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This case report highlights the unusual presentation and management of nonrheumatic myocarditis in a 24-year-old male, an age demographic not commonly associated with myocardial complications following Group A streptococcal pharyngitis. The patient, devoid of any prior medical history, manifested symptoms one day after being diagnosed with Group A streptococcal pharyngitis, a stark contrast to the typical progression of myocardial complications. The swift onset of symptoms and the patient's subsequent clinical presentation necessitated a comprehensive diagnostic approach. The patient's symptoms were successfully alleviated with amoxicillin and anti-inflammatory therapy, underscoring its potential efficacy in managing nonrheumatic myocarditis. This case serves as a poignant reminder of the importance of maintaining a broad differential diagnosis, especially in atypical presentations, and the pivotal role of timely clinical intervention. The insights from this report contribute to the broader understanding of nonrheumatic myocarditis, emphasizing the significance of tailored diagnostic and therapeutic strategies to ensure optimal patient outcomes.
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Meiotic recombination is a fundamental process that generates genetic diversity by creating new combinations of existing alleles. Although human crossovers have been studied at the pedigree, population and single-cell level, the more frequent non-crossover events that lead to gene conversion are harder to study, particularly at the individual level. Here we show that single high-fidelity long sequencing reads from sperm can capture both crossovers and non-crossovers, allowing effectively arbitrary sample sizes for analysis from one male. Using fifteen sperm samples from thirteen donors we demonstrate variation between and within donors for the rates of different types of recombination. Intriguingly, we observe a tendency for non-crossover gene conversions to occur upstream of nearby PRDM9 binding sites, whereas crossover locations have a slight downstream bias. We further provide evidence for two distinct non-crossover processes. One gives rise to the vast majority of non-crossovers with mean conversion tract length under 50bp, which we suggest is an outcome of standard PRDM9-induced meiotic recombination. In contrast ~2% of non-crossovers have much longer mean tract length, and potentially originate from the same process as complex events with more than two haplotype switches, which is not associated with PRDM9 binding sites and is also seen in somatic cells.
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Late Ediacaran strata from Newfoundland, Canada (~574-560 Ma) document near-census palaeocommunities of some of the earliest metazoans. Such preservation enables reproductive strategies to be inferred from the spatial distribution of populations of fossilized benthic organisms, previously revealing the existence of both propagule and stoloniferous reproductive modes among Ediacaran frondose taxa. Here, we describe 'conga lines': linear arrangements of more than three closely spaced fossil specimens. We calculate probabilistic models of point maps of 13 fossil-bearing bedding surfaces and show that four surfaces contain conga lines that are not the result of chance alignments. We then test whether these features could result from passive pelagic propagules settling in the lee of an existing frond, using computational fluid dynamics and discrete phase modelling. Under Ediacaran palaeoenvironmental conditions, preferential leeside settlement at the spatial scale of the conga lines is unlikely. We therefore conclude that these features are novel and do not reflect previously described reproductive strategies employed by Ediacaran organisms, suggesting the use of mixed reproductive strategies in the earliest animals. Such strategies enabled Ediacaran frondose taxa to act as reproductive generalists and may be an important facet of early metazoan evolution.
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Imunoterapia Adotiva , Linfoma de Células T , Receptores de Antígenos Quiméricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imunoterapia Adotiva/efeitos adversos , Linfoma de Células T/etiologia , Linfoma de Células T/genética , Linfoma de Células T/imunologia , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologiaRESUMO
The driving forces behind the evolution of early metazoans are not well understood, but key insights into their ecology and evolution can be gained through ecological analyses of the in situ, sessile communities of the Avalon assemblage in the Ediacaran (~565 million years ago). Community structure in the Avalon is thought to be underpinned by epifaunal tiering and ecological succession, which we investigate in this study in 18 Avalon communities. Here we found that Avalon communities form four distinctive Community Types irrespective of succession processes, which are instead based on the dominance of morphologically distinct taxa, and that tiering is prevalent in three of these Community Types. Our results are consistent with emergent neutrality, whereby ecologically specialized morphologies evolve as a consequence of neutral (stochastic or reproductive) processes within niches, leading to generalization within the frond-dominated Community Type. Our results provide an ecological signature of the first origination and subsequent loss of disparate morphologies, probably as a consequence of community restructuring in response to ecological innovation. This restructuring led to the survival of non-tiered frondose generalists over tiered specialists, even into the youngest Ediacaran assemblages. Such frondose body plans also survive beyond the Ediacaran-Cambrian transition, perhaps due to the greater resilience afforded to them by their alternative ecological strategies.
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Ecossistema , Animais , Fósseis/anatomia & histologia , Evolução Biológica , Invertebrados/anatomia & histologia , Invertebrados/fisiologiaRESUMO
The rise of animals across the Ediacaran-Cambrian transition marked a step-change in the history of life, from a microbially dominated world to the complex macroscopic biosphere we see today.1,2,3 While the importance of bioturbation and swimming in altering the structure and function of Earth systems is well established,4,5,6 the influence of epifaunal animals on the hydrodynamics of marine environments is not well understood. Of particular interest are the oldest "marine animal forests,"7 which comprise a diversity of sessile soft-bodied organisms dominated by the fractally branching rangeomorphs.8,9 Typified by fossil assemblages from the Ediacaran of Mistaken Point, Newfoundland,8,10,11 these ancient communities might have played a pivotal role in structuring marine environments, similar to modern ecosystems,7,12,13 but our understanding of how they impacted fluid flow in the water column is limited. Here, we use ecological modeling and computational flow simulations to explore how Ediacaran marine animal forests influenced their surrounding environment. Our results reveal how organism morphology and community structure and composition combined to impact vertical mixing of the surrounding water. We find that Mistaken Point communities were capable of generating high-mixing conditions, thereby likely promoting gas and nutrient transport within the "canopy." This mixing could have served to enhance local-scale oxygen concentrations and redistribute resources like dissolved organic carbon. Our work suggests that Ediacaran marine animal forests may have contributed to the ventilation of the oceans over 560 million years ago, well before the Cambrian explosion of animals.
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Organismos Aquáticos , Fósseis , Oceanos e Mares , Animais , Organismos Aquáticos/fisiologia , Ecossistema , HidrodinâmicaRESUMO
Human aging is marked by the emergence of a tapestry of clonal expansions in dividing tissues, particularly evident in blood as clonal hematopoiesis (CH). CH, linked to cancer risk and aging-related phenotypes, often stems from somatic mutations in a set of established genes. However, the majority of clones lack known drivers. Here we infer gene-level positive selection in whole blood exomes from 200,618 individuals in UK Biobank. We identify 17 additional genes, ZBTB33, ZNF318, ZNF234, SPRED2, SH2B3, SRCAP, SIK3, SRSF1, CHEK2, CCDC115, CCL22, BAX, YLPM1, MYD88, MTA2, MAGEC3 and IGLL5, under positive selection at a population level, and validate this selection pattern in 10,837 whole genomes from single-cell-derived hematopoietic colonies. Clones with mutations in these genes grow in frequency and size with age, comparable to classical CH drivers. They correlate with heightened risk of infection, death and hematological malignancy, highlighting the significance of these additional genes in the aging process.
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Hematopoiese Clonal , Mutação , Humanos , Hematopoiese Clonal/genética , Envelhecimento/genética , Idoso , Seleção Genética , Masculino , Pessoa de Meia-Idade , Adulto , Feminino , Exoma/genéticaRESUMO
Introduction: Children with type 1 diabetes require close monitoring with visits every 3-4 months. COVID-19-induced telemedicine expansion may alleviate the challenge of high visit frequency that children with type 1 diabetes face. However, telemedicine's impact on access to care may be limited if patients lack adequate support for telemedicine. The purpose of this study was to evaluate the impact of telemedicine care coordination services on visit frequency in an urban medical center without care coordination services versus a rural outreach program with established care coordination services serviced by the same providers. Methods: We evaluated EHR data from 790 children receiving care between July 2018 and December 2021 at a single academic center in Oregon. We estimated differences in likelihood of adequately timed monitoring care over time by patient care coordination services status using Generalized Estimating Equations. Results: Just prior to telemedicine expansion, patients receiving care coordination services were 25.6 % less likely to receive adequately timed monitoring care (95 % CI: 51.6 %, 114 %). Following telemedicine expansion, likelihood of adequately timed monitoring care increased from 28.8 % to 58.2 % among those receiving care coordination services and decreased from 38.7 % to 22.0 % among those not receiving care coordination services; increases in adequately timed monitoring care were 3.55 times greater in patients receiving care coordination services relative to those not (95 % CI: 2.10, 6.01). Discussion: For pediatric patients with type 1 diabetes, telemedicine care coordination may be an important factor for increasing visit adherence and may increase the number of patients meeting goal visit frequency beyond levels seen prior to widespread telemedicine availability.
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AIMS AND METHOD: In response to recommendations for improving the quality and coordination of care delivered by eating disorder services, a whole-team training programme was commissioned by Health Education England in 2020. This paper describes the development and evaluation of the Eating Disorder Services for Adults (EDSA) whole-team training course, delivered to National Health Service adult eating disorder community teams in England. Course participants (n = 561) in the first two EDSA training cohorts (2021 and 2022) were asked to complete questionnaires at intake and after each session, asking about their views on the training. RESULTS: All course aspects were rated as highly enjoyable, meeting participants' training needs and fostering reflective practice. Thematic analysis identified themes relating to key innovative features of the course and suggestions for improvements. CLINICAL IMPLICATIONS: Preliminary evaluation suggests that EDSA is valued by clinicians to enhance their knowledge, skills and ability to improve eating disorder patient care.
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Aminofenóis , Benzodioxóis , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Indóis , Pirazóis , Humanos , Masculino , Benzodioxóis/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Indóis/uso terapêutico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Aminofenóis/uso terapêutico , Pirazóis/uso terapêutico , Quinolonas/uso terapêutico , Combinação de Medicamentos , Piridinas/uso terapêutico , Adulto , Pirróis/uso terapêutico , Resultado do Tratamento , Quinolinas/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico , Mutação , PirrolidinasRESUMO
Most children with developmental disabilities (DD), such as intellectual disabilities and autism, live in low- and middle-income countries (LMICs), where services are usually limited. Various governmental, non-governmental and research organisations in LMICs have developed awareness-raising campaigns and training and education resources on DD in childhood relevant to LMICs. This study aimed to comprehensively search and review freely available materials in the academic and grey literature, aimed at awareness raising, training and education on DD among non-specialist professionals and community members in LMICs. We consulted 183 experts, conducted key-word searches in five academic databases, four grey-literature databases and seventeen customised Google search engines. Following initial screening, we manually searched relevant systematic reviews and lists of resources and conducted forwards and backwards citation checks of included articles. We identified 7327 articles and resources after deduplication. We then used a rigorous multi-step screening process to select 78 training resources on DD relevant to LMICs, of which 43 aimed at informing and/or raising awareness DD, 16 highlighted specific strategies for staff in health settings and 19 in education settings. Our mapping analysis revealed that a wealth of materials is available for both global and local use, including comics, children's books, flyers, posters, fact sheets, blogs, videos, websites pages, social media channels, handbooks and self-education guides, and training programmes or sessions. Twelve resources were developed for cross-continental or global use in LMICs, 19 were developed for and/or used in Africa, 23 in Asia, 24 in Latin America. Most resources were developed within the context where they were intended to be used. Identified gaps included a limited range of resources on intellectual disabilities, manuals for actively delivering training to staff in education settings and resources targeted at eastern European LMICs: future intervention development and adaptation efforts should address such gaps, to ensure capacity building materials exist for a sufficient variety of DD, settings and geographical areas. Beyond identifying these gaps, the value of the review lies in the compilation of summary tables of information on all freely available resources found, to support their selection and use in wider contexts. Information on the resource content, country of original development and copyright is provided to facilitate resource sharing and uptake.