Cholesterol delivery to the adrenal glands estimated by adrenal venous sampling: An in vivo model to determine the contribution of circulating lipoproteins to steroidogenesis in humans.

Background: Cholesterol, required for adrenal steroid hormone synthesis, is at least in part derived from circulating lipoproteins. The contribution of high-density lipoproteins (HDL) and low-density lipoproteins (LDL) to adrenal steroidogenesis in humans is unclear.

Objective: The aim of the study was to determine the extent to which HDL and LDL are taken up by the adrenal glands using samples obtained during adrenal venous sampling (AVS).

Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance.

Background: Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the extent to which the association of BCAA with insulin resistance is attributable to altered leptin and adiponectin levels in individuals with varying degrees of glucose tolerance.

The Relationship Between Pain Characteristics, Peer Difficulties, and Emotional Functioning Among Adolescents Seeking Treatment for Chronic Pain: A Test of Mediational Models.

Objective: To evaluate patterns of relationships between pain characteristics, peer difficulties, and emotional functioning in a sample of adolescents seeking treatment for chronic pain.

Methods: Participants were 172 adolescents (age M = 14.88 years; 76% female, 88% White) with heterogeneous chronic pain disorders who completed measures of pain characteristics, peer difficulties, and emotional functioning before their new patient appointment in a pain management clinic.

Non-invasive Investigations for the Diagnosis of Fontan-Associated Liver Disease in Pediatric and Adult Fontan Patients.

Fontan-associated liver disease (FALD) is a serious complication related to the chronically elevated venous pressure and low cardiac output of this abnormal circulation. However, diagnostic markers for this condition are limited. We hypothesized that specific tests for fibrosis developed for other chronic liver diseases would identify a higher prevalence of FALD than ultrasound and standard laboratory tests and that identified abnormalities would correlate with time post-Fontan.

Novel LC/MS/MS and High-Throughput Mass Spectrometric Assays for Monoacylglycerol Acyltransferase Inhibitors.

Monoacylglycerol acyltransferase enzymes (MGAT1, MGAT2, and MGAT3) convert monoacylglycerol to diacylglycerol (DAG). MGAT1 and MGAT2 are both implicated in obesity-related metabolic diseases. Conventional MGAT enzyme assays use radioactive substrates, wherein the product of the MGAT-catalyzed reaction is usually resolved by time-consuming thin layer chromatography (TLC) analysis.

Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase II study.

Background Circulating tumor cells (CTCs) and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in CTCs and tumor tissue were evaluated as prognostic or predictive markers of CXCR4 peptide antagonist LY2510924 plus carboplatin-etoposide (CE) versus CE in extensive-stage disease small cell lung cancer (ED-SCLC). Methods This exploratory analysis of a phase II study evaluated CXCR4 expression in baseline tumor tissue and peripheral blood CTCs and in post-treatment CTCs. Optimum cutoff values were determined for CTC counts and CXCR4 expression in tumors and CTCs as predictors of survival outcome.

Using quality improvement methods to increase use of pain prevention strategies for childhood vaccination.

Aim: To increase evidence-based pain prevention strategy use during routine vaccinations in a pediatric primary care clinic using quality improvement methodology.

Methods: Specific intervention strategies (., comfort positioning, nonnutritive sucking and sucrose analgesia, distraction) were identified, selected and introduced in three waves, using a Plan-Do-Study-Act framework.

Does a lack of physical activity explain the rheumatoid arthritis lipid profile?

Background: In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile.

Parent and Child Report of Pain and Fatigue in JIA: Does Disagreement between Parent and Child Predict Functional Outcomes?

While previous research in juvenile idiopathic arthritis (JIA) has identified discrepancy between parent and child perception of disease-related symptoms such as pain, the significance and impact of this disagreement has not been characterized. We examined the extent to which parent-child discordance in JIA symptom ratings are associated with child functional outcomes. Linear regression and mixed effects models were used to test the effects of discrepancy in pain and fatigue ratings on functional outcomes in 65 dyads, consisting of youth with JIA and one parent.

The Impact of a Junior Faculty Fellowship Award on Academic Advancement and Retention.

Purpose: Academic faculty experience barriers to career development and promotion. In 1996, Harvard Medical School (HMS) initiated an intramural junior faculty fellowship to address these obstacles. The authors sought to understand whether receiving a fellowship was associated with more rapid academic promotion and retention.

Use of Smartphones to Prospectively Evaluate Predictors and Outcomes of Caregiver Responses to Pain in Youth with Chronic Disease.

This study examined outcomes and predictors of different types of responses to child pain used by caregivers of youth with chronic disease. Sixty-six children and adolescents (ages 7-18) with juvenile idiopathic arthritis answered questions about pain, pain interference in activities, and mood on a smartphone three times per day for one month, while a caregiver contemporaneously answered questions about their own mood and use of protecting, monitoring, minimizing, or distracting responses to their child's pain. Multilevel models were used to evaluate (a) how a child's pain and pain interference changes after a caregiver uses different types of pain responses; (b) the extent to which caregiver responses to pain vary across days; and (c) whether variability in caregiver responses to pain is predicted by changes in child pain characteristics, child mood, and/or caregiver mood.

Association of N-Linked Glycoprotein Acetyls and Colorectal Cancer Incidence and Mortality.

Background: Acute phase proteins highlight the dynamic interaction between inflammation and oncogenesis. GlycA, a novel nuclear magnetic resonance (NMR) inflammatory marker that identifies primarily circulating N-acetyl glycan groups attached to acute phase proteins, may be a future CRC risk biomarker.

Methods: We examined the association between GlycA and incident CRC and mortality in two prospective cohorts (N = 34,320); Discovery cohort: 27,495 participants from Women's Health Study (WHS); Replication cohort: 6,784 participants from Multi-Ethnic Study of Atherosclerosis (MESA).

Models of Care for addressing chronic musculoskeletal pain and health in children and adolescents.

Chronic musculoskeletal pain among children and adolescents is common and can negatively affect quality of life. It also represents a high burden on the health system. Effective models of care for addressing the prevention and management of pediatric musculoskeletal pain are imperative.

Chronic disease, medications and lifestyle: perceptions from a regional Victorian Aboriginal community.

Background: Poor medication management may contribute to the increased morbidity and mortality of Aboriginal people in Australia. Yet while there is extensive literature about the perceptions of healthcare providers on this issue, there is limited information on the perceptions of Aboriginal people themselves.

Objectives: To investigate the perceptions of a group of Aboriginal people attending a Victorian regional Aboriginal Health Service (AHS) with diagnosed medical conditions requiring medications, of their lifestyle, disease management and medication usage.

Screening and Development of New Inhibitors of FtsZ from M. Tuberculosis.

A variety of commercial analogs and a newer series of Sulindac derivatives were screened for inhibition of M. tuberculosis (Mtb) in vitro and specifically as inhibitors of the essential mycobacterial tubulin homolog, FtsZ. Due to the ease of preparing diverse analogs and a favorable in vivo pharmacokinetic and toxicity profile of a representative analog, the Sulindac scaffold may be useful for further development against Mtb with respect to in vitro bacterial growth inhibition and selective activity for Mtb FtsZ versus mammalian tubulin.

Metabolic tracing of monoacylglycerol acyltransferase-2 activity in vitro and in vivo.

Monoacylglycerol acyltransferase 2 (MGAT2) catalyzes the synthesis of diacylglycerol (DAG) from free fatty acids (FFA) and sn-monoacylglycerol (MG), the two major hydrolysis products of dietary fat. To demonstrate MGAT2-mediated cellular activity of triglyceride (TG) synthesis, we utilized 1-oleoyl-glycerol-d5 as a substrate to trace MGAT2-driven 1-oleoyl-glycerol-d5 incorporation into TG in HEK293 cells stably expressing human MGAT2. The oleoyl-glycerol-d5 incorporated major TG species were then quantified by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) in a 96-well format.

Utility of high density lipoprotein particle concentration in predicting future major adverse cardiovascular events among patients undergoing angiography.

Background: HDL-C is recognized to be inversely associated with cardiovascular (CV) risk. However, attenuation of the association of HDL-C with CV risk may occur after adjustment for other lipoprotein parameters and in various disease states, especially in the setting of acute coronary syndrome (ACS). Recently, the number of HDL particles (HDL-P) has been suggested to improve CV risk prediction.

Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children.

Background: Glycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation.

Plasma phospholipid transfer protein activity is inversely associated with betaine in diabetic and non-diabetic subjects.

Background: The choline metabolite, betaine, plays a role in lipid metabolism, and may predict the development of cardiovascular disease and type 2 diabetes mellitus (T2DM). Phospholipid transfer protein (PLTP) and lecithin:cholesterol acyltransferase (LCAT) require phosphatidylcholine as substrate, raising the possibility that there is an intricate relationship of these protein factors with choline metabolism. Here we determined the relationships of PLTP and LCAT activity with betaine in subjects with and without T2DM.

Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides.

Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4.

Discovery of novel potent imidazo[1,2-b]pyridazine PDE10a inhibitors.

Design and optimization of a novel series of imidazo[1,2-b]pyridazine PDE10a inhibitors are described. Compound 31 displays excellent pharmacokinetic properties and was also evaluated as an insulin secretagogue in vitro and in vivo.

Proceedings of the 2016 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Scientific Meeting : Toronto, Canada. 14-17 April 2016.

P1 Serologic evidence of gut-driven systemic inflammation in juvenile idiopathic arthritis Lampros Fotis, Nur Shaikh, Kevin Baszis, Anthony French, Phillip Tarr P2 Oral health and anti-citrullinated peptide antibodies (ACPA) in juvenile idiopathic arthritis Sriharsha Grevich, Peggy Lee, Sarah Ringold, Brian Leroux, Hannah Leahey, Megan Yuasa, Jessica Foster, Jeremy Sokolove, Lauren Lahey, William Robinson, Joshua Newsom, Anne Stevens P3 Novel autoantigens for endothelial cell antibodies in pediatric rheumatic diseases identified by proteomics Rie Karasawa, Mayumi Tamaki, Megumi Tanaka, Toshiko Sato, Kazuo Yudoh, James N. Jarvis P4 Transcriptional profiling reveals monocyte signature associated with JIA patient poor response to methotrexate Halima Moncrieffe, Mark F. Bennett, Monica Tsoras, Lorie Luyrink, Huan Xu, Sampath Prahalad, Paula Morris, Jason Dare, Peter A.