Biomarkers of Inflammation in Heart Failure Patients with Reduced and Preserved Ejection Fractions: Multi-Ethnic Study of Atherosclerosis

Purpose Examine the relationships between high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor-α receptor-1 (sTNF-R1) and the cumulative risk of heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fractions in a diverse, population-based sample. Methods Study sample included 6,814 adult (45-84 years of age) men and women who participated in the Multi-Ethnic Study of Atherosclerosis and were free of cardiovascular disease at baseline. Cox regression was used to calculate the hazard ratios (HR) associated with elevated baseline hs-CRP (\u3e 3-10 mg/L), IL-6 (\u3e 75th percentile) and sTNF-R1 (\u3e 75th percentile) and risk of overall HF, HFrEF (ejection fraction [EF] \u3c 50%), and HFpEF (EF ≥ 50%). Results During ~11.2 years of follow-up there were 178 incident HF diagnoses. Elevated hs-CRP, IL-6 and sTNF-R1 were associated with a significant increased risk of HF overall (HR 1.76; 95% Confidence interval [CI] 1.22-2.52, HR 1.57; 95% 1.07-2.30, and HR 1.91; 95% CI 1.08-3.38, respectively). Elevated hs-CRP was a significant predictor in both HFrEF and HFpEF (HR 2.05; 95% CI 1.26-3.35, and HR 1.89; 95% CI 1.09-3.28, respectively). Baseline IL-6 concentrations were significantly associated with increased risk of HFrEF in nonsmokers only (HR 2.33; 95% CI 1.04-5.23) and of HFpEF in African Americans only (HR 5.89; 95% CI 1.52-22.80).Conclusions In a diverse sample of U.S. adults, elevated hs-CRP, IL-6 and sTNF-R1 were significant predictors of HF. Furthermore, both hs-CRP and IL-6 were significant predictors in HFrEF and HFpEF

The Second-Shell Metal Ligands of Human Arginase Affect Coordination of the Nucleophile and Substrate†

ABSTRACT: The active sites of eukaryotic arginase enzymes are strictly conserved, especially the first- and second-shell ligands that coordinate the two divalent metal cations that generate a hydroxide molecule for nucleophilic attack on the guanidinium carbon of L-arginine and the subsequent production of urea and L-ornithine. Here by using comprehensive pairwise saturation mutagenesis of the first- and second-shell metal ligands in human arginase I, we demonstrate that several metal binding ligands are actually quite tolerant to amino acid substitutions. Of>2800 double mutants of first- and second-shell residues analyzed, we found more than 80 unique amino acid substitutions, of which four were in first-shell residues. Remarkably, certain second-shell mutations could modulate the binding of both the nucleophilic water/hydroxide molecule and substrate or product ligands, resulting in activity greater than that of the wild-type enzyme. The data presented here constitute the first comprehensive saturation mutagenesis analysis of a metallohydrolase active site and reveal that the strict conservation of the second-shell metal binding residues in eukaryotic arginases does not reflect kinetic optimization of the enzyme during the course of evolution. Arginases (EC 3.5.3.1) are typically homotrimeric enzymes with an R/β fold comprising an eight-strand β-sheet surrounded by several helices. The enzyme contains a dinuclear metal center tha

A National Professional Development System for Youth Workers

A persistent challenge in the youth development field is the lack of a systemic approach to attracting, developing and sustaining its workforce, particularly direct service workers. While serious efforts to address workforce development have dotted the youth work landscape, especially over the last 15 years, much of this progress has been organization-specific rather than across the field or systemic (Quinn, 2004). In 2004, 30 individuals who were knowledgeable about the issues came together to address the challenge of attracting, developing and retaining youth workers. They represented diverse sectors of the field, including direct service workers, national youth-serving agencies, local and national intermediary organizations, federal agencies and corporate and foundation philanthropies. They took the bold step of designing an initial framework and strategy for a coordinated national professional development system for youth workers. They also agreed to pursue the next steps to collectively create the system (Stone, Garza, & Borden, 2005)

The Post Master\u27s Certificate Program in Early Education Research, Policy, and Practice

The Massachusetts Department of Early Education and Care (EEC) has selected the University of Massachusetts Boston to lead this innovative initiative. The development of a Post Master’s Certificate Program in Early Education Research, Policy, and Practice will build much-needed capacity for advanced graduate study in early education in Massachusetts. This model program is designed to address the demand for new leadership in the rapidly advancing field of early education and care

Online Surveys: Increasing Your Research and Evaluation Capacity

Online surveys are increasingly viewed as a method to expand research and evaluation capacity. This article focuses on a case study utilizing online surveys for data collection conducted by researchers at the Pennsylvania State University and the University of Arizona. The National Youth Participation Study makes use of computer technology and the interest youth have in such technology. Online methods, survey design, techniques when surveying youth and lessons learned in developing the online study are shared by the authors

Online Surveys: Increasing Your Research and Evaluation Capacity

Online surveys are increasingly viewed as a method to expand research and evaluation capacity. This article focuses on a case study utilizing online surveys for data collection conducted by researchers at the Pennsylvania State University and the University of Arizona. The National Youth Participation Study makes use of computer technology and the interest youth have in such technology. Online methods, survey design, techniques when surveying youth and lessons learned in developing the online study are shared by the authors

Adiposity, fitness, health-related quality of life and the reallocation of time between children’s school day activity behaviours: a compositional data analysis

Sedentary time (ST), light (LPA), and moderate-to-vigorous physical activity (MVPA) constitute the range of school day activity behaviours. This study investigated whether the composition of school activity behaviours was associated with health indicators, and the predicted changes in health when time was reallocated between activity behaviours. Accelerometers were worn for 7-days between October and December 2010 by 318 UK children aged 10–11, to provide estimates of school day ST, LPA, and MVPA. BMI z-scores and percent waist-to-height ratio were calculated as indicators of adiposity. Cardiorespiratory fitness (CRF) was assessed using the 20-m shuttle run test. The PedsQL™ questionnaire was completed to assess psychosocial and physical health-related quality of life (HRQL). Log-ratio multiple linear regression models predicted health indicators for the mean school day activity composition, and for new compositions where fixed durations of time were reallocated from one activity behaviour to another, while the remaining behaviours were unchanged. The school day activity composition significantly predicted adiposity and CRF (p = 0.04–0.002), but not HRQL. Replacing MVPA with ST or LPA around the mean activity composition predicted higher adiposity and lower CRF. When ST or LPA were substituted with MVPA, the relationships with adiposity and CRF were asymmetrical with favourable, but smaller predicted changes in adiposity and CRF than when MVPA was replaced. Predicted changes in HRQL were negligible. The school day activity composition significantly predicted adiposity and CRF but not HRQL. Reallocating time from ST and LPA to MVPA is advocated through comprehensive school physical activity promotion approaches. Trial registration: ISRCTN03863885.</p

Occupational therapy consensus recommendations for functional neurological disorder

BACKGROUND: People with functional neurological disorder (FND) are commonly seen by occupational therapists; however, there are limited descriptions in the literature about the type of interventions that are likely to be helpful. This document aims to address this issue by providing consensus recommendations for occupational therapy assessment and intervention. METHODS: The recommendations were developed in four stages. Stage 1: an invitation was sent to occupational therapists with expertise in FND in different countries to complete two surveys exploring their opinions regarding best practice for assessment and interventions for FND. Stage 2: a face-to-face meeting of multidisciplinary clinical experts in FND discussed and debated the data from stage 1, aiming to achieve consensus on each issue. Stage 3: recommendations based on the meeting were drafted. Stage 4: successive drafts of recommendations were circulated among the multidisciplinary group until consensus was achieved. RESULTS: We recommend that occupational therapy treatment for FND is based on a biopsychosocial aetiological framework. Education, rehabilitation within functional activity and the use of taught self-management strategies are central to occupational therapy intervention for FND. Several aspects of occupational therapy for FND are distinct from therapy for other neurological conditions. Examples to illustrate the recommendations are included within this document. CONCLUSIONS: Occupational therapists have an integral role in the multidisciplinary management of people with FND. This document forms a starting point for research aiming to develop evidence-based occupational therapy interventions for people with FND

Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model for Best Disease

PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5′- and 3′-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. All exons and the flanking splice junctions were screened by direct sequencing. RESULTS. The clinical phenotype and pathology of cmr closely resemble lesions of BMD. Canine VMD2 spans 13.7 kb of genomic DNA on CFA18 and shows a high level of conservation among eukaryotes. The transcript is predominantly expressed in RPE/choroid and encodes bestrophin, a 580-amino acid protein of 66 kDa. Immunocytochemistry of normal canine retina demonstrated specific localization of protein to the RPE basolateral plasma membranes. Two disease-specific sequence alterations were identified in the canine VMD2 gene: a C73T stop mutation in cmr1 and a G482A missense mutation in cmr2. CONCLUSIONS. The authors propose these two spontaneous mutations in the canine VMD2 gene, which cause cmr, as the first naturally occurring animal model of BMD. Further development of the cmr models will permit elucidation of the complex molecular mechanism of these retinopathies and the development of potential therapies

Craftivism as Inquiry: Holding Life’s Threads

In this article, we share insights regarding an arts-based research project where carers of people with dementia conveyed their experiences in cloth. Carers face high rates of mental ill health and burnout, while forming a largely undervalued and unrecognised workforce. Through this project, carers’ knowledge was valued and amplified using an innovative methodology – craftivism. During a series of five workshops in 2021, a small group of carers, researchers and artists gathered online to develop an exhibition of craftivist textile works. They evoked the complexity of their makers’ journeys supporting loved ones at the end of life, finding joy and meaning despite grief and isolation. Making and crafting, together, we built community and highlighted the importance of the relationships at the heart of care: holding life’s threads. This article contributes to a growing literature surrounding arts-based methods in qualitative research, advocacy, and community life, while providing another platform to share and celebrate the stories of all those involved in the project