuration was determined by X-ray crystallography to prove that nucleophilic attack at the benzylic carbon of (R)-styrene oxide proceeds with 100% inversion at the benzylic carbon to afford the (S)-alcohol (4b).

Human observers can discriminate two attributes from the same object more efficiently than attributes from two different objects even if the retinal locations of the attributes are the same in the single and dual object cases. The single object advantage challenges the spatial spotlight view of attention and suggests that attentional selection can be object based. We report that the single object advantage is reliably reduced when an object working memory task is performed concurrently, whereas concurrent verbal and spatial working memory tasks have no effect. This selective interference effect provides support for the existence of object-based attentional processes that also contribute to the short-term retention of objects in working memory. These results are consistent with the hypothesis that both attentional and memory subsystems are organized along domain-specific lines, and suggest the importance of attention in rehearsal operations. The contributions of inferior temporal and parietal mechanisms that have been implicated in attending to and remembering objects are considered.

53 diabetic patients took part in a study to assess the safety of reusing plastic disposable syringes for insulin injection. Each patient used the same plastic syringe for 7 days. The syringe needles were changed when blunt. No patient developed signs of infection at the injection site. Bacteriological assessment of the used syringes and needles showed no contamination in any of the syringes, although one needle was contaminated. The effectiveness of bacteriostatic additives to insulin preparations was demonstrated. The presence of these additives renders safe the practice of a diabetic patient reusing a plastic disposable syringe over a 7-day period.