Issues potentially affecting quality of life arising from long-term medicines use: a qualitative study

Background Polypharmacy is increasing and managing large number of medicines may create a burden for patients. Many patients have negative views of medicines and their use can adversely affect quality of life. No studies have specifically explored the impact of general long-term medicines use on quality of life. Objective To determine the issues which patients taking long-term medicines consider affect their day-to-day lives, including quality of life. Setting Four primary care general practices in North West England Methods Face-to-face interviews with adults living at home, prescribed four or more regular medicines for at least 1 year. Interviewees were identified from primary care medical records and purposively selected to ensure different types of medicines use. Interviews were recorded, transcribed and analysed thematically. Results Twenty-one interviews were conducted and analysed. Patients used an average of 7.8 medicines, 51 % were preventive, 40 % for symptom relief and 9 % treatment. Eight themes emerged: relationships with health professionals, practicalities, information, efficacy, side effects, attitudes, impact and control. Ability to discuss medicines with health professionals varied and many views were coloured by negative experiences, mainly with doctors. All interviewees had developed routines for using multiple medicines, some requiring considerable effort. Few felt able to exert control over medicines routines specified by health professionals. Over half sought additional information about medicines whereas others avoided this, trusting in doctors to guide their medicines use. Patients recognised their inability to assess efficacy for many medicines, notably those used for prophylaxis. All were concerned about possible side effects and some had poor experiences of discussing concerns with doctors. Medicines led to restrictions on social activities and personal life to the extent that, for some, life can revolve around medicines. Conclusion There is a multiplicity and complexity of issues surrounding medicines use, which impact on day-to-day lives for patients with long-term conditions. While most patients adapt to long-term medicines use, others did so at some cost to their quality of life

Genetic characterization of morphologically variant strains of Paracoccidioides brasiliensis

Molecular characterization of Paracoccidioides brasiliensis variant strains that had been preserved under mineral oil for decades was carried out by random amplified polymorphic DNA analysis (RAPD). On P. brasiliensis variants in the transitional phase and strains with typical morphology, RAPD produced reproducible polymorphic amplification products that differentiated them. A dendrogram based on the generated RAPD patterns placed the 14 P. brasiliensis strains into five groups with similarity coefficients of 72%. A high correlation between the genotypic and phenotypic characteristics of the strains was observed. A 750 bp-RAPD fragment found only in the wild-type phenotype strains was cloned and sequenced. Genetic similarity analysis using BLASTx suggested that this RAPD marker represents a putative domain of a hypothetical flavin-binding monooxygenase (FMO)-like protein of Neurospora crassa.FiocruzBritish Council Progra

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Inter-organizational governance and trilateral trust building: a case study of crowdsourcing-based open innovation in China

In a case study of a Chinese crowdsourcing intermediary, we explore the impact of inter-organizational governance on trilateral trust-building. We show that formal control and relational governance mechanisms are essential for swift and knowledge-based trust in R&D crowdsourcing. The case also indicates that Chinese businesses continue to use guanxi (informal personal connections) as a relational and contingent mechanism to maintain affect-based trust, but guanxi is shown to inhibit the growth of Internet-based crowdsourcing for open innovation in China

Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes

Prions are self-perpetuating aggregated proteins that are not limited to mammalian systems but also exist in lower eukaryotes including yeast. While much work has focused around chaperones involved in prion maintenance, including Hsp104, little is known about factors involved in the appearance of prions. De novo appearance of the [PSI+] prion, which is the aggregated form of the Sup35 protein, is dramatically enhanced by transient overexpression of SUP35 in the presence of the prion form of the Rnq1 protein, [PIN+]. When fused to GFP and overexpressed in [ps−] [PIN+] cells, Sup35 forms fluorescent rings, and cells with these rings bud off [PSI+] daughters. We investigated the effects of over 400 gene deletions on this de novo induction of [PSI+]. Two classes of gene deletions were identified. Class I deletions (bug1Δ, bem1Δ, arf1Δ, and hog1Δ) reduced the efficiency of [PSI+] induction, but formed rings normally. Class II deletions (las17Δ, vps5Δ, and sac6Δ) inhibited both [PSI+] induction and ring formation. Furthermore, class II deletions reduced, while class I deletions enhanced, toxicity associated with the expanded glutamine repeats of the huntingtin protein exon 1 that causes Huntington's disease. This suggests that prion formation and polyglutamine aggregation involve a multi-phase process that can be inhibited at different steps.National Institutes of Health (U.S.) (grant GM56350)National Institutes of Health (U.S.) (NSRA F32 postdoctoral fellowship GM072340)National Institutes of Health (U.S.) (grant GM25874)Howard Hughes Medical Institut

Children reading to dogs: a systematic review of the literature

Background Despite growing interest in the value of human-animal interactions (HAI) to human mental and physical health the quality of the evidence on which postulated benefits from animals to human psychological health are based is often unclear. To date there exist no systematic reviews on the effects of HAI in educational settings specifically focussing on the perceived benefits to children of reading to dogs. With rising popularity and implementation of these programmes in schools, it is essential that the evidence base exploring the pedagogic value of these initiatives is well documented. Methods Using PRISMA guidelines we systematically investigated the literature reporting the pedagogic effects of reading to dogs. Because research in this area is in the early stages of scientific enquiry we adopted broad inclusion criteria, accepting all reports which discussed measurable effects related to the topic that were written in English. Multiple online databases were searched during January-March 2015; grey literature searches were also conducted. The search results which met the inclusion criteria were evaluated, and discussed, in relation to the Oxford Centre for Evidence Based Medicine levels of evidence; 27 papers were classified as Level 5, 13 as Level 4, 7 as Level 2c and 1 as Level 2b. Conclusion The evidence suggests that reading to a dog may have a beneficial effect on a number of behavioural processes which contribute to a positive effect on the environment in which reading is practiced, leading to improved reading performance. However, the evidence base on which these inferences are made is of low quality. There is a clear need for the use of higher quality research methodologies and the inclusion of appropriate controls in order to draw causal inferences on whether or how reading to dogs may benefit children’s reading practices. The mechanisms for any effect remain a matter of conjectur

Sí Se Puede: Using Participatory Research to Promote Environmental Justice in a Latino Community in San Diego, California

Community-based participatory research (CBPR) increasingly is seen as a potent tool for studying and addressing urban environmental health problems by linking place-based work with efforts to help effect policy-level change. This paper explores a successful CBPR and organizing effort, the Toxic Free Neighborhoods Campaign, in Old Town National City (OTNC), CA, United States, and its contributions to both local policy outcomes and changes in the broader policy environment, laying the groundwork for a Specific Plan to address a host of interlocking community concerns. After briefly describing the broader research of which the OTNC case study was a part, we provide background on the Environmental Health Coalition (EHC) partnership and the setting in which it took place, including the problems posed for residents in this light industrial/residential neighborhood. EHC’s strong in-house research, and its training and active engagement of promotoras de salud (lay health promoters) as co-researchers and policy change advocates, are described. We explore in particular the translation of research findings as part of a policy advocacy campaign, interweaving challenges faced and success factors and multi-level outcomes to which these efforts contributed. The EHC partnership's experience then is compared with that of other policy-focused CBPR efforts in urban environmental health, emphasizing common success factors and challenges faced, as these may assist other partnerships wishing to pursue CBPR in urban communities

Trajectories in chronic disease accrual and mortality across the lifespan in Wales, UK (2005–2019), by area deprivation profile: linked electronic health records cohort study on 965,905 individuals

BACKGROUND: Understanding and quantifying the differences in disease development in different socioeconomic groups of people across the lifespan is important for planning healthcare and preventive services. The study aimed to measure chronic disease accrual, and examine the differences in time to individual morbidities, multimorbidity, and mortality between socioeconomic groups in Wales, UK. METHODS: Population-wide electronic linked cohort study, following Welsh residents for up to 20 years (2000–2019). Chronic disease diagnoses were obtained from general practice and hospitalisation records using the CALIBER disease phenotype register. Multi-state models were used to examine trajectories of accrual of 132 diseases and mortality, adjusted for sex, age and area-level deprivation. Restricted mean survival time was calculated to measure time spent free of chronic disease(s) or mortality between socioeconomic groups. FINDINGS: In total, 965,905 individuals aged 5–104 were included, from a possible 2.9 m individuals following a 5-year clearance period, with an average follow-up of 13.2 years (12.7 million person-years). Some 673,189 (69.7%) individuals developed at least one chronic disease or died within the study period. From ages 10 years upwards, the individuals living in the most deprived areas consistently experienced reduced time between health states, demonstrating accelerated transitions to first and subsequent morbidities and death compared to their demographic equivalent living in the least deprived areas. The largest difference were observed in 10 and 20 year old males developing multimorbidity (−0.45 years (99% CI: −0.45, −0.44)) and in 70 year old males dying after developing multimorbidity (−1.98 years (99% CI: −2.01, −1.95)). INTERPRETATION: This study adds to the existing literature on health inequalities by demonstrating that individuals living in more deprived areas consistently experience accelerated time to diagnosis of chronic disease and death across all ages, accounting for competing risks. FUNDING: UK Medical Research Council, Health Data Research UK, and Administrative Data Research Wales

Trajectories in chronic disease accrual and mortality across the lifespan in Wales, UK (2005-2019), by area deprivation profile : linked electronic health records cohort study on 965,905 individuals

Funding: This work was supported by Health Data Research UK (HDRUK) Measuring and Understanding Multimorbidity using Routine Data in the UK (MUrMuRUK, HDR-9006; CFC0110). Health Data Research UK (HDR-9006) is funded by: UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, the National Institute for Health Research (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. This work also was co-funded by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR) through grant number MR/S027750/1. The work was supported by the ADR Wales programme of work, part of the Economic and Social Research Council (part of UK Research and Innovation) funded ADR UK (grant ES/S007393/1).Background  Understanding and quantifying the differences in disease development in different socioeconomic groups of people across the lifespan is important for planning healthcare and preventive services. The study aimed to measure chronic disease accrual, and examine the differences in time to individual morbidities, multimorbidity, and mortality between socioeconomic groups in Wales, UK. Methods  Population-wide electronic linked cohort study, following Welsh residents for up to 20 years (2000-2019). Chronic disease diagnoses were obtained from general practice and hospitalisation records using the CALIBER disease phenotype register. Multi-state models were used to examine trajectories of accrual of 132 diseases and mortality, adjusted for sex, age and area-level deprivation. Restricted mean survival time was calculated to measure time spent free of chronic disease(s) or mortality between socioeconomic groups. Findings  In total, 965,905 individuals aged 5-104 were included, from a possible 2·9m individuals following a 5-year clearance period, with an average follow-up of 13·2 years (12·7 million person-years). Some 673,189 (69·7 %) individuals developed at least one chronic disease or died within the study period. From ages 10 years upwards, the individuals living in the most deprived areas consistently experienced reduced time between health states, demonstrating accelerated transitions to first and subsequent morbidities and death compared to their demographic equivalent living in the least deprived areas. The largest difference were observed in 10 and 20 year old males developing multimorbidity (-0·45 years (99%CI:-0·45,-0·44)) and in 70 year old males dying after developing multimorbidity (-1·98 years (99%CI:-2·01,-1·95)). Interpretation  This study adds to the existing literature on health inequalities by demonstrating that individuals living in more deprived areas consistently experience accelerated time to diagnosis of chronic disease and death across all ages, accounting for competing risks.Publisher PDFPeer reviewe