Developing clinical decision tools to implement chronic disease prevention and screening in primary care: the BETTER 2 program (building on existing tools to improve chronic disease prevention and screening in primary care).

BackgroundThe Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Family Practice (BETTER) trial demonstrated the effectiveness of an approach to chronic disease prevention and screening (CDPS) through a new skilled role of a 'prevention practitioner'(PP). The PP has appointments with patients 40-65 years of age that focus on primary prevention activities and screening of cancer (breast, colorectal, cervical), diabetes and cardiovascular disease and associated lifestyle factors. There are numerous and occasionally conflicting evidence-based guidelines for CDPS, and the majority of these guidelines are focused on specific diseases or conditions; however, primary care providers often attend to patients with multiple conditions. To ensure that high-level evidence guidelines were used, existing clinical practice guidelines and tools were reviewed and integrated into blended BETTER tool kits. Building on the results of the BETTER trial, the BETTER tools were updated for implementation of the BETTER 2 program into participating urban, rural and remote communities across Canada.MethodsA clinical working group consisting of PPs, clinicians and researchers with support from the Centre for Effective Practice reviewed the literature to update, revise and adapt the integrated evidence algorithms and tool kits used in the BETTER trial. These resources are nuanced, based on individual patient risk, values and preferences and are designed to facilitate decision-making between providers across the target diseases and lifestyle factors included in the BETTER 2 program. Using the updated BETTER 2 toolkit, clinicians 1) determine which CDPS actions patients are eligible to receive and 2) develop individualized 'prevention prescriptions' with patients through shared decision-making and motivational interviewing.ResultsThe tools identify the patients' risks and eligible primary CDPS activities: the patient survey captures the patient's health history; the prevention visit form and integrated CDPS care map identify eligible CDPS activities and facilitate decisions when certain conditions are met; and the 'bubble diagram' and 'prevention prescription' promote shared decision-making.ConclusionThe integrated clinical decision-making tools of BETTER 2 provide resources for clinicians and policymakers that address patients' complex care needs beyond single disease approaches and can be adapted to facilitate CDPS in the urban, rural and remote clinical setting.Trial registrationThe registration number of the original RCT BETTER trial was ISRCTN07170460

Equine Polyclonal Antibodies Prevent Acute Chikungunya Virus Infection in Mice

Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen that causes chikungunya disease (CHIK); the disease is characterized by fever, muscle ache, rash, and arthralgia. This arthralgia can be debilitating and long-lasting, seriously impacting quality of life for years. Currently, there is no specific therapy available for CHIKV infection. We have developed a despeciated equine polyclonal antibody (CHIKV-EIG) treatment against CHIKV and evaluated its protective efficacy in mouse models of CHIKV infection. In immunocompromised (IFNAR−/−) mice infected with CHIKV, daily treatment for five consecutive days with CHIKV-EIG administered at 100 mg/kg starting on the day of infection prevented mortality, reduced viremia, and improved clinical condition as measured by body weight loss. These beneficial effects were seen even when treatment was delayed to 1 day after infection. In immunocompetent mice, CHIKV-EIG treatment reduced virus induced arthritis (including footpad swelling), arthralgia-associated cytokines, viremia, and tissue virus loads in a dose-dependent fashion. Collectively, these results suggest that CHIKV-EIG is effective at preventing CHIK and could be a viable candidate for further development as a treatment for human disease

Structure-Function Analysis of Diacylglycerol Acyltransferase Sequences from 70 Organisms

<p>Abstract</p> <p>Background</p> <p>Diacylglycerol acyltransferase families (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Understanding the roles of DGATs will help to create transgenic plants with value-added properties and provide clues for therapeutic intervention for obesity and related diseases. The objective of this analysis was to identify conserved sequence motifs and amino acid residues for better understanding of the structure-function relationship of these important enzymes.</p> <p>Results</p> <p>117 DGAT sequences from 70 organisms including plants, animals, fungi and human are obtained from database search using tung tree DGATs. Phylogenetic analysis separates these proteins into DGAT1 and DGAT2 subfamilies. These DGATs are integral membrane proteins with more than 40% of the total amino acid residues being hydrophobic. They have similar properties and amino acid composition except that DGAT1s are approximately 20 kDa larger than DGAT2s. DGAT1s and DGAT2s have 41 and 16 completely conserved amino acid residues, respectively, although only two of them are shared by all DGATs. These residues are distributed in 7 and 6 sequence blocks for DGAT1s and DGAT2s, respectively, and located at the carboxyl termini, suggesting the location of the catalytic domains. These conserved sequence blocks do not contain the putative neutral lipid-binding domain, mitochondrial targeting signal, or ER retrieval motif. The importance of conserved residues has been demonstrated by site-directed and natural mutants.</p> <p>Conclusions</p> <p>This study has identified conserved sequence motifs and amino acid residues in all 117 DGATs and the two subfamilies. None of the completely conserved residues in DGAT1s and DGAT2s is present in recently reported isoforms in the multiple sequences alignment, raising an important question how proteins with completely different amino acid sequences could perform the same biochemical reaction. The sequence analysis should facilitate studying the structure-function relationship of DGATs with the ultimate goal to identify critical amino acid residues for engineering superb enzymes in metabolic engineering and selecting enzyme inhibitors in therapeutic application for obesity and related diseases.</p

School Smoking Policy Characteristics and Individual Perceptions of the School Tobacco Context: Are They Linked to Students’ Smoking Status?

The purpose of this study was to explore individual- and school-level policy characteristics on student smoking behavior using an ecological perspective. Participants were 24,213 (51% female) Grade 10–11 students from 81 schools in five Canadian provinces. Data were collected using student self-report surveys, written policies collected from schools, interviews with school administrators, and school property observations to assess multiple dimensions of the school tobacco policy. The multi-level modeling results revealed that the school a student attended was associated with his/her smoking behavior. Individual-level variables that were associated with student smoking included lower school connectedness, a greater number of family and friends who smoked, higher perceptions of student smoking prevalence, lower perceptions of student smoking frequency, and stronger perceptions of the school tobacco context. School-level variables associated with student smoking included weaker policy intention indicating prohibition and assistance to overcome tobacco addiction, weaker policy implementation involving strategies for enforcement, and a higher number of students smoking on school property. These findings suggest that the school environment is important to tobacco control strategies, and that various policy dimensions have unique relationships to student smoking. School tobacco policies should be part of a comprehensive approach to adolescent tobacco use

Evolutionary view of acyl-CoA diacylglycerol acyltransferase (DGAT), a key enzyme in neutral lipid biosynthesis

<p>Abstract</p> <p>Background</p> <p>Triacylglycerides (TAGs) are a class of neutral lipids that represent the most important storage form of energy for eukaryotic cells. DGAT (acyl-CoA: diacylglycerol acyltransferase; EC 2.3.1.20) is a transmembrane enzyme that acts in the final and committed step of TAG synthesis, and it has been proposed to be the rate-limiting enzyme in plant storage lipid accumulation. In fact, two different enzymes identified in several eukaryotic species, DGAT1 and DGAT2, are the main enzymes responsible for TAG synthesis. These enzymes do not share high DNA or protein sequence similarities, and it has been suggested that they play non-redundant roles in different tissues and in some species in TAG synthesis. Despite a number of previous studies on the DGAT1 and DGAT2 genes, which have emphasized their importance as potential obesity treatment targets to increase triacylglycerol accumulation, little is known about their evolutionary timeline in eukaryotes. The goal of this study was to examine the evolutionary relationship of the DGAT1 and DGAT2 genes across eukaryotic organisms in order to infer their origin.</p> <p>Results</p> <p>We have conducted a broad survey of fully sequenced genomes, including representatives of Amoebozoa, yeasts, fungi, algae, musses, plants, vertebrate and invertebrate species, for the presence of DGAT1 and DGAT2 gene homologs. We found that the DGAT1 and DGAT2 genes are nearly ubiquitous in eukaryotes and are readily identifiable in all the major eukaryotic groups and genomes examined. Phylogenetic analyses of the DGAT1 and DGAT2 amino acid sequences revealed evolutionary partitioning of the DGAT protein family into two major DGAT1 and DGAT2 clades. Protein secondary structure and hydrophobic-transmembrane analysis also showed differences between these enzymes. The analysis also revealed that the MGAT2 and AWAT genes may have arisen from DGAT2 duplication events.</p> <p>Conclusions</p> <p>In this study, we identified several DGAT1 and DGAT2 homologs in eukaryote taxa. Overall, the data show that DGAT1 and DGAT2 are present in most eukaryotic organisms and belong to two different gene families. The phylogenetic and evolutionary analyses revealed that DGAT1 and DGAT2 evolved separately, with functional convergence, despite their wide molecular and structural divergence.</p

Innovative solutions to enhance safe and green environments for ageing well using co-design through Patient and Public Involvement.

Background: There is a need to develop innovative solutions to enhance safe and green physical environments, which optimise health, wellbeing and community participation among older adults. In order to develop solutions that meet the needs of a diverse ageing population, an interdisciplinary approach is needed. Our aim was to identify the needs of older people in relation to ageing well in the environment by bringing together knowledge from different perspectives using Patient and Public Involvement. Methods: An international consortium (Retrofit living For ageing well through Understanding and Redesign of Built environments consortium: ReFURB) was established in April 2018, including ten core members, to (i) explore cutting-edge solutions to safe living for ageing populations and (ii) develop innovative approaches to everyday physical environments, which bring about health benefits. We used a co-design, interdisciplinary framework involving older adults, carers, physiotherapists, geriatricians, engineers, human movement experts, geographers and psychologists from the UK and Australia. This engaged people in a one day workshop that comprised a series of presentations from international speakers on urban design, social connectedness, hazards and injury prevention, and the physical environment. Small group discussions (facilitated by consortium members) followed presentations to consider the opportunities, challenges and barriers encountered with ageing, which included the use of creative engagement activities (LEGO® Serious Play, mind maps, poster gallery walk), to help participants share personal stories and reflect on the issues raised. Thematic coding was used to synthesise the outputs of the small group work. Results: Five themes were identified across the workshops, comprising: access and transport; involvement of the whole community; restoration rather than redesign; assistive and digital technology; and intergenerational approaches. These dimensions related to the physical, social and nature-based qualities of everyday environments, as they pertain to ageing well. Conclusions: Co-design was a valuable tool that helped understand the perceptions of participants and essential to develop effective interventions and solutions. Participants highlighted several issues affecting people as they age and key environmental considerations to promote wellbeing, activity, and participation. The consortium identified gaps in the existing evidence base and are now planning activities to further develop research ideas in collaboration with our co-design participants