Co-ordinated care for people affected by rare diseases: the CONCORD mixed-methods study

This study found evidence of a lack of co-ordinated care for people affected by rare diseases, which could have negative impacts on the physical and mental health of patients and families

Experiences of coordinated care for people in the UK affected by rare diseases: cross-sectional survey of patients, carers, and healthcare professionals

BackgroundPoorly coordinated care can have major impacts on patients and families affected by rare conditions, with negative physical health, psychosocial and financial consequences. This study aimed to understand how care is coordinated for rare diseases in the United Kingdom.MethodsWe undertook a national survey in the UK involving 760 adults affected by rare diseases, 446 parents/carers of people affected by rare diseases, and 251 healthcare professionals who care for people affected by rare diseases.ResultsFindings suggested that a wide range of patients, parents and carers do not have coordinated care. For example, few participants reported having a care coordinator (12% patients, 14% parents/carers), attending a specialist centre (32% patients, 33% parents/carers) or having a care plan (10% patients, 44% parents/carers). A very small number of patients (2%) and parents/carers (5%) had access to all three—a care coordinator, specialist centre and care plan. Fifty four percent of patients and 33% of parents/carers reported access to none of these. On the other hand, a higher proportion of healthcare professionals reported that families with rare conditions had access to care coordinators (35%), specialist centres (60%) and care plans (40%).ConclusionsCare for families with rare conditions is generally not well coordinated in the UK, with findings indicating limited access to care coordinators, specialist centres and care plans. Better understanding of these issues can inform how care coordination might be improved and embrace the needs and preferences of patients and families affected by rare conditions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity

Defense responses of lentil (Lens culinaris) genotypes carrying non-allelic ascochyta blight resistance genes to Ascochyta lentis infection.

Ascochyta blight of lentil is an important fungal disease in many lentil-producing regions of the world causing major yield and grain quality losses. Quick shifts in aggressiveness of the population of the causal agent Ascochyta lentis mandates developing germplasm with novel and durable resistance. In the absence of complete resistance, lentil genotypes CDC Robin and 964a-46 have frequently been used as sources of partial resistance to ascochyta blight and carry non-allelic ascochyta blight resistance genes. RNA-seq analysis was conducted to identify differences in the transcriptome of CDC Robin, 964a-46 and the susceptible check Eston after inoculation with A. lentis. Candidate defense genes differentially expressed among the genotypes had hypothetical functions in various layers of plant defense, including pathogen recognition, phytohormone signaling pathways and downstream defense responses. CDC Robin and 964a-46 activated cell surface receptors (e.g. receptor like kinases) tentatively associated with pathogen-associated molecular patterns (PAMP) recognition and nucleotide-binding site leucine-rich repeat (NBS-LRR) receptors associated with intracellular effector recognition upon A. lentis infection, and differed in their activation of salicylic acid, abscisic acid and jasmonic acid / ethylene signal transduction pathways. These differences were reflected in the differential expression of downstream defense responses such as pathogenesis-related proteins, and genes associated with the induction of cell death and cell-wall reinforcement. A significant correlation between expression levels of a selection of genes based on quantitative real-time PCR and their expression levels estimated through RNA-seq demonstrated the technical and analytical accuracy of RNA-seq for identification of genes differentially expressed among genotypes. The presence of different resistance mechanisms in 964a-46 and CDC Robin indicates their value for pyramiding gene leading to more durable resistance to ascochyta blight

Evaluate of action adaptogenica of roots the Pfaffia glomerata (Sprengel) Petersen - Amaranthaceae

Pesquisou-se a especie Pfaffia glomerata (Spreng.) Pedersen, cujas raizes sao referidas como um dos ginsengs brasileiros e empregadas para fortalecer a memoria e aumentar a resistencia fica. A planta foi coletada no municipio de Porto Rico (PR), montada em exsicatas, identificada por especialista botanico e avaliada quanto a qualidade de acordo com normas farmacopeicas. Obteve-se extratos hidroalcoolicos das raizes pelo processo da turbolise, que foram liofilizados e armazenados em dessecador a vacuo em freezer. Realizou-se testes agudos com camundongos jovens: screening farmacologico, teste de movimentacao espontanea, teste de coordenacao motora, teste de tempo de sono induzido pelo pentobarbital sodico e teste de esquiva passiva com escopolamina como agente amnesico. Realizou-se tambem testes com ratos jovens e idosos submetidos a administracao cronica: teste de discriminacao direita-esquerda (labirinto em T), teste de esquiva passiva, movimentacao espontanea e avaliacao da evolucao ponderal. O estudo toxicologico pre-clinico envolveu a toxicologia de uma dose (aguda), a toxicologia de doses repetidas (cronica) por 90 dias, a avaliacao da evolucao ponderal, a movimentacao espontanea e avaliacao sanguinea dos parametros bioquimicas e hematologicos bem como da anatomia-patologica do coracao, figado e rins dos animais. O estudo clinico envolveu 38 voluntarios normais, de idade entre 50-75 anos e de diferentes padroes de atividade fisica. Aplicou-se testes psicometricos basais (Teste de Atencao Concentrada, Wechsler Memory Scale e Teste de Matrizes Progressivas), bem como realizou-se um teste ergoespirometrico em bicicleta ergometrica com protocolo de aumento progressivo de cargas ate exaustao. Mediu-se o VO2 maximo, a carga maxima, a frequencia cardiaca submaxima e niveis de lactato no inicio e final do exercicio. Os voluntarios tomaram duas capsulas diarias de extrato seco da planta (300 mg por capsula) ou placebo (500 mg de acucar mascavo), durante seis meses. Nesse periodo, os mesmos foram acompanhados por consultas mensais. Ao final do tratamento, repetiram-se os testes psicometricos e a ergoespirometria. A especie utilizada neste trabalho foi identificada como Pfaffia glomerata (Sprengei) Pedersen - Amaranthaceae, cujos exemplares estao depositados no acervo do Herbarium Friburgense (FCAB) sob o numero 5426. Os dados da CLAE/HPLC evidenciaram os seguintes teores de b-ecdisona: O,76 por cento...(au)BV UNIFESP: Teses e dissertaçõe

Experiences of coordinated care for people in the UK affected by rare diseases: cross-sectional survey of patients, carers, and healthcare professionals

Background: Poorly coordinated care can have major impacts on patients and families affected by rare conditions, with negative physical health, psychosocial and financial consequences. This study aimed to understand how care is coordinated for rare diseases in the United Kingdom. // Methods: We undertook a national survey in the UK involving 760 adults affected by rare diseases, 446 parents/carers of people affected by rare diseases, and 251 healthcare professionals who care for people affected by rare diseases. // Results: Findings suggested that a wide range of patients, parents and carers do not have coordinated care. For example, few participants reported having a care coordinator (12% patients, 14% parents/carers), attending a specialist centre (32% patients, 33% parents/carers) or having a care plan (10% patients, 44% parents/carers). A very small number of patients (2%) and parents/carers (5%) had access to all three—a care coordinator, specialist centre and care plan. Fifty four percent of patients and 33% of parents/carers reported access to none of these. On the other hand, a higher proportion of healthcare professionals reported that families with rare conditions had access to care coordinators (35%), specialist centres (60%) and care plans (40%). // Conclusions: Care for families with rare conditions is generally not well coordinated in the UK, with findings indicating limited access to care coordinators, specialist centres and care plans. Better understanding of these issues can inform how care coordination might be improved and embrace the needs and preferences of patients and families affected by rare conditions