A Mixed Method Study: Defining the Core Learning Needs of Nurses Delivering Care to Children and Young People with Rheumatic Disease to Inform Paediatric Musculoskeletal Matters, a Free Online Educational Resource.

Children and young people with rheumatic diseases and their families are often supported by nurses who may not have had specialist training in paediatric rheumatology. The purpose of our study was to establish the core learning needs of all nurses who may encounter these children and young people in their clinical practice and use this information to inform the content and format of Paediatric Musculoskeletal Matters Nursing (PMM-Nursing) Engagement with nurses working in different roles and with various levels of experience in musculoskeletal medicine informed these learning needs and PMM-Nursing content. Mixed methods ascertained learning needs under the following themes: (1) Need for increased awareness about rheumatic disease; (2) Impact of experience and nursing role; (3) Need for increased knowledge about rheumatic disease and management. In addition, our methods informed design components for an impactful learning and information resource. Representatives from stakeholder nursing groups, social sciences, and web development used this information to create a suitable framework for PMM-Nursing. The content of PMM-Nursing is now live and freely available.

An Integrative Review Exploring Psycho-Social Impacts and Therapeutic Interventions for Parent Caregivers of Young People Living with Duchenne's Muscular Dystrophy.

The purpose of this integrative review was to explore psycho-social impacts and therapeutic interventions for parent caregivers of young people living with Duchenne's Muscular Dystrophy (DMD). Electronic databases were searched for research publications between 2010 and 2020. This included Medline, CINAHL, PsycINFO, ERIC, ERC, and AMED. Four central themes emerged: Living with DMD; Knowing and telling; Transitioning; and Building resilience. The impact on parents caring for a child with DMD affected all aspects of their lives, changed over time, and had identifiable peak stress points. Unmet parental information and support needs left parents struggling in their role. Transition required changes to parenting behaviors and required adaptation and resilience. It is proposed that future investment should focus on anticipating family need, targeting intervention cognizant of predictable stress points and building resilience through social community. Parents may then be better positioned to support their child in looking forward.

Understanding the service-user's perspective.

The mothers' distress and anxiety appears to have been underestimated by the nurses, who were concerned mainly with technical and safety issues. Further support for, and provision of information to, parents may improve their care experiences.

Research essentials.

A RESEARCHER needs to select a methodology and methods that fit the purpose of the study and will be able to answer the questions it poses. Clarifying viewpoints about epistemology (the philosophical theory of knowledge) and ontology (the nature of reality) is also important because these perspectives can affect the choice of study design. Consideration must also be given to any specific criteria in the research proposal bid criteria.

Paediatric musculoskeletal matters (pmm)--collaborative development of an online evidence based interactive learning tool and information resource for education in paediatric musculoskeletal medicine.

BACKGROUND: We describe the collaborative development of an evidence based, free online resource namely 'paediatric musculoskeletal matters' (pmm). This resource was developed with the aim of reaching a wide range of health professionals to increase awareness, knowledge and skills within paediatric musculoskeletal medicine, thereby facilitating early diagnosis and referral to specialist care. METHODS: Engagement with stakeholder groups (primary care, paediatrics, musculoskeletal specialties and medical students) informed the essential 'core' learning outcomes to derive content of pmm. Representatives from stakeholder groups, social science and web development experts transformed the learning outcomes into a suitable framework. Target audience representatives reviewed the framework and their opinion was gathered using an online survey (n = 74) and focus groups (n = 2). Experts in paediatric musculoskeletal medicine peer reviewed the content and design. RESULTS: User preferences informed design with mobile, tablet and web compatible versions to facilitate access, various media and formats to engage users and the content presented in module format (i.e. Clinical assessment, Investigations and management, Limping child, Joint pain by site, Swollen joint(s) and Resources). CONCLUSIONS: We propose that our collaborative and evidence-based approach has ensured that pmm is user-friendly, with readily accessible, suitable content, and will help to improve access to paediatric musculoskeletal medicine education. The content is evidence-based with the design and functionality of pmm to facilitate optimal and 'real life' access to information. pmm is targeted at medical students and the primary care environment although messages are transferable to all health care professionals involved in the care of children and young people.

United States Voluntary Children's Chemical Evaluation Program (VCCEP) risk assessment for children exposed to benzene.

As part of the Voluntary Children's Chemical Evaluation Program (VCCEP) program, a risk assessment was performed to evaluate the risks to children from environmental benzene exposures. This paper summarizes this risk assessment. Risk was characterized using two distinct methods: USEPA's default type of risk assessment, which used the Reference Dose (RfD) and Cancer Slope Factor (CSF) to characterize non-cancer and cancer risks, as well as a Margin of Safety (MOS) approach that utilized a point of departure (POD). The exposures for most scenarios evaluated in this VCCEP risk assessment are lower than both the cancer and non-cancer PODs by several orders of magnitude, indicating a large MOS and corresponding low potential for toxicity at these exposures. The highest benzene exposures likely experienced by children, associated with the lowest MOS, are from cigarette smoke. In addition, the potential for age-related differences in the sensitivity towards benzene-induced toxicity was investigated. In general, this risk assessment does not indicate that children are likely to be at a elevated risk of AML or hematopoietic toxicity associated with environmental exposures to benzene.

Recombinant and in vitro expression systems for hydrogenases: new frontiers in basic and applied studies for biological and synthetic H2 production.

This review focuses on recent progress in developing heterologous and recombinant expression as well as in vitro maturation systems for the biosynthesis of active [FeFe] and [NiFe]-hydrogenases, which catalyze the reversible reaction, H2 <--> 2e- + 2H+. Activities of [FeFe] and [NiFe]-hydrogenases produced from different recombinant and in vitro maturation approaches are compared. Examples of how hydrogenase expression supports basic and applied studies of these enzymes are presented, and barriers to achieving more viable biological and synthetic H2-production systems and catalysts are addressed.

Working with a united vision.

The Great North Children's Hospital will open later this year, heralding a new era of health care for children and their families in Newcastle upon Tyne.

The histone chaperone anti-silencing function 1 stimulates the acetylation of newly synthesized histone H3 in S-phase.

Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. We have found that budding yeast lacking Asf1 has greatly reduced levels of histone H3 acetylated at lysine 9. Lysine 9 is acetylated on newly synthesized budding yeast histone H3 prior to its assembly onto newly replicated DNA. Accordingly, we found that the vast majority of H3 Lys-9 acetylation peaked in S-phase, and this S-phase peak of H3 lysine 9 acetylation was absent in yeast lacking Asf1. By contrast, deletion of ASF1 has no effect on the S-phase specific peak of H4 lysine 12 acetylation; another modification carried by newly synthesized histones prior to chromatin assembly. We show that Gcn5 is the histone acetyltransferase responsible for the S-phase-specific peak of H3 lysine 9 acetylation. Strikingly, overexpression of Asf1 leads to greatly increased levels of H3 on acetylation on lysine 56 and Gcn5-dependent acetylation on lysine 9. Analysis of a panel of Asf1 mutations that modulate the ability of Asf1 to bind to histones H3/H4 demonstrates that the histone binding activity of Asf1 is required for the acetylation of Lys-9 and Lys-56 on newly synthesized H3. These results demonstrate that Asf1 does not affect the stability of the newly synthesized histones per se, but instead histone binding by Asf1 promotes the efficient acetylation of specific residues of newly synthesized histone H3.

Structural basis for the histone chaperone activity of Asf1.

Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. The structure of the globular domain of Asf1 bound to H3/H4 determined by X-ray crystallography to a resolution of 1.7 Angstroms shows how Asf1 binds the H3/H4 heterodimer, enveloping the C terminus of histone H3 and physically blocking formation of the H3/H4 heterotetramer. Unexpectedly, the C terminus of histone H4 that forms a mini-beta sheet with histone H2A in the nucleosome undergoes a major conformational change upon binding to Asf1 and adds a beta strand to the Asf1 beta sheet sandwich. Interactions with both H3 and H4 were required for Asf1 histone chaperone function in vivo and in vitro. The Asf1-H3/H4 structure suggests a "strand-capture" mechanism whereby the H4 tail acts as a lever to facilitate chromatin disassembly/assembly that may be used ubiquitously by histone chaperones.

ASF1 binds to a heterodimer of histones H3 and H4: a two-step mechanism for the assembly of the H3-H4 heterotetramer on DNA.

The first step in the formation of the nucleosome is commonly assumed to be the deposition of a histone H3-H4 heterotetramer onto DNA. Antisilencing function 1 (ASF1) is a major histone H3-H4 chaperone that deposits histones H3 and H4 onto DNA. With a goal of understanding the mechanism of deposition of histones H3 and H4 onto DNA, we have determined the stoichiometry of the Asf1-H3-H4 complex. We have established that a single molecule of Asf1 binds to an H3-H4 heterodimer using gel filtration, amino acid, reversed-phase chromatography, and analytical ultracentrifugation analyses. We demonstrate that Asf1 blocks formation of the H3-H4 heterotetramer by a mechanism that likely involves occlusion of the H3-H3 dimerization interface.