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Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.
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Nephrocalcinosis is a widespread challenge in intensive production of salmon smolt. There is however no consensus on its aetiology, which makes it problematic to implement proper measures to limit its development. We performed a survey of nephrocalcinosis prevalence and environmental factors in 11 different hatcheries in Mid-Norway as well as a 6-month monitoring in one of the hatcheries. A multivariate analysis indicated that the most influencing factor for the prevalence of nephrocalcinosis was the supplementation of sea water during smolt production. In the 6-month monitoring, the hatchery introduced salinity in the production water prior to the change in day length. Mismatch in those environmental signals may increase the risk for developing nephrocalcinosis. Salinity fluctuations prior to smoltification can cause osmotic stress and result in unbalanced levels of ions in fish blood. This was clearly illustrated in our study, as the fish experienced chronic hypercalcaemia and hypermagnesaemia. Both magnesium and calcium are excreted over the kidneys and it is possible that their prolonged, elevated levels in plasma resulted in an oversaturation of the urine when finally excreted. This again could have led to the aggregation of calcium deposits within the kidney. This study indicates a relationship between osmotic stress induced by salinity changes in juvenile Atlantic salmon and the development of nephrocalcinosis. Other factors that may affect the severity of nephrocalcinosis are currently subjects for discussion.
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Doenças dos Peixes , Nefrocalcinose , Salmo salar , Animais , Nefrocalcinose/epidemiologia , Nefrocalcinose/etiologia , Nefrocalcinose/veterinária , Cálcio , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/etiologia , OsmorregulaçãoRESUMO
The Superconducting Analyzer for MUlti-particles from RAdioIsotope (SAMURAI) Pion-Reconstruction and Ion-Tracker Time Projection Chamber (SπRIT TPC) was designed to enable measurements of heavy ion collisions with the SAMURAI spectrometer at the RIKEN radioactive isotope beam factory and provides constraints on the equation of state of neutron-rich nuclear matter. The SπRIT TPC has a 50.5 cm drift length and an 86.4 × 134.4 cm2 pad plane with 12 096 pads that are equipped with the generic electronics for TPCs. The SπRIT TPC allows for an excellent reconstruction of particles and provides isotopic resolution for pions and other light charged particles across a wide range of energy losses and momenta. The details of the SπRIT TPC are presented, along with discussion of the TPC performance based on cosmic rays and charged particles emitted in heavy ion collisions.
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The increasing replacement of fish oil (FO) by vegetable oils (VO) in aquafeeds for marine carnivorous species may lead to modifications of the dietary arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) levels and ratios that may compromise the fish immune status. Therefore, this study aimed to assess how different dietary ratios of ARA, EPA, and DHA modulate the immune response of gilthead sea bream juveniles. For that purpose, four isoproteic and isolipidic plant-based diets were formulated to include different dietary Long-Chain-Polyunsaturated Fatty Acids (LC-PUFA) ratios (%DM): Diet A (2.0% ARA: 0.2% EPA: 0.1% DHA); Diet B (1.0% ARA: 0.4% EPA: 0.4% DHA); Diet C (0% ARA: 0.6% EPA: 0.6% DHA); Diet D (0% ARA: 0.3% EPA: 1.5% DHA). Fish were fed the experimental diets for 56 days and then the haematological profile, humoral innate immune parameters, and expression of immune-related genes in the gut were determined. Our results showed that fish fed diet B exhibited an increase in the monocyte numbers, alternative complement activity, and bactericidal activity against Photobacterium damselae compared to the values found in fish fed other diets. Contrarily, peroxidase, antiproteases, and proteases activity and nitric oxide levels were not affected by the dietary treatments. Immune-related gene expression in the distal intestine did not show differences between dietary treatments. Overall, a diet with a balanced n-6 (ARA) and n-3 (EPA+DHA) LC-PUFA ratio seemed to better modulate the fish innate immune response, thus better preparing the fish innate immune system against potential immunological insults.
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The present work assessed the effects of dietary ratios of essential fatty acids, arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), on liver and intestine oxidative status, intestinal histomorphology and gut microbiota of gilthead sea bream. Four isoproteic and isolipidic plant-based diets were formulated containing a vegetable oil blend as the main lipid source. Diets were supplemented with ARA/EPA/DHA levels (%DM) equivalent to: 2%:0.2%:0.1% (Diet A); 1.0%:0.4%:0.4% (Diet B); 0%:0.6%:0.6% (Diet C); 0%:0.3%:1.5% (Diet D) and tested in triplicate groups for 56 days. Lipid peroxidation was higher in fish fed diets C and D while no differences were reported between diets regarding total, oxidized, and reduced glutathione, and oxidative stress index. Glutathione reductase was higher in fish fed diet A than diets C and D. No histological alterations were observed in the distal intestine. Lower microbiota diversity was observed in intestinal mucosa of fish fed diet C than A, while diets C and D enabled the proliferation of health-promoting bacteria from Bacteroidetes phylum (Asinibacterium sp.) and the absence of pathogenic species like Edwardsiella tarda. Overall, results suggest that a balance between dietary ARA/EPA + DHA promotes gilthead sea bream juveniles' health however higher dietary content of n-3 LC-PUFA might limited the presence of microbial pathogens in intestinal mucosa.
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Ração Animal , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Ácido Araquidônico/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Microbioma Gastrointestinal , Estresse Oxidativo , Dourada/metabolismo , Dourada/microbiologia , Animais , Glutationa Redutase/metabolismo , Mucosa Intestinal , Intestinos/microbiologia , Peroxidação de Lipídeos , Fígado/metabolismoRESUMO
BACKGROUND: Post-operative hypoxemia is prevalent in hospitalized patients and may adversely affect recovery. However, little data exist on the post-discharge phase or details on duration, severity and potential risk factors. Thus, we investigated the incidence and risk factors for severe desaturation during the first post-operative week after THA/TKA by continuous nocturnal oxygen saturation monitoring. METHODS: The study was a secondary analysis of a prospective cohort study of 112 patients undergoing fast-track THA/TKA. Patients with known sleep apnoea were excluded. Oxygen saturation and heart rate were recorded by a wireless wrist-worn pulse oximeter 2 nights before and 7 nights after surgery. Data on demographics, opioid consumption and cognitive function were collected from medical charts, patient diaries and clinical testing respectively. The primary outcome was occurrence of severe desaturation defined as periods with saturation <85% lasting ≥10 minutes. Secondary outcomes included description of various saturation levels and relevant risk factors. RESULTS: Severe oxygen desaturation occurred in 35% of the patients during the first post-operative week. Duration and severity of hypoxemic episodes increased after the first post-operative day. Pre-operative episodes of hypoxemia significantly increased the risk of post-operative hypoxemic events (OR 2.4-4.4, CI 0.4-46), while pre- and post-operative opioid use, age, gender, ASA classification, type of surgery or anaesthesia were significantly related to the development of post-operative hypoxemia. CONCLUSIONS: One third of the patients suffered from increased and prolonged episodes of severe nocturnal hypoxemia during the first week after THA/TKA discharge. Increased risk for severe hypoxemic episodes was related to pre-operative hypoxemia.
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Artroplastia de Quadril , Artroplastia do Joelho , Assistência ao Convalescente , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Hospitais , Humanos , Hipóxia/epidemiologia , Hipóxia/etiologia , Alta do Paciente , Estudos ProspectivosRESUMO
OBJECTIVE: Ambient exposure to fine particles is associated with increased cardiovascular morbidity and mortality. Associations between occupational particulate matter (PM) exposure and cardiovascular disease have been studied less. The objective of this study was to examine associations between PM exposure and endothelial function among workers in Norwegian smelters. METHODS: We examined endothelial function with Endo-PAT equipment after a working day (WD) and on a day off (DO) in 59 furnace workers recruited from three metal smelters in Norway. The difference in baseline pulse amplitude (BPA) and reactive hyperemia index (RHI) between the 2 days was analysed in relation to individual exposure to PM < 250 nm (PM250) or the respirable aerosol fraction of particles, and adjusted for relevant covariates. RESULTS: The exposure to PM250 ranged from 0.004 to 5.7 mg/m3. The mean BPA was significantly higher on WD relative to DO (772 vs. 535, p = 0.001). This difference was associated with PM concentrations among participants ≥ 34 years, but not among the younger workers. Reactive hyperemia was significantly lower on workdays relative to days off (1.70 vs. 1.84, p = 0.05). This difference was observed only among participants above the age 34. No associations with PM exposure were observed. CONCLUSIONS: PM exposure was associated with higher BPA among participants older than 34 years. BPA reflects microvessel pulsatility. Our results may indicate an age-dependent cardiovascular susceptibility to PM exposure. Endothelial function measured by RHI was reduced on WD among participants 34 years and older, but we found no associations between PM exposure and RHI.
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Poluentes Ocupacionais do Ar/efeitos adversos , Hiperemia/induzido quimicamente , Hiperemia/epidemiologia , Manganês/efeitos adversos , Exposição Ocupacional/efeitos adversos , Silício/efeitos adversos , Adulto , Distribuição por Idade , Poluentes Ocupacionais do Ar/análise , Poluição do Ar/efeitos adversos , Monitoramento Ambiental/métodos , Humanos , Indústrias , Manganês/análise , Pessoa de Meia-Idade , Noruega/epidemiologia , Exposição Ocupacional/análise , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/análise , Pulso Arterial , Silício/análiseRESUMO
Multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) is a clinically heterogeneous disorder affecting fatty acid and amino acid metabolism. Presentations range from a severe neonatal form with hypoglycemia, metabolic acidosis, and hepatomegaly with or without congenital anomalies to later-onset lipid storage myopathy. Genetic testing for MADD traditionally comprises analysis of ETFA, ETFB, and ETFDH. Patients may respond to pharmacological doses of riboflavin, particularly those with late-onset MADD due to variants in ETFDH. Increasingly other genes involved in riboflavin transport and flavoprotein biosynthesis are recognized as causing a MADD phenotype. Flavin adenine dinucleotide synthase (FADS) deficiency caused by biallelic variants in FLAD1 has been identified in nine previous cases of MADD. FLAD1 missense mutations have been associated with a riboflavin-responsive phenotype; however the effect of riboflavin with biallelic loss of function FLAD1 mutations required further investigation. Herein we describe a novel, truncating variant in FLAD1 causing MADD in an 8-year-old boy. Fibroblast studies showed a dramatic reduction in FADS protein with corresponding reduction in the FAD synthesis rate and FAD cellular content, beyond that previously documented in FLAD1-related MADD. There was apparent biochemical and clinical response to riboflavin treatment, beyond that previously reported in cases of biallelic loss of function variants in FLAD1. Early riboflavin treatment may have attenuated an otherwise severe phenotype.
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INTRODUCTION: Millions of patients undergo major abdominal surgery worldwide each year, and the post-operative phase carries a high risk of respiratory and circulatory complications. Standard ward observation of patients includes vital sign registration at regular intervals. Patients may deteriorate between measurements, and this may be detected by continuous monitoring. The aim of this study was to compare the number of micro events detected by continuous monitoring to those documented by the widely used standardized Early Warning Score (EWS). METHODS: Fifty patients were continuously monitored with peripheral arterial oxygen saturation (SpO2 ), heart rate (HR), and respiratory rate (RR) the first 4 days after major abdominal cancer surgery. EWS was monitored as routine practice. Number and duration of events were analyzed using Fisher's exact test and Wilcoxon rank sum test. RESULTS: Continuous monitoring detected a SpO2 <92% in 98% of patients vs 16% of patients detected by EWS (P < .0001). Micro events of SpO2 <92% lasting longer than 60 minutes were found in 58% of patients by continuous monitoring vs 16% by the EWS (P < .0001). Fifty-two percent of patients had micro events of SpO2 <85% lasting longer than 10 minutes. Continuous monitoring found tachycardia in 60% of patients vs 6% by the EWS. Frequency of events for bradycardia, tachypnea, and bradypnea showed similar patterns. CONCLUSION: Very low SpO2 and tachycardia in post-operative patients are common and under-diagnosed by the EWS. Continuous monitoring can discover these micro events and potentially contribute to earlier detection and, potentially, result in prevention of clinical complications.
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Abdome/cirurgia , Monitorização Fisiológica/métodos , Complicações Pós-Operatórias/diagnóstico , Sinais Vitais/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/fisiopatologiaRESUMO
BACKGROUND: Vibration-induced white finger (VWF) is often assessed using the Stockholm Workshop Scale (SWS) and cold challenge plethysmography. However, long-term longitudinal studies using both methods are scarce. AIMS: To study the long-term course and prognostic factors of VWF assessed with the SWS and photoplethysmography (PPG), and to examine the effects of lifestyle on PPG score, regardless of VWF status. METHODS: Forty male construction workers were examined with a test battery and clinical examination in 1994 and 2016/17. RESULTS: At baseline, the sample comprised 27 workers with, and 13 without, symptoms of hand-arm vibration syndrome (HAVS). Thirty-five workers reported vibration exposure during follow-up. The mean age of the workers was 60 years (45-78) at follow-up. The paired t-test showed that PPG scores deteriorated from 1994 to 2017 in the 27 workers with HAVS in 1994 (mean difference 2.7 min, 95% confidence interval (CI) 0.2-5.2). However, there was no statistically significant change in SWS scores in these workers over time. Smoking and age were associated with PPG score deterioration. Vibration exposure during follow-up predicted SWS score deterioration: 1000 h of exposure predicted a deterioration stage of 0.09 (95% CI 0.03-0.16). Analysis of all 40 workers showed that 2017 PPG scores were associated with positive serum cotinine and self-reported smoking during follow-up. CONCLUSIONS: Whereas age and smoking predicted a PPG deterioration, continued vibration exposure predicted worsening of white finger symptoms. The association of PPG score and smoking should be considered in diagnostic and prognostic factor evaluations.
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Indústria da Construção/estatística & dados numéricos , Síndrome da Vibração do Segmento Mão-Braço/complicações , Idoso , Indústria da Construção/métodos , Seguimentos , Síndrome da Vibração do Segmento Mão-Braço/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Exposição Ocupacional/estatística & dados numéricosRESUMO
Essentials PSGL-1+ microvesicles (MVs) may be important in venous thromboembolism (VTE). We measured plasma levels and parental origin of PSGL-1+ MVs in patients with unprovoked VTE. VTE patients had higher plasma levels of PSGL-1+ MVs than healthy controls. The PSGL-1+ MVs originated mainly from monocytes and endothelial cells. SUMMARY: Background Microvesicles (MVs) express antigens from their parental cells and have a highly procoagulant surface. Animal studies suggest that P-selectin glycoprotein ligand-1-positive (PSGL-1+ ) MVs play a role in the pathogenesis of venous thromboembolism (VTE). Objective The aim of this study was to determine plasma levels, the cellular origin and the morphological characteristics of PSGL-1+ MVs in patients with unprovoked VTE. Methods We conducted a population-based case-control study in 20 patients with a history of unprovoked VTE and 20 age- and sex-matched healthy controls recruited from the general population. Plasma levels, the cellular origin and the morphological characteristics of PSGL-1+ MVs were evaluated using flow cytometry, electron microscopy and confocal microscopy. Results Plasma levels of PSGL-1+ MVs were associated with increased risk of VTE. The odds ratio per one standard deviation increase in PSGL-1+ MVs was 3.11 (95% confidence interval [CI], 1.41-6.88) after adjustment for age and sex, and 2.88 (95% CI, 1.29-6.41) after further adjustment for body mass index. The PSGL-1+ MVs originated mainly from monocytes and endothelial cells determined by double staining with markers of parental cells using flow cytometry and transmission electron microscopy. Scanning electron microscopy of PSGL-1-labeled plasma-derived MVs displayed dominantly spherical vesicles that varied between 50 and 300 nm in diameter. Conclusions Increased plasma levels of PSGL-1+ MVs are associated with the risk of unprovoked VTE. Large population-based prospective studies are required to validate our findings.
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Mouthrot, or bacterial stomatitis, is a disease which mainly affects farmed Atlantic salmon, (Salmo salar, L.), smolts recently transferred into salt water in both British Columbia (BC), Canada, and Washington State, USA. It is a significant fish welfare issue which results in economic losses due to mortality and antibiotic treatments. The associated pathogen is Tenacibaculum maritimum, a bacterium which causes significant losses in many species of farmed fish worldwide. This bacterium has not been proven to be the causative agent of mouthrot in BC despite being isolated from affected Atlantic salmon. In this study, challenge experiments were performed to determine whether mouthrot could be induced with T. maritimum isolates collected from outbreaks in Western Canada and to attempt to develop a bath challenge model. A secondary objective was to use this model to test inactivated whole-cell vaccines for T. maritimum in Atlantic salmon smolts. This study shows that T. maritimum is the causative agent of mouthrot and that the bacteria can readily transfer horizontally within the population. Although the whole-cell oil-adjuvanted vaccines produced an antibody response that was partially cross-reactive with several of the T. maritimum isolates, the vaccines did not protect the fish under the study's conditions.
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Annotated genomes can provide new perspectives on the biology of species. We present the first de novo whole genome sequencing for the pink-footed goose. In order to obtain a high-quality de novo assembly the strategy used was to combine one short insert paired-end library with two mate-pair libraries. The pink-footed goose genome was assembled de novo using three different assemblers and an assembly evaluation was subsequently performed in order to choose the best assembler. For our data, ALLPATHS-LG performed the best, since the assembly produced covers most of the genome, while introducing the fewest errors. A total of 26,134 genes were annotated, with bird species accounting for virtually all BLAST hits. We also estimated the substitution rate in the pink-footed goose, which can be of use in future demographic studies, by using a comparative approach with the genome of the chicken, the mallard and the swan goose. A substitution rate of 1.38×10-7 per nucleotide per generation was obtained when comparing the genomes of the two closely-related goose species (the pink-footed and the swan goose). Altogether, we provide a valuable tool for future genomic studies aiming at particular genes and regions of the pink-footed goose genome as well as other bird species.
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Gansos/genética , Genoma , Animais , Anotação de Sequência Molecular , Sequenciamento Completo do GenomaRESUMO
Surgical interventions come with complications and highly reported mortality after major surgery. The mortality may be a result of delayed detection of severe complications due to lower monitoring frequency in the general wards. Several studies have shown that continuous monitoring is superior to the manually intermittent recorded monitoring in terms of detecting abnormal physiological signs. Hopefully improved observations may result in earlier detection and clinical intervention. This narrative review will describe current monitoring possibilities for postoperative patients and how it may prevent complications. Several wireless systems are being developed for monitoring vital parameters, but many of these are not yet validated for critically ill patients. The ultimate goal with patient monitoring and detect of events is to prevent postoperative complications, death and costs in the health care system. A few studies indicate that monitoring systems detect deteriorating patients earlier than the nurses, and this was associated with less clinical instability. An important caveat of future devices is to assess their effect in relevant patient populations and not only in healthy test-subjects. Implementation of novel technologies is expensive although expected to be cost-effective if just few adverse events can be prevented. The future is here with promising devices and the possibility to give an unprecedented precise risk estimation of adverse post-surgical events. Next step is to integrate existing evidence based treatment algorithms to demonstrate the clinical efficacy of implementing the new technology.
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Monitorização Fisiológica/instrumentação , Gravidade do Paciente , Complicações Pós-Operatórias/prevenção & controle , Análise Custo-Benefício , Humanos , Quartos de Pacientes , Complicações Pós-Operatórias/mortalidade , Tecnologia sem FioRESUMO
Disinfection of hatching eggs is essential to ensure high quality production of broilers. Different protocols are followed in different hatcheries; however, only limited scientific evidence on how the disinfection procedures impact the microbiome is available. The aim of the present study was to characterize the microbiome and aerobic bacterial load of hatching eggs before disinfection and during the subsequent disinfection steps. The study included a group of visibly clean and a group of visibly dirty eggs. For dirty eggs, an initial wash in chlorine was performed, hereafter all eggs were submitted to two times fumigation and finally spray disinfection. The eggshell microbiome was characterized by sequencing of the total amount of 16S rRNA extracted from each sample, consisting of shell surface swabs of five eggs from the same group. In addition, the number of colony forming units (cfu) under aerobic conditions was established for each disinfection step. The disinfection procedure reduced the bacterial load from more than 104 cfu (initially visibly clean eggs) and 105 cfu (initially visibly dirty eggs) to less than 10 cfu per sample after disinfection for both groups of eggs. The microbiome of both initially visibly clean and initially visibly dirty eggs had the highest abundances of the phyla Firmicutes, Proteobacteria and Bacteroidetes. Within the phyla Firmicutes the relative abundances of Clostridiales decreased while Lactobacillus increased from before to after final disinfection. In conclusion, the investigated disinfection procedure is effective in reducing the bacterial load, and by adding a chlorine wash for initially visibly dirty eggs, the microbiome of initially visibly clean and initially visibly dirty eggs had a highly similar microflora after the final disinfection step.
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Bactérias Aeróbias/isolamento & purificação , Galinhas/microbiologia , Desinfecção , Casca de Ovo/microbiologia , Microbiota , Óvulo/microbiologia , Animais , Chipre , RNA Bacteriano/análise , RNA Ribossômico 16S/análiseRESUMO
Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS), which causes 15% of pediatric cancer deaths. High-risk NBL is characterized by N-Myc amplification and segmental chromosomal gains and losses. Owing to limited disease models, the etiology of NBL is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying NBL based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9.5 trunk neural tube explants. Based on pathology and gene expression analysis, we report the first successful transformation of wild-type NCCs into NBL by enforced expression of N-Myc, to generate phenotypically and molecularly accurate tumors that closely model human MYCN-amplified NBL. Using comparative genomic hybridization, we found that NCC-derived NBL tumors acquired copy number gains and losses that are syntenic to those observed in human MYCN-amplified NBL including 17q gain, 2p gain and loss of 1p36. When p53-compromised NCCs were transformed with N-Myc, we generated primitive neuroectodermal tumors with divergent differentiation including osteosarcoma. These subcutaneous tumors were metastatic to regional lymph nodes, liver and lung. Our novel experimental approach accurately models human NBL and establishes a new system with potential to study early stages of NBL oncogenesis, to functionally assess NBL oncogenic drivers and to characterize NBL metastasis.
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Transformação Celular Neoplásica/genética , Proteína Proto-Oncogênica N-Myc/genética , Crista Neural/patologia , Neuroblastoma/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Modelos Animais de Doenças , Feminino , Xenoenxertos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Proteína Proto-Oncogênica N-Myc/metabolismo , Crista Neural/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Multiple acyl-CoA dehydrogenation deficiency is genetically heterogenous metabolic disease with mutations in genes involved in electron transfer to the mitochondrial respiratory chain. Disease symptoms vary from severe neonatal form to late-onset presentation with metabolic acidosis, lethargy, vomiting, muscle pain and weakness. Riboflavin therapy has been shown to ameliorate diseases symptoms in some of these patients. Recently, mutations in FAD synthase have been described to cause multiple acyl-CoA dehydrogenation deficiency. We describe here the effect of riboflavin supplementation therapy in a previously reported adult patient with multiple acyl-CoA dehydrogenation deficiency having compound heterozygous gene variations in FLAD1 (MIM: 610595) encoding FAD synthase. We present thorough clinical history including laboratory investigations, muscle MRI, muscle biopsy and spiroergometric analyses comprising of a follow-up of 20 years. Our data suggest that patients with adult-onset multiple acyl-CoA dehydrogenation deficiency with FLAD1 gene mutations also benefit from long-term riboflavin therapy.
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Mutação da Fase de Leitura , Deficiência Múltipla de Acil Coenzima A Desidrogenase/dietoterapia , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Mutação de Sentido Incorreto , Riboflavina/uso terapêutico , Adulto , Feminino , Heterozigoto , Humanos , Deficiência Múltipla de Acil Coenzima A Desidrogenase/patologia , Músculo Esquelético , Resultado do TratamentoRESUMO
Isobutyryl-CoA Dehydrogenase Deficiency (IBDD) is an inherited disorder of valine metabolism caused by mutations in ACAD8. Most reported patients have been diagnosed through newborn screening programmes due to elevated C4-carnitine levels and appear clinically asymptomatic. One reported non-screened patient had dilated cardiomyopathy and anaemia at the age of two years. We report a 13 month old girl diagnosed with IBDD after developing hypoglycaemic encephalopathy (blood glucose 1.9 mmol/l) during an episode of rotavirus-induced gastroenteritis. Metabolic investigations demonstrated an appropriate ketotic response (free fatty acids 2594 µmol/l, 3-hydroxybutyrate 3415 µmol/l), mildly elevated plasma lactate (3.4 mmol/l), increased C4-carnitine on blood spot and plasma acylcarnitine analysis and other metabolic abnormalities secondary to ketosis. After recovery, C4-carnitine remained increased and isobutyrylglycine was detected on urine organic acid analysis. Free carnitine was normal in all acylcarnitine samples. IBDD was confirmed by finding a homozygous c.845C > T substitution in ACAD8. The patient was given, but has not used, a glucose polymer emergency regimen and after ten years' follow-up has had no further episodes of hypoglycaemia nor has she developed cardiomyopathy or anaemia. Psychomotor development has been normal to date. Though we suspect IBDD did not contribute to hypoglycaemia in this patient, patients should be followed-up carefully and glucose polymer emergency regimens may be indicated if recurrent episodes of hypoglycaemia occur.
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Skin and soft tissue infections (SSTIs) due to Staphylococcus aureus have become increasingly common in the outpatient setting; however, risk factors for differentiating methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) SSTIs are needed to better inform antibiotic treatment decisions. We performed a case-case-control study within 14 primary-care clinics in South Texas from 2007 to 2015. Overall, 325 patients [S. aureus SSTI cases (case group 1, n = 175); MRSA SSTI cases (case group 2, n = 115); MSSA SSTI cases (case group 3, n = 60); uninfected control group (control, n = 150)] were evaluated. Each case group was compared to the control group, and then qualitatively contrasted to identify unique risk factors associated with S. aureus, MRSA, and MSSA SSTIs. Overall, prior SSTIs [adjusted odds ratio (aOR) 7·60, 95% confidence interval (CI) 3·31-17·45], male gender (aOR 1·74, 95% CI 1·06-2·85), and absence of healthcare occupation status (aOR 0·14, 95% CI 0·03-0·68) were independently associated with S. aureus SSTIs. The only unique risk factor for community-associated (CA)-MRSA SSTIs was a high body weight (⩾110 kg) (aOR 2·03, 95% CI 1·01-4·09).
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Infecções Comunitárias Adquiridas/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/fisiologia , Pessoa de Meia-Idade , Atenção Primária à Saúde , Fatores de Risco , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Texas/epidemiologia , Adulto JovemRESUMO
The natural food for Atlantic salmon (Salmo salar) in freshwater has relatively lower levels of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) than found in prey for post-smolt salmon in seawater. Land-locked salmon such as the Gullspång population feed exclusively on freshwater type lipids during its entire life cycle, a successful adaptation derived from divergent evolution. Studying land-locked populations may provide insights into the molecular and genetic control mechanisms that determine and regulate n-3 LC-PUFA biosynthesis and retention in Atlantic salmon. A two factorial study was performed comparing land-locked and farmed salmon parr fed diets formulated with fish or rapeseed oil for 8 weeks. The land-locked parr had higher capacity to synthesise n-3 LC-PUFA as indicated by higher expression and activity of desaturase and elongase enzymes. The data suggested that the land-locked salmon had reduced sensitivity to dietary fatty acid composition and that dietary docosahexaenoic acid (DHA) did not appear to suppress expression of LC-PUFA biosynthetic genes or activity of the biosynthesis pathway, probably an evolutionary adaptation to a natural diet lower in DHA. Increased biosynthetic activity did not translate to enhanced n-3 LC-PUFA contents in the flesh and diet was the only factor affecting this parameter. Additionally, high lipogenic and glycolytic potentials were found in land-locked salmon, together with decreased lipolysis which in turn could indicate increased use of carbohydrates as an energy source and a sparing of lipid.